Behavioural studies on the ethanol leaf extract of Grewia carpinifolia in Wistar rats.

Background: Grewia carpinifolia is a plant commonly used in the tropics to manage various central nervous system (CNS) disorders. However, despite its widespread use no scientific work has been reported to validate these claims. Objectives: To evaluate the activity of G. carpinifolia as it affects behaviour using animal model. Methods: Twenty five adult Wistar rats were randomly divided into five groups (A-E). Group A served as control (given only distilled water), Groups B,C, D and E were administered with single oral dose of ethanol extract of G. carpinifolia leaf at 100, 200, 400 and 800 mg/kg body weight respectively for twenty eight days consecutively. Subsequently, open field test, negative geotaxis and hanging wire test were performed. Body and brain weights were measured and histological examination of the brain was also performed. Results: At the tested doses, the extract significantly increased the time spent on the hanging wire and decreased locomotor activity at 800 mg/kg. No significant difference was observed in body and brain weights of extract treated groups when compared with the control. No visible histological lesion was also observed. Conclusion: The plant extract may improve muscular strength at tested doses and possess CNS depressant activity at 800 mg/ kg.

Effects of Ageratum Conyzoides on Semen Characteristics and Sperm Morphology in Rats Exposed to Sodium Arsenite

Arsenite is a major environmental toxicant that is well known to cause reproductive injury. The sperm protective potential of Ageratum conyzoides Linn in arsenic-treated rats was carried out in this study taking advantage of the antioxidant constituents and its androgenic activities. Twenty-four male albino rats aged 16 weeks, weighing 225 to 228g were used. They were grouped into 4(A-Da) with each group containing 6 rats. Group A was orally treated with 100mg/kg ethanol leaf extract of Ageratum conyzoides L., daily for 14 days, group B (single oral dose of sodium arsenite 2.5 mg/kg body weight), C (Ageratum conyzoides extract daily for 14 days and sodium arsenite (SA) given on the 14th day) and group D (Propylene glycol as negative control). It was observed that group B had a more lower (p<0.05) percentage motility (26.7±6.67%) when compared across the groups while group A had a significantly higher (p<0.05) mean value (63.3±3.33%). The sperm motility of rats in group D was significantly higher (p<0.05) than groups B and C. This implies that A. conyzoides extract had no adverse effect on the sperm motility of the rats and also ameliorates the adverse effect of arsenite on sperm motility. The mean value obtained for sperm liveability, semen volume and Sperm concentration followed a similar pattern although, the differences were not significant (p>0.05) for semen volume and the Sperm concentration of rats across the groups. The total sperm abnormality obtained across the groups ranges between 10.44 and 14.27% with group B treated with sodium arsenite (SA) having the highest value when compared with groups A and D, although, the differences were not significant (P>0.05). The study concluded that ethanol leaf extract of Ageratum conyzoides has no negative effect on sperm motility, liveability characteristics and morphology and also protected spermatozoa against arsenic reproductive toxicity in wistar strain albino rats..

A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis

Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB) control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR) and extensively drug-resistant TB based on single nucleotide polymorphism (SNP) mutations present in the rpoB, katG, inhA, ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 for rpoB, katG, inhA, ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours.

Bioequivalence evaluation of new microparticulate capsule and marketed tablet dosage forms of lornoxicam in healthy volunteers

Purpose: To compare oral bioavailability and pharmacokinetic parameters of different lornoxicam formulations and to assess similarity in plasma level profiles by statistical techniques. Methods: An open-label, two-period crossover trial was followed in 24 healthy Pakistani volunteers (22 males, 2 females). Each participant received a single dose of lornoxicam controlled release (CR) microparticles and two doses (morning and evening) of conventional lornoxicam immediate release (IR) tablet formulation. The microparticles were prepared by spray drying method. The formulations were administered again in an alternate manner after a washout period of one week. Pharmacokinetic parameters were determined by Kinetica 4.0 software using plasma concentration-time data. Moreover, data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann’s two one-sided t-test procedure. Results: Peak plasma concentration (Cmax) was 20.2 % lower for CR formulation compared to IR formulation (270.90 ng/ml vs 339.44 ng/ml, respectively) while time taken to attain Cmax (tmax) was 5.25 and 2.08 h, respectively. Area under the plasma drug level versus time (AUC) curve was comparable for both CR and IR formulations. The 90 % confidence interval (CI) values computed for Cmax, AUC0-24, and AUC0-∞ , after log transformation, were 87.21, 108.51 and 102.74 %, respectively, and were within predefined bioequivalence range (80 - 125 %). Conclusion: The findings suggest that CR formulation of lornoxicam did not change the overall pharmacokinetic properties of lornoxicam in terms of extent and rate of lornoxicam absorption.

Bioadhesive drug delivery system of diltiazem hydrochloride for improved bioavailability in cardiac therapy

Purpose: To prepare and evaluate bioadhesive buccal films of diltiazem hydrochloride (a L-type calcium channel blocker) for overcoming the limitations of frequent dosing, low bioavailability and gastrointestinal discomfort of oral delivery. Methods: Buccal films were prepared by solvent casting technique using sodium carboxymethylcellulose, polyvinyl pyrrolidone K-30 and polyvinyl alcohol. The films were evaluated for weight, thickness, surface pH, swelling index, in vitro residence time, folding endurance, in vitro release, ex-vivo permeation (across porcine buccal mucosa) and drug content uniformity. Results: The drug content of the formulations was uniform with a range of 18.94 ± 0.066 (F2) to 20.08 ± 0.07 mg per unit film (F1). The films exhibited controlled release ranging from 58.76 ± 1.62 to 91.45 ± 1.02 % over a period > 6 h. The films containing 20 mg diltiazem hydrochloride, polyvinyl alcohol (10 %) and polyvinyl pyrrolidone (1 % w/v) i.e. formulation F5, showed moderate swelling, convenient residence time and promising drug release, and thus can be selected for further development of a buccal film for potential therapeutic uses. Conclusion: The developed formulation is a potential bioadhesive buccal system for delivering diltiazem directly to systemic circulation, circumventing first-pass metabolism, avoiding gastric discomfort and improving bioavailability at a minimal dose.