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Biomedical subjects

Richa Shrivastava

Publications and source records attributed to Richa Shrivastava.

10 recordsLinked to original sources

Dengue and dengue haemorrhagic fever: implications of host genetics.

Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.

Alleles↗

A comparative study on rat intestinal epithelial cells and resident gut bacteria (ii) effect of arsenite.

OBJECTIVE: In order to use facultative gut bacteria as an alternate to animals for the initial gastrointestinal toxicity screening of heavy metals, a comparative study on rat intestinal epithelial cells and resident gut bacteria was undertaken. METHODS: in vitro growth rate of four gut bacteria, dehydrogenase (DHA) and esterase (EA) activity test, intestinal epithelial and bacterial cell membrane enzymes and in situ effect of arsenite were analysed. RESULTS: Growth profile of mixed resident population of gut bacteria and pure isolates of Escherichia coli, Pseudomonas sp., Lactobacillus sp., and Staphylococcus sp. revealed an arsenite (2-20 ppm) concentration-dependent inhibition. The viability pattern of epithelial cells also showed similar changes. DHA and EA tests revealed significant inhibition (40%-72%) with arsenite exposure of 5 and 10 ppm in isolated gut bacteria and epithelial cells. Decrease in membrane alkaline phosphatase and Ca2+ -Mg2+ -ATPase activities was in the range of 33%-55% in four bacteria at the arsenite exposure of 10 ppm, whereas it was 60%-65% in intestinal epithelial villus cells. in situ incubation of arsenite using intestinal loops also showed more or less similar changes in membrane enzymes of resident gut bacterial population and epithelial cells. CONCLUSION: The results indicate that facultative gut bacteria can be used as suitable in vitro model for the preliminary screening of arsenical gastrointestinal cytotoxic effects.

Animals↗

Macrophage and dengue virus: friend or foe?

The cells of monocyte-macrophage (Mphi) lineage play important roles both in innate and adaptive immune responses. They are the first line of defence in body and their job is to phagocytose a foreign invader, the pathogen, digest it and remove it. Mphi help body in mounting the antigenspecific immune response by presenting the digested pathogen antigen in conjunction with major histocompatibility complex (MHC) class II molecules to recruit B and T lymphocytes response. Usually Mphi succeed in their job of eliminating most pathogens from the body but sometimes the pathogen strikes a "friendship" with them and starts using them for its benefit. A number of pathogens, including dengue virus (DV), subvert Mphi and use them for their replication, increasing the severity of damage to the body. This duality may be related to the fact that Mphi serve as efficient host cell for DV replication, in addition to being responsible for innate immunity and for initiating adaptive immune responses. This review gives a brief overview of the various roles of Mphi (enmity and friendship) during dengue virus infection.

Animals↗

Interaction of viral proteins with metal ions: role in maintaining the structure and functions of viruses.

Metal ions are integral part of some viral proteins and play an important role in their survival and pathogenesis. Zinc, magnesium and copper are the commonest metal ion that binds with viral proteins. Metal ions participate in maturation of genomic RNA, activation and catalytic mechanisms, reverse transcription, initial integration process and protection of newly synthesized DNA, inhibition of proton translocation (M2 protein), minus- and plus-strand transfer, enhance nucleic acid annealing, activation of transcription, integration of viral DNA into specific sites and act as a chaperone of nucleic acid. Metal ions are also required for nucleocapsid protein-transactivation response (TAR)-RNA interactions. In certain situations more than one metal ion is required e.g. RNA cleavage by RNase H. This review underscores the importance of metal ions in the survival and pathogenesis of a large group of viruses and studies on structural basis for metal binding should prove useful in the early design and development of viral inhibitors.

Coenzymes↗

Dengue vaccines: problems and prospects.

The extent of cumulative disease burden caused by dengue virus has attained an unprecedented level in recent times with sharp increase in the size of human population at risk. Dengue disease presents highly complex medical, economic and ecologic problems. The surge in publications on the development of dengue vaccines, taking advantage of new generation of biotechnology techniques indicates the profound interest and urgency in the scientific and medical communities in combating this disease. This review summarizes the importance of critical subjects like pathogenesis of dengue haemorrhagic fever and inadequacy of animal model that have adversely affected dengue vaccine development. Further, the remarkable progresses so far made in dengue vaccine research not only employing a diverse range of new strategies but also re-using old techniques to improve the existing vaccines, have been presented. The efficacy and safety of some of the new vaccine candidates have been evaluated and proven in human preclinical/clinical trials. Besides the technical advancement in vaccine development, vaccine safety and vaccine formulation have been examined.

Animals↗

Effects of dengue virus infection on peripheral blood cells of mice exposed to hexavalent chromium with drinking water.

BACKGROUND & OBJECTIVE: The occupational and non-occupational exposure to hexavalent chromium Cr (VI) is common. The effect of chromium compromises the immune response of the host. Dengue virus (DV) infection causes various changes in the peripheral blood cells. It is, therefore, possible that the chromium toxicity may affect the disease process during DV infection. The present study aims to study the effects of dengue virus infection on peripheral blood cells of mice fed Cr (VI) with drinking water. METHODS: One group of mice was given ad libitum drinking water containing Cr (VI) and the other group used as the normal control mice was given plain water to drink. At the 3, 6 and 9 wk of Cr (VI) drinking, a set of mice from each group was inoculated intracerebrally (ic) with DV and studied at the 4th and 8th day post inoculation. RESULTS: It was observed that Cr (VI) drinking led to reduction in lymphocytes, haemoglobin and the haematocrit values while the granulocyte, monocyte and platelet counts were increased. On the other hand, most of the parameters were decreased following inoculation of normal mice with DV. In Cr (VI)-fed mice the effects of DV infection were minimal. The most significant finding of these experiments was that the reduction in platelet counts following inoculation with DV was markedly less in Cr (VI)-fed mice than that in DV-inoculated normal control mice. INTERPRETATION & CONCLUSION: Cr(VI) compounds have been declared as a potent occupational carcinogen. On the contrary, Cr(III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate, are used as micronutrients and nutritional supplements, and have been shown to exhibit health benefits in animals and humans. Whether therapeutic doses of chromium (III) compounds may be able to prevent the DV-induced fall in platelet counts, needs to be investigated.

Administration, Oral↗

Suboptimal chlorine treatment of drinking water leads to selection of multidrug-resistant Pseudomonas aeruginosa.

The present study was undertaken to investigate the spectrum of bacteria present in the River Gomti water before and after chlorination for drinking purposes. We observed that the strains of Pseudomonas aeruginosa that survived chlorination on three out of seven occasions were resistant to almost all the antibiotics tested. The chlorine-resistant bacteria had mucoid colonies and grew better at 24 degrees C. All attempts to isolate the plasmid responsible for chlorine resistance were unsuccessful. Laboratory experiments using different strains of the P. aeruginosa in distilled water showed that only the resistant strain survived chlorine treatment at a dose of < or =500 microg/L. Similar results were obtained when water collected from seven different sites on the River Gomti was treated with graded doses of chlorine. At the higher dose of chlorine, all the bacteria died in 30 min, whereas with lower doses all the bacteria survived. The present study underscores the importance of measuring water chlorine concentrations to assure they are sufficiently high to remove pathogenic bacteria from drinking water. To our knowledge, this is the first report in the literature of the selection of multidrug-resistant bacteria by suboptimal chlorine treatment of water.

Anti-Bacterial Agents↗

Gut microflora & toxic metals: chromium as a model.

The gastrointestinal tract (GIT) is exposed to various environmental pollutants including metals, that contaminate food and water which may have toxic effects on body. GIT has large amount of microbes that live in symbiosis and help the host in different ways. The resident gut microflora have a significant role to play in detoxification and elimination of the harmful metals from the body. Chromium is a naturally occurring heavy metal found commonly in environment in trivalent (Cr III) and hexavalent (Cr VI) forms. Cr (VI) compounds have been shown to be potent occupational carcinogens. The reduction of Cr (VI) to Cr (III) results in the formation of reactive intermediates that together with oxidative stress and oxidative tissue damage, and a cascade of cellular events including modulation of apoptosis regulatory gene p53 contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. The data discussed here with reference to chromium show that gut microflora have a marked capacity to cope with the increased load of ingested metals and may contribute significantly in the protection against metal toxicity.

Apoptosis↗

Various cells of the immune system and intestine differ in their capacity to reduce hexavalent chromium.

The cells of the immune system form a strong line of defence against foreign substances. The present study was undertaken to investigate the capacity of different cells of Wistar rats to reduce potentially carcinogenic hexavalent chromium (Cr-VI) into less toxic trivalent chromium in vitro. 5 x 10(6) cells were incubated with 10 or 25 microg ml(-1) of Cr (VI) in the form of K2Cr2O7 at 37 degrees C in the presence of 5% CO2 in air. At various time periods the remaining amount of Cr (VI) was measured and the percentage of Cr (VI) reduced was calculated. Among the single cell suspensions from the splenic cells a peak reduction of 55% was observed with the total spleen cells, 40% with the B-lymphocyte-enriched subpopulation, 10% with T-lymphocytes and 24% with the macrophages. The reduction by splenic and peritoneal macrophages was similar. Total thymocytes reduced 54% of the Cr (VI). Since the most common route of entry of chromium is through drinking water and food, intestinal cells were also investigated. Among the intestinal cells the maximum reduction of 100% (of 10 microg ml(-1)) was observed with the upper villus cells and 72% with the middle villus cells while reduction was the least (4%) with the crypt cells. The reduction in the intestinal loop in situ was 100%. The time taken by each cell type for the peak reduction to Cr (VI) was markedly different. The findings thus show that the capacity of different cells in the body differs vastly in their capacity and time taken to reduce hexavalent chromium. The most efficient handling of Cr (VI) by the intestine, due to the presence of a variety of cells and bacteria, protects the body from its adverse effects.

Animals↗

Effects of chromium on the immune system.

Chromium is a naturally occurring heavy metal found commonly in the environment in trivalent, Cr(III), and hexavalent, Cr(VI), forms. Cr(VI) compounds have been declared as a potent occupational carcinogen among workers in chrome plating, stainless steel, and pigment industries. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that together with oxidative stress oxidative tissue damage and a cascade of cellular events including modulation of apoptosis regulatory gene p53, contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. On the other hand, chromium is an essential nutrient required to promote the action of insulin in body tissues so that the body can use sugars, proteins and fats. Chromium is of significant importance in altering the immune response by immunostimulatory or immunosuppressive processes as shown by its effects on T and B lymphocytes, macrophages, cytokine production and the immune response that may induce hypersensitivity reactions. This review gives an overview of the effects of chromium on the immune system of the body.

Animals↗