A convenient 'one-pot' synthesis and in vitro microbiological evaluation of novel 2,7-diaryl-[1,4] -diazepan-5-ones

A convenient method for the 'one-pot' synthesis of novel target molecule 2,7-diaryl-[1,4]-diazepan-5-ones from the respective 2,6-diaryl-piperidin-4-ones was catalyzed by NaHSO4.Al2O3 heterogeneous catalyst in dry media under microwave irradiation in solvent-free conditions. Moreover, the catalyst could be recovered and re-used up to 4 times after washing with ethyl acetate. They were evaluated for potential antibacterial activity against Staphylococcus aureus, beta-Haemolytic streptococcus, Vibreo cholerae, Salmonella typhii, Escherichia coli, Klebsiella pneumonia, Pseudomonas and antifungal activity against Aspergillus flavus, Aspergillus fumigatus, Mucor, Candida albicans and Rhizopus. Structure-Activity Relationship (SAR) led to the conclusion that, of all the compounds 25-32 tested, compound 30 exerted strong in vitro antibacterial activity against S. aureus, S. typhii, and Pseudomonas and all the compounds 25-32 were less active against E. coli, whereas all the compounds 25-32 displayed potent in vitro antifungal activity against all the fungal strains used, except compound 30, which was more effectual against Mucor.     

Curcuminoids-loaded liposomes in combination with arteether protects against Plasmodium berghei infection in mice

Present communication deals with the docking study of hybrid phenyl thiazolyl-1,3,5-triazine analogues (1a-36d) on three selected different binding site viz., α, β and γ of wild type Pf-DFHR-TS. In admiration of excellent H-bond scoring, with regard to cycloguanil and to a large extent similar scoring with WR99210, compound 4a, 12b, 21c, 23c, 28d, 29d, 34d, and 35d were selected for in vitro antimalarial activity against 3D7 strain of Plasmodium falciparum. Findings from the study disclose that a significant correlation was exist between in vitro results and in silico prediction (r(2)=0.543). Furthermore, investigation of structure-activity relationships elucidate crucial structural requirement for site specific binding of ligands.     

A cohort study of lymphatic filariasis on socio economic conditions in Andhra Pradesh, India

Background

To assess the impact of socioeconomic variables on lymphatic filariasis in endemic villages of Karimnagar district, Andhra Pradesh, India.

Methods

A pilot scale study was conducted in 30 villages of Karimnagar district from 2004 to 2007. These villages were selected based on previous reports from department of health, Government of Andhra Pradesh, epidemiology, entomology and socioeconomic survey was conducted as per protocol. Collected data were analysed statistically by Chi square test, Principal Component Analysis, Odds ratio, Bivariate, multivariate logistic regression analysis.

Results

Total of 5,394 blood samples collected and screened for microfilaria, out of which 199 were found to be positive (3.7%). The socioeconomic data of these respondents/participants were correlated with MF prevalence. The socioeconomic variables like educational status (Odds Ratio (OR) = 2.6, 95% Confidence Interval (CI) = 1.1–6.5), house structure (hut OR = 1.9, 95% CI = 1.2–3.1; tiled OR = 1.3, 95% CI = 0.8–2) and participation in mass drug administration program (OR = 1.8, 95% CI = 1.3–2.6) were found to be highly associated with the occurrence of filarial disease. The socioeconomic index was categorized into low (3.6%; OR-1.1, 95% CI: 0.7–1.5) medium (4.9%; OR-1.5, 95% CI = 1–2.1) and high (3.3%) in relation to percentage of filarial parasite prevalence. A significant difference was observed among these three groups while comparing the number of cases of filaria with the type of socioeconomic conditions of the respondents (P = 0.067).

Conclusions

From this study it is inferred that age, education of family, type of house structure and awareness about the filarial disease directly influenced the disease prevalence. Beside annual mass drug administration program, such type of analysis should be undertaken by health officials to target a few socioeconomic factors to reduce the disease burden. Health education campaigns in the endemic villages and imparting of protection measures against mosquitoes using insecticide treated bed nets would substantially reduce the disease in these villages.     

Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration

In patients with cystic fibrosis (CF) and asthma, elevated levels of interleukin-8 (IL-8) are found in the airways. IL-8 is a CXC chemokine that is a chemoattractant for neutrophils through CXCR1 and CXCR2 G protein-coupled receptors. We hypothesized that IL-8 acts directly on airway smooth muscle cells (ASMC) in a way that may contribute to the enhanced airway responsiveness and airway remodeling observed in CF and asthma. The aim of this study was to determine whether human ASMC (HASMC) express functional IL-8 receptors (CXCR1 and CXCR2) linked to cell contraction and migration. Experiments were conducted on cells harvested from human lung specimens. Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2. Intracellular Ca²⁺ concentration ([Ca²⁺]_i) increased from 115 to 170 nM in response to IL-8 (100 nM) and decreased after inhibition of phospholipase C (PLC) with U-73122. On blocking the receptors with specific neutralizing antibodies, changes in [Ca²⁺]_i were abrogated. IL-8 also contracted the HASMC, decreasing the length of cells by 15%, and induced a 2.5-fold increase in migration. These results indicate that HASMC constitutively express functional CXCR1 and CXCR2 that mediate IL-8-triggered Ca²⁺ release, contraction, and migration. These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF. chemokines; lung; signal transduction     

A web based relational database management system for filariasis control

The present study describes a RDBMS (relational database management system) for the effective management of Filariasis, a vector borne disease. Filariasis infects 120 million people from 83 countries. The possible re-emergence of the disease and the complexity of existing control programs warrant the development of new strategies. A database containing comprehensive data associated with filariasis finds utility in disease control. We have developed a database containing information on the socio-economic status of patients, mosquito collection procedures, mosquito dissection data, filariasis survey report and mass blood data. The database can be searched using a user friendly web interface.

Availability     

TM-MOTIF: an alignment viewer to annotate predicted transmembrane helices and conserved motifs in aligned set of sequences

Multiple sequence alignments become biologically meaningful only if conserved and functionally important residues and secondary structural elements preserved can be identified at equivalent positions. This is particularly important for transmembrane proteins like G-protein coupled receptors (GPCRs) with seven transmembrane helices. TM-MOTIF is a software package and an effective alignment viewer to identify and display conserved motifs and amino acid substitutions (AAS) at each position of the aligned set of homologous sequences of GPCRs. The key feature of the package is to display the predicted membrane topology for seven transmembrane helices in seven colours (VIBGYOR colouring scheme) and to map the identified motifs on its respective helices /loop regions. It is an interactive package which provides options to the user to submit query or pre-aligned set of GPCR sequences to align with a reference sequence, like rhodopsin, whose structure has been solved experimentally. It also provides the possibility to identify the nearest homologue from the available inbuilt GPCR or Olfactory Receptor cluster dataset whose association is already known for its receptor type. AVAILABILITY: The database is available for free at mini@ncbs.res.in.     

Data base management system for lymphatic filariasis--a neglected tropical disease

Background

Researchers working in the area of Public Health are being confronted with large volumes of data on various aspects of entomology and epidemiology. To obtain the relevant information out of these data requires particular database management system. In this paper, we have described about the usages of our developed database on lymphatic filariasis.

Methods

This database application is developed using Model View Controller (MVC) architecture, with MySQL as database and a web based interface. We have collected and incorporated the data on filariasis in the database from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India.

Conclusion

The importance of this database is to store the collected data, retrieve the information and produce various combinational reports on filarial aspects which in turn will help the public health officials to understand the burden of disease in a particular locality. This information is likely to have an imperative role on decision making for effective control of filarial disease and integrated vector management operations.     

Management of filariasis using prediction rules derived from data mining

The present paper demonstrates the application of CART (classification and regression trees) to control a mosquito vector (Culex quinquefasciatus) for bancroftian filariasis in India. The database on filariasis and a commercially available software CART (Salford systems Inc. USA) were used in this study. Baseline entomological data related to bancroftian filariasis was utilized for deriving prediction rules. The data was categorized into three different aspects, namely (1) mosquito abundance, (2) meteorological and (3) socio-economic details. This data was taken from a database developed for a project entitled "Database management system for the control of bancroftian filariasis" sponsored by Ministry of Communication and Information Technology (MC&IT), Government of India, New Delhi. Predictor variables (maximum temperature, minimum temperature, rain fall, relative humidity, wind speed, house type) were ranked by CART according to their influence on the target variable (month). The approach is useful for forecasting vector (mosquito) densities in forthcoming seasons.