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Biomedical subjects

J Gandy

Publications and source records attributed to J Gandy.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effects of selected chemicals on the glutathione status in the male reproductive system of rats.

Previous studies have suggested a significant role for reproductive tract glutathione in protecting against chemical-induced germ-cell mutations. Therefore, a number of compounds were tested for their ability to perturb glutathione levels in the testes and epididymides as well as liver following single acute dosages to rats. Phorone (250 mg/kg), isophorone (500 mg/kg), and diethyl maleate (500 mg/kg) significantly reduced glutathione in the liver and in both reproductive organs examined. Methyl iodide (100 mg/kg), trimethyl phosphate (600 mg/kg), naphthalene (500 mg/kg), acetaminophen (1500 mg/kg), and pentachlorophenol (25 mg/kg) affected hepatic and epididymal glutathione, but had little or no effect on testicular levels. The ability of isophorone to enhance the covalent binding of tritiated ethyl methanesulfonate (3H-EMS) to spermatocytes was assessed. Perturbation of reproductive tract glutathione by isophorone treatment significantly enhanced the extent of 3H-EMS-induced binding to sperm heads. The temporal pattern of ethylations in sperm heads was consistent with the stage of sperm development known to be susceptible to ethylations by EMS. Therefore, chemical-induced lowering of glutathione in the male reproductive tract may be a mechanism for potentiation of chemical-induced germ-cell mutations.

Animals↗
PubMed1990

Effect of general anaesthesia on whole body protein turnover in patients undergoing elective surgery.

To determine if general anaesthesia alone or in conjunction with surgery alters body protein turnover, we studied six healthy, unpremedicated females undergoing elective total abdominal hysterectomy. Changes in protein metabolism, synthesis and breakdown were estimated by an isotope dilution technique using a continuous infusion of the stable isotope tracer, L-[1-13C]leucine, before anaesthesia (4 h), during anaesthesia alone (1 h), during anaesthesia and surgery (1 h) and in the recovery period (2 h). General anaesthesia comprised thiopentone, pancuronium, enflurane (1 MAC) and oxygen-enriched air. An isotopic steady state in plasma 13C-alpha-ketoisocaproate (13C alpha-KIC) and expired 13C-carbon dioxide were obtained during the four periods. Collections of plasma and expired air were made during the steady state periods and plasma alpha-KIC enrichment measured to indicate precursor pool labelling from which leucine flux (equal to protein breakdown in the post-absorptive state) and oxidation were calculated, and whole body protein synthesis was derived. Whole body protein breakdown did not change with anaesthesia, but decreased with both surgery and during the acute recovery period (P less than 0.05). Protein synthesis did not change with anaesthesia and surgery, but decreased significantly after surgery (P less than 0.05).

Adult↗
PubMed1989

Effect of acute propanil exposure on the immune response of C57Bl/6 mice.

Propanil is a herbicide that is used extensively in rice farming to kill weeds without damaging the rice plant. The immunotoxic effects of acute exposure to propanil were determined in adult C57Bl/6 female mice exposed intraperitoneally to propanil at doses of 0, 10, 25, 50, 100, 200, or 400 mg/kg body wt. One week following exposure, the immune competency of the animals was assessed. Contact hypersensitivity response (CHR), blastogenic response to T- and B-cell-specific mitogens, and mixed lymphocyte reaction (MLR) were significantly depressed only in propanil-treated animals at 400 mg/kg. However, the number of splenic antibody-producing cells was also significantly depressed in a dose-dependent manner at the lower doses of 50, 100, and 200 mg/kg. In addition, a significant reduction in the thymus weight and an increase in absolute and relative spleen weight were also measured in animals treated with 200 and 400 mg/kg. The increase in spleen weight also showed a concomitant rise in spleen cellularity. These data indicate that propanil has a dose-dependent immunotoxic effect on the adult mouse that affects primarily the humoral response.

Anilides↗
PubMed1989

Chronic morpholine exposure of rats.

The chronic toxicity and carcinogenic potential of morpholine were evaluated in 60 Sprague-Dawley rats/sex/group receiving morpholine at mean inhalation exposure concentrations of 0, 10, 50 and 150 ppm for 6 hr/day, 5 days/week, for 104 weeks. Survival, body weight gains, organ weights, hematology, and clinical chemistries were normal in exposed groups and comparable to those of the control animals. The incidences of palpable tissue masses and of histologically confirmed neoplasia were comparable among all groups, including the control groups, and were typical of the strain and age of the rats tested. In-life clinical examinations revealed increased incidences of irritation around the eyes and nares, chromadacryorrhea, and urine stains on the fur, predominantly in high-dose animals. Morpholine exposure was associated with corneal irritation seen by ophthalmoscopic examination and confirmed microscopically as keratitis limited to the highest exposure group. Irritation of the maxillary and nasoturbinates as indicated by infiltration of neutrophils, focal squamous metaplasia of the turbinate epithelium, and necrosis of the turbinate bone was observed in high-dose animals. Therefore, chronic exposure of rats to morpholine for 2 years at concentrations of 150 ppm or less revealed no carcinogenic potential or chronic systemic toxicity. Consistent with its known irritating properties, morpholine produced only local irritation, which was limited almost exclusively to high-dose animals.

Administration, Inhalation↗
PubMed1988

Antagonism of bromobenzene-induced hepatotoxicity by the alpha-adrenergic blocking agents, phentolamine and idazoxan.

The coadministration of phentolamine, an alpha-adrenoreceptor antagonist, was found to be effective in antagonizing the hepatotoxicity produced by bromobenzene in B6C3F1 mice. Multiple doses of phentolamine, administered in dosages of 10 mg/kg, attenuated almost completely the acute lethality resulting from a 0.5 ml/kg dosage of bromobenzene. Consistent with this decline in lethality, the coadministration of phentolamine significantly altered the magnitude of hepatocellular necrosis, the elevation of serum alanine aminotransferase activity, and the glutathione depression normally produced by this dose of bromobenzene. These protective effects were not limited to phentolamine. Idazoxan, an adrenergic antagonist more specific for alpha 2-receptors, was equally effective in antagonizing the bromobenzene-induced hepatotoxicity. Measurements of serum catecholamine levels revealed that the administration of hepatotoxic doses of bromobenzene elevates serum epinephrine levels. Furthermore, the phentolamine antagonism of the bromobenzene hepatotoxicity could be correlated to elevated serum epinephrine levels in both a temporal and dose-dependent manner. Although the mechanism of the phentolamine antagonism remains to be established, one promising hypothesis involves its prevention of an epinephrine-mediated compromise in the glutathione-dependent detoxification of bromobenzene.

Adrenergic alpha-Antagonists↗
PubMed1988

Antagonism of bromobenzene-induced hepatotoxicity by phentolamine: evidence for a metabolism-independent intervention.

A previous study has revealed that phentolamine markedly antagonizes the bromobenzene-induced hepatotoxicity and lethality in B6C3F1 mice. One potential mechanism by which phentolamine may diminish the bromobenzene-induced hepatotoxicity is by a direct or indirect interference with the metabolism of bromobenzene to toxic metabolites. In the present study, phentolamine cotreatment failed to alter the elimination of bromobenzene from serum or the distribution of bromobenzene to liver. This suggests that phentolamine cotreatment does not indirectly interfere with bromobenzene bioactivation secondary to changes in bromobenzene absorption, distribution, or elimination. Further, a phentolamine concentration 10- to 20-fold greater than those measured in vivo failed to alter the in vitro metabolism of bromobenzene to its ortho- and para-phenolic metabolites. It is believed that para-bromophenol represents the rearrangement product of the hepatotoxic 3,4-epoxide and that ortho-bromophenol is a product of the nonhepatotoxic 2,3-epoxide pathway. Thus, it appears that phentolamine does not antagonize bromobenzene-induced hepatotoxicity by inhibiting the formation of hepatotoxic intermediates, nor by enhancing metabolism via the nonhepatotoxic pathway. On the basis of these studies, we conclude that phentolamine antagonism of bromobenzene-induced hepatotoxicity occurs through a mechanism independent of bromobenzene bioactivation.

Adrenergic alpha-Antagonists↗
PubMed1987

A phosphorothionate isomer protects against the pneumotoxicity caused by O,O,S-trimethyl phosphorothioate.

O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity in many organophosphorus insecticides, causes pneumotoxicity in rats at low doses (20 mg/kg) resulting in increases in bronchopulmonary lavage lactate dehydrogenase (LDH) activity and morphological alterations of bronchiolar epithelium. Coadministration of the nontoxic isomer, O,O,O-trimethyl phosphorothioate (OOO-TMP), at 1% of the toxicant dose, has been found to protect against the increase in LDH levels and morphological changes in bronchioles caused by OOS-TMP. Since OOO-TMP appears to require metabolic activation for pneumotoxicity, the effects of OOO-TMP on pulmonary and hepatic P-450 content and P-450-mediated monooxygenases were examined as a possible biochemical mechanism of antagonism. Oral treatment with OOO-TMP (0.5, 1.0, and 4.0 mg/kg) decreased pulmonary P-450 levels by 23 to 50% at 2 and 6 hr, while no changes were detected in hepatic P-450 levels. Lung microsomal 7-ethoxycoumarin O-deethylase (7-Ec) was inhibited by 71 to 100%, while liver 7-Ec was inhibited by 26 to 52%. p-Nitroanisole demethylase activity was decreased 22 to 47% following treatment with the two highest dose levels of OOO-TMP. These results further support the view that the lung is a target organ of delayed toxicity produced by OOS-TMP, and that the antagonistic effect of OOO-TMP is due to alterations in the metabolic activation processes of OOS-TMP in the lung and/or liver.

Animals↗
PubMed1986

Managing purchasing and inventory with bar codes. Part II.

Automated identification systems (bar coding) have proven their worth in a number of diverse manufacturing and materials handling environments. Whether this technology can be broadly applied with equal effectiveness in the health care setting still remains largely unproven. One thing is certain, however. Before bar code technology can be effectively applied in any setting, the materials manager must understand several basic concepts: How materials flow through his physical plant; How, where and in what amounts they are used; and How and when they are expensed. With this information, it is possible to create a systematized approach to materials cost containment, of which bar coding is one element. In the following article, the author illustrates how purchasing and inventory control can be made more time and labor efficient through the use of bar code technology.

Electronic Data Processing↗
PubMed1986

Designing and implementing a bar code system.

Used as part of a comprehensive materials management system, bar coding can help: reduce inventory, operating costs, space requirements, and loss due to pilferage and damage; increase productivity, stock rotation, and patient charge capture; improve material throughput, handling efficiencies, and audit-trail accuracy; and generate more accurate and meaningful management data. But the decision to bar code should come only after an extensive evaluation of off-setting costs and benefits, organizational needs, potential applications, and a thorough review of available hardware and software packages. The focus of this, the first of a two-part article on the design and implementation of an automatic identification system, will center on bar code use for SPD inventory, patient charges, linen supply system, and capital asset management.

Cost-Benefit Analysis↗
PubMed1985

Cellular responses to O,O,S-trimethyl phosphorothioate-induced pulmonary injury in rats.

O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity of many organophosphorus insecticides, causes a delayed toxicity in rats and mice which is associated with morphological and biochemical changes in the lung. Oral administration of doses as low as 20 mg/kg alters bronchiolar epithelial morphology and causes an increase in bronchopulmonary lavage lactate dehydrogenase levels. In the present study, the effects of OOS-TMP on alveolar and bronchiolar cells were examined by determining the patterns of cellular regeneration in rats at periods of 12 hr, 24 hr, 3 days, and 7 days after treatment. Dividing cells were labeled with tritiated thymidine and studied with autoradiographic techniques. The results showed that OOS-TMP treatment initiated proliferation of alveolar type II cells within 24 hr. The proliferative response of type II cells continued to increase in 3-day and 7-day treatment groups. Labeled alveolar type I cells began to appear after 3 days, indicating that type II cells were dividing to replace damaged type I cells. Cells of the alveoli were thickened and showed vacuolization. In the bronchioles, labeled Clara cells were increased on Day 3 and Day 7 while the number of labeled ciliated cells remained near control levels throughout all time points, indicating that in bronchiolar epithelium, OOS-TMP stimulates the proliferation of Clara cells but does not damage ciliated cells. The binding of tritiated OOS-TMP to lung tissue was also examined by autoradiography. It was found that [3H]OOS-TMP binds to all regions of lung tissue.

Animals↗
PubMed1985

Development of tolerance to a pneumotoxic impurity of malathion.

O,O,S-Trimethyl phosphorothioate (OOS-Me) is a pneumotoxic impurity present in various organophosphorus insecticides. OOS-Me produces morphological alteration of bronchiolar epithelial Clara cells accompanied by an increase in pulmonary lavage lactate dehydrogenase activity and severe weight loss in rats. Tolerance to the pneumotoxicity of OOS-Me was induced rapidly by oral pretreatments with small doses of OOS-Me itself. O,O-Dimethyl-S-ethyl phosphorothioate (OOS-Et), a pneumotoxic trialkyl phosphorothioate that is closely related in structure to OOS-Me, also produced a tolerance by oral pretreatment with small doses of OOS-Et itself. Pretreatment of rats with OOS-Me produced tolerance to OOS-Et, pretreatment did not produce tolerance to OOS-Me. Pretreatment of rats with tolerance-inducing doses of OOS-Me or OOS-Et had no effect on pulmonary or hepatic monooxygenase activities. Malathion and phenthoate carboxylesterases in pulmonary and hepatic microsomes were inhibited by these pretreatments. Activity of superoxide dismutase in lung or glutathione content in lung or liver was not affected by these pretreatments. Although the mechanism(s) remains unknown, the present study demonstrated the tolerance development to the chemical-induced pneumotoxicity.

Administration, Oral↗
PubMed1984

Sequential and dose-dependent alterations in rat bronchiolar epithelium during O,O,S-trimethyl phosphorothioate induced delayed toxicity.

The sequential and dose-dependent effects of O,O,S-trimethyl phosphorothioate (OOS-Me) on rat lung bronchiolar epithelium were investigated using scanning electron microscopy. At 12 h after oral treatment (20 mg/kg), there was a small increase in debris in the bronchioles and, by 24 h, there was much debris as well as phagocytic cells in the bronchioles. After 3 days, there was a decrease in the number of bronchiolar Clara cells as determined by the loss of their characteristic apical bulges. Concomitantly, there was a significant increase in lactate dehydrogenase activity in bronchopulmonary lavage fluid. By day 7, the Clara cells appeared to be reforming and, by day 14, the morphology of bronchiolar epithelium had returned to normal. Dose-dependent studies revealed a threshold dose level of OOS-Me between 10 and 20 mg/kg which produced the observed effects in Clara cells. Both sequential and dose-dependent effects of OOS-Me on Clara cells were correlated with changes in bronchopulmonary lavage lactate dehydrogenase activity.

Animals↗
PubMed1984

Morphological alterations of rat lung bronchiolar epithelium produced by various trialkyl phosphorothioates.

A single oral administration of O, O, S-trimethyl phosphorothioate (OOS-Me), an impurity in widely used organophosphorus insecticides, causes delayed toxicity (delayed death) which is accompanied by morphological changes in the bronchiolar epithelium of rat lungs. A series of simple O,O-dimethyl and O,O-diethyl S-alkyl phosphorothioate esters, which induce delayed toxicity, were examined for their effect on rat bronchiolar epithelium. The structural analogues synthesized and tested include O, O-dimethyl S-ethyl phosphorothioate, O,O-dimethyl S-isopropyl phosphorothioate, O,O,S-triethyl phosphorothioate, and O,O-diethyl S-methyl phosphorothioate. The present investigation demonstrated that these analogues of OOS-Me which cause delayed toxicity produce body weight loss, accompanied by morphological alterations of terminal bronchiolar epithelium, i.e. loss of the apical bulge of non-ciliated Clara cells. Another impurity which produces delayed toxicity, O,S,S-trimethyl phosphorodithioate, was also capable of producing similar effects at near the LD50 level.

Administration, Oral↗
PubMed1983

Selective inhibition of rat pulmonary monooxygenase by O,O,S-trimethyl phosphorothioate treatment.

The effects of oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity present in widely used organophosphorus insecticides, were studied using pulmonary and hepatic microsomal enzymes of rats. The animals were treated with OOS at 10,20 and 40 mg/kg, and were killed on day 3 after treatment. Their relative lung weights increased markedly at 20 and 40 mg/kg, increasing 94% at the highest dose, whereas the weight of liver decreased. At 20 mg/kg OOS, the cytochrome P-450 content of the lung and liver decreased to 83 and 80% of the control levels respectively. Pulmonary microsomal 7-ethoxycoumarin (7-Ec) O-deethylase decreased in a dose-dependent manner; activities were less than 10% of control at the 40 mg/kg dose. The activity of pulmonary coumarin hydroxylase also decreased following OOS treatment, but the decrease was not dose-dependent since no activity was detectable at doses over 10 mg/kg. In contrast, the effect of OOS treatment on hepatic monooxygenase activity was moderate. 7-Ec deethylase activity was not affected by OOS treatment at any dose level, while p-nitroanisole (p-NA) demethylase activity was decreased only at the 40 mg/kg dose of OOS. Pulmonary malathion carboxylesterase activity was not affected by OOS treatment. In contrast, a dose-dependent decrease was observed in the liver carboxylesterase. Time course effects of OOS treatment on these parameters were examined by treating rats at 20 mg/kg. The animals were killed 0.5, 1,3 and 7 days after the treatment. The 7-Ec deethylase activity of pulmonary microsomes was decreased on days 0.5, 1 and 3 after treatment, the maximum decrease being observed on day 1. Significant decreases were not observed in hepatic microsomal activities of 7-Ec deethylase or p-nitroanisole demethylase throughout the experimental period; rather, these activities were higher on day 7. Hepatic microsomal malathion carboxylesterase was lower on days 0.5, 1 and 3 after OOS treatment.

Animals↗