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Biomedical subjects

S K Jain

Publications and source records attributed to S K Jain.

At least 37 records · Page 2Linked to original sources

A study to evaluate surrogate markers of insulin resistance in forty euglycemic healthy subjects.

OBJECTIVE: Insulin resistance (IR) is increasingly being recognized as an important pathophysiological determinant of not only diabetes but also a number of other clinical states. Methods for directly estimating IR like euglycemic clamp technique and Insulin suppression test (IST) are experimentally demanding and impractical tool for large scale epidemiological studies. We evaluated several surrogate markers of IR in 40 healthy subjects. METHODS: Study included 40 euglycemic normal healthy north Indian subjects (33 males, 7 females) of mean +/- SD age 38.9 +/- 8.6 yrs, BMI 20.5 +/- 3.6 kg/m2 and WHR 0.87 +/- 0.05. All subjects were tested for fasting and postprandial (2 hr post 75 gm glucose) glucose and insulin. Then all the subjects underwent IST by modified Harano's method (simultaneous infusion of 20% dextrose @ 6mg/kg/min and plain human insulin @ 50 mU/kg/hr). Metabolic clearance rate for glucose (MCR = glucose infusion rate/steady state plasma glucose, ml/kg/min) was calculated for 120-150 min of infusion. Correlation of MCR with various surrogate markers which included fasting glucose (FG), fasting insulin (FI), fasting glucose/insulin ratio (FGIR), 120 min glucose (PPG), 120 min insulin (PPI), 120 min glucose/insulin ratio (PPGIR), homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), fasting glucose insulin product (FIGP), insulin sensitivity index (ISI), fasting insulin resistance index (FIRI), insulin ratio (IRa) and insulinogenic index (II) were evaluated. RESULTS: MCR was found to be significantly (p <0.05) correlated with FI (r= -0.347), PPI (r= -0.402), PPG (r= -0.317), PPGIR (r= 0.356), HOMA-IR (r= -0.348), FIGP (r= -0.348), and FIRI (r= -0.348). CONCLUSIONS: Among the surrogate markers which were significantly correlated to MCR, there was no significant superiority of one marker over the other. We suggest that measuring insulin levels alone in a single fasting sample can serve as a simple, cheap and convenient indirect qualitative index of IR.

Adult↗

Quick control of bubonic plague outbreak in Uttar Kashi, India.

A localized outbreak of bubonic plague occurred in village Dangud (population 332), district Uttar Kashi, Uttaranchal, India in the second week of October 2004. 8 cases were considered outbreak associated based on their clinical and epidemiological characteristics; 3 (27.3%) of them died within 48 hours of developing illness. All the 3 fatal cases and five surviving cases had enlargement of inguinal lymph nodes. None of them had pneumonia. The age of the cases ranged from 23-70 years and both sexes were affected. No such illness was reported from adjoining villages. The outbreak was fully contained within two weeks of its onset by supervised comprehensive chemoprophylaxis using tetracycline. A total of approximately 1250 persons were given chemoprophylaxis in three villages. There was no clear history of rat fall in the village. No flea was found on rodents or animals. 16 animal serum samples were found to be negative for antibodies against F-1 antigen of Y. pestis. However, Y. pestis was isolated from two rodents (Rattus rattus and Mus musculus) trapped in the village. One case and three animal sera showed borderline sero-positivity against rickettsial infection. The diagnosis of plague was confirmed by detection of four fold rise of antibody titre against F-1 antigen of Yersinia pestis in paired sera of three cases (one of the WHO approved criteria of diagnosis of confirmed plague). This outbreak and the occurrence of earlier outbreaks of plague in Surat (Gujarat) and Beed (Maharashtra) in 1994 and in district Shimla (Himachal Pradesh) in 2002 confirm that plague infection continue to exist in sylvatic foci in many parts of India which is transmitted to humans occasionally. Thus, there is a strong need for the States to monitor the plague activity in known sylvatic foci regularly and have a system of surveillance to facilitate prompt diagnosis and treatment of cases to control the disease. This investigation highlights that with high index of suspicion the disease can be diagnosed early and mounting of supervised comprehensive response can prevent the disease to proceed to pneumonic stage where man to man transmission gets established and outbreak assumes larger dimensions.

Adult↗

Adverse drug reactions observed during DOTS.

A total of 8.37% of the 1195 patients treated at NDTB Centre with DOTS under RNTCP between January 2002 to June 2003 presented with adverse drug reactions. Patients showing any sort of adverse reactions were studied in detail by personal interviews and a semi-structured questionnaire. The profile of patients presenting with adverse reactions showed that majority of the patients (53%) had gastrointestinal reactions, the commonest presenting complaint being nausea and vomiting. General aches and pains were complained by about 35% and giddiness was the presenting complaint in 27% irrespective of the use of streptomycin, although giddiness was observed more often in Category II patients (59%). Skin rash and itching was complained by about 17% of patients and 11% complained of arthralgia, while only 1% had hepatotoxicity during treatment. Majority of the adverse reactions (67%) were observed within the first four weeks of treatment and only 0.25% of patients treated with DOTS had interruption of treatment for short periods.

Adolescent↗

Study of unusual phenomenon of contact firing on gelatine block using .38 Special revolver--forensic importance.

Gunshot wounds in suicide cases are self-inflicted wounds. Self-inflicted wounds in suicide cases are usually caused by contact firing and are of great forensic significance. Evaluation of contact wound may be associated with difficulties if the bore gets obstruction prior to firing. This paper investigates the phenomenon and interprets the results of test firing conducted on 20% gelatine block at 10 degrees C, using .38 Special revolver with obstruction of a bullet in the bore. Test firings were conducted in three different muzzle-target contact conditions keeping the muzzle pressed against the gel block in each case. The physical evidence and the wound ballistic parameter namely bullet track, remaining velocity of the bullets and volume of permanent cavity have been studied. When compared with the results of contact firing conducted with the same firearm without having any bore obstruction under similar conditions, it has been found that the physical evidence and the wound ballistic parameters would be helpful for interpretation of such unusual incidents for forensic inference.

Journal Article↗

Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects.

AIMS/HYPOTHESIS: Maternal diabetes increases oxidative stress in embryos. Maternal diabetes also inhibits expression of embryonic genes, most notably, Pax-3, which is required for neural tube closure. Here we tested the hypothesis that oxidative stress inhibits expression of Pax-3, thereby providing a molecular basis for neural tube defects induced by diabetic pregnancy. METHODS: Maternal diabetes-induced oxidative stress was blocked with alpha-tocopherol (vitamin E), and oxidative stress was induced with the complex III electron transport inhibitor, antimycin A, using pregnant diabetic or non-diabetic mice, primary cultures of neurulating mouse embryo tissues, or differentiating P19 embryonal carcinoma cells. Pax-3 expression was assayed by quantitative RT-PCR, and neural tube defects were scored by visual inspection. Oxidation-induced DNA fragmentation in P19 cells was assayed by electrophoretic analysis. RESULTS: Maternal diabetes inhibited Pax-3 expression and increased neural tube defects, and alpha-tocopherol blocked these effects. In addition, induction of oxidative stress with antimycin A inhibited Pax-3 expression and increased neural tube defects. In cultured embryo tissues, high glucose-inhibited Pax-3 expression, and this effect was blocked by alpha-tocopherol and GSH-ethyl ester, and Pax-3 expression was inhibited by culture with antimycin A. In differentiating P19 cells, antimycin A inhibited Pax-3 induction but did not induce DNA strand breaks. CONCLUSION/INTERPRETATION: Oxidative stress inhibits expression of Pax-3, a gene that is essential for neural tube closure. Impaired expression of essential developmental control genes could be the central mechanism by which neural tube defects occur during diabetic pregnancy, as well as other sources of oxidative stress.

Animals↗

Subcutaneous phaeohyphomycosis on face caused by Cladophialophora bantiana.

We report the case of a patient suffering from subcutaneous phaeohyphomycosis caused by Cladophialophora bantiana. The face of the upper site was involved with small, stellate, pyogranulomatous foci and low inflammation. The patient was treated by topical and systemic corticosteriod and amphotericin B. After 3 months of treatment, the patient showed good response.

Amphotericin B↗

Artemisinin, a novel antimalarial drug: biochemical and molecular approaches for enhanced production.

Artemisinin, a sesquiterpene lactone containing an endoperoxide bridge, has been isolated from the aerial parts of Artemisia annua L. plants. It is effective against both drug-resistant and cerebral malaria-causing strains of Plasmodium falciparum. The relatively low yield (0.01-0.8 %) of artemisinin in A. annua is a serious limitation to the commercialization of the drug. Therefore, the enhanced production of artemisinin either in cell/tissue culture or in the whole plant of A. annua is highly desirable. It can be achieved by a better understanding of the biochemical pathway leading to the synthesis of artemisinin and its regulation by both exogenous and endogenous factors. Furthermore, genetic engineering tools can be employed to overexpress gene(s) coding for enzyme(s) associated with the rate limiting step(s) of artemisinin biosynthesis or to inhibit the enzyme(s) of other pathway competing for its precursors. These aspects which may be employed to enhance the yield of artemisinin both in vitro and in vivo are discussed in this review.

Animals↗

Familial aggregation of autoimmune thyroiditis in first-degree relatives of patients with juvenile autoimmune thyroid disease.

Several studies have shown aggregation of autoimmune thyroiditis in families by estimation of thyroid antibodies. However, the prevalence by concurrent estimation with fine-needle aspiration cytology (FNAC) and thyroid antibodies has not been previously reported. We therefore studied 222 first-degree relatives (group 1) of 71 index cases diagnosed as lymphocytic thyroiditis on FNAC and 81 family members (group 2) of 23 goitrous children diagnosed as colloid goiter on FNAC for comparison. Successful FNAC conducted in 122 group 1 subjects revealed lymphocytic thyroiditis in 51 (42%), whereas lymphocytic thyroiditis was diagnosed in only 5 goitrous subjects (13%) in group 2. Among group 1 subjects with FNAC-proven lymphocytic thyroiditis, antithyroid peroxidase (TPO) antibodies were found in 35 (67%), while in anti-TPO antibody positive goitrous relatives of group 1, lymphocytic thyroiditis was found in 36 (78%). Eight new cases of overt hypothyroidism and 45 new cases of subclinical hypothyroidism were diagnosed among group 1 subjects. Our study suggests: (1). familial clustering of autoimmune thyroiditis; (2). if only FNAC or thyroid antibodies is used for diagnosis of autoimmune thyroiditis in children, 22%-33% of cases are likely to be missed; and (3). serum thyrotropin (TSH) should be offered to all first-degree relatives of patients with juvenile autoimmune thyroiditis.

Adolescent↗

Effect of oral magnesium supplementation on the lipid profile and blood glucose of patients with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVES: Controversial reports are available regarding the effect of magnesium (Mg) on lipid profile and glycaemic control in diabetic patients. The present study was designed on 1) compare serum Mg levels in diabetic patients with those of non-diabetic controls and 2) to assess the effect of oral Mg supplementation on lipid profile and blood glucose of these patients. METHODS: The study included 40 patients of type 2 diabetes mellitus (DM) and 54 age and sex matched non-diabetic controls. After the baseline investigations of all the subjects (n=94) including blood glucose, serum lipid and magnesium, the diabetic patients (study group) were supplemented with 600 mg of Mg oxide daily for 12 weeks. They were followed up every four weeks (for a total duration of twelve weeks) and investigated for the above parameters. RESULTS: Mean serum magnesium at baseline in the diabetic patients was significantly lower than that in controls (1.44 +/- 0.48 mg/dl Vs 2.29 +/- 0.33 mg/dl; p < 0.001). A significant fall in serum total cholesterol, LDL cholesterol and triglycerides and a rise in HDL cholesterol levels was observed 4 to 8 weeks after initiation of magnesium supplementation and continued till the end of the study i.e. 12 weeks. Fasting and post-prandial blood glucose levels did not show any significant change after twelve weeks of magnesium supplementation when compared with baseline. CONCLUSIONS: A significant hypomagnesemia was observed in diabetic patients as compared to controls and Mg supplementation resulted in a beneficial effect on the lipid profile of these patients with no significant effect on blood glucose levels.

Administration, Oral↗

Rofecoxib-beta-cyclodextrin inclusion complex for solubility enhancement.

Complex formation of rofecoxib and beta-cyclodextrin in aqueous solution and in solid state and the possibility of improving the solubility and dissolution rate of rofecoxib via complexation with cyclodextrin were investigated. Phase solubility studies indicated the formation of an 1:1 complex in solution and the value of apparent stability constant was 769 M(-1). Solid inclusion complexes of rofecoxib and cyclodextrin were prepared by the kneading method in different molar ratios. Differential scanning calorimetry studies indicated the formation of solid inclusion complexes of rofecoxib and cyclodextrin at different molar ratios and the solid complexes exhibited a higher rate of dissolution than the physical mixture and the pure drug.

Algorithms↗

Protection by live Mycobacterium habana vaccine against Mycobacterium tuberculosis H37Rv challenge in mice.

BACKGROUND & OBJECTIVES: In recent years the efficacy of BCG vaccine against tuberculosis has been questioned and there is no alternative vaccine available. Several strategies are being applied to get a satisfactory vaccine. Two approaches are generally considered: the subunit vaccines and the whole cell vaccines. The objective of this investigation was to evaluate an avirulent mycobacteria, Mycobacterium habana, as a whole cell vaccine to protect mice from infection of M. tuberculosis H37Rv. METHODS: AKR and immunocompromised SJL/J mice were immunized with live M. habana vaccine. These mice were challenged with M. tuberculosis H37Rv eight weeks later along with unimmunized control mice. Protection by M. habana vaccine was measured through several parameters, which included survival of challenged mice, dissemination of challenge strain and histopathology of lung tissues. RESULTS: M. habana vaccinated animals were healthier than the unvaccinated mice after challenge with M. tuberculosis and survived with significant increase in mean survival time. The viable count of challenge strain was at least 100-fold less in vaccinated mice than the control mice. The lung tissues in unvaccinated mice showed marked bronchopneumonia with clusters of acid fast bacilli, whereas vaccinated mice showed small areas of damage and evidence of protection subsequently. INTERPRETATION & CONCLUSION: It may be concluded from the evidence presented here that mice vaccinated with M. habana were protected from challenge with M. tuberculosis in both normal and immunocompromised states.

Animals↗

Quadriparesis in a young female suffering from rheumatoid arthritis.

Cervical spine is involved in a significant proportion of patients suffering from rheumatoid arthritis. Although cervical spine disease may often be 'benign', neurological complications are not uncommon. Patients of rheumatoid arthritis should be screened for cervical spine involvement and appropriately treated with combination of anti-rheumatic drugs. We report a case of quadriparesis secondary to subluxation and disc herniation at C4-C5 level in a young woman with rheumatoid arthritis of short duration.

Adult↗

Prevalence of initial drug resistance to M. tuberculosis in new sputum positive RNTCP patients.

There is an increased prevalence of drug resistant M. tuberculosis strains and of these, multi drug resistant organisms are of particular concern. With the implementation of Revised National Tuberculosis Control Programme (RNTCP) allover the state of Delhi, Initial drug resistance (IDR) to Isoniazid and Rifampicin assumes great importance and needs to be monitored on a regular basis. We undertook to study the IDR against the first line essential drugs i.e. Isoniazid (H), Rifampicin (R), Ethambutol (E) and Streptomycin (S) from April 1999 to March 2000 in newly diagnosed sputum positive cases of pulmonary tuberculosis attending TB clinics under RNTCP in Delhi. A total of 157 consecutive new smear positive patients attending TB clinics under RNTCP were taken into the study. All sputum samples were subjected to culture and drug sensitivity tests on LJ medium after decontamination of samples by Petroff's method. Resistance was expressed as the percentage of colonies that grow on critical concentration of the drugs. To determine the proportion of resistance, the number of colonies on the control and the number of colonies on the drug medium were determined. A total of 94.77% samples were sensitive to the four first line essential drugs and IDR to any drug was 5.22%. The resistance to Rifampicin alone was nil but the resistance to Isoniazid alone was 2.24%. Combined resistance to both Rifampicin and Isoniazid was 2.98 %. The incidence of resistance to first line drugs in tuberculosis is not very high among new sputum positive patients attending TB clinics under RNTCP.

Antitubercular Agents↗

Haem polymerase as a novel target of antimalarial action of cyproheptadine.

An antihistaminic drug, cyproheptadine (20-25mg/kg x 4 days), showed significant schizontocidal activity in the blood against a lethal multidrug-resistant (MDR) strain of Plasmodium yoelii nigeriensis (highly resistant to chloroquine, mefloquine, and quinine); the protection of mice ranged between 75 and 100%. A combination of cyproheptadine (15 mg/kg) and chloroquine improved antimalarial activity compared to treatment with either drug alone, whereas a combination of cyproheptadine with quinine or mefloquine did not improve its antimalarial activity. Chloroquine and cyproheptadine inhibited haem polymerization activity in cell-free extracts and in in vivo experiments with MDR P. yoelii, but the combination did not cause a more significant inhibition than found with either drug alone. Cyproheptadine has been shown to produce dose-dependent inhibition of haem polymerization activity both in vitro and in vivo. The mechanism of the antimalarial action of cyproheptadine and its enhanced antimalarial activity with chloroquine could be due, in part, to their inhibitory effect on haem polymerization.

Animals↗

Bacterially expressed and refolded receptor binding domain of Plasmodium falciparum EBA-175 elicits invasion inhibitory antibodies.

Malaria parasites make specific receptor-ligand interactions to invade erythrocytes. A 175 kDa Plasmodium falciparum erythrocyte binding antigen (EBA-175) binds sialic acid residues on glycophorin A during invasion of human erythrocytes. The receptor-binding domain of EBA-175 lies in a conserved, amino-terminal, cysteine-rich region, region F2 of EBA-175 (PfF2), that is homologous to the binding domains of other erythrocyte binding proteins such as Plasmodium vivax Duffy binding protein. We have developed methods to produce recombinant PfF2 in its functional form. Recombinant PfF2 was expressed in Escherichia coli, purified from inclusion bodies, renatured by oxidative refolding and purified to homogeneity by ion-exchange and gel filtration chromatography. Refolded PfF2 has been characterized using biochemical and biophysical methods and shown to be pure, homogenous and functional in that it binds human erythrocytes with specificity. Immunization with refolded PfF2 yields high titre antibodies that efficiently inhibit P. falciparum invasion of erythrocytes in vitro. Importantly, antibodies raised against PfF2 block invasion by a P. falciparum field isolate that invades erythrocytes using multiple pathways. These observations support the development of recombinant PfF2 as a vaccine candidate for P. falciparum malaria.

Animals↗