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Biomedical subjects

M Das

Publications and source records attributed to M Das.

At least 127 records · Page 7Linked to original sources

Effect of metanil yellow, orange II and their blend on hepatic xenobiotic metabolizing enzymes in rats.

The effects of Metanil yellow, Orange II and their blend on hepatic xenobiotic metabolizing enzymes were compared. Parenteral administration of Metanil yellow and Orange II to rats at a dose of 80 mg/kg body weight for 3 days caused a significant induction of ethoxyresorufin-O-deethylase (40-190%), aniline hydroxylase (27-92%), aryl hydrocarbon hydroxylase (50-62%) and aminopyrine N-demethylase (42-49%) activities. Metanil yellow and Orange II brought about a substantial increase in cytosolic quinone reductase (34-82%) and glutathione S-transferase (23-43%) activities and significant depletion of glutathione levels with a concomitant increase in lipid peroxide formation. A blend (1:1) of Metanil yellow and Orange II showed a synergistic or additive effect on these hepatic parameters, suggesting that the addition of these two prohibited dyes together in foodstuffs may give rise to more toxic effects than are produced by each dye individually.

Aminopyrine N-Demethylase↗

Characterization of integrins in cultured human renal cortical tubule epithelial cells.

We have characterized the integrins present on cultured tubule epithelial cells from human renal cortexes, enriched for proximal cells, using fluorescence microscopy, immunoprecipitation, and cell adhesion assays. By immunofluorescence, the alpha 3-integrin subunit stained most intensely and was present on all cells predominantly at cell-cell contacts. The alpha 6-subunit was present on all cells in a pattern consistent with extracellular matrix contacts. The alpha 5-subunit was present on most cells in a cell-matrix contact pattern; alpha V-subunit was weakly positive and occasionally seen in cell-matrix contacts. The alpha 2-subunit was present on clusters of distal tubule cells, predominantly at cell-cell contacts. Immunoprecipitation revealed the predominant integrin to be alpha 3 beta 1 with some alpha 2 beta 1, presumably contributed by distal cells. The alpha 5 beta 1-, alpha 6 beta 1-, alpha 6 beta 4-, and alpha V beta 3-integrins, as well as trace amounts of alpha 1 beta 1-integrins, were also present. The alpha 4 beta 1-integrin was not detected. Initial attachment to fibronectin was mediated by alpha V beta 3- and alpha 5 beta 1-integrins; initial attachment to laminin was mediated by the alpha 6 beta 1- and alpha 3 beta 1- integrins and, in some preparations, by an unidentified integrin; and initial attachment to collagen type IV was mediated by alpha V beta 3-integrin and an unidentified beta 1-integrin. After extensively immunodepleting membrane extracts with anti-alpha 1, -alpha 2, -alpha 3, -alpha 4, -alpha 5, -alpha 6, and -alpha V antibodies, an anti-beta 1 antibody still precipitated an integrin. Its electrophoretic mobility differs from the laminin-binding alpha 7 beta 1-integrin. Thus we have identified many of the integrins on cortical tubule cells and their role in mediating initial attachment to extracellular matrix. However, the cell adhesion assays and immunoprecipitations suggest the presence of an unidentified beta 1-integrin that may mediate renal tubule cell attachment to laminin and collagen.

Cell Adhesion↗

Age determination and longevity in fishes.

It is possible to determine the age of fishes with reasonable accuracy by reading the 'growth rings' (annuli) in hard parts (scale, otolith, opercular bone, vertebra and cross-section of dorsal or pectoral spine and fin rays). Primary growth increments in 'otoliths' can also be used as an alternative method of age determination. The traditional methods could be supplemented with more reliable fluorochrome and microradiographic techniques. The suitability of the use of hard parts and the techniques may vary among the species. It is essential that the 'true rings' be distinguished from other types of rings, such as false rings, larval rings and spawning rings through repeated examination of samples to avoid confusion and inaccuracy in age determination. The causes and the periodicity of ring formation may vary from species to species. The growth history of fishes could be traced by back calculation of length attained at different ages. Among the different types of growth equations, the Von Bertalanffy's model appears to be the most suitable for fishes of both temperate and tropical regions. With slight modification, the same model may also serve to estimate the maximum theoretical calculated age (longevity) of fishes. The longevity of fishes show wide variations. The life-span may be short, intermediate and long. Whereas the lowest range of life-span (1-2 years) is exhibited by some species of lampreys and teleosts, there are species of dogfishes, sturgeons, paddlefishes, rockfishes and eels which have the life-span (70-152 years) in the highest range. A number of factors (size, sex, temperature, diet, reproduction, age at maturity and genetic composition) are believed to influence the longevity of fishes.

Age Determination by Skeleton↗

Bio-metabolism of green S and indigo carmine through caecal microflora of rats.

Bio-metabolism of two permitted food colours viz., Green S and Indigo Carmine, through caecal microflora of rats was investigated. Incubation of Green S with caecal flora resulted in one coloured and two fluorescent metabolites with the corresponding Rf values of 0.83, 0.33, 0.22, respectively. Indigo carmine was metabolized by caecal microflora to four [corrected] fluorescent metabolites with Rf values of 0.09, 0.27, 0.5 and 0.72. The DI 50 value of Green S was considerably higher (456 min) as compared to that of Indigo carmine (54 min). These results suggest that Green S and Indigo carmine are biotransformed to a variety of metabolites by rat caecal microflora.

Animals↗

Effect of sanguinarine on the transport of essential nutrients in an everted gut sac model: role of Na+,K(+)-ATPase.

The effect of the argemone alkaloid, sanguinarine, was studied on the active transport of D-glucose and some of the L-amino acids in everted sacs of the small intestine of rats. Sanguinarine (1.0 mumole) was found to inhibit (61%) the transport of D-glucose, while an alkaloid concentration of 0.1 mumole was ineffective. Both 0.1 and 1.0 mumole of sanguinarine had no effect on the transport of the L-amino acids including aspartic acid, lysine, and tyrosine. Sanguinarine showed a dose dependent inhibition of intestinal and hepatic Na+,K(+)-ATPase in a non-competitive manner. The inhibition of Na+,K(+)-ATPase by sanguinarine may in turn inhibit the active transport of D-glucose which requires a sodium pump.

Alkaloids↗

Both surface proteins (VP4 and VP7) of an asymptomatic neonatal rotavirus strain (I321) have high levels of sequence identity with the homologous proteins of a serotype 10 bovine rotavirus.

The nucleotide sequence of genes 4 and 9, encoding the outer capsid proteins VP4 and VP7 of a serotype 10 tissue culture-adapted strain, I321, representative of asymptomatic neonatal rotaviruses isolated from neonates in Bangalore, India, were determined. Comparison of nucleotide and deduced amino acid sequences of I321 VP4 and VP7 with previously published sequences of various serotypes revealed that both genes were highly homologous to the respective genes of serotype 10 bovine rotavirus, B223. The VP4 of I321 represents a new human P serotype and the I321 and related strains represent the first description of neonatal rotaviruses that appear to derive both surface proteins from an animal rotavirus.

Amino Acid Sequence↗

Modulation by ascorbic acid of the cutaneous and hepatic biochemical effects induced by topically applied benzanthrone in mice.

Modulation of biochemical markers by ascorbic acid was investigated in mice to which benzanthrone (BA) was applied topically (150 nmol/mouse) twice a week for 34 wk. After BA exposure without ascorbic acid, in the skin there were significant decreases in the activities of aryl hydrocarbon hydroxylase (AHH; 38% decrease relative to controls) and ethoxyresorufin-O-deethylase (EROD; 39%), and enhancement of the activities of quinone reductase (41% increase), tyrosinase (82%) and histidine decarboxylase (HDC; 190%). BA exposure also caused significant inhibition of hepatic AHH, EROD and glutathione-S-transferase activities, with concomitant increases in the activities of histidase (52%) and HDC (58%). Ascorbic acid given orally (5 mg/mouse) or topically (1 mg/mouse) twice weekly for 34 wk to BA-treated mice resulted in substantial protection against the effects of BA on these enzyme markers in both the skin and the liver. These results suggest that ascorbic acid could be useful in preventing the biochemical and toxicological manifestations caused by BA in laboratory animals.

Administration, Topical↗

Serotypic and genotypic characterization of human serotype 10 rotaviruses from asymptomatic neonates.

Human rotaviruses were isolated from asymptomatic neonates at various hospitals and clinics in the city of Bangalore, India, and were found to be subgroup I specific and possess long RNA patterns (M. Sukumaran, K. Gowda, P. P. Maiya, T. P. Srinivas, M. S. Kumar, S. Aijaz, R. R. Reddy, L. Padilla, H. B. Greenberg, and C. D. Rao, Arch. Virol. 126:239-251, 1992). Three of these strains were adapted to tissue culture and found by serotype analysis and neutralization assays to be of serotype 10, a serotype commonly found in cattle but infrequently found in humans and not previously identified in neonates. By RNA-RNA hybridization, a high level of relatedness to a serotype 10 bovine rotavirus strain and a low-to-medium level of relatedness to a human rotavirus strain were observed. Since this human isolate shares a genogroup with bovine rotavirus, it is likely that it originated by interspecies transmission. A human rotavirus strain isolated from asymptomatic neonates and similar to bovine rotavirus might represent a good vaccine candidate.

Animals↗

Comparative study of the biodisposition of benzanthrone in different rodent species.

The bio-elimination and organ retention of [14C]benzanthrone, an anthraquinone dye intermediate, were determined in rats, mice and guinea pigs. Urinary excretion of benzanthrone during 96 hr was higher in guinea pigs (28%) compared with rats and mice (19%). However, faecal elimination during 96 hr was higher in rats (39%) and mice (42%) than in guinea pigs (25%). Urinary elimination of benzanthrone in rats and mice was highest between 12 and 24 hr, while guinea pigs showed a peak value between 24 and 48 hr. The maximum amount of radiolabelled benzanthrone was eliminated through faeces at 24-48 hr in all the three animal species. The retention of [14C]benzanthrone in the liver was comparable in rats (11.2%) and mice (11.9%), while in guinea pigs it was substantially higher (21.9%). The testes of rats and mice were devoid of radioactivity, whereas those of guinea pigs showed a marginal retention (1.25%) of 14C. The present study suggests that guinea pigs are more prone to benzanthrone toxicity than are rats and mice since the bio-elimination of this compound is slower and its organ retention is higher in this species.

Animals↗

Effect of extraneous supplementation of ascorbic acid on the bio-disposition of benzanthrone in guinea pigs.

The bio-elimination and organ retention of orally administered [14C]benzanthrone, an anthraquinone dye intermediate, were determined in control and ascorbic acid-supplemented guinea pigs. Urinary excretion of benzanthrone in control and ascorbic acid-treated animals during 96 hr was 27.9 and 30.5%, respectively, with peak elimination at 48 hr. Faecal elimination in control and supplemented animals during 96 hr was 24.5 and 38.8%, respectively, with a peak at 48 hr. The organ retention of radiolabelled benzanthrone at the end of 96 hr was of the order of 39% in control animals (gastro-intestinal tract 16%; liver 22%; testis 1.2%); ascorbic acid supplementation reduced benzanthrone retention to 19.5% (gastro-intestinal tract 12.7%; liver 6.8%). Overall, pretreatment of guinea pigs with ascorbic acid caused a 32% enhancement in the clearance of radiolabelled benzanthrone through the urine and faeces, while organ retention was reduced by about 50%. A prophylactic dose of ascorbic acid may prevent benzanthrone-induced toxic symptoms in exposed workers.

Animals↗

An out-break of epidemic dropsy in the Barabanki District of Uttar Pradesh, India: a limited trial for the scope of antioxidants in the management of symptoms.

An attempt was made to explore the scope of the bio-antioxidants in the management of symptoms of epidemic dropsy caused by argemone alkaloids, sanguinarine and dihydrosanguinarine. The study was performed on 24 randomly selected epidemic dropsy cases who consumed argemone contaminated mustard oil. On examination the cases revealed characteristic pitting edema over limbs (95.8%) accompanied by tenderness (79.2%) and diffuse erythema (95.8%). Tachycardia was present in 1/3 of the examined cases while elevated jugular venous pressure was seen in over 40% of the cases. In two of the cases, reddish-purplish blotches over lower limbs, not raised and which blanched on pressure, was an unusual feature. Chest X-ray revealed pulmonary congestion in 5 cases. ECG performed in 3 cases with severe breathlessness, showed non-specific ST-T changes most marked in L2,L3, avF and V2-V6 which reversed on recovery. Treatment with a combination of antioxidants, riboflavin and tocopherol showed improvement in pain in lower limbs (75%), edema (83.3%) and erythema (66.6%).

Adolescent↗

A dose-finding study with remoxipride in the acute treatment of schizophrenic patients.

Two hundred and forty-two patients with acute schizophrenia were enrolled in a double-blind, comparative, dose-finding study of a novel antipsychotic, remoxipride. Remoxipride was evaluated in a low (30 to 90 mg), medium (120 to 240 mg) and a high (300 to 600 mg) dose range and compared with a haloperidol (15 to 45 mg), which was administered to a similar group of patients. The results support the antipsychotic effect of remoxipride, with maximum efficacy occurring at daily doses between 120 mg and 600 mg. Side-effects were more frequent at doses of remoxipride over 300 mg. In all groups, remoxipride caused consistently fewer extrapyramidal side-effects than haloperidol. The antipsychotic effect of remoxipride may be derived from specific blockade of dopamine D2 receptors in the mesolimbic tract. The findings also suggest that remoxipride may have a therapeutic effect on negative symptoms of schizophrenia.

Dose-Response Relationship, Drug↗

Effect of age on second messenger generation in neutrophils.

Neutrophils from healthy elderly donors generate significantly less diacylglycerol (DAG) and inositol triphosphate (IP3) than neutrophils from young donors, following stimulation by the chemotactic peptide, formyl-methionyl-leucylphenylalanine (FMLP). The defect in signal transduction occurred at a point proximal to the generation of IP3 and DAG, since the reduction in FMLP-induced superoxide generation was corrected if the intervening signal transduction steps were bypassed, either by priming with a substimulatory dose (1.62 nmol/L) of phorbol myristate acetate (PMA), by ionophore elevation of cytosolic calcium, or by using a stimulatory dose of PMA (1.62 mumol/L). FMLP receptor number and affinity were unaffected by aging. On FMLP activation, neutrophils from old, as compared with young, volunteers showed significantly greater and more long-lasting decreases in the concentrations of phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-bisphosphate (PIP2). This indicates a reduction with age in the metabolically active precursor pools responsible for the generation of IP3 and DAG. In contrast, aging had little effect on the production of phosphatidic acid (PA), which has recently been suggested to serve as a major activator of the NADPH oxidase. This may explain why the decrease in IP3 and DAG production was not accompanied by a comparable decrement in superoxide generation, which was only 17% lower in the old than in young donor neutrophils. Thus, aging is associated with reductions in the concentration of critically important phosphoinositides, resulting in diminution in the ability to produce key second messengers. Although the aged neutrophil is largely able to compensate for the decrements in signal transduction, its reserve capacity is compromised, making it particularly vulnerable to external insults that also impair function.

Adolescent↗

Bio-elimination and organ retention profile of benzanthrone in scorbutic and non-scorbutic guinea pigs.

The retention and bio-elimination of benzanthrone (BA) in scorbutic and non-scorbutic guinea pigs was investigated to understand the protective role of ascorbic acid. Oral intubation of 14C-BA to scorbutic and non-scorbutic guinea pigs showed a total recovery of around 91% radioactivity through urine, faeces and tissues. Recovery of radiolabelled BA through urine (28%) and faeces (22%) up to 96 hrs averaged 50%, whereas residual radioactivity in liver and testis experienced a recovery of 29% in scorbutic animals. In non-scorbutic animals there was an increased recovery of radioactivity through urine (37%) and faeces (31%) with a decrease in retention (10%) in liver and testis. These results suggest that ascorbic acid facilitates the mobilization and bio-elimination of BA and thereby can decrease the toxicity of the compound.

Animals↗

Thyroid hormone decreases the expression of epidermal growth factor receptor.

The receptors for epidermal growth factor (EGF) and thyroid hormone (T3) are prototypes, respectively, of transmembrane signaling proteins and nuclear transcription regulatory proteins. Oncogenic homologs of these two receptor genes, v-erbB and v-erbA, cooperate with each other in cellular transformation and blockage of erythrocytic differentiation. As a first step toward investigating this cooperation, we have studied the relationship between the normal homologs of these two receptors in A431 cells. Treatment of these cells with T3 has no significant effect on EGF receptor gene transcription but leads to a drastic decrease in the steady-state level of receptor mRNA. The down-regulatory effect is visible by 2 h and persists up to 8 h, but EGF receptor mRNA returns to normal (sometimes higher than normal) level by 48-72 h. The T3-induced decrease in EGF receptor mRNA (found during 2-8 h of T3 treatment) is due to a specific destabilization of EGF receptor mRNA. The 5.6-kb mRNA that encodes the full-length transmembrane EGF receptor is preferentially degraded. The half-life of the 2.6-kb mRNA that encodes the aberrant C-terminally truncated receptor is unaffected by T3. In other studies we found that T3 decreases the rate of synthesis of the full-length EGF receptor protein and reduces its steady-state amount. Overall the results demonstrate a negative regulatory effect of T3 in post-transcriptional control of EGF receptor expression, and raise interesting questions regarding the mechanism of this down-regulation, and the possible roles of T3 receptors in the control of EGF receptor function.

Blotting, Northern↗