MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Current Pharmaceutical Design' source. Wed, 08 Feb 2012 14:04:09 +0100 http://www.medworm.com/index.php?rid=5625720&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250770%26dopt%3DAbstract Authors: Flordellis CS PMID: 22250770 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625720 Tue, 17 Jan 2012 05:00:00 +0100 5625720 http://www.medworm.com/index.php?rid=5625752&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239563%26dopt%3DAbstract Authors: Fusar-Poli P PMID: 22239563 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625752 Tue, 10 Jan 2012 05:00:00 +0100 5625752 http://www.medworm.com/index.php?rid=5625751&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239564%26dopt%3DAbstract Authors: Stanghellini G, Fusar-Poli P Abstract Early psychopathological attempts to characterize the vulnerability to schizophrenia were based on the phenomenological method. From the beginning, phenomenologically-oriented psychopathologists have searched the basic vulnerability underlying schizophrenic phenomena in two main domains: depersonalization and derealisation/desocialization. Schizophrenic persons undergo a special kind of depersonalisation: the living body becomes a functioning body, a thing-like mechanism in which feelings, perceptions, and actions take place as if they happened in an outer space. They also endure a special kind of derealisation/de-socialization: the interpersonal scene becomes like a theatre stage, pervaded with a sense of unreality, on which the main ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625751 Tue, 10 Jan 2012 05:00:00 +0100 5625751 http://www.medworm.com/index.php?rid=5625750&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239565%26dopt%3DAbstract Authors: Yung AR, Fusar-Poli P, Nelson B Abstract Although prodromal symptoms of psychosis have long been recognized, the clinical management of psychotic disorders conventionally begins at the first episode of frank psychosis, and, until recently, the period immediately preceding the first episode received relatively little attention. Over the last fifteen years, there has been increasingly academic and clinical interest in people presenting with potentially prodromal symptoms. This clinical syndrome has been termed an "At Risk Mental State", and operationalised criteria, the "Ultra High Risk (UHR)", or at "Clinical High Risk" criteria, have been developed to identify the syndrome. We will review here the mainstreams of the UHR paradigms focusing on the conceptual basis, potential... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625750 Tue, 10 Jan 2012 05:00:00 +0100 5625750 http://www.medworm.com/index.php?rid=5625749&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239566%26dopt%3DAbstract Authors: Schultze-Lutter F, Ruhrmann S, Fusar-Poli P, Bechdolf A, Schimmelmann BG, Klosterkötter J Abstract Recent focus on early detection and intervention in psychosis has renewed interest in subtle psychopathology beyond positive and negative symptoms. Such self-experienced sub-clinical disturbances are described in detail by the basic symptom concept. This review will give an introduction into the concept of basic symptoms and describe the development of the current instruments for their assessment, the Schizophrenia Proneness Instrument, Adult (SPI-A) and Child and Youth version (SPI-CY), as well as of the two at-risk criteria: the at-risk criterion Cognitive-Perceptive Basic Symptoms (COPER) and the high-risk criterion Cognitive Disturbances (COGDIS). Further, an overview of... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625749 Tue, 10 Jan 2012 05:00:00 +0100 5625749 http://www.medworm.com/index.php?rid=5625748&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239567%26dopt%3DAbstract Authors: Bechdolf A, Ratheesh A, Wood SW, Tecic T, Conus P, Nelson B, Cotton SM, Chanen AM, Amminger GP, Ruhrmanna S, Schultze-Lutter F, Klosterkötter J, Fusar-Poli P, Yung AR, Berk M, McGorry PD Abstract Bipolar affective disorder (BD) is a severe, recurrent and disabling disorder with devastating consequences for individuals, families and society. Although these hazards and costs provide a compelling rationale for development of early detection and early intervention strategies in BD, the development of at-risk criteria for first episode mania is still in an early stage of development. In this paper we review the literature with respect to the clinical, neuroantomical and neuropsychological data, which support this goal. We also describe our recently developed bipolar at-risk cr... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625748 Tue, 10 Jan 2012 05:00:00 +0100 5625748 http://www.medworm.com/index.php?rid=5625747&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239568%26dopt%3DAbstract Authors: Nelson B, Fusar-Poli P, Yung AR Abstract The continuum model of psychosis posits that psychotic symptoms are distributed throughout the population, with diagnosable clinical disorder existing at a certain point along this continuum. The total continuum is made up mainly of non-clinical cases with clinical cases of psychosis representing only a small proportion of the total extended psychosis phenotype. This paper is a narrative review of studies of psychotic experiences in the general population. The evidence indicatesreasonably high prevalence rates of psychotic experiences in the general population, substantially higher than the prevalence of psychotic disorders, and that they are associated with increased risk of future onset of diagnosable disorder, particularly when t... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625747 Tue, 10 Jan 2012 05:00:00 +0100 5625747 http://www.medworm.com/index.php?rid=5625746&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239569%26dopt%3DAbstract Authors: Fusar-Poli P, Hobson R, Raduelli M, Ballotin U Abstract The Comprehensive Assessment of the At Risk Mental State (CAARMS) is a semi-structured interview designed to assess attenuated psychotic symptoms in people at ultra high risk of developing psychosis (UHR). It is widely used worldwide but no studies have ever assessed its psychometric properties in the Italian population.Here we tested the reliability and validity of the Italian version of the CAARMS. Psychometric properties (inter-rater reliability, internal coherence, construct validity, concurrent validity and predictive validity) were assessed in an Italian sample of ARMS subjects, first-episode subjects and matched controls. We found the Italian version of CAARMS demonstrates adequate validity and reliability and ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625746 Tue, 10 Jan 2012 05:00:00 +0100 5625746 http://www.medworm.com/index.php?rid=5625745&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239570%26dopt%3DAbstract Abnormal bodily experiences may be a marker of early schizophrenia? Curr Pharm Des. 2012 Jan 10; Authors: Stanghellini G, Ballerini M, Fusar-Poli P, Cutting J Abstract The purpose of this study is to answer the following question: What are the typical features of abnormal bodily experiences (ABEs) in persons affected by acute first-episode schizophrenia? Our overall objective is to contribute to enhance early diagnosis of schizophrenia, and providing supplementary diagnostic criteria especially for ultra-high risk patients. In a group of 39 patients with first-episode schizophrenia selected from a sample of 393 psychotic patients, 30 (76.9 %) reported ABEs. By means of a phenomenologically-based qualitative method of inquiry, we recognized four subtypes of ABEs whose main c... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625745 Tue, 10 Jan 2012 05:00:00 +0100 5625745 http://www.medworm.com/index.php?rid=5625744&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239571%26dopt%3DAbstract Authors: Giuliano AJ, Li H, Mesholam-Gately RI, Sorenson S, Woodberry KA, Seidman LJ Abstract Cognitive dysfunction is a hallmark feature of schizophrenia and is evident across all phases of the illness. While prior meta-analyses have elucidated the level and pattern of cognitive deficits in the premorbid and post-onset periods of psychosis, no meta-analyses of studies of the putative prodromal period have been published. Our primary aim is to provide a meta-analysis of neurocognitive findings from 14 studies of psychosis risk syndrome (PRS) individuals published through February 2011, and compare the resulting profile with that synthesized by meta-analyses from other periods of the disorder. Meta-analysis of 1215 PRS individuals with a mean age of 19.2 (± 3.3) and 851 healthy con... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625744 Tue, 10 Jan 2012 05:00:00 +0100 5625744 http://www.medworm.com/index.php?rid=5625743&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239572%26dopt%3DAbstract Authors: Smieskova R, Fusar-Poli P, Riecher-Rössler A, Borgwardt S Abstract Over the past decade, vulnerability- and psychosis-associated structural and functional brain abnormalities in a population at high clinical risk to develop psychosis were intensively studied. We reviewed the results from studies comparing at-risk mental state (ARMS) individuals with and without subsequent transition to psychosis. Additionally, we introduced a new concept of splitting ARMS population according to the duration of the psychosis risk syndrome and their probability to develop psychosis. Studying the ARMS individuals still vulnerable to psychosis but with lower risk to transit can disclose the possible protective - resilience factors or characteristics. Resilience, understood as ability to reco... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625743 Tue, 10 Jan 2012 05:00:00 +0100 5625743 http://www.medworm.com/index.php?rid=5625742&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239573%26dopt%3DAbstract Authors: Karlsgodt KH, Jacobson SC, Seal M, Fusar-Poli P Abstract Schizophrenia is a disorder with a pronounced developmental component. Accordingly, there is a growing interest in characterizing developmental changes in the period leading up to disease onset, in an effort to develop effective preventative interventions. One of the ongoing neurodevelopmental changes known to occur in the late adolescent period that often overlaps with the prodromal phase and time of onset is white matter development and myelination. In this critical review, a disruption in the normal trajectory of white matter development could potentially play an important role in the onset of psychosis. We seek to summarize the existing state of research on white matter development in prodromal subjects, with a p... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625742 Tue, 10 Jan 2012 05:00:00 +0100 5625742 http://www.medworm.com/index.php?rid=5625741&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239574%26dopt%3DAbstract Authors: Dauvermann MR, Mukherjee P, Moorhead WT, Stanfield AC, Fusar-Poli P, Lawrie SM, Whalley HC Abstract Measures of cortical folding ('gyrification') and connectivity are both reported to be disrupted in schizophrenia. There are also reports that increases in prefrontal gyrification may be predictive of subsequent illness in individuals at familial risk of the disorder. Such measures therefore have important potential clinical relevance. The nature of the relationship between cortical morphology and underlying connectivity is however unclear. In the current study we sought to explore the relationship between measures of gyrification and functional connectivity in a cohort of individuals at high genetic risk for the disorder. The theoretical background is based on the hypothesi... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625741 Tue, 10 Jan 2012 05:00:00 +0100 5625741 http://www.medworm.com/index.php?rid=5625740&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239575%26dopt%3DAbstract Authors: Valli I, Tognin S, Fusar-Poli P, Mechelli A Abstract Cognitive impairment is one of the key features of schizophrenia, with the largest effect sizes identified for verbal learning and memory, however little is known about its features in the time that precedes psychosis onset. Here we review a total of thirty-two studies that examined memory and learning in populations at clinical and genetic high-risk for psychosis. These studies can be divided into three different categories based on their design. Some were cross-sectional and examined neuropsychological differences between high-risk individuals and healthy controls. A second type of studies included a clinical follow-up that allowed dividing participants based on their outcome to examine abnormalities specific of subseq... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625740 Tue, 10 Jan 2012 05:00:00 +0100 5625740 http://www.medworm.com/index.php?rid=5625739&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239576%26dopt%3DAbstract Authors: Howes OD, Fusar-Poli P, Bloomfield M, Selvaraj S, McGuire P Abstract Schizophrenia is a chronic psychotic disorder that remains a considerable cause of global disease burden. Cognitive impairments are common and contribute significantly to the morbidity of the disorder. Over the last two decades or so molecular imaging studies have refined understanding of the pathophysiology underlying the development of psychosis and cognitive impairments. Firstly they have consistently implicated presynaptic dopaminergic dysfunction in the disorder, finding that dopamine synthesis capacity, dopamine release and baseline dopamine levels are increased in the illness. Secondly recent findings show that dopamine synthesis capacity is elevated in those that go on to develop psychosis in the ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625739 Tue, 10 Jan 2012 05:00:00 +0100 5625739 http://www.medworm.com/index.php?rid=5625738&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239577%26dopt%3DAbstract Authors: Egerton A, Fusar-Poli P, Stone JM Abstract Increasing evidence suggests that abnormalities in glutamatergic transmission may be associated with psychosis risk. Genetic polymorphisms associated with schizophrenia converge on NMDA receptor signalling pathways, and transgenic animal models and human neuroimaging studies have shown the functional impact of these risk alleles. Animal models have also shown that environmental risk factors, such as stress, cannabis use and maternal infection can result in glutamatergic dysfunction, and in vivo magnetic resonance spectroscopy (MRS) studies have detected glutamatergic abnormalities in individuals at clinical or genetic risk of psychosis. Glutamatergic dysfunction may impact on dopaminergic transmission, and ultimately lead to the e... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625738 Tue, 10 Jan 2012 05:00:00 +0100 5625738 http://www.medworm.com/index.php?rid=5625737&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239578%26dopt%3DAbstract Authors: Crossley NA, Constante M, Fusar-Poli P, Bramon E Abstract Electroencephalography and Magnetoencephalography have provided valuable information about the brain functioning in psychosis. In the last few years, authors have demonstrated that there are neurophysiological alterations already in the prodromal period, before the development of psychosis. This makes them promising tools for predicting a future transition to psychosis. In this paper we review the latest studies using event-related potentials (ERP) in subjects clinically at high-risk of developing psychosis. We particularly focus in the P300, Mismatch-Negativity (MMN) and P50 paradigms, discussing the main findings, but also the limitations and challenges in electrophysiological studies in this population. PMID:... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625737 Tue, 10 Jan 2012 05:00:00 +0100 5625737 http://www.medworm.com/index.php?rid=5625736&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239579%26dopt%3DAbstract Authors: De Peria L, Crescinia A, Destea G, Fusar-Polia P, Sacchettia E, Vitaa A Abstract A number of structural brain imaging studies and meta-analytic reviews have shown that multiple subtle brain abnormalities are consistently found in schizophrenia and bipolar disorder. Several studies suggest that schizophrenia and affective psychoses share a largely common pattern of brain abnormalities. Aim of the present study was to compare, by means of a meta-analytic approach, brain structural abnormalities, as detected by Magnetic Resonance Imaging (MRI) found at the onset of schizophrenia and bipolar disorder in order to address the question of the specificity of brain abnormalities across diagnostic groups. Forty-five studies were identified as suitable for analysis. In both schizophr... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625736 Tue, 10 Jan 2012 05:00:00 +0100 5625736 http://www.medworm.com/index.php?rid=5625735&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239580%26dopt%3DAbstract Discussion: These results suggest that theat-risk mental state is associated with cingulate volume reductions in particular in the left caudal anterior cingulate cortex (CACC). These abnormalities do not only seem to occur with transition to psychosis, but may be a correlate of an increased vulnerability to psychosis. PMID: 22239580 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625735 Tue, 10 Jan 2012 05:00:00 +0100 5625735 http://www.medworm.com/index.php?rid=5625734&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239581%26dopt%3DAbstract Authors: Emanuele E, Martinelli V, Abbiati V, Fusar-Poli P, Politi P Abstract Recent years have witnessed numerous attempts at identifying the biological correlates of impending psychosis. Biochemical markers may theoretically provide a powerful approach to identify at-risk individuals, potentially leading to more effective intervention strategies to treat them. Hopefully, future developments in the field of research biochemistry in patients at risk mental states or prodromal symptoms will make this approach ideal for screening and monitoring purposes. In this review, we provide an overview of the different biochemical markers which have been recently demonstrated to be altered in the biological fluids of patients with impending psychosis. We will also examine the practical issues ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625734 Tue, 10 Jan 2012 05:00:00 +0100 5625734 http://www.medworm.com/index.php?rid=5625733&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239582%26dopt%3DAbstract Authors: Andrea M, Fusar-Poli P, Diana P, Alessandro PS, Stefania T, Joseph K, Cynthia F, Marco P, Muriel W, Timothea T, Elvira B, Robin M, Philip M Abstract Recent studies have described G72 and DAAO as susceptibility genes for schizophrenia and bipolar disorder. Both genes modulate glutamate neurotransmission, which plays a key role in neurocognitive function and is thought to be altered in these disorders. Moreover, in vitro transcription studies indicate that the two genes interact with each other at the molecular level. However, it is unclear how these genes affect cortical function and whether their effects interact with each other. The aim of this study was therefore to examine the impact of G72 rs746187 and DAAO rs2111902 genotypes on brain function in schizophrenia, bipola... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625733 Tue, 10 Jan 2012 05:00:00 +0100 5625733 http://www.medworm.com/index.php?rid=5625732&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239583%26dopt%3DAbstract In conclusion, there remain numerous gaps in our understanding of the relation between migration, ethnicity, social contexts and the onset of psychosis and we propose future research avenues to address these. In particular, there is a need for multilevel approaches integrating disciplines and methodologies across the psychosis continuum. PMID: 22239583 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625732 Tue, 10 Jan 2012 05:00:00 +0100 5625732 http://www.medworm.com/index.php?rid=5625731&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239584%26dopt%3DAbstract Authors: Holtzman CW, Shapiro DI, Trotman HD, Walker EF Abstract Stress plays a role in most conceptualizations of the etiology of psychotic disorders. This is based on extensive research showing an association between the incidence of psychosis and psychosocial stress exposure (e.g., stressful life events and trauma) in both childhood and the weeks preceding a psychotic episode. There is also evidence of increased sensitivity to stressful events, and dysregulation of biological stress systems. To better understand the relation of stress with the initial emergence of psychosis, research has increasingly focused on the psychosis prodrome, the period of functional decline that precedes clinical illness. Preliminary results suggest that increased incidence of early childhood trauma, h... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625731 Tue, 10 Jan 2012 05:00:00 +0100 5625731 http://www.medworm.com/index.php?rid=5625730&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239585%26dopt%3DAbstract CONCLUSION: Few studies on the effects of cognitive training programs have been conducted in first episode or in early schizophrenia and no studies have been conducted in the prodromal phase of the disease. Although preliminary positive results have been achieved, more empirical research is needed to confirm the efficacy of cognitive remediation in the early course of schizophrenia, and future studies should address the issue of the usefulness of cognitive remediation in the prodromes of psychosis. PMID: 22239585 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625730 Tue, 10 Jan 2012 05:00:00 +0100 5625730 http://www.medworm.com/index.php?rid=5625729&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239586%26dopt%3DAbstract Authors: Kolliakou A, Fusar-Poli P, Atakan Z Abstract Cannabis is the most widely used illicit substance in the world and due to the high levels of use observed among young people with psychosis, most research has focused on the causal relationship between cannabis use and mental health problems. Despite a large interest in developing intervention models to target this group, there are as yet no established and effective methods of prevention and intervention focusing on cannabis use. In this paper we present the available evidence for the effectiveness of substance use treatments in patients with co-morbid severe mental illness, as well as exploring the prevention and early intervention initiatives for substance use in the general population. PMID: 22239586 [PubMed - as suppli... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625729 Tue, 10 Jan 2012 05:00:00 +0100 5625729 http://www.medworm.com/index.php?rid=5625728&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239587%26dopt%3DAbstract Authors: Ruhrmanna S, Klosterköttera J, Bodatscha M, Bechdolfa A, Schimmelmann BG, Nikolaidesa A, Hilbolla D, Schultze-Lutter F Abstract Over the last couple of decades, the treatment of psychoses has much advanced; yet, despite all progress, the individual and societal burden associated with psychosis and particularly schizophrenia has largely remained unchanged. Therefore, much hope is currently placed on indicated prevention as a mean to fight these burdens before they set in. Though the number of studies investigating pharmacological interventions is still limited, encouraging results have been reported from the pioneering trials, despite several methodological limitations. Furthermore, it has become clear that persons characterized by the at-risk criteria are already ill and ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625728 Tue, 10 Jan 2012 05:00:00 +0100 5625728 http://www.medworm.com/index.php?rid=5625727&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239588%26dopt%3DAbstract Authors: Addington J, Marshall C, French P Abstract There is a strong impetus in the psychosis research field to develop interventions that aim to prevent the onset of psychotic disorders. Over the past 15 years there has been a tremendous development in the work aimed at understanding the pre-psychotic period. More recently there has been a focus on developing and testing treatments both pharmacological and psychological that could potentially prevent or delay the onset of psychosis. One of the psychological treatments that has received the most attention is cognitive behavior therapy (CBT). Relatively few trials have been completed and this paper reviews the existing trials. Implications of these trials for the treatment of this early phase as well as for designing future studies... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625727 Tue, 10 Jan 2012 05:00:00 +0100 5625727 http://www.medworm.com/index.php?rid=5625726&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239589%26dopt%3DAbstract Authors: Hauser M, Juckel G Abstract Pychoeducation is a useful and required intervention in subjects with elevated-risk state of psychosis. Psychoeducation is, however, an under-investigated area in the field of early identification and prevention. Psychoeducation with this particular patient group needs to adapt to several unique features, e.g. the diagnostic uncertainty ("say it only in subjunctive") and problems of stigmatization. More research regarding the subjective psychoeducational needs of individuals at elevated risk for psychosis as well as more explicit provision and evaluation of psychoeducation in the elevated-risk state is strongly desirable. PMID: 22239589 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625726 Tue, 10 Jan 2012 05:00:00 +0100 5625726 http://www.medworm.com/index.php?rid=5625725&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239590%26dopt%3DAbstract Conclusions: This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder. PMID: 22239590 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625725 Tue, 10 Jan 2012 05:00:00 +0100 5625725 http://www.medworm.com/index.php?rid=5625724&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239591%26dopt%3DAbstract Authors: Mossaheb N, Schloegelhofer M, Schaefer MR, Fusar-Poli P, Smesny S, McGorry P, Berger G, Amminger GP Abstract The role of polyunsaturated fatty acids and their metabolites for the cause and treatment of psychotic disorders are widely discussed. The efficacy as an augmenting agent in chronic schizophrenia seems to be small or not present, however epidemiological data, as well as some recent controlled studies in emerging psychosis point towards possible preventive effects of long-chain polyunsaturated fatty acids in early and very early stages of psychotic disorders and some potential secondary or tertiary beneficial long-term effects in later, more chronic stages, in particular for metabolic or extra-pyramidal side effects. In this comprehensive review, we describe the phys... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625724 Tue, 10 Jan 2012 05:00:00 +0100 5625724 http://www.medworm.com/index.php?rid=5625723&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239592%26dopt%3DAbstract Conclusions: The potential longer term economic benefits of early detection and early intervention are required. PMID: 22239592 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625723 Tue, 10 Jan 2012 05:00:00 +0100 5625723 http://www.medworm.com/index.php?rid=5625722&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239593%26dopt%3DAbstract Authors: Broome M, Fusar-Poli P Abstract In this paper we try to examine some of the philosophical issues that arise from the clinical and scientific study of the prodromal phase of psychotic illness. These issues can be broadly grouped into ethical concerns and those relating to the philosophy of psychology and science. Specifically, we discuss the notion of the prodrome as a discrete disorder as opposed to being a segment of the continuum of psychosis, and whether we can define psychopathology purely via the use of neuroscientific variables and concepts. We argue that many psychopathological terms have definitions that rely on normative notions that themselves may not be able to be reduced to terms in cognitive neuroscience and hence a purely neuroscientific conception of psychop... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625722 Tue, 10 Jan 2012 05:00:00 +0100 5625722 http://www.medworm.com/index.php?rid=5625721&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22239594%26dopt%3DAbstract Ethical Implications for Clinical Practice and Future Research in "At Risk" Individuals. Curr Pharm Des. 2012 Jan 10; Authors: Singh F, Mirzakhanian H, Fusar-Poli P, de la Fuente-Sandoval C, Cadenhead KS Abstract The last 15 years have witnessed a shift in schizophrenia research with increasing interest in earlier stages of illness with the hope of early intervention and ultimately prevention of psychotic illness. Large-scale longitudinal studies have identified clinical and biological risk factors associated with increased risk of psychotic conversion, which together with symptomatic and demographic risk factors may improve the power of prediction algorithms for psychotic transition. Despite these advances, 45-70% of at risk subjects in most samples do not convert to frank... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5625721 Tue, 10 Jan 2012 05:00:00 +0100 5625721 http://www.medworm.com/index.php?rid=5579972&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229561%26dopt%3DAbstract Authors: Cecconi S PMID: 22229561 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579972 Tue, 10 Jan 2012 05:00:00 +0100 5579972 http://www.medworm.com/index.php?rid=5579971&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229562%26dopt%3DAbstract Authors: De Felici M, Farini D Abstract The cell cycle of the primordial germ cells (PGCs), the embryonic precursors of the gametes, is characterized by a mitotic phase common to both sexes and a mitotic-meiotic switch in the female. In the present work, we will review the progress achieved in the last decade in studying intrinsic and extrinsic regulatory signals of such processes, with particular reference to the mouse PGCs. Besides to achieve a better understanding of how the gamete population is established in mammals, information about the players controlling the PGC cycle will result useful to clarify other intriguing aspects of germ cell biology such as the origin of germ cell tumours and the mechanisms allowing the maintenance of totipotency in the germ line. PMID: 22229... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579971 Tue, 10 Jan 2012 05:00:00 +0100 5579971 http://www.medworm.com/index.php?rid=5579970&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229563%26dopt%3DAbstract Authors: Sergio L, Bebbere D, Ariu F, Pescatori M, Pau S, Zedda MT, Bogliolo L Abstract Assisted reproductive technologies (ART) are successfully applied in several mammals, including humans, thanks to the ability of oocytes and embryos to face maturation, fertilization and first development in vitro. However, efficiency and safety of ART represent main issues. Mammalian oocytes and early embryos are transcriptionally inactive, and rely exclusively on maternal RNAs and proteins, deposited during oocyte growth, until embryonic genome activation (EGA). Such transcriptional quiescence needs complex post-transcriptional and post-translational mechanisms to coordinate meiotic maturation, fertilization, and reprogramming of the nascent genome. These events are the final outcome of comple... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579970 Tue, 10 Jan 2012 05:00:00 +0100 5579970 http://www.medworm.com/index.php?rid=5579969&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229564%26dopt%3DAbstract Authors: Diamanti-Kandarakis E, Christakou C, Marinakis E Abstract Polycystic ovary syndrome (PCOS) is a complex syndrome of unclear etiopathogenesis characterized by heterogeneity in phenotypic manifestations. The clinical phenotype of PCOS includes reproductive and hormonal aberrations, namely anovulation and hyperandrogenism, which coexist with metabolic disturbances. Reflecting the crosstalk between the reproductive system and metabolic tissues, obesity not only deteriorates the metabolic profile but also aggravates ovulatory dysfunction and hyperandrogenism. Although the pathogenesis of PCOS remains unclear ,the syndrome appears to involve environmental and genetic components. Starting from early life and extending throughout lifecycle, environmental insults may affect suscept... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579969 Tue, 10 Jan 2012 05:00:00 +0100 5579969 http://www.medworm.com/index.php?rid=5579968&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229565%26dopt%3DAbstract Authors: Virant-Klun I, Stimpfel M, Skutella T Abstract The human ovary is a complex endocrine gland, which is responsible for production of different hormones and provides mature and competent oocytes for reproduction. Additionally, it produces various substances, such as growth factors and cytokines which are involved in the complex signalling pathways of folliculogenesis or oogenesis. The abnormalities of ovarian function might lead to infertility or manifestation of aggressive cancer. Therefore, stem cells in adult human ovaries are of great interest to reproductive medicine for improved understanding of the mechanisms leading to ovarian infertility or cancer formation, yet they represent a difficult scientific subject, because it is still generally accepted that they do not ex... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579968 Tue, 10 Jan 2012 05:00:00 +0100 5579968 http://www.medworm.com/index.php?rid=5579967&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229566%26dopt%3DAbstract Authors: Lappi M, Borini A Abstract Thanks to the recent advances in cancer care, more and more young women can survive but suffer from infertility as a result of cancer treatment that had to be submitted. There are a variety of methods to preserve fertility, as chemoprotection, ovariopexy, and some assisted reproductive technologies, although some of these are promising but still highly experimental techniques. Cryopreservation of embryos for example is already established, while the oocyte banking is still considered an experimental practice. Many experiments have been conducted around the world on the cryopreservation of ovarian tissue and maturation of ovarian follicles, in an attempt to demonstrate its potential use in fertility preservation. Although in recent years there has... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579967 Tue, 10 Jan 2012 05:00:00 +0100 5579967 http://www.medworm.com/index.php?rid=5579966&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229567%26dopt%3DAbstract Authors: Shimizu T, Hoshino Y, Miyazaki H, Sato E Abstract The female reproductive organs such as ovary, uterus, and placenta are some of the few adult tissues that exhibit regular intervals of rapid growth, and are highly vascularized and have high rates of blood flow. Angiogenesis is a process of vascular growth that is mainly limited to the reproductive system in healthy adult animals. The development of new blood vessels in the ovary and uterus is essential to guarantee the necessary supply of nutrients and hormones. The genetic and molecular mechanisms that control the development of capillary blood vessels in reproductive organs are beginning to be elucidated. Reproductive organs contain and produce angiogenic factors which may act alone or in concert to regulate the process ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579966 Tue, 10 Jan 2012 05:00:00 +0100 5579966 http://www.medworm.com/index.php?rid=5579965&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229568%26dopt%3DAbstract Application of RNA interference for control of female reproductive functions. Curr Pharm Des. 2012 Jan 10; Authors: Sirotkin AV Abstract RNA interference, a recently discovered new mechanism controlling gene expression via small RNAs, was shown to be involved in characterization and control of basic ovarian cell functions. The main classes of small RNAs, as well as their expression in ovaries have been described. Furthermore, the successful application of RNA interference for study and control of basic ovarian functions (fertility, proliferation, apoptosis, secretory activity, luteogenesis, oocyte maturation and related ovarian cell malignant transformation) and production of recombinant proteins have been demonstrated. Application of RNA interference in reproductive biolog... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579965 Tue, 10 Jan 2012 05:00:00 +0100 5579965 http://www.medworm.com/index.php?rid=5579964&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229569%26dopt%3DAbstract Authors: Grasemann H PMID: 22229569 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579964 Tue, 10 Jan 2012 05:00:00 +0100 5579964 http://www.medworm.com/index.php?rid=5579963&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229570%26dopt%3DAbstract Authors: Ratjen F, Grasemann H Abstract Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to abnormalities in transepithelial ion transport in the airways of affected patients. Lung disease is the major contributor to morbidity and mortality in patients with cystic fibrosis but recommended therapeutic interventions so far have focused on symptom control rather than treatment of the underlying causes of the disease. New therapies that are currently in pre-clinical and clinical testing include CFTR pharmacotherapy, drugs targeting other ion channels, and hydrators of the cystic fibrosis airways. The current status of these and other new developments in the treatment of cystic fibrosis are reviewed. PMID: 222295... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579963 Tue, 10 Jan 2012 05:00:00 +0100 5579963 http://www.medworm.com/index.php?rid=5579962&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229571%26dopt%3DAbstract Authors: Griesenbach U, Alton EW Abstract Although the development of gene therapy for cystic fibrosis (CF) was high priority for many groups in academia and industry in the first 10 to 15 years after cloning the gene, more recently active research into CF gene therapy is only being performed by a small number of committed, mainly academic, groups. However, despite the warning enthusiasm, which is largely due to the realisation that gene transfer into lungs is more difficult than originally thought and the fact that meaningful clinical trials are expensive and difficult to perform, gene therapy continues to hold promise for the treatment of CF lung disease. Problems related to repeat administration of adenovirus and adeno-associated virus-based vectors led to a focus on non-viral v... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579962 Tue, 10 Jan 2012 05:00:00 +0100 5579962 http://www.medworm.com/index.php?rid=5579961&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229572%26dopt%3DAbstract Authors: Dorfman R Abstract Since the discovery of the CFTR gene mutations which cause cystic fibrosis (CF) in 1989 the average life expectancy of CF patients has almost doubled and now exceeds 37 years. The advances in molecular diagnostics and medical treatments expanded beyond the CF patient population as some of the newest treatments are also being tested for treatment of complex diseases such as COPD and other inherited disorders. Rapid development of CF therapeutics is important for the cystic fibrosis community and is an excellent example for other nonprofit organizations, disease foundations and pharmaceutical companies alike. Better understanding of disease variability and underlying molecular mechanisms through genetic association studies aimed to identify novel CF modifi... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579961 Tue, 10 Jan 2012 05:00:00 +0100 5579961 http://www.medworm.com/index.php?rid=5579960&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229573%26dopt%3DAbstract Authors: Hofmann T Abstract The field of inhaled antibiotics that target Pseudomonas aeruginosa infections has made substantial contributions to the health, disease management, and life expectancies of individuals with cystic fibrosis (CF) over the last three decades [1-3]. This paper reviews some of the recent clinical developments in the field of inhaled antibiotics for CF and briefly describes formulations and ongoing developments for US and/or European regulatory approvals. Lung delivery technologies, in regards to inhaled antibiotics for CF, are also reviewed. PMID: 22229573 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579960 Tue, 10 Jan 2012 05:00:00 +0100 5579960 http://www.medworm.com/index.php?rid=5579959&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229574%26dopt%3DAbstract Authors: Waters V Abstract The development of antimicrobial treatments for respiratory pathogens in cystic fibrosis (CF) has been an integral component to the increased survival of CF patients over the past fifty years. Despite significant treatment advances, however, respiratory failure secondary to chronic bacterial pulmonary infection remains the primary cause of death in CF patients. The purpose of this review is to discuss emerging pathogens (other than Pseudomonas) in CF by describing the characteristics of the organism, their clinical significance in CF, their mechanisms of antimicrobial resistance and the current treatment approaches including newer pharmaceutical modalities. This review will focus on the following pathogens: Burkholderia cepacia complex, Stenotrophomonas m... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579959 Tue, 10 Jan 2012 05:00:00 +0100 5579959 http://www.medworm.com/index.php?rid=5579958&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229575%26dopt%3DAbstract Authors: Grasemann H, Ratjen F Abstract The concentrations of nitric oxide are decreased in airways of patients with cystic fibrosis. The reasons for this nitric oxide deficiency are incompletely understood but may include reduced production from nitric oxide synthases due to decreased expression the enzymes in airway epithelial cells, reduced availability of L-arginine, the substrate for nitric oxide synthases, and the presence of endogenous inhibitors of the enzymes in the airways. As nitric oxide plays a role in a number of important physiological processes in the lung including host defense against pathogens such as Pseudomonas aeruginosa, inflammation and the regulation of vascular and broncho motor tone, the lack of nitric oxide may contribute to lung disease in cystic fibros... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579958 Tue, 10 Jan 2012 05:00:00 +0100 5579958 http://www.medworm.com/index.php?rid=5579957&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229576%26dopt%3DAbstract Authors: Kyriazis I, Ellul J, Katsakiori P, Panayotakopoulos G, Flordellis C Abstract The Protease-Activated Receptors ( PARs ) are G-protein-coupled receptors ( GPCRs ) characterized by a unique mechanism of activation. They carry built in their extended N-terminal structure their own activating agonist, in the form of a cryptic tethered ligand , unmasked by an irreversible proteolytic cleavage. Besides, PARs display several other particular properties that converge and create interacting and intertwined layers of molecular processes regulating receptor's selective signaling with important biological and pharmacological consequences. These include the operation of multiple proteases, co-factors and protease inhibitors expressed in many types of cells and tissues, creating a dynami... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579957 Tue, 10 Jan 2012 05:00:00 +0100 5579957 http://www.medworm.com/index.php?rid=5579956&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229577%26dopt%3DAbstract Authors: George L, Arnau C, Leonardo P Abstract G-protein coupled receptors (GPCRs) comprise the largest family of proteins in our body, which have many important physiological functions and are implicated in the pathophysiology of many serious diseases. GPCRs therefore are significant targets in pharmaceutical research. GPCRs share the common architecture of seven plasma membrane-spanning segments connected to each other with three extracellular and three intracellular loops. In addition, GPCRs contain an extracellular N-terminal region and an intracellular Cterminal tail. GPCRs could stimulate different intracellular G-proteins (internal stimuli) and signaling pathways after their interaction with different ligands (external stimuli). The exceptional functional plasticity of GPCR... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579956 Tue, 10 Jan 2012 05:00:00 +0100 5579956 http://www.medworm.com/index.php?rid=5579955&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229578%26dopt%3DAbstract Authors: Lymperopoulos A, Rengo G, Koch WJ Abstract Despite significant advances in pharmacological and clinical treatment, heart failure (HF) remains the number one killer disease in the western world. HF is a chronic and progressive clinical syndrome mainly characterized by reduction in left ventricular ejection fraction and adverse remodeling of the myocardium. One of its hallmark molecular abnormalities is elevation of cardiac G proteincoupled receptor (GPCR) kinase (GRK)-2, originally termed beta-adrenergic receptor kinase-1 (βARK1), a member of the GRK family of serine/threonine protein kinases which phosphorylate and desensitize GPCRs. Up-regulated GRK2 in the heart underlies the diminished contractile responsiveness of the heart to positive inotropes, as it abrogates the p... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579955 Tue, 10 Jan 2012 05:00:00 +0100 5579955 http://www.medworm.com/index.php?rid=5579954&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229579%26dopt%3DAbstract Authors: Flordellis CS Abstract Components of 7TMR signaling machinery once considered as rigid, fixed and inflexible entities, operating in a one-dimensional way, homogeneous spatially and temporally, are now proved to be structurally plastic, flexible and dynamic in space and time. 7TMRs are thought to exist as ensembles of multiple, inter-convertible, pre-existing conformations and this conformational diversity provides a structural plasticity and the molecular mechanism for the functional diversity of 7TMRs. Furthermore, 7TMRs appear to function not as monomers, but rather as higher order structures, within which allosteric mechanisms affect ligand binding, G protein selection and receptor mobility and signalling of GPCR protomers. Moreover, their function is regulated through ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579954 Tue, 10 Jan 2012 05:00:00 +0100 5579954 http://www.medworm.com/index.php?rid=5579953&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229580%26dopt%3DAbstract Authors: Michele C, Cipolletta E, Iaccarino G Abstract G protein receptor kinase 2 (GRK2) has been for years mainly considered the negative regulator of the cardiac β adrenergic signaling. However GRK2 is a ubiquitous molecule and its kinase activity and scaffold properties brought to several investigations which have evidenced its involvement in pathophysiology of extra-cardiac diseases. Later discoveries, moreover, indicated that this molecule is also able to influence other pathways such as insulin signaling by an inhibitory role similar to what described years before on βAR signaling. The importance of this novel function is in particular related to the possibility that this molecule can regulate the cellular metabolism, modifying the ability of cells to utilize different sub... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579953 Tue, 10 Jan 2012 05:00:00 +0100 5579953 http://www.medworm.com/index.php?rid=5579952&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229581%26dopt%3DAbstract Authors: Panaro MA, Cianciulli A Abstract Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopamine neurons in the substantia nigra pars compacta. To date, although a bulk of evidence suggests that the etiology of PD is multifactorial, none of the mechanisms yet proposed have been considered conclusive. Activated glia seem to play a critical role in the degeneration of nigral dopaminergic neurons in PD, by secreting a complex array of cytokines, chemokines, proteolytic enzymes, reactive oxygen/nitrogen species and complement proteins that may have deleterious effects on the dopaminergic system. Recently, it has been reported that microglia activation and immunity are key factors contributing to disease progression. Here, we r... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579952 Tue, 10 Jan 2012 05:00:00 +0100 5579952 http://www.medworm.com/index.php?rid=5579951&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229582%26dopt%3DAbstract Authors: Weber MS, Menge T, Lehmann-Horn K, Kronsbein HC, Zettl U, Sellner J, Hemmer B, Stüve O Abstract Recent years have broadened the spectrum of therapeutic strategies and specific agents for treatment of multiple sclerosis (MS). While immune-modulating drugs remain the first-line agents for MSpredominantly due to their benign safety profile, our growing understanding of key processes in initiation and progression of MS has pioneered development of new agents with specific targets. One concept of these novel drugs is to hamper migration of immune cells towards the affected central nervous system (CNS). The first oral drug approved for MS therapy, fingolimodinhibits egress of lymphocytes from lymph nodes; the monoclonal antibody natalizumab prevents inflammatory CNS infiltratio... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5579951 Tue, 10 Jan 2012 05:00:00 +0100 5579951 http://www.medworm.com/index.php?rid=5566684&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22211684%26dopt%3DAbstract Authors: Magrone T, Jirillo E PMID: 22211684 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5566684 Sun, 01 Jan 2012 05:00:00 +0100 5566684 http://www.medworm.com/index.php?rid=5566683&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22211685%26dopt%3DAbstract Authors: Andrade JP, Assunção M Abstract Dietary antioxidant compounds, due to their pivotal role in the modulation of cellular redox mechanisms, are gaining attention of researchers in the field of brain aging and related degenerative diseases. In this perspective, green tea (GT) can be an excellent resource, as it contains large amounts of brain-accessible polyphenols. Many of these compounds are monomeric catechins, which have been shown to exert antioxidant effects, acting directly as radical scavengers or metal-chelators. In the current article, we review the general properties of GT, the direct antioxidant action of its polyphenols and the fine modulation of signaling systems related to survival and antioxidant defenses in the central nervous system of aging rats. The effec... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5566683 Sun, 01 Jan 2012 05:00:00 +0100 5566683 http://www.medworm.com/index.php?rid=5566682&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22211686%26dopt%3DAbstract Authors: Li F, Gong Q, Dong H, Shi J Abstract The polyphenolic compound resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phytochemical which has been found in more than 70 plant species, including herbs and human food products such as grapes, berries, and peanuts. Resveratrol was first isolated in 1940; however, little attention was paid to it until its benefits in coronary heart disease were studied in 1992. Since then, increasing evidence has indicated that resveratrol may be useful in treating cardiovascular diseases, cancers, pain, inflammation, tissue injury, and in reducing the risk of neurodegenerative disorders, especially Alzheimer's disease (AD). AD is characterized by a progressive dementia, and is one of the most common neurodegenerative disorders in the... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5566682 Sun, 01 Jan 2012 05:00:00 +0100 5566682 http://www.medworm.com/index.php?rid=5566681&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22211687%26dopt%3DAbstract Authors: Marzulli G, Magrone T, Kawaguchi K, Kumazawa Y, Jirillo E Abstract The onset of neurodegenerative diseases has become more frequent than in the past also in relation to inappropriate dietary habits adopted in the western world. Nutraceuticals are currently investigated in order to prevent or retard the outcome of the so-called diet-related diseases, even including neurodegenerative pathologies. Here, we have in vitro studied the ability of fermented grape marc (FGM) from Negroamaro (N) and Koshu (K) Vitis vinifera to modulate the function of human peripheral blood mononuclear cells (PBMCs). Actually, both FGMs were able to increase the release and the intracellular content of inflammatory and anti-inflammatory cytokines, the induction of FoxP3 (a biomarker of T regulatory ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5566681 Sun, 01 Jan 2012 05:00:00 +0100 5566681 http://www.medworm.com/index.php?rid=5566680&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22211688%26dopt%3DAbstract Authors: Ozawa Y, Sasaki M, Takahashi N, Kamoshita M, Miyake S, Tsubota K Abstract Although a large variety of pharmaceutical therapies for treating disease have been developed in recent years, there has been little progress in disease prevention. In particular, the protection of neural tissue is essential, because it is hardly regenerated. The use of nutraceuticals for maintaining the health has been supported by several clinical studies, including cross-sectional and interventional studies for age-related macular disease. However, mechanistic evidence for their effects at the molecular level has been very limited. In this review, we focus on lutein, which is a xanthophyll type of carotenoid. Lutein is not synthesized in mammals, and must be obtained from the diet. It is delivered... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5566680 Sun, 01 Jan 2012 05:00:00 +0100 5566680 http://www.medworm.com/index.php?rid=5566679&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22211689%26dopt%3DAbstract Authors: Kim HG, Oh MS Abstract Alzheimer's disease (AD) is a chronic neurodegenerative disorder and is the most common cause of progressive dementia in aging. Research on AD therapy has been partly successful in terms of developing symptomatic treatments, but there have been a number of failures with regard to developing disease-modifying therapies. The pathogenesis of AD remains unclear and the present one-drug, one-target paradigm for anti-AD treatment appears to be clinically unsuccessful. In many countries, traditional herbal medicines are used to prevent or treat neurodegenerative disorders, and some have been developed as nutraceuticals or functional foods. This review briefly introduces progress in the development of anti-AD treatments and then focuses on recent advances in... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5566679 Sun, 01 Jan 2012 05:00:00 +0100 5566679 http://www.medworm.com/index.php?rid=5566678&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22211690%26dopt%3DAbstract Authors: Gadad BS, Subramanya PK, Pullabhatla S, Shantharam IS, Rao KS Abstract α-Synuclein aggregation is centrally implicated in Parkinson's disease (PD). It involves multi-step nucleated polymerization process via the formation of dimers, soluble toxic oligomers and insoluble fibrils. In the present study, we synthesized a novel compound viz., Curcumin-glucoside (Curc-gluc), a modified form of curcumin and studied its anti-aggregating potential with α-synuclein. Under aggregating conditions in vitro, Curc-gluc prevents oligomer formation as well as inhibits fibril formation indicating favorable stoichiometry for inhibition. The binding efficacies of Curc-gluc to both α-synuclein monomeric and oligomeric forms were characterized by micro-calorimetry. It was observed that titra... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5566678 Sun, 01 Jan 2012 05:00:00 +0100 5566678 http://www.medworm.com/index.php?rid=5566677&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22211691%26dopt%3DAbstract Authors: Mythri RB, Bharath MS Abstract Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequentl... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5566677 Sun, 01 Jan 2012 05:00:00 +0100 5566677 http://www.medworm.com/index.php?rid=5537372&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22114897%26dopt%3DAbstract Authors: Frati C, Savi M, Graiani G, Lagrasta C, Cavalli S, Prezioso L, Rossetti P, Mangiaracina C, Ferraro F, Madeddu D, Musso E, Stilli D, Rossini A, Falco A, Angelis AD, Rossi F, Urbanek K, Leri A, Kajstura J, Anversa P, Quaini E, Quaini F Abstract The introduction of stem cells in cardiology provides new tools in understanding the regenerative processes of the normal and pathologic heart and opens new options for the treatment of cardiovascular diseases. The feasibility of adult bone marrow autologous and allogenic cell therapy of ischemic cardiomyopathies has been demonstrated in humans. However, many unresolved questions remain to link experimental with clinical observations. The demonstration that the heart is a self-renewing organ and that its cell turnover is regulated by ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537372 Sun, 25 Dec 2011 01:00:09 +0100 5537372 http://www.medworm.com/index.php?rid=5537371&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188446%26dopt%3DAbstract Authors: Victor VM PMID: 22188446 [PubMed - in process] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537371 Thu, 01 Dec 2011 05:00:00 +0100 5537371 http://www.medworm.com/index.php?rid=5537370&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188447%26dopt%3DAbstract Authors: Victor VM, Rocha M, Herance R, Hernandez-Mijares A Abstract Diabetes is a chronic disease and as a consequence of the overproduction of reactive oxygen species (ROS), is related with oxidative stress. There are different sources of ROS, of which mitochondria is the main one. Oxidative stress seems to play an important role in mitochondria- mediated disease processes, though the exact molecular mechanisms responsible remain elusive. There are evidences which supports the idea that impaired mitochondrial function is a cause of the insulin insensitivity in different type of cells that arised as a result of an insufficient supply of energy or defects in the insulin signaling pathway. ROS are generally necessary for the proper functioning of the cell, but excessive ROS producti... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537370 Thu, 01 Dec 2011 05:00:00 +0100 5537370 http://www.medworm.com/index.php?rid=5537369&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188448%26dopt%3DAbstract Authors: Vina J, Gambini J, Lopez-Grueso R, Abdelaziz KM, Jove M, Borras C Abstract One of the most significant achievements of the twentieth century is the increase in human lifespan. In any period studied, females live longer than males. We showed that mitochondrial oxidative stress is higher in males than females and that the higher levels of estrogens in females protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. The chemical structure of estradiol confers antioxidant properties to the molecule. However, the low concentration of estrogens in females makes it unlikely that they exhibit significant antioxidant capacity in the organism. Therefore we studied the mechanisms enabling estradiol to be antioxidant at physiological levels... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537369 Thu, 01 Dec 2011 05:00:00 +0100 5537369 http://www.medworm.com/index.php?rid=5537368&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188449%26dopt%3DAbstract Authors: Fuente Mde L, Cruces J, Hernandez O, Ortega E Abstract The aging process is accompanied by an impairment of the physiological systems including the immune system. This system is an excellent indicator of health. We have also observed that several functions of the immune cells are good markers of biological age and predictors of longevity. In agreement with the oxidation-inflammation theory that we have proposed, the chronic oxidative stress that appears with age affects all cells and especially those of the regulatory systems, such as the nervous, endocrine and immune systems and the communication between them. This fact prevents an adequate homeostasis and, therefore, the preservation of health. We have also proposed an involvement of the immune system in the aging proces... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537368 Thu, 01 Dec 2011 05:00:00 +0100 5537368 http://www.medworm.com/index.php?rid=5537367&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188450%26dopt%3DAbstract Authors: Leonarduzzi G, Sottero B, Testa G, Biasi F, Poli G Abstract The complex system of molecular communications underlying cell biochemistry and function involves numerous components including kinases, phosphatases and transcription factors, which are known to be sensitive to cellular and tissue redox changes. Reactive oxygen species (ROS), whose constitutive generation in cells and tissues is amplified under pro-oxidant conditions, are now unanimously recognized to be important triggers and modulators of cell signaling, and consequently of cell behavior. This review considers the major signaling pathways that mediate gene regulation in response to ROS. PMID: 22188450 [PubMed - in process] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537367 Thu, 01 Dec 2011 05:00:00 +0100 5537367 http://www.medworm.com/index.php?rid=5537366&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188451%26dopt%3DAbstract Authors: Kastle M, Grune T Abstract Living in an oxygen containing environment is automatically connected to oxidative stress. Beside lipids and nucleic acids, especially proteins are very susceptible for oxidative modifications. These oxidative modifications comprise alterations of single amino acids, like the formation of protein carbonyls and methionine sulfoxide, or the aggregation of whole proteins. Due to the ongoing accumulation of protein aggregates during the aging process, the cellular protein quality control system becomes more and more overwhelmed. One essential element of the protein quality control machinery is the ubiquitin proteasomal system which plays therefore a crucial part in the aging process, too. Ubiquitination of proteins is a three step mechanism to tag pr... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537366 Thu, 01 Dec 2011 05:00:00 +0100 5537366 http://www.medworm.com/index.php?rid=5537365&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188452%26dopt%3DAbstract Authors: Blanchet L, Buydens MC, Smeitink JA, Willems PH, Koopman WJ Abstract Mitochondrial dysfunction has been implicated in many human diseases and off-target drug effects. Isolated deficiency of mitochondrial complex I (CI), the first complex of the oxidative phosphorylation (OXPHOS) system, can arise from mutations in nuclear DNA (nDNA)-encoded subunits. In humans, these mutations are generally associated with neurodegenerative disorders like Leigh or Leigh-like syndrome with onset in early childhood. Currently, no cure or mitigative treatment is available for these diseases. To aid the future design of rational treatment strategies, insight into the pathophysiology of CI mutations is required. To this end, we quantitatively compared various cell physiological readouts between... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537365 Thu, 01 Dec 2011 05:00:00 +0100 5537365 http://www.medworm.com/index.php?rid=5537364&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188453%26dopt%3DAbstract Authors: Gogvadze V Abstract During the last years, there have been a number of reports that prove involvement of mitochondria in the pathogenesis of variety of disorders including cancer and neurodegenerative diseases. Alteration of vital mitochondrial functions - production of ATP, calcium buffering capacity, abnormal production of reactive oxygen species, can be potentially responsible for pathogenesis of cancer and neurodegenerative diseases. Involvement of mitochondria in various types of cell death makes them attractive targets for tumor cell elimination. This review describes the role of mitochondria in tumor cells and how targeting of mitochondria can be used as a tool in fighting cancer. PMID: 22188453 [PubMed - in process] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537364 Thu, 01 Dec 2011 05:00:00 +0100 5537364 http://www.medworm.com/index.php?rid=5537363&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188454%26dopt%3DAbstract Authors: Apostolova N, Blas-Garcia A, Esplugues JV Abstract Mitochondria are crucial, multifunctional organelles which actively regulate cellular homeostasis. Their complex and diverse role includes maintenance of the cellular energetic balance through hosting several catabolic pathways which result in the process of oxidative phosphorylation, as well as enabling various fundamental anabolic processes and controlling Ca2+ distribution. Moreover, mitochondria are the main cellular generator of reactive oxygen species, which act as second messengers and when over-produced provoke a state of oxidative stress, a condition implicated in many pathologies. Importantly, mitochondria are directly involved in triggering different and complexly interconnected programs promoting cell survival ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537363 Thu, 01 Dec 2011 05:00:00 +0100 5537363 http://www.medworm.com/index.php?rid=5537362&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188455%26dopt%3DAbstract Authors: Rocha M, Banuls C, Bellod L, Jover A, Victor VM, Hernandez-Mijares A Abstract Phytosterols, which are structurally related to cholesterol, are found in all plant foods with highest concentration occurring in vegetable oils and nuts. Phytosterols are known to reduce serum low-density lipoprotein cholesterol level without changing high-density lipoprotein cholesterol or triglyceride levels. Daily consumption of phytosterols-enriched foods is widely used as a therapeutic option to lower plasma cholesterol and atherosclerotic disease risk. The cholesterol-lowering action of phytosterols is thought to occur, at least in part, through competitive replacement of dietary and biliary cholesterol in mixed micelles, which undermines the absorption of cholesterol. The aim of this revi... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537362 Thu, 01 Dec 2011 05:00:00 +0100 5537362 http://www.medworm.com/index.php?rid=5537361&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188456%26dopt%3DAbstract Authors: Blas-Garcia A, Apostolova N, Esplugues JV Abstract Thirty years after the discovery of HIV infection, there are numerous antiretroviral drugs that control the disease when administered in a potent combination referred to as Highly Active Antiretroviral Therapy (HAART). This therapy reduces the viral load and improves immune system reconstitution, leading to a significant reduction of HIV-related morbidity and mortality. However, HAART does not completely eliminate HIV, so treatment must continue throughout the patient's life. Prolonged use of HAART has been related to long-term adverse events that can compromise patient health. These deleterious effects have been reported for the majority of antiretroviral drugs and are the most common causes for therapy discontinuation. I... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5537361 Thu, 01 Dec 2011 05:00:00 +0100 5537361 http://www.medworm.com/index.php?rid=5444124&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103844%26dopt%3DAbstract Authors: Heneberg P Abstract Since the times of P. Ehrlich, F. D. von Recklinghausen, and O.Westphal, the research on mast cells and basophils made significant progression towards the recognition of their involvement in antimicrobial functions and of their role in mobilizing inflammation in wound healing, allergy, and autoimmunity. However, the role of mast cells in normal physiology is still poorly understood. Only in recent years, these cells are increasingly recognized as important effectors in number of pathways related mostly to tissue remodeling. The mast cells are capable to orchestrate inflammatory reactions and angiogenesis, they are frequently present near pre-neoplastic epithelial cells, etc. Absolute mast cell deficiency, as in the cross of Min mice to the C57BL/6-KitWs... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444124 Tue, 22 Nov 2011 05:00:00 +0100 5444124 http://www.medworm.com/index.php?rid=5444123&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103845%26dopt%3DAbstract Authors: Reid AC, Brazin JA, Morrey C, Silver RB, Levi R Abstract Enhanced production of angiotensin II and excessive release of norepinephrine in the ischemic heart are major causes of arrhythmias and sudden cardiac death. Mast cell-dependent mechanisms are pivotal in the local formation of angiotensin II and modulation of norepinephrine release in cardiac pathophysiology. Cardiac mast cells increase in number in myocardial ischemia and are located in close proximity to sympathetic neurons expressing angiotensin AT1- and histamine H3-receptors. Once activated, cardiac mast cells release a host of potent pro-inflammatory and pro-fibrotic cytokines, chemokines, preformed mediators (e.g., histamine) and proteases (e.g., renin). In myocardial ischemia, angiotensin II (formed locally f... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444123 Tue, 22 Nov 2011 05:00:00 +0100 5444123 http://www.medworm.com/index.php?rid=5444122&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103846%26dopt%3DAbstract Authors: Heneberg P Abstract Cancer microenvironment is increasingly recognized as an important factor affecting cancer onset and progression. Since Wirchow reported in 1863 that tumors contain inflammatory cells, the field shifted significantly forward, and immune cells residing in tumors appear to be attractive targets of cancer therapies. For some methods, such as stem/progenitor cell isolation from both cancer and healthy tissues, removal of contaminating immune cells is crucial to achieve consistent, reproducible and accurate results. Despite current methods of lineage negative selection accounts for removal of over 99 % of immune cells from stem/progenitor cell isolates, the vast majority of lineage antibody cocktails retain basophils, dendritic cells, and mast cells. Here we... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444122 Tue, 22 Nov 2011 05:00:00 +0100 5444122 http://www.medworm.com/index.php?rid=5444121&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103847%26dopt%3DAbstract Authors: Kennelly R, Conneely JB, Bouchier-Hayes D, Winter DC Abstract Mast cells are largely found at interfaces between the environment and the internal milieu. Early knowledge of the mast cell suggested a role predominantly associated with allergy and pathologic response to antigens, but more recent research has shown a myriad of functions is likely. Wound healing is a complex process of lysis and reconstitution controlled by a series of cell signalling proteins. Mast cells have been shown to play a significant role in the early inflammatory stage of wound healing and also influence proliferation and tissue remodelling in skin. Emerging work implicates the mast cell as a modulator of intestinal healing particularly following surgical anastomosis. The study of mast cells and woun... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444121 Tue, 22 Nov 2011 05:00:00 +0100 5444121 http://www.medworm.com/index.php?rid=5444120&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103848%26dopt%3DAbstract Authors: Azuma YT, Nakajima H, Takeuchi T Abstract Interleukin-19 (IL-19) is a member of the IL-10 family of cytokines. The last ten years from the finding of IL-19, investigations underline the role of IL-19 in the immunological diseases. It is known that expression of IL-19 is increased in the epidermis of patients with psoriasis, which is a Th1 dominant disease. Increased concentration of IL-19 has also been found in the serum of patients with asthma, which is a Th2 dominant disease. There is an increasing body of data demonstrating that IL-19 is associated with the pathogenesis of both Th1 and Th2 dominant diseases. Regarding the role of IL-19 on the innate immunity and inflammation, interestingly, in vitro studies have shown that lipopolysaccharide can stimulate human monocyte... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444120 Tue, 22 Nov 2011 05:00:00 +0100 5444120 http://www.medworm.com/index.php?rid=5444119&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103849%26dopt%3DAbstract Authors: Saadoun D, Terrier B, Cacoub P Abstract Polarization of naïve T cells in a certain functional direction is influenced not only by antigen type and concentration, but also by co-stimulatory signals, the local cytokine environment and transcription factors that activate or inhibit specific T cell lineage programs through positive or negative feedback loops. Interleukin-25 (IL-25) is a recently identified member of the IL-17 cytokine family. It has the ability to influence innate and adaptative immunity. Within the IL-17 family, IL-25 possesses the lowest degree of homology to IL- 17A, does not share common biological functions with other members of the IL-17 cytokine family, and instead has been been implicated in the promotion of Th2 immunity. IL-25 drives the expression o... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444119 Tue, 22 Nov 2011 05:00:00 +0100 5444119 http://www.medworm.com/index.php?rid=5444114&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103850%26dopt%3DAbstract Authors: Wolanczyk-Medrala A, Barg W, Medrala W Abstract Introduction of flow cytometric technique to the research on basophil activation has led to significant achievements in allergy diagnosis in vitro. Most of the studies employing the flow cytometry used CD63 as a marker of basophil activation and only some of them used CD203c. Recently discovered basophil activation markers, including CD164, opened new possibilities for solving majority of current diagnostic needs. Use of allergen-induced CD164 upregulation in diagnosis of pollen allergy has been validated, and this encourages to further studies on other diagnostic usefulness of this marker. There are some hopeful data indicating that it might be useful in diagnosis of allergy caused by variety of other allergens, including dr... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444114 Tue, 22 Nov 2011 05:00:00 +0100 5444114 http://www.medworm.com/index.php?rid=5444102&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103851%26dopt%3DAbstract Authors: Shefler I, Salamon P, Hershko AY, Mekori YA Abstract In addition to being major effector cells in the elicitation of allergic responses, mast cells have been found to play a significant role in the establishment of innate and adaptive immune responses. This occurs, in part, by regulating the phenotype and function of immune cells such as T cells, B cells and dendritic cells, and by acting as antigen presenting cells. Indeed, mast cells have been found to be activated in various T cell-mediated inflammatory processes and to reside in close physical proximity to T cells. Such observations have led investigators to propose a functional relationship between these two cell populations. Mast cells can interact with other cells including T cells in several ways such as cell-cell ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444102 Tue, 22 Nov 2011 05:00:00 +0100 5444102 http://www.medworm.com/index.php?rid=5444101&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103852%26dopt%3DAbstract Authors: Suzuki Y, Inoue T, Ra C Abstract The three heavy metals, mercury, gold and silver commonly and specifically induce aberrant immunological responses leading to autoimmune disorders in genetically susceptible animals and humans. The disorders are characterized by autoantibody production, increases in serum IgG and IgE, polyclonal activation of B and T lymphocytes and renal immune complex deposition and glomerulonephritis. Mast cells play key roles in allergic and inflammatory reactions. A growing body of evidence suggests that mast cells are key players in innate and adaptive immunity and involved in autoimmune diseases. Mast cells are also direct targets for autoimmunity-inducing metals both in vitro and in vivo and play a role in the development of metal-induced autoimmune... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444101 Tue, 22 Nov 2011 05:00:00 +0100 5444101 http://www.medworm.com/index.php?rid=5444100&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103853%26dopt%3DAbstract Authors: Shenker BJ, Ali H, Boesze-Battaglia K Abstract It is well established that mast cells play a key regulatory role in allergy and inflammation involving engagement of antigen with IgE bound to high-affinity IgE receptors (FcεRI). The most aggressive efforts in regulating mast cell function have focused on selectively inhibiting cell activation and subsequent mediator synthesis and release, or alternatively, blocking the action of proinflammatory mediators in order to prevent or reduce disease severity. More recently, the goal for rationally designed pharmacotherapy has shifted focus to targeting and disrupting signaling pathways leading to inhibition of specific cell function(s). In this context, the PI-3K/PIP3/Akt pathway represents a potent target for pharmacologic interv... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444100 Tue, 22 Nov 2011 05:00:00 +0100 5444100 http://www.medworm.com/index.php?rid=5444099&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103854%26dopt%3DAbstract Authors: Triggiani M, Loffredo S, Granata F, Staiano RI Abstract Benzene is a carcinogenic compound used in industrial manufacturing and a common environmental pollutant mostly derived from vehicle emissions and cigarette smoke. Benzene exposure is associated with a variety of clinical conditions ranging from hematologic diseases to chronic lung disorders. Beside its direct toxicity, benzene exerts multiple effects after being converted to reactive metabolites such as hydroquinone and benzoquinone. Mast cells and basophils are primary effector cells involved in the development of respiratory allergies such as rhinitis and bronchial asthma and they play an important role in innate immunity. Benzene and its metabolites can influence mast cell and basophil responses either directly or... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5444099 Tue, 22 Nov 2011 05:00:00 +0100 5444099 http://www.medworm.com/index.php?rid=5426698&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074420%26dopt%3DAbstract Authors: Jampilek J PMID: 22074420 [PubMed - in process] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426698 Sun, 20 Nov 2011 00:42:02 +0100 5426698 http://www.medworm.com/index.php?rid=5426697&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074421%26dopt%3DAbstract Authors: Stefano AD, Sozio P, Cerasa LS, Iannitelli A Abstract L-Dopa is the mainstay of Parkinson's disease therapy; this drug is usually administered orally, but it is extensively metabolized in the gastrointestinal tract, so that relatively little arrives in the bloodstream as intact L-Dopa. The peripheral conversion of L-Dopa by amino acid decarboxylase to dopamine is responsible for the typical gastrointestinal and cardiovascular side effects. To minimize the conversion to dopamine outside the central nervous system, L-Dopa is usually given in combination with peripheral inhibitors of amino acid decarboxylase. In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for t... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426697 Sun, 20 Nov 2011 00:42:02 +0100 5426697 http://www.medworm.com/index.php?rid=5426696&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074422%26dopt%3DAbstract This article brings together the known basic facts about these prodrugs, particularly about the different mechanisms of the antimicrobial action of salicylanilides, including salicylanilide toxicity and undesired effects. The largest part of this group consists of antimicrobial salicylanilide esters with different organic acids, e.g. acetates, carbamates, esters with N-protected amino acids, and mutual antibacterial compounds with known antibacterial agents ( -lactames and linezolid), with the activity and structure-activity relationships of these compounds being of particular interest. This review summarizes the activity of salicylanilides as potential virulence inhibitors attributable to a blockade of the type III secretion pathway. Many salicylanilide ester derivatives have been demonst... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426696 Sun, 20 Nov 2011 00:42:02 +0100 5426696 http://www.medworm.com/index.php?rid=5426680&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074423%26dopt%3DAbstract Authors: Dolezal M, Kesetovic D, Zitko J Abstract Design, results of in vitro antimycobacterial evaluation, and study of structure-activity relationships of various pyrazinecarboxylic acid reversible derivatives are presented. This review deals with some pyrazinamide analogues/prodrugs derived from Nphenylpyrazine- 2-carboxamides (1), arylaminopyrazine-2,5-dicarbonitriles (2), aryl/alkylsulphanylpyrazines (3,4), and aroylpyrazines (5) effecting >50% inhibition in the primary antimycobacterial screen. The promising pyrazine candidates for further antimycobacterial evaluation were discovered. Results give good view onto structure-activity relationships of these analogues and promise even better activity of new compounds prepared after some structure optimization experiments. P... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426680 Sun, 20 Nov 2011 00:42:02 +0100 5426680 http://www.medworm.com/index.php?rid=5426671&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074424%26dopt%3DAbstract Authors: Chung MC, Bosquesi PL, Dos Santos JL Abstract In therapeutics research, the nitro compounds are part of an important group of drugs with multiple pharmacological activities. However, in drug design, the inclusion of a nitro group in a molecule changes the physico-chemical and electronic properties and is associated with increased mutagenicity and carcinogenicity. In addition, several studies have related the relationship between the antimicrobial and/or anti-protozoal activity and the mutagenic effect to reduction of the nitro group. This work reviews the toxicity of nitro compounds and shows how the use of prodrugs can increase the biological activity and decrease the genotoxicity of nitro compounds, without any modification in nitro reduction behavior, but rather by phys... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426671 Sun, 20 Nov 2011 00:42:02 +0100 5426671 http://www.medworm.com/index.php?rid=5426670&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074425%26dopt%3DAbstract Authors: Tietze LF, Schmuck K Abstract The treatment of cancer with common anti-proliferative agents generally suffers from an insufficient differentiation between normal and malignant cells which results in extensive side effects. To enhance the efficacy and reduce the normal tissue toxicity of anticancer drugs, numerous selective tumor therapies have emerged including the highly promising approaches ADEPT (Antibody-Directed Enzyme Prodrug Therapy), GDEPT (Gene-Directed Enzyme Prodrug Therapy) and PMT (Prodrug Monotherapy). These allow a selective release of cytotoxic agents from non-toxic prodrugs at the tumor site either by targeted antibody-enzyme conjugates, enzyme encoding genes or by exploiting physiological and metabolic aberrations in cancerous tissue. Herein, recent devel... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426670 Sun, 20 Nov 2011 00:42:02 +0100 5426670 http://www.medworm.com/index.php?rid=5426669&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074426%26dopt%3DAbstract Authors: Musiol R, Serda M, Polanski J Abstract Photodynamic therapy (PDT), the concept of cancer treatment through the selective uptake of a light-sensitive agent followed by exposure to a specific wavelength, is limited by the transport of a photosensitizer (PS) to the tumor tissue. Porphyrin, an important PS class, can be used in PDT in the form of its prodrug molecule 5-aminolevulinic acid (5-ALA). Unfortunately, its poor pharmacokinetic properties make this compound difficult to administer. Two different methods for eliminating this problem can be distinguished. The first approach is to play with its formulation in order to improve the drug's applicability. The second approach, which is to find possible 5- ALA prodrugs, is an example of the double-prodrug method, a strategy of... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426669 Sun, 20 Nov 2011 00:42:02 +0100 5426669 http://www.medworm.com/index.php?rid=5426668&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074427%26dopt%3DAbstract Authors: Pavana B, Dalpiaz A Abstract Hydrophilic drugs, or neuroactive agents characterized by high molecular weight, do not have the physico-chemical properties required for passive diffusion across the blood brain barrier (BBB). The prodrug approach by lipidization of hydrophilic drugs generally allows to sensibly increase their permeability across BBB, even if this phenomenon is often not associated to an effective entry into the brain of the lipidized drugs. It has been understood that active efflux transporters (AET) can have a very important role in extruding from the brain not only prodrugs obtained by lipidization processes, but also lipophilic drugs. On the other hand, it has been also demonstrated that carrier mediated transporters (CMT), able to transfer essential nutri... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426668 Sun, 20 Nov 2011 00:42:02 +0100 5426668 http://www.medworm.com/index.php?rid=5426667&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074428%26dopt%3DAbstract Authors: Bílková E, Imramovsky A, Sedlák M Abstract Glucocorticoid drugs are commonly used in the treatment of many acute and chronic inflammatory diseases. However, application of these steroids is limited because of their physico-chemical properties, such as very low water solubility. Glucocorticoids also exhibit serious adverse side effects. Therefore, new drug delivery systems are being developed, with the aim of improving the physicochemical properties of glucocorticoids while avoiding undesirable side effects associated with systemic administration. Here we discuss the design and synthesis of conjugates of prednisolone (PD), methylprednisolone (MPD) and similar glucocorticoids. In this review, possibilities for targeting inflammatory sites, and reducing dosages and adminis... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426667 Sun, 20 Nov 2011 00:42:02 +0100 5426667 http://www.medworm.com/index.php?rid=5426666&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074429%26dopt%3DAbstract Authors: Jarmila V, Vavríková E Abstract Chitosan is a linear polysaccharide with a good biodegradability, biocompatibility, and no toxicity, which provide it with huge potential for future development. The chitosan molecule appears to be a suitable polymeric complex for many biomedical applications. This review gathers current findings on the antibacterial, antifungal, antitumour and antioxidant activities of chitosan derivatives and concurs with our previous review presenting data collected up to 2008. Antibacterial activity is based on molecular weight, the degree of deacetylation, the type of substitutents, which can be cationic or easily form cations, and the type of bacterium. In general, high molecular weight chitosan cannot pass through cell membranes and forms a film tha... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426666 Sun, 20 Nov 2011 00:42:02 +0100 5426666 http://www.medworm.com/index.php?rid=5426664&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074430%26dopt%3DAbstract Authors: Rizzo M, Mikhailidis DP Abstract Cardiovascular disease (CVD) still represents a leading cause of death worldwide [1,2]. Despite aggressive treatment guidelines, the persistent residual risk of events has prompted research into new approaches aimed at reducing the atherosclerotic burden [3,4]. The present issue of the journal focuses on new developments in the prevention and treatment of vascular disease. We discuss the reviews included in this issue as well as other topics. PMID: 22074430 [PubMed - in process] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426664 Tue, 01 Nov 2011 04:00:00 +0100 5426664 http://www.medworm.com/index.php?rid=5426662&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074431%26dopt%3DAbstract Authors: Ahmed BA, Seda O, Lavoie JL Abstract Over the last few years, the implication of the (pro)renin receptor [(P)RR] in the pathogenesis of end-organ damage has been shown through many different studies. The (P)RR plays a dual role when stimulated by renin or prorenin as it enhances both cell surface production of angiotensin and stimulates angiotensin-independent intracellular signaling cascades. Since Ichihara's group demonstrated activation of prorenin when it was bound to antibodies targeted against a specific region in the renin prosegment, they designed a complementary decapeptide to this region called the handle region to use as a potential (P)RR blocker (PRRB). The effects of systemic administration of the PRRB on the development and progression of different renal, car... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426662 Tue, 01 Nov 2011 04:00:00 +0100 5426662 http://www.medworm.com/index.php?rid=5426660&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074432%26dopt%3DAbstract Authors: Lioudaki E, Ganotakis ES, Mikhailidis DP Abstract Cholelithiasis is a common disease worldwide. The majority of gallstones can occur when the bile is supersaturated with cholesterol. Dyslipidaemia, obesity, insulin resistance are associated with an increased risk for cholesterol gallstone formation as well as with vascular risk. Statins and ezetimibe are used to treat dyslipidaemia and appear to have some effect on bile composition and cholesterol gallstone formation. Statin (e.g. pravastatin, simvastatin, fluvastatin and lovastatin) monotherapy or combined with ursodeoxycholic acid (UDCA) have shown reductions in bile cholesterol saturation, preventing gallstone formation and even dissolving pre-existing stones. However, this effect was not consistently reported in all st... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426660 Tue, 01 Nov 2011 04:00:00 +0100 5426660 http://www.medworm.com/index.php?rid=5426659&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074433%26dopt%3DAbstract Authors: Mikhailidis DP, Lioudaki E, Ganotakis ES Abstract Several cross-sectional studies have reported a relationship between elevated serum activity of liver enzymes [e.g. alanine aminotransferase (ALT) and gamma-glutamyltransferase (γGT)] and metabolic syndrome (MetS) and/or diabetes mellitus (DM). Raised serum activity of liver enzymes independently predicted the future development of MetS and DM as well as cardiovascular (CV) events and/or total/CV mortality in prospective studies. However, this association was not consistently demonstrated and it appears to be independent of alcohol intake. Even though these associations can be partly attributed to non-alcoholic fatty liver disease (NAFLD) and insulin resistance, there may be additional underlying mechanisms that contribute... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426659 Tue, 01 Nov 2011 04:00:00 +0100 5426659 http://www.medworm.com/index.php?rid=5426658&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074434%26dopt%3DAbstract Authors: Breimer LH, Mikhailidis DP Abstract Normal aerobic metabolism is associated with reactive oxygen species (ROS) that can damage cellular macromolecules. Analogous free radicals are formed by exposure to ionizing radiation and many dietary products are considered to contain free radical generators. During the past 15 years epidemiological studies and animal experiments have identified bilirubin as a molecule at the crossroads of the protection of the body against ROS. The studies have focused on bilirubin as a biomarker of arterial disease. This review assesses the current state of evidence and sets the data in context. There is no definitive evidence from prospective studies of a causal protective effect from bilirubin in arterial disease or that various genetic polymorphis... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426658 Tue, 01 Nov 2011 04:00:00 +0100 5426658 http://www.medworm.com/index.php?rid=5426650&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074435%26dopt%3DAbstract Authors: Tselepis AF, Rizzo M, Goudevenos IA Abstract Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a calcium-independent phospholipase A2 that circulates in plasma in association with lipoprotein particles, whereas in atherosclerotic plaques it is co-localized with macrophages. Lp-PLA2 generates two proinflammatory mediators, lysophosphatidylcholine and oxidized nonesterified fatty acids, which play a role in the development of atherosclerotic lesions and formation of a necrotic core, leading to more vulnerable plaques. Epidemiologic studies demonstrate that increased circulating levels of Lp-PLA2 predict an increased risk of myocardial infarction, stroke and cardiovascular mortality. Furthermore, histologic examination of diseased human coronary arteries reveals intense pr... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426650 Tue, 01 Nov 2011 04:00:00 +0100 5426650 http://www.medworm.com/index.php?rid=5426649&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074436%26dopt%3DAbstract We present illustrative examples of specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicate a pathogenic role for HSP60 but also its potential as a biomarker with applications for diagnosis, assessing prognosis and response to treatment, as well as for preventing and treating CVD. PMID: 22074436 [PubMed - in process] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426649 Tue, 01 Nov 2011 04:00:00 +0100 5426649 http://www.medworm.com/index.php?rid=5426627&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074437%26dopt%3DAbstract In conclusion, non-adherence and discontinuation of statin therapy significantly increased the incidence of cardiovascular and cerebrovascular events as well as all-cause mortality in high-risk patients. Patients would therefore benefit from closer adherence assessment and education programs aimed at increasing awareness of the risk associated with discontinuation of statin therapy. PMID: 22074437 [PubMed - in process] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426627 Tue, 01 Nov 2011 04:00:00 +0100 5426627 http://www.medworm.com/index.php?rid=5426620&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074438%26dopt%3DAbstract Authors: Gouni-Berthold I, Berthold HK Abstract Evidence suggests that patient gender is associated with the quality of care provided in the treatment of cardiometabolic diseases. The majority of findings suggest that female patients receive less intensified care than male patients. However, the question whether physician gender plays a role in the quality of care has been debated for some time. For example, it has been postulated that the practice styles of female physicians, such as spending more time with a patient, hearing and listening more effectively, and including more preventive measures, may result in more efficient clinical encounters that may positively affect clinical outcomes. This narrative review examines the existing evidence regarding the effects of physician gend... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426620 Tue, 01 Nov 2011 04:00:00 +0100 5426620 http://www.medworm.com/index.php?rid=5426604&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22074439%26dopt%3DAbstract Authors: Haidara M, Mikhailidis DP, Yassin HZ, Dobutovic B, Smiljanic KT, Soskic S, Mousa SA, Rizzo M, Isenovic ER Abstract The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5426604 Tue, 01 Nov 2011 04:00:00 +0100 5426604 http://www.medworm.com/index.php?rid=5266521&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933138%26dopt%3DAbstract Authors: Malorni W, Vona R PMID: 21933138 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266521 Tue, 20 Sep 2011 04:00:00 +0100 5266521 http://www.medworm.com/index.php?rid=5266520&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933139%26dopt%3DAbstract Authors: Adams V, Anker SD, Schuler G Abstract Cachexia is often associated with severe loss of skeletal muscle mass and a reduced energy metabolism. The maintenance of muscle mass can be generally regarded as a simple balance between protein synthesis and protein degradation. Several evidences are available in the current literature favoring a model in which myofilaments are released from the sarcomere by the action of calcium-activated calpains followed by the degradation of the myofilaments by the ubiquitin proteasome system. The initiation of the protein breakdown machinery is regulated by several factors like inflammatory cytokines, angiotensin II, insulin / insulin like growth factor 1 and reactive oxygen species. These factors also have the capability to influence PGC-1alpha... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266520 Tue, 20 Sep 2011 04:00:00 +0100 5266520 http://www.medworm.com/index.php?rid=5266519&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933140%26dopt%3DAbstract Authors: Nagoshi T, Yoshimura M, Rosano GM, Lopaschuk GD, Mochizuki S Abstract The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metabolized. In contrast, glucose becomes an important preferential substrate for metabolism and ATP generation under specific pathological conditions, because it can provide greater efficiency in producing high energy products per oxygen consumed compared to fatty acids. Manipulations that shift energy substrate utilization away from fatty acids toward glucose can improve the cardiac function an... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266519 Tue, 20 Sep 2011 04:00:00 +0100 5266519 http://www.medworm.com/index.php?rid=5266518&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933141%26dopt%3DAbstract Authors: Smaili SS, Ureshino RP, Rodrigues L, Rocha KK, Carvalho JT, Oseki KT, Bincoletto C, Lopes GS, Hirata H Abstract Glutamate is an important neurotransmitter in neurons and glial cells and it is one of the keys to the neuron-glial interaction in the brain. Besides, glutamate transmission is strongly dependent on calcium homeostasis and on mitochondrial function. In the present work we presented several aspects related to the role of mitochondria in glutamate signaling and in brain diseases. We focused on glutamate-induced calcium signaling and its relation to the organelle dysfunction with cell death processes. In addition, we have discussed how alterations in this pathway may lead or aggravate a variety of neurodegenerative diseases. We compiled information on how mitochondr... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266518 Tue, 20 Sep 2011 04:00:00 +0100 5266518 http://www.medworm.com/index.php?rid=5266517&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933142%26dopt%3DAbstract Authors: Calcerrada P, Peluffo G, Radi R Abstract Nitric oxide participates in a wide array of physiological processes, ranging from neurotransmission to precursor of cytotoxic effector molecules of the immune system. Although nitric oxide is a mildly reactive intermediary, it can act as a precursor of strong oxidants under pathological conditions associated with oxidative stress including cardiovascular, inflammatory and neurodegenerative disorders. Peroxynitrite, the reaction product of nitric oxide with superoxide radicals, emerges as one of the principal players of nitric oxide-derived toxicity due to its facile formation and ability to react with several critical cellular targets including, thiols, proteins, lipids and DNA. The extent of "nitroxidative stress" is determined by... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266517 Tue, 20 Sep 2011 04:00:00 +0100 5266517 http://www.medworm.com/index.php?rid=5266516&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933143%26dopt%3DAbstract Authors: Manole MD, Tehranian-Depasquale R, Du L, Bayır H, Kochanek PM, Clark RS Abstract Both classic and emerging literature point to sex-based disparity in neuronal metabolism. While detectable under baseline conditions, this phenomenon appears to be exaggerated or sometimes unmasked in neurons by cellular stress. A complex sex-dependent response to nutrient deprivation, excitotoxicity, oxidative/nitrositive stress, oxygen-glucose deprivation, and chemical toxicity has been observed in neurons in vitro, as well as after various insults including ischemic or traumatic brain injury in vivo. Importantly, sex-based disparity in response to diverse therapeutics has been seen in neurons in culture, contemporary animal models of brain injury, and in human disease. These have clear imp... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266516 Tue, 20 Sep 2011 04:00:00 +0100 5266516 http://www.medworm.com/index.php?rid=5266515&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933144%26dopt%3DAbstract Authors: Pierdominici M, Vacirca D, Delunardo F, Ortona E Abstract The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that forms a multisubunit complex with numerous protein partners and it regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. A central role for mTOR in regulating T cell homeostasis is emerging. In various autoimmune diseases abnormal functioning, differentiation and/or activation of T cells have been documented and recent studies have detailed anomalous activation of various signaling axes including the mTOR pathway in these cells. In this review we summarize recent studies on the involvement of mTOR in T cell differentiation and metabolism, supporting a key role for this molecule ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266515 Tue, 20 Sep 2011 04:00:00 +0100 5266515 http://www.medworm.com/index.php?rid=5266514&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933145%26dopt%3DAbstract Authors: Viña J, Lloret A, Giraldo E, Badia MC, Alonso MD Abstract Alzheimer's disease (AD) is closely related to the occurrence of oxidative stress. It was claimed that all pathophysiological mechanisms involved in the onset and progression of AD are related to oxidative stress. Thus, it is important to evaluate if there is oxidative stress as well as the mechanism by which this happens in AD patients as well as in animal models of AD. Extracellular plaques of amyloid β peptides (Aβ), a hallmark of the disease, have been postulated to be more protective than damaging in terms of oxidative stress because they may be chemical sinks in which heavy metals are placed. More than a decade ago we reasoned that damage due to Aβ might be caused not by extracellular, but rather intracell... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266514 Tue, 20 Sep 2011 04:00:00 +0100 5266514 http://www.medworm.com/index.php?rid=5266513&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933146%26dopt%3DAbstract Authors: Garcia-Ruiz C, Marí M, Colell A, Morales A, Fernandez-Checa JC Abstract Fatty liver disease is one of most prevalent metabolic liver diseases, which includes alcoholic (ASH) and nonalcoholic steatohepatitis (NASH). Its initial stage is characterized by fat accumulation in the liver, that can progress to steatohepatitis, a stage of progression of the disease in which steatosis is accompanied by inflammation, hepatocellular death, oxidative stress and fibrosis. Recent evidence in experimental models as well as in patients with steatohepatitis have uncovered a role for cholesterol and sphingolipids, particularly ceramide, in the transition from steatosis to steatohepatitis, insulin resistance and hence disease progression. Cholesterol accumulation and its trafficking to mito... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266513 Tue, 20 Sep 2011 04:00:00 +0100 5266513 http://www.medworm.com/index.php?rid=5266512&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933147%26dopt%3DAbstract Authors: Nencioni L, Sgarbanti R, Amatore D, Checconi P, Celestino I, Limongi D, Anticoli S, Palamara AT, Garaci E Abstract Reactive oxygen and nitrogen species play complex roles in the physiological regulation of cell metabolism and in many disease processes as well, including viral infections. Viral replication occurs within living cells and is totally dependent on its host's biosynthetic machinery. Many intracellular signaling pathways exploited by viruses for their own replication are regulated by the oxidoreductive (redox) state of the host cell. Consequently, factors that alter the balance between reactive oxygen/nitrogen species and antioxidant molecules/enzymes-including metabolic conditions like malnutrition, obesity, and diabetes-can influence cells' susceptibility to vi... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266512 Tue, 20 Sep 2011 04:00:00 +0100 5266512 http://www.medworm.com/index.php?rid=5266511&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933148%26dopt%3DAbstract Authors: Del Principe D, Vona R, Giordani L, Straface E, Giammarioli AM Abstract Fibrosis may represent the final step induced by autoimmune mechanism(s). This may be due to the excess in fibroblast recruitment, activation and differentiation in myofibroblasts. These events may be triggered by cytokines, chemokines and growth factors released by lymphocytes or macrophages. Autophagy is an essential conserved homeostatic process that has long been appreciated for cell adaptation to nutrient deprivation. Autophagy is also recognized as an important component of both innate and acquired immunity to pathogens. Recently, dysregulation of autophagy in haematopoietic cells has been suggested to amplify the autoimmune responses. On the other hand, it is possible that defective autophagy in... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5266511 Tue, 20 Sep 2011 04:00:00 +0100 5266511 http://www.medworm.com/index.php?rid=5234695&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919874%26dopt%3DAbstract Authors: Templin C, Kränkel N, Lüscher TF, Landmesser U Abstract Cardiovascular disease disease remains the leading cause of morbidity and mortality in the developed countries. This review summarizes current pre-clinical and clinical evidence for the potential role and mechanisms of action of stem and progenitor cells in vascular and cardiac repair and regeneration. Apart from cell transplantation strategies, approaches to maintain stem cell niche function and targeting mobilization/recruitment of specific stem/progenitor cell populations may aid in preserving vascular and cardiac function. Moreover, with the use of patient-derived induced pluripotent stem cells, the field of regenerative medicine is entering a new era. Potential applications of induced pluripotent stem cells and... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234695 Thu, 15 Sep 2011 04:00:00 +0100 5234695 http://www.medworm.com/index.php?rid=5234694&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919875%26dopt%3DAbstract Authors: Van Linthout S, Spillmann F, Schultheiss HP, Tschöpe C Abstract Diabetic cardiopathy includes a specific cardiomyopathy, which occurs in the absence of coronary heart disease under diabetes mellitus. Hallmarks of diabetic cardiomyopathy are besides others interstitial inflammation, cardiac oxidative stress, interstitial and perivascular fibrosis, cardiac apoptosis, intramyocardial microangiopathy, endothelial dysfunction, abnormal intracellular Ca(2+)-handling, cardiomyocyte hypertrophy, and impaired cardiac stem cells. Since mesenchymal stromal cells have been shown to have anti-diabetic as well as cardioprotective features, we summarize in this review how they can indirectly affect diabetic cardiomyopathy via their influence on the metabolic trigger hyperglycemia, and h... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234694 Thu, 15 Sep 2011 04:00:00 +0100 5234694 http://www.medworm.com/index.php?rid=5234693&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919876%26dopt%3DAbstract Authors: Thorrez L, Sampaolesi M Abstract The field of stem cell research was revolutionized with the advent of induced pluripotent stem cells. By reprogramming somatic cells to pluripotent stem cells, most ethical concerns associated with the use of embryonic stem cells are overcome, such that many hopes from the stem cell field now seem a step closer to reality. Several methods and cell sources have been described to create induced pluripotent stem cells and we discuss their characteristics in terms of feasibility and efficiency. From these cells, cardiac progenitors and cardiomyocytes can be derived by several protocols and most recent advances as well as remaining limitations are being discussed. However in the short time period this technology has been around, evidence emerges... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234693 Thu, 15 Sep 2011 04:00:00 +0100 5234693 http://www.medworm.com/index.php?rid=5234692&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919877%26dopt%3DAbstract Authors: Dauwe DF, Janssens S Abstract Despite timely reperfusion and subsequent optimal postinfarct pharmacotherapy and device-based treatment, the outcome in patients with severe myocardial infarction remains unfavourable. Myocardial salvage is incomplete, resulting in adverse left ventricular remodeling with concomitant morbidity and mortality. The combined risk of recurrent myocardial infarction, death or readmission for heart failure amounts to 25 % within the first year, highlighting the need for additional treatment strategies. Recent and rapidly evolving insights in cardiac biology, recognizing endogenous repair capabilities of the adult human heart, paved the path towards progenitor or stem cell based cardiac protection and repair strategies following ischemic injury. We c... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234692 Thu, 15 Sep 2011 04:00:00 +0100 5234692 http://www.medworm.com/index.php?rid=5234691&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919878%26dopt%3DAbstract Authors: Tschöpe C, Miteva K, Schultheiss HP, Van Linthout S Abstract Inflammatory cardiomyopathy is associated with a diffuse inflammation in the heart accompanied with cardiac fibrosis, cardiomyocyte apoptosis, and reduced capillary density. On the other hand, mesenchymal stromal cells (MSCs) have immunomodulatory, anti-fibrotic, anti-apoptotic, and pro-angiogenic features, making them attractive candidates for the treatment of inflammatory cardiomyopathy. The potential of MSC application for the treatment of myocarditis is supported by their beneficial effects in experimental models of acute and chronic inflammatory cardiomopathy. This review summarizes the cardioprotective features of MSCs and describes how MSCs are primed by the inflammatory environment to exert their protect... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234691 Thu, 15 Sep 2011 04:00:00 +0100 5234691 http://www.medworm.com/index.php?rid=5234690&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919879%26dopt%3DAbstract Authors: Cui Y, Madeddu P Abstract Although definition and mechanistic understanding of pro-angiogenic progenitor cells remains unsatisfactory, general agreement highlights their role in regenerative process following tissue injury and ischemia. Furthermore, stem-cell based therapy represents a hot topic of cardiovascular medicine. Recent studies provide new insights on the signalling pathways that modulate stem/progenitor cell mobilization from bone marrow, homing to ischemic area and participation in vascular remodelling and tissue healing. This review focuses on current knowledge and emerging concepts on stem cell/progenitor cell trafficking in relation to changes in surrounding environment and epigenetic modifications caused by risk factors and comorbidities. PMID: 21919879... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234690 Thu, 15 Sep 2011 04:00:00 +0100 5234690 http://www.medworm.com/index.php?rid=5234689&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919880%26dopt%3DAbstract Authors: Rodrigo SF, van Ramshorst J, Beeres SL, Bax JJ, Schalij MJ, Atsma DE Abstract Over the last decade, much was learned about the biology of several types of stem and progenitor cells. It has become apparent that various cell sources may have the capacity to promote cardiomyogenesis and new blood vessel formation through different mechanisms, forming the rationale for cell-based therapy in patients with chronic ischemic heart disease. After initial clinical studies have provided evidence for safety of cell administration, larger randomized trials demonstrated variable effects on myocardial perfusion and contractile performance. Although cell-based therapy is a promising strategy for the treatment of myocardial disease, many questions remain to be answered with respect to the ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234689 Thu, 15 Sep 2011 04:00:00 +0100 5234689 http://www.medworm.com/index.php?rid=5234688&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919881%26dopt%3DAbstract Authors: Strunk D Abstract A constantly growing body of research has been performed mainly over the past decade and a half, aiming to facilitate our still limited understanding of the biology and function of various different cell types which collectively have been termed endothelial progenitor cells. This review intends to critically outline aspects of terminology, origin and applicability of the somatic progenitors which are thought to maintain integrity and support regeneration of the inner lining of vessels through proliferation. Despite reasonable progress in the field, we are still not confident regarding the precise phenotype and function of endothelial progenitor cells. Model systems that have been developed to study the vascular regenerative potential of human endothelial ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234688 Thu, 15 Sep 2011 04:00:00 +0100 5234688 http://www.medworm.com/index.php?rid=5234687&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919882%26dopt%3DAbstract Authors: Choi YH, Nasseri B, Stamm C Abstract More than 10 years ago, the first clinical application of cardiac cell therapy was performed in a patient undergoing coronary bypass grafting (CABG). Ever since, catheter-based cell delivery approaches have dominated the field, but surgical cell therapy continues to provide important information on safety and efficacy of various cell therapy strategies. The open chest offers unrivalled simplicity and precision of intramyocardial cell injection, and the cardiac surgical patient population includes those with very advanced heart disease who are in greatest need of innovative regeneration concepts. In this review, the clinical experience with cardiac surgical cell therapy is summarized and critically appraised. PMID: 21919882 [PubMed -... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234687 Thu, 15 Sep 2011 04:00:00 +0100 5234687 http://www.medworm.com/index.php?rid=5234686&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919883%26dopt%3DAbstract Authors: Van Linthout S PMID: 21919883 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234686 Thu, 15 Sep 2011 04:00:00 +0100 5234686 http://www.medworm.com/index.php?rid=5234685&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919884%26dopt%3DAbstract Authors: Noda M, Yoshioka T PMID: 21919884 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5234685 Thu, 15 Sep 2011 04:00:00 +0100 5234685 http://www.medworm.com/index.php?rid=5221169&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902661%26dopt%3DAbstract Authors: Czaja AJ Abstract Current corticosteroid regimens are effective in autoimmune hepatitis, but therapy can be complicated by side effects, disease progression, incomplete response, and relapse after drug withdrawal. The aims of this review are to describe the promising pharmacological, molecular and cellular interventions for autoimmune hepatitis and to stimulate further investigations that can refresh or replace current treatments. Murine models that introduce pertinent human disease-related antigens by vaccination or viral infection promise a resource by which to evaluate new treatments. Promising new drug therapies include the calcineurin-inhibitors (cyclosporine, tacrolimus), next generation purine antagonists (mycophenolate mofetil, 6-thioguanine nucleotides), next gene... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221169 Fri, 09 Sep 2011 04:00:00 +0100 5221169 http://www.medworm.com/index.php?rid=5221168&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902662%26dopt%3DAbstract Authors: Yao J, Brinton RD Abstract Alzheimer's is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. The progressive and multifaceted degenerative phenotype of Alzheimer's suggests that successful treatment strategies necessarily will be equally multi-faceted and disease stage specific. Traditional therapeutic strategies based on the pathological aspect of the disease have achieved success in preclinical models which has not translated into clinical therapeutic efficacy. Meanwhile, increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mi... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221168 Fri, 09 Sep 2011 04:00:00 +0100 5221168 http://www.medworm.com/index.php?rid=5221167&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902663%26dopt%3DAbstract Authors: Jomova K, Valko M Abstract Iron is a redox active metal involved in the oxidation-reduction reactions and regulation of cell growth and differentiation. Iron is an integral part of many proteins and enzymes that maintains various physiological functions. Most of the human body's iron is contained in red blood cells. Despite iron being an abundant trace metal in food, millions of people worldwide suffer from anemia. Iron deficiency results in impaired production of iron-containing proteins and inhibition of cell growth. In contrast, abnormal iron uptake has been related to the most common hereditary disease hemochromatosis, leading to tissue damage derived from free radical toxicity. In addition, disruption of iron regulation plays a key role in the etiology of Alzheimer's ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221167 Fri, 09 Sep 2011 04:00:00 +0100 5221167 http://www.medworm.com/index.php?rid=5221166&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902664%26dopt%3DAbstract Authors: Arduino DM, Esteves AR, Silva DF, Martins-Branco D, Santos D, Pimentel DF, Cardoso SM Abstract Cellular homeostasis relies on quality control systems so that damaged biologic structures are either repaired or degraded and entirely replaced by newly formed proteins or even organelles. The clearance of dysfunctional cellular structures in long-lived postmitotic cells, like neurons, is essential to eliminate, per example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized proteins. Short-lived proteins are degraded mainly by proteases and proteasomes whether most long-lived proteins and all organelles are digested by autophagy in the lysosomes. Recently, it was established an interplay between the ubiquitin-proteasome system and macroautophagy, so that both degr... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221166 Fri, 09 Sep 2011 04:00:00 +0100 5221166 http://www.medworm.com/index.php?rid=5221165&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902665%26dopt%3DAbstract Authors: Nobre RJ, de Almeida LP Abstract Alzheimer's and Parkinson's diseases represent the most prevalent neurodegenerative disorders worldwide. Current pharmacological or surgical treatments provide symptomatic benefits, particularly in the early stages, but none can delay or stop the progression of these diseases. There is an urgent need for new therapies able to modify disease progression. Gene therapy, mainly based on viral vectors, is presently being assumed as an important alternative to conventional treatments. After decades of preclinical developments, we are now facing an important period, in which several viral vector-mediated gene therapies are being tested in Phase 1 and Phase 2 clinical trials, with some of them showing promising results. This review intends to prese... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221165 Fri, 09 Sep 2011 04:00:00 +0100 5221165 http://www.medworm.com/index.php?rid=5221164&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902666%26dopt%3DAbstract Authors: Srivastava S, Haigis MC Abstract Aging is the major known risk factor for the onset of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Mitochondria plays a central role in aging as mitochondrial dysfunction increases with age and produces harmful levels of reactive oxygen species which leads to cellular oxidative stress (free-radical theory of aging). Oxidative stress is highly damaging to cellular macromolecules and is also a major cause of the loss and impairment of neurons in neurodegenerative disorders. A growing body of evidence suggests that modulation of sirtuin activity and restricting calorie intake has a strong neuroprotective effect. SIRT1 induction by the use of pharmacological activators or by calorie restriction (CR) ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221164 Fri, 09 Sep 2011 04:00:00 +0100 5221164 http://www.medworm.com/index.php?rid=5221162&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902667%26dopt%3DAbstract In conclusion, NAP (davunetide) provided potent neuroprotection in a broad range of neurodegenerative models, protecting the neuroglial cytoskeleton in vitro and inhibiting tau pathology (tauopathy) in vivo. Based on these extensive preclinical results, davunetide (NAP) is now being evaluated in a Phase II/III study of the tauopathy, progressive supranuclear palsy (PSP); (Allon Therapeutics Inc.). PMID: 21902667 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221162 Fri, 09 Sep 2011 04:00:00 +0100 5221162 http://www.medworm.com/index.php?rid=5221161&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902668%26dopt%3DAbstract Authors: Coppieters N, Dragunow M Abstract Epigenetic alterations have been associated with several human diseases including Alzheimer's disease (AD). AD is a complex neurodegenerative disease characterized by a progressive decline in cognitive functions, neuronal cell loss and by the presence of β amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in the cortex. Mutations in specific genes have been identified but can only explain a small percentage of the AD cases. The origins of the sporadic cases of AD are still not known but there is evidence for a role of epigenetics in the etiology of the disease. In this review we focus on discussing the roles of DNA methylation and hydroxymethylation in the development and potential treatment of AD. We discuss papers showing that th... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221161 Fri, 09 Sep 2011 04:00:00 +0100 5221161 http://www.medworm.com/index.php?rid=5221160&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902669%26dopt%3DAbstract Authors: Cardoso SM Abstract During the past decades, we have witnessed significant advances in our understanding of the molecular etiology of Parkinson's disease (PD). The unearthing of the causative genes for hereditary PD accelerated not only the studies of the molecular mechanisms underlying this pathology, but also set mitochondria at the center of PD pathology. In this review we revisit mitochondrial key role and propose a hypothesis for PD, that allows the unification of both sporadic and familial PD forms. In light of this we also discuss new promising disease-modified therapies. PMID: 21902669 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221160 Fri, 09 Sep 2011 04:00:00 +0100 5221160 http://www.medworm.com/index.php?rid=5221159&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902670%26dopt%3DAbstract Authors: Correia SC, Cardoso S, Santos RX, Carvalho C, Santos MS, Perry G, Smith MA, Moreira PI Abstract Mitochondria fulfill a number of essential cellular functions, being recognized that the strict regulation of the structure, function and turnover of these organelles is an immutable control node for the maintenance of neuronal integrity and homeostasis. Many lines of evidence posit that mitochondria constitute a convergence point of preconditioning - a paradigm that affords robust brain tolerance in the face of neurodegenerative insults. Indeed, it has been described that preconditioning activates an adaptive reprogramming of mitochondrial biology in response to a noxious stress-stimulus, which in turn will contribute to augment both mitochondrial and neuronal tolerance. Mitoch... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221159 Fri, 09 Sep 2011 04:00:00 +0100 5221159 http://www.medworm.com/index.php?rid=5221158&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902671%26dopt%3DAbstract Authors: Bonda DJ, Smith MA, Perry G, Lee HG, Wang X, Zhu X Abstract Mitochondrial dynamics play a crucial role in the pathobiology underlying Alzheimer's disease (AD) and Parkinson's disease (PD). Although a complete scientific understanding of these devastating conditions has yet to be realized, alterations in mitochondrial fission and fusion, and in the protein complexes that orchestrate mitochondrial fission and fusion, have been well established in AD- and PD-related neurodegeneration. Whether fission/fusion disruption in the brain is a causal agent in neuronal demise or a product of some other upstream disturbance is still a matter of debate; however, in both AD and PD, the potential for successful therapeutic amelioration of degeneration via mitochondrial protection is high.... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221158 Fri, 09 Sep 2011 04:00:00 +0100 5221158 http://www.medworm.com/index.php?rid=5221157&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902672%26dopt%3DAbstract Authors: Swerdlow RH Abstract Several sporadic neurodegenerative diseases display phenomena that directly or indirectly relate to mitochondrial function. Data suggesting altered mitochondrial function in these diseases could arise from mitochondrial DNA (mtDNA) are reviewed. Approaches for manipulating mitochondrial function and minimizing the downstream consequences of mitochondrial dysfunction are discussed. PMID: 21902672 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5221157 Fri, 09 Sep 2011 04:00:00 +0100 5221157 http://www.medworm.com/index.php?rid=5180147&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21875413%26dopt%3DAbstract Authors: Mori M, Manetti F, Bottamanetti M, Botta M Abstract Protein-protein and protein-nucleic acid interactions are involved in many regulatory cellular pathways, playing a key role in cell growth and proliferation, as well as in the progression and development of various diseases such as infectious diseases. Especially in the anti-AIDS research, protein-protein and protein-nucleic acid complexes are being considered as promising targets for pharmaceutical interventions aimed at overcoming the drug resistance observed for most of the classic enzyme inhibitors. Consequently, more and more protein-protein and protein-nucleic acid interaction inhibitors have being identified and developed as candidate agents for antiretroviral therapy. Here, we review the state of the art in the di... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5180147 Mon, 29 Aug 2011 23:00:00 +0100 5180147 http://www.medworm.com/index.php?rid=5160105&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864260%26dopt%3DAbstract Authors: Fierabracci A PMID: 21864260 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design) Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160105 Wed, 24 Aug 2011 23:00:00 +0100 5160105 http://www.medworm.com/index.php?rid=5160104&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864261%26dopt%3DAbstract Authors: Pozzilli P, Guglielmi C, Maggi D, Carlone A, Buzzetti R, Manfrini S Abstract In type 1 diabetes, beta cells are attacked and destroyed by auto reactive T cells causing major impairment of blood glucose metabolism and, ultimately, the development of life-threatening complications. Currently, the treatment of this chronic disease is based on the use of endogenous insulin and no curative therapies are available. Treatment approaches in this respect need to be directed toward the primary causes of the disease tackling beta cells' auto reactive T cells. The goal of any curative intervention in type 1 diabetes is the preservation of insulin-secreting cells. This may be achieved by the abrogation of the pathogenic reactivity to beta cell auto antigens while preserving full capaci... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160104 Wed, 24 Aug 2011 23:00:00 +0100 5160104 http://www.medworm.com/index.php?rid=5160103&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864262%26dopt%3DAbstract Authors: Katz U, Zandman-Goddard G Abstract Intravenous Immunoglobulins (IVIg) are administered both as replacement therapy for certain immunodeficiencies and as immunomodulatory therapy for some autoimmune diseases. While the treatment with IVIg is approved in only a few autoimmune diseases, the number of off-label indications is increasing. The varied mechanisms by which IVIg attains its beneficial effect are diverse. There is much evidence for the beneficial and safety profile for IVIg in low as well as high-dose protocols. Patients prone to develop thrombotic events should be advised about the risk of IVIg therapy especially at high doses. This paper updates the mechanisms of action of IVIg as well as recent off-label indications. PMID: 21864262 [PubMed - as supplied by pub... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160103 Wed, 24 Aug 2011 23:00:00 +0100 5160103 http://www.medworm.com/index.php?rid=5160102&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864263%26dopt%3DAbstract Authors: Geiler J, Buch M, McDermott MF Abstract Rheumatoid arthritis (RA), the most common autoimmune disease, is characterized by persistent synovitis and systemic inflammation. Genetic predisposition as well as autoantibodies and environmental factors, such as smoking, are associated with an increased risk of RA. Traditionally RA has been treated with disease modifying anti-rheumatic drugs (DMARDs) but in the last 15 years or so the introduction of biological response modifiers has revolutionized the treatment of RA. Among these anti-tumor necrosis factor (TNF) agents were the first to be successfully used in treating RA. The goal in treating RA is to induce remission or very low disease activity; remission is now accepted as the ultimate therapeutic goal by adoption of a "treat... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160102 Wed, 24 Aug 2011 23:00:00 +0100 5160102 http://www.medworm.com/index.php?rid=5160101&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864264%26dopt%3DAbstract Authors: Phillips BE, Trucco M Abstract Type 1 Diabetes is an autoimmune disease most often associated with elevated and uncontrolled blood glucose levels. Therefore patient education and treatment compliance is often focused on disease maintenance through insulin treatment and blood glucose control. Unfortunately insulin therapy alone does not prevent the formation of diabetic complications. In order to find a real cure, the underlying pathology of the disease must be directly addressed. Diabetes is caused by the initial rapid destruction of the insulin producing beta cells of the pancreas by autoreactive T-cells. The autoimmune process is also maintained through dendritic cell auto-antigen presentation and the production of autoantibodies by B cells. Only through some forms of im... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160101 Wed, 24 Aug 2011 23:00:00 +0100 5160101 http://www.medworm.com/index.php?rid=5160100&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864265%26dopt%3DAbstract Authors: Rosado MM, Diamanti AP, Capolunghi F, Carsetti R Abstract The paradigm that T cells are the prime effectors of autoimmune diseases has been recently challenged by growing evidence that B-lymphocytes play a role in the development, re-activation and persistence of autoimmune disorders. B-cells of different subsets may play different roles in autoimmune pathologies due to their ability to secrete antibodies, produce cytokines, present antigen and form ectopic germinal centers. Thus, a given therapeutic approach or drug may have distinct outcomes depending on which specific B cell subset is targeted. Immunosuppressive therapies such as azathioprine (AZA), cyclophosphamide (CyC) or methotrexate (MTX) are conventionally used in autoimmune diseases with the aim of reducing disea... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160100 Wed, 24 Aug 2011 23:00:00 +0100 5160100 http://www.medworm.com/index.php?rid=5160099&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864266%26dopt%3DAbstract Authors: Rotondi M, Chiovato L Abstract The recruitment, trafficking, and in situ maintenance of specific subsets of activated lymphocytes constitute crucial steps for the initiation and perpetuation of chronic autoimmune inflammation. The fact that, after IFN-γ stimulation, thyrocytes secrete CXCR3-binding chemokines, which in turn recruits Th1 lymphocytes expressing CXCR3 and secreting IFN-γ, strongly supports the concept that the interferon-γ inducible chemokines (CXCL9, CXCL10, and CXCL11) and their receptor CXCR3 play an important role in the initiation of autoimmune thyroid diseases (AITD). Thus, interfering with CXCR3 might result in the abrogation of the inflammatory process. The understanding of these pathogenetic mechanisms suggested novel therapeutic approaches, with ... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160099 Wed, 24 Aug 2011 23:00:00 +0100 5160099 http://www.medworm.com/index.php?rid=5160098&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864267%26dopt%3DAbstract Authors: Fierabracci A, Ayroldi E Abstract Autoimmune diseases are an heterogeneous group of disorders and epidemiological studies demonstrate that their incidence is increasing worldwide. It is known that a complex interaction of genetic and environmental factors underlies their complex etiopathogenesis. In the light of the aforegoing the exact molecular key events were difficult to be explored; these represent the leading step to the prevention and treatment of autoimmune disorders. Novel therapeutic approaches are nowadays under investigation and specific treatments have been preferentially applied in experimental models of disease. New results were brought about and fascinating new pathways for treatment of autoimmunity were launched in the past years. Nevertheless novel target... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160098 Wed, 24 Aug 2011 23:00:00 +0100 5160098 http://www.medworm.com/index.php?rid=5160097&cid=s_37258_13_f&fid=37258&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864268%26dopt%3DAbstract Authors: Ayroldi E, Bastianelli A, Cannarile L, Petrillo MG, Delfino DV, Fierabracci A Abstract Psoriasis is a chronic inflammatory disease with a complex pathophysiology and a multigenic background. Autoimmunity and genetic hallmarks couple to confer the disease, which is characterized by chronic plaques (85-90% of all cases) and/or psoriasis arthritis (PsA), and involve the peripheral and sacro-iliac joints, nails, and skeleton. Dissecting the ethiopathogenetic mechanisms of psoriasis and PsA is a major basic research challenge. One important question is whether a single inflammatory mediator can be responsible for the interactive network that forms between immune cells and cytokines in this disease. Despite much progress, no research has yet been able to define a single model to... Current Pharmaceutical Design journals http://www.medworm.com/rss/comments.php?id=5160097 Wed, 24 Aug 2011 23:00:00 +0100 5160097