Search PubMed⌕ Search

Biomedical subjects

B N Gupta

Publications and source records attributed to B N Gupta.

At least 91 records · Page 5Linked to original sources
PubMed1987

Toxicity of inhaled methyl isocyanate in F344/N rats and B6C3F1 mice. I. Acute exposure and recovery studies.

Male and female F344/N rats and B6C3F1 mice were exposed to lethal and sublethal concentrations of methyl isocyanate by inhalation. Mortality, clinical signs, body and organ weights, and changes in clinical pathology and hematology were monitored immediately after 2-hr exposures and during the ensuing 3 months. Additional studies investigated the possible involvement of cyanide in the toxicity of methyl isocyanate. During exposures, signs of restlessness, lacrimation, and a reddish discharge from the nose and mouth were evident in rats and mice. Following exposures, rats and mice were dyspneic and weak. Deaths of rats and mice exposed to lethal concentrations (20 to 30 ppm) began within 15-18 hr, with males more prone to early death than females. A second wave of deaths occurred after 8 to 10 days, affecting primarily female rats and mice exposed to 20 to 30 ppm of methyl isocyanate, and male and female rats exposed to 10 ppm. Most deaths occurred during the first month following the exposures and were preceded by periods of severe respiratory distress. Body weights decreased in proportion to dose early, but then weight gain resumed in survivors at control rates. The only organ with a consistent, dose-related weight change was the lung, which was heavier throughout the studies in animals exposed to high concentrations of methyl isocyanate. No significant clinical pathology, or hematologic changes were observed in exposed rats. Blood and brain cholinesterase were not inhibited. Studies attempting to measure cyanide in the blood of methyl isocyanate-exposed rats, and attempting to affect lethality with a cyanide antidote (sodium nitrite and sodium thiosulfate) gave negative results.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Two-hour methyl isocyanate inhalation and 90-day recovery study in B6C3F1 mice.

B6C3F1 mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 90-day recovery period. Sixteen of eighty (20%) male mice in the 30 ppm group died following exposure. There were no other unscheduled deaths in the mice. Five mice/sex/group were examined at 2 hr or at 1, 3, 7, 14, 28, 49, or 91 days following exposure. Chemical-related changes were restricted to the respiratory system. At 30 ppm there were extensive necrosis and erosion of the respiratory and olfactory epithelium in the nasal cavity. Severe necrosis and epithelial erosion were also found in the trachea and main bronchi. Regeneration of the mucosal epithelium occurred rapidly in the nasal cavity and airways. In the turbinates, mild incomplete olfactory epithelial regeneration persisted to day 91 in the male mice. Intraluminal fibrotic projections covered by respiratory epithelium and bronchial fibrosis were found in the major airways of the 30 ppm male and female mice by day 7. The intraluminal fibrosis persisted to day 91. In males with severe bronchial fibrosis, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, persistent pulmonary changes were not found. These studies indicate that methyl isocyanate inhalation at or near lethal concentrations can cause persistent fibrosis of the major bronchi in mice.

Animals↗
PubMed1987

Two-hour methyl isocyanate inhalation exposure and 91-day recovery: a preliminary description of pathologic changes in F344 rats.

The accidental release of methyl isocyanate (MIC) in Bhopal, India, was reportedly responsible for the deaths of more than 2,000 people. To study the pathology of acute inhalation exposure to MIC, the tissues of male and female Fischer 344 rats were evaluated immediately after a single 2-hr exposure to 0, 3, 10, or 30 ppm MIC, and through day 91. Early gross pathologic changes in the 30 ppm-exposed rats included a reddish white encrustation around the mouth and nose, a small thymus, and distension of the gastrointestinal tract with gas. Lungs (middle and median lobes) showed consolidation and hemorrhage and failed to deflate when the chest cavity was opened. Microscopic changes in the upper respiratory tract 3 hr after exposure included marked erosion and separation of olfactory and respiratory epithelia from the basement membrane with accumulation of serofibrinous fluid. On day 1, acute inflammation and fibrinopurulent exudate partially blocked the nasal passages. Epithelial cells had sloughed from the nasopharynx, trachea, bronchi, and major bronchioles, leaving the basement membrane covered with fibrin and exudate. Granulomatous inflammation and intraluminal fibrosis of the airways were observed by day 3, with increased intraluminal fibrosis by day 7. Lower airways became blocked by exfoliated cells, mucous plugs, and/or intraluminal fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Ultrastructural changes in the nasal mucosa of Fischer 344 rats and B6C3F1 mice following an acute exposure to methyl isocyanate.

Male rats and male mice received a single 2-hr exposure to 0 (control), 10, or 30 ppm of methyl isocyanate and were sacrificed after 1, 3, 14, or 90 days to assess the ultrastructural changes in the nasal mucosa by transmission electron microscopy. One day after exposure to methyl isocyanate, there were widespread areas of necrosis and degeneration of the respiratory and olfactory epithelium of rats and mice in the 10 ppm and 30 ppm groups. Qualitatively the ultrastructural findings were similar for both exposure groups and species. Degeneration followed by rapid regeneration was observed for both respiratory and olfactory epithelia but was most striking for olfactory epithelium in the dorsal meatus. Three days after the exposure, the olfactory epithelium was two to three cell layers thick due to a loss of supporting cells, olfactory neurons, and basal cells. By 14 days after exposure, the olfactory epithelium was composed of a heterogeneous cell population three to five cell layers thick. At 90 days following exposure, the epithelium was of normal thickness (eight to ten cell layers), with normal architectural arrangement, and composed of well-differentiated cells that appeared similar to those of controls. There were several findings that suggested the epithelial cells of Bowman's glands were the progenitor for the regenerating supporting cells of the olfactory epithelium. This study demonstrated that the respiratory and olfactory epithelium is capable of complete structural regeneration after an acute destruction by methyl isocyanate.

Animals↗
PubMed1986

Sensitization of aortic and cardiac baroreceptors by arginine vasopressin in mammals.

Vasopressin facilitates the baroreflex control of the circulation. The peptide may act at several sites to augment the baroreflex. In this study we examined the effect of vasopressin on aortic baroreceptors in anaesthetized rabbits and on left ventricular mechanoreceptors in anaesthetized cats. Vasopressin (16 mu./kg. min) did not change resting nerve discharge in single fibres from aortic baroreceptors. Vasopressin (16 mu./kg. min) significantly enhanced the response of single aortic nerve fibre discharge to elevation in arterial pressure. The slope relating nerve activity to mean arterial pressure increased from 0.24 +/- 0.05 (mean +/- S.E. of mean) to 0.50 +/- 0.16 impulses/cardiac cycle. mmHg (P less than 0.05) in ten aortic medullated fibres and from 0.06 +/- 0.03 to 0.18 +/- 0.04 impulses/cardiac cycle. mmHg (P less than 0.05) in three non-medullated fibres. Vasopressin (16 mu./kg. min) did not change resting nerve discharge in single fibres from left ventricular mechanoreceptors. Vasopressin (16 mu./kg. min) significantly enhanced the response of single nerve fibre discharge from left ventricular mechanoreceptors in response to elevation of left ventricular end-diastolic pressure. The slope relating nerve activity to left ventricular end-diastolic pressure increased from 0.24 +/- 0.07 to 0.32 +/- 0.07 impulses/cardiac cycle. mmHg (P less than 0.05) in six medullated fibres and from 0.10 +/- 0.01 to 0.15 +/- 0.02 impulses/cardiac cycle. mmHg (P less than 0.05) in four non-medullated fibres. These data show that vasopressin sensitizes high and low pressure baroreceptors and suggest a mechanism by which vasopressin may facilitate the baroreflex control of the circulation.

Action Potentials↗
PubMed1984

Reproductive toxicity of dimethyl methyl phosphonate (DMMP) in the male Fischer 344 rat.

Dimethyl methyl phosphonate (DMMP) has been considered for use by the U.S. Armed Forces as a nerve gas simulant in a variety of experimental situations to simulate the physical properties of nerve gases, but not the neurotoxic properties. Dimethyl methyl phosphonate is also used as a flame retardant for urethane foams and polyester resins. This study was conducted to determine the reproductive toxicity of DMMP after subchronic dosing. DMMP was administered to male Fischer 344 rats by gavage 5 days/week for 90 days at dosages of 0, 250, 500, 1000, and 2000 mg/kg, and all animals survived this dosing schedule. At Day 84, the rats were mated to untreated female Fischer 344 rats. There was a dose-related decrease in sperm count, sperm motility, and the male fertility index. The male fertility index was 70, 75, 60, 40, and 0% in the 0, 250, 500, 1000, and 2000 mg/kg dose groups. DMMP acted as a dominant lethal mutagen as demonstrated by an increase in the number of resorptions with increasing doses of the drug. The percentage of resorptions in the control group was 6.1% and increased to 14.9, 37.8, and 79.1% in the 250, 500, and 1000 mg/kg groups, respectively. The testes of the male rats were examined histologically to determine the relationship between reproductive function and pathologic abnormalities. DMMP altered reproductive function at all dose levels, while histologic abnormalities of the testis were seen only in the high-dose group. Changes in the testes of the high-dose animals were characterized by lack of spermatogenesis or by degeneration, vacuolization, and necrosis of cells in the spermatogenic tubules. Histopathologic abnormalities of the kidney were seen in some animals from each of the dosed groups and microscopic changes of the prostate were seen in some of the high-dose animals.

Animals↗
PubMed1984

Central abnormality in baroreflex control of renal nerves in hypertension.

The purpose of our study was to determine if there is a central abnormality in the arterial baroreceptor reflex control of renal nerve activity in renal hypertension. We recorded simultaneously the changes in aortic (input) and renal (output) nerve traffic during phenylephrine-induced increases in arterial pressure in 14 normotensive and 11 hypertensive rabbits [mean arterial pressure (+/- SE) in conscious state 106 +/- 2 and 141 +/- 6 mmHg, respectively]. Changes in aortic nerve traffic were considered representative of changes in total arterial baroreceptor input to the central nervous system. Renal nerve traffic was inhibited by 5.2 +/- 0.5% per mmHg rise in arterial pressure in normotensive rabbits but by only 2.5 +/- 0.3% per mmHg in hypertensive rabbits (P less than 0.05). Increases of aortic nerve traffic during increases in arterial pressure were similar in the two groups. These data suggest that there is a central abnormality in the baroreflex control of renal nerve activity in renal hypertensive rabbits. This hypothesis was tested further by sectioning vagal, carotid, and aortic nerves and stimulating electrically the left aortic depressor nerve while recording changes in blood pressure and renal sympathetic nerve traffic. Decreases of renal traffic during stimulation of myelinated fibers alone were strikingly impaired (P less than 0.001) at all frequencies in hypertensive rabbits. Responses were not impaired significantly during stimulation of myelinated plus nonmyelinated fibers. Arterial pressure decreases were not different during stimulation of myelinated fibers or of both myelinated and nonmyelinated fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1983

Effects of a polybrominated biphenyl mixture in the rat and mouse. I. Six-month exposure.

A 1973 environmental accident in Michigan resulted in exposure of humans via the food chain to polybrominated biphenyl (PBB). To better characterize the toxicity of the halogenated polycyclic aromatic hydrocarbon class of chemicals, rodents were dosed with PBB and their target organs examined for morphological, histological, biochemical, and selected endocrine changes. Male and female rats and mice were given 125 po doses of PBB over a 6-month period at 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg of body weight/day (5 days/week). There was a dose-related decrease in body weight gain in both male and female rats and male mice. Thymus weights were significantly decreased in all rats exposed to 0.3 mg/kg or more of PBB. Dose-related hepatotoxic effects were observed in both rats and mice characterized by marked increase in liver weight with accentuation of hepatic lobular markings. Microscopically, there were moderate to marked swelling, disorganization, and single cell necrosis of hepatocytes, fatty infiltration, bile duct proliferation, and presence of atypical hyperplastic foci. Hepatic porphyrin levels were markedly increased in both rats and mice primarily in females. There was a significant decrease in serum thyroxine (T4) and triiodothyronine (T3) suggesting that PBB may interfere with thyroid hormone secretion. There was a significant dose-related increase in serum cholesterol and gamma-glutamyl transpeptidase, and a decrease in serum glucose.

Animals↗
PubMed1983

Effects of a polybrominated biphenyl mixture in the rat and mouse. II. Lifetime study.

This study was undertaken to characterize the long-term toxic and carcinogenic potential of a polybrominated biphenyl (PBB) mixture in rats and mice of both sexes. Fischer 344 rats and B6C3F1 mice were given 125 po doses of PBB over a 6-month period at 0 (control), 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg body weight/day (5 days/week) and observed for an additional 23 months for rats and 24 months for mice (lifetime observation). The treatments (0.3 mg/kg or higher dosages) shortened the survival time in male rats whereas no such effect was observed in treated females. There was also evidence of shortened survival time in mice treated with 10.0 mg/kg PBB. As observed by uv light, hepatic porphyrin markedly increased at the 6-month observation, then tended to decrease, primarily in mice, following cessation of exposure. Significantly higher incidences of atypical hepatocellular foci, neoplastic nodules, hepatocellular carcinomas, and cholangiocarcinomas were observed in exposed rats. The incidence of hepatocellular carcinoma was also increased in both male (95%) and female (88%) mice (highest dose level) compared with control male (48%) and female (0%) mice. The incidence of hepatic neoplasms appeared to be dose dependent in both species. Liver tumors were observed primarily in those groups of animals to which PBB was given in doses sufficient to induce readily observable hepatic toxicity. Under the conditions of this experiment, polybrominated biphenyl mixture (Firemaster FF-1) was carcinogenic for Fischer 344 rats and B6C3F1 mice of both sexes. Lesions included neoplastic nodules, hepatocellular carcinomas, and cholangiocarcinomas in rats and hepatocellular carcinomas in mice. Other manifestations of toxicity included porphyrogenic effects and hepatotoxicity. A significantly higher incidence of chronic progressive nephropathy was observed in male rats of the 1.0, 3.0, and 10.0 mg/kg dosage groups when compared with control males. Gastric ulcers and hyperplastic gastropathy of the glandular portion of the stomach were observed more frequently in male rats, primarily in the high dosage groups.

Animals↗
PubMed1983

The comparative effects of 1,2-dibromo-3-chloropropane (DBCP) and its metabolites, 3-chloro-1,2-propaneoxide (epichlorohydrin), 3-chloro-1,2-propanediol (alphachlorohydrin), and oxalic acid, on the urogenital system of male rats.

Reported similarities in the acute toxic effects of 1,2-dibromo-3-chloropropane (DBCP), 3-chloro-1,2-propaneoxide (epichlorohydrin, ECH), 3-chloro-1,2-propanediol (alphachlorohydrin, ACH), and oxalic acid (OA) have been suggested as presumptive evidence that the metabolism of DBCP to OA, via ECH and ACH, is the cause of the resulting injuries to the kidney and, perhaps, to the epididymis and testis. To test this hypothesis, the comparative toxicities of these four chemicals were studied in male rats after single subcutaneous (sc) injections of maximally tolerated (nonlethal) doses. Kidney, testicular, and liver functions were monitored, and the occurrences of morphological changes in these and several other organs were evaluated 24 hr, 3, 8, 25, and 75 days post-treatment. DBCP caused renal dysfunction (alterations in urine composition and reduced glomerular filtration rate) and marked necrosis of the proximal tubular epithelium in the outer medulla of the kidney. ACH and OA also elicited renal dysfunction, but ACH produced only a mild swelling of the proximal tubular epithelium in the renal cortex and OA produced a focal necrosis anatomically associated with crystal deposition. ECH caused a swelling of the proximal tubular epithelium in the renal cortex, but not frank kidney dysfunction. DBCP also caused a reversible vacuolization of the tubular epithelium in the caput epididymis, progressive testicular atrophy, and a reduction of cauda epididymal sperm concentration. ACH and ECH produced similar effects, as well as epididymal sperm granulomas, spermatocoeles, and an increase in the number of morphologically abnormal spermatozoa. OA failed to produce discernible epididymal or testicular lesions at any time during the study. The development of similar lesions in the epididymis and testis following DBCP, ECH, or ACH treatments is consistent with the theory of metabolism of these chemicals to a common causative gonadotoxic agent. Oxalic acid (OA), however, would not appear to be the common gonadal toxicant. Differences in the effects, both morphological and functional, of DBCP, ECH, ACH, and OA on the kidney, moreover, indicate that DBCP nephropathy is not mediated through metabolism to OA and suggest, as well, that it differs causally from that induced by ECH or ACH. Therefore, the metabolism of DBCP to ECH or ACH, and of ECH or ACH to OA, is insufficient to explain totally the toxic effects of these agents on the urogenital system in male rats.

Animals↗
PubMed1983

Behavior of left ventricular mechanoreceptors with myelinated and nonmyelinated afferent vagal fibers in cats.

The purpose of this study was to determine the behavior of left ventricular mechanoreceptors with myelinated vagal afferents and to compare them with endings with nonmyelinated vagal afferents. Single unit activity was recorded from 13 endings with nonmyelinated vagal afferents (conduction velocity 2.1 +/- 0.3 m/sec) and from 16 endings with myelinated vagal afferents (conduction velocity 7.3 +/- 1.3 m/sec). Resting discharge frequencies of nonmyelinated afferents and of myelinated vagal afferents were 1.7 +/- 0.3 and 2.7 +/- 0.5 imp/sec (P less than 0.1), respectively (at left ventricular end diastolic pressure of 6 mm Hg for both groups). Ten of 16 myelinated vagal afferents had pulse synchronous discharge under basal condition, whereas only 3 of 13 nonmyelinated vagal afferents had such activity. During aortic occlusion, the discharge of myelinated vagal afferents increased 1.7 +/- 0.3 imp/sec per mm Hg, whereas nonmyelinated vagal afferents increased significantly (P less than 0.05) less (0.5 +/- 0.1 imp/sec per mm Hg). Discharge for both groups was linearly related to left ventricular end-diastolic pressure but not to left ventricular systolic pressure. Increases in left ventricular systolic pressure alone did not increase firing for either group. During aortic occlusion, the maximum discharge rates of myelinated vagal afferents (43 +/- 7 imp/sec) were significantly higher than those of nonmyelinated vagal afferents (14 +/- 3 imp/sec) at left ventricular end-diastolic pressure of 30 +/- 2 and 24 +/- 2 mm Hg, respectively. Both groups increased their discharge during volume expansion with myelinated vagal afferents showing greater sensitivity than nonmyelinated vagal afferents. All endings studied were in the inferoposterior wall of the left ventricle. All nonmyelinated vagal afferents were in or near the epicardium. In contrast, myelinated vagal afferents were equally distributed between the endocardium and the epicardium. Myelinated vagal afferents had discrete receptive fields (1-2 mm2) whereas those of nonmyelinated vagal afferents were much larger (1 cm2). In conclusion, the discharge of left ventricular endings with nonmyelinated vagal afferents and myelinated vagal afferents both appear to be determined mainly by changes in left ventricular end-diastolic pressure. They may be located at different depths in the left ventricular wall. Myelinated vagal afferents have greater sensitivity and maximum firing frequencies than nonmyelinated vagal afferents.

Action Potentials↗
PubMed1982

The diuretic and natriuretic responses to stimulation of left atrial receptors in dogs with different blood volumes.

The diuretic and natriuretic responses to stimulation of atrial receptors were compared in two groups of anaesthetized dogs, one group with a high blood volume and another group with a low blood volume. A diuretic response to stimulation of the atrial receptors was obtained in the two groups of animals. Both the diuretic and the natriuretic responses to stimulation of the atrial receptors were greater in the dogs with high blood volume than in the dogs with low blood volume. In a second series of experiments, a diuretic response to stimulation of the atrial receptors was demonstrated in both groups of animals following surgical denervation of the kidney. In the denervated kidney, a large increase in heart rate, associated with stimulation of the atrial receptors, significantly contributed to the diuretic response in the dogs with high blood volume but not to the response in dogs with low blood volume. In the denervated kidney, a natriuretic response was only obtained in the dogs with high blood volume in which a large increase in heart rate was associated with stimulation of the atrial receptors. The present results show that the diuretic and natriuretic responses to stimulation of atrial receptors are greater in dogs with high blood volume than in dogs with low blood volume, and that increases in heart rate, associated with stimulation of atrial receptors, significantly contribute to the diuretic and natriuretic responses in acutely denervated kidneys in the dogs with high blood volume.

Animals↗
PubMed1981

Teratogenic evaluation of 2-nitro-p-phenylenediamine, 4-nitro-o-phenylenediamine, and 2,5-toluenediamine sulfate in the mouse.

Pregnant outbred albino (CD-1) mice were given 2-nitro-p-phenylenediamine (2NPPD; 32-256 mg/kg/day), 4-nitro-o-phenylenediamine (4NOPD; 16-1024 mg/kg/day) or 2,5-toluenediamine sulfate (2,5TDS; 16-64 mg/kg/day) by subcutaneous injection on Days 6-15 of gestation. The mice were killed on Day 18, the general health and reproductive health of the dams evaluated, and the fetuses examined and processed in order to characterize external, visceral, and skeletal malformations. The 32 and 128 through 256 mg/kg/day dose levels of 2NPPD produced a significant (p less than 0.05) reduction in average weight gain by the dam during pregnancy. There was also a significance reduction in average fetal weight at 128 mg/kg/day and above. Although 2NPPD administration led to a significant increase in the average percentage of malformed fetuses at 160 mg/kg/day and above, these effects occurred only at dosages which produced significant maternal toxicity. Teratogenic effects were observed with 4NOPD, as administration of this dye led to a significance increase in the average percent of malformed fetuses at 256 mg/kg/day and above. A significant reduction in average weight gain by the dam during pregnancy also was observed at these dose levels, as well as significant reduction in average fetal weight. Although 2,5TDS killed 4 of 31 dams at 48 mg/kg/day, and 9 of 11 dams at 64 mg/kg/day, this compound did not cause a significant increase in the average percent of malformed fetuses. There were indications of embryotoxicity, however, as dosages of 32 mg/kg/day and above led to significant reductions in average fetal weight.

Abnormalities, Drug-Induced↗