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 'Fundamental and Clinical Pharmacology' source. Wed, 08 Feb 2012 14:04:16 +0100 http://www.medworm.com/index.php?rid=5648043&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2012.01026.x AbstractBecause the magnitude of spontaneous bacterial clearance can be similar or even higher than treatment effect, depending upon experimental model and bacterial strain used, this work investigated the value of rendering rats immunosuppressed to facilitate bacterial implantation and reduce spontaneous bacterial clearance. In a first step, rats received a single intravenous cyclophosphamide dose 4 days before infection. Three different doses were tested: 10, 20, and 40 mg/kg. After modeling with NONMEM V, the cyclophosphamide dose required to maintain white blood cell count <1.0 × 103/μL from day 4 to day 5 was 30 mg/kg. In a second step, influence of immunosuppression on lung bacterial titers was characterized. Rats were given one of the three intravenous cyclophosphamid... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648043 Wed, 01 Feb 2012 05:00:00 +0100 5648043 http://www.medworm.com/index.php?rid=5609010&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01013.x AbstractThe present study was carried out to investigate the effects of long‐acting phosphodiesterase five inhibitor, tadalafil, on pulmonary hypertension induced by chronic hypobaric hypoxia in rats. Adult Albino Wistar rats were exposed to 2 weeks of hypobaric hypoxia for 8 h daily and treated with tadalafil or tempol, a standard antioxidant agent. Right ventricular systolic pressure (RVSP) was taken as an index for pulmonary arterial pressure; malondialdehyde, reduced glutathione and superoxide dismutase were chosen as the markers of oxidative stress; serum tumour necrosis factor alpha (TNF‐α) levels and inflammatory changes in lungs were assessed for inflammation. Chronic hypobaric hypoxia was found to induce pulmonary hypertension, as it significantly (P < 0.001) incre... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5609010 Fri, 20 Jan 2012 18:16:16 +0100 5609010 http://www.medworm.com/index.php?rid=5582002&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01024.x (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582002 Fri, 13 Jan 2012 23:10:16 +0100 5582002 http://www.medworm.com/index.php?rid=5582001&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01025.x In conclusion, our data demonstrated that apocynin induces both endothelium‐independent relaxant effects involving inhibition of Ca2+mobilization and activation of KATP channels in vascular smooth muscle cells and endothelium‐dependent effects mediated by NO. These results should provide a basis for caution when interpreting results on the vascular effects of apocynin. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582001 Fri, 13 Jan 2012 23:07:34 +0100 5582001 http://www.medworm.com/index.php?rid=5560298&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01021.x AbstractCroton zehntneri, a plant native to northeastern Brazil, is widely used in folk medicine to treat gastrointestinal problems and has rich essential oil content. The effects of the essential oil of Croton zehntneri (EOCZ) and its main constituent anethole on several models of gastric lesions were studied in mice and rats. Oral treatment with EOCZ and anethole, both at doses of 30–300 mg/kg, caused similar and dose‐dependent gastroprotection against ethanol‐ and indomethacin‐induced gastric damage, but did not change cold‐restraint stress‐induced ulcers in rats. Furthermore, EOCZ and anethole (both at 30 and 300 mg/kg) similarly and significantly increased the mucus production by the gastric mucosa, measured by Alcian blue binding, in ethanol‐induced ulcer model. How... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5560298 Tue, 03 Jan 2012 05:00:00 +0100 5560298 http://www.medworm.com/index.php?rid=5487002&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01012.x AbstractThe currently available diuretics increase the urinary excretion of sodium chloride by selective inhibition of specific sodium transporters in the loop of Henle and distal nephron. In recent years, the molecular cloning of the diuretic‐sensitive sodium transporters at distal convoluted tubule has improved our understanding of the cellular mechanisms of action of each class of diuretics. Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure. Loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter‐1 and exert their diuretic action by binding to the Na+‐K+‐2Cl− co‐transporter type 2 in the thick ascending limb and the Na+‐ Cl− co‐transporter in the distal convoluted tubule... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5487002 Wed, 07 Dec 2011 05:00:00 +0100 5487002 http://www.medworm.com/index.php?rid=5476702&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01011.x AbstractPlant drugs are known to play a major role in the management of liver diseases. There are many plants and their extracts that have been shown to possess hepatoprotective activities. There are more than 300 preparations in Indian system of medicine for the treatment of jaundice and chronic liver diseases. About 600 commercial herbal formulations with claimed hepatoprotective activity are being sold all over the globe. The active phytochemical fraction that imparts hepatoprotective activity has been identified in many plants. These phytochemicals can be isolated and developed as single‐ingredient drugs, with quality and standards of modern medicine. The major problem faced with herbal products is their standardization and their quality assurance. There can be batch‐to‐batch var... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476702 Mon, 05 Dec 2011 05:00:00 +0100 5476702 http://www.medworm.com/index.php?rid=5476701&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01014.x In this study, we investigated any roles of Rho/Rho‐kinase pathway in the vasoconstriction of the rat conductance and capacitance vessels by hyperosmolar glucose solution. Isolated aortic, mesenteric and renal rings were suspended and exposed to hyperosmolar glucose, sucrose and NaCl in the organ chambers filled with Krebs solution gassed with 95% O2 and 5% CO2 and maintained at 37 °C. The effect of a Rho‐kinase inhibitor, (+)‐(R)‐trans‐4‐(1‐aminoethyl)‐N‐(4‐pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y‐27632, 10−5 m), was tested on the contraction induced by hypertonic solutions. Endothelial integrity was also assessed after hyperosmolar glucose exposure. Moreover, the activity and expression of Rho‐kinase (ROCK‐2) as well as RhoA transloc... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476701 Mon, 05 Dec 2011 05:00:00 +0100 5476701 http://www.medworm.com/index.php?rid=5560297&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01023.x In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk‐guided therapy in CVD prevention. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5560297 Thu, 01 Dec 2011 05:00:00 +0100 5560297 http://www.medworm.com/index.php?rid=5552426&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01019.x AbstractCisplatin treatment caused a significant increase in the life span of ascites Dalton’s lymphoma (DL) Tumor‐bearing (TB) mice. However, as compared to cisplatin (CP) alone, combination treatment with ascorbic acid plus CP resulted in better therapeutic efficacy against murine DL. Cisplatin treatment of TB mice resulted in the appearance of thickened and irregular arrangement of mitochondrial cristae in the liver, kidney and DL tumor cells. Combination treatment of the hosts with ascorbic acid and CP lessened deformities in the mitochondria of liver and kidney, while in tumor cells, this increased the formation of vacuoles and disruption in mitochondrial cristae. Cisplatin treatment decreased the succinate dehydrogenase (SDH) activity in the mitochondria of kidney and DL cells an... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552426 Thu, 01 Dec 2011 05:00:00 +0100 5552426 http://www.medworm.com/index.php?rid=5544703&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01020.x AbstractSeveral studies suggest that free radicals may play a role in cholestatic liver injury. The aim of this work was to evaluate the role of trolox in chronic bile duct ligation (BDL). Liver injury was induced by 28‐day BDL to male Wistar rats. Animals were divided in four groups of six rats. Trolox was administered daily (50 mg/kg, p.o.). Alanine aminotransferase (ALT) was quantified in serum. Fibrosis was assessed measuring liver hydroxyproline content. Reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, catalase (CAT), and glutathione peroxidase (GPx) activities were measured in liver. Transforming growth factor‐β (TGF‐β), interleukin‐6 (IL‐6), and interleukin‐10 (IL‐10) were determined by western blot and quantified densitometrically. Our results sh... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5544703 Thu, 01 Dec 2011 05:00:00 +0100 5544703 http://www.medworm.com/index.php?rid=5515576&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01022.x AbstractOxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Trigonelline is the major component of Mirabilis jalapa L., which has been used to treat diabetes in China. The present study was designed to evaluate the beneficial effects of trigonelline against hyperglycemia, hyperlipidemia, β cell damage and antioxidant of pancreas in diabetic rats. Diabetic rats were induced by intraperitoneal injection 35 mg/kg streptozotocin and a high‐carbohydrate/high‐fat diet. Rats were divided into four groups: normal control, diabetic control, trigonelline‐treated diabetic, and glibenclamide‐treated diabetic. After 4‐week treatment, blood glucose, serum insulin, total cholesterol (TC), and t... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515576 Thu, 01 Dec 2011 05:00:00 +0100 5515576 http://www.medworm.com/index.php?rid=5494990&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01016.x This study was designed to investigate the effects of melatonin (MEL) and erythropoietin (EPO), which is a known anti‐inflammatory and antiapoptotic agent, in dinitrobenzene sulfonic acid (DNBS)–induced colitis in pinealectomized (Px) rats. In microscopically results, epithelial and goblet cell loss, absence of crypts, and increased colonic caspase‐3 activity were observed in the DNBS group. Also, in flow cytometric analysis, the percentage of CD4+ T cells was highest in the DNBS group. Treatment with MEL or EPO had a curative effect on DNBS‐induced colitis. The MEL + EPO groups showed significantly greater improvement when compared with the other treatment groups. Our results indicate that the combination of EPO and MEL may exert more beneficial effects than either agent used ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5494990 Thu, 01 Dec 2011 05:00:00 +0100 5494990 http://www.medworm.com/index.php?rid=5487001&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01015.x In conclusion, oxidative stress appears to mediate the deleterious cardiovascular effects of IH and, in particular, the increased myocardial susceptibility to infarction. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5487001 Thu, 01 Dec 2011 05:00:00 +0100 5487001 http://www.medworm.com/index.php?rid=5476700&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01018.x This study was aimed to examine: (i) the effects of systemically and locally peripherally administered topiramate in the rat inflammatory pain model and (ii) the potential role and site(s) of gamma‐aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate’s antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro‐inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of systemic and local peripheral topiramate on carrageenan‐induced hyperalgesia and (ii) the effects of systemic and local peripheral bicuculline (selective GABAA receptor antagonist), naloxone (nonselective opioid receptor antagonist), and yohimbine (selective α2‐adrenergic receptor antagonist) on topiramate‐induced antihyperalgesia. Systemic ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476700 Thu, 01 Dec 2011 05:00:00 +0100 5476700 http://www.medworm.com/index.php?rid=5449862&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01009.x AbstractThe rapid replication rate of HIV‐1 RNA and its inherent genetic variation have led to the production of many HIV‐1 variants with decreased drug susceptibility. The capacity of HIV to develop drug resistance mutations is a major obstacle to long‐term effective anti‐HIV therapy. Incomplete suppression of viral replication with an initial drug regimen diminishes the clinical benefit to the patient and may promote the development of broader drug resistance that may cause subsequent treatment regimens to be ineffective. The increased clinical use of combination antiretroviral treatment for HIV‐1 infection has led to the selection of viral strains resistant to multiple drugs, including strains resistant to all licensed nucleoside analog RT inhibitors and protease inhibitors. T... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5449862 Mon, 28 Nov 2011 06:46:33 +0100 5449862 http://www.medworm.com/index.php?rid=5422291&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01010.x AbstractPrevious studies suggest that the antinociceptive action of paracetamol (acetaminophen, APAP) might involve descending inhibitory pain pathways and the opioidergic system: this study explores this issue in humans with naloxone, the opioid antagonist. After ethical approval, 12 healthy male volunteers were included in this randomized, controlled, double‐blind, crossover, four‐arm study. They were administered intravenous paracetamol (APAP 1 g) or saline (placebo, pl) followed at 100 min with IV naloxone (Nal 8 mg) or saline, every week for 4 weeks. The amplitude of cerebral potentials evoked by thermal/painful stimuli applied on the arm was recorded nine times over 150 min, witnessing of pain integration at central level. Amplitude changes as well as areas under the cu... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5422291 Sat, 19 Nov 2011 06:40:48 +0100 5422291 http://www.medworm.com/index.php?rid=5387111&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00999.x AbstractLASSBio‐985 is a sulfonamide compound designed as a simplified structure of a nonselective phosphodiesterase type 4 (PDE‐4) inhibitor that promotes vasodilatory activity in vitro. PDE are enzymes responsible for the hydrolysis of cyclic adenosine 3′,5′‐ monophosphate and cyclic guanosine 3′,5′‐monophosphate. Five different isozymes of PDE are found in vascular smooth muscle (PDE1–PDE5). Aortic rings, with or without endothelium, from male normotensive and spontaneously hypertensive rats (SHR) were prepared for isometric tension recording. Blood pressure was measured in Wistar Kyoto (WKY) rats and SHR during intravenous infusion of LASSBio‐985 (10 mg/kg/min) during 15 min. LASSBio‐985 induced a concentration‐dependent vasodilation in aortic rings from nor... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5387111 Thu, 10 Nov 2011 07:49:18 +0100 5387111 http://www.medworm.com/index.php?rid=5387112&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01006.x This article describes the design and methodology of the POWER study (Physicians’ Observational Work on Patient Education According to their Vascular Risk). POWER is an open‐label multinational postmarketing study of the angiotensin II‐receptor blocker eprosartan. The Systemic Coronary Risk Evaluation (SCORE) model has been used to estimate total cardiovascular risk and changes in total cardiovascular risk status during treatment for patients recruited in all countries other than Canada. Framingham Heart Study equations have been used to estimate risk in the Canadian contingent of POWER. Observations from POWER will provide insights into how clinicians try to achieve blood pressure goals within the framework of total cardiovascular risk management and how they integrate their treatme... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5387112 Fri, 04 Nov 2011 04:00:00 +0100 5387112 http://www.medworm.com/index.php?rid=5387118&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01002.x AbstractContemporary research indicates promising anticonvulsant effect of curcumin. However, its poor oral bioavailability is a major hindrance toward its pharmacological action. Thus, this study was carried out to evaluate the acute effect of liposome‐entrapped curcumin on increasing current electroshock seizures (ICES) test, pentylenetetrazole (PTZ)‐induced seizures, and status epilepticus in mice. Liposome‐entrapped curcumin in doses 25 and 50 mg/kg demonstrated significant increase in seizure threshold current and latency to myoclonic and generalized seizures in ICES test and PTZ‐induced seizures, respectively. Similarly, liposomal‐entrapped curcumin also increased the latency to the onset and decreased the duration of seizures during status epilepticus in mice. To conclud... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5387118 Wed, 02 Nov 2011 04:00:00 +0100 5387118 http://www.medworm.com/index.php?rid=5387117&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01004.x AbstractAccumulated evidence has demonstrated that aldosterone is a key player in the pathogenesis of cardiovascular (CV) disease. Multiple clinical trials have documented that intervention in the aldosterone pathway can reduce blood pressure and lower albuminuria and improve outcome in patients with heart failure or myocardial infarction. Recent studies have unraveled details about the role of aldosterone at the cellular level in CV disease. The relative importance of glucocorticoids and aldosterone in terms of mineralocorticoid receptor activation is currently being debated. Also, studies are addressing which aldosterone modulator to use, which timing of treatment to aim for, and in which population to intervene. This review provides an overview of recent developments in the understandin... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5387117 Wed, 02 Nov 2011 04:00:00 +0100 5387117 http://www.medworm.com/index.php?rid=5387116&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01005.x AbstractStepwise multiple regression analyses were applied to 44 atazanavir pharmacokinetic profiles from 44 HIV‐1 infected patients concomitantly treated with raltegravir with the goal of identifying limited sampling strategies for the prediction of drug AUC0–12. Atazanavir trough‐based equations failed to reliably predict daily drug exposure in patients with low drug bioavailability. Conversely, different algorithms based on few samples and associated with good correlation, acceptable bias and imprecision with the measured atazanavir AUC0–12 were identified. These models could be used to predict atazanavir exposure for clinic or research purposes. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5387116 Wed, 02 Nov 2011 04:00:00 +0100 5387116 http://www.medworm.com/index.php?rid=5387115&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01007.x AbstractChronic obstructive pulmonary disease (COPD) has become a global epidemic disease with an increased morbidity and mortality in the world. Inflammatory process progresses and contributes to irreversible airflow limitation. However, there is no available therapy to better control the inflammatory progression and therefore to reduce the exacerbations and mortality. Thus, the development of efficient anti‐inflammatory therapies is a priority for patients with COPD. β2‐Adrenoceptor agonists and anticholinergic agents are widely used as first line drugs in management of COPD because of their efficient bronchodilator properties. At present, many studies in vitro and some data obtained in laboratory animals reveal the potential anti‐inflammatory effects of these bronchodilators but ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5387115 Wed, 02 Nov 2011 04:00:00 +0100 5387115 http://www.medworm.com/index.php?rid=5387114&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01003.x AbstractNephrotoxicity of the anticancer drug cisplatin (CP) involves the generation of reactive oxygen species in renal cortex, and emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer actions. Therefore, we tested here the possible ameliorative effect of emodin on CP nephrotoxicity in rats. Emodin was given orally (10 mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Five days after CP treatment, rats were killed, and blood and urine samples, and kidneys were collected for the assessment of histopathological renal damage and apoptosis, and for biochemical estimation of creatinine and urea concentrations in plasma and urine, several cytosolic antioxidant enzyme activit... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5387114 Wed, 02 Nov 2011 04:00:00 +0100 5387114 http://www.medworm.com/index.php?rid=5387113&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01008.x AbstractOver the last few years, a number of cases of extrapyramidal disorders associated with trimetazidine (TMZ) use has been reported. Here, we report on a series of 21 cases. All but one of the patients (mean age 74) had been taking TMZ for several years. The indication for prescription of TMZ could not be identified in seven cases. The TMZ‐associated adverse drug reactions were typical parkinsonism (akinesia and/or rigidity and/or rest tremor) in 17 cases, gait disorders in three cases (one with orthostatic tremor), and restless leg syndrome in one case. Discontinuation of TMZ led to complete disappearance of the symptoms in 16 cases and a significant reduction in the five other patients. TMZ has the same piperazine core as the dopamine antagonists flunarizine and cinnarizine (both ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5387113 Wed, 02 Nov 2011 04:00:00 +0100 5387113 http://www.medworm.com/index.php?rid=5360509&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00995.x AbstractInsulin and the inhibition of the renin–angiotensin system have independent benefits for ischemia–reperfusion injury, but their combination has not been tested. Our aim was to evaluate the effects of insulin+captopril on insulin/angiotensin signaling pathways and cardiac function in the isolated heart subjected to ischemia–reperfusion. Isolated hearts were perfused (Langendorff technique) with Krebs–Henseleit (KH) buffer for 25 min. Global ischemia was induced (20 min), followed by reperfusion (30 min) with KH (group KH), KH+angiotensin‐I (group A), KH+angiotensin‐I+captopril (group AC), KH+insulin (group I), KH+insulin+angiotensin‐I (group IA), or KH+insulin+angiotensin‐I+captopril (group IAC). Group A had a 24% reduction in developed pressure and an increase... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5360509 Mon, 31 Oct 2011 04:31:02 +0100 5360509 http://www.medworm.com/index.php?rid=5347693&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01001.x In conclusion, SG‐Gc presents anti‐inflammatory effect involving the inhibition of histamine and arachidonic acid metabolites and also antinociceptive activity, especially the inflammatory pain with participation of the opioid system. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5347693 Wed, 26 Oct 2011 12:25:44 +0100 5347693 http://www.medworm.com/index.php?rid=5336026&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00994.x (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5336026 Sat, 22 Oct 2011 05:43:15 +0100 5336026 http://www.medworm.com/index.php?rid=5324121&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.01000.x AbstractPopulation pharmacokinetics and simulation techniques currently play an important role in new drug development. This paper illustrates the potential value of those methods in postmarketing safety assessment, using buflomedil in elderly patients as an example. We retrospectively assessed the risk of buflomedil overdosing associated with the latest dosing recommendations of the French Drug Agency (AFSSAPS). First, buflomedil concentrations measured in 24 elderly patients were analysed with a nonparametric population approach. Then, the pharmacokinetic model was used to perform a 1000‐patient Monte Carlo simulation for the two recommended buflomedil dosage regimens. The maximum concentrations calculated after 10 days of therapy were compared with levels observed in reported cases ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5324121 Mon, 17 Oct 2011 04:00:00 +0100 5324121 http://www.medworm.com/index.php?rid=5304570&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00996.x Conclusion: Montelukast may be a beneficial remedy for cisplatin‐induced renal dysfunction. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5304570 Tue, 11 Oct 2011 04:00:00 +0100 5304570 http://www.medworm.com/index.php?rid=5324120&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00997.x AbstractThe aim of this study was to evaluate potential drug–drug interaction between lithium and levofloxacin. The study was conducted on New Zealand white rabbits with three groups having two subgroups each (n = 12). The first group compared the pharmacokinetic (Pk) parameters of lithium when lithium was given as a single dose (56 mg/kg) and when lithium was co‐administered with levofloxacin (35 mg/kg). The second group compared the Pk parameters of lithium when lithium was given for 6 days alone and when levofloxacin was given on the sixth day after lithium steady‐state levels were achieved. The third group compared the Pk parameters of lithium when lithium was given alone for 8 days and levofloxacin was given on days 6, 7, and 8 along with lithium. Apart from this, cr... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5324120 Sat, 01 Oct 2011 04:00:00 +0100 5324120 http://www.medworm.com/index.php?rid=5304569&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00998.x In this study, we therefore investigated the possible antihyperalgesic and antiallodynic effects of levobupivacaine in diabetic animal model. Actions of systemically (intraperitoneal) or locally (intraplantar) administrated levobupivacaine on streptozotocin‐induced diabetic rats with painful neuropathy were examined using a thermal plantar test and a dynamic plantar aesthesiometer. Effects of levobupivacaine were compared with those of a well‐known amide local anaesthetic lidocaine. Levobupivacaine was more potent than lidocaine in all tests employed on diabetic rats. After intraperitoneal injections to diabetic rats, levobupivacaine, but not lidocaine, produced pronounced antihyperalgesic and antiallodynic effects. However, intraplantar administration of both levobupivacaine and lidoc... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5304569 Sat, 01 Oct 2011 04:00:00 +0100 5304569 http://www.medworm.com/index.php?rid=5260913&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00993.x This study aimed at evaluating the effectiveness of Gelsemium 5CH and 15CH on provoked anxiety in healthy volunteers, in comparison with placebo. This was a double‐blind, single‐centre, randomized, placebo‐controlled study. Eligible healthy men or women aged from 18 to 40 years without a history of psychiatric disorders were randomly allocated to receive Gelsemium 5 or 15CH or placebo. Anxiety was proved by performance of the Stroop colour word test (SCWT). The primary end‐point was anxiety assessed by the State measure of the State‐Trait Anxiety Inventory (STAI‐S) as the absolute value and difference with baseline, according to the treatment received. We included 180 healthy volunteers. The distribution into each treatment group was homogenous. There was no statistical diffe... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5260913 Thu, 29 Sep 2011 05:32:24 +0100 5260913 http://www.medworm.com/index.php?rid=5237944&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00992.x In conclusion, one large dose of EPO, given shortly before CPB, did not protect against cardiac and cerebral ischemia and inflammatory response occurring during CABG surgery with CPB. Although the long‐term clinical implications remain unknown, the findings do not support use of EPO at this dose as a cytoprotective agent in patients undergoing cardiac surgery. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5237944 Thu, 22 Sep 2011 07:43:07 +0100 5237944 http://www.medworm.com/index.php?rid=5237945&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00991.x AbstractTo evaluate the safety profile of eight oral nonsteroidal anti‐inflammatory drugs (NSAIDs) available in France, using data reported through the French pharmacovigilance system. Data (from 2002 to 2006) were analysed for aceclofenac, diclofenac, ketoprofen, meloxicam, naproxen, nimesulide, piroxicam and tenoxicam, focusing on the reported rates of serious adverse drug reactions (ADRs) in the following system organ classes: gastrointestinal, hepatic, cutaneous, renal and cardiovascular. A total of 42 389 serious ADR reports were identified, and 38 506 were included in a case/noncase analysis. Ketoprofen was associated with the highest cumulative reported rate of serious ADRs (0.78 cases per million defined daily doses), followed by diclofenac (0.58), nimesulide (0.52), naproxen... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5237945 Tue, 20 Sep 2011 04:00:00 +0100 5237945 http://www.medworm.com/index.php?rid=5237946&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00988.x We examined the protective properties of SF against AP‐induced oxidative stress in dopaminergic neuroblastoma cells. Human neuroblastoma SK‐N‐SH cells were treated with SF (0.5–5 μm), and 24 h later, haloperidol, risperidone or paliperidone (100 μm) was administered, either alone or in combination with dopamine (100 μm). To determine the antioxidant properties of SF, quinone oxidoreductase (NQO1) activity, glutathione S‐transferase activity, and glutathione (GSH) levels were determined. Oxidative stress was measured by the increase in thiobarbituric acid reactive substances (TBARS) and in protein‐bound quinones. Cell viability was also assessed. SF treatment increased GSH levels and induced NQO1 activity in SK‐N‐SH cells. Haloperidol was the only AP that increase... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5237946 Mon, 19 Sep 2011 04:00:00 +0100 5237946 http://www.medworm.com/index.php?rid=5225945&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00989.x This study examined two types of refeeding experiments after prolonged fasting. Firstly, rats with ad libitum access to food were compared to rats with ad libitum access to food and kaolinite pellets. Animals were randomly put into the different groups when the third phase of fasting (phase III) reached by each individual was detected. In a second set of experiments, rats starting phase III were refed with free access to food and kaolinite pellets. When animals had regained their body mass prior to fasting, they were euthanized for chemical, morphological, and proteomic analyses. Although kaolinite ingestion did not change the time needed for regaining prefasting body mass, daily food ingestion was seen to decrease by 6.8% compared with normally refed rats, without affecting lipid composit... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5225945 Sun, 18 Sep 2011 23:21:16 +0100 5225945 http://www.medworm.com/index.php?rid=5225946&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00975.x In this study, the effects of simvastatin on the blood pressure and on the antihypertensive activity of ramipril in hypertensive hypercholesterolemic animals and patients were evaluated. In hypertensive hypercholesterolemic animals, repeated administration of simvastatin slightly but significantly decreased the systolic blood pressure, enhanced its progressive reductions induced by repeated administration of ramipril and corrected the compromised lipid profile. Concomitantly, repeated administration of simvastatin, ramipril or simvastatin in combination with ramipril to these animals, increased nitric oxide (NO) production and decreased the elevated serum malondialdehyde (MDA) and high sensitivity C‐reactive protein (hs‐CRP) levels. The effects of combined treatment were greater than t... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5225946 Tue, 13 Sep 2011 04:00:00 +0100 5225946 http://www.medworm.com/index.php?rid=5196597&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00986.x AbstractPrasugrel is the most recent development of thienopyridine‐type antiplatelet drugs. Like the earlier‐generation thienopyridines, i.e. ticlopidine and clopidogrel, prasugrel is also an inactive prodrug that requires metabolic processing in vivo to generate the active antiplatelet metabolite. The efficacy of this bioactivation is the key determinant for the pharmacodynamic potency of the compound, i.e. the irreversible blockade of the platelet P2Y12‐ADP receptor. Prasugrel is rapidly absorbed from the gut. After oral administration of standard‐loading doses of 60 mg, maximum plasma levels of the active metabolite are achieved within 1 h, effective, maximum inhibition of platelet aggregation at 1–2 h. Bioconversion of prasugrel into the active metabolite requires two m... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5196597 Sun, 04 Sep 2011 23:00:00 +0100 5196597 http://www.medworm.com/index.php?rid=5196596&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00987.x In conclusion, when administered orally to Swiss mice, the ConBr lectin displayed antinociceptive activity, both peripheral and central, mediated by the opioid system and involving δ‐and κ‐receptors and the lectin domain. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5196596 Sun, 04 Sep 2011 23:00:00 +0100 5196596 http://www.medworm.com/index.php?rid=5196595&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00990.x This study was a cross‐sectional observational study. The prescriptions of patients for any chronic medical condition and drug therapy received at the first point of contact with health care services for present medical emergency were analyzed for information. The prescriptions were also analyzed for potential DDI. Data were expressed as mean ± SD or median and inter‐quartile range. Multiple logistic regression was used for variables likely to be associated with incidence of DDI. Of total 710 patients, 565 prescriptions were available for analysis. Of the chronic diseases, hypertension (17.7%) and diabetes mellitus (16.8%) were the commonest. Alcoholic liver disease had maximum average number of drugs prescribed (3.9). Supplements were the most commonly prescribed pharmacological ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5196595 Sun, 04 Sep 2011 23:00:00 +0100 5196595 http://www.medworm.com/index.php?rid=5161938&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00973.x This study investigates a possible antidepressant activity of rip II using two predictive tests for antidepressant activity in rodents: the forced swimming test (FST) and tail suspension test (TST). Additionally, the mechanisms involved in the antidepressant‐like effect in mice were also assessed. Rip II was acute administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at doses of 25 and 50 mg/kg. Results showed that ripII at both tested doses and administration routes produced a significant decrease of immobility time in FST and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an α1‐adrenoceptor antagonist), SCH23390 (15 μg/kg, i.p., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p‐chloropheny... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5161938 Sat, 20 Aug 2011 23:00:00 +0100 5161938 http://www.medworm.com/index.php?rid=5144077&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00980.x This article provides an overview of the phase III clinical development programmes for these novel OACs, with special focus on rivaroxaban. With encouraging data already emerging, the promise of a simplified single‐drug approach for VTE treatment is on the horizon. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5144077 Wed, 17 Aug 2011 23:00:00 +0100 5144077 http://www.medworm.com/index.php?rid=5120082&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00979.x AbstractVitamin K antagonists have been used as oral anticoagulants (OACs) for over five decades, yet their use in real‐world practice is problematic primarily because of their narrow therapeutic window, exacerbated by extensive food and drug interactions, necessitating regular coagulation monitoring and dose adjustment. Around half of patients receiving warfarin are within the therapeutic range, exposing them to the dangers of under‐anticoagulation (i.e. thrombosis formation) or over‐anticoagulation (i.e. bleeding). A new generation of OACs with improved pharmacology promises to revolutionize antithrombotic management. Rivaroxaban, apixaban (both oral direct Factor Xa inhibitors) and dabigatran (a direct thrombin inhibitor) all exhibit predictable anticoagulant responses and few dru... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5120082 Tue, 09 Aug 2011 23:00:00 +0100 5120082 http://www.medworm.com/index.php?rid=5196594&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00984.x AbstractThienopyridines have become the cornerstone of treatment for percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y12 inhibitors are more potent, more predictable, and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high‐risk percutaneous coronary intervention (PCI). Four new P2Y12 inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral pro‐drug leading to irreversible blockade of the P2Y12 receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct‐acting and reversible inhibitor of the P2Y12 receptor with potentially more pleiotropic effects. Cangrelor is an in... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5196594 Sun, 31 Jul 2011 23:00:00 +0100 5196594 http://www.medworm.com/index.php?rid=5184167&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00983.x AbstractPharmacogenetics have been touted as the future of personalized medicine where genetic biomarkers will guide therapeutic approach. The currently approved thienopyridines, prasugrel and clopidogrel, are prodrugs requiring conversion to active metabolite through the cytochrome P450 system. Genetic variation has been associated with the pharmacokinetic, pharmacodynamic, and clinical response to clopidogrel, but not to prasugrel. This review aims to summarize the recent pharmacogenetic findings associated with the response to thienopyridine treatment. Additionally, considerations for the incorporation of genetic biomarkers into clinical practice will be discussed in the context of thienopyridines. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5184167 Sun, 31 Jul 2011 23:00:00 +0100 5184167 http://www.medworm.com/index.php?rid=5170440&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00982.x AbstractOral anticoagulation in atrial fibrillation is obligatory to lower the risk of spontaneous cerebrovascular and systemic thromboembolism. For this purpose, vitamin K antagonists (coumarins) have been recommended as the most effective drugs for a long time. However, problems with the practical use of these agents, e.g. the need for frequent and regular coagulation controls, the inter‐individual differences in maintaining a stable therapeutic range, as well as drug or food interactions, have led to the search and investigation of alternative compounds characterized by a more simple use (e.g. without regular controls of therapeutic levels), high efficacy, as well as low risk of bleeding. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apix... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5170440 Sun, 31 Jul 2011 23:00:00 +0100 5170440 http://www.medworm.com/index.php?rid=5161937&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00969.x AbstractThe implication of oxidative stress associated with increased oxidant production in mammalian and human cells characterized by the release of free radicals, resulting in cellular degeneration, is involved in many ocular diseases, such as age‐related macular degeneration, retinopathy of prematurity, retinal light damage, primary open‐angle glaucoma (POAG), and cataract. Cataract is the leading cause of blindness, accounting for 50% of blindness worldwide. Glaucoma, the leading cause of irreversible blindness, is considered as a progressive optic neuropathy often caused by elevated intraocular pressure (IOP) consequent to abnormally high resistance to aqueous humor (AH) drainage via the trabecular meshwork (TM) and Schlemm’s canal. Morphological and biochemical analyses of the ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5161937 Sun, 31 Jul 2011 23:00:00 +0100 5161937 http://www.medworm.com/index.php?rid=5144076&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00965.x AbstractSeveral recent major randomized clinical trials (RCTs) using renal outcomes resulted in conflicting results. We searched MEDLINE via PubMed with the search request ‘(dialysis OR end‐stage renal disease) and creatinine’ in six major general journals and two leading journals of nephrology; 123 articles were found; 17/123 were relevant RCTs. Some disagreement among surrogate endpoints in 11/15 articles (missing data in two RCTs) and between surrogate and hard renal endpoints in 10/13; the intervention effects were in the opposite direction in 4/15, mostly in patients with cardiovascular disease, but discrepancies and conflicting results were also found among renal trials. Among our selected RCTs, 14/17 used composite endpoints: vital and renal endpoints were mixed in 11/14 trial... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5144076 Sun, 31 Jul 2011 23:00:00 +0100 5144076 http://www.medworm.com/index.php?rid=5132259&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00981.x AbstractRivaroxaban, an oral, direct factor Xa inhibitor, is a small molecule drug capable of inhibiting not only free factor Xa with high selectivity but also prothrombinase‐bound and clot‐associated factor Xa in a concentration‐dependent manner. Clinical studies have demonstrated predictable anticoagulation and confirmed dose‐proportional effects for rivaroxaban in humans with a rapid onset (within 2–4 h) and a half‐life of 7–11 h and 11–13 h for young and elderly subjects, respectively. For a 10 mg dose, the oral bioavailability of rivaroxaban is high (80–100%) and is not affected by food intake. These favourable pharmacological properties underpin the use of rivaroxaban in fixed dosing regimens, with no need for dose adjustment or routine coagulation monitorin... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5132259 Sun, 31 Jul 2011 23:00:00 +0100 5132259 http://www.medworm.com/index.php?rid=5120081&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00985.x This article discusses the reasons for antiplatelet function variability of clopidogrel and presents clinical data of the new ADP‐receptor inhibitors by reviewing the recently published trials and prespecified post hoc analyses of these trials as well as the potential use of the new antiplatelet agents in the near future. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5120081 Sun, 31 Jul 2011 23:00:00 +0100 5120081 http://www.medworm.com/index.php?rid=5109599&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00974.x AbstractThe possible protective effect of captopril, an angiotensin‐converting enzyme inhibitor, vs. telmisartan, an angiotensin II‐receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor‐α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administr... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5109599 Sun, 31 Jul 2011 23:00:00 +0100 5109599 http://www.medworm.com/index.php?rid=5088641&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00971.x AbstractThe inhibitory effect of aqueous‐ethanolic extract of Zataria multiflora Boiss (Labiatae) and carvacrol on histamine (H1) receptors was examined on tracheal chains of guinea‐pigs. The effects of three concentrations of aqueous‐ethanolic extract, carvacrol, 10 nm chlorpheniramine, and saline on histamine (H1) receptors were tested on three groups of guinea‐pig tracheal chains as follows: incubated trachea with (i) indomethacin (n = 9), (ii) indomethacin, propranolol, and atropine (n = 7), and (iii) indomethacin and propranolol (n = 6). The EC50 (effective concentration of histamine causing 50% of maximum response) obtained in the presence of chlorpheniramine for all concentrations of the extract and carvacrol in all three groups was significantly higher than th... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5088641 Sun, 31 Jul 2011 23:00:00 +0100 5088641 http://www.medworm.com/index.php?rid=5088640&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00972.x AbstractThe anti‐ulcerogenic potentials of low doses of rutin and cimetidine in ethanol‐, acetic acid‐, and stress‐induced ulcers in rats have been evaluated and compared in this study. In each model, male Wistar rats were randomly divided into six groups (I–VI). Groups II–VI were administered 1 mL/100 g ethanol orally, 0.05 mL of 20% acetic acid submucosally or kept in a cold chamber for 6 h to induce ulcer in the ethanol‐, acetic acid‐, and stress‐induced ulceration model, respectively. Thereafter, group III was post‐treated with 300 mg/kg cimetidine and groups IV–VI with 20, 40, and 80 mg/kg rutin, respectively, while the control (group I) received distilled water in Tween 20. One hour after post‐treatment, all groups were killed and the gastric ulcer... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5088640 Sun, 31 Jul 2011 23:00:00 +0100 5088640 http://www.medworm.com/index.php?rid=5079593&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00978.x AbstractGeophagia is found in various animal species and in humans. We have previously shown that spontaneously ingested kaolinite interacts with the intestinal mucosa modifies nutrient absorption and slows down gastric emptying and intestinal transit in rats in vivo. However, the precise mechanisms involved are not elucidated. The aim of this work was to investigate the effects of controlled kaolinite ingestion on food intake, gut morphology and in vitro motility in rats. Male Wistar rats were fed with 5% kaolinite in standard food pellets during 7, 14 and 28 days. Body mass and food consumption were measured daily. Intestinal morphological and proteomic analyses were conducted. The length of mucosal lacteals was evaluated. Plasmatic levels of leptin and adiponectin were determined. Fin... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5079593 Sun, 31 Jul 2011 23:00:00 +0100 5079593 http://www.medworm.com/index.php?rid=5079594&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00976.x In this study, simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination were administered to arthritic rats, first to determine their effects on the inflammatory response, employing a low‐dose adjuvant‐induced arthritis model in rats. Arthritis was induced by the subcutaneous injection of a suspension of Mycobacterium tuberculosis (100 μg) in mineral oil [complete Freund’s adjuvant used (CFA)] into the plantar surface of the hind paws. Simvastatin40mg/kg, atorvastatin10mg/kg, ezetimibe10mg/kg, ezetimibe10mg/kg + simvastatin20mg/kg or 40mg/kg were given intragastrically and the treatment began on the day of CFA injection and continued daily up to the 28th day after arthritis induction. The ezetimibe + simvastatin combination was more effective in re... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5079594 Sat, 30 Jul 2011 23:00:00 +0100 5079594 http://www.medworm.com/index.php?rid=5070346&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00963.x AbstractThe latest estimates of the World Health Organization indicate that there are 161 million visually impaired individuals worldwide, 37 million of whom are blind, with a yearly increase of 1–2 million. The scientists developed and patented the lubricant eye drops formulated as 1%N‐acetylcarnosine prodrug of l‐carnosine containing a mucoadhesive cellulose‐based compound combined with corneal absorption promoters in an ocular drug delivery system. Carcinine is suitable for the systemic administration (per oral) for ophthalmic therapeutic indications. The HPLC analysis was developed to search the pathways of ocular metabolic activities of 1%N‐acetylcarnosine and the bioactivation of this drug molecule promoting transcorneal uptake of l‐carnosine in the aqueous humor. A... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5070346 Thu, 28 Jul 2011 02:42:45 +0100 5070346 http://www.medworm.com/index.php?rid=5079595&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00968.x In conclusion, the present study provides evidence that the antidepressant‐like effect of ripIII is dependent on its interaction with the serotonergic, noradrenergic (α1‐ and α2‐ receptors), and dopaminergic (dopamine D2 receptors) systems. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5079595 Tue, 26 Jul 2011 23:00:00 +0100 5079595 http://www.medworm.com/index.php?rid=5070347&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00961.x AbstractIntroduction of new agents for the treatment for colorectal cancer (CRC) has been accompanied by the publication of guidelines. The COLCHIC cohort was set up to evaluate CRC treatment practices and the use of these innovative and expensive agents. Patients initiating CRC treatment at the Bordeaux teaching hospital between 1 March 2005 and 1 March 2006 were identified, and treatment courses from 1 March 2005 to 31 December 2006 were studied; 192 patients were included, 188 with analysable data: 43 patients initiated 51 courses for non‐metastatic cancer, 153 initiated 366 courses for metastatic cancer, eight patients initiated courses for both non‐metastatic and metastatic cancer. Most treatments were used for indications found in guidelines published during the study (83.9%). Of... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5070347 Tue, 26 Jul 2011 23:00:00 +0100 5070347 http://www.medworm.com/index.php?rid=5070348&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00977.x This study was designed to explore the modulation of the effects of PHOS on cognitive function by melatonin (MEL). Cognitive function was assessed using step‐down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP‐SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the PHOS (1.74 mg/kg/day; p.o.)‐treated group at weeks 6 and 8 as compared to the control group. Two‐week treatment with MEL (5 mg/kg/day; i.p.) antagonized the effect of PHOS on SDL as well as TL. PHOS alone produced a significant increase in the brain MDA levels and decrease in the brain NP‐... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5070348 Mon, 25 Jul 2011 23:00:00 +0100 5070348 http://www.medworm.com/index.php?rid=5052875&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00970.x AbstractIKs blockade might be a promising way to treat tachyarrhythmia because of the accumulation of activated potassium channels. However, IKs blockade during ischemia/reperfusion has not been investigated. Thus, the electrophysiological effects of two IKs blockers, chromanol 293B (10 μm) and HMR 1556 (1 μm), were assessed in an in vitro model of border zone between normal and ischemic/reperfused right ventricular myocardium from guinea‐pigs, and classic electrophysiological parameters and the incidence of arrhythmias were studied. HMR 1556 and chromanol 293B exhibited slight conventional class III effects on action potential duration in the normal zone (NZ) (APD90: −2 ± 5%, not significant (NS); +6 ± 3%, NS; and +5 ± 1%, P < 0.05, respectively, in control... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5052875 Sat, 23 Jul 2011 16:27:45 +0100 5052875 http://www.medworm.com/index.php?rid=5039914&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00967.x AbstractRemifentanil belongs to opioid drugs, and its pharmacokinetic characteristics make it unique in this class of drugs and appropriate for use during intubation without neuromuscular blockage. This up‐to‐date review aims to summarize the findings of recent studies regarding remifentanil and intubation. Remifentanil combined either with propofol or with inhaled anesthetic agents has been proved to provide acceptable intubating conditions. Regarding children patients, remifentanil can be used safely, and as far as intubating conditions are concerned, its effectiveness is as excellent as with neuromuscular blockage. Strong evidence exists that illuminates the usefulness of the drug in cases of difficult airway as well as in neuromuscular diseases. Beyond all these favorable character... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5039914 Wed, 20 Jul 2011 16:46:29 +0100 5039914 http://www.medworm.com/index.php?rid=5039915&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00966.x AbstractEfficacy of probiotics in the management of human inflammatory bowel disease (IBD) has been approved in the recent years. In the present work, the efficacy of a new biodegradable nanoparticles (NPs) of encapsulated and lyophilized probiotic extract (LPE) was examined in murine colitis. Colitis was induced by rectal instillation of trinitrobenzen sulfonic acid to male Wistar rats. The safety and effective dose of LPE was determined in a pilot study. To ease delivery into colon, LPE was encapsulated in chitosan‐coated‐poly (lactide co glycolide acid) NPs. After induction of colitis, animals in different groups received test compound in three doses by gavage for 10 days. Groups of sham, control (saline), and standard (dexamethasone) were also assigned. Colonic pathological exami... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5039915 Mon, 18 Jul 2011 23:00:00 +0100 5039915 http://www.medworm.com/index.php?rid=4954611&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00960.x AbstractThe present study was undertaken to investigate the effects of triple oral therapy and different combination of rosiglitazone, atorvastatin, and glimepiride on streptozotocin (STZ)‐induced diabetic rats. The various biochemical parameters studied included glycosylated hemoglobin (A1c), fasting plasma sugar levels, triglycerides, low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL) cholesterol, and very low‐density lipoprotein (VLDL) cholesterol in diabetic and normal rats. The present study demonstrates that atorvastatin could increase the effect of rosiglitazone and glimepiride and lipid‐lowering effect of combination of rosiglitazone and glimepiride (GLIM). According to our finding, similar results for rosiglitazone plus atorvastatin were obtained i... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4954611 Tue, 21 Jun 2011 23:00:00 +0100 4954611 http://www.medworm.com/index.php?rid=4986296&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00964.x AbstractIn vitro screening of chemotherapeutic agents is routinely carried out in static monolayer cell cultures. However, drugs administered to patients act in the presence of various microenvironments in vivo. For example, in lung tumors, mechanical forces are constantly present and do affect the physiological response of the lung tissue to a variety of therapeutic agents. We hypothesized that mechanical forces may affect the response of lung tumors to chemotherapeutic agents and studied the effects under simulated conditions. First, we examined the effects of simulated forces that approximate normal respiration on the proliferation and morphology of NCI‐H358 and A549 cell lines. Then, we studied the effects of the simulated forces on the ability of Paclitaxel, Doxorubicin, Cisplatin, ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4986296 Tue, 31 May 2011 23:00:00 +0100 4986296 http://www.medworm.com/index.php?rid=4954610&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00958.x AbstractPropofol has shown antioxidant properties, but no study has focused on liver resection surgery. The aim of this study was to investigate the effect of an anesthesia with propofol compared with desflurane on oxidative stress and hepatic function during and after partial hepatectomy. This was a prospective randomized study performed on two parallel groups. The primary endpoint was malondialdehyde (MDA) plasma concentration 30 min after hepatic vascular unclamping. Hepatic damages were evaluated by plasma levels of alpha‐glutathione S‐transferase (α‐GST) 120 min after hepatic vascular unclamping and of aminotransferases at 120 min and on days 1, 2, 5, and 10. Liver function recovery was assessed by monoethylglycinexylidide (MEGX) formation 15 min after lidocaine injecti... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4954610 Tue, 31 May 2011 23:00:00 +0100 4954610 http://www.medworm.com/index.php?rid=4937198&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00962.x This study was designed to assess and compare the PK properties of mildronate capsules after single escalating oral dose and multiple doses in healthy Chinese volunteers. Volunteers were randomly assigned to receive a single dose of 250, 500, 1000, 1250 or 1500 mg of mildronate capsules. Those who received the 500‐mg dose continued on the multiple‐dose phase and received 500 mg three times a day for 13 days. Plasma drug concentrations were analysed by ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC‐MS/MS). Tolerability was assessed throughout the study. A total of 40 Chinese volunteers were enrolled in the study. No period or sequence effect was observed. Area under the concentration and Cmax were increased proportionally with the dose levels,... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4937198 Tue, 31 May 2011 23:00:00 +0100 4937198 http://www.medworm.com/index.php?rid=4885885&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00957.x In conclusion, EVR and SRL are both subject to an apically directed efflux mediated by P‐gp. TAC mainly inhibits this efflux mechanism, while the effect of cyclosporine appears to be more complex with mechanisms to be confirmed by further studies. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4885885 Tue, 31 May 2011 23:00:00 +0100 4885885 http://www.medworm.com/index.php?rid=4885884&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00959.x AbstractClinical features at onset of Creutzfeldt–Jakob disease (CJD) may mimic symptoms of Lewy bodies dementia. Clinical evolution, neuroimaging, metabolism exploration, and cerebrospinal fluid investigations may help establishing the diagnosis. However, CJD definite diagnosis requires postmortem autopsy. This symptom overlap led us to successfully prescribe an anticholinesterasic treatment, rivastigmine, to a patient for whom a probable CJD disease was finally diagnosed. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4885884 Tue, 31 May 2011 23:00:00 +0100 4885884 http://www.medworm.com/index.php?rid=4885883&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00952.x AbstractThe aim of this study was to investigate the effect of SCH 58261, a selective adenosine A2A receptor (A2AR) antagonist, on kainic acid (KA)‐induced seizures in 21‐day‐old rats. Rats were pretreated with SCH 58261 (1 or 3 mg/kg) by intraperitoneal (i.p.) route 30 min before KA (10 mg/kg, i.p.) administration. The appearance of clonic seizures, the latency for the onset of the first clonic seizure episode, and the number of deaths induced by KA were evaluated. To test the hypothesis of the oxidative imbalance induced by KA exposure, reactive species (RS) levels, catalase (CAT), glutathione peroxidase (GPx), and glutathione S‐transferase (GST) activities in the brains of rats were measured. Both doses of SCH 58261 prolonged the latency for the onset of the first clonic s... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4885883 Tue, 31 May 2011 23:00:00 +0100 4885883 http://www.medworm.com/index.php?rid=4885882&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00955.x AbstractMacrophages are important drug targets as they mediate a wide variety of infectious diseases. Visceral leishmaniasis (VL), schistosomiasis, brucellosis, and salmonellosis are some of the well‐known infectious diseases in which macrophages play a prominent pathophysiological role. For instance, VL parasites exclusively house in the macrophages of liver and spleen. They are resistant to lysosomal degradation by unknown mechanisms, they survive and thrive safely within macrophages, they multiply, and they ultimately affect visceral organs, leading to severe pathological and sometimes even fatal conditions. The majority of routinely used drugs administered in free form distribute all over the body via systemic circulation, leading to relatively low therapeutic activity and a certain ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4885882 Tue, 31 May 2011 23:00:00 +0100 4885882 http://www.medworm.com/index.php?rid=4885881&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00956.x In this study, we hypothesized that liquiritin apioside (LA), a main flavonoid component from Glycyrrhiza uralensis, had antioxidant properties by inducing glutathione (GSH) biosynthesis via the inhibition of cytokines and protected lung epithelial cells against cigarette smoke‐mediated oxidative stress. A549 cells were treated with cigarette smoke extract (CSE) and/or LA. ICR mice were exposed to cigarette smoke (CS) for four days with increasing exposure time for up to 6 h per day to elicit epithelial cells injury. One hour before smoke exposure, mice were treated with LA by gavage; 18 h after the last CS exposure all examinations were performed. Treatment with LA concentration‐dependently prevented CSE‐induced cytotoxicity, increase of TGF‐β and TNF‐α mRNA expression, depl... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4885881 Tue, 31 May 2011 23:00:00 +0100 4885881 http://www.medworm.com/index.php?rid=4885880&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00954.x This study investigated the effect of the herbal antidepressant St John’s wort, an inducer of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of oral S‐ketamine. In a randomized cross‐over study with two phases, 12 healthy subjects were pretreated with oral St John’s wort or placebo for 14 days. On day 14, they were given an oral dose of 0.3 mg/kg of S‐ketamine. Plasma concentrations of ketamine and norketamine were measured for 24 h and pharmacodynamic variables for 12 h. St John’s wort decreased the mean area under the plasma concentration–time curve (AUC0–∞) of ketamine by 58% (P < 0.001) and decreased the peak plasma concentration (Cmax) of ketamine by 66% (P < 0.001) when compared with placebo. Mean Cmax of norketamine... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4885880 Tue, 31 May 2011 23:00:00 +0100 4885880 http://www.medworm.com/index.php?rid=4885887&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00945.x AbstractThe combination of lapatinib and capecitabine is approved in Her2+ metastatic breast cancer. However, the pharmacological mechanisms for this association have not been fully elucidated. In this non‐clinical study, we evaluated the efficacy of this association on a panel of six human breast cancer cell lines as a means to identify the molecular determinants of response to this combination. Cell viability was evaluated after concomitant/sequential exposure, and response/resistance determinants for each drug such as dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), thymidine phosphorylase, Bax, Bcl2, P21 levels, and phospho p42/44 and HER1/2 signaling pathway were studied. Lapatinib proved to markedly downregulate TS activity, thus suggesting a subsequent better effi... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4885887 Sun, 29 May 2011 23:00:00 +0100 4885887 http://www.medworm.com/index.php?rid=4885886&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00953.x The objectives were to elucidate its cardiac electrophysiological properties. Patch‐clamp technique was used to assess the IKr‐, IKs‐, and INa‐blocking effects of bupropion. Langendorff retroperfusion technique on isolated guinea‐pig hearts was used to evaluate the MAPD90‐, MAP amplitude‐, phase 0 dV/dt‐, and ECG‐modulating effects of bupropion and of two gap junction intercellular communication inhibitors: glycyrrhetinic acid and heptanol. To evaluate their effects on cardiac intercellular communication, fluorescence recovery after photobleaching (FRAP) technique was used. Bupropion is an IKr blocker. IC50 was estimated at 34 μm. In contrast, bupropion had hardly any effect on IKs and INa. Bupropion had no significant MAPD90‐modulating effect. However, as glycyrrhet... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4885886 Sun, 29 May 2011 23:00:00 +0100 4885886 http://www.medworm.com/index.php?rid=4831766&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00951.x AbstractTo explore for the first time the tolerability and efficacy of naftazone in patients with Parkinson’s disease (PD). Proof‐of‐concept, randomized, double‐blind, placebo‐controlled, multiple‐cross‐over n‐of‐1 study in patients with PD with wearing‐off and dyskinesias. Naftazone was titrated up to 120 mg/day during an initial single‐blind dose‐finding phase. Seven patients entered the placebo‐controlled phase (four consecutive 28‐day cross‐overs). Three outcome measures were used to collect preliminary indices of efficacy: (i) 48‐h ON‐OFF diaries; (ii) Unified PD Rating Scale (UPDRS) part III while ON; (iii) seven‐point Likert scale to assess “patients’ discomfort caused by dyskinesias” (Q1) and ‘disability during OFF‐periods’ (Q2). A ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4831766 Wed, 18 May 2011 17:01:39 +0100 4831766 http://www.medworm.com/index.php?rid=4814321&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00950.x This study confirms that theft, forged prescription and internet are few used and permits to highlight diversion of prescription drugs. It is important to inform healthcare professionals on the different prescription drugs that are illegally obtained. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4814321 Thu, 12 May 2011 17:18:01 +0100 4814321 http://www.medworm.com/index.php?rid=4790391&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00949.x AbstractThe relationships between virological (darunavir resistance–associated mutations), pharmacological (darunavir trough plasma concentration), combined virological/pharmacological [darunavir genotypic inhibitory quotient (GIQ)] parameters and virological response were evaluated in experienced patients infected with human immunodeficiency virus. In this retrospective study (48 patients), the relationship between these parameters and the virological response was investigated by multivariate logistic regression. Darunavir GIQ is defined as the ratio between darunavir trough plasma concentration and the count of darunavir resistance–associated mutations (V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V) corrected or not corrected by the count of mutations with positive imp... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4790391 Fri, 06 May 2011 16:28:42 +0100 4790391 http://www.medworm.com/index.php?rid=4759510&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00946.x In this study, the effect of tolbutamide on major organogenesis period and the possible involvement of apoptosis in mediating congenital malformations have been carried out. In the present study design, post‐implantation rat embryos of day 11 were cultured for 24 h with various concentrations of tolbutamide, i.e., 10, 100, and 1000 μg/mL cultures, respectively. The growth and developmental of each embryo was evaluated and compared with control ones for the presence of any malformations. The tolbutamide decreased all growth and developmental parameters in a concentration‐dependent manner, when compared with control. However, exposure to tolbutamide at 10 μg/mL culture did not show any significant effect on embryonic growth and development in vitro. In parallel to this, flow cyto... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4759510 Thu, 28 Apr 2011 15:41:22 +0100 4759510 http://www.medworm.com/index.php?rid=4755030&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00947.x AbstractNa+/K+‐ATPase and N‐methyl‐d‐aspartate (NMDA) receptor in hippocampus play very important roles in the regulation of learning and memory. Here, we showed that dihydroouabain (DHO, 10−5–10−3 m), a Na+/K+‐ATPase inhibitor, significantly potentiated NMDA current in rat hippocampal CA1 pyramidal neurons, which was blocked by PP2 (the selective Src tyrosine kinase inhibitor) and PD‐98059 [the selective inhibitor of the mitogen‐activated protein kinases (MAPK) cascade]. These findings reported here uncover that Src mediates the cross‐talk between Na+/K+‐ATPase and NMDA receptor to transduce the signals from Na+/K+‐ATPase to the MAPK cascade and provide new insights into therapeutic target for deeper understanding of the nature of cognitive disorder. (Source: F... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4755030 Wed, 27 Apr 2011 16:21:19 +0100 4755030 http://www.medworm.com/index.php?rid=4755031&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00943.x AbstractVitamin A has been characterized as a potential neurotoxin, because ingestion of such vitamin – or its derivatives, the retinoids – at moderate to high doses elicits a myriad of deleterious effects, from acute intoxication involving head‐ache, confusion, and ‘pseudo tumor cerebri’ to chronic, and perhaps irreversible, abnormalities, including irritability, anxiety, depression, and suicide ideation. Nevertheless, it still remains to be found the mechanism by which vitamin A induces cognitive decline. Based on the fact that vitamin A at clinical doses is a potent pro‐oxidant agent to the central nervous system, we performed the present work to analyze whether a cotreatment with L‐NAME at 30 mg/kg (four times a week) was able to prevent (or minimize) the biochemical an... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4755031 Mon, 25 Apr 2011 23:00:00 +0100 4755031 http://www.medworm.com/index.php?rid=4698550&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00939.x In this study, we performed a case–control study of patients with breast cancer and healthy controls in a Saudi population using TaqMan‐based real‐time PCR. We found an increased breast cancer risk associated with the MDM2 GG [odds ratio (OR) = 2.79, 95% confidence interval (CI) = 2.04–3.92] and TG [OR = 1.43, 95% CI = 1.12–2.02] genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.19, 95% CI = 1.54–3.06) compared with the Arg/Arg genotype. The gene–gene interaction of MDM2 and TP53 polymorphisms increased breast cancer risk in a multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.71, 95% CI = 3.49–17.54). These findings suggest that polymorphisms of MDM2 and TP53 ge... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4698550 Sun, 10 Apr 2011 23:00:00 +0100 4698550 http://www.medworm.com/index.php?rid=4698549&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00944.x AbstractEmerging evidence from preclinical, clinical and epidemiological studies suggests that vitamin D3 plays vital roles in several diseases in addition to bone disorders. According to new medical evidence, it is being recommended that vitamin D3 intake to be increased for maximal benefits in human health. However, it is necessary to consider potential side effects of increased intake of vitamin D3. Vitamin D3 exerts its actions through the vitamin D receptor, which is known to be an important regulator of P‐glycoprotein (P‐gp). As P‐gp plays a significant role in limiting drug bioavailability, we undertook a study to compare single‐dose digoxin (a P‐gp substrate) pharmacokinetics in eight healthy male subjects before and after vitamin D3 supplementation (1000 IU per day). T... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4698549 Sun, 10 Apr 2011 23:00:00 +0100 4698549 http://www.medworm.com/index.php?rid=4698548&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00948.x AbstractRadioligand binding studies revealed that Ang IV binds to insulin‐regulated aminopeptidase (IRAP)/’AT4 receptors’ with high affinity. Yet, as these experiments were routinely carried out in the presence of chelators, only the catalytic zinc‐depleted apo‐form of IRAP was labelled. While the chelators remove the catalytic zinc from IRAP and protect Ang IV from proteolytic degradation, the aminopeptidase N selective inhibitor ‘7B’ only exerts the latter effect. By using 7B along with the new stable Ang IV‐analog [3H]AL‐11, we here show that the native enzyme is only a low‐affinity target for Ang IV. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4698548 Sun, 10 Apr 2011 23:00:00 +0100 4698548 http://www.medworm.com/index.php?rid=4698547&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00940.x AbstractWe previously reported that acute exposure to intermittent hypoxia results in delayed cardioprotection against ischemia/reperfusion (I/R) injury and that the hypoxia‐inducible factor (HIF)‐1α, a transcriptional factor stabilized by hypoxia, as well as inducible nitric oxide synthase (iNOS) play a key role in this form of preconditioning. As cobalt chloride (CoCl2) is known to promote HIF‐1α stabilization by inhibiting prolyl hydroxylase activity, we hypothesized that CoCl2 could mimic the cardioprotective effects of hypoxia. Two groups of rats were administered 30 mg/kg twice of CoCl2 or sterile water. Twenty‐four hours later, hearts were perfused in Langendorff mode and subjected to an I/R protocol. Infarct size and functional recovery were studied. The role of iNOS wa... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4698547 Sun, 10 Apr 2011 23:00:00 +0100 4698547 http://www.medworm.com/index.php?rid=4698546&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00942.x AbstractCarbon tetrachloride (CCl4) is a well‐known model for inducing chemical hepatic injury in Swiss albino mice. The present study was designed to examine the ability of lycorine a natural alkaloid compound to prevent CCl4‐induced hepatotoxicity in the Swiss albino mice. After the experimental period of 8 weeks, CCl4 significantly increased the generation of lipid peroxidation products, it reflected by high levels of malondialdehyde, hepatic marker enzymes like aspartate transaminase, Alanine transaminase, Lactate dehydrogenase, alkaline phosphatase and lipids profiles. These increases were accompanied by significant decreases of glutathione (GSH); vitamin C content and significant reduction in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione‐S�... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4698546 Thu, 31 Mar 2011 23:00:00 +0100 4698546 http://www.medworm.com/index.php?rid=4686565&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00941.x In conclusion, the protective effects of DMP appear to be independent of gastric acid secretion and may be associated with counteracting the oxidative stress by replenishing glutathione and reducing the pool of transition metals. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4686565 Thu, 31 Mar 2011 23:00:00 +0100 4686565 http://www.medworm.com/index.php?rid=4601646&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00889.x This study was designed to investigate the potential differences between Spaniards and Ecuadorian Mestizo people regarding CYP2A6*1A, CYP2A6*1B1, CYP2A6*1x2A, CYP2A6*9A, and CYP2A6*4A variant alleles at the CYP2A6 gene and also to compare the observed frequencies with those previously reported in different ethnic groups. DNA from 234 Spaniard and 300 Ecuadorian subjects were analyzed by either PCR or PCR‐restriction fragment length polymorphism. Differences between Spaniards and Mestizo Ecuadorians were detected in relation to the frequencies of the alleles linked to either absent enzyme activity, CYP2A6*4A (4 and 7.1%, respectively), or reduced CYP2A6 enzyme activity, CYP2A6*9A (6.4 and 10.3%, respectively). CYP2A6*4A and CYP2A6*9A frequencies in Ecuadorians were higher than those in Af... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4601646 Thu, 17 Mar 2011 16:41:12 +0100 4601646 http://www.medworm.com/index.php?rid=4595251&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00937.x AbstractK‐depleted and control rats were anesthetized and infused with terbutalin. In controls, plasma K concentration (pK) decreased by 0.7 mm (P = 0.01). In moderate hypokalemia terbutalin‐induced decrease in pK was reduced by 0.3 mm for each 1 mm decrease in pK (n = 8, R2 = 0.82, P = 0.002) and by 0.2 mm for each 10 mmol/g wet wt. decrease in muscle K content (n = 8, R2 = 0.66, P = 0.01). Hence, for baseline pK of 4, 3 and 2 mm, decrease in pK was 0.7, 0.4 and 0.1 mm, respectively. In severe hypokalemia (1.7 mm), terbutain induced no further reduction in pK. The combined infusion of insulin and terbutalin showed no additive effect. Normalization of pK by KCl infusion in severe hypokalemia immediately abolished protection against terbutalin... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4595251 Wed, 16 Mar 2011 16:46:19 +0100 4595251 http://www.medworm.com/index.php?rid=4581849&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00938.x The objectives of this study was to investigate of the influences of high‐dose (20 mg/kg/day) methyl prednisolone (HDMP) and granulocyte colony stimulating factor (G‐CSF) in shortening the duration of chemotherapy‐induced neutropenia encountered in children with ALL receiving maintenance therapy. Sixty‐four non‐febrile neutropenic attacks developed in 29 patients with ALL receiving St Jude XIII maintenance protocol were evaluated retrospectively. The patients were clinically followed up without drugs for shortening the duration of neutropenia in 21 (32.8%) attacs, while HDMP and G‐CSF were administered in 26 (40.6%) and 17 (26.6%) attacks, respectively. After the detection of neutropenia, restoration of neutrophil counts at 2nd or 4th days to the levels that allow resuming th... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4581849 Mon, 14 Mar 2011 17:56:43 +0100 4581849 http://www.medworm.com/index.php?rid=4581850&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00933.x AbstractStudies in animals and in healthy volunteers have demonstrated the central serotonergic analgesic mechanism of action of paracetamol involving the inhibition of this analgesia by tropisetron, a 5‐HT3 antagonist. This randomized, double‐blind, controlled study aims at studying this interaction in post‐operative patients after ear surgery. Thirty‐six patients are included in two parallel groups with intravenous paracetamol (1 g) and either tropisetron (T, 5 mg/mL) or placebo (c, NaCl 0.9%) administered at the end of surgery. Numerical pain evaluations are performed every 30 min, six times after awakening. The difference between the sums of numerical scales of both groups [9 ± 10 (T) vs. 6 ± 7 (c)] is not significant, but the tropisetron group displays higher p... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4581850 Mon, 14 Mar 2011 00:00:00 +0100 4581850 http://www.medworm.com/index.php?rid=4571686&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00936.x AbstractThe present study was designed to investigate the possible role of endogenous opioids and KATP channels in glycerol‐induced acute renal failure (ARF) in rats. The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 mL/kg), and the animals were sacrificed after 24 h of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Naltrexone (2.5, 5.0 and 10.0 mg/kg s.c.), glibenclamide (5.0 and 10.0 mg/kg i.p.), and minoxidil (25 and 50 mg/kg) were employed to explore the role of endogenous opioids and KATP channels in rhabdomyolysis‐induced ARF. Pretreatment with naltrexone and glibenclamide attenuated hy... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4571686 Fri, 11 Mar 2011 16:40:49 +0100 4571686 http://www.medworm.com/index.php?rid=4571689&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00932.x AbstractThe aim of this study was to assess the strength of hemostatic effects of ezetimibe, administered alone or in combination with simvastatin, in patients with isolated hypercholesterolemia. One hundred and four patients with isolated primary hypercholesterolemia were randomized to one of four treatment groups, simultaneously treated for 90 days with ezetimibe (10 mg daily), simvastatin (40 mg daily), ezetimibe (10 mg daily) plus simvastatin (40 mg daily), or placebo. Plasma lipids/lipoproteins and hemostatic cardiovascular risk factors were assessed on the day of randomization and after 30 and 90 days of therapy. Despite improving lipid/lipoprotein profile by both simvastatin and ezetimibe, only simvastatin reduced plasma levels/activity of fibrinogen, factor VII, factor ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4571689 Fri, 11 Mar 2011 00:00:00 +0100 4571689 http://www.medworm.com/index.php?rid=4571688&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00934.x AbstractIn addition to its regulatory effect on bone mass, calcitonin has been shown to relieve pain and alleviate peripheral circulatory disturbance in patients with Raynaud’s syndrome and complex regional pain syndrome. In the present study, we investigated whether calcitonin ameliorates diminished blood flow and enhanced arterial contraction in response to noradrenaline in chronic constriction injury (CCI) of the sciatic nerve in rats. Following surgically induced CCI, laser Doppler flowmetry studies showed a significant decrease in plantar skin blood flow of the ipsilateral hind paw compared to the contralateral side. A subcutaneous bolus injection of elcatonin (20 U/kg), a synthetic derivative of eel calcitonin, significantly improved decreased skin blood flow in the ipsilateral s... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4571688 Fri, 11 Mar 2011 00:00:00 +0100 4571688 http://www.medworm.com/index.php?rid=4571687&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00935.x AbstractIn the present study, we have investigated the effect of the peroxisome proliferator‐activated receptor α (PPARα) agonist fenofibrate on airway reactivity and the role of the endothelial nitric oxide synthase (eNOS)/NO pathway in this effect. Airway reactivity to methacholine was assessed in C57BL/6 mice treated or not with fenofibrate by whole‐body plethysmography. In some experiments, animals were administered with the NOS inhibitor L‐NAME, one hour before airway reactivity measurement. Expression and phosphorylation of eNOS were evaluated in lung homogenates from fenofibrate and control animals using Western blotting. Fenofibrate dose and time dependently decreased airway reactivity to methacholine in mice. A statistically significant (P < 0.05) reduction was obse... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4571687 Fri, 11 Mar 2011 00:00:00 +0100 4571687 http://www.medworm.com/index.php?rid=4513534&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00914.x We report a case of left bundle branch block in a 35‐year‐old woman treated with INF beta‐1a for multiple sclerosis. Five years after INF therapy, she presented loss of consciousness, retrosternal pains, short breath and lowered tolerance of effort. ECG and Holter 24‐h ECG monitoring revealed permanent complete left bundle branch block. Nine months after stopping INF, no abnormalities were found at ECG and echocardiogram examination. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4513534 Thu, 24 Feb 2011 00:00:00 +0100 4513534 http://www.medworm.com/index.php?rid=4513533&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00925.x AbstractAnxiety following heart failure (HF) and/or myocardial infarction (MI) can impede recovery and constitute a major risk factor for further cardiac events. The present study was aimed to evaluate anxiety following doxorubicin (DOX)‐induced cardiomyopathy, a rodent model for HF, in mice. Furthermore, the study investigated the effect of alprazolam on anxiety and cardiomyopathy in this model. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg i.v. Alprazolam was administered at doses of 0.5, 1 and 2 mg/kg po for 7 days’ pre‐ and 7 days’ post‐DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogel’s conflict test. On 14th day, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and hea... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4513533 Thu, 24 Feb 2011 00:00:00 +0100 4513533 http://www.medworm.com/index.php?rid=4513532&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00926.x AbstractThe aim of this study was to investigate whether puerarin protects against high glucose (HG)‐induced apoptosis by suppressing calpain activation in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to normal glucose (NG) (5.5 mm) or HG (33 mm) for 48 h; then, apoptosis and caspase‐3 activity were determined. The expression of heme oxygenase‐1 (HO‐1) mRNA was evaluated by RT‐PCR analysis. The activation of calpain and HO activity were also assessed. Compared with the NG group, exposure of HUVECs to HG for 48 h resulted in significant increases in calpain and caspase‐3 activity as well as apoptosis, which were prevented by co‐incubation with puerarin (1–100 μm) in a concentration‐dependent manner. HO‐1 mRNA expression and HO activity ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4513532 Thu, 24 Feb 2011 00:00:00 +0100 4513532 http://www.medworm.com/index.php?rid=4490814&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00928.x AbstractThe involvement of cGMP/KATP pathway in effects of sildenafil on experimental colitis was investigated. Sildenafil significantly attenuated colonic injury markers. These effects were reversed by the addition of glibenclamide or ODQ, indicating the involvement of ATP‐sensitive potassium channels (KATP) and cGMP, respectively. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4490814 Wed, 16 Feb 2011 00:00:00 +0100 4490814 http://www.medworm.com/index.php?rid=4490813&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00910.x AbstractCurrent study aims to evaluate the efficacy of baicalein (BE), a naturally occurring bioactive flavanoid (5,6,7‐trihydroxy‐flavone), at a dose of 12 mg/kg body wt in Swiss albino mice exposed to tobacco‐specific carcinogen benzo(a)pyrene [B(a)P] (50 mg/kg body wt) for its ability to mitigate pulmonary adenoma formation and growth. Under coarse observation, B(a)P‐administered mice, after 16 weeks, developed macroscopically detectable tumors, whereas oral treatment with BE to the lung cancer–induced mice significantly reduced tumor incidence in 16‐week pre‐ and posttreated groups. A detailed histopathological examination of lung was conducted to determine the degree of cancer progression. Incidence of anaplasia, hyperplasia, dysplasia, severe dysplasia, and adenoc... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4490813 Wed, 16 Feb 2011 00:00:00 +0100 4490813 http://www.medworm.com/index.php?rid=4513531&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00927.x In this study, an attempt has been made to investigate the in vivo genotoxicity of FS at the hepatotoxic equivalent doses using the chromosomal aberration and the comet assay in the bone marrow cells of mice as the endpoints of evaluation. The animals were treated with FS at the doses of 2.5, 5, 10, 20, 40, and 80 mg/kg/body weight (bw) intraperitoneal (ip) for both single (24 h) and repeated dose (seven consecutive days) toxicity studies. FS toxicity in the hepatocytes was evaluated using the parameters, such as, alanine‐/aspartate‐aminotransferase (ALT/AST), single cell gel electrophoresis (comet), tissue histology, DNA fragmentation, and TUNEL assay as the endpoints. The results clearly demonstrate that FS produced toxic responses in the hepatocytes as evident from increased ALT... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4513531 Tue, 01 Feb 2011 00:00:00 +0100 4513531 http://www.medworm.com/index.php?rid=4490812&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00929.x We report a 34‐year‐old woman with multiple sclerosis who developed, while being treated with interferon β‐1a, myalgia and associated with wrist synovitis. Clinical and immunologic investigations were in favor of systemic lupus erythematosus. Interferon therapy was maintained. Under corticosteroids and antipaludeen treatment, the patient did not develop any other lupic manifestations. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4490812 Tue, 01 Feb 2011 00:00:00 +0100 4490812 http://www.medworm.com/index.php?rid=4451483&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00921.x AbstractAgonists of μ‐opioid receptors are currently used in the management of cancer pain. However, several data suggest that the analgesic effect of morphine can diminish during the development of experimental tumors. By using a thermal test, we have studied whether the analgesic effect evoked by morphine is altered in mice bearing two painful bone tumors. The analgesic effect evoked by systemic morphine remained unaltered after the intratibial inoculation of B16‐F10 melanoma cells and was potentiated after the inoculation of NCTC 2472 osteosarcoma cells. Although the number of spinal μ‐opioid receptors measured by western blot studies was not augmented in osteosarcoma‐bearing mice, the analgesia evoked by intrathecal (i.t.) morphine was also enhanced. The analgesic response pr... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4451483 Tue, 01 Feb 2011 00:00:00 +0100 4451483 http://www.medworm.com/index.php?rid=4400958&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00917.x This study was carried out to estimate the allele and genotype frequencies of common variants in CYP2E1, CYP2A6 and CYP3A5 in South Indian population. Six hundred and fifty‐two unrelated healthy volunteers of South Indian origin (Andhra Pradesh, Karnataka, Kerala and Tamil Nadu) were included in this study. Polymerase chain reaction–restriction fragment length polymorphism, allele‐specific PCR, real‐time PCR, SNaPshot and gene sequencing methods were used for the identification of gene polymorphisms. The frequencies of CYP2E1*1B, CYP2E1*5B and CYP2E1*6 alleles in South Indian population were 14.3, 1.3 and 22.4%, respectively. The frequencies of CYP2A6*2, CYP2A6*4A and CYP2A6*5 alleles were found to be 1, 8.9 and 0.7%, respectively. The distribution of CYP3A5*3 allele was 63.5%. The... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4400958 Thu, 27 Jan 2011 15:35:50 +0100 4400958 http://www.medworm.com/index.php?rid=4400961&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00919.x AbstractThe effects of ethanol were examined on three tests of exploratory activity in two mouse strains. Although ethanol reduced open‐field rearing in both strains, it increased ambulation only in the less active BALB/cAnN@Ico strain, not in the C57BL/6JIco strain. Likewise, ethanol increased open and enclosed arm entries in the elevated plus‐maze only in the more anxious BALB/cAnN@Ico strain. However, both strains injected with ethanol emerged faster than placebo from a small chamber at doses not affecting behaviors in the other two tests. Significant correlations were found between emergence latencies on one hand and either slow stereotyped movements or open and enclosed arm entries on the other. The strain‐specific effects may be attributable to differences in GABAA‐related re... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4400961 Tue, 25 Jan 2011 00:00:00 +0100 4400961 http://www.medworm.com/index.php?rid=4400960&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00922.x AbstractPreclinical studies have demonstrated antinociceptive synergism between dexketoprofen (DEX) and tramadol (TRM) in acute animal models of nociception. The aim of the present study was to investigate the type of interaction between DEX and TRM in a chronic musculoskeletal pain model in mice, which fairly replicates the characteristics of chronic osteoarticular pain in humans. Inflammation was induced by a subplantar injection of complete Freund’s adjuvant (CFA) in male CF1 mice. Nociceptive thresholds were evaluated using the hot plate, the nocifensive spontaneous behavior and the acetone tests, while plasma extravasation (PE) was assessed with Evan’s blue. We used the following experimental groups: control (no inflammation), acute (1 day after CFA injection), and chronic infla... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4400960 Tue, 25 Jan 2011 00:00:00 +0100 4400960 http://www.medworm.com/index.php?rid=4400959&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2011.00924.x This study was carried out to identify the medication prescribing errors (MPEs) pertaining to cardiovascular/antidiabetic medications in prescriptions issued to hypertensive and diabetic hypertensive patients. A retrospective, nationwide audit of prescriptions (n = 2773) issued by primary care physicians (n = 194) of 20 health centres in Bahrain was carried out. Approximately one‐quarter of prescriptions ordered by two‐thirds of primary care physicians had errors. No significant differences with respect to overall errors were evident in prescriptions ordered by the family physicians and general practitioners. The most common error (in 8.0% of prescriptions) was prescribing β‐blockers or diuretics (thiazide) or their combinations to patients on lipid‐lowering drugs. Prescri... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4400959 Tue, 25 Jan 2011 00:00:00 +0100 4400959 http://www.medworm.com/index.php?rid=4362941&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00915.x AbstractTo assess the conditions of prescriptions and tolerance of antiplatelet drugs (APD) in the elderly and to detail the parameters that influence the tolerance of these drugs. Prospective survey in a Department of Geriatric Medicine. Two hundred nineteen patients 70 years and older treated with one or two APD prior to admission were included during 7 months in 2008. We recorded the type of APD, associated diseases, main associated or co‐prescribed drugs which could interact with APD and the bleeding adverse events including cutaneous bleeding. The mean age of the 219 patients was 84.5 ± 6.7 years (70–101 years), women 59.4%. Among patients 64.8% received aspirin (mainly 75 mg), 28.3% received clopidogrel and 6.8% received their combination; 16.9% of prescriptions we... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4362941 Wed, 19 Jan 2011 15:33:16 +0100 4362941 http://www.medworm.com/index.php?rid=4356527&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00920.x AbstractThe electrophysiological (standard intracellular microelectrode technique) and pro‐arrhythmic (occurrence of early after‐depolarization) effects of five class III agents acting on delayed rectifier current (IK), rapid (IKr), and/or slow (IKs) components have been studied in rabbit Purkinje fibers taken near the septum and submitted in vitro to reduced stimulation rate (from 1 to 0.5 Hz) in the absence or presence of epinephrine (10 nm) during normoxic conditions. There were two IKr blockers (d‐sotalol and dofetilide), two IKs blockers (chromanol 293B and HMR 1556), and a non‐selective IK blocker (azimilide). d‐sotalol, dofetilide, and azimilide lengthened APD60 and APD90 in a concentration‐dependent manner. Both d‐sotalol and dofetilide showed pro‐arrhythmia at ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4356527 Mon, 17 Jan 2011 18:35:29 +0100 4356527 http://www.medworm.com/index.php?rid=4339222&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00923.x AbstractMenopause has been reported to be associated with increased oxidative stress and metabolic disorders among women worldwide. Disarrangements in the redox state similar to those observed in women during the decline of ovarian hormonal activity can be obtained experimentally through rat bilateral ovariectomy. The search for alternative treatments to improve life quality in postmenopausal woman is really important. The aim of this study was to evaluate biochemical and oxidative stress parameters that distinguish sham‐operated female rats from Wistar rats bilaterally ovariectomized (OVX). Additionally, we have also investigated the effects of retinol palmitate (a vitamin A supplement) low‐dose supplementation (500 or 1500 IU/kg/day, during 30 days) upon blood and plasma antioxid... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4339222 Thu, 13 Jan 2011 16:00:23 +0100 4339222 http://www.medworm.com/index.php?rid=4332433&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00918.x In conclusion, the potentiation of OA‐induced contraction by indomethacin is more likely due to the increase in lipoxygenase products by the shift of arachidonic acid towards lipoxygenase pathway. Because some of the lipoxygenase products are potent vanilloid agonists, the stimulation of TRPV1 receptors besides leukotriene receptors seems to participate in the potentiation of contraction response in sensitized guinea‐pig tracheas. PAF, adenosine, endothelins, and the neuropeptides present in the afferent neurons do not contribute to the potentiation of OA‐induced contraction by indomethacin. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4332433 Wed, 12 Jan 2011 15:57:12 +0100 4332433 http://www.medworm.com/index.php?rid=4332434&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00908.x The objective of this study was to assess IVIg use in three French university hospitals in 2006. All IVIg administrations were evaluated during 6 months (12 September 2005–12 March 2006) in French university hospitals of Marseille. Different data were recorded for each administration: patient characteristics, indication, formulation and quantity. During the study period, 2802 administrations of IVIg (corresponding to a total quantity of 76 780 g) have been recorded. Four hundred and thirty‐five patients received at least one of these administrations. The five most reported indications were multifocal motor neuropathy (11.0% of total quantity), chronic inflammatory demyelinating polyradiculoneuropathy (10.2%), corticoresistant dermatomyositis (10.2%), immune thrombocytopaenia (9.9... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4332434 Tue, 11 Jan 2011 00:00:00 +0100 4332434 http://www.medworm.com/index.php?rid=4319308&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00906.x AbstractDoctor‐shopping is a patient behaviour characterized by simultaneous consultations of several physicians during the same period. Some case reports have described an abuse of tianeptine, an atypical antidepressant. Our objective was to assess the extent of abuse of this drug with a method quantifying doctor‐shopping in comparison with other antidepressants and benzodiazepines (BZD). All dispensations of antidepressants and BZD during the year 2005 in a French area of 4.5 million inhabitants were extracted from a reimbursement database. For each patient, two quantities were computed: quantity dispensed and obtained by doctor‐shopping. Tianeptine and other drugs were compared using their doctor‐shopping indicator (DSI), defined as the percentage of drug obtained by doctor‐sh... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319308 Fri, 07 Jan 2011 17:34:23 +0100 4319308 http://www.medworm.com/index.php?rid=4319316&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00907.x The objectives of this study are to assess the relevance of the medication error reporting system in a French teaching hospital, to enable the collection of medication error reports and to take corrective actions to reduce occurrence. This is a prospective pilot study based on blame‐free reporting by healthcare professionals. The study setting is five medical/surgical departments in a French teaching hospital over a 6‐month period. The main outcomes of this study are types, frequency, and consequences of medication errors reported. Over a 6‐month period, 47 medication errors were reported. Twenty‐eight (60%) were related to the prescription process, of which 17 were prescribing errors, 10 were because of data capture error and one was because of software malfunction. Ten medication... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319316 Fri, 07 Jan 2011 00:00:00 +0100 4319316 http://www.medworm.com/index.php?rid=4319315&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00911.x In conclusion, estradiol and progesterone have different modulating effects on cardiac repolarization: estradiol can concentration‐dependently prolong the cardiac repolarization time and thus may reduce the repolarization reserve and increase the susceptibility of female rabbits to sotalol‐induced arrhythmias, whereas progesterone may shorten the cardiac repolarization time at concentrations above 10 μm, thus protecting the heart from drug‐induced arrhythmias. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319315 Fri, 07 Jan 2011 00:00:00 +0100 4319315 http://www.medworm.com/index.php?rid=4319314&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00905.x AbstractAn HIV‐infected patient with very low atazanavir (ATV) plasma trough concentrations despite clinical signs of poor drug tolerability was described. By therapeutic drug monitoring (TDM), the authors found that the patient had an atypical ATV pharmacokinetics characterized by rapid drug absorption followed by very fast drug clearance probably attributable to his genetic background. This case underlines the importance of traditional and pharmacogenetic‐based TDM for the individualization of ATV therapy in HIV‐1 patients. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319314 Fri, 07 Jan 2011 00:00:00 +0100 4319314 http://www.medworm.com/index.php?rid=4319313&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00913.x AbstractMacrophages represent major cellular targets of various drugs, especially antibiotics and anti‐viral drugs. Factors that may govern intracellular accumulation of drugs in these cells, especially those related to activity of drug transporters, are consequently likely important to consider. The present study was therefore designed to extensively characterize expression of solute carrier (SLC) and ATP‐binding cassette (ABC) transporters in primary human macrophages generated from blood monocytes. Using quantitative polymerase chain reaction assays, these cells were found to exhibit very high or high levels of mRNA expression of concentrative nucleoside transporter (CNT) 3, equilibrative nucleoside transporter 3, monocarboxylate transporter (MCT) 1, MCT4, peptide/histidine transpor... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319313 Fri, 07 Jan 2011 00:00:00 +0100 4319313 http://www.medworm.com/index.php?rid=4319312&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00916.x AbstractPolycystic ovary syndrome (PCOS) is a persisting challenge to clinical and basic research scientists as none of the presently available medications have been fully able to combat these consequences. The aim of the present review is to summarize the different lines of treatment available for the different symptomologies that women with PCOS presents. In this comprehensive review, search was made for various treatment options available for PCOS by using Cochrane library, Pubmed, Medline, in addition to the relevant printed medical journals and periodicals. The search results revealed that oral contraceptives containing oestrogen and progesterone regularize the menstruation, antiandrogens like spironolactone and drosperinone have proven to be effective in hirsutism and acne, clomiphen... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319312 Fri, 07 Jan 2011 00:00:00 +0100 4319312 http://www.medworm.com/index.php?rid=4319311&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00901.x AbstractThe aim of this study was to assess the effect of ursodeoxycholic acid (UDCA) on the morphological and functional adaptive response of the jejunal remnant after massive intestinal resection in a cat model of short bowel syndrome (SBS). UDCA was administered to animals at a daily oral dose of 15 mg/kg for 6 weeks following a 85% jejunoileal resection. Resection alone caused extensive hyperplasia of jejunal mucosa, as evidenced by a significant increase in the weight of jejunal mucosa per unit length as well as by significant increases in DNA and protein concentration but no change in the protein/DNA ratio. Morphometric analysis using microscopy revealed no changes in jejunal mucosa thickness, jejunal crypt depth, villus height and villus surface area, although villus thickness w... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319311 Fri, 07 Jan 2011 00:00:00 +0100 4319311 http://www.medworm.com/index.php?rid=4319310&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00909.x In this study, we investigated in vivo and in vitro effect of arginine on parameters of oxidative stress namely thiobarbituric acid‐reactive substances (TBA‐RS) and total radical‐trapping antioxidant parameter (TRAP) in plasma and on the antioxidant enzymes activities catalase (CAT), glutathione peroxidase (GSH‐Px), and superoxide dismutase (SOD) in erythrocytes of rats. Results showed that acute administration reduced TRAP and CAT activity and increased TBA‐RS. Furthermore, in vitro studies did not alter oxidative parameters studied. The influence of Nω‐nitro‐l‐arginine methyl ester (l‐NAME) and antioxidants (α‐tocopherol plus ascorbic acid) on the effects elicited by arginine was also studied. In addition, simultaneous injection of l‐NAME or treatment with antioxi... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319310 Fri, 07 Jan 2011 00:00:00 +0100 4319310 http://www.medworm.com/index.php?rid=4319309&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00912.x In this study, we investigated the participation of the BDNF/TrK pathway and oxidative stress during the development of hypertension in spontaneously hypertensive rats (SHR). In SHR and normotensive rats (WKY) at 6 and 13 weeks of age, we studied (i) plasma antioxidant capacity, (ii) production of superoxide and NAD(P)H oxidase activity in aorta (iii) plasma BDNF and vascular expression of BDNF, TrKB, NAD(P)H oxidase subunits, AT1 receptor, and MCP‐1. In 6‐ and 13‐week‐old SHR aorta, superoxide level was twice than in WKY aorta. At 13 weeks, when blood pressure in SHR was 60 mmHg higher in SHR than in WKY, an enhancement of NAD(P)H oxidase activity in SHR was associated with an increase in p47phox, AT1, and BDNF expression in vessels. MCP‐1 expression increased with blood p... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4319309 Fri, 07 Jan 2011 00:00:00 +0100 4319309 http://www.medworm.com/index.php?rid=4273006&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00902.x AbstractHigh‐dose benzodiazepine (BDZs) represents an important risk factor for dependence, particularly in a prison environment. In Lyon’s prison, BDZs and/or opioid maintenance treatment are often prescribed to patients with mental disorders. The aim of this retrospective study was to assess the impact of psychiatrist and pharmacist collaboration on reducing the BDZs dose prescribed to prisoner patients. Since 2001, clinicians and pharmacists have been holding monthly meetings to develop prescribing guidelines and discuss those patients receiving high‐dose BDZs. All prescribed psychotropic drugs were noted for each included patient in the control (before guidelines) and intervention groups. Criteria used to define each patient profile included age, diagnosis (mental disorder), and ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4273006 Wed, 01 Dec 2010 00:00:00 +0100 4273006 http://www.medworm.com/index.php?rid=4260096&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00903.x AbstractThe complexity of modern biomedical research continues to increase. Research‐to‐practice gaps are now widely pervasive; these widening fissures between the disciplines of research and clinical medicine can only be abridged if the translational processes are methodically backed up by robust methods, many of which are yet to be developed. This primarily relates to the development of biomarkers, biostatistical methods, accelerated human study designs including phase 0 trials and smarter decision‐making tools among other features. This brief review highlights the tribulations that have contributed to the lack of technology transfer including lapses in communication between researchers and practitioners, and related factors in service deliverance such as the health care policies, ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4260096 Wed, 01 Dec 2010 00:00:00 +0100 4260096 http://www.medworm.com/index.php?rid=4220933&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00904.x AbstractAn important step in the development of new drugs is to evaluate the extent of their metabolism during absorption in the small intestine. Reliable in vitro systems to do this can expediate the development process, but the current systems are often unsuitable because they lack the appropriate metabolic enzymes (e.g. Caco‐2 cell monolayers) or are not representative of the physiological conditions present in the intact intestinal cells (e.g. isolated microsomes). The aim of this study was to validate the use of isolated intestinal epithelial cells (enterocytes), equivalent to hepatocytes, to evaluate Phase I drug metabolism. A method was developed to prepare enterocytes from rat and pig (as metabolically closer to man) that maintained good viability and activity for up to 90 min ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4220933 Wed, 01 Dec 2010 00:00:00 +0100 4220933 http://www.medworm.com/index.php?rid=4215281&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00896.x In this study, we investigated the role of abamectin in acute lung injury (ALI) induced by Lipopolysaccharide (LPS), and the invovment of MAPK and NF‐κB. BALB/C mice were administered abamectin (PBS) orally, followed by a dose of 0.5 mg/kg of LPS. After 10 h, tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) in bronchoalveolar lavage fluid (BALF) were measured using enzyme‐linked immunosorbent assay. The number of total cells, neutrophils, and macrophages in the BALF were determined. The right lung was then excised for histological examination and analysis of myeloperoxidase (MPO) activity. Phosphorylation of MAPK family and IκB were detected by western blot. We found that 2 mg/kg of abamectin had significant protective effects on ALI. Mice treated with LPS alo... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4215281 Wed, 01 Dec 2010 00:00:00 +0100 4215281 http://www.medworm.com/index.php?rid=4197975&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00900.x In conclusion, eugenol ameliorates GM‐induced nephrotoxicity and oxidative damage by scavenging oxygen free radicals, decreasing lipid peroxidation and improving intracellular antioxidant defense. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4197975 Thu, 25 Nov 2010 04:32:14 +0100 4197975 http://www.medworm.com/index.php?rid=4197978&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00897.x In conclusion, our results suggest that the increase of NO levels in gastric tissue after pretreatment with carbenoxolone activates the NO/cGMP/KATP channels pathway, the principal gastroprotective mechanism of carbenoxolone. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4197978 Wed, 24 Nov 2010 00:00:00 +0100 4197978 http://www.medworm.com/index.php?rid=4197977&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00898.x AbstractMicroparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation or apoptosis. Microparticles from monocytes have been implicated in atherosclerosis and vascular inflammation, but their direct effects on endothelial cells are not completely elucidated. The present study was designed to dissect the signaling pathways of monocytic microparticles in endothelial cells with respect to both NO pathway and reactive oxygen species. Microparticles were produced by treatment of human monocytic cell line THP‐1 with the apoptotic agent VP‐16. Human endothelial cells were treated with monocytic microparticles and then, we studied their effects on nitrosative and oxidative stresses. Incubation of human endothelial cells with microparticles... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4197977 Wed, 24 Nov 2010 00:00:00 +0100 4197977 http://www.medworm.com/index.php?rid=4197976&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00899.x AbstractWe have investigated the modulatory efficacy of naringenin on circulatory lipid peroxidation and anti‐oxidant status, hepatic alcohol metabolizing enzymes in rats with ethanol induced hepatotoxicity. Rats were divided into four groups: groups 1 and 2 received isocaloric glucose and 0.5% carboxymethyl cellulose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg body weight everyday for the total experimental period of 60 days. In addition, groups 2 and 4 were given naringenin (50 mg/kg) everyday for the last 30 days of the experiment. The results showed significantly elevated levels/activities of bilirubin, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4197976 Wed, 24 Nov 2010 00:00:00 +0100 4197976 http://www.medworm.com/index.php?rid=4172810&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00894.x In conclusion, although the antipyretic effect of ibuprofen involves the blockage of central production of PGE2 and the endogenous release of AVP, differently from low dose of indomethacin, ibuprofen not only reduced the fever induced by PGE2‐dependent, but also, that induced by PGE2‐independent endogenous pyrogens. Moreover, ibuprofen does not affect the hypothalamic synthesis/release of IL‐1β and IL‐6. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172810 Wed, 17 Nov 2010 07:27:15 +0100 4172810 http://www.medworm.com/index.php?rid=4172821&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00882.x AbstractRecent observations suggest the existence of clonazepam abuse. To determine its importance in France, a quantitative and systematic synthesis of all clonazepam data of several epidemiological tools of the Centers for Evaluation and Information on Pharmacodependence (CEIP) network has been performed in comparison with data on others benzodiazepines (BZD). Data on clonazepam and other BZD have been analysed from different epidemiological tools: OSIAP survey that identifies drugs obtained by means of falsified prescriptions, Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) survey that describes modalities of use and data from regional French health reimbursement system. In OSIAP survey, the proportion of clonazepam falsified prescriptions among all BZD fal... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172821 Tue, 16 Nov 2010 00:00:00 +0100 4172821 http://www.medworm.com/index.php?rid=4172820&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00883.x The objective of this study was to combine a model of 6‐OHDA‐induced parkinsonism and of L‐DOPA‐induced dyskinesia in rats to establish a reliable preclinical model. Two stereotaxic injections of 6‐OHDA were administered in the left striatum. This model led to 90–100% of rats with a marked contralateral circling behaviour, significant limb use asymmetry (20%), a decrease in ipsilateral striatal dopamine content (70%) and degeneration of dopamine neurons in the substantia nigra (70%). Chronic treatment with L‐DOPA was administered for 35 days and consisted of three phases with incremental daily doses. The third phase resulted in 83–90% of rats developing severe abnormal involuntary movements (AIMs) which included limb and locomotive dyskinesia, axial dystonia and orolingua... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172820 Tue, 16 Nov 2010 00:00:00 +0100 4172820 http://www.medworm.com/index.php?rid=4172819&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00884.x AbstractThe therapeutic index of cyclosporin A (CsA), an immunosuppressive drug, is limited by its nephrotoxic effect. Oxidative stress is suggested to play a crucial role as pathogenic factors. The present study aimed at investigating the effects of caffeic acid phenethyl ester (CAPE), a phenolic antioxidant, on renal function, morphology, and oxidative stress following CsA treatment. Rats were treated with vehicle, CsA (50 mg/kg), and CsA plus CAPE (10 and 30 μmol/kg) for 10 days. Renal function, histopathology, and tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were evaluated 24 h after the last treatment. CsA produced nephrotoxicity as indicated by a significant increase in serum creatinine and blood urea nitrogen, but decrease creatinine and urea clearance ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172819 Tue, 16 Nov 2010 00:00:00 +0100 4172819 http://www.medworm.com/index.php?rid=4172818&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00885.x This study was designed to investigate the expression regulation of LOX‐1 by ox‐LDL and the potential underlying mechanisms in cultured rat vascular smooth muscle cells (VSMCs). VSMCs were treated with ox‐LDL, and the expressions of LOX‐1 mRNA and proteins were determined by RT‐PCR and western blotting, respectively. The intracellular reactive oxygen species (ROS) production was monitored by flow cytometry with fluorescence probe, DCFH2‐DA. The effect of several inhibitors including aspirin, NDGA, allopurinol, apocynin, and rotenone on ox‐LDL‐induced ROS formation and LOX‐1 expression was also investigated. The roles of NF‐κB p65 and JNK were explored. Ox‐LDL significantly induced LOX‐1 expression at both mRNA and protein levels in a dose‐dependent and time‐dep... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172818 Tue, 16 Nov 2010 00:00:00 +0100 4172818 http://www.medworm.com/index.php?rid=4172817&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00886.x In this study, we investigated the effects of florfenicol on nitric oxide (NO) and prostaglandin E2 (PGE2) production as well as on inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) expression in LPS‐stimulated murine RAW 264.7 macrophages. We also analysed the effects of florfenicol on mitogen‐activated protein kinase (MAPK) pathways. Florfenicol significantly inhibited LPS‐induced NO and PGE2 production. Consistent with these observations, mRNA and protein expression of iNOS and COX‐2 were also inhibited by florfenicol in a dose‐dependent manner. Furthermore, phosphorylation of p38 and extracellular signal‐regulated kinase 1/2 (ERK1/2) in LPS‐stimulated RAW 264.7 cells was suppressed by florfenicol. However, c‐Jun N‐terminal kinase (JNK) phosphoryl... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172817 Tue, 16 Nov 2010 00:00:00 +0100 4172817 http://www.medworm.com/index.php?rid=4172816&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00887.x AbstractIndomethacin (IM), a non‐steroidal anti‐inflammatory drug, has the capacity to induce hepatic and renal injuries when administrated systemically. The aim of this study is to assess the IM absorption from complexed forms when orally administered to rats, by means of a comparative evaluation of its capacity to induce hepatic and renal injury in different forms, namely IM acid, IM sodium salt or IM complexed with hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD), using freeze‐ and spray‐drying methods.A total of 135 Wistar rats weighing 224.4 ± 62.5 g were put into 10 groups. They were allowed free access to water but were maintained on fast for 18 h before the first administration until the end of the experiment. Water and HP‐β‐CD (control groups) and IM acid for... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172816 Tue, 16 Nov 2010 00:00:00 +0100 4172816 http://www.medworm.com/index.php?rid=4172815&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00888.x AbstractTo evaluate the effects of 1‐year treatment with orlistat plus l‐carnitine compared to orlistat alone on body weight, glycemic and lipid control, and inflammatory parameters in obese type 2 diabetic patients. Two hundred and fifty‐eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA1c) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take orlistat 120 mg three times a day plus l‐carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated the following parameters at baseline and after 3, 6, 9, and 12 months : body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172815 Tue, 16 Nov 2010 00:00:00 +0100 4172815 http://www.medworm.com/index.php?rid=4172814&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00890.x AbstractAntiplatelet agents play an essential role in the treatment of acute coronary syndrome (ACS). Numerous clinical trials have established the value of antiplatelet therapies for ACS. Aspirin (ASA), thienopyridines and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS. Thienopyridines are a class of drugs that function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet receptors. Currently, clopidogrel, a second generation thienopyridine, is the main drug of choice and the combination of aspirin and clopidogrel is administered orally for the treatment of ACS. Recently, a third generation of thienopyridines has been introduced represented by prasugrel that has demonstrated promising results i... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172814 Tue, 16 Nov 2010 00:00:00 +0100 4172814 http://www.medworm.com/index.php?rid=4172813&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00891.x This study investigated the cardiovascular responses to the essential oil of Aniba canelilla (EOAC) and its main constituent 1‐nitro‐2‐phenylethane (NP) in spontaneously hypertensive rats (SHRs). In anesthetized SHRs, intravenous (i.v.) bolus injections of EOAC (1–20 mg/kg) or NP (1–10 mg/kg) elicited dose‐dependent hypotensive and bradycardiac effects, which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by EOAC and NP both at 10 mg/kg was absent after left ventricle injection, fully abolished by bilateral vagotomy and perineural treatment of both cervical vagus nerves with capsaicin (250 μg/mL) while remained unaltered by i.v. pretreatment with capsazepine (1 mg/kg) or ondansetron (30 μg/kg). In conscious SHRs, NP ... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172813 Tue, 16 Nov 2010 00:00:00 +0100 4172813 http://www.medworm.com/index.php?rid=4172812&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00892.x This study was undertaken to assess the effects of eugenol (EUG) on tracheal muscle (TM) and the putative mechanisms underlying these effects. Cumulatively increasing concentrations (1–1000 μm) of EUG did not affect the resting tonus of TM. However, EUG (1–2000 μm) reduced the contractions induced by electrical field stimulation (IC50 = 842.3 ± 52.7 μm), an effect that was unaltered by either 10 μm montelukast (IC50 = 816.1 ± 70.1 μm) or 2 μm indomethacin (IC50 = 693.1 ± 170.8 μm). EUG also completely relaxed the sustained contractile responses to 80 mM K+ (IC50 = 597.3 ± 60.6 μm) and 1 μm carbamoylcholine (IC50 = 571.3 ± 148.8 μm), an effect that was unaltered by indomethacin (2 μm). Under Ca2+‐free cond... Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172812 Tue, 16 Nov 2010 00:00:00 +0100 4172812 http://www.medworm.com/index.php?rid=4172811&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00893.x In conclusion, combination of silibinin and UDCA by inhibition of NF‐κB and other relevant inflammatory factors of colitis is a good candidate for management of Crohn’s disease. (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4172811 Tue, 16 Nov 2010 00:00:00 +0100 4172811 http://www.medworm.com/index.php?rid=4156166&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00895_2.x (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4156166 Fri, 12 Nov 2010 04:31:35 +0100 4156166 http://www.medworm.com/index.php?rid=4156165&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.0895_1.x (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4156165 Fri, 12 Nov 2010 04:31:34 +0100 4156165 http://www.medworm.com/index.php?rid=4032689&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00879.x Abstract (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4032689 Thu, 30 Sep 2010 23:00:00 +0100 4032689 http://www.medworm.com/index.php?rid=4032688&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00881.x Abstract (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4032688 Thu, 30 Sep 2010 23:00:00 +0100 4032688 http://www.medworm.com/index.php?rid=4014692&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00876.x Abstract (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4014692 Thu, 30 Sep 2010 14:04:38 +0100 4014692 http://www.medworm.com/index.php?rid=3984482&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00875_3.x (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=3984482 Tue, 21 Sep 2010 07:07:38 +0100 3984482 http://www.medworm.com/index.php?rid=3984481&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00875_2.x (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=3984481 Tue, 21 Sep 2010 07:07:37 +0100 3984481 http://www.medworm.com/index.php?rid=3984480&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00875_1.x (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=3984480 Tue, 21 Sep 2010 07:07:36 +0100 3984480 http://www.medworm.com/index.php?rid=4014695&cid=s_32544_13_f&fid=32544&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1472-8206.2010.00877.x Abstract (Source: Fundamental and Clinical Pharmacology) Fundamental and Clinical Pharmacology journals http://www.medworm.com/rss/comments.php?id=4014695 Tue, 31 Aug 2010 23:00:00 +0100 4014695