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Biomedical subjects

A K Sinha

Publications and source records attributed to A K Sinha.

At least 19 recordsLinked to original sources

Methotrexate used in combination with aminolaevulinic acid for photodynamic killing of prostate cancer cells.

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA) to drive production of an intracellular photosensitiser, protoporphyrin IX (PpIX), is a promising cancer treatment. However, ALA-PDT is still suboptimal for thick or refractory tumours. Searching for new approaches, we tested a known inducer of cellular differentiation, methotrexate (MTX), in combination with ALA-PDT in LNCaP cells. Methotrexate alone promoted growth arrest, differentiation, and apoptosis. Methotrexate pretreatment (1 mg l(-1), 72 h) followed by ALA (0.3 mM, 4 h) resulted in a three-fold increase in intracellular PpIX, by biochemical and confocal analyses. After exposure to 512 nm light, killing was significantly enhanced in MTX-preconditioned cells. The reverse order of treatments, ALA-PDT followed by MTX, yielded no enhancement. Methotrexate caused a similar relative increase in PpIX, whether cells were incubated with ALA, methyl-ALA, or hexyl-ALA, arguing against a major effect upon ALA transport. Searching for an effect among porphyrin synthetic enzymes, we found that coproporphyrinogen oxidase (CPO) was increased three-fold by MTX at the mRNA and protein levels. Transfection of LNCaP cells with a CPO-expressing vector stimulated the accumulation of PpIX. Our data suggest that MTX, when used to modulate intracellular production of endogenous PpIX, may provide a new combination PDT approach for certain cancers.

Aminolevulinic Acid↗

Impact of volume guarantee ventilation on arterial carbon dioxide tension in newborn infants: a randomised controlled trial.

OBJECTIVE: To compare the effects of the two modes of ventilation, synchronous intermittent positive pressure ventilation (SIPPV) and SIPPV with Volume Guarantee (VG), on arterial carbon dioxide tension (PaCO(2)) immediately after neonatal unit admission. STUDY DESIGN: Randomised study of ventilation mode for premature inborn infants admitted to two tertiary neonatal units. After admission, infants were randomised to receive either SIPPV or VG using a Dräger Babylog 8000 plus ventilator. In the SIPPV group, peak airway pressure was set clinically. In the VG group, desired tidal volume was set at 4 ml/kg, with the ventilator adjusting peak inspiratory pressure to deliver this volume. The study was completed once the first arterial PaCO(2) was available, with the desirable range defined as 5-7 kPa. RESULTS: PaCO(2) was significantly higher in the VG group (VG: 5.7 kPa, SIPPV: 4.9 kPa; p=0.03). The VG group had fewer out-of-range PaCO(2) values (VG: 42%, SIPPV: 57%) and fewer instances of hypocarbia <5 kPa (VG: 32%, SIPPV: 57%) but neither difference achieved statistical significance. Regression analysis showed PaCO(2) was negatively correlated with gestation (r=-0.41, p=0.01) and also with the mode of ventilation (r=0.32, p<0.05). In the VG group, all infants 23-25 weeks' gestation had out-of-range PaCO(2) values. VG significantly reduced the incidence of out-of-range PaCO(2) and hypocarbia in infants over 25 weeks' gestation (VG: 27%, SIPPV: 61%; p<0.05). CONCLUSION: Using this strategy, VG appears feasible in the initial stabilisation of infants over 25 weeks' gestation, with a halving of the incidence of hypocarbia. In the small number of babies studied below this gestation, VG was not found to be effective.

Arteries↗

Aflatoxin B(1) contamination of parboiled rice samples collected from different states of India: A multi-centre study.

Under a multi-centre study conducted by the Indian Council of Medical Research, 1,511 samples of parboiled rice were collected from rural and urban areas of 11 states representing different geographical regions of India. These samples were analysed for contamination with aflatoxin B(1.) The presence of aflatoxin B(1) at levels=5 microg g(-1) was found in 38.5% of the total number of samples of the parboiled rice. About 17% of the total samples showed the presence of aflatoxin B(1) above the Indian regulatory limit of 30 microg kg(-1). No statistically significant difference in percentage of samples contaminated with >30 microg kg(-1) was observed between pooled rural (19.4%) and urban (14.5%) data. A median value of 15 microg kg(-1) of aflatoxin B(1) was observed in samples from Assam, Bihar and Tripura. In all other states surveyed the median value was <5 microg?kg(-1).

Aflatoxin B1↗

Restoration by aspirin of impaired plasma maspin level in human breast cancer.

Maspin, an anti breast cancer protein, is produced in the normal mammary cells but not in malignant cells in breast cancer. We investigated the effect of aspirin induced increase of plasma nitric oxide (NO) on plasma maspin production in breast cancer patients. Fifteen breast cancer patients (35-65 years), who had not yet undergone any cancer therapy, and an equal number of age matched normal female volunteers participated in the study. They were asked not to take any medication for two weeks. All participants then ingested 150 mg of aspirin. Plasma NO and maspin levels were determined before and at 60 min after the ingestion of aspirin. It was found that the maspin level in plasma increased to 4.63+/-0.02 nM from the basal 0.95+/-0.012 nM (p<0.001) with increase of plasma NO from 0.60+/-0.03 microM to 2.08+/-0.030 microM (p<0.001) in breast cancer patients. In normal volunteers the basal maspin increased from 4.76+/-0.041 to 9.36+/-0.036 nM (p<0.001) with increase of NO from 2.15+/-0.08 to 3.36+/-0.04 microM (p<0.001) at the same period. These results indicated that the ingestion of aspirin might be beneficial for breast cancer through increased maspin production.

Aged↗

Blood flow in the common carotid artery in term and preterm infants: reproducibility and relation to cardiac output.

AIM: To assess the reproducibility of, and determine normative data for, flow volume measurements from the right common carotid artery (CCA) and its relation to left ventricular output (LVO) in stable term and preterm babies using Doppler ultrasound. METHODS: Right CCA flow volume was measured using a near focus, high frequency transducer by obtaining intensity weighted mean velocity and right CCA diameter. LVO was determined using standard Doppler techniques. Reproducibility studies were performed on 30 newborn infants by two observers. Normative data were obtained from 40 spontaneously breathing preterm babies and 21 term babies. RESULTS: The intraobserver coefficient of variation for CCA flow measurements was 10.5% for observer 1 and 15.4% for observer 2, whereas the interobserver coefficient of variation was 16.4%. In term and preterm infants, right CCA flow was about 20 ml/kg/min, accounting for 11% of cardiac output. Among the preterm infants, there was a positive correlation of right CCA flow with gestation (r = 0.61, p<0.001), weight (r = 0.64, p<0.001), and LVO (r = 0.59, p<0.001). Right CCA diameter also increased with weight (r = 0.63, p<0.001) and gestation (r = 0.58, p<0.001). The proportion of LVO distributed to the right CCA did not increase with gestation, nor did the right CCA flow per kg body weight. CONCLUSIONS: It is possible to perform reproducible measurements of flow volume in the CCA of newborn infants. In stable, spontaneously breathing babies, both cardiac output and carotid flow increased with gestation and body weight. The proportion of cardiac output distributed to the right CCA remained relatively constant across gestation.

Birth Weight↗

Aflatoxin B1 contamination in wheat grain samples collected from different geographical regions of India: A multicenter study.

In a multicenter study conducted by the Indian Council of Medical Research, 1,646 samples of wheat grain collected from rural and urban areas of 10 states representing different geographical regions of India were analyzed for aflatoxin B1 (AFB1). AFB1 concentrations of > or = 5 microg kg(-1) were recorded in 40.3% of the samples, and concentrations above the Indian permissible regulatory limit of 30 microg kg(-1) were found in 16% of the samples. The proportion of samples with AFB1 concentrations above the Indian regulatory limit ranged from 1.7 to 55.8% in different states, with the minimum in Haryana and the maximum in Orissa. The variation in wheat contamination among states seems to be mainly the result of unsatisfactory storage conditions. Median AFB1 concentrations of 11, 18, and 32 microg kg(-1) were observed in samples from Uttar Pradesh, Assam, and Orissa, respectively; concentrations in other states were <5 microg kg(-1). The maximum AFB1 concentration of 606 microg kg(-1) was observed in a sample from the state of Uttar Pradesh. The calculated probable daily intakes of AFB1 through consumption of contaminated wheat for the population in some states were much higher than the suggested provisional maximum tolerable daily intake. Human health hazards associated with such AFB1 exposure over time cannot be ruled out.

Aflatoxin B1↗

Management of mine spoil for crop productivity with lignite fly ash and biological amendments.

Long-term field trials using lignite fly ash (LFA) were carried out in rice crops during the period 1996-2000 at Mine I, Neyveli Lignite Corporation, Tamil Nadu. LFA, being alkaline and endowed with an excellent pozzolanic nature, silt loam texture, and plant nutrients, has the potential to improve the texture, fertility, and crop productivity of mine spoil. The rice crops were the first, third, fifth, and sixth crops in rotation. The other crops, such as green gram (second) and sun hemp (fourth), were grown as green manure. For experimental trials, LFA was applied at various dosages (0, 5, 10, 20, 50, 100, and 200 t/ha), with and without press mud (10 t/ha), before cultivation of the first crop. Repeat applications of LFA were made at the same dosages in treatments of up to 50 t/ha (with and without press mud) before cultivation of the third and fifth crops. Press mud, a lightweight organic waste product from the sugar industry, was used as an organic amendment and source of plant nutrients. Also, a recommended dosage of chemical fertilizer, along with gypsum, humic acid, and biofertilizer as supplementing agents, was applied in all the treatments, including control. With one-time and repeat applications of LFA, from 5 to 20 t/ha (with and without press mud), the crop yield (grain and straw) increased significantly (p < 0.05), in the range from 3.0 to 42.0% over the corresponding control. The maximum yield was obtained with repeat applications of 20 t/ha of LFA with press mud in the third crop. The press mud enhanced the yield in the range of 1.5-10.2% with various dosages of LFA. The optimum dosage of LFA was 20 t/ha for both one-time and repeat applications. Repeat applications of LFA at lower dosages of up to 20 t/ha were more effective in increasing the yield than the corresponding one-time applications of up to 20 t/ha and repeat applications at 50 t/ha. One-time and repeat applications of LFA of up to 20 t/ha (with and without press mud), apart from increasing the yield, evinced improvement in the texture and fertility of mine spoil and the nutrient content of crop produce. Furthermore, some increase in the content of trace and heavy metals and the level of gamma-emitters in the mine spoil and crop produce was observed, but well within the permissible limits. The residual effect of LFA on succeeding crops was also encouraging in terms of eco-friendliness. Beyond 20 t/ha of LFA, the crop yield decreased significantly (p < 0.05), as a result of the formation of hardpan in the mine spoil and possibly the higher concentration of soluble salts in the LFA. However, the adverse effects of soluble salts were annulled progressively during the cultivation of succeeding crops. A plausible mechanism for the improved fertility of mine spoil and the carryover or uptake of toxic trace and heavy metals and gamma-emitters in mine spoil and crop produce is also discussed.

Agriculture↗

Heparin for prolonging peripheral intravenous catheter use in neonates.

BACKGROUND: Peripheral intravenous (PIV) catheters are widely used in modern medical practice. However, mechanical or infectious complications often necessitate their removal and/or replacement. Heparin has been shown to be effective in prolonging the patency of peripheral arterial catheters and central venous catheters, but may result in life threatening complications, especially in preterm neonates. OBJECTIVES: The primary objective was to determine the effectiveness of heparin versus placebo or no treatment on duration of PIV catheter patency, defined as number of hours of catheter use. The secondary objectives were to assess the effects of heparin on catheter blockage, phlebitis or thrombophlebitis, catheter related sepsis, and complications including abnormality of coagulation profile, allergic reactions to heparin, heparin induced thrombocytopenia, intraventricular/intracranial hemorrhage and mortality. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966-February 2005), EMBASE (1980-February 2005), CINAHL (1982-February 2005), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2004). No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized trials of heparin administered as flush or infusion versus placebo or no treatment were included. Studies which included a neonatal population and reported on at least one of the outcomes were included. DATA COLLECTION AND ANALYSIS: The methodological quality of the studies was assessed using criteria for blinding of randomization, blinding of intervention, completeness of follow-up and blinding of outcome assessment. Data on relevant outcomes were extracted and the effect size was estimated by calculating WMD (weighted mean difference, 95%CI), RR (relative risk, 95% CI) and RD (risk difference, 95% CI). MAIN RESULTS: Ten eligible studies were identified. Heparin was administered either as a flush solution, or as an additive to the total parenteral nutrition solution. Five studies reported data on the duration of use of the first catheter. Two of these studies found no statistically significant effect of heparin; two studies showed a statistically significant increase and one study showed a statistically significant decrease in the duration of PIV catheter use in the heparin group. The results were not combined for meta-analysis due to significant heterogeneity of the treatment effect (p < 0.01). In addition, there were marked differences between the studies in terms of the methodological quality, the dose, the timing, the route of administration of heparin and the outcomes reported. From a limited number of studies, there were no significant differences between the heparin and the placebo/no treatment groups in the risks of infiltration, phlebitis and intracranial hemorrhage. AUTHORS' CONCLUSIONS IMPLICATIONS FOR PRACTICE: The effect of heparin on the duration of peripheral intravenous catheter use varied across the studies. Because of clinical heterogeneity and heterogeneity in treatment effect, recommendations for heparin use in neonates with PIV catheters cannot be made. IMPLICATIONS FOR RESEARCH: There are insufficient data concerning the effect of heparin for prolonging PIV catheter use in neonates. Further research on the effectiveness, the optimal dose, and the safety of heparin is required.

Anticoagulants↗

Cytokine release induced by killed bacteria associated with anti-IFN-gamma antibody in Shigella infection.

An effort was made to analyze the effect of in vitro stimulation on macrophages using killed Shigella dysenteriae type-1 (KSD1) coupled with anti-Interferon Gamma (anti-IFN-gamma) antibody. The stimulated macrophages were co-cultured with primed or non-primed T-cells from Shigella infected patients. T-cell cultures were also established by co-culturing KSD1 coupled with or without PHA stimulated macrophages. Emulsified KSD1 coupled with anti-IFN-gamma antibody was found to act as a potent immunogen, inducing the release of Th1 cytokine from primed T-cells cultured in acute stage of the disease. It was observed that the levels of IFN-gamma and IL-2 production rather than IL-4 and IL-6 were increased as the disease became more severe. On comparison, the subsequent values of IL-6, IFN-gamma, IL-4 and IL-2 were found to be less significant in healthy primed T-cell cultures. This was also associated with a substantial production of superoxide ions (O2-), which probably inhibits the colonization of intracellular Shigella due to the presence of anti-IFN-gamma antibodies. On the other hand KSD1 with or without PHA failed to induce such responses. The above findings reflect that in the presence of anti-IFN-gamma antibody, KSD1 acts as a potential immunogen for eliciting cellular immunity against shigellosis.

Coculture Techniques↗

Three-dimensional mesoporous titanosilicates prepared by modified sol-gel method: Ideal gold catalyst supports for enhanced propene epoxidation.

Mesoporous titanosilicates with 1-12 mol % Ti content and with three-dimensional wormhole-like mesoporosity are prepared by a modified sol-gel technique. Sorption analysis shows that there is little change in the surface properties with increasing Ti concentration in the samples, implying that Ti atoms either are well-dispersed on the walls of the silica matrix or are present inside the framework with no pore blocking effect. Spectroscopic analysis shows that the Ti atoms are atomically dispersed in the silica matrix even at very high Ti concentration and there is no observable Ti aggregate (anatase) present in the samples. These titanosilicate samples after Au deposition followed by trimethylsilylation (for enhanced hydrophobicity) are highly efficient catalysts for vapor-phase propene epoxidation using O2 and H2. It was possible to achieve commercially desirable performance with about 7% propene conversion, >90% propene oxide selectivity, and about 40% hydrogen efficiency.

Journal Article↗

Synthesis of CdS nanoparticles in colloidal state and its possible interaction with tyrosine.

The basic objective is to develop a simpler method of preparation of the colloidal CdS nanoparticles with greater stability and to study interaction with tyrosine molecules. Average size of the particles in the colloid is found to be about 3 nm as probed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements. Effect of both sulfide enriched CdS as well as Cd(2+) enriched CdS on tyrosine is investigated both through absorbance and emission spectroscopy. Quenching of tyrosine emission followed Stern-Volmer relation and was found to be independent of temperature, indicating possible static quenching. However, Forster transfer between tyrosine and CdS can be suspected to mimic static quenching in addition to the charge transfer complexes. In the presence of Cd(2+) enriched CdS nanoparticles, the emission of tyrosine in phosphate buffer shows typical spectral broadening and a long wavelength increase in fluorescence emission. This may be attributed to the sensitized emission of CdS itself.

Cadmium Compounds↗

Phosphotidylinositol-3 kinase-mediated signals in mice immunized with the 57 kDa major antigenic outer-membrane protein of Shigella dysenteriae type 1.

Antigen-specific T-cell signalling via T-cell antigen receptor stimulation was carried out in BALB/c mice immunized with the 57 kDa major antigenic component of Shigella dysenteriae 1 outer-membrane proteins. In presence of anti-CD3, the 57 kDa antigen was found to increase the level of IL-2 significantly instead of IL-4. IL-2 production in T cells was consistent with an increase in intracellular free Ca(2+) [(Ca(2+))i] concentration. The antigen-specific modulation was observed during T-cell signalling, with enhanced release of [(Ca(2+))i]. IL-2-receptor stimulation via IL-2 did not significantly induce the release of IL-2 with consistent intracellular Ca(2+) production. Furthermore, the protein tyrosine kinase was activated during anti-CD3 stimulation, which up-regulated the phosphatidylinositol kinase of p85-mediated serine kinase protein kinase-C of p70. Phosphoinositide-specific kinases are regulated by the phosphorylation of tyrosine kinase through the activation of the T-cell antigen receptor. The above findings indicate that phosphotidylinositol-3 kinase-mediated signals are up-regulated through [(Ca(2+))i], which is essential for Th1-type responses.

Animals↗

Detection of thyroid malignancy in a hot nodule by fluorine-18-fluorodeoxyglucose positron emission tomography.

Carcinoma of the thyroid arising in an autonomously functioning or "hot" nodule is uncommon. The majority of thyroid carcinomas present as a "cold" nodule on radionuclide scintigraphy. We report a poorly-differentiated thyroid carcinoma developing in a long-standing "hot" nodule in a 51-year-old Chinese woman. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG PET) showed focal FDG uptake in the thyroid nodule, as well as in the cervical and pulmonary hilar lymph nodes. This case illustrates that the incidence of thyroid carcinoma in a "hot" nodule is not negligible. The role of FDG PET in the differentiation of benign from malignant thyroid nodules is still unclear. In contrast, FDG PET has been shown to have a role in the follow-up of thyroid cancer patients after thyroidectomy and subsequent radioactive iodine-131 (I-131) ablation. It may be useful in the identification and localisation of recurrent cancer foci in patients with elevated thyroglobulin levels but a negative I-131 whole body scan.

Carcinoma↗

Impaired binding of insulin to erythrocyte membrane receptor and the activation of nitric oxide synthase by the hormone in human breast cancer.

PURPOSE: Nitric oxide, a messenger molecule has been reported as having various antineoplastic properties. The activation of insulin-activated nitric oxide synthase (IANOS) was found to be related to the production of NO as a result of the binding of insulin to its receptor through the activation of tyrosine kinase in erythrocyte membrane. As nitric oxide is reported to be a systemic anticancer agent, studies were carried out to determine the role of insulin receptor binding that lead to the activation of tyrosine kinase and IANOS in erythrocytes in breast cancer. METHODS: Blood samples were collected from female breast cancer patients who, at the time of participation in the study, had not undergone any therapeutic intervention but had opted for surgery. The binding of insulin to its receptor in erythrocyte membrane and the activation of both receptor tyrosine kinase and IANOS due to the hormone binding were determined and compared with the appropriate control. RESULTS: It was found that the impaired NO synthesis in erythrocyte membrane in breast cancer was related to the marked decrease of insulin binding sites of the high-affinity hormone receptor population. This impaired insulin binding to high-affinity receptors resulted in the impairment of both reaction velocity (Vmax) of the IANOS and receptor tyrosine kinase activation. CONCLUSION: These results indicated that the impairment of interaction between insulin and its high-affinity receptors in erythrocyte membrane might be a critical pathophysiological event in the development of breast cancer.

Adult↗

Resurgence of natural colourants: a holistic view.

Today, natural colourants are emerging globally, leaving synthetic colourants behind in the race, due to the realisation that are safer and ecofriendly in nature. In this context, a brief review of natural colourant sources, their classification, chemical constituents responsible for producing different colours, its activities and effect of different mordants on the hue is discussed.

Animals↗

Ultrasound-assisted conversion of toxic beta-asarone into nontoxic bioactive phenylpropanoid: isoacoramone, a metabolite of Piper marginatum and Acorus tararinowii.

Ultrasound-assisted synthesis of bioactive isoacoramone (1), a metabolite of Piper marginatum and Acorus tararinowii, has been achieved by oxidation of toxic beta-asarone (2) with potassium permanganate/copper sulphate/alumina into asaronaldehyde (3) followed by treatment with ethylmagnesium iodide to provide 1-(2,4,5-trimethoxy)phenyl-1-propanol (4) which upon further oxidation with potassium permanganate/copper sulphate afforded 1 in 64% yield (overall 32%). Toxicological evaluation of 1 reveals it to be nontoxic up to 60 mg/kg b.w.

Acorus↗

Role of anti-CD3 in modulation of Th1-type immune response in Shigella dysenteriae infection.

A murine model was used to evaluate the role of anti-CD3 in modulating a Th1-type response by restimulation of T-cells after immunization with the 57 kDa immunodominant antigen of Shigella dysenteriae 1 outer-membrane proteins (OMPs), followed by Shigella infection after immunization. To observe the effect of anti-CD3, other T-cell cultures were also established following anti-CD1, anti-IL2 and phytohaemagglutinin stimulation. Anti-CD3 stimulation of reconstituted T-cells showed 'mean' levels of CD4 and CD25 were enhanced by 34.5 and 31.1 % in immunized mice, which was comparable to 53.2 and 50.7 %, respectively, in challenged-immunized mice, and were dominant over CD8+ T-cells. Levels of IL2 generated by anti-CD3-stimulated T-cells of immunized mice were greater than those of unstimulated T-cells and were significantly elevated in challenged-immunized mice. The reactivity of T-cells indicated their complete responsiveness, as anti-CD3 antibody might not inhibit the migration of the macrophages but rather inhibit IL4. These macrophage factors synergistically act with anions towards an activated response, which in turn provokes IL2 secretion with a low degree of internalization of its receptor. Thus, sharing of IL2 to form a high-affinity receptor complex with CD4+ T-cells through motive signals suggested a generalized T-cell activation with increased humoral responses. Macrophage migration inhibition factor (MIF) and IL4 responses during anti-CD3 stimulation of immunized mice indicated that the role of anti-CD3 in generation of O2- is due to a synergistic effect by Th1 subsets of Th0 cells. The above findings should have implications for understanding the immunoregulatory role of anti-CD3 associated with 57 kDa antigen in immunoprophylactic measures.

Animals↗