Physicochemical Characterization of Efavirenz–Cyclodextrin Inclusion Complexes

Efavirenz (EFV) is an oral antihuman immunodeficiency virus type 1 drug with extremely poor aqueous solubility. Thus, its gastrointestinal absorption is limited by the dissolution rate of the drug. The objective of this study was to characterize the inclusion complexes of EFV with β-cyclodextrin (β-CD), hydroxypropyl β-CD (HPβCD), and randomly methylated β-CD (RMβCD) to improve the solubility and dissolution of EFV. The inclusion complexation of EFV with cyclodextrins in the liquid state was characterized by phase solubility studies. The solid-state characterization of various EFV and CD systems was performed by X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy analyses. Dissolution studies were carried out in distilled water using US Pharmacopeia dissolution rate testing equipment. Phase solubility studies provided an A_L-type solubility diagram for β-CD and A_P-type solubility diagram for HPβCD and RMβCD. The phase solubility data enabled calculating stability constants (K _s) for EFV-βCD, EFV-HPβCD, and EFV-RMβCD systems which were 288, 469, and 1,073 M⁻¹, respectively. The physical and kneaded mixtures of EFV with CDs generally provided higher dissolution of EFV as expected. The dissolution of EFV was substantially higher with HPβCD and RMβCD inclusion complexes prepared by the freeze drying method. Thus, complexation with HPβCD and RMβCD could possibly improve the dissolution rate-limited absorption of EFV.     

Acyl-chlorodeoxy-glycerophosphorylcholines,Part II: Total synthesis of “cyclic lysolecithin”

Reaction of 1-fattyacyl-sn-glycero-3-phosphorylcholine with triphenylphosphine — carbon tetrachloride gave 3-fattyacyl-2-chloro-2-deoxy-sn-glycero-1-phosphorylcholine together with small amounts of other chlorodeoxy isomers. 1-Chloro-1-deoxy-2-palmitoyl-rac-glycero-3-phosphorylcholine was prepared by total synthesis from 3-chloro-2-iodopropyl palmitate. The main step in the synthesis involves the nucleophilic displacement of iodide at C-2 with dibenzyl phosphate anion, which proceeds with an acyloxy migration, leading to the key intermediate 1-chloro-1-deoxy-2-palmitoyl-rac-glycero-3-(dibenzyl phosphate). Hydrogenolysis of this phosphate triester, followed by esterification with choline acetate gave the final product. The properties of the products support an earlier conclusion that the so-called “cyclic lysolecithin” is a mixture of isomeric acyl-chloro-deoxy-glycero-phosphorylcholines in which 1-chloro-1-deoxy-2-acyl-glycero-3-phosphorylcholine is the major component.     

Molecular and functional characterization of endophytic fungi from traditional medicinal plants

This study reports the isolation of 63 endophytic fungal isolates from two traditional medicinal plants, Ocimum sanctum and Sapindus detergens from different locations of Amritsar, India. The functional characterization of the fungi for their ability to produce anti bacterial and anti cancer agent was carried out. Sixteen strains were characterized at molecular level by sequencing the amplified ITSI-5.8-ITSII region of rDNA. The phylogenetic tree resolved the endophytic fungi into different clades. The fungal endophytes belonging to order Pleosporales (Alternaria sp., Phoma sojicola and Exserohilum sp.) were functionally versatile as they produced diverse biomolecules including antibacterial agent active against Mycobacterium smegmatis, as well as cytotoxic activity against different human cancer cell lines of lung, ovary, breast, prostrate, neuroblastoma and colon.     

Effect of Incorporation of Mahua Extract, Fining Agent and Ageing on the Quality Characteristics of Red Wine

Mahua (Madhuca longfolia) extract and black grapes (Vitis vinifera) must samples 100:0 (grape:mahua), 95:5 (grape:mahua) and 90:10 (grape:mahua) were analyzed for quality characteristics. Samples were kept for fermentation and monitored for quality analysis for 15 days. 90:10 (grape:mahua) sample was found to be best on the basis of ranking test and subjected to clarification using bentonite and gelatine. Sample treated with a combination of 0.02 g/100 g bentonite and 0.04 g/100 g gelatin showed better results for anthocyanin (52.2 mg/100 g) and tannin (0.038%w/v). After ageing of 3 months TSS was found highest (2.7ºBx) in the non-clarified sample and lowest (2.1ºBx) in sample treated with 0.06 g/100 g bentonite and 0.03 g/100 g gelatine. pH was highest (3.29) in sample treated with 0.06 g/100 g bentonite and 0.03 g/100 g gelatine and lowest (3.16) in sample with 0.04 g/100 g bentonite and 0.03 g/100 g gelatine. Anthocyanin content was highest (56.1 mg/100 g) in control sample and lowest (29.22 mg/100 g) in sample treated with 0.04 g/100 g bentonite and 0.02 g/100 g gelatin. Tannin content was found to be highest (0.079%w/v) in control sample and lowest (0.03%w/v) in sample treated with 0.02 g/100 g bentonite and 0.04 g/100 g gelatine.     

Porous silicon based potentiometric triglyceride biosensor

A novel method for estimating triglycerides is reported. Porous silicon, prepared from p-type (100) crystalline silicon was thermally oxidized and used to immobilise lipase, an enzyme, which hydrolyses triglycerides resulting in the formation of fatty acids. This causes a change in the pH of the solution. Enzyme solution-oxidized porous silicon-crystalline silicon structure was used to detect changes in pH during the hydrolysis of tributyrin as a shift in the capacitance-voltage (C-V) characteristics. Detailed calibration of the sensor is included.     

Trend in Annual Risk of Tuberculous Infection in North India

Setting

Six selected districts in Northern India.

Objectives

To find out the trend in Annual risk of tuberculous infection (ARTI) in north India.

Study Design

Two rounds of community level surveys were conducted during 2000–2001 and 2009–10 respectively. Representative samples of children 1–9 years of age were tuberculin tested and maximum transverse diameter of induration was recorded in mm at about 72 hours. ARTI was computed from the estimated Prevalence of infection using mirror-image technique and anti-mode method.

Results

ARTI was found to decline from 1.9% (confidence interval: 1.7–2.1) at round I to 1.1% (confidence interval: 0.8–1.3) at round II at the rate of 8% per year during the intervening period.

Conclusion

A significant reduction in the risk of tuberculous infection among children was observed between two rounds of surveys carried out at an interval of about 9 years.     

Thiophilic interaction chromatography of prostate-specific antigen

Prostate-specific antigen (PSA) protein and complexes of PSA with α₁-antichymotrypsin (PSA-ACT) or α₂-macroglobulin (PSA-A₂M) prepared in vitro, have strong affinity for different thiophilic gels (T-gel). Free PSA, and these PSA complexes can be isolated due to their affinity for T-gels. The average recovery of PSA from several of the T-gels, based upon ELISA measurements, was 84 to 94%. The data suggest that T-gel affinity can be explored for the purification of free and complexed PSA from various biologic fluids.     

How Do Patients Who Fail First-Line TB Treatment but Who Are Not Placed on an MDR-TB Regimen Fare in South India?

Setting

Seven districts in Andhra Pradesh, South India

Objectives

To a) determine treatment outcomes of patients who fail first line anti-TB treatment and are not placed on an multi-drug resistant TB (MDR-TB) regimen, and b) relate the treatment outcomes to culture and drug susceptibility patterns (C&DST).

Design

Retrospective cohort study using routine programme data and Mycobacterium TB Culture C&DST between July 2008 and December 2009.

Results

There were 202 individuals given a re-treatment regimen and included in the study. Overall treatment outcomes were: 68 (34%) with treatment success, 84 (42%) failed, 36 (18%) died, 13 (6.5%) defaulted and 1 transferred out. Treatment success for category I and II failures was low at 37%. In those with positive cultures, 81 had pan-sensitive strains with 31 (38%) showing treatment success, while 61 had drug-resistance strains with 9 (15%) showing treatment success. In 58 patients with negative cultures, 28 (48%) showed treatment success.

Conclusion

Treatment outcomes of patients who fail a first-line anti-TB treatment and who are not placed on an MDR-TB regimen are unacceptably poor. The worst outcomes are seen among category II failures and those with negative cultures or drug-resistance. There are important programmatic implications which need to be addressed.