Pivotal Bioequivalence Study of Clopacin®, a Generic Formulation of Clopidogrel 75 mg Film-Coated Tablets.

Introduction: Clopacin(®) (Acino Pharma AG) is a proprietary, besylate salt and lactose-free formulation of the widely-used anti-platelet treatment, clopidogrel. This study aimed to evaluate the bioequivalence of Clopacin(®) with the originator as reference drug, using a guideline-compliant trial design: open-labeled, randomized, single-dose (clopidogrel 75 mg tablet), two-period, crossover trial in 48 healthy male volunteers, with a 7 day wash-out period.

Methods: Plasma samples were collected at intervals and extracted before quantifying clopidogrel concentrations using a fully validated LC-MS/MS method.

Molecular targets of the antiinflammatory Harpagophytum procumbens (devil's claw): inhibition of TNFα and COX-2 gene expression by preventing activation of AP-1.

Harpagophytum procumbens (Hp) is often used in the supportive treatment of inflammatory and degenerative diseases of the skeletal system. Although the clinical efficacy in osteoarthritis has been demonstrated in clinical trials, the molecular target(s) of Hp are unclear. This study quantified the effects of the ethanol Hp extract (60% v/v ethanol, sole active ingredient of Pascoe®-Agil), on the expression and release of the major pro-inflammatory mediators in LPS-stimulated human monocytes and the intracellular signalling pathways involved in inflammation.

Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities.

The effect of a standardised dry extract from Silybum marianum (HEPAR-PASC®) on the enzyme kinetics of cytochrome-P450 isoenzymes (CYP) was investigated with primary human hepatocytes and human liver microsomes in order to assess the potential for drug-drug interactions. A cytotoxic effect on hepatocytes was observed at concentrations at and above 50 μg/ml. The EC(50) value was calculated to be 72.

Anxiolytic activity of a phytochemically characterized Passiflora incarnata extract is mediated via the GABAergic system.

The purpose of this research was to assess the anxiolytic properties of a phytochemically characterized commercial extract from Passiflora incarnata (PI; Passifloraceae) in the elevated plus maze test in mice. Using an HPLC method, the flavonoids homoorientin, orientin, vitexin, and isovitexin were identified as major compounds. Following oral administration, the extract exerted an anxiolytic effect that was comparable to diazepam (1.

Antioxidant therapy in critical care--is the microcirculation the primary target?

This review presents the rationale for the therapeutic use of antioxidants in treating critically ill patients; it is not a systematic review of the clinical evidence that has been assessed recently by others. Clinical and nonclinical evidence is presented to support the notion that natural antioxidants are of therapeutic value in treating cardiovascular shock. Oxidative stress is a major promoter and mediator of the systemic inflammatory response.

Rationale and impact of vitamin C in clinical nutrition.

Purpose Of Review: The impact of vitamin C on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. Parenteral administration can increase the benefit of vitamin C supplementation as is evident in critically ill patients. The aim here is to assess recent evidence of the clinical benefit and underlying effects of parenteral vitamin C in conditions of oxidative stress.

Functional screening of traditional antidepressants with primary cortical neuronal networks grown on multielectrode neurochips.

We optimized the novel technique of multielectrode neurochip recordings for the rapid and efficient screening of neuroactivity. Changes in the spontaneous activity of cultured networks of primary cortical neurons were quantified to evaluate the action of drugs on the firing dynamics of complex network activity. The multiparametric assessment of electrical activity changes caused by psychoactive herbal extracts from Hypericum, Passiflora and Valeriana, and various combinations thereof revealed a receptor-specific and concentration-dependent inhibition of the firing patterns.

Gastric perception thresholds are low and sensory neuropeptide levels high in helicobacter pylori-positive functional dyspepsia.

Background And Aims: In functional dyspepsia (FD) decreased perception levels can be shown on gastric distension. Substance P (SP) and calcitonin gene-related peptide (CGRP) are involved in the sensitization of afferent neuronal pathways due to chronic inflammation. The role of Helicobacter pylori-induced gastric mucosal inflammation in the pathogenesis of FD is controversial.

Brain-derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a model of allergic airway inflammation.

Brain-derived neurotrophic factor (BDNF) is a candidate molecule for mediating functional neuronal changes in allergic bronchial asthma. Recently, enhanced production of BDNF during allergic airway inflammation caused by infiltrating T-cells and macrophages as well as by resident airway epithelial cells has been described. It was the aim of this study to investigate the effect of enhanced BDNF levels on lung function and airway inflammation in a mouse model of allergic inflammation.

Immunohistochemical detection of the calcitonin receptor-like receptor protein in the microvasculature of rat endothelium.

Calcitonin-gene-related peptide and adrenomedullin have similar and potent vascular effects, which appear to be mediated by the G protein-coupled calcitonin receptor-like (CRL) receptor. Using immunohistochemical and Western blot analyses, we have obtained novel evidence that CRL receptor is expressed in the rat vascular endothelium using an antibody to rat CRL receptor that we have raised and fully characterised. These results are an important basis for further studies aimed at determining the so far ill-defined functional significance of the extensive distribution of CRL receptor in the vascular endothelium.

Virokinin, a bioactive peptide of the tachykinin family, is released from the fusion protein of bovine respiratory syncytial virus.

Tachykinins, an evolutionary conserved family of peptide hormones in both invertebrates and vertebrates, are produced by neuronal cells as inactive preprotachykinins that are post-translationally processed into different neuropeptides such as substance P, neurokinin A, and neurokinin B. We show here that furin-mediated cleavage of the bovine respiratory syncytial virus fusion protein results in the release of a peptide that is converted into a biologically active tachykinin (virokinin) by additional post-translational modifications. An antibody directed to substance P cross-reacted with the C terminus of mature virokinin that contains a classical tachykinin motif.

Expression and distribution of the calcitonin receptor-like receptor in the developing rat heart.

During ontogenesis the 52 amino acid peptide adrenomedullin is first expressed in the heart and it is essential for normal cardiovascular development. Recent work suggests that most adrenomedullin effects are conveyed via the calcitonin receptor-like receptor (CRLR) in combination with appropriate receptor activity-modifying proteins (RAMPs). Here, we investigated the expression of these components during the development of the rat heart, focusing on the period of coronary vascular development.

Alternative splicing in single cells dissected from complex tissues: separate expression of prepro-tachykinin A mRNA splice variants in sensory neurones.

Tachykinins play an important role in peripheral inflammatory diseases and disorders of the CNS. Most members of the tachykinin family are generated by alternative post-transcriptional splicing of the prepro-tachykinin (PPT) A gene. Here, we examined the simultaneous expression of PPT-A splice variants in individual neurones of the nodose ganglion.

Calcitonin receptor-like receptor is expressed on gastrointestinal immune cells.

Background/aims: Pharmacological and morphological studies suggest that the gut mucosal immune system and local neuropeptide-containing neurones interact. We aimed to determine whether gut immune cells are targets for calcitonin gene-related peptide (CGRP), which has potent immune regulatory properties.

Methods: Using density gradient centrifugation, rat lamina propria mononuclear cells (LP-MNCs) and intra-epithelial lymphocytes (IELs) were isolated.

Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues.

We report here on the characterization and immunohistochemical localization in human tissues of calcitonin receptor-like receptor (CRLR) which was recently found to mediate the effects of both calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM). Western blot analysis using antibodies raised against the first extracellular loop and the carboxy-terminal part of hCRLR, respectively, detected two major bands corresponding to about 70 and 60 kDa in membrane preparations of cultured endothelial cells and numerous organs including lung, heart ventricle and kidney. Immunohistochemical analysis of the cardiovascular system revealed CRLR-like immunoreactivity (CRLR-LI) in the endothelium of all blood vessels including large and small arteries, veins and capillaries, and in heart muscle cells and endocardium.

Leptin receptor expression in nodose ganglion cells projecting to the rat gastric fundus.

Recent studies suggest that in addition to adipocytes the chief cells of the gastric fundic mucosa are a site of leptin production. In order to assess the possible role of vagal afferent neurons in transmitting leptin signals from the stomach to the brain, leptin receptor (OB-R) expression was investigated in rat nodose ganglion cells and their projection to the stomach determined by retrograde tracing. Reverse transcription-polymerase chain reaction combined with laser-assisted cell picking revealed that large and small diameter neurons express both the long (OB-Rb) and short (OB-Ra) splice variants of the OB-R.