Pharmacology

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity
Galanin was first identified 30 years ago as a "classic neuropeptide," with actions primarily as a modulator of neurotransmission in the brain and peripheral nervous system. Other structurally-related peptides-galanin-like peptide and alarin-with diverse biologic actions in brain and other tissues have since been identified, although, unlike galanin, their cognate receptors are currently unknow...


Early Clinical Development Planning via Biomarkers, Clinical Endpoints, and Simulation: A Case Study to Optimize for Phase 3 Dose Selection
This study investigated a framework that leverages the relationship between biomarkers and a target clinical endpoint to optimize an early development plan. Different biomarker designs were assessed for proof of concept (PoC) and dose finding (DF) to improve phase 2b (Ph2b) design as well as phase 3 (Ph3) dose choice. A case study using a Bayesian trivariate normal distribution model for 2 biom...
The use of antidepressants and the risk of chronic atrial fibrillation
Serotonin stimulation of the 5HT4 receptor might be responsible for an increased risk of atrial fibrillation (AF). Thus, we assessed whether the use of antidepressants (ADs) is associated with an increased risk of chronic AF (cAF). Using the UK Clinical Practice Research Datalink, a nested case-control analysis was conducted within a cohort of new AD users having a diagnosis of depression and/o...


D-optimal experimental approach for designing topical microemulsion of itraconazole: Characterization and evaluation of antifungal efficacy against a standardized Tinea pedis infection model in Wistar rats
The study aims to statistically develop a microemulsion system of an antifungal agent, itraconazole for overcoming the shortcomings and adverse effects of currently used therapies. Following preformulation studies like solubility determination, component selection and pseudoternary phase diagram construction, a 3-factor D-optimal mixture design was used for optimizing a microemulsion having des...
Selenium as an alternative peptide label – comparison to fluorophore-labelled penetratin
In the present study, the impact on peptide properties of labelling peptides with the fluorophore TAMRA or the selenium (Se) containing amino acid SeMet was evaluated. Three differently labelled variants of the cell-penetrating peptide (CPP) penetratin (Pen) were synthesized, PenMSe, TAMRA-PenMSe and TAMRA-Pen. The labelled peptides were characterized in terms of hydrodynamic radius, secondary ...


Statistical investigation of simulated intestinal fluid composition on the equilibrium solubility of biopharmaceutics classification system class II drugs
A drug’s solubility and dissolution behaviour within the gastrointestinal tract is a key property for successful administration by the oral route and one of the key factors in the biopharmaceutics classification system. This property can be determined by investigating drug solubility in human intestinal fluid (HIF) but this is difficult to obtain and highly variable, which has led to the deve...
The relationship between alcohol taxes and binge drinking: evaluating new tax measures incorporating multiple tax and beverage types
U. S. studies contribute heavily to of the literature about the tax elasticity of demand for alcohol, and most U. S. studies have relied on specific excise (volume-based) taxes for beer as a proxy for alcohol taxes. The purpose of this paper was to compare this conventional alcohol tax measure with more comprehensive tax measures (incorporating multiple tax and beverage types) in analyses of th...

Reaction Phenotyping: Advances in the Experimental Strategies Used to Characterize the Contribution of Drug-Metabolizing Enzymes
During the process of drug discovery, the pharmaceutical industry is faced with numerous challenges. One challenge is the successful prediction of the major routes of human clearance of new medications. For compounds cleared by metabolism, accurate predictions help provide an early risk assessment of their potential to exhibit significant interpatient differences in pharmacokinetics via routes ...
Transporter-Mediated Uptake of UDP-Glucuronic Acid by Human Liver Microsomes: Assay Conditions, Kinetics, and Inhibition
This study characterized the kinetics, variability, and factors that affect UDP–glucuronic acid (UDP-GlcUA) uptake by human liver microsomes (HLM). Biphasic kinetics were observed for UDP-GlcUA uptake by HLM. Uptake affinities (assessed as Kd) of the high- and low-affinity components differed by more than an order of magnitude (13 ± 6 vs. 374 ± 175 µM), but were compar...

Effect of Propofol on the Release of [3H] Acetylcholine from Rat Hippocampal Synaptosomes
Several studies have demonstrated that propofol interferes with acetylcholine (ACh) release in the central nervous system but the mechanism (s) involved remains unclear. The present study aimed to evaluate the mechanism (s) by which this agent interferes with the release of this neurotransmitter from rat hippocampal synaptosomes. Synaptosomes labeled with [3H]ACh were superfused using an appara...
Genetic Diversity Analysis in the Genus Aloe vera (L.) Using RAPD and ISSR Markers
Aloe vera L. (Aloe barbadensis Miller) is an ayurvedic, xerophytic, succulent, medicinal plant commonly known as Aloe vera and it is used worldwide in drug and cosmetic industry. In the present investigation, genetic diversity in 12 elite accessions of Aloe vera, collected from different geographical regions of India, were evaluated using Random Amplified Polymorphic DNA (RAPD) and Inter Simple...

Study of Pharmacokinetic Properties of Cyclosporine A after Subcutaneous Injection in Cynomolgus Monkey
Intramuscular or intravenous injection of Cyclosporine A (CyA) has been performed in some transplantation animal studies, including non-human primates. However, the pharmacokinetics after subcutaneous (s.c.) injection of CyA in cynomolgus monkey has not been reported. In this study CyA was administered subcutaneously in cynomolgus monkeys at three doses and investigated the pharmacokinetics. Si...
Antioxidant and Antimutagenic Potential of Seeds and Pods of Green Cardamom (Elettaria cardamomum)
The present study reports the antioxidant and antimutaganic potential of the aqueous (30 and 70%) and acidified (0.5 and 1 N) methanolic extracts from seeds and pods of green cardamom (Elettaria cardamomum). The Total Phenolic Compounds (TPC) of extracts were determined by Follin-Ciocalteu reagent. Antioxidant activity of the extracts produced was evaluated by the measurements of 2, 2,-diphenyl...
Evaluation of in vitro Efficacy of Vitamin D3 on the Osteogenic Differentiation and Mineralization Capabilities of Fetal and Adult Osteoblasts of Rabbit Reflects Therapeutic Potential
The ability of the osteoblasts to lay the extracellular matrix and mineralize determines the efficiency of bone formation. Vitamin D injections are used to enhance bone mineralization in clinical cases. The present study was designed to evaluate the in vitro efficacy of Vitamin D on the osteoblastic activity in both fetal and adult osteoblasts. The long bone was collected from fetal and adult r...
Berberine Attenuates Isoniazid-Induced Hepatotoxicity by Modulating Peroxisome Proliferator-Activated Receptor γ, Oxidative Stress and Inflammation
The antituberculosis drug-induced hepatotoxicity is a leading cause of liver injury in many countries. The current study aimed to investigate the possible protective effects of the isoquinoline alkaloid berberine against isoniazid (INH)-induced hepatotoxicity in rats. The experimental rats received 100 mg kg-1 b.wt. INH and concurrently administered berberine at doses of 25 and 50 mg kg-1 orall...