Prevalence of systemic lupus erythematosus (SLE) was studied in the northern Indian population by means of a two-pronged approach: (a) antinuclear antibody (ANA) screening of the general population by a new well-standardized finger-prick 'filter paper' technique (sensitivity and specificity: 95.4% and 86.2%, respectively); and (b) a questionnaire survey carried out primarily by trained personnel in the community (sensitivity and specificity: 100% and 68.6% respectively). The low specificity of the two methods was improved by the introduction of a step of secondary screening by the authors, thus excluding false positives. ANA screening of 52,062 individuals yielded 13 positive results, of which only two were found to be true cases of SLE after secondary screening. Questionnaire survey of 39,826 individuals similarly yielded 3393 positive results. On secondary screening, only one of these persons was found to be a case of SLE. Thus, three cases of SLE were detected in a population survey of 91,888, giving a point prevalence of 3.2 per 100,000 (95% CI = 0-6.86 per 100,000). The reported prevalence of SLE ranges from 14 to 60 per 100,000. Thus, the prevalence of SLE in India is comparatively low. Although the reasons for low prevalence are not clear, the study used highly sensitive methodology and it is therefore unlikely that SLE cases were missed. It is hypothesized that SLE is a disease of modernization and therefore its prevalence in a predominantly rural population like that of India is low.

Fifty patients with histologically proven carcinoma of the gallbladder were examined by computed tomography (CT). The gallbladder masses were categorized into two broad groups: group 1 (74%) included patients in whom the gallbladder was identified along with a mass lesion; and group 2 (26%), where a large mass was present in the gallbladder fossa with no identifiable gallbladder. Group 1 was further divided into three types according to the nature of the tumor: Type 1, mass almost filling the entire gallbladder lumen; Type 2, a polypoidal mass projecting into the lumen; type 3, an infiltrating tumor seen as focal or diffuse wall thickening. Liver involvement, in the form of localized invasion in the vicinity of the primary gallbladder malignancy, was the most common associated finding (80%). Other ancillary features included presence of calculi, lymphadenopathy, and biliary obstruction. CT was found useful for characterizing and defining the extent of carcinoma of the gallbladder. However, it may not consistently demonstrate involvement of the gastrointestinal tract, omentum, and abdominal wall. CT can also be used for aspiration/biopsy guidance of the gallbladder mass in selected cases.

Survival in patients with systemic lupus erythematosus (SLE) in developed countries has improved considerably over the last 2 decades. In India, however, survival in patients with SLE reported 5 years ago from this tertiary referral centre was very poor. The present study was conducted to examine trends, if any, towards improvement in the survival of patients with SLE attending the same centre during the period 1981-1990. No statistically significant change in survival was noted. It appears that improvement in the survival of SLE patients would require an overall improvement in the standard of medical care in India.

Efflux pumps play a major role in the increasing antimicrobial resistance rendering a large number of drugs of no use. Large numbers of pathogens are becoming multidrug resistant due to inadequate dosage and use of the existing antimicrobials. This leads to the need for identifying new efflux pump inhibitors. Design of novel targeted therapies using inherent complexity involved in the biological network modeling has gained increasing importance in recent times. The predictive approaches should be used to determine antimicrobial activities with high pathogen specificity and microbicidal potency. Antimicrobial peptides, which are part of our innate immune system, have the ability to respond to infections and have gained much attention in making resistant strain sensitive to existing drugs. In this review paper, we outline evidences linking host-directed therapy with the efflux pump activity to infectious disease.

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Leishmania parasites possess an exceptional oxidant and chemical defense mechanism, involving a very unique small molecular weight thiol, trypanothione (T[SH]2), that helps the parasite to manage its survival inside the host macrophage. The reduced state of T[SH]2 is maintained by NADPH-dependent trypanothione reductase (TryR) by recycling trypanothione disulfide (TS2). Along with its most important role as central reductant, T[SH]2 have also been assumed to regulate the activation of iron-sulfur cluster proteins (Fe/S). Fe/S clusters are versatile cofactors of various proteins and execute a much broader range of essential biological processes viz., TCA cycle, redox homeostasis, etc. Although, several Fe/S cluster proteins and their roles have been identified in Leishmania, some of the components of how T[SH]2 is involved in the regulation of Fe/S proteins remains to be explored. In pursuit of this aim, a systems biology approach was undertaken to get an insight into the overall picture to unravel how T[SH]2 synthesis and reduction is linked with the regulation of Fe/S cluster proteins and controls the redox homeostasis at a larger scale. In the current study, we constructed an in silico kinetic model of T[SH]2 metabolism. T[SH]2 reduction reaction was introduced with a perturbation in the form of its inhibition to predict the overall behavior of the model. The main control of reaction fluxes were exerted by TryR reaction rate that affected almost all the important reactions in the model. It was observed that the model was more sensitive to the perturbation introduced in TryR reaction, 5 to 6-fold. Furthermore, due to inhibition, the T[SH]2 synthesis rate was observed to be gradually decreased by 8 to 14-fold. This has also caused an elevated level of free radicals which apparently affected the activation of Fe/S cluster proteins. The present kinetic model has demonstrated the importance of T[SH]2 in leishmanial cellular redox metabolism. Hence, we suggest that, by designing highly potent and specific inhibitors of TryR enzyme, inhibition of T[SH]2 reduction and overall inhibition of most of the downstream pathways including Fe/S protein activation reactions, can be accomplished.

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