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Biomedical subjects

R Shanker

Publications and source records attributed to R Shanker.

At least 55 records · Page 3Linked to original sources
PubMed1989

Influence of thyroid hormone on myosin heavy chain mRNA and other messenger RNAs in the rat heart.

The level of myosin heavy chain (MHC) alpha mRNA and of MHC-beta mRNA was quantitated in the rat heart using a specific cDNA probe. In hypothyroid and diabetic hearts MHC-beta mRNA predominates, whereas in normal hearts MHC-alpha mRNA represents 80% of all MHC mRNA. Administration of 0.2 mg T3/100 g body wt. to hypothyroid rats led to an increase in MHC-alpha mRNA beginning at 3 h after injection and continued to rise until at 24 h control level of MHC-alpha mRNA were reached. In contrast, after administration of 2 units regular insulin to diabetic rats, MHC-alpha mRNA levels showed a small but significant increase already 30 min after insulin administration reaching a peak at 3 h and returning to diabetic values 5 h after insulin. The T3 response of other cardiac mRNAs was quantitated using in vitro translation, separation of 35S methionine labeled translational products and their quantitation by digital matrix photometry. An mRNA (spot 72b) coding for a translational product with a Mr 81,000 and pI of 5.4 showed a 3-fold increase in its level 1 h after T3 administration. In view of the rapid response of spot 72b and the early response of MHC-alpha mRNA to insulin, it is currently unclear if the T3 response of MHC-alpha mRNA represents a primary effect of T3.

Animals↗
PubMed1989

Dermal exposure to kerosene.

Young healthy albino male mice were subjected to repeated exposure to kerosene by wrapping each of their hind feet with a muslin cloth (1 x 10 cm) wetted with kerosene (0.1 ml). Exposure varied from 15 to 60 min/day for 7 consecutive days. Repeated exposure to kerosene produced histologic changes in the foot pad skin and popliteal lymph nodes of mice and systemic toxic manifestations such as variation in hematologic profile, significant decreases in relative weight of thymus, spleen and abdominal lymph nodes and altered histology. Three weeks of non-exposure rest indicated the reversible nature of kerosene-induced toxicity. Furthermore, observations made in 24 human subjects chronically exposed to kerosene in an automobile workshop revealed high incidence of oil acne and dermatitis of varying degrees. The study demonstrates a need for caution where ever prolonged dermal exposure to kerosene in occupational situations obtains.

Adult↗
PubMed1988

Relative toxicity of metabolites of benzene in mice.

Repeated ip administration of hydroquinone (10 mg/kg/day), benzoquinone (2 mg/kg/day) or benzenetriol (6.25 mg/kg/day) to rats for 6 weeks produced significant decreases in RBC and bone marrow cell counts and hemoglobin content, together with relative changes in organ weights. In addition, benzoquinone and benzenetriol elicited histological injuries in liver, thymus, spleen, kidney and peripheral lymph nodes which warrant further investigation.

Animals↗
PubMed1987

Neutron activation analysis of respirable mica samples and their pathological effects in lungs of rats.

Instrumental and radiochemical neutron activation analyses (INAA, RNAA) have been used to quantify the different elements present in mica samples derived from Indian mines and a factory, together with USGS standards using high-resolution gamma-ray spectrometry. Both samples revealed the presence of several toxic elements in appreciable quantities. When tested in a rat model system over a period of 360 days after intratracheal injection of mica samples of respirable size (50 mg/animal), the animals which received the factory sample containing shellac exhibited enhanced dust-induced pulmonary reaction together with characteristic abscess formation at later periods. The significance of these findings is discussed.

Aluminum Silicates↗
PubMed1987

2,5-Hexanedione-induced immunomodulatory effect in mice.

The immunotoxic potential of 2,5-hexanedione (2,5-Hxdn), the end metabolite of n-hexane/methyl n-butyl ketone, was evaluated in a mouse model involving multiple pathomorphological, hematological, and immunological assays. Young adult male Swiss albino mice were given either single or seven consecutive oral doses of 0.2 X LD50 of 2.5-Hxdn. None of the treated mice exhibited any sign of hind limb weakness up to 1 week. On the eighth day, half the animals were sacrificed for initial pathomorphological studies of various organs and the other half were subjected to several immune function tests. The results revealed treatment-related reduction in cellularity of spleen, thymus, and mesentric lymph nodes and pathotoxicological changes. Further, immune function tests such as delayed-type hypersensitivity reaction, plaque-forming cell assay, phagocytosis by adherent peritoneal exudate cells, and resistance to endotoxin shock were considerably impaired. These results suggest that 2,5-Hxdn treatment causes profound impairment of immunity in mice even before the onset of peripheral neuropathy.

Animals↗
PubMed1987

Time course of response of individual messenger RNAs in the rat heart to T3.

The time course of response of specific mRNAs following administration of triiodothyronine (T3) to hypothyroid rats was examined. We were particularly interested in identifying mRNAs showing a rapid response. Hypothyroid rats were injected with 0.2 mg of T3/100 g body wt and total cardiac RNA was prepared 0.5, 1, 2, 3, 5, 12 and 24 h later. RNA was translated in vitro in the presence of [35S]-methionine, the labeled peptides separated by two-dimensional electrophoresis and quantitated by digital matrix photometry. Of a total of 427 translational products 13 were identified to be selectively responsive to thyroid hormone. A specific mRNA coding for a protein designated as spot 72b (Mr 81,600, pI 5.34) was observed to show the most rapid response to T3. Administration of T3 to the hypothyroid animal resulted in an increase in the level of spot 72b by 2.6-fold within 1 h. The lag time between injection of T3 and response of other specific mRNA species varied between 5 to 24 h. These results demonstrate the diversity of response of individual cardiac mRNAs. The specific T3 responsive mRNA species described in the heart have not been demonstrated in other tissues indicating that induction of distinctive mRNA species is highly tissue specific. Relatively late responses may represent indirect effects of T3 mediated by interaction with other hormonal or metabolic signals. The rapid induction of spot 72b suggests it may result from the interaction of T3 with the nuclear receptor leading to a direct effect on the expression of this gene in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Safety evaluation of a barrier cream.

A barrier cream containing propylene glycol, silica, xylene, dioctyl adipate and amyl acetate was applied topically for 3 months in 3 species of animal. Patch tests were carried out in human volunteers up to 72 h. The cream produced slight erythema in rats, guinea pigs and rabbits, but the irritation indices remained within safe limits. Histologically, mild focal thickening and moderate thickening of stratum corneum were observed in rats and guinea pigs, respectively, after 3 months of daily application. Patch testing in human volunteers indicated that the barrier cream is reasonably safe for human use.

Adipates↗
PubMed1986

Modulation of benzene toxicity by an interferon inducer (6MFA).

Repeated intraperitoneal administration of benzene (1.0 ml/kg body wt) for 3 days produced leucopenia, lymphocytopenia and an increased number of nucleated cells in the bone marrow and significantly decreased organ weights of thymus (P less than 0.001) and spleen (P less than 0.001) in female albino rats. Iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly increased as a result of benzene exposure. Prior administration of 6MFA, an interferon inducer with immunomodulating potential, was found to ameliorate some of the adverse effects of benzene as well as restoration of hepatic architecture histologically. Lipid peroxidation and iron content were both normalised, whereas superoxide dismutase activity was further increased and the number of lymphocytes and bone marrow cells returned to normal. Pretreatment of animals with 6MFA was able to enhance the SRBC antibody titre in benzene-treated immunosuppressed animals. The beneficial effects of 6MFA in the amelioration of the acute toxicity of benzene therefore assume certain significance.

Animals↗
PubMed1986

Effect of 2,5-hexanedione on lymphoid organs of rats: a preliminary report.

Preliminary studies related to immunotoxicologic effects of 2,5-hexanedione, the final major metabolite of n-hexane/MnBk, were carried out in rats following single or repeated exposures. Female albino rats were given either single or seven consecutive oral doses of 0.1, 0.2, or 0.5 X LD50 of 2,5-hexanedione, and a time-related kinetic study was performed using hematology, histology, cellularity, and organ weight/body weight as major parameters. Following single exposure of 2,5-hexanedione to rats, a dose-dependent thymic atrophy was evident at the end of 7 days. The atrophy was reversible when the animals were given 7 days nonexposure rest. In contrast, there was no thymic atrophy when the animals were exposed for 7 consecutive days. Significant decline in the cellular populations of various lymphoid organs was also observed in rats exposed either to single or repeated doses of 2,5-hexanedione. Results obtained in the present study indicate that 2,5-hexanedione, a known potent neurotoxic substance, adversely affects the lymphoid organs of the immune system in rats.

Animals↗
PubMed1986

Rapid effects of insulin on in vitro translational activity of specific mRNA in diabetic rat heart.

We studied the time course of response of specific cardiac mRNA after administration of insulin to diabetic rats. The primary aim was to identify specific cardiac mRNA, which show a rapid response to insulin administration. Diabetic rats were injected with 2 U of regular insulin intravenously, and total cardiac RNA was prepared 0.5, 1.5, 3, 5, 12, and 24 h later. RNA was translated in vitro in the presence of [35S]methionine and the translational products separated by two-dimensional electrophoresis and quantitated by digital matrix photometry. A rapid change in the translational activity of five specific mRNA species was observed within 0.5 h after administration of insulin to the diabetic animal. One translational product exhibits a more delayed response at 1.5 h. The predominance of three of these products was increased, while that of three was decreased. Two specific mRNA coding for translation products designated as spots 97 and 106 show the most significant change, with a dramatic decrease of 15-fold and 6.5-fold, respectively, within 0.5 h after insulin administration. The change in levels of these specific mRNA species could result from effects of insulin at various sites of mRNA synthesis or degradation. However, the rapidity of the response is compatible with a direct effect of insulin on gene expression. The very quick response of these specific mRNA species to insulin could thus serve as a useful model system to examine the molecular mechanisms of insulin action in the heart.

Animals↗
PubMed1986

Acute and short-term toxicity studies on p-aminodiphenylamine.

p- Aminodiphenylamine (p-ADPA), an aromatic amine of wide industrial applications, also finds human exposure through hair dye preparations or via ingestion of a common food colouring metanil yellow. Acute and short-term toxicity studies in albino rats have been done following the biochemical markers, hematology and tissue histopathology. The acute LD50 value of p-ADPA is 0.847 g/kg body weight which qualifies for the 'moderately toxic' category. In short-term studies, animals were fed p-ADPA, mixed in routine laboratory diet at the concentrations of 0.0 (control), 0.1, 0.25, 0.5 and 0.75% (w/w), daily for 90 days. Feed intake and body weight gain in the highest dosed group were reduced. Hematological examinations exhibited moderate anemic conditions with decreased red blood cells, increased erythrocyte sedimentation rate and lowered packed cell volume suggesting normocytic normochromic anemia at 0.25% onward levels of p-ADPA intake. There was significant increase in the activities of acid/alkaline phosphatases and GOT/GPT in serum with simultaneous depletion from liver at the levels of 0.5 and 0.75% p-ADPA intake, suggesting biochemical lesions of the liver. Testicular LDH and hyaluronidase were lowered at 0.5 and 0.75% levels indicating partial arrest of spermatogenesis. These findings were supported histopathologically. The study warrants careful consideration on its exposure, industrially or through common food color or hair dye preparations.

Anemia↗
PubMed1985

Effect of 2,5-hexanediol on immunocompetence of mice.

A preliminary study on immunotoxicologic evaluation of 2,5-hexanediol (one of the principal metabolites of n-hexane), involving multiple immunological parameters, was carried out in mice. Mice were exposed to 2,5-hexanediol at a 1/5 LD50 dose level for 7 days. Pathotoxicological changes such as marked reduction in absolute and relative lymphoid organ weights, histological abnormalities in thymus, spleen, and adrenal, and reduction in cellularity of lymphoid organs were found. Immune function tests such as delayed hypersensitivity reactions, plaque-forming cell assays, serum antibody titer against SRBC, and resistance to endotoxin shock were also markedly impaired. Results obtained in this study showed that 2,5-hexanediol causes impairment to immunocompetence in mice.

Administration, Oral↗