Comparative pharmacokinetics study of two different clindamycin capsule formulations: a randomized, two-period, two-sequence, two-way crossover clinical trial in healthy volunteers

The comparative pharmacokinetic (PK) study of two brands of clindamycin hydrochloride (CAS 21462-39-5) was carried out on 32 healthy Indian subjects in an open label randomized, two way crossover, two period, two sequence, two treatment trial with a minimum washout period of 7 days. Plasma samples were collected at 10 min interval for the 1st hour, at 1 h interval for the next 6 h, at 2 h interval for next 12 h and finally at the 24th hour (pre-dose as baseline value) after drug administration. The concentrations of clindamycin in plasma were determined using high performance liquid chromatography (HPLC) technique with UV detector [lower limit of quantitation (LLOQ) 0.05 microg x mL(-1)). All PK parameters were calculated from data on clindamycin content in plasma using a non-compartmental model. Primary PK parameters were maximum plasma concentration (Cmax), area under the curve from zero to t(th) hour (AUCT) and area under the curve from zero to infinite (AUCI), whereas secondary PK parameters were elimination half-life (t half), elimination rate constant (K el) and time to reach maximum plasma concentration (Tmax). All primary PK parameters (log transformed) were subjected to ANOVA analysis and two one-sided Student's t-test (TOST) to construct the 90% confidence intervals. The result of ANOVA showed that all primary PK parameters at 90% confident intervals were within the limit of 80-125%. All the values such as 95.7-109.00% for Cmax, 99.5-117% for AUCT and 99.1% to 114% for AUCI showed pharmacokinetic equivalence and indicated that this comparative pharmacokinetic study was well designed to conclude that the test formulation and reference formulation were pharmacokinetically equivalent and hence bioequivalent with respect to rate and extent of absorption.     

An antibacterial from Hypericum acmosepalum inhibits ATP-dependent MurE ligase from Mycobacterium tuberculosis

In a project to characterise new antibacterial chemotypes from plants, hyperenone A and hypercalin B were isolated from the hexane and chloroform extracts of the aerial parts of Hypericum acmosepalum. The structures of both compounds were characterised by extensive one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and were confirmed by mass spectrometry. Hyperenone A and hypercalin B exhibited antibacterial activity against multidrug-resistant strains of Staphylococcus aureus, with minimum inhibition concentration ranges of 2-128 mg/L and 0.5-128 mg/L, respectively. Hyperenone A also showed growth-inhibitory activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG at 75 mg/L and 100mg/L. Neither hyperenone A nor hypercalin B inhibited the growth of Escherichia coli and both were non-toxic to cultured mammalian macrophage cells. Both compounds were tested for their ability to inhibit the ATP-dependent MurE ligase of M. tuberculosis, a crucial enzyme in the cytoplasmic steps of peptidoglycan biosynthesis. Hyperenone A inhibited MurE selectively, whereas hypercalin B did not have any effect on enzyme activity.     

Percutaneous drainage of peridiverticular abscess followed by primary sigmoidectomy

This case report discusses the treatment of a large peridiverticular abscess by sonography-guided percutaneous catheter placement. Primary sigmoid resection was performed successfully at a later time.     

In vitro efficacies of nitazoxanide and other thiazolides against Neospora caninum tachyzoites reveal antiparasitic activity independent of the nitro group

The thiazolide nitazoxanide [2-acetolyloxy-N-(5-nitro-2-thiazolyl)benzamide] (NTZ) exhibits a broad spectrum of activities against a wide variety of intestinal and tissue-dwelling helminths, protozoa, and enteric bacteria infecting animals and humans. The drug has been postulated to act via reduction of its nitro group by nitroreductases, including pyruvate ferredoxin oxidoreductase. In this study, we investigated the efficacies of nitazoxanide and a number of other thiazolides against Neospora caninum tachyzoites in vitro. We employed real-time-PCR-based monitoring of tachyzoite adhesion, invasion, and intracellular proliferation, as well as electron microscopic visualization of the effects imposed by nitazoxanide. In addition, we investigated several modified versions of this drug. These modifications included on one hand the replacement of the nitro group on the thiazole ring with a bromide, thus removing the most reactive group, and on the other hand the differential positioning of methyl groups on the salicylate ring. We show that the thiazole-associated nitro group is not necessarily required for the action of the drug and that methylation of the salicylate ring can result in complete abrogation of the antiparasitic activity, depending on the positioning of the methyl group. These findings indicate that other mechanisms besides the proposed mode of action involving the pyruvate ferredoxin oxidoreductase enzyme could be responsible for the wide spectrum of antiparasitic activity of NTZ and that modifications in the benzene ring could be important in these alternative mechanisms.     

Status of adolescent girls in a rural south Indian population

The objectives were to assess the nutritional status of rural adolescent girls, to measure their knowledge about maternal and child nutritional needs, to measure their dietary intake, and to determine the sociocultural aspects of these girls. 47 adolescent girls aged 13-18 years attending a workshop on health and development organized by the Center of Maternal and Child Health, Vellore, India, participated. Their height and weight were measured; their hemoglobin concentration was determined; and other relevant data were collected about diet, knowledge, and nutrition by means of interviews and group discussions. 55% were agricultural laborers, while the remaining 45% worked occasionally. 14% had primary, 12% had secondary, and 10.2% had high school level education. In addition to attending school, 16.3% worked on the farm and 12% picked flowers. The mean height of all the age groups was below the expected standard for the age group. The growth of 34.7% of the subjects was very poor. The difference in height was much more significant in the younger age group (13-15 years) than in the older age group (16-18 years). Although all the subjects were normal for weight for height, only 51.2% had normal weight for their age group. The overall mean hemoglobin value was 10.0 g/dl. 73.5% of the subjects had a hemoglobin value below 12 g/dl (WHO standard) and could be classified as anemic. The mean hemoglobin level increased with increasing age, the lowest being at the age of 13 (9.8 g/dl) and the highest at the age of 17 years (11.9 g/dl). The mean age of menarche was 14.3 years. The diet was predominantly rice. Consumption of vegetables, milk, and meat was very low, which might have been responsible for the high prevalence of anemia in the girls. 91% of them were not aware that anemia could result from menstrual blood loss. 75% of them were aware of nutritional blindness and 48% of protein energy malnutrition. The girls reported sex discrimination in school and in the family.     

Bioengineered humanized livers as better three-dimensional drug testing model system

AIM To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses.RESULTS The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available ex-vivo and in vivo models for identifying cellular and molecular dynamics of pharmacological drugs.CONCLUSION The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.