Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India

Background

Excessive time between diagnosis and initiation of tuberculosis (TB) treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP) focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation.

Objectives

To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB.

Methods

Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire.

Results

2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35%) patients had >7 days between diagnosis and treatment and 262(13%) had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0–128 days). Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5–2.3) and 1.6 (95% CI 1.3–1.8) times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment delays.     

Optimization of a new heteropolysaccharide production by a native isolate of Leuconostoc sp. CFR-2181

Aim:  This work is aimed at optimizing the production of a new heteropolysaccharide (HePS) of Leuconostoc sp. CFR-2181 by standardizing the fermentation conditions in a low cost semi-synthetic medium.
Methods and Results:  Both nutritional and cultural parameters, such as carbon source and its concentration, initial pH of the exopolysaccharide (EPS) medium, fermentation temperature and fermentation period were optimized. Fermentation of the EPS medium (pH 6·7), containing sucrose at 5% (w/v) and 5% (v/v) inoculum, at 25 ° C resulted in maximum production of HePS (18·38 g l⁻¹) by the isolate in 4 h of fermentation.
Conclusions:  The isolate was found to produce good amount of HePS in just 4 h in a low cost semi-synthetic EPS medium.
Significance and Impact of the Study:  This is the first report on rapid production of HePS by any lactic culture, which can significantly reduce the cost of the EPS.     

Effect of UV irradiation on aflatoxin reduction: a cytotoxicity evaluation study using human hepatoma cell line

In this proof-of-concept study, the efficacy of a medium-pressure UV (MPUV) lamp source to reduce the concentrations of aflatoxin B₁, aflatoxin B₂, and aflatoxin G₁ (AFB_1, AFB₂, and AFG₁) in pure water is investigated. Irradiation experiments were conducted using a collimated beam system operating between 200 to 360 nm. The optical absorbance of the solution and the irradiance of the lamp are considered in calculating the average fluence rate. Based on these factors, the UV dose was quantified as a product of average fluence rate and treatment time. Known concentrations of aflatoxins were spiked in water and irradiated at UV doses ranging from 0, 1.22, 2.44, 3.66, and 4.88 J cm^?2. The concentration of aflatoxins was determined by HPLC with fluorescence detection. LC-MS/MS product ion scans were used to identify and semi-quantify degraded products of AFB₁, AFB₂, and AFG₁. It was observed that UV irradiation significantly reduced aflatoxins in pure water (p < 0.05). Irradiation doses of 4.88 J cm^?2 reduced concentrations 67.22% for AFG₁, 29.77% for AFB₂, and 98.25% for AFB₁ (p < 0.05). Using this technique, an overall reduction of total aflatoxin content of ≈95% (p < 0.05) was achieved. We hypothesize that the formation of ˙OH radicals initiated by UV light may have caused photolysis of AFB₁, AFB₂, and AFG₁ molecules. In cell culture studies, our results demonstrated that the increase of UV dosage decreased the aflatoxin-induced cytotoxicity in HepG₂ cells. Therefore, our research finding suggests that UV irradiation can be used as an effective technique for the reduction of aflatoxins.     

Synthesis and antimicrobial studies of novel 1-benzhydryl-piperazine sulfonamide and carboxamide derivatives

A series of novel substituted 1-benzhydryl-piperazine sulfonamide 8(a-f) and benzamides 9(a-h) were synthesized and their antimicrobial activities evaluated in vitro by paper disc diffusion and micro dilution method against standard strains of Gram-positive (Staphylococcus aureus ATCC 25953, Staphylococcus epidermis 25212, Bacillus cereus 11778, Bacillus substilis 6051) and Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 2853, Proteus vulgaris ATCC 2853 and Salmonella typhi ATCC 9484) bacteria. Among the synthesized new compounds 8d, 8e, 9c, 9e, 9f and 9 h showed potent antimicrobial activities compared to the standard drug streptomycin.     

Glipizide matrix transdermal systems for diabetes mellitus: preparation, in vitro and preclinical studies

The aim of the present investigation was to prepare glipizide matrix transdermal systems using the combinations of ethyl cellulose/polyvinylpyrrolidone and Eudragit RL-100/Eudragit RS-100. The systems were evaluated for various in vitro (drug content, drug permeation, scanning electron microscopy and drug-polymer interactions) and in vivo (acute and long-term hypoglycemic activity, biochemical and histopathological studies, skin irritation and pharmacokinetic studies in mice) parameters. Drug content of the patches was found to be more than 98%. Variations in drug permeation profiles were observed among various formulations. The scanning electron microscopy of the patches showed the formation of pores on the surface after in vitro permeation studies. The drug-polymer interaction results suggested no interaction between drug and polymers. The in vivo results revealed that the patches successfully prevented the severe hypoglycemia in the initial hours and they were also effective on chronic application. The transdermal route exhibited negligible skin irritation and produced better improvement with all the tested in vivo parameters compared to oral administration.     

Insect Barcode Information System

Insect Barcode Information System called as Insect Barcode Informática (IBIn) is an online database resource developed by the National Bureau of Agriculturally Important Insects, Bangalore. This database provides acquisition, storage, analysis and publication of DNA barcode records of agriculturally important insects, for researchers specifically in India and other countries. It bridges a gap in bioinformatics by integrating molecular, morphological and distribution details of agriculturally important insects. IBIn was developed using PHP/My SQL by using relational database management concept. This database is based on the client– server architecture, where many clients can access data simultaneously. IBIn is freely available on-line and is user-friendly. IBIn allows the registered users to input new information, search and view information related to DNA barcode of agriculturally important insects.This paper provides a current status of insect barcode in India and brief introduction about the database IBIn.

Availability

http://www.nabg-nbaii.res.in/barcode     

Protective Effects of Triphala on Dermal Fibroblasts and Human Keratinocytes

Human skin is body’s vital organ constantly exposed to abiotic oxidative stress. This can have deleterious effects on skin such as darkening, skin damage, and aging. Plant-derived products having skin-protective effects are well-known traditionally. Triphala, a formulation of three fruit products, is one of the most important rasayana drugs used in Ayurveda. Several skin care products based on Triphala are available that claim its protective effects on facial skin. However, the skin protective effects of Triphala extract (TE) and its mechanistic action on skin cells have not been elucidated in vitro. Gallic acid, ellagic acid, and chebulinic acid were deduced by LC-MS as the major constituents of TE. The identified key compounds were docked with skin-related proteins to predict their binding affinity. The IC₅₀ values for TE on human dermal fibroblasts (HDF) and human keratinocytes (HaCaT) were 204.90 ± 7.6 and 239.13 ± 4.3 μg/mL respectively. The antioxidant capacity of TE was 481.33 ± 1.5 mM Trolox equivalents in HaCaT cells. Triphala extract inhibited hydrogen peroxide (H₂O₂) induced RBC haemolysis (IC₅₀ 64.95 μg/mL), nitric oxide production by 48.62 ± 2.2%, and showed high reducing power activity. TE also rescued HDF from H₂O₂-induced damage; inhibited H₂O₂ induced cellular senescence and protected HDF from DNA damage. TE increased collagen-I, involucrin and filaggrin synthesis by 70.72 ± 2.3%, 67.61 ± 2.1% and 51.91 ± 3.5% in HDF or HaCaT cells respectively. TE also exhibited anti-tyrosinase and melanin inhibition properties in a dose-dependent manner. TE increased the mRNA expression of collagen-I, elastin, superoxide dismutase (SOD-2), aquaporin-3 (AQP-3), filaggrin, involucrin, transglutaminase in HDF or HaCaT cells, and decreased the mRNA levels of tyrosinase in B16F10 cells. Thus, Triphala exhibits protective benefits on skin cells in vitro and can be used as a potential ingredient in skin care formulations.     

Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism

Evidence suggests that chromium supplementation may alleviate symptoms associated with diabetes, such as high blood glucose and lipid abnormalities, yet a molecular mechanism remains unclear. Here, we report that trivalent chromium in the chloride (CrCl3) or picolinate (CrPic) salt forms mobilize the glucose transporter, GLUT4, to the plasma membrane in 3T3-L1 adipocytes. Concomitant with an increase in GLUT4 at the plasma membrane, insulin-stimulated glucose transport was enhanced by chromium treatment. In contrast, the chromium-mobilized pool of transporters was not active in the absence of insulin. Microscopic analysis of an exofacially Myc-tagged enhanced green fluorescent protein-GLUT4 construct revealed that the chromium-induced accumulation of GLUT4-containing vesicles occurred adjacent to the inner cell surface membrane. With insulin these transporters physically incorporated into the plasma membrane. Regulation of GLUT4 translocation by chromium did not involve known insulin signaling proteins such as the insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, and Akt. Consistent with a reported effect of chromium on increasing membrane fluidity, we found that chromium treatment decreased plasma membrane cholesterol. Interestingly, cholesterol add-back to the plasma membrane prevented the beneficial effect of chromium on both GLUT4 mobilization and insulin-stimulated glucose transport. Furthermore, chromium action was absent in methyl-beta-cyclodextrin-pretreated cells already displaying reduced plasma membrane cholesterol and increased GLUT4 translocation. Together, these data reveal a novel mechanism by which chromium may enhance GLUT4 trafficking and insulin-stimulated glucose transport. Moreover, these findings at the level of the cell are consistent with in vivo observations of improved glucose tolerance and decreased circulating cholesterol levels after chromium supplementation.     

Synthesis and efficacy of 1-[bis(4-fluorophenyl)-methyl]piperazine derivatives for acetylcholinesterase inhibition, as a stimulant of central cholinergic neurotransmission in Alzheimer's disease

The cholinergic hypothesis of Alzheimer's disease (AD) has spurred the development of numerous structural classes of compounds with different pharmacological profile aimed at increasing central cholinergic neurotransmission. Thus proving a symptomatic treatment for this disease are cholinomimetics with the pharmacological profile of acetyl cholinesterase (AchE) inhibitors. The novel bioactive 1-[bis(4-fluorophenyl)-methyl]piperazine derivatives were synthesized under mild conditions using different aryl/alkyl halides and heterocyclic alkyl halides with 1-[bis(4-fluorophenyl)-methyl]piperazine in the presence of powdered potassium carbonate in N,N-dimethylformamide. All the synthesized compounds were characterized by spectroscopic techniques, elemental analysis and were screened for their efficacy as AchE inhibitor. Some derivatives in this class showed good inhibition against AchE as compared to neostigmine as standard.