Design and Evaluation of a Novel Gas Formation-Based Multiple-Unit Gastro-Retentive Floating Drug Delivery System for Quetiapine Fumarate

Purpose: To develop a gastro-retentive formulation of quetiapine fumarate in the form of floating minitablets.Methods: The system consisted of core units prepared by direct  compression process, which were coated with three successive layers, namely, an inner seal coat, effervescent layer and an outer polymeric layer of polymethacrylates.Results: Mini-tablets coated with Eudragit RS 30D (5, 7.5 and 10%)  released . 85% of the drug after 12 h, while those coated with Eudragit RL 30D (5, 7.5 and 10%) released . 85% drug within the same period. Drug release kinetic studies showed that drug diffusion fitted best to zero order and Higuchi models, indicating that drug release was anomalous  non-Fickian transport. In vivo gastric residence time results indicate that the units remained in the stomach for about 6 h (n = 3). There was nosignificant change in dissolution profiles before and after storage at 40‹C and 75% RH for 6 months.Conclusion: The developed floating mini-tablets of quetiapine fumarate exhibit prolonged release for .12 h, and thus may improve bioavailability and minimize fluctuations in plasma drug concentrations. Keywords: Mini-tablets; Floating delivery system; Effervescence, Polymeric membrane, Controlled release, Quetiapine fumarat

Synthesis, Anticonvulsant Activity and In silco Studies of Schiff Bases of 2-Aminothiophenes via Guanidine- Catalyzed Gewald Reaction

Purpose: To synthesize Schiff bases of 2-aminothiophenes and evaluate their anticonvulsant activity and in silco propertiesMethods: 2-Amino-N-o-tolyl-5,6-dihydro-4H-cylcopenta[b]thiophene-3-carboxamide was synthesized using 1,1,3,3-tetramethylguanidine lactate as a basic catalyst and by microwave irradiation. 2- substitued-o-tolyl-5,6-dihyro-4H-cylcopenta[b]thiophene-3-carboxamide was prepared by reacting with different substituted aromatic aldehydes. The synthesized compounds were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR) and mass spectrometry (MS) while their anticonvulsant activity was screened against maximum electroshockinduced seizure (MES), and pentylenetetrazole-induced seizure (PTZ) against phenytoin and diazepam as reference standards. Molecular docking (in silico) studies were performed using 4-aminobutyrateaminotransferase in order to predict possible protein-ligand interactions.Results: Among the 21 synthesized compounds, 2b, 2d, 2f, 2k, 2m, 2n and 2o showed good to moderate activity against MES and PTZ-induced convulsions. Compounds 2b, 2d, 2f, 2k and 2m exhibited lower activity against PTZ than against MES model while compounds 2n and 2o afforded greater protection against PTZ than against MES model. In silico results also revealed maximum binding affinity to GABA-AT protein which was higher than other compoundsConclusion: The synthesized compounds showed potent anticonvulsant activity. Molecular docking results should give an insight into how further modification of lead compound can be carried out for higher inhibitory activity.Keywords: Ionic liquid, 2-Aminothiophenes, Anticonvulsant, In silco studies, Molecular docking

Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma

Breast cancer is a malignant neoplasm originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. ILCs and IDCs vary from each other with respect to various histological, biological and clinical features. Remarkably, ductal tumors tending to form glandular structures, whereas lobular tumors are less cohesive and tends to invade in single file. The high degree of similarity in the prognoses of IDC and ILC makes it beneficial to develop a differential diagnostic protocol to classify the two conditions. The main goal of the study is to construct the genetic regulatory network from the microarray data using biological knowledge and constraint-based inferences, in order to explore the potential significant gene regulatory networks that can differentiate IDC and ILC and thereby understand the complex interactions that are influenced by the genetic networks. Out of the 54676 genes present on the GPL570 platform- 29 genes exhibited 4 fold up regulation in case of IDC and 22 in the case of ILC. The ductal and lobular tumors displayed a striking difference in the expression of genes associated with cell adhesion, protein folding, and protein phosphorylation and invasion. Construction of separate gene regulation networks for IDC and ILC on the basis of gene expression altercation can be utilized in understanding the distinction in the possible mechanism that underlies the pathological differences between the two, which can be exploited in identifying diagnostic or therapeutic targets

Tolerability and efficacy of single dose albendazole, diethylcarbamazine citrate (DEC) or co-administration of albendazole with DEC in the clearance of Wuchereria bancrofti in asymptomatic microfilaraemic volunteers in Pondicherry, South India: a hospital-based study

BACKGROUND: The tolerability and efficacy of single dose albendazole (400 mg), diethylcarbamazine citrate (DEC) (6 mg/kg bodyweight) or co-administration of albendazole (400 mg) + DEC (6 mg/kg bodyweight) was studied in 54 asymptomatic Wuchereria bancrofti microfilaraemic volunteers in a double blind hospital-based clinical study. RESULTS: There was no significant difference in the overall incidence of adverse reactions between the three drug groups [42.1% (albendazole), 52.9% (DEC) and 61.1% (albendazole + DEC); P > 0.05]. The mean score of adverse reaction intensity did not differ significantly between the DEC and albendazole + DEC groups. However, the values in these two groups were significantly higher compared to that of albendazole alone [1.8 ± 3.0 (albendazole) vs. 5.6 ± 7.1 (DEC), 6.7 ± 6.6 (albendazole + DEC); P < 0.05]. By day 360 post-therapy there was no significant difference between the three drug groups in relation to the clearance of microfilaria [26.3% (albendazole), 17.6% (DEC), 27.8% (albendazole + DEC)], reduction in geometric mean parasite density [94.7% (albendazole), 89.5% (DEC), 95.4% (albendazole + DEC)] or reduction in filarial antigenaemia [83% (albendazole), 87% (DEC), 75% (albendazole + DEC)]. Furthermore, there was a significant decrease in mean geometric parasite density (P < 0.05) as well as antigenaemia optical density values (P < 0.01) between pre-therapy levels and day 360 post-therapy in all three groups. CONCLUSIONS: This study has shown that single dose albendazole (400 mg) has similar efficacy in the clearance of microfilaria as that of DEC or the co-administration of the two drugs. The results strengthen the rationale of using albendazole for mass annual single dose administration for the control of transmission of lymphatic filariasis

Metabolism of 2-Chloro-4-Nitrophenol in a Gram Negative Bacterium, Burkholderia sp. RKJ 800

A 2-Chloro-4-nitrophenol (2C4NP) degrading bacterial strain designated as RKJ 800 was isolated from a pesticide contaminated site of India by enrichment method and utilized 2C4NP as sole source of carbon and energy. The stoichiometric amounts of nitrite and chloride ions were detected during the degradation of 2C4NP. On the basis of thin layer chromatography, high performance liquid chromatography and gas chromatography-mass spectrometry, chlorohydroquinone (CHQ) and hydroquinone (HQ) were identified as major metabolites of the degradation pathway of 2C4NP. Manganese dependent HQ dioxygenase activity was observed in the crude extract of 2C4NP induced cells of the strain RKJ 800 that suggested the cleavage of the HQ to γ-hydroxymuconic semialdehyde. On the basis of the 16S rRNA gene sequencing, strain RKJ 800 was identified as a member of genus Burkholderia. Our studies clearly showed that Burkholderia sp. RKJ 800 degraded 2-chloro-4-nitrophenol via hydroquinone pathway. The pathway identified in a gram negative bacterium, Burkholderia sp. strain RKJ 800 was differed from previously reported 2C4NP degradation pathway in another gram-negative Burkholderia sp. SJ98. This is the first report of the formation of CHQ and HQ in the degradation of 2C4NP by any gram-negative bacteria. Laboratory-scale soil microcosm studies showed that strain RKJ 800 is a suitable candidate for bioremediation of 2C4NP contaminated sites

Mean Dietary Salt Intake in Urban and Rural Areas in India: A Population Survey of 1395 Persons.

BACKGROUND: The scientific evidence base in support of population-wide salt reduction is strong, but current high-quality data about salt intake levels in India are mostly absent. This project sought to estimate daily salt consumption levels in selected communities of Delhi and Haryana in north India and Andhra Pradesh in south India. METHODS AND RESULTS: In this study, 24-hour urine samples were collected using an age- and sex-stratified sampling strategy in rural, urban, and slum areas. Salt intake estimates were made for the overall population of each region and for major subgroups by weighting the survey data for the populations of Delhi and Haryana, and Andhra Pradesh. Complete 24-hour urine samples were available for 637 participants from Delhi and Haryana and 758 from Andhra Pradesh (65% and 68% response rates, respectively). Weighted mean population 24-hour urine excretion of salt was 8.59 g/day (95% CI 7.68-9.51) in Delhi and Haryana and 9.46 g/day (95% CI 9.06-9.85) in Andhra Pradesh (P=0.097). Estimates inflated to account for the minimum likely nonurinary losses of sodium provided corresponding estimates of daily salt intake of 9.45 g/day (95% CI 8.45-10.46) and 10.41 g/day (95% CI 9.97-10.84), respectively. CONCLUSIONS: Salt consumption in India is high, with mean population intake well above the World Health Organization recommended maximum of 5 g/day. A national salt reduction program would likely avert much premature death and disability

Risk Assessment of a Synthetic Pyrethroid, Bifenthrin on Pulses

This work was undertaken to determine the pre-harvest interval of bifenthrin and to minimize its residues in pulses and thereby ensure consumer safety and avoid non-compliance in terms of residues violations in export market. Furthermore the residue dynamics in the soil under pulses was explored to assess the environmental safety. The residues of bifenthrin dissipated following first order kinetics. The residues in harvest time grains were below the maximum residue limit (MRL) of 0.02 mg/kg applicable for European Union. In soil the degradation rate was fast with a half life of 2–3 days. This work is of high practical significance to the domestic and export pulse industry of India to ensure safety compliance in respect of bifenthrin residues, keeping in view the requirements of international trade

A novel pathway producing dimethylsulphide in bacteria is widespread in soil environments

The volatile compound dimethylsulphide (DMS) is important in climate regulation, the sulphur cycle and signalling to higher organisms. Microbial catabolism of the marine osmolyte dimethylsulphoniopropionate (DMSP) is thought to be the major biological process generating DMS. Here we report the discovery and characterisation of the first gene for DMSP-independent DMS production in any bacterium. This gene, mddA, encodes a methyltransferase that methylates methanethiol (MeSH) and generates DMS. MddA functions in many taxonomically diverse bacteria including sediment-dwelling pseudomonads, nitrogen-fixing bradyrhizobia and cyanobacteria, and mycobacteria, including the pathogen Mycobacterium tuberculosis. The mddA gene is present in metagenomes from varied environments, being particularly abundant in soil environments, where it is predicted to occur in up to 76% of bacteria. This novel pathway may significantly contribute to global DMS emissions, especially in terrestrial environments, and could represent a shift from the notion that DMSP is the only significant precursor of DMS

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

BACKGROUND:There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. METHODS:We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. FINDINGS:At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. CONCLUSIONS:This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry ACTRN12607000099426

Zinc oxide nanoparticle-coated films: fabrication, characterization, and antibacterial properties

In this article, novel antibacterial PVC-based films coated with ZnO nanoparticles (NPs) were fabricated, characterized, and studied for their antibacterial properties. It was shown that the ZnO NPs were coated on the surface of the PVC films uniformly and that the coating process did not affect the size and shape of the NPs on the surface of PVC films. Films coated with concentrations of either 0.2 or 0.075 g/L of ZnO NPs exhibited antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, but exhibited no antifungal activity against Aspergillus flavus and Penicillium citrinum. Smaller particles (100 nm) exhibited more potent antibacterial activity than larger particles (1000 nm). All ZnO-coated films maintained antibacterial activity after 30 days in water