Biomedical subjects
Publications and source records attributed to N Sethi.
A new male antifertility agent, styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide (DMSO), was injected into the vas deferens of rats. The morphological changes detected were confined only to the mucosa. After four weeks, the vas deferens lumen was flushed with the solvent DMSO, and the mucosal structures returned to normal.
The male mediated teratogenic potential of a new antifertility compound, styrene maleic anhydride (SMA), was evaluated in rabbits. No teratogenic potential was observed at the doses of 1.25 mg, 2.5 mg and 5.0 mg used in our experiment.
The effects of two commonly used fertilizers, diammonium phosphate and urea, on hematological parameters (hemoglobin, red blood cell count, hematocrit, and total leucocyte count) of fresh water fish Clarias batrachus were studied. The toxic effect of diammonium phosphate was more pronounced than that of urea. The toxic effect of diammonium phosphate resulted in a sudden fall of hematological parameters--Hb, RBC count, Hct--at higher concentrations, and at lower concentrations gradual decreases were seen over comparatively longer durations. In urea intoxication, slight decreases in the three parameters were seen at lower concentrations during shorter intervals, while at higher concentrations, significant decreases during shorter intervals were observed. Total leucocyte count (TLC) increased during toxicity with both fertilizers, but higher elevations in TLC were produced by diammonium phosphate than by urea.
In male Charles Foster rats, polymer styrene maleic anhydride was injected into the lumen of the vas deferens at dose levels of 1.0, 2.5, and 5.0 mg in each vas deferens of Groups II, III, and IV, respectively, while controls (Group I) received 0.03 ml dimethyl sulfoxide in each vas deferens. The rats were observed for 6 months for toxicity. No change in any of the toxicity parameters in test animals as compared to controls was revealed. Hence, the polymer is safe at the doses used within 6 months of injection.
A subacute toxicity study of a potent tetanus toxoid (250 Lf) was carried out in guinea pigs. The toxoid was injected subcutaneously at the nape of the neck at dose levels of 1.0, 1.5, and 2.0 ml in Groups II, III, and IV, respectively. In the controls (Group I) 2.0 ml of aluminum phosphate suspension was given in each injection. Periodic evaluations of body weight, food/water intake, general observable behavior, hematology, and blood chemistry in toxoid-injected guinea pigs were similar to those in control guinea pigs. Thus, the toxoid did not cause any side effects up to four times the dose proposed for humans.
Since the naturally acquired tetanus antitoxin titre in Indian population is mostly less than protective levels, to minimise the incidence of morbidity, Glaxo Laboratories (India) Ltd., Bombay have prepared a single dose potent tetanus vaccine of 250 Lf as compared to 5 Lf previous tetanus toxoid. Subacute toxicity study revealed that this toxoid (250 Lf) injected at different dose levels (1-2 ml/rat/injection x 4) is non-toxic to rats.
Charles Foster male and female rats were exposed only once to 3.52 and 35.32 ppm doses of methyl isocyanate in separate experiments for 10 min each in an acute toxicity study, while in subacute toxicity experiments, they were exposed to 0.212, 0.265, and 0.349 ppm doses for 30 min daily, for 6 days, by inhalation. Clinical signs, mortality, body and organ weights, and changes in hematology and clinical pathology were routinely monitored to determine the principal organ sites damaged on exposure to the gas. During exposure, animals were observed to have congestion in eyes, lachrymation, nasal secretion and dyspnea, progressively increasing ataxia, and immobility. Uncoordinated movements were also observed, indicating effects on the nervous system. Upon microscopic examination of the viscera, pathological findings confined to bronchial tree, lung parenchyma, liver, and kidneys were observed.
Injection of a polymer, styrene maleic anhydride (SMA), into the lumen of the vas deferens of rats, was observed to have effective and reversible contraception. The safety evaluation of the polymer, for 90 days, was carried out in Charles Foster male rats. There have been no significant changes in any of the toxicity parameters in the test animals as compared to the control animals. Hence, it is concluded that the compound is non-toxic to rodents.
Methemoglobin toxicities of primaquine and compound N1-(3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl) 1,4-pentanediamine, CDRI Code 80/53, have been compared in beagles. Primaquine administration at 3 mg/kg for 7 days produced significantly high (P less than 0.001) methemoglobinemia and the levels increased 10.55-fold. Compound 80/53 at 3.75 mg/kg x 7 days produced a marginal increase in methemoglobinemia (3.24-fold; P less than 0.02). The methemoglobin formed by primaquine administration was 3.65-fold (P less than 0.001) higher than that formed after administration of compound 80/53. There was no significant change in other hematological parameters and liver function tests.
Mutagenicity testing is an important aspect of the toxicological evaluation of environmental chemicals for safety. Methyl isocyanate (MIC), a very hazardous chemical used for the manufacture of insecticides, was studied for its genotoxic effects on the somatic cells of mice after inhalation exposure by means of an in vivo micronucleus test and chromosomal analysis of bone marrow cells. Animals were exposed for 10 min to different concentrations (2.40, 4.80 or 7.20 microliters) of MIC in a 22 litre chamber at 0 and 24 h. Bone marrow smears prepared 6 h after the second treatment were examined for the occurrence of micronuclei (MN) in polychromatic (P) and normochromatic (N) erythrocytes. The frequencies of cells with MN and the P/N ratio did not differ significantly from those of the control at all the exposure levels. Chromosomal preparations revealed few structural and numerical abnormalities. Aberrations encountered were of the chromatid type only. Quantitative analyses failed to exhibit any significant increase in aberration rates in the three treated groups. Numerical abnormalities were within the control range.
The effect of cannabis extract, on the hepatic aminopyrine-N-demethylase activity was studied in rats. Daily administration of cannabis extract for 15 consecutive days increased the aminopyrine-N-demethylase activity which was significant on day 15 post-treatment at 2 and 10 mg/kg doses. At 20 mg/kg, a significant increase was observed from day 7 which continued up to day 15. These findings suggest that cannabis extract can induce hepatic aminopyrine-N-demethylase activity.
Hysterectomy specimens were obtained from ten adult female rhesus monkeys treated with levonorgestrel-releasing intrauterine devices (IUDs) for a period of three, six and twelve months. The effect of levonorgestrel on the endometria, ovaries and fallopian tubes of removed uteri was examined in luteal phase of cycle. A uniform suppression of endometrium with glandular atrophy and pseudodecidualization of stromal cells was observed in endometrial biopsies, whereas ovaries and tubal epithelium exhibited normal physiological changes as evidenced by presence of ovulatory stigma along with well formed corpus luteum and secretory activity of tubal epithelium.
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The present work, involving clinical, behavioral, and biochemical studies, was undertaken to elucidate the probable mechanism of the observed antianxiety effects of cannabis. The population for the clinical study consisted of 50 male chronic cannabis users who were otherwise healthy and 50 matched controls. When evaluated on Taylor's Manifest Anxiety Scale (TMA), these subjects had low anxiety scores as compared with the controls. To explore the possible interaction of cannabis with the benzodiazepine receptors, behavioral and biochemical studies in mice were devised, involving acute and chronic cannabis administration. Behavioral study revealed that mice under chronic cannabis treatment scored significantly higher on foot shock-induced aggression, but this was significantly blocked by benzodiazepine receptor antagonist. Furthermore, chronic cannabis treatment significantly (p less than 0.001) increased the frequency of licking response periodically punished by shocks. This confirms the antianxiety effect of cannabis, which also appears to be mediated through a benzodiazepine receptor, as it was reduced significantly (p less than 0.001) by a benzodiazepine receptor blocker. Specific 3H-diazepam binding was carried out in frontal cortex to assess both the population and affinity of benzodiazepine receptors. Our results indicate that acute cannabis treatment has no significant effect, whereas chronic cannabis treatment significantly increased 3H-diazepam binding as compared with controls. Scatchard analysis further reveals that increased affinity is responsible for increased binding to these receptors. It is therefore our contention that the antianxiety effect of cannabis is mediated through central benzodiazepine receptors.
Crude metabolites of 21 of 60 fungal cultures isolated from some of the common cereals collected from different parts of India were found to be toxic. Of these toxin-producing fungi, 79% caused hepatic pathology of varying severity in mice. Serum glutamate pyruvate transaminase values and blood urea nitrogen were found to be high in such experimental animals.
'Tube-locked' morulae and blastocysts were recovered from the ampulla of the oviduct of centchroman-treated mice between Days 4 and 12 post coitum and transferred to the uteri of pseudopregnant female mice. Pregnancy and implantation rates were lower and the post-implantation resorption rate was higher in the treated than in the control group. There was little difference in the pregnancy or implantation rates between embryos recovered on Days 4 or 12 post coitum, but the resorption rate increased with increasing duration of embryos in the oviducts and was 100% for the Day-12 embryos. The resorption rate was similar even when these embryos were transferred to the sterile uterine horn of unilaterally pregnant mice. Centchroman did not produce any deleterious effect on embryos which survived until Day 19 of pregnancy in foster mothers. The average fetal weight was also comparable to those of control fetuses.
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