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 'Infectious Disorders Drug Targets' source. Wed, 08 Feb 2012 18:15:42 +0100 http://www.medworm.com/index.php?rid=5644058&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280310%26dopt%3DAbstract In this study, we tested for antibody reactivity against synthetic Tat representative of five HIV subtypes in HIV positive patients receiving ART with undetectable viral loads (< 40 copies/mL) over the course of one year. Anti-Tat IgG were detected in 86% of patients during the course of the study. Anti-Tat IgG appeared transiently in 34% of cases, 32% had anti-Tat IgG appear after the study started and this remained persistent while 20% were persistently positive from the study debut. 14% were consistently negative. No significant correlation was found between anti-Tat IgG and CD4+ T cell, CD8+ T cell and B cell counts. Despite the stable undetectable viral load, the appearance of anti-Tat IgG demonstrates that Tat is actively secreted into the plasma from HIV infected cells. PMID:... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5644058 Thu, 26 Jan 2012 05:00:00 +0100 5644058 http://www.medworm.com/index.php?rid=5363549&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22034931%26dopt%3DAbstract Authors: Moseley GW, Jans DA PMID: 22034931 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363549 Tue, 18 Oct 2011 04:00:00 +0100 5363549 http://www.medworm.com/index.php?rid=5363548&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22034932%26dopt%3DAbstract This article reviews current evidence for the role of tetraspanins in the uptake, trafficking and spread of viruses as well as intracellular bacteria, fungi and parasites. Finally, the prospects of targeting tetraspanins for therapeutic intervention in infections caused by such pathogens are discussed. PMID: 22034932 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363548 Tue, 18 Oct 2011 04:00:00 +0100 5363548 http://www.medworm.com/index.php?rid=5363547&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22034933%26dopt%3DAbstract Authors: Williamson CD, De Biasi RL, Colberg-Poley AM Abstract A wide variety of viruses cause significant morbidity and mortality in humans. However, targeted antiviral therapies have been developed for only a subset of these viruses, with the majority of currently licensed antiviral drugs targeting viral entry, replication or exit steps during the viral life cycle. Due to increasing emergence of antiviral drug resistant viruses, the isolation of multiple viral subtypes, and toxicities of existing therapies, there remains an urgent need for the timely development of novel antiviral agents, including those targeting host factors essential for viral replication. This review summarizes viral products that target mitochondria and their effects on common mitochondria regulated pathways... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363547 Tue, 18 Oct 2011 04:00:00 +0100 5363547 http://www.medworm.com/index.php?rid=5363546&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22034934%26dopt%3DAbstract Authors: Oksayan S, Ito N, Moseley G, Blondel D Abstract Vesicular stomatitis virus (VSV) and Rabies Virus (RABV) are the prototypic members of the rhabdovirus family. These viruses have a particularly broad host range, and despite the availability of vaccines, RABV still causes more than 50,000 human deaths a year. Trafficking of the virion or viral particles is important at several stages of the replicative life cycle, including cellular entry, localization into the cytoplasmic inclusion bodies which primarily house the transcription and replication of the viral genome, and migration to the plasma membrane from whence the virus is released by budding. Intriguingly, specific viral proteins, VSV M and RABV P have also been shown to undergo intracellular trafficking independent of t... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363546 Tue, 18 Oct 2011 04:00:00 +0100 5363546 http://www.medworm.com/index.php?rid=5363545&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22034935%26dopt%3DAbstract Authors: Younessi P, Jans DA, Ghildyal R Abstract Picornavirus infection is characterised by host cell shutoff, wherein host transcription and translation processes are severely impaired. Picornavirus proteins interact with host cell proteins, resulting in alterations in the host cell synthetic, signalling and secretory machinery, and facilitating transcription and translation of viral proteins to achieve increased virus replication and assembly. Among the many cellular pathways affected, recent studies have shown that disruption of nucleocytoplasmic trafficking via inhibition of the functions of the nuclear pore may be a common means of picornavirus-induced pathogenesis. Disruption of nuclear pore functions results in nuclear proteins being relocalised to the cytoplasm and reduced... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363545 Tue, 18 Oct 2011 04:00:00 +0100 5363545 http://www.medworm.com/index.php?rid=5363544&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22034936%26dopt%3DAbstract Authors: Glover DJ Abstract Improved understanding of the signals that direct the intracellular transport of endogenous mammalian proteins, as well as the means by which viral invaders hijack transport pathways during infection, has revealed a plethora of methods for enhancing drug and gene delivery. Multi-component delivery vectors with virus-like functionality are being developed to assemble with therapeutic DNA into structured nanoparticles that are internalized and actively transported to specific locations within mammalian cells. Furthermore, the mimicking of viral mechanisms can be extended to nuclear maintenance and replication of exogenous DNA, through either site-specific integration into safe genomic regions, or extra-chromosomal maintenance as episomally replicating plas... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363544 Tue, 18 Oct 2011 04:00:00 +0100 5363544 http://www.medworm.com/index.php?rid=5142800&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827430%26dopt%3DAbstract Authors: Bernstein DI Abstract Cytomegalovirus (CMV) is a leading cause of congenital infection worldwide and therefore is recognized as an important target for vaccine development. Data from natural infections and work done with animal models, including models of congenital infection, provide the rationale for their development. CMV vaccine evaluations were begun in the mid 1970's with an attenuated live virus vaccine, Towne, but this vaccine has not consistently provided protection. Most recently, data from a trial with a subunit glycoprotein B (gB) vaccine administered with the adjuvant MF59 became available. This trial, conducted in post-partum women, demonstrated that the vaccine decreased CMV infections, increasing optimism that a protective CMV vaccine could be developed. Ot... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142800 Wed, 29 Jun 2011 23:00:00 +0100 5142800 http://www.medworm.com/index.php?rid=5142798&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827431%26dopt%3DAbstract Authors: James SH, Prichard MN Abstract Infections due to resistant human cytomegalovirus (CMV) are an emerging problem, particularly in immunocompromised hosts. When managing such patients, clinicians should be aware of the possibility of developing CMV antiviral resistance, especially while on prolonged therapy or if severe immunosuppression is present. CMV resistance to current antiviral agents is mediated by alterations in either the UL97 kinase or DNA polymerase, encoded by the UL97 and UL54 genes, respectively. UL97 mutations are capable of conferring resistance to ganciclovir, while UL54 mutations can impart resistance to ganciclovir, cidofovir, and foscarnet. If treatment failure is suspected to be due to antiviral resistance, CMV resistance analysis should be obtained. Phe... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142798 Wed, 29 Jun 2011 23:00:00 +0100 5142798 http://www.medworm.com/index.php?rid=5142797&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827432%26dopt%3DAbstract Authors: Ahmed A Abstract Cytomegalovirus (CMV) is an opportunistic pathogen associated with significant morbidity and mortality in immunocompromised hosts. Antiviral agents specifically targeting CMV were initially developed during the human immunodeficiency virus (HIV) epidemic to treat end-organ disease in patients with acquired immunodeficiency syndrome (AIDS). There are currently four antiviral drugs licensed for the treatment of CMV infections: ganciclovir (GCV), valganciclovir (VGCV), foscarnet (FOS), and cidofovir (CDV). The role of these agents has evolved from the treatment of disease to include prevention of CMV infection and disease, primarily in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. The potential use of these drugs is be... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142797 Wed, 29 Jun 2011 23:00:00 +0100 5142797 http://www.medworm.com/index.php?rid=5142796&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827433%26dopt%3DAbstract Authors: Ross SA, Novak Z, Pati S, Boppana SB Abstract Cytomegalovirus (CMV) is recognized as the most common congenital viral infection in humans and an important cause of morbidity and mortality in immunocompromised hosts. This recognition of the clinical importance of invasive CMV disease in the setting of immunodeficiency and in children with congenital CMV infection has led to the development of new diagnostic procedures for the rapid identification of CMV. Diagnosis of acute maternal CMV infection by the presence of immunoglobulin (Ig)M and low-avidity IgG requires confirmation of fetal infection, which is typically performed using polymerase chain reaction (PCR) assays for CMV on amniotic fluid. Viral culture of the urine and saliva obtained within the first two weeks of lif... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142796 Wed, 29 Jun 2011 23:00:00 +0100 5142796 http://www.medworm.com/index.php?rid=5142795&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827434%26dopt%3DAbstract Authors: Schleiss MR Abstract Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. Congenital CMV disease frequently produces serious neurodevelopmental disability, as well as vision impairment and sensorineural hearing loss. Development of a CMV vaccine is therefore considered to be a major public health priority. The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular pr... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142795 Wed, 29 Jun 2011 23:00:00 +0100 5142795 http://www.medworm.com/index.php?rid=5142794&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827435%26dopt%3DAbstract Authors: Russell MY, Palmer A, Michaels MG Abstract Disease caused by cytomegalovirus (CMV) infection can clinically manifest in a variety of ways in the immunodeficient host and lead to significant morbidity and mortality. Infections can be primary, occur as a result of reactivation of latent virus, or infection with a new strain of CMV. Cell-mediated immunity is the main defense against CMV disease. This component of the immune system is frequently affected in children who are born prematurely, have undergone solid organ transplantation or hematopoietic stem cell transplantation, or have infection with human immunodeficiency virus. Accordingly, these children are at increased risk for severe disease due to CMV. In addition, CMV itself alters cell-mediated immunity and may predisp... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142794 Wed, 29 Jun 2011 23:00:00 +0100 5142794 http://www.medworm.com/index.php?rid=5142793&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827436%26dopt%3DAbstract Authors: Elliott SP Abstract Cytomegalovirus (CMV) remains the most common cause of congenitally-acquired infection in the United States and is a leading infectious cause of sensorineural hearing loss, cognitive delay, and permanent neurologic sequelae. Although most cases of congenital CMV infection are asymptomatic, significant morbidity and mortality exist for symptomatic infants and may also occur in asymptomatic ones. Diagnosis remains relatively straightforward, but treatment options are limited and associated with some toxicity. Efforts at prevention via vaccination, screening, and improved epidemiology deserve high priority to limit the impact of this common infection. PMID: 21827436 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142793 Wed, 29 Jun 2011 23:00:00 +0100 5142793 http://www.medworm.com/index.php?rid=5142792&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827437%26dopt%3DAbstract Authors: Cantey JB, Sánchez PJ Abstract Congenital infections are those that are acquired transplacentally by the fetus from an infected mother. They constitute a major public health burden, affecting millions of infants and children worldwide. Despite significant advances in medical diagnostics, the majority of newborns with congenital infections are not recognized, since many of these infections may not cause clinically-apparent disease in the newborn period. Nonetheless, these infections - whether they are apparent or silent - have the potential to adversely impact the neurodevelopmental outcomes of these vulnerable children. PMID: 21827437 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142792 Wed, 29 Jun 2011 23:00:00 +0100 5142792 http://www.medworm.com/index.php?rid=5142791&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827438%26dopt%3DAbstract Authors: Tolan RW PMID: 21827438 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142791 Wed, 29 Jun 2011 23:00:00 +0100 5142791 http://www.medworm.com/index.php?rid=4971738&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679139%26dopt%3DAbstract Authors: Nseir S, Zerimech F, Jaillette E, Artru F, Balduyck M Microaspiration of contaminated oropharyngeal secretions and gastric contents frequently occurs in intubated critically ill patients, and plays a major role in the pathogenesis of ventilator-associated pneumonia. Risk factors for microaspiration include impossible closure of vocal cords, longitudinal folds in high-volume low-pressure polyvinyl chloride cuffs, and underinflation of tracheal cuff. Zero positive end expiratory pressure, low peak inspiratory pressure, tracheal suctioning, nasogastric tube and enteral nutrition increase the risk for microaspiration. Other patient related factors include supine position, coma, sedation, and hyperglycemia. Technetium 99 labelled enteral feeding is probably the most accurate marker... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971738 Wed, 15 Jun 2011 23:00:00 +0100 4971738 http://www.medworm.com/index.php?rid=4971737&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679140%26dopt%3DAbstract Authors: Poissy J, Senneville E Infection is a major cause of morbidity and mortality in intensive care units (ICU). The impact on prognostic of an inadequate antibiotic therapy is well established. The problem is due to the growing spread of resistant microorganisms, including both Gram-negative and Gram-positive pathogens, especially in the case of ICU-acquired infections. In this context, antibiotics with broad spectrum activity are usually required. Moreover, these antibiotics should reach high concentrations in tissues, especially in lungs, and should exert a bactericidal activity for the most severely ill patients, especially those with bloodstream infections. A frequent problem in clinical practice is the lack of data validating their use in the context of critically ill patient... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971737 Wed, 15 Jun 2011 23:00:00 +0100 4971737 http://www.medworm.com/index.php?rid=4971736&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679141%26dopt%3DAbstract Authors: Tzovaras N, Karvouniaris M, Makris D, Zakynthinos E Aim: To review available evidence for the role of adjunctive therapies in severe pneumonia. Methods: We focused on therapies that have recently attracted interest such as glucocorticosteroids (GCs), statins and recombinant activated protein-C. Results: Experimental animal and human studies showed that GCs are able to modulate the inflammatory response and may offer a benefit in patients with severe sepsis. Randomized trials in pneumonia are few, mostly limited to septic shock and ARDS patients. Recombinant activated protein C is a potent anticoagulant and profibrinolytic enzyme which can inhibit the systemic inflammatory response. Available data, although limited, showed that activated protein C can reduce mortality in severe... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971736 Wed, 15 Jun 2011 23:00:00 +0100 4971736 http://www.medworm.com/index.php?rid=4971735&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679142%26dopt%3DAbstract Authors: Roux D, Ricard JD P. aeruginosa is the bacteria most commonly responsible for hospital-acquired and ventilator-associated pneumonia. Numerous factors are encoded in its genome, and they explain its high virulence. P. aeruginosa also develops a quorum sensing (QS), which coordinates the expression of these factors. The type III secretion system, a needle-complex, allows exotoxin injections into eukaryotic cells and is involved in the pathogenesis of acute pneumonia. This pathogen develops a high level of resistance to all antibiotics, which leads to a shortage of treatment options for many patients. Thus, new preventive or therapeutic approaches are in development. Immunotherapy that uses monoclonal antibodies has been successfully tested in blocking the type III secretion syst... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971735 Wed, 15 Jun 2011 23:00:00 +0100 4971735 http://www.medworm.com/index.php?rid=4971734&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679143%26dopt%3DAbstract Authors: Baudry T, Ader F Several forms of supportive techniques for respiration in intensive care units (ICU) are currently available. The most widely used is invasive mechanical ventilation through the use of an endotracheal tube (ETT). ETTs are proved to be important contributors to the pathogenesis and development of ventilator-acquired pneumonia (VAP) as artificial airways interfere with a number of respiratory tract defence mechanisms and facilitate bacterial colonisation of the tracheobronchial tree. The occurrence of VAP is known to be one of the leading cause of morbidity and mortality in ICUs. On that basis, non-invasive techniques have been developed through the use of patient-ventilator interfaces in the form of facial masks which allow the development of ventilatory modali... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971734 Wed, 15 Jun 2011 23:00:00 +0100 4971734 http://www.medworm.com/index.php?rid=4971733&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679144%26dopt%3DAbstract Authors: De Angelis G, Restuccia G, Cauda R, Tacconelli E The role of antibiotic pressure in the selection of antibiotic-resistant bacteria is still under debate in the scientific community and often confounded by scarce data on antibiotic usage. Several studies demonstrated that prior antibiotic exposure is likely to increase patient's colonization and infection by antimicrobial-resistant bacteria. Of even more concern is the significant mortality associated with these infections, in particular in critically ill patients. Therefore, the control of antibiotic usage in intensive care units (ICUs) is of paramount importance. Antibiotic stewardship programmes have been demonstrated to represent a useful intervention to reduce the inappropriate antibiotic usage in hospitalized patients. A ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971733 Wed, 15 Jun 2011 23:00:00 +0100 4971733 http://www.medworm.com/index.php?rid=4971732&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679145%26dopt%3DAbstract Authors: Blazejewski C, Guerry MJ, Preau S, Durocher A, Nseir S Hospital-acquired infections (HAI) represent the most common adverse event in the intensive care unit (ICU). Their prevalence is high and they are associated with increased morbidity and mortality The environment plays a central role in the transmission of hospital-acquired pathogens (HAP) and in the pathogenesis of HAI. Many bacteria, especially multidrug resistant ones, can survive for several months in the hospital environment in particular in areas close to the patients. It has been proven that pathogens are transmitted from the environment to the patients. Many studies have concluded that current cleaning methods are microbiologically ineffective. This failure concerns daily cleaning as well as terminal cleaning after... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971732 Wed, 15 Jun 2011 23:00:00 +0100 4971732 http://www.medworm.com/index.php?rid=4971731&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679146%26dopt%3DAbstract Authors: Florescu DF, Kalil AC Infection, inflammatory response, activation of coagulation cascade and sepsis are tightly interconnected. In the initial phase, sepsis is characterized by a pro-inflammatory state, while in the late phase, by an anti-inflammatory state which favors cytomegalovirus reactivation. Cytomegalovirus infection would accentuate the sepsis-induced immunologic effects increasing the risk for other infections. The rate of CMV infection is 17% in critically ill non-immunocompromised patients, up to 30% in hematopoietic stem cell transplant and up to 60% in solid organ transplant recipients. Cytomegalovirus infection in critically ill patients is associated with prolonged ventilator support, nosocomial infections, prolonged hospital and/or ICU stay and increased mort... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971731 Wed, 15 Jun 2011 23:00:00 +0100 4971731 http://www.medworm.com/index.php?rid=4971730&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679147%26dopt%3DAbstract Authors: Loïez C, Herwegh S, Courcol RJ Real-time PCR methods are able to rapidly detect a wide panel of microorganisms. These methods are of interest in critically ill patients to determine the presence of bacteria in the blood and other biological samples, especially in those patients with prior antimicrobial treatment. In intensive care unit (ICU), the LightCycler SeptiFast (LC-SF) Test provides 1.5 to 2 fold higher positivity rate compared with conventional blood cultures. Although identification of the bacterium by LC-SF is rapid and sensitive, susceptibility test could not be performed using this technique, except the methicillin-resistance for Staphylococci. The conventional cultures remain necessary for samples in ICU because of the high incidence of multidrug-resistant bacter... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971730 Wed, 15 Jun 2011 23:00:00 +0100 4971730 http://www.medworm.com/index.php?rid=4971729&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679148%26dopt%3DAbstract Authors: Nseir S, Wallet F PMID: 21679148 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4971729 Wed, 15 Jun 2011 23:00:00 +0100 4971729 http://www.medworm.com/index.php?rid=4720848&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21488828%26dopt%3DAbstract Authors: Vigant F, Lee B The Paramyxoviridae family comprises of several genera that contain emerging or re-emerging threats for human and animal health with no real specific effective treatment available. Hendra and Nipah virus are members of a newly identified genus of emerging paramyxoviruses, Henipavirus. Since their discovery in the 1990s, henipaviruses outbreaks have been associated with high economic and public health threat potential. When compared to other paramyxoviruses, henipaviruses appear to have unique characteristics. Henipaviruses are zoonotic paramyxoviruses with a broader tropism than most other paramyxoviruses, and can cause severe acute encephalitis with unique features among viral encephalitides. There are currently no approved effective prophylactic or therapeuti... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720848 Tue, 12 Apr 2011 23:00:00 +0100 4720848 http://www.medworm.com/index.php?rid=4720846&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21488829%26dopt%3DAbstract Authors: Mutton K, Guiver M Encephalitis is an inflammatory process involving the parenchyma of the brain. It typically presents as a clinical syndrome characterised by fever, headache and altered conscious level, often with focal neurological deficits and fits. The clinical presentation overlaps with other diseases of the central nervous system including viral and bacterial meningitis, and brain abscess. The causes of encephalitis are legion, and include principally viral but also bacterial, parasitic and fungal pathogens. Noninfectious aetiologies, especially autoimmune conditions such as potassium channel voltage gated antibodies and anti-NDMA receptor antibodies, are increasingly recognised. Diagnosis comes from clinical examination, neuroimaging and laboratory testing. With such a... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720846 Tue, 12 Apr 2011 23:00:00 +0100 4720846 http://www.medworm.com/index.php?rid=4720844&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21488830%26dopt%3DAbstract Authors: Stahl JP, Mailles A, Morand P Encephalitis is an inflammation of the brain structures: neurons, vessels or glial cells. However, a consensual definition of the syndrome is difficult to obtain, and it is even more difficult to define encephalitis due a specific agent. Most virus can be responsible for infectious encephalitis, but the number of encephalitis cases is very limited with regards of the incidence of benign infections from these pathogens. Viruses responsible for encephalitis can be animal-borne, vector-borne or human-to-human transmitted, they can infect preferentially immunocompetent or immunosuppressed patients, and some of them have demonstrated their epidemic potential. Herpes simplex encephalitis is recognized worldwide as the most frequent infectious encephalit... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720844 Tue, 12 Apr 2011 23:00:00 +0100 4720844 http://www.medworm.com/index.php?rid=4720842&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21488831%26dopt%3DAbstract Authors: Dutta K, Nazmi A, Basu A Chemotherapy in Japanese encephalitis (JE) is at present entirely supportive and not targeted at the virus. There are no available drugs to effectively counter the viral infection, thereby making the fight against JE a daunting task. With approximately 50,000 reported cases per year, nearly 10,000 deaths and 3 billion people living in endemic regions, it is imperative that the hunt for an effective drug be expedited. Prophylactic measures are effective against JE, but the problem plaguing all is the underdevelopment and inefficiency of medical services in developing countries. Combined to that are difficulties to earn a living and illiteracy, that leaves significant proportions of the population in these countries uninformed about the magnitude of the ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720842 Tue, 12 Apr 2011 23:00:00 +0100 4720842 http://www.medworm.com/index.php?rid=4720840&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21488832%26dopt%3DAbstract Authors: Dacheux L, Delmas O, Bourhy H Rabies remains one of the most ancient and deadly of human infectious diseases. This viral zoonosis is transmitted principally by the saliva of infected dogs, inducing a form of encephalomyelitis that is almost invariably fatal. Since the first implementation, by Louis Pasteur in 1885, of an efficient preventive post-exposure treatment, more effective protocols and safer products have been developed, providing almost 100% protection if administered early enough. However, this disease still represents a major, but neglected public health problem, with an estimated 50,000 human deaths due to rabies reported each year, mostly in Africa and Asia. Once the first clinical signs appear, there is no effective treatment. A ray of hope emerged in 2004, with... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720840 Tue, 12 Apr 2011 23:00:00 +0100 4720840 http://www.medworm.com/index.php?rid=4720833&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21488833%26dopt%3DAbstract This study summarizes the development of drugs for EV-related infections based on molecular targets blocking various steps in the viral replication cycle. PMID: 21488833 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720833 Tue, 12 Apr 2011 23:00:00 +0100 4720833 http://www.medworm.com/index.php?rid=4720831&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21488834%26dopt%3DAbstract Authors: Rozenberg F, Deback C, Agut H Herpes simplex virus (HSV) is the cause of herpes simplex encephalitis (HSE), a devastating human disease which occurs in 2-4 cases per million/year. HSE results either from a primary infection or virus reactivation, in accordance with the common pattern of HSV infection which is a chronic lifelong process. However its pathophysiology remains largely unknown and its poor prognosis is in contrast with the usually good tolerance of most clinical herpetic manifestations. HSE is due to HSV type 1 (HSV-1) in most cases but HSV type 2 (HSV-2) may be also implicated, especially in infants in the context of neonatal herpes. Polymerase chain reaction detection of HSV DNA in cerebrospinal fluid is the diagnosis of choice for HSE. Acyclovir, a nucleoside ana... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720831 Tue, 12 Apr 2011 23:00:00 +0100 4720831 http://www.medworm.com/index.php?rid=4720829&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21488835%26dopt%3DAbstract Authors: Dacheux L PMID: 21488835 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720829 Tue, 12 Apr 2011 23:00:00 +0100 4720829 http://www.medworm.com/index.php?rid=4720851&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470098%26dopt%3DAbstract Authors: Bai H, Zhou Y, Hou Z, Xue X, Meng J, Luo X The progress of transcription is synthesized by complex molecules, among which DNA-dependent RNA polymerase (RNAP) is the central enzyme. The prokaryotic RNAP is a large protein composed of core subunits (α2, β and β') and a σ factor that is required for specific recognition of the promoter site and the initiation of transcription. Despite its ubiquity, structural and functional similarities, bacterial RNAPs do not share extensive sequence homology with eukaryotic RNAPs. Bacterial RNAP is attractive target for the development of anti-bacterial drugs as its inactivation would lead to bacterial cell death. This review will present the state of knowledge on the assembly and function of RNAP subunits in bacteria with special focus on ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720851 Thu, 17 Mar 2011 00:00:00 +0100 4720851 http://www.medworm.com/index.php?rid=4720850&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470099%26dopt%3DAbstract Authors: Vicente E, Villar R, Pérez-Silanes S, Aldana I, Goldman RC, Mong A New drugs active against drug-resistant tuberculosis are urgently needed to extend the range of TB treatment options to cover drug resistant infections. Quinoxaline derivatives show very interesting biological properties (antibacterial, antiviral, anticancer, antifungal, antihelmintic, insecticidal) and evaluation of their medicinal chemistry is still in progress. In this review we report the properties and the recent developments of quinoxaline 1,4-di-N-oxide derivatives as potential anti-tuberculosis agents. Specific agents are reviewed that have excellent antitubercular drug properties, are active on drug resistant strains and non-replicating mycobacteria. The properties of select analogs that have in vivo ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720850 Thu, 17 Mar 2011 00:00:00 +0100 4720850 http://www.medworm.com/index.php?rid=4720849&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470100%26dopt%3DAbstract Conclusions: This article highlights possible risks for individual long-term effects, when chromium-picolinate is used freely as a therapeutic nutritional modality agent without application of advanced diagnostic tools to predict risks and individual outcomes. Targeted measures require a creation of new guidelines for advanced Diabetes care. PMID: 21470100 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4720849 Thu, 17 Mar 2011 00:00:00 +0100 4720849 http://www.medworm.com/index.php?rid=4607524&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406048%26dopt%3DAbstract Authors: Nachega JB, Marconi VC, van Zyl GU, Gardner EM, Preiser W, Hong SY, Mills EJ, Gross R Poor adherence to combined antiretroviral therapy (cART) has been shown to be a major determinant of virologic failure, emergence of drug resistant virus, disease progression, hospitalizations, mortality, and health care costs. While high adherence levels can be achieved in both resource-rich and resource-limited settings following initiation of cART, long-term adherence remains a challenge regardless of available resources. Barriers to optimal adherence may originate from individual (biological, socio-cultural, behavioral), pharmacological, and societal factors. Although patients and providers should continuously strive for maximum adherence to cART, there is accumulating evidence that each ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607524 Tue, 15 Mar 2011 00:00:00 +0100 4607524 http://www.medworm.com/index.php?rid=4607523&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406049%26dopt%3DAbstract Authors: Sabarinath SN, Wu B, Peloquin C, Derendorf H Drug development continues to be time consuming, expensive and less efficient, while drug therapy is often administered at suboptimal levels. This is particularly true with anti-infectives for HIV and tuberculosis. The application of pharmacometric principles and models to drug development and pharmacotherapy will improve the drug approval process and selection of optimal dosage regimens or therapeutic combinations. In this review we mainly focus on the utilities of pharmacometrics in the dose selections of anti-retroviral and anti-tubercular drugs. We will examine how pharmacometrics have been useful in the area of dose selections, preclinical to clinical scaling, subpopulation selections, combination therapies, adherence assessmen... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607523 Tue, 15 Mar 2011 00:00:00 +0100 4607523 http://www.medworm.com/index.php?rid=4607522&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406050%26dopt%3DAbstract Authors: Marais BJ, Schaaf HS, Donald PR Childhood tuberculosis (TB) continues to be a neglected disease in areas where limited resources restrict the focus of national TB control programmes to only the most infectious sputum smear-positive cases. However, appreciation that children contribute a significant proportion to the global TB disease burden and suffer severe TB-related morbidity and mortality is growing. The World Health Organization (WHO) published guidelines on the management of paediatric TB in 2006 and child friendly drug formulations have been made available to deserving nations via the Global Drug Facility (GDF) since 2008. These advances also served to emphasize the considerable programmatic barriers that remain in resource-limited settings. This review provides an over... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607522 Tue, 15 Mar 2011 00:00:00 +0100 4607522 http://www.medworm.com/index.php?rid=4607521&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406051%26dopt%3DAbstract Authors: Nachega JB, Rosenkranz B, Simon G, Chaisson RE, Diacon A, Taljaard J The global impact of the HIV epidemic on the prevention and management of tuberculosis has resulted in added levels of complexity for physicians and other health- care workers caring for these patients. In addition to the usual difficulties associated with drug toxicities and regimen adherence, the concomitant treatment of HIV and tuberculosis is complicated by drug interactions between antiretroviral agents and the antituberculous containing rifampin-based regimens, and the frequent occurrence of the tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). Currently, the best antitubercular regimens include a rifamycin, usually rifampin, because of the high cost of rifabutin. Two nucleo... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607521 Tue, 15 Mar 2011 00:00:00 +0100 4607521 http://www.medworm.com/index.php?rid=4607520&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406052%26dopt%3DAbstract Authors: Hong SY, Nachega JB, Kelley K, Bertagnolio S, Marconi VC, Jordan MR Antiretroviral therapy (ART) scale-up in resource limited settings (RLS) has been successful, utilizing a standardized population-based approach to ART delivery. An unintended consequence of treatment scale-up is the inevitable emergence of HIV drug resistance (HIVDR) in populations even when patient adherence to ART is optimally supported. HIVDR has the potential to undermine the dramatic gains that ART has had in reducing the morbidity and mortality of HIV-infected patients in RLS. Sustaining and expanding ART coverage in RLS will depend upon the ability of ART programs to deliver ART in a way that minimizes the emergence of HIVDR. Fortunately, current evidence demonstrates that HIVDR in RLS has neither emer... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607520 Tue, 15 Mar 2011 00:00:00 +0100 4607520 http://www.medworm.com/index.php?rid=4607519&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406053%26dopt%3DAbstract Conclusion: The established benefits of ARV therapy in children of all ages can be enhanced by appropriate pharmacokinetic data on established antiretroviral agents and child-friendly drug formulations. Besides new suppressive treatment options in treatment experienced patients with multi-class resistant virus the new drug classes provide potential for novel means of disease modification and reduction of vertical transmission. Novel drug classes and delivery systems in development provide potential for further reduction in vertical transmission of HIV, rapid virological suppression and improved neurological outcomes in children and adults. PMID: 21406053 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607519 Tue, 15 Mar 2011 00:00:00 +0100 4607519 http://www.medworm.com/index.php?rid=4607518&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406054%26dopt%3DAbstract Authors: Zeier MD, Nachega JB Since the identification of the Human Immunodeficiency Virus (HIV) as the cause of the syndrome of Acquired Immunodeficiency Syndrome (AIDS), there has been an evolution of compounds targeting the replication of the virus in an effort to delay clinical progression. In this review, we revise the mechanism of action of the different groups of drugs. We shortly revisit the older and perhaps lesser used as well as the more recently approved drugs and mention some of the compounds still under investigation. PMID: 21406054 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607518 Tue, 15 Mar 2011 00:00:00 +0100 4607518 http://www.medworm.com/index.php?rid=4607517&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406055%26dopt%3DAbstract Authors: Nachega JB, Rosenkranz B PMID: 21406055 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607517 Tue, 15 Mar 2011 00:00:00 +0100 4607517 http://www.medworm.com/index.php?rid=4607525&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21394965%26dopt%3DAbstract Authors: Escobedo AA, Cimerman S, Almirall P PMID: 21394965 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4607525 Tue, 01 Feb 2011 00:00:00 +0100 4607525 http://www.medworm.com/index.php?rid=4490136&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303334%26dopt%3DAbstract Authors: Kwaan HC, Ison MG PMID: 21303334 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490136 Tue, 01 Feb 2011 00:00:00 +0100 4490136 http://www.medworm.com/index.php?rid=4490135&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303335%26dopt%3DAbstract Authors: Young JA This is a review of the epidemiology and management of infectious complications of contemporary management of chronic leukemias. Patients with chronic leukemias typically are affected by nuisance infections due to the underlying hematologic condition, particularly hypogammaglobulinemia in CLL patients. With active treatment, particularly those agents that cause defects in cell-mediated immunity, the incidence of opportunistic infections increases although endogenous bacterial, mycobacterial, and fungal infections also occur. Exogenous treatment with immunoglobulin and antimicrobial prophylaxis, particularly anti-Pneumocystis prophylaxis, may be indicated in select patients. Routine vaccinations should be maintained in these patients and vaccination early in the course... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490135 Tue, 01 Feb 2011 00:00:00 +0100 4490135 http://www.medworm.com/index.php?rid=4490134&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303336%26dopt%3DAbstract Authors: Tessier J, Sifri CD Bacterial infections are a serious complication of hematologic malignancies and the therapies used to treat them. Neutropenia can result from the malignancy itself or develop as a complication of chemotherapy and remains a major risk factor for the development of infections in these patients. In addition, the mechanical and chemotherapeutic interventions applied to patients with hematologic malignancies impose additional challenges to host defenses against bacterial invasion. The bacteria responsible for most infections in this patient population have continued to evolve as different therapeutic, preventive, and preemptive strategies are introduced into the armamentarium for leukemias, lymphomas, and myelomas. Both Gram-negative and Gram-positive pathogens ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490134 Tue, 01 Feb 2011 00:00:00 +0100 4490134 http://www.medworm.com/index.php?rid=4490133&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303337%26dopt%3DAbstract Authors: Magauran CE, Salgado CD Hematopoietic Stem Cell Transplantation (HSCT) has revolutionized the outcome of many malignant and non-malignant disorders; however, infection still accounts for a substantial number of deaths after both allogeneic and autologous transplants. Hospital-acquired infections (HAI) such as bloodstream infections, pneumonias, and diarrhea are common in this population and account for significant morbidity and cost of care. Also, there is renewed focus on epidemiologically important organisms as the cause of HAI, most notably methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, multi-drug resistant gram-negative bacilli, and Clostridium difficile. We review the infectious risks of HSCT, including those due to HAI as well as measures... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490133 Tue, 01 Feb 2011 00:00:00 +0100 4490133 http://www.medworm.com/index.php?rid=4490132&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303338%26dopt%3DAbstract This article reviews the epidemiology and prophylactic strategies available for these opportunistic viral pathogens. PMID: 21303338 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490132 Tue, 01 Feb 2011 00:00:00 +0100 4490132 http://www.medworm.com/index.php?rid=4490131&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303339%26dopt%3DAbstract Authors: Ison MG Influenza results in annual epidemics of respiratory viral illness during the winter; when a novel virus enters the human population, a pandemic may result with a larger proportion of the population sickened. Unlike the mild and typically self-limited disease seen in immunocompetent patients, immunocompromised patients frequently have a more severe course. These individuals shed virus for a prolonged period of time, have a high rate of viral pneumonia, more frequently develop bacterial and fungal super-infections, and may develop late-onset airflow obstruction. Further, antiviral resistance develops more frequently in immunosuppressed patients. Although the cornerstone of prevention of influenza is vaccination, vaccine efficacy in patients with hematologic malignancies... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490131 Tue, 01 Feb 2011 00:00:00 +0100 4490131 http://www.medworm.com/index.php?rid=4490130&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303340%26dopt%3DAbstract Authors: Kwaan HC Anemia most frequently accompanies infection in varying degrees and in different forms. Anemia of inflammation is the most common and is due to over-expression of hepcidin. This is followed by hemolytic anemia, red cell aplasia and blood loss. The degree of anemia may not necessarily be proportional to the severity of the infection, nor is it specific for the type of infection. A clear understanding of these diverse causes and a recognition that they often occur in combination can be of enormous assistance in forming a proper diagnosis and an appropriate management plan. PMID: 21303340 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490130 Tue, 01 Feb 2011 00:00:00 +0100 4490130 http://www.medworm.com/index.php?rid=4490129&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303341%26dopt%3DAbstract Authors: Lindholm PF, Annen K, Ramsey G The use of blood donor history and state-of-the-art FDA-licensed serological and nucleic acid testing (NAT) assays have greatly reduced the "infectious window" for several transfusion-transmitted pathogens. Currently transmission of human immunodeficiency virus (HIV), Human T-cell Lymphotropic Virus (HTLV), hepatitis viruses and West Nile Virus are rare events. The seroprevalence of cytomegalovirus in the donor population is high and cytomegalovirus infection can cause significant complications for immunocompromised recipients of blood transfusion. Careful use of CMV seronegative blood resources and leukoreduction of blood products are able to prevent most CMV infections in these patients. Currently, bacterial contamination of platelet concentrat... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490129 Tue, 01 Feb 2011 00:00:00 +0100 4490129 http://www.medworm.com/index.php?rid=4490128&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303342%26dopt%3DAbstract Authors: Mediouni S, Baillat G, Darque A, Ravaux I, Loret E Tat is a regulatory viral protein known as transactivator of HIV-1 genes but Tat is also secreted in the blood from HIV-1 infected cells. Extra cellular Tat can cross cellular membranes to trigger apoptosis and might explain the incapacity of the cellular immunity to eliminate HIV-1 infected cells. There is a controversy regarding Tat structure with studies suggesting that Tat would be a naturally unfolded protein. Here, we show that synthetic Tat variants need to be folded to have a transactivation activity in a cellular assay but this folding is unstable regarding the buffers and/or pH used as solvent. We show also that the recognition of a Tat variant versus peptides, covering its sequence, was different. Using an indirect ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490128 Tue, 01 Feb 2011 00:00:00 +0100 4490128 http://www.medworm.com/index.php?rid=4490127&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21303343%26dopt%3DAbstract Authors: Kirchmair J, Distinto S, Liedl KR, Markt P, Rollinger JM, Schuster D, Spitzer GM, Wolber G Computational chemistry has always played a key role in anti-viral drug development. The challenges and the quickly rising public interest when a virus is becoming a threat has significantly influenced computational drug discovery. The most obvious example is anti-AIDS research, where HIV protease and reverse transcriptase have triggered enormous efforts in developing and improving computational methods. Methods applied to anti-viral research include (i) ligand-based approaches that rely on known active compounds to extrapolate biological activity, such as machine learning techniques or classical QSAR, (ii) structure-based methods that rely on an experimentally determined 3D structure of... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4490127 Tue, 01 Feb 2011 00:00:00 +0100 4490127 http://www.medworm.com/index.php?rid=4356732&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189123%26dopt%3DAbstract Authors: Kirchmair J, Distinto S, Liedl KR, Markt P, Rollinger JM, Schuster D, Spitzer GM, Wolber G Computational chemistry has always played a key role in anti-viral drug development. The challenges and the quickly rising public interest when a virus is becoming a threat has significantly influenced computational drug discovery. The most obvious example is anti-AIDS research, where HIV protease and reverse transcriptase have triggered enormous efforts in developing and improving computational methods. Methods applied to anti-viral research include (i) ligand-based approaches that rely on known active compounds to extrapolate biological activity, such as machine learning techniques or classical QSAR, (ii) structure-based methods that rely on an experimentally determined 3D structure of... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4356732 Tue, 28 Dec 2010 00:00:00 +0100 4356732 http://www.medworm.com/index.php?rid=4356712&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189124%26dopt%3DAbstract Authors: Mediouni S, Baillat G, Darque A, Ravaux I, Loret E Tat is a regulatory viral protein known as transactivator of HIV-1 genes but Tat is also secreted in the blood from HIV-1 infected cells. Extra cellular Tat can cross cellular membranes to trigger apoptosis and might explain the incapacity of the cellular immunity to eliminate HIV-1 infected cells. There is a controversy regarding Tat structure with studies suggesting that Tat would be a naturally unfolded protein. Here, we show that synthetic Tat variants need to be folded to have a transactivation activity in a cellular assay but this folding is unstable regarding the buffers and/or pH used as solvent. We show also that the recognition of a Tat variant versus peptides, covering its sequence, was different. Using an indirect ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4356712 Tue, 28 Dec 2010 00:00:00 +0100 4356712 http://www.medworm.com/index.php?rid=4067112&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20929436%26dopt%3DAbstract Authors: Shevchuk NA PMID: 20929436 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4067112 Thu, 30 Sep 2010 23:00:00 +0100 4067112 http://www.medworm.com/index.php?rid=3867202&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701569%26dopt%3DAbstract Authors: Schuster RK The discovery history of opisthorchiid flukes dates back more than 200 years. The life cycle of these liver flukes includes prosobranch snails as the first and a big variety of freshwater fish as the second intermediate hosts. Opisthorchis felineus, O. viverrini and Clonorchis sinensis are species of major medical importance, while sporadic cases of human infection with other representatives of this family are also documented in the literature. There are estimations that 17 million people are infected and more than 350 million people are at risk, mainly in Asian countries. Although opisthorchiid flukes live in the bile ducts of the liver and in the gall bladder, they can affect surrounding liver tissue and even other organs. They are also known to induce the produc... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867202 Mon, 09 Aug 2010 23:00:00 +0100 3867202 http://www.medworm.com/index.php?rid=3867201&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701570%26dopt%3DAbstract Authors: Sawanyawisuth K, Sawanyawisuth K Eosinophilic meningitis caused by Angiostrongylus cantonensis is an emerging infectious disease. It is the most common form of human angiostrongyliasis. The diagnosis is made by clinical criteria including the presence of cerebrospinal fluid eosinophils and a history of exposure to A. cantonensis larvae, e.g., from raw freshwater snails or contaminated vegetables. Among various treatment options, corticosteroid is the only effective treatment. PMID: 20701570 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867201 Mon, 09 Aug 2010 23:00:00 +0100 3867201 http://www.medworm.com/index.php?rid=3867200&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701571%26dopt%3DAbstract Authors: Mordvinov VA, Furman DP Opisthorchosis is a helminthiasis affecting mainly the hepatobiliary system and pancreas; its most dramatic complication is malignization of the organs infected by the parasites. The causative agents of opisthorchosis are two species of liver flukes, the trematodes belonging to the family Opisthorchiidae-Opisthorchis felineus and O. viverrini. The Chinese liver fluke, Clonorchis sinensis, also member of the family Opisthorchiidae, causes clonorchosis, a disease very close in symptomatology. According to different estimations, up to 40 million people are currently infected with these liver flukes and up to 600-750 million people in Eurasian countries constitute the risk group. These parasites colonize ever-increasing new areas in Eurasia where this disea... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867200 Mon, 09 Aug 2010 23:00:00 +0100 3867200 http://www.medworm.com/index.php?rid=3867199&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701572%26dopt%3DAbstract We describe a pan-phylum comparison of genomes that is underway. This comparative genomics approach is expected to identify molecular characteristics that are conserved among all nematodes, and hence applicable to nematode pathogens throughout the phylum, including species from the genus Trichinella. T. spiralis expression data for muscle larvae has been integrated with genome sequences to identify specific genes and proteins with relevance to control of this stage of the parasite. Examples are discussed in which genomic information may advance understanding of T. spiralis biology and new methods for treating infections by this parasite. PMID: 20701572 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867199 Mon, 09 Aug 2010 23:00:00 +0100 3867199 http://www.medworm.com/index.php?rid=3867198&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701573%26dopt%3DAbstract Authors: Helmy MM Cyclosporiasis is a protracted, relapsing gastroenteritis and has a short recorded history. Cyclospora cayetanensis is an enigmatic parasite since its discovery highlights the need for isolation of cases of infection that could be part of widespread outbreaks. It is associated with diarrhoea among children in developing countries in the Americas, where C. cayetanensis is endemic; traveller's diarrhoea and/or food and waterborne outbreaks sometimes occur in the developed countries. In SubSaharan Africa and Egypt, cyclosporiasis has been reported to occur in both immunocompromised and immunocompetent patients. Zoonotic species of Cyclospora have also been identified worldwide in primates, indicating likely endemicity of this underreported disease. This can be attributed... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867198 Mon, 09 Aug 2010 23:00:00 +0100 3867198 http://www.medworm.com/index.php?rid=3867197&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701574%26dopt%3DAbstract Authors: Hagel I, Giusti T A. lumbricoides is the largest of the common nematode parasites of man and has been associated with intestinal pathology, respiratory symptoms and malnutrition in children from endemic areas. Current anthelmintic treatments have proven to be safe. However, a reduced efficacy of single dose drugs has been reported. In veterinary practice, anthelmintic drug resistance is an irreversible problem. Thus, research and development of sensitive tools for early detection of drug resistance as well as new anthelmintic approaches are urgently needed. In this review, we summarized data providing information about current drug therapy against A. lumbricoides and other intestinal helminths, new drugs in experimental trials, future drugs perspectives and the identification ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867197 Mon, 09 Aug 2010 23:00:00 +0100 3867197 http://www.medworm.com/index.php?rid=3867196&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701575%26dopt%3DAbstract Authors: Escobedo AA, Almirall P, Robertson LJ, Franco RM, Hanevik K, Mørch K, Cimerman S lthough giardiasis has been a threat to mankind for thousands of years, this protozoan infection was, until recently, relatively neglected. Giardia duodenalis is recognised as a major cause of parasite-induced diarrhoea in humans and animals, and is currently an important public health problem, placing a heavy burden on both diagnostic and treatment services at health care institutions, mostly in developing countries, but also in highly developed countries. Steady progress in recent years, using a combination of molecular, immunological, and clinical approaches, has substantially increased our understanding of Giardia and important aspects of the clinical manifestations that it causes. The purp... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867196 Mon, 09 Aug 2010 23:00:00 +0100 3867196 http://www.medworm.com/index.php?rid=3867195&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701576%26dopt%3DAbstract Authors: Silva CV, Costa-Cruz JM The Taenia saginata taeniasis-cysticercosis complex is a cosmopolitan zoonosis of great medical, veterinary and economic importance where humans play an important role as the carrier of adult stage and cattle as carrier of the larval stage of the parasite. Here we reviewed aspects concerning diagnosis, vaccine development, biological control and treatment of the disease. PMID: 20701576 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867195 Mon, 09 Aug 2010 23:00:00 +0100 3867195 http://www.medworm.com/index.php?rid=3867194&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701577%26dopt%3DAbstract Authors: Magauran CE, Salgado CD Hematopoietic Stem Cell Transplantation (HSCT) has revolutionized the outcome of many malignant and non-malignant disorders; however, infection still accounts for a substantial number of deaths after both allogeneic and autologous transplants. Hospital-acquired infections (HAI) such as bloodstream infections, pneumonias, and diarrhea are common in this population and account for significant morbidity and cost of care. Also, there is renewed focus on epidemiologically important organisms as the cause of HAI, most notably methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, multi-drug resistant gram-negative bacilli, and Clostridium difficile. We review the infectious risks of HSCT, including those due to HAI as well as measures... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867194 Mon, 09 Aug 2010 23:00:00 +0100 3867194 http://www.medworm.com/index.php?rid=3867193&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701578%26dopt%3DAbstract Authors: Ison MG Influenza results in annual epidemics of respiratory viral illness during the winter; when a novel virus enters the human population, a pandemic may result with a larger proportion of the population sickened. Unlike the mild and typically self-limited disease seen in immunocompetent patients, immunocompromised patients frequently have a more severe course. These individuals shed virus for a prolonged period of time, have a high rate of viral pneumonia, more frequently develop bacterial and fungal super-infections, and may develop late-onset airflow obstruction. Further, antiviral resistance develops more frequently in immunosuppressed patients. Although the cornerstone of prevention of influenza is vaccination, vaccine efficacy in patients with hematologic malignancies... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867193 Mon, 09 Aug 2010 23:00:00 +0100 3867193 http://www.medworm.com/index.php?rid=3867192&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701579%26dopt%3DAbstract Authors: Young JA This is a review of the epidemiology and management of infectious complications of contemporary management of chronic leukemias. Patients with chronic leukemias typically are affected by nuisance infections due to the underlying hematologic condition, particularly hypogammaglobulinemia in CLL patients. With active treatment, particularly those agents that cause defects in cell-mediated immunity, the incidence of opportunistic infections increases although endogenous bacterial, mycobacterial, and fungal infections also occur. Exogenous treatment with immunoglobulin and antimicrobial prophylaxis, particularly anti-Pneumocystis prophylaxis, may be indicated in select patients. Routine vaccinations should be maintained in these patients and vaccination early in the course... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867192 Mon, 09 Aug 2010 23:00:00 +0100 3867192 http://www.medworm.com/index.php?rid=3867191&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701580%26dopt%3DAbstract Authors: Tessier J, Sifri CD Bacterial infections are a serious complication of hematologic malignancies and the therapies used to treat them. Neutropenia can result from the malignancy itself or develop as a complication of chemotherapy and remains a major risk factor for the development of infections in these patients. In addition, the mechanical and chemotherapeutic interventions applied to patients with hematologic malignancies impose additional challenges to host defenses against bacterial invasion. The bacteria responsible for most infections in this patient population have continued to evolve as different therapeutic, preventive, and preemptive strategies are introduced into the armamentarium for leukemias, lymphomas, and myelomas. Both Gram-negative and Gram-positive pathogens ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867191 Mon, 09 Aug 2010 23:00:00 +0100 3867191 http://www.medworm.com/index.php?rid=3867190&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701581%26dopt%3DAbstract This article reviews the epidemiology and prophylactic strategies available for these opportunistic viral pathogens. PMID: 20701581 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867190 Mon, 09 Aug 2010 23:00:00 +0100 3867190 http://www.medworm.com/index.php?rid=3867189&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701582%26dopt%3DAbstract Authors: Lindholm PF, Annen K, Ramsey G The use of blood donor history and state-of-the-art FDA-licensed serological and nucleic acid testing (NAT) assays have greatly reduced the "infectious window" for several transfusion-transmitted pathogens. Currently transmission of human immunodeficiency virus (HIV), Human T-cell Lymphotropic Virus (HTLV), hepatitis viruses and West Nile Virus are rare events. The seroprevalence of cytomegalovirus in the donor population is high and cytomegalovirus infection can cause significant complications for immunocompromised recipients of blood transfusion. Careful use of CMV seronegative blood resources and leukoreduction of blood products are able to prevent most CMV infections in these patients. Currently, bacterial contamination of platelet concentrat... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867189 Mon, 09 Aug 2010 23:00:00 +0100 3867189 http://www.medworm.com/index.php?rid=3867188&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20701583%26dopt%3DAbstract Authors: Kwaan HC Anemia most frequently accompanies infection in varying degrees and in different forms. Anemia of inflammation is the most common and is due to over-expression of hepcidin. This is followed by hemolytic anemia, red cell aplasia and blood loss. The degree of anemia may not necessarily be proportional to the severity of the infection, nor is it specific for the type of infection. A clear understanding of these diverse causes and a recognition that they often occur in combination can be of enormous assistance in forming a proper diagnosis and an appropriate management plan. PMID: 20701583 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3867188 Mon, 09 Aug 2010 23:00:00 +0100 3867188 http://www.medworm.com/index.php?rid=3845581&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20687894%26dopt%3DAbstract Authors: López-Estraño C PMID: 20687894 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3845581 Sat, 31 Jul 2010 23:00:00 +0100 3845581 http://www.medworm.com/index.php?rid=3586586&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20480551%26dopt%3DAbstract Authors: Donaldson T, Kim K New antimalarials are needed due to the rapid development of resistance to currently deployed drugs. Because Plasmodium species are unable to synthesize purines, purine salvage pathways have been proposed as novel anti-malarial targets. The purine salvage pathway in Plasmodium is streamlined with adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and hypoxanthine-xanthine-guanine-phosphoribosyltransferase (HXGPRT) representing the major pathway for purine acquisition. Plasmodium falciparum enzymes PfADA and PfPNP have unique dual specificity that enable them to act upon methylthiopurines resulting from polyamine synthesis. Thus Plasmodium ADA and PNP function in both purine salvage and purine recycling. Genetic studies have confirmed the import... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3586586 Sat, 22 May 2010 05:09:05 +0100 3586586 http://www.medworm.com/index.php?rid=3567138&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20462397%26dopt%3DAbstract Authors: Waters NC PMID: 20462397 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3567138 Sun, 16 May 2010 03:48:05 +0100 3567138 http://www.medworm.com/index.php?rid=3523293&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20429861%26dopt%3DAbstract Authors: Padilla-Vaca F, Anaya-Velázquez F Entamoeba histolytica is able to invade human tissues by means of several molecules and biological properties related to the virulence. Pathogenic amebas use three major virulence factors, Gal/GalNAc lectin, amebapore and proteases, for lyse, phagocytose, kill and destroy a variety of cells and tissues in the host. Responses of the parasite to host components such as mucins and bacterial flora influence the behavior of pathogenic amebas altering their expression of virulence factors. The relative virulence of different strains of E. histolytica has been shown to vary as a consequence of changes in conditions of in vitro cultivation which implies substantial changes in basic metabolic aspects and factors directly and indirectly related to am... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3523293 Wed, 28 Apr 2010 23:00:00 +0100 3523293 http://www.medworm.com/index.php?rid=3523292&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20429862%26dopt%3DAbstract Authors: Tian HF, Chen B, Wen JF Giardiasis is a worldwide parasitic disease caused by the protozoan Giardia lamblia in humans and other animals, especially live stocks. Here, we briefly review the current state of therapeutic availability for gidardiasis, including chemical drugs and vaccines, and the dilemma in the prevention and treatment of this disease, including the emergence of drug resistance and the shortage of vaccine (especially for humans). Future efforts and progress in controlling giardiasis are expected in three aspects: clarification of the drug resistance mechanisms, development of efficient vaccines, and identification of more targets for new drugs and vaccines. PMID: 20429862 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3523292 Wed, 28 Apr 2010 23:00:00 +0100 3523292 http://www.medworm.com/index.php?rid=3523291&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20429863%26dopt%3DAbstract Authors: Lalle M Giardia duodenalis (syn. G. lamblia, G. intestinalis) is a flagellated protozoan, member of the order Diplomonadidae, that parasitizes the upper part of the small intestine of mammals, including human, pets and livestock. G. duodenalis is the causative agent of giardiasis, the most common non-bacterial and non-viral diarrheal diseases affecting humans worldwide. Recently, giardiasis was included in the 'Neglected Disease Initiative', estimating that 280 million people are infected each year with G. duodenalis. Transmission occurs via the faecal-oral route by ingestion of cysts, the infective stage of the parasite, either by direct person-to-person transmission or indirectly through water and food. There are several effective drugs that have been approved for the treatm... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3523291 Wed, 28 Apr 2010 23:00:00 +0100 3523291 http://www.medworm.com/index.php?rid=3523290&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20429864%26dopt%3DAbstract Authors: López-Camarillo C, Hernández de la Cruz ON, Vivas JG, Retana JF, Valdez MP, Rosas IL, Marchat LA The messenger RNA precursors (pre-mRNA) 3'-end processing occurs in a two-step co-transcriptional coupled reaction, denoted as cleavage and polyadenylation. Both processes depend on trans-acting factors interacting in a coordinated manner with cis-sequence motifs located at the 3' untranslated region of transcripts. In this paper, we reviewed mechanisms involved in pre-mRNA processing in eukaryotic organisms, including our own findings about sequences and proteins potentially involved in mRNA 3'-end formation in the protozoan parasite Entamoeba histolytica. Interestingly, protein sequence comparisons among E. histolytica, yeast, and human pre-mRNA processing machineries showe... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3523290 Wed, 28 Apr 2010 23:00:00 +0100 3523290 http://www.medworm.com/index.php?rid=3523289&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20429865%26dopt%3DAbstract Authors: Vanhamme L African trypanosomes are responsible for sleeping sickness in man and nagana in cattle, which are both tremendous health burdens in Africa. Most African trypanosome species are killed by human serum. This is due to a serum trypanolytic particle specific of some old world monkeys and great apes, an HDL subclass containing two proteins which appeared recently in mammalian evolution, apolipoprotein L1 and haptoglobin related protein. Nevertheless, two African trypanosome species, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense are able to infect humans, because they developed resistance to trypanolysis. Resistance to human serum in Trypanosoma brucei rhodesiense is due to a single gene called SRA. This mechanism of lysis-resistance is therefore an examp... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3523289 Wed, 28 Apr 2010 23:00:00 +0100 3523289 http://www.medworm.com/index.php?rid=3523288&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20429866%26dopt%3DAbstract Authors: Gopalakrishnan AM, López-Estraño C Apicomplexans comprise some of the most life threatening parasites infecting human and livestock and includes Plasmodium and Toxoplasma, the causative agents of malaria and toxoplasmosis respectively, in humans as well as Neospora caninum (abortion in livestock, neosporosis in dogs), Cryptosporidium (Diarrheal cryptosporidiosis and opportunistic infections in AIDS patients) and Eimeria (poultry coccidiosis). These parasites are characterized by a complex life cycle usually alternating between sexual and asexual cycles in different hosts. The need to adapt to different host environments demands a tight regulation of gene expression during parasite development. Therefore, the understanding of parasite biology will facilitate the control o... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3523288 Wed, 28 Apr 2010 23:00:00 +0100 3523288 http://www.medworm.com/index.php?rid=3523287&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20429867%26dopt%3DAbstract Authors: Gobert GN Schistosomiasis is a wide-spread parasitic disease of many tropical and sub-tropical countries. The current central control measure is the use of single drug praziquantel, although the mode of action is not fully realised and the possibility resistance is a concern. The preferred alternative control strategy would involve a target vaccine, which unfortunately hasn't yet been realised. A useful research tool for better understanding the immunological elimination of an active infection is vaccination with live, radiation attenuation parasites. Both of these important research approaches, whether defining the current drug regime or the immunological interactions between the host and parasite, can be better understood through the profiling of the transcriptional status o... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3523287 Wed, 28 Apr 2010 23:00:00 +0100 3523287 http://www.medworm.com/index.php?rid=3468688&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20384586%26dopt%3DAbstract Authors: Delis HC, Chamorro A PMID: 20384586 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3468688 Wed, 31 Mar 2010 23:00:00 +0100 3468688 http://www.medworm.com/index.php?rid=3411148&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334617%26dopt%3DAbstract Authors: Phillips MA, Rathod PK Malaria remains a globally prevalent infectious disease that leads to significant morbidity and mortality. While there are a number of drugs approved for its treatment, drug resistance has compromised most of them, making the development of new drugs for the treatment and prevention of malaria essential. The completion of the Plasmodium falciparum genome and a growing understanding of parasite biology are fueling the search for novel drug targets. Despite this, few targets have been chemically validated in vivo. The pyrimidine biosynthetic pathway illustrates one of the best examples of successful identification of anti-malarial drug targets. This review focuses on recent studies to exploit the fourth enzyme in the de novo pyrimidine biosynthetic pathway... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3411148 Wed, 24 Mar 2010 00:00:00 +0100 3411148 http://www.medworm.com/index.php?rid=3411147&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334618%26dopt%3DAbstract Authors: Trenholme KR, Brown CL, Skinner-Adams TS, Stack C, Lowther J, To J, Robinson MW, Donnelly SM, Dalton JP, Gardiner DL Novel targets for new drug development are urgently required to combat malaria, a disease that puts half of the world's population at risk. One group of enzymes identified within the genome of the most lethal of the causative agents of malaria, Plasmodium falciparum, that may have the potential to become new targets for antimalarial drug development are the aminopeptidases. These enzymes catalyse the cleavage of the N-terminal amino acids from proteins and peptides. P. falciparum appears to encode for at least nine aminopeptidases, two neutral aminopeptidases, one aspartyl aminopeptidase, one aminopeptidase P, one prolyl aminopeptidase and four methionine aminop... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3411147 Wed, 24 Mar 2010 00:00:00 +0100 3411147 http://www.medworm.com/index.php?rid=3411146&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334619%26dopt%3DAbstract Authors: Spry C, van Schalkwyk DA, Strauss E, Saliba KJ In the absence of an effective vaccine against malaria suitable for widespread deployment, the control of this lethal infectious disease relies heavily on antimalarial chemotherapies. The most virulent of the parasites that cause malaria (Plasmodium falciparum) has, however, developed resistance to all antimalarial agents in clinical use, and there is a desperate need for new antimalarial agents that target previously unexploited parasite processes. P. falciparum requires an extracellular supply of pantothenate to support its proliferation during the erythrocytic stage of its development in humans. This requirement highlights the mechanisms involved in the utilization (uptake and metabolism) of pantothenate as potential targets fo... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3411146 Wed, 24 Mar 2010 00:00:00 +0100 3411146 http://www.medworm.com/index.php?rid=3411135&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334620%26dopt%3DAbstract Authors: Donaldson T, Kim K New antimalarials are needed due to the rapid development of resistance to currently deployed drugs. Because Plasmodium species are unable to synthesize purines, purine salvage pathways have been proposed as novel anti-malarial targets. The purine salvage pathway in Plasmodium is streamlined with adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and hypoxanthine-xanthine-guanine-phosphoribosyltransferase (HXGPRT) representing the major pathway for purine acquisition. Plasmodium falciparum enzymes PfADA and PfPNP have unique dual specificity that enable them to act upon methylthiopurines resulting from polyamine synthesis. Thus Plasmodium ADA and PNP function in both purine salvage and purine recycling. Genetic studies have confirmed the import... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3411135 Wed, 24 Mar 2010 00:00:00 +0100 3411135 http://www.medworm.com/index.php?rid=3411134&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334621%26dopt%3DAbstract Authors: Kozlov S, Waters NC, Chavchich M Cancer and malaria are life threatening diseases killing millions of people each year. In spite of our best efforts, both continue to resist full control and eradication. If untreated, both malaria and cancer can lead to death. Only a few antimalarial drugs have been developed over the last decades and new drugs are urgently needed to combat drug-resistant parasites. Significant progress has been made in understanding the molecular mechanisms of cancer and designing new anticancer therapies. However, similar to malaria, majority of cancers quickly develop resistance to single target-based therapy. Novel cancer therapeutics are being developed with the aim of targeting multiple signalling pathways in tumour cells, an approach that may be applica... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3411134 Wed, 24 Mar 2010 00:00:00 +0100 3411134 http://www.medworm.com/index.php?rid=3411131&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334622%26dopt%3DAbstract Authors: Chung DW, Le Roch KG The human malarial parasite, Plasmodium falciparum, is responsible for one of the most infectious diseases of the world and is quickly gaining resistance to the commonly used antimalarial treatments. New data are continually reinforcing the idea that biological functions associated with the ubiquitin proteasome system (UPS) are not just limited to non-lysomal degradation of proteins but consist of a wide array of regulatory mechanisms such as cell cycle progression, transcriptional regulation, gene expression and trafficking. While there is much effort in understanding the UPS in many eukaryotic organisms, the Plasmodium UPS has been relatively understudied despite its potential as a therapeutic drug target. However, in vitro proteasome inhibitors studies ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3411131 Wed, 24 Mar 2010 00:00:00 +0100 3411131 http://www.medworm.com/index.php?rid=3411129&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334623%26dopt%3DAbstract Authors: Pesce ER, Cockburn IL, Goble JL, Stephens LL, Blatch GL Ongoing research into the chaperone systems of malaria parasites, and particularly of Plasmodium falciparum, suggests that heat shock proteins (Hsps) could potentially be an excellent class of drug targets. The P. falciparum genome encodes a vast range and large number of chaperones, including 43 Hsp40, six Hsp70, and three Hsp90 proteins (PfHsp40s, PfHsp70s and PfHsp90s), which are involved in a number of fundamental cellular processes including protein folding and assembly, protein translocation, signal transduction and the cellular stress response. Despite the fact that Hsps are relatively conserved across different species, PfHsps do exhibit a considerable number of unique structural and functional features. One PfHsp... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3411129 Wed, 24 Mar 2010 00:00:00 +0100 3411129 http://www.medworm.com/index.php?rid=3411125&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334624%26dopt%3DAbstract Authors: Jirage D, Keenan SM, Waters NC Protein kinases are pursued drug targets in numerous diseases including parasitic infections such as malaria. Plasmodium falciparum, the deadliest malarial parasite, relies on numerous protein kinases to regulate growth and differentiation through a complex life cycle that alternates between an invertebrate and vertebrate host. Many of the protein kinases are uncharacterized, however genetic and biochemical approaches have identified homologues of known eukaryotic kinases families as well as unique families of plasmodial kinases. Several classes of protein kinases have been studied, revealing that not only are these kinases essential for parasite viability, but that structure-based drug design strategies can be applicable to identify protein kina... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3411125 Wed, 24 Mar 2010 00:00:00 +0100 3411125 http://www.medworm.com/index.php?rid=3292242&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166968%26dopt%3DAbstract Authors: Urbanek C, Palm F, Grau AJ There is increasing evidence that acute bacterial and viral infection represent trigger factors that temporarily elevate the risk of ischemic stroke. During and after influenza epidemics vascular death rates and hospitalizations for stroke are increased. Influenza vaccination is an effective measure to reduce hospitalization and mortality in the elderly and work incapacity in adults of working age. Results of several observational studies support the hypothesis that influenza vaccination is associated with reduced odds of stroke. As randomized studies are lacking, a causal role of influenza vaccination in stroke prevention is not proven, however. According to current guidelines in many countries, that recommend the vaccination in all patients with ch... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3292242 Thu, 18 Feb 2010 00:00:00 +0100 3292242 http://www.medworm.com/index.php?rid=3292241&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166969%26dopt%3DAbstract Authors: Smith CJ, Tyrrell PJ Infection is the commonest complication of stroke and has a major impact on morbidity and mortality. The relationships between susceptibility to infection after stroke and the influence of infection on stroke outcome are complex, but have considerable clinical relevance. Both pharmacological and non-pharmacological interventions in acute stroke may affect the risk of developing infection by influencing potentially modifiable risk factors, for example exposure to infectious organisms (dysphagia/aspiration), or immune susceptibility to infectious challenge. Treatment of infection itself may also reduce ischaemic injury, and influence outcome following stroke. In this review we discuss the role of current and emerging treatments for stroke and their effects o... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3292241 Thu, 18 Feb 2010 00:00:00 +0100 3292241 http://www.medworm.com/index.php?rid=3292240&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166970%26dopt%3DAbstract Authors: Nagel MA, Mahalingam R, Cohrs RJ, Gilden D While arteriosclerotic disease and hypertension, with or without diabetes, are the most common causes of stroke, viruses may also produce transient ischemic attacks and stroke. The three most-well studied viruses in this respect are varicella zoster virus (VZV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV), all of which are potentially treatable with antiviral agents. Productive VZV infection in cerebral arteries after reactivation (zoster) or primary infection (varicella) has been documented as a cause of ischemic and hemorrhagic stroke, aneurysms with subarachnoid and intracerebral hemorrhage, arterial ectasia and as a co-factor in cerebral arterial dissection. CMV has been suggested to play a role in the pathogenesi... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3292240 Thu, 18 Feb 2010 00:00:00 +0100 3292240 http://www.medworm.com/index.php?rid=3292239&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166971%26dopt%3DAbstract Authors: Engel O, Meisel A Infectious diseases are the most common medical complication after cerebral ischemia, inpairing both the neurological and the general medical outcome. The most frequent infectious complications are bacterial pneumonia and urinary tract infections. There is a growing body of evidence that a secondary immunosuppressive state accounts for the increased risk of infection following stroke. Infections do not only have an important impact on outcome after stroke but also are known risk factors for stroke. Thus, suitable models for investigating the relation between infections and stroke are urgently needed. Elucidating the underlying mechanisms might facilitate the development of new therapeutic strategies and improve patient outcome. Here we present recent insights... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3292239 Thu, 18 Feb 2010 00:00:00 +0100 3292239 http://www.medworm.com/index.php?rid=3292238&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166972%26dopt%3DAbstract Authors: Emsley HC, Hopkins SJ Infections occur commonly following stroke and adversely influence outcome. Dysphagia, greater stroke severity and increasing age are associated with post-stroke infection, but post-stroke immunodepression is now recognised as an independent factor associated with increased susceptibility. Counter-regulatory responses, triggered by the pro-inflammatory response to stroke, appear to effect systemic immunodepression via suppression of both innate and adaptive immune responses. Experimental and clinical studies have identified a range of anti-inflammatory and immunosuppressive changes, including reduced mononuclear phagocyte and natural killer cell function, induction of anti-inflammatory cytokines, apoptotic lymphocyte loss and altered T lymphocyte activity... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3292238 Thu, 18 Feb 2010 00:00:00 +0100 3292238 http://www.medworm.com/index.php?rid=3292237&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166973%26dopt%3DAbstract Authors: Elkind MS Atherosclerosis is a chronic inflammatory process, and several common bacterial and viral infections have been hypothesized to contribute to the inflammation of the vascular wall that leads to atherosclerosis. More recently, investigators have found preliminary evidence that the aggregate burden of these chronic infections, rather than any single organism, may contribute to atherosclerosis and risk of clinical vascular events, including ischemic stroke. This aggregate burden of infections, which has been variably labeled "infectious burden" or "pathogen burden," may be associated with stroke through mechanisms independent of atherosclerosis, as well, including platelet aggregation and endothelial dysfunction. Host factors, moreover, may interact with infectious burde... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3292237 Thu, 18 Feb 2010 00:00:00 +0100 3292237 http://www.medworm.com/index.php?rid=3292236&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166974%26dopt%3DAbstract Authors: Connor M, Neurol FC Human immunodeficiency virus (HIV) infection causes stroke through several mechanisms. Stroke results from opportunistic infection and neoplasia, HIV induced cardiac disease, HIV associated cerebral vasculopathy, and perhaps of HIV induced facilitation of some forms of systemic vasculitis and prothrombotic haematological conditions. HIV causes more ischaemic stroke than cerebral haemorrhage. Although stroke is currently a relatively infrequent manifestation of HIV infection, the incidence of stroke in HIV infected individuals is likely to increase with current combination antiretroviral therapy. HIV infection per se induces endothelial activation and dyslipidaemia, predisposing to accelerated atherosclerosis. Antiretroviral therapy, which increases life exp... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3292236 Thu, 18 Feb 2010 00:00:00 +0100 3292236 http://www.medworm.com/index.php?rid=3292235&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166975%26dopt%3DAbstract Authors: Amlie-Lefond C, Fullerton HJ Major infections-sepsis, meningitis, encephalitis-have long been recognized as causes of pediatric arterial ischemic stroke. However, minor infections may also contribute to the pathogenesis of stroke, either by causing a systemic prothrombotic state or direct or indirect vascular injury. A focal cerebral arteriopathy has been identified in a large proportion of otherwise healthy children present with a first ischemic stroke. Both histologic data and small association studies suggest that varicella zoster virus can cause this childhood arteriopathy. Other viruses have been implicated in case reports. New data demonstrate an association between recent upper respiratory infection and this arteriopathy, suggesting a non-specific effect of infection. T... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3292235 Thu, 18 Feb 2010 00:00:00 +0100 3292235 http://www.medworm.com/index.php?rid=2939791&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19860715%26dopt%3DAbstract Authors: Chen YW PMID: 19860715 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2939791 Thu, 29 Oct 2009 20:04:07 +0100 2939791 http://www.medworm.com/index.php?rid=2939790&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19860716%26dopt%3DAbstract Authors: Anderson WF The application of structural genomics methods and approaches to proteins from organisms causing infectious diseases is making available the three dimensional structures of many proteins that are potential drug targets and laying the groundwork for structure aided drug discovery efforts. There are a number of structural genomics projects with a focus on pathogens that have been initiated worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was recently established to apply state-of-the-art high throughput structural biology technologies to the characterization of proteins from the National Institute for Allergy and Infectious Diseases (NIAID) category A-C pathogens and organisms causing emerging, or re-emerging infectious diseases. The targe... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2939790 Thu, 29 Oct 2009 20:04:04 +0100 2939790 http://www.medworm.com/index.php?rid=2606522&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19594421%26dopt%3DAbstract Authors: Chim N, McMath LM, Beeby M, Goulding CW The waning effectiveness of established tuberculosis treatments due to the rise of multi and extensively drug-resistant strains of Mycobacterium tuberculosis, coupled with the synergism of HIV infection, demands basic research efforts to inform focused drug development programs. Structural genomics projects provide rich sources of information for the rational design of anti-tubercular drugs, aiming to exploit unique and novel protein features and interactions based on atomic resolution structures. This review compiles structures of M. tuberculosis proteins elucidated since January 2007 that are promising avenues for drug design, encompassing proteins involved with known and experimental anti-tuberculosis drugs, metabolism, dealing with t... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2606522 Thu, 16 Jul 2009 15:28:16 +0100 2606522 http://www.medworm.com/index.php?rid=2606521&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19594422%26dopt%3DAbstract We describe the methodologies, experience and technologies developed by SG, which range from improvements to cloning protocols to improved procedures for crystallographic structure solution that may be applied in "traditional" structural biology laboratories particularly those performing drug discovery. We also discuss the conditions that must be met to convert the present high-throughput structure determination pipeline into a high-output structure-based drug discovery system. PMID: 19594422 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2606521 Thu, 16 Jul 2009 15:28:13 +0100 2606521 http://www.medworm.com/index.php?rid=2606520&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19594423%26dopt%3DAbstract Authors: Dhaliwal B, Chen YW The design of new medications is an intensive, time-consuming and costly process. Over the years, a rational approach that exploits the structural knowledge of a biological target has led to many successes. This procedure can be expedited using computer-aided modelling techniques. The structure-based approach to drug design relies on knowing the three-dimensional structure of the target macromolecule. If an experimental structure has not been determined yet, a good approximation of the protein target structure can be obtained through computational modelling, provided that some structures of its homologues are available to serve as templates. The vast majority of drugs currently on the market act by disrupting the interaction between a protein and its physio... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2606520 Thu, 16 Jul 2009 15:28:11 +0100 2606520 http://www.medworm.com/index.php?rid=2606519&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19594424%26dopt%3DAbstract Authors: Vomaske J, Streblow DN Chemokines are small cytokines that are part of a large family of molecules that bind to G-protein coupled receptors, which, as a family, are the most widely targeted group of molecules in the treatment of disease. Chemokines are critical for recruiting and activating the cells of the immune system during inflammation especially during viral infections. However, a number of viruses including the large herpes virus human cytomegalovirus (HCMV) encode mechanisms to impede the effects of chemokines or has gained the ability to use these molecules to its own advantage. The Human Cytomegalovirus (HCMV)-encoded chemokine receptor US28 is the best characterized of the four unique chemokine receptor-like molecules found in the HCMV genome. US28 has been studied ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2606519 Thu, 16 Jul 2009 15:28:09 +0100 2606519 http://www.medworm.com/index.php?rid=2606518&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19594425%26dopt%3DAbstract Authors: Durand E, Verger D, Rêgo AT, Chandran V, Meng G, Fronzes R, Waksman G Gram-negative bacteria have evolved diverse secretion systems/machineries to translocate substrates across the cell envelope. These various machineries fulfil a wide variety of functions but are also essential for pathogenic bacteria to infect human or plant cells. Secretion systems, of which there are seven, utilize one of two secretion mechanisms: (i) the one-step mechanism, whereby substrates are translocated directly from the bacterial-cytoplasm to the extracellular medium or into the eukaryotic-target cell; (ii) the two-step mechanism, whereby substrates are first translocated across the bacterial-inner membrane; once in the periplasm, substrates are targeted to one of the secretion systems that me... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2606518 Thu, 16 Jul 2009 15:28:07 +0100 2606518 http://www.medworm.com/index.php?rid=2606517&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19594426%26dopt%3DAbstract Authors: Myler PJ, Stacy R, Stewart L, Staker B, Van Voorhis WC, Varani G, Buchko GW The NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium established to apply structural genomics approaches to potential drug targets from NIAID priority organisms for biodefense and emerging and re-emerging diseases. The mission of the SSGCID is to determine approximately 400 protein structures over the next five years. In order to maximize biomedical impact, ligand-based drug-lead discovery campaigns will be pursued for a small number of high-impact targets. Here we review the center's target selection processes, which include pro-active engagement of the infectious disease research and drug therapy communities to identify drug targets, essential enzymes, v... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2606517 Thu, 16 Jul 2009 15:28:05 +0100 2606517 http://www.medworm.com/index.php?rid=2533869&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519478%26dopt%3DAbstract Authors: de Brevern AG PMID: 19519478 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533869 Sun, 31 May 2009 23:00:00 +0100 2533869 http://www.medworm.com/index.php?rid=2533868&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519479%26dopt%3DAbstract Authors: Bhaduri A, Kalaimathy S, Sowdhamini R Genome sequencing efforts of taxonomically proximate organisms successfully divulged proteomic diversity embedded within closely related organisms. The Salmonella enterica subspecies represents a group of enterobacteric pathogens known to share similar genomic content yet possess diverse host specificity and distinct disease symptoms. Study of Salmonella enterica subspecies proteomes reports an overestimation of the proximity among the subspecies. Interestingly, orthology comparison among Salmonella typhi and Salmonella typhimurium across the proteome suggested the metabolic proteins possessed the highest propensity of the divergence, while proteins involved in environment information processing and genetic information processing are least... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533868 Sun, 31 May 2009 23:00:00 +0100 2533868 http://www.medworm.com/index.php?rid=2533867&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519480%26dopt%3DAbstract Authors: Tyagi N, Swapna LS, Mohanty S, Agarwal G, Gowri VS, Anamika K, Priya ML, Krishnadev O, Srinivasan N In this article we review the organism-wide biological data available for Plasmodium falciparum (P. falciparum), a malarial parasite, in relation to the data available for other organisms. We provide comparisons at different levels such as amino acid sequences of proteins encoded in the genomes, protein-protein interaction features, metabolic and signaling pathways and processes. Our comparative analyses highlights that P. falciparum is highly diverged compared to most other eukaryotes at all these levels. Despite the extensive variation some of the physical associations between proteins, such as RNA polymerase complex and CDK-cyclin complex are expected to be conserved given th... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533867 Sun, 31 May 2009 23:00:00 +0100 2533867 http://www.medworm.com/index.php?rid=2533866&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519481%26dopt%3DAbstract Authors: Combet C, Bettler E, Terreux R, Garnier N, Deléage G Hepatitis C is a viral infection of the liver that results in acute hepatitis and chronic liver disease, including cirrhosis and liver cancer. An estimated 170 million persons are chronically infected worldwide. The Hepatitis C virus is the pathogen agent responsible for hepatitis C. HCV is an enveloped RNA-positive virus of the flaviviridae family. The HCV genome shows remarkable sequence variability. This variability leads to the classification of HCV into 6 genotypes, numerous subtypes and HCV exists in each infected patient as quasi-species. The genotype may be linked to the severity of the disease and to the efficiency of the combination treatment with interferon and ribavirin. To date, no vaccine to prevent or cur... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533866 Sun, 31 May 2009 23:00:00 +0100 2533866 http://www.medworm.com/index.php?rid=2533865&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519482%26dopt%3DAbstract Authors: Wang T, Duan Y The CC-chemokine receptor 5 (CCR5), a membrane protein belonging to the G-protein coupled receptor super-family, has been identified as an essential co-receptor for HIV entry into the cells, and small molecules that inhibit HIV entry by targeting CCR5 have been in fast development as antiviral agents. This review focuses on computational studies of predicting the CCR5 structure and its interactions with known small molecule inhibitors and discusses how the recently solved GPCR structures would provide new insights into the modeling of CCR5-inhibitor binding. In addition, this review pays a particular attention to the design of the inhibitors that specifically interrupt the viral entry co-receptor activity of CCR5 while preserving its normal chemokine receptor fu... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533865 Sun, 31 May 2009 23:00:00 +0100 2533865 http://www.medworm.com/index.php?rid=2533864&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519483%26dopt%3DAbstract Authors: de Brevern AG, Autin L, Colin Y, Bertrand O, Etchebest C The Duffy Antigen/Receptor for Chemokine (DARC) is a seven segment transmembrane protein. It was firstly discovered as a blood group antigen and was the first specific gene locus assigned to a specific autosome in man. It became more famous as an erythrocyte receptor for malaria parasites (Plasmodium vivax and Plasmodium knowlesi), and finally for chemokines. DARC is an unorthodox chemokine receptor as (i) it binds chemokines of both CC and CXC classes and (ii) it lacks the Asp-Arg-Tyr consensus motif in its second cytoplasmic loop hence cannot couple to G proteins and activate their signaling pathways. DARC had also been associated to cancer progression, numerous inflammatory diseases, and possibly to AIDS. In this revi... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533864 Sun, 31 May 2009 23:00:00 +0100 2533864 http://www.medworm.com/index.php?rid=2533863&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519484%26dopt%3DAbstract Authors: de Beer TA, Wells GA, Burger PB, Joubert F, Marechal E, Birkholtz L, Louw AI Malaria remains one of the most burdensome human infectious diseases, with a high rate of resistance outbreaks and a constant need for the discovery of novel antimalarials and drug targets. For several reasons, Plasmodial proteins are difficult to characterise structurally using traditional physical approaches. However, these problems can be partially overcome using a number of in silico approaches. This review describes the peculiarities of malaria proteins and then details various in silico strategies to select and allow descriptions of the molecular structures of drug target candidates as well as subsequent rational approaches for drug design. Chiefly, homology modelling with specific focus on uniq... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533863 Sun, 31 May 2009 23:00:00 +0100 2533863 http://www.medworm.com/index.php?rid=2533862&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519485%26dopt%3DAbstract Authors: Murphy DJ, Brown JR The resurgence of drug resistant tuberculosis (TB) is a major global healthcare problem. Mycobacterium tuberculosis (MTB), TB's causative agent, evades the host immune system and drug regimes by entering prolonged periods of nonproliferation or dormancy. The identification of genes essential to the bacterium in its dormancy phase infections is a key strategy in the development of new anti-TB therapeutics. The rapid expansion of TB-related genomic data sources including DNA sequences, transcriptomic and proteomic profiles, and genome-wide essentiality data, present considerable opportunities to apply advanced computational analyses to predict potential drug targets. However, the translation of in silico predictions to effective clinical therapies remains a s... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533862 Sun, 31 May 2009 23:00:00 +0100 2533862 http://www.medworm.com/index.php?rid=2533861&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519486%26dopt%3DAbstract Authors: Tomlinson SM, Malmstrom RD, Watowich SJ Dengue virus (DENV), a member of the family Flaviviridae, presents a tremendous threat to global health since an estimated 2.5 billion people worldwide are at risk for epidemic transmission. DENV infections are primarily restricted to sub-tropical and tropical regions; however, there is concern that the virus will spread into new regions including the United States. There are no approved antiviral drugs or vaccines to combat dengue infection, although DENV vaccines have entered Phase 3 clinical trials. Drug discovery and development efforts against DENV and other viral pathogens must overcome specificity, efficacy, safety, and resistance challenges before the shortage of licensed drugs to treat viral infections can be relieved. Current d... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533861 Sun, 31 May 2009 23:00:00 +0100 2533861 http://www.medworm.com/index.php?rid=2533860&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519487%26dopt%3DAbstract Authors: Doppelt-Azeroual O, Moriaud F, Adcock SA, Delfaud F Resolved three-dimensional protein structures are a major source of information for understanding protein functional properties. The current explosive growth of publicly available protein structures is producing large volumes of data for computational modelling and drug design methods. Target-based in silico drug design tools aid design and optimize compounds to bind to specific targets. MED-SuMo is a powerful technology for comparing local regions on protein surfaces, allowing similarities to be discovered and explored. This is a target-based tool that can exploit all available macromolecule structures. Its computational efficiency differentiates its approach from widely used methods such as docking and scoring, or map-based... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533860 Sun, 31 May 2009 23:00:00 +0100 2533860 http://www.medworm.com/index.php?rid=2533859&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519488%26dopt%3DAbstract Authors: Breton V, da Costa AL, de Vlieger P, Kim YM, Maigne L, Reuillon R, Sarramia D, Truong NH, Nguyen HQ, Kim D, Wu YT The recent years have seen the emergence of diseases which have spread very quickly all around the world either through human travels like SARS or animal migration like avian flu. Among the biggest challenges raised by infectious emerging diseases, one is related to the constant mutation of the viruses which turns them into continuously moving targets for drug and vaccine discovery. Another challenge is related to the early detection and surveillance of the diseases as new cases can appear just anywhere due to the globalization of exchanges and the circulation of people and animals around the earth, as recently demonstrated by the avian flu epidemics. For 3 years n... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533859 Sun, 31 May 2009 23:00:00 +0100 2533859 http://www.medworm.com/index.php?rid=2533858&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519489%26dopt%3DAbstract Authors: Vellay SG, Latimer NE, Paillard G Text mining has become an integral part of all research in the medical field. Many text analysis software platforms support particular use cases and only those. We show an example of a bibliographic tool that can be used to support virtually any use case in an agile manner. Here we focus on a Pipeline Pilot web-based application that interactively analyzes and reports on PubMed search results. This will be of interest to any scientist to help identify the most relevant papers in a topical area more quickly and to evaluate the results of query refinement. Links with Entrez databases help both the biologist and the chemist alike. We illustrate this application with Leishmaniasis, a neglected tropical disease, as a case study. PMID: 19519489 ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2533858 Sun, 31 May 2009 23:00:00 +0100 2533858 http://www.medworm.com/index.php?rid=2264304&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275697%26dopt%3DAbstract Authors: Sabatier JM PMID: 19275697 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264304 Sun, 01 Mar 2009 05:00:00 +0100 2264304 http://www.medworm.com/index.php?rid=2264302&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275698%26dopt%3DAbstract Authors: de Lamballerie X, Ninove L, Charrel RN Chikungunya virus is a typical emerging virus which has been responsible for several million cases of human infections since 2004. No antiviral treatment is currently available. The antimalarial chloroquine has been used in the past but recent studies suggest that it is not or poorly active in vivo. A number of tracks are currently under investigation (inhibition of viral enzymes, of virus entry or maturation, enhancement of immunological response) and new animal models have been made available, including a mouse model and a non-human primate model. We review here the main perspectives of chikungunya antiviral treatment. PMID: 19275698 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264302 Sun, 01 Mar 2009 05:00:00 +0100 2264302 http://www.medworm.com/index.php?rid=2264300&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275699%26dopt%3DAbstract Authors: Stein LL, Loomba R Hepatitis B virus infection (HBV) is a significant global health problem. Despite the success of universal hepatitis B vaccination in many countries, more than 350 million individuals worldwide are chronically infected and 15- 40% of those will develop cirrhosis and/or hepatocellular carcinoma if left untreated. Available therapies for chronic hepatitis B (CHB) infection are effective at decreasing viremia and improving measured clinical outcomes, however, no single therapy is optimal. As such, alternative drug therapies and the investigation of their role in the management of CHB are warranted. Significant improvements in the understanding of the HBV life cycle, viral genomics, and virus-host interactions continue to lead to the development of novel viral t... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264300 Sun, 01 Mar 2009 05:00:00 +0100 2264300 http://www.medworm.com/index.php?rid=2264298&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275700%26dopt%3DAbstract Authors: Billaud G, Thouvenot D, Morfin F Herpes simplex virus (HSV) and Epstein Barr Virus (EBV) are Herpesviridae. Although infections are often subclinical, HSV can cause mild to severe diseases, especially in immunocompromised patients. EBV infections are also often asymptomatic but this virus may be associated to carcinoma in immunocompetent patients and to severe diseases in immunocompromised patients. These viruses establish latency, in neuronal cells for HSV and in B-cells for EBV, and may reactivate, with or without symptoms. There are few drugs licensed for the treatment of HSV infections. Most of them target the viral DNA polymerase, in which acyclovir remains the reference treatment some thirty years after its discovery. The emergence of resistant viral strains, mainly in i... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264298 Sun, 01 Mar 2009 05:00:00 +0100 2264298 http://www.medworm.com/index.php?rid=2264296&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275701%26dopt%3DAbstract Authors: Rohde G Human Rhinoviruses (HRV) are by far the most common respiratory viruses responsible for most cases of the common cold and important pathogens in acute exacerbations of asthma and COPD. The molecular pathogenesis of HRV infection is quite completely understood. However there is still no approved specific treatment against HRV infections. The aim of this article is therefore to give an overview of the principles of rhinovirus infection, the associated therapeutic targets and to review up-to-date virus-specific clinical trials. PMID: 19275701 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264296 Sun, 01 Mar 2009 05:00:00 +0100 2264296 http://www.medworm.com/index.php?rid=2264294&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275702%26dopt%3DAbstract Authors: Paula T, Pablo R, Eugenia V, Pablo B, Sabino P, José M, Antonio M, Dolores HM, Pablo L, Javier GS, Vincente S The Flaviviridae family comprises the genus Flavivirus, Hepacivirus and Pestivirus. These viruses are responsible for considerable human and animal disease and mortality worldwide. Flaviviruses cause a range of acute febrile illnesses along with encephalitic or haemorrhagic diseases. Chronic hepatitis C virus (HCV) infection is the most important hepacivirus human disease and remains a global health threat with nearly 200 million carriers worldwide. Current treatment consists in the use of peginterferon alfa (pegIFN) plus ribavirin (RBV) for 24 to 72 weeks, depending on HCV genotype, baseline viral load and the achievement of rapid virological response during ther... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264294 Sun, 01 Mar 2009 05:00:00 +0100 2264294 http://www.medworm.com/index.php?rid=2264289&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275703%26dopt%3DAbstract Authors: Torre D, Pugliese A Among emergent and re-emergent viral infections, influenza, hemorrhagic fevers, including hantaviruses, constitute one of the major threats to human beings. Advances in immunopathogenesis of these viral infections have improved initial supportive treatments and led to recognition and adoption of several useful antiviral agents. This review focuses on therapeutic and preventive aspects of these viral infections, and evaluates old and new promising agents are in the pipeline of pharmaceutical companies, and finally addresses therapeutic aspects in the treatment of these viral pathogens. However, it should be stressed that only prevention based in particular on research and development of new vaccines may be able in future to control and eventually eradicate t... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264289 Sun, 01 Mar 2009 05:00:00 +0100 2264289 http://www.medworm.com/index.php?rid=2264283&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275704%26dopt%3DAbstract Authors: Boross P, Bagossi P, Weber IT, Tözsér J Human T-lymphotropic virus type 1 (HTLV-1), the first known human retrovirus, induces various human diseases with a long latency period. The mechanism by which the virus causes diseases is still unknown. Studies indicate that viral replication is important at least for the development of HTLV-1 associated myelopathy, and therefore treatments based on our knowledge of human immunodeficiency virus type-1 (HIV-1) can be utilized to develop potent antiretroviral therapies targeting the replication enzymes reverse transcriptase, protease and integrase as well as the envelope glycoproteins. Furthermore, accessory gene products such as Tax and HBZ may also provide targets for chemotherapy. Treatment targeting these viral proteins may ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264283 Sun, 01 Mar 2009 05:00:00 +0100 2264283 http://www.medworm.com/index.php?rid=2264279&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275705%26dopt%3DAbstract Authors: Wainberg MA, Martinez-Cajas JL HIV-1 drug regimens now offer more potent, less toxic and more durable choices. However, strategies addressing convenient sequential use of active antiretroviral combinations are rarely presented in the literature. Studies have seldom directly addressed this issue, despite it being a matter of daily use in clinical practice. This is, in part, because of the complexity of HIV-1 resistance information. Nevertheless, several principles can effectively assist the planning of antiretroviral drug sequencing. The introduction of tenofovir, abacavir and emtricitabine into current nucleoside backbone options, with each of them selecting for an individual pattern of resistance mutations, now permits sequencing in the context of previously popular thymidine... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264279 Sun, 01 Mar 2009 05:00:00 +0100 2264279 http://www.medworm.com/index.php?rid=2264276&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275706%26dopt%3DAbstract Authors: Gene OG, Julia BE, Vanessa MR, Victoria WJ, Thomas GW, Lisa HE The development of antiviral drugs for Ebola and Marburg viruses has been slow. To date, beyond supportive care, no effective treatments, prophylactic measures, therapies, or vaccines are approved to treat or prevent filovirus infections. In this review, we examine the current treatments available to administer care for filovirus infection, the potential therapeutic targets that can be used for filovirus drug development, and the various drug targeting techniques used against filoviruses. PMID: 19275706 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264276 Sun, 01 Mar 2009 05:00:00 +0100 2264276 http://www.medworm.com/index.php?rid=2264273&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275707%26dopt%3DAbstract Authors: Andrei G, De Clercq E, Snoeck R Human cytomegalovirus (HCMV) infections are usually benign and self-limiting in the immunocompetent population; however, HCMV is a well-recognized problem among immunocompromised patients (in particular immunosuppressed patients with stem cell or solid organ transplantation, AIDS, or cancer). In this group of patients, HCMV infections are a significant cause of morbidity and mortality. Additionally, congenital HCMV infections are a leading cause of birth defects and infections in children, occurring in 1 to 2% of all live births. Currently available drugs for the treatment of HCMV diseases in the immunocompromised host include ganciclovir (GCV), its oral prodrug valganciclovir (VGCV), cidofovir (CDV), foscavir (FOS), and fomivirsen. Except for f... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264273 Sun, 01 Mar 2009 05:00:00 +0100 2264273 http://www.medworm.com/index.php?rid=2264270&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275708%26dopt%3DAbstract Authors: Tong TR Coronaviruses are important human and animal pathogens of the order Nidovirales. Several new members were discovered following the emergence of SARS-CoV in human populations, including two human coronaviruses and several animal coronaviruses. They cause respiratory and gastrointestinal illnesses and have been found in the brains of patients with multiple sclerosis. The high mortality of SARS, the identification of a natural reservoir, and the well-founded fear of provoking antibody-enhanced disease as a result of vaccination fueled the ongoing efforts in anti-coronavirus drug discovery. This review presents the results of current research. PMID: 19275708 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2264270 Sun, 01 Mar 2009 05:00:00 +0100 2264270 http://www.medworm.com/index.php?rid=2201983&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200014%26dopt%3DAbstract Authors: Geissen M, Mella H, Saalmüller A, Eiden M, Proft J, Pfaff E, Schätzl HM, Groschup MH Until now it is still not clear which structural elements of the prion protein (PrP) are involved in its conversion process. Characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit PrP(res) formation by dominant inhibitory mutations. To address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3F4-tagged PrP. The mutants were expressed by retroviral transduction in three different scrapie infected cell lines (ScN2a; SMB[RC040]; SMB[22F]). The convertibility was affected not only by introducing the insertion ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2201983 Sun, 01 Feb 2009 05:00:00 +0100 2201983 http://www.medworm.com/index.php?rid=2174551&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200009%26dopt%3DAbstract Authors: Schätzl HM PMID: 19200009 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174551 Sun, 01 Feb 2009 05:00:00 +0100 2174551 http://www.medworm.com/index.php?rid=2174550&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200010%26dopt%3DAbstract Authors: Krammer C, Vorberg I, Schätzl HM, Gilch S Prion diseases are infectious and fatal neurodegenerative disorders of man and animals which are characterized by spongiform degeneration in the central nervous system. In human diseases, the manifestation can be sporadic, familial or acquired by infection. Prion disorders are caused by the accumulation of an aberrantly folded isoform of the cellular prion protein (PrP(c)), commonly named PrP(Sc). Although prion diseases are usually rare, they have the potential to be transferred within and also between species by infection processes, giving then raise even to epidemic scenarios. As pathology is obviously restricted to the central nervous system pre-mortem diagnosis is usually hard to achieve. Promising approaches towards the deve... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174550 Sun, 01 Feb 2009 05:00:00 +0100 2174550 http://www.medworm.com/index.php?rid=2174549&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200011%26dopt%3DAbstract Authors: Teruya K, Kawagoe K, Kimura T, Chen CJ, Sakasegawa Y, Dohura K Recent outbreaks of variant Creutzfeldt-Jakob disease and iatrogenic Creutzfeldt-Jakob disease have aroused great concern in many countries and have necessitated the development of suitable therapies. We have demonstrated that sulfated glycans such as pentosan polysulfate and fucoidan, and amyloidophilic compounds such as amyloid dye derivatives, styrylbenzoazole derivatives, and phenylhydrazine derivatives have efficacies in prion-infected animals. Amyloidophilic compounds present potentialities not only as therapeutic candidates but also as prion amyloid imaging probes for use in nuclear medicine technology such as positron emission tomography. A representative of styrylbenzoazole compounds has been used recently... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174549 Sun, 01 Feb 2009 05:00:00 +0100 2174549 http://www.medworm.com/index.php?rid=2174548&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200012%26dopt%3DAbstract This article analyzes the development of tetracyclines as a therapeutic tool in TSE in the light of recent results obtained in our laboratories. PMID: 19200012 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174548 Sun, 01 Feb 2009 05:00:00 +0100 2174548 http://www.medworm.com/index.php?rid=2174547&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200013%26dopt%3DAbstract Authors: Voisset C, Saupe SJ, Galons H, Blondel M Prion diseases are fatal and incurable infectious neurodegenerative disorders affecting humans and other mammals. Prions are composed essentially if not solely of PrP(Sc), a misfolded form of the host-encoded PrP protein. PrP(Sc) catalyzes the transconformation of the normal endogenous PrP (PrP(C)) into more PrP(Sc). Prion replication thus corresponds to the propagation of an altered folding state of PrP. Several prion proteins have also been identified in the simple model organism Saccharomyces cerevisiae. Yeast prion-based screening assays have allowed identification of drugs active against mammalian prions, thus revealing the existence of common prion propagation mechanisms conserved from yeast to human. To identify these conserved t... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174547 Sun, 01 Feb 2009 05:00:00 +0100 2174547 http://www.medworm.com/index.php?rid=2174546&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200014%26dopt%3DAbstract Authors: Geissen M, Mella H, Saalmüller A, Eiden M, Proft J, Pfaff E, Schätzl HM, Groschup MH Until now it is still not clear which structural elements of the prion protein (PrP) are involved in its conversion process. Characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit PrP(res) formation by dominant inhibitory mutations. To address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3F4-tagged PrP. The mutants were expressed by retroviral transduction in three different scrapie infected cell lines (ScN2a; SMB[RC040]; SMB[22F]). The convertibility was affected not only by introducing the insertion ... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174546 Sun, 01 Feb 2009 05:00:00 +0100 2174546 http://www.medworm.com/index.php?rid=2174545&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200015%26dopt%3DAbstract Authors: Nicoll AJ, Collinge J Prions are unique in that the infectious particles contain no detectable nucleic acid and appear to consist of aggregated forms of misfolded cellular prion protein. Prions form distinct strains and can transmit disease between species. Whilst the molecular basis of prion diseases is beginning to be unravelled, much remains unknown including the atomic structure of the infectious and toxic species. In contrast, the structure and folding properties of the cellular prion protein are well characterised and, although its precise function remains enigmatic, constitutive knockout of protein expression in mice produces apparently healthy animals but which are fully resistant to prion infection. Furthermore, recent data show that neuronal knockout of the gene enco... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174545 Sun, 01 Feb 2009 05:00:00 +0100 2174545 http://www.medworm.com/index.php?rid=2174544&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200016%26dopt%3DAbstract Authors: Relaño-Ginés A, Gabelle A, Lehmann S, Milhavet O, Crozet C Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal prion protein named PrP(Sc). PrP(Sc) results from the post-translational conformational modification of the host-encoded protein PrP(C). To date there is no treatment for this inexorably fatal disease. Hence, a major focus of research consists in the identification of new molecules that could interfere with in vivo prion propagation. Promising therapeutic approaches to block the production of PrP(Sc) are based on PrP RNA interference, passive or active immunization, dominant negative inhibition of PrP(Sc) formation, as well as inhibition of interactions between PrP(Sc) and other cofactors. Although these anti-prion... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174544 Sun, 01 Feb 2009 05:00:00 +0100 2174544 http://www.medworm.com/index.php?rid=2174543&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200017%26dopt%3DAbstract Authors: Vana K, Zuber C, Pflanz H, Kolodziejczak D, Zemora G, Bergmann AK, Weiss S The 37 kDa/67 kDa laminin receptor (LRP/LR) represents a key player for cell adhesion, is associated with the metastatic potential of solid tumors and is required for maintenance of cell viability by preventing apoptosis. LRP/LR acts as a receptor for viruses such as Sindbis virus, Venezuelean Equine Encephalitis (VEE) virus, Adeno-associated-viruses (AAV) and Dengue Virus, the latter causing 50 to 100 million infections in humans per year. LRP/LR acts further as a receptor for prions and represents a multifunctional protein subcellularly located to the nucleus, the cytoplasm and the cell surface. The receptor represents an alternative target for therapy of viral infections, cancer and prion disorders a... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174543 Sun, 01 Feb 2009 05:00:00 +0100 2174543 http://www.medworm.com/index.php?rid=2174542&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200018%26dopt%3DAbstract Authors: Sim VL, Caughey B The transmissible spongiform encephalopathies are rapidly progressive and invariably fatal neurodegenerative diseases for which there are no proven efficacious treatments. Many approaches have been undertaken to find ways to prevent, halt, or reverse these prion diseases, with limited success to date. However, as both our understanding of pathogenesis and our ability to detect early disease increases, so do our potential therapeutic targets and our chances of finding effective drugs. There is increasing pressure to find effective decontaminants for blood supplies, as variant Creutzfeldt Jakob Disease (vCJD) has been shown to be transmissible by blood, and to find non-toxic preventative therapies, with ongoing cases of Bovine Spongiform Encephalopathy (BSE) an... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174542 Sun, 01 Feb 2009 05:00:00 +0100 2174542 http://www.medworm.com/index.php?rid=2174541&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19200019%26dopt%3DAbstract Authors: Zerr I The progress in understanding disease pathology and phenomenology in prion disorders and recent advances in diagnostic techniques might allow researchers to think about therapeutic trials in CJD patients. Some attempts have been made in the past. Drugs tested involved a variety of compounds, which belong to antimicrobial, antiinflammatory or analgesic substance classes. Most papers on this subject describe single case reports. Controlled trials are virtually not available and a double-blinded study was published for flupirtine only. Despite it has been demonstrated that a clinical trial is feasible, the clinicians might face several specific problems when evaluating the efficacy of the drug in CJD, such as rareness of the disease, lack of appropriate preclinical test an... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174541 Sun, 01 Feb 2009 05:00:00 +0100 2174541 http://www.medworm.com/index.php?rid=2041673&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075795%26dopt%3DAbstract Authors: Garcia-Sanz JA PMID: 19075795 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2041673 Mon, 01 Dec 2008 05:00:00 +0100 2041673 http://www.medworm.com/index.php?rid=2041672&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075796%26dopt%3DAbstract Authors: Vernal R, Garcia-Sanz JA In addition to the T helper 1 (Th1) and Th2 lymphocyte subsets, two new subpopulations Th17 and regulatory T (Treg) cells have recently been described. Th17 cells, which produce high levels of interleukin (IL)-17, are dependent on the transcription factor orphan nuclear receptor RORC2/RORgammat and have been implicated in exacerbating the immune response to infections. Conversely, Treg cells, either thymus-derived or generated upon TCR activation of naîve T cells, express the transcription factor forkhead box P3 (Foxp3) and have regulatory functions mediated through either direct cell-cell contact or immuno-suppressive cytokines, being able to suppress the activation of T, B and NK cells. Based on the current knowledge of Th17 and Treg cell functi... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2041672 Mon, 01 Dec 2008 05:00:00 +0100 2041672 http://www.medworm.com/index.php?rid=2041671&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075797%26dopt%3DAbstract Authors: Erard F, Ryffel B Toll like receptors (TLR) play a critical role in the recognition and response of pathogens by the innate immune system. Pathogen engagement of the TLR-MyD88 pathway favours the development of a protective Th1-biased T cell response. Interruption of TLR recognition or signalling has profound effects on innate immunity. Agonists or antagonists of specific TLRs modulate the host response to microbial infections and have effects beyond infectious control and may be used as immunostimulators in vaccine, cancer, inflammatory disorders and allergy. PMID: 19075797 [PubMed - in process] (Source: Infectious Disorders Drug Targets) Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2041671 Mon, 01 Dec 2008 05:00:00 +0100 2041671 http://www.medworm.com/index.php?rid=2041670&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075798%26dopt%3DAbstract Authors: Nakagawa J Posttranscriptional regulation of gene expression plays a pivotal role as a fast control system for T-cells and B-cells operating in the defense reactions against rapidly growing infectious agents. The framework of this machinery involves cis-acting elements in the mRNAs of relevant cytokines and trans-acting factors interacting with these elements. The cis- and trans-acting factors enforce rapid mRNA decay with other proteins such as nucleases in the decay machinery. The most prominent cis-element contains A + U- rich sequence (ARE), and is located in the 3'-untranslated region of the target mRNAs. Some ARE-binding proteins promote the rapid decay, and others protect the mRNA from degradation. The 5'-end of nascent mRNA undergoes capping which protects the 5'-end t... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2041670 Mon, 01 Dec 2008 05:00:00 +0100 2041670 http://www.medworm.com/index.php?rid=2041669&cid=s_37267_20_f&fid=37267&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075799%26dopt%3DAbstract Authors: Villate O, Rastrojo A, López-Díez R, Hernández-Torres F, Aguado B Genome complexity and diversity can be due to Alternative Splicing (AS), a process by which one gene can generate multiple mRNA isoforms and then several proteins. This is part of a normal process of variation on an individual, and when it is disrupted or modified, may trigger disease. To date, there are many pathologies described due to the effects of altered splicing isoforms, and effort is focused on the description of new ones. The design of drug target has to consider splicing, as in many occasions, a drug might have effect on different isoforms, instead of on the particular one implicated in the pathology. Interestingly, the strategies used to alter splicing can be used to modify a form towa... Infectious Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2041669 Mon, 01 Dec 2008 05:00:00 +0100 2041669