Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N-substituted-2-(4-phenylethynyl-phenyl)-1H-benzimidazoles and N-substituted 2[4-(4,4-dimethyl-thiochroman-6-yl-ethynyl)-phenyl)-1H-benzimidazoles

Synthesis of a series of novel and functionalized benzimidazole derivatives by the condensation of OPDA with 4-bromobenzoic acid and subsequent reactions of the product obtained with phenylacetylene and 6-ethynyl-4,4-dimethylthiochroman utilising Sonogashira coupling has been reported. The Sonogashira coupling products were then alkylated at the benzimidazole -NH with different electrophilic reagents leading to functionalized derivatives. All the compounds synthesized were screened for their potential anti-bacterial, anti-asthmatic and anti-diabetic properties, which exhibited moderate activities in screening studies in vitro.     

Tracking Progress Toward Elimination of Iodine Deficiency Disorders in Jharkhand, India

Research question:

What is the current status of Iodine Deficiency Disorders (IDD) in the state of Jharkhand?

Objectives:

(1) To determine the status of iodine deficiency in the state. (2) To determine the availability and cost of adequately iodized salt at the retail shops. (3) To study the perceptions of the community regarding iodine deficiency, salt and iodized salt.

Design:

A cross-sectional community-based survey.

Study setting:

Thirty clusters selected through the probability proportion to size (PPS) sampling in the state of Jharkhand.

Study participants:

Children aged 6-12 years, households, retail shopkeepers and opinion leaders.

Study tool:

Quantitative and qualitative methodology using a pretested questionnaire and focus group discussion used to carry out the community-based survey.

Results:

Total goiter rate (TGR) was 0.9%. Median urinary iodine level was 173.2 µg/L. The proportion of individuals with urinary iodine levels less than 100 and 50 µg/L were 26.4% and 10%, respectively. Slightly less than two-thirds (64.2%) of the households were found to be consuming adequately iodized salt as measured by titration (greater than 15 ppm). Iodized salt was available across the state and the cost varied between Re. 1 and Rs. 8 per kilogram. A common belief among the community was that iodized salt is equivalent to refined packet salt that is further equivalent to expensive salt.

Conclusion:

The results of the present survey show that the iodine nutrition in the state of Jharkhand is optimal. Considering that the consumption of adequately iodized salt should increase from 64.2% to the goal of more than 90%, sustained efforts are required in this place to consolidate the current coverage of adequately iodized salt and increase it to greater than 90%.     

Training interventions for general practitioners providing an occupational health service in the British Army

BACKGROUND: General practitioners (GPs) working in the British Army, whether civilian or military, are responsible for providing a first line occupational health (OH) service in addition to their primary health care role. Despite the medical classification system being well established, previous publications have shown considerable inconsistency in the knowledge among GPs. AIM: The aim of this audit cycle was to test effectiveness of training interventions designed for GPs, providing the first line OH service. METHOD: The audit cycle was divided into three stages. The Stages I and III were audits examining the standard of OH records initiated by GPs during a 4-month period (pre- and post-training). The Stage II was a training intervention. Statistical significance was assessed with the chi-square test. RESULTS: The stage one audit showed a statistically significant standard difference between the medical boards initiated by civilian and military GPs. This gap was bridged and the overall standard of the OH records improved significantly after the training. CONCLUSIONS: Appropriate training can enhance a first line OH service provided by GPs. The training must be reinforced at regular intervals. Both OH specialists and GPs can complement each other so as to identify, intervene and prevent work-related ill-health.     

Cronobacter spp. (previously Enterobacter sakazakii) invade and translocate across both cultured human intestinal epithelial cells and human brain microvascular endothelial cells

The mechanism of Cronobacter pathogenesis in neonatal meningitis and potential virulence factors (aside from host cell invasion ability) remain largely unknown. To ascertain whether Cronobacter can invade and transcytose across intestinal epithelial cells, enter into the blood stream and then transcytose across the blood-brain-barrier, we have utilized human intestinal INT407 and Caco-2 cells and brain microvascular endothelial cell (HBMEC) monolayers on Transwell filters as experimental model systems. Our data indicate a wide range of heterogeneity with respect to invasion efficiency among twenty-three Cronobacter isolates screened. For selected isolates, we observed significant levels of transcytosis for Cronobacter sakazakii across tight monolayers of both Caco-2 and HBMEC, mimicking in vivo ability to cross the intestine as well as the blood brain barrier, and at a frequency equivalent to that of a control meningitis-causing Escherichia coli K1 strain. Finally, EM analysis demonstrated intracellular Cronobacter bacteria within host vacuoles in HBMEC, as well as transcytosed bacteria at the basolateral surface. These data reveal that certain Cronobacter isolates can invade and translocate across both cultured human intestinal epithelial cells and HBMEC, thus demonstrating a potential path for neonatal infections of the central nervous system (CNS) following oral ingestion.     

Molecular docking studies of novel palmitoyl-ligands for cyclooxygenase-2

An in silico approach was adopted to identify potential cyclooxygenase-2 inhibitors through molecular docking studies. The in vivo studies indicated that synthetic palmitoyl derivatives of salicylic acid, para amino phenol, para amino benzoic acid, and anthranilic acid possessed significant pharmacological activities like anti-inflammatory, analgesic, and antipyretic activities. None of the tested substances produced any significant gastric lesions in experimental animals. In an attempt to understand the ligand-protein interactions in terms of the binding affinity, the above synthetic molecules were subjected to docking analysis using AutoDock. The palmitoyl derivatives palmitoyl anthranilic acid, palmitoyl para amino benzoic acid, palmitoyl para amino phenol, and palmitoyl salicylic acid showed better binding energy than the known inhibitor diclofenac bound to 1PXX. All the palmitoyl derivatives made similar interactions with the binding site residues of cyclooxygenase-2 as compared to that of the known inhibitor. Thus, structure-based drug discovery approach was successfully employed to identify some promising pro-drugs for the treatment of pain and inflammation.