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Biomedical subjects

J M Baden

Publications and source records attributed to J M Baden.

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

Nitrous oxide alters body laterality in rats.

Seventy timed-pregnant Sprague-Dawley rats were exposed to either air (control) or 75% nitrous oxide (N2O) for 24 hours on day 8 of gestation. Four rats from each group were killed on days 11-16, 18, and 20, and laparotomy was performed. The viability of the embryos/fetuses was determined, as was the side of tail flexion on days 11 and 12, the direction from which the umbilical artery emerged from the body on days 13 and 14, the side of the body facing the placenta on days 15 and 16, and the side to which the aortic arch curved on days 18 and 20. Mean mortality rate in the control group was 8.9 +/- 6.1% (+/- S.D.), and there were no control embryos/fetuses with altered laterality except the 9% that faced left on day 16. In contrast, N2O treatment on day 8 of gestation resulted in significantly increased mortality (40.8 +/- 3.3%) beginning on day 14 of gestation and increased incidence of altered laterality overall (31.3%) and at all stages of development. The mechanisms underlying these events remain to be defined, as do the implications of our findings for pregnant surgical patients and occupationally exposed workers.

Animals↗
PubMed1990

Interlitter variability and developmental stage of day 11 rat embryos produced by overnight and morning short-period breeding regimens.

Day 11 rat embryos produced by overnight and morning short-period breeding regimens were compared for differences in interlitter variability and stage of development. Female Sprague-Dawley rats were mated either overnight (5 PM-9 AM, n = 22) or for 3 hr in the morning (8-10 AM, n = 20), and the presence of a vaginal plug was determined (day 0). At 11 AM on day 11 of gestation, rats were killed and embryos were examined for crown-rump length, somite number, and general morphology; protein content was determined later. There were no differences in mean number of implantations, live embryos, and abnormalities between the two regimens. There were significant differences in mean crown-rump length, somite number, and protein content but not in the magnitude of their variances. The difference in mean somite number was 1.2 (23.7 vs. 24.9), which corresponds to a time difference in development of approximately 2 hr. The range of mean somite number in morning short-period breeding group was 3.2 (22.2-25.4), corresponding to approximately 5.3 hr. These results are inconsistent with the popularly held hypothesis that the timing of fertilization is the major cause of interlitter variability.

Animals↗
PubMed1989

Susceptible period of nitrous oxide teratogenicity in Sprague-Dawley rats.

The susceptible period of nitrous oxide (N2O) teratogenicity was studied in 170 Sprague-Dawley rats. Seven groups of 20 timed-pregnant rats were exposed to 60% N2O for 24 hours on each of days 6-12 of gestation; a control group of 30 timed-pregnant rats was exposed to air on day 9. On day 20 of gestation, dams were killed and reproductive indices were determined; their fetuses were subsequently examined for external, skeletal, and visceral abnormalities. There were no differences among the groups in the number of implantations and live fetuses, mean fetal weight, and sex ratio. The incidence of fetal wastage was higher than control in N2O-treated groups exposed on days 8 and 11 of gestation. Skeletal malformations of the ribs and vertebrae were increased following exposure on day 9 of gestation. However, the specific minor anomaly, cervical rib, was increased only following exposure on day 8 of gestation. The incidences of right-sided aortic arch and left-sided umbilical artery, abnormalities indicative of altered laterality, were increased following exposure on day 8 of gestation. Nitrous oxide administration during organogenesis causes several reproductive defects by mechanisms which remain to be determined.

Abnormalities, Drug-Induced↗
PubMed1989

Hepatotoxicity and metabolism of isoflurane in rats with cirrhosis.

A rat model was used to determine whether isoflurane exacerbates liver dysfunction and whether its metabolism is changed in the presence of cirrhosis. Male Wistar rats were gavaged weekly with carbon tetrachloride until cirrhosis was well advanced. They and control rats without pretreatment with carbon tetrachloride and without cirrhosis were then exposed to 1.45% (1 MAC) isoflurane for 3 hours. Blood and urine samples were taken before, immediately, as well as 4, 24, 48, and 72 hours after anesthesia to measure liver function and isoflurane defluorination. After the last samples had been obtained, the rats were sacrificed and the liver removed for histologic examination and in vitro metabolic studies. Serum levels of SGOT and SGPT and inorganic fluoride production in rats with cirrhosis were similar to those in control rats without cirrhosis. Concentrations of cytochromes b5 and p-450 and specific activities of microsomal defluorinase and several cytosolic enzymes were significantly lower in cirrhotic than in noncirrhotic liver, but their total amounts in whole liver were the same. The results imply that cirrhosis does not increase the risk of acute hepatotoxicity of isoflurane. They also demonstrate that metabolism of isoflurane and perhaps other volatile anesthetics may be unaffected in rats with cirrhosis, even though liver architecture is severely disrupted.

Animals↗
PubMed1988

Halothane prevents nitrous oxide teratogenicity in Sprague-Dawley rats; folinic acid does not.

The teratogenic effects of nitrous oxide (N2O) administered with halothane or folinic acid (FA) were studied in two separate experiments using a total of 206 timed-pregnant Sprague-Dawley rats. In each experiment, rats were exposed to either 1) air (n = 30-40); 2) N2O (50-75% for 24 h on day 8 of pregnancy, n = 20-30); 3) test agent (i.e., 0.27% halothane for 24 h on day 8 of pregnancy; or 5 mg/kg/day of FA on day 5-13 of pregnancy, subcutaneously by osmotic pump, n = 20-30); or 4) N2O + test agent (n = 20-30). Cesarean sections were performed on day 20, and fetuses were examined for visceral and skeletal abnormalities. There were no differences in pregnancy rate, number of implantations and live fetuses per rat, and fetal weight among any of the groups. Treatment with N2O resulted in significantly higher incidences of resorptions and of major visceral and minor skeletal abnormalities. Halothane administered with N2O protected against these effects; folinic acid did not. Using an additional 65 nonpregnant rats, hepatic methionine synthase activity was measured after treatment with 50% N2O, 50% N2O plus 0.27% halothane, or 50% N2O plus 5 mg/kg/day of folinic acid. Methionine synthase activity was equally depressed in all groups. These findings do not support the commonly held theory that inactivation of methionine synthase is the sole cause of N2O teratogenicity; rather, they suggest a multifactorial etiology, which may include changes in uterine blood flow.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1988

Carcinogen bioassay of isoflurane in mice.

A carcinogen bioassay of isoflurane was performed in groups of Swiss/Webster mice exposed to either air (n = 181), 0.1% isoflurane (n = 167), or 0.4% isoflurane (n = 165), for 4 h per day, 5 days per week. After 78 weeks of exposure, mice were left untreated for 3 weeks and were then killed. Mice killed at this time when they were 86 weeks of age, and those killed or dying at other times during the study were subjected to complete gross and microscopic examination. Throughout most of the study, mean body weights of mice exposed to 0.1% isoflurane and 0.4% isoflurane were less by 1-5% and 5-8%, respectively, than that of mice exposed to air alone. Otherwise, no gross toxic treatment effects were noted. The first neoplastic lesion was detected 23 weeks after starting treatment and, by the end of the study, 190 tumors had been detected in 179 mice. However, there were no statistical differences among the groups in the number of mice with a particular tumor at a specific site, the ratio of benign to malignant tumors, or the time to tumor appearance. It was concluded that isoflurane is unlikely to have carcinogenic potential and is a remarkably non-toxic anesthetic in mice.

Animals↗
PubMed1988

Reproductive and teratogenic effects of sufentanil and alfentanil in Sprague-Dawley rats.

The reproductive and teratogenic effects of sufentanil and alfentanil were studied in a total of 168 Sprague-Dawley rats in two separate experiments. Either sufentanil (10, 50, or 100 micrograms.kg-1.day-1) or alfentanil (8 mg.kg-1.day-1) were administered continuously from day 5 through day 20 of pregnancy using subcutaneously implanted osmotic minipumps. Cesarean sections were performed on day 20 of pregnancy, reproductive indexes were determined, and the 1484 fetuses were examined for external, visceral, and skeletal abnormalities. No significant adverse reproductive or teratogenic effects were observed with either narcotic.

Abnormalities, Drug-Induced↗
PubMed1988

Rat whole embryo culture: an in vitro model for testing nitrous oxide teratogenicity.

The teratogenic effects of nitrous oxide (N2O) on postimplantation rat embryos were studied using a whole embryo culture system to separate the direct effects of N2O from those that are maternally mediated. A total of 100, 10-day-old rat embryos were cultured in either a control atmosphere (75% N2, 20% O2, and 5% CO2), or a N2O atmosphere (75% N2O, 20% O2, and 5% CO2). After 22 h of culture embryos were examined microscopically, and protein and DNA contents were determined. DNA content was significantly lower in the embryos exposed to N2O compared with the controls. Additionally, three malformed embryos and four embryos with left-sided tails were observed in the N2O group, whereas no abnormalities were observed in the control group. There were no differences in crown-rump length, somite numbers, limb bud index, and protein content between the two groups of embryos. The positive findings in this study indicate that whole embryo culture is useful for studying the mechanisms of N2O teratogenicity.

Abnormalities, Drug-Induced↗
PubMed1987

Reproductive and teratogenic effects of nitrous oxide, fentanyl and their combination in Sprague-Dawley rats.

The reproductive and teratogenic effects of 35% and 50% nitrous oxide, fentanyl 500 micrograms kg-1/day and their combinations were studied using a total of 419 timed-pregnant Sprague-Dawley rats. On day 7 of pregnancy, osmotic minipumps which delivered either fentanyl 500 micrograms kg-1/day or normal saline for 2 weeks were implanted subcutaneously in the back of the rats. Animals then were exposed to air, 35% nitrous oxide or 50% nitrous oxide for 24 h on day 9 of pregnancy. On day 21 of pregnancy, Caesarean sections were performed and all 2693 offspring were preserved and subsequently examined microscopically for external, visceral and skeletal abnormalities. There were no reproductive or teratogenic effects observed with 35% nitrous oxide, but adverse effects were observed with 50% nitrous oxide. The addition of fentanyl to the nitrous oxide increased the mortality rate among the rats, but did not significantly add to the adverse reproductive or teratogenic effects of nitrous oxide.

Abnormalities, Drug-Induced↗
PubMed1987

Mutagenicity of the combination of a volatile anaesthetic and nitrous oxide.

The mutagenic potential of halothane, enflurane and isoflurane in combination with nitrous oxide was investigated using the sex-linked recessive lethal assay in the fruit fly Drosophila melanogaster. Male wild-type flies were exposed for 1 h to 1 or 2% volatile anaesthetic with various concentrations of nitrous oxide up to 75%. They were then mated with untreated females of the Basc marker strain. A brooding pattern was used to assess mutagenicity at different germ cell stages. The rate of lethal mutations was assessed in the F2 generation. Halothane produced a dose-dependent increase in the rate of lethal mutations, but the mutagenicity was independent of the presence of nitrous oxide and of the stage of germ cell formation. Neither enflurane nor isoflurane was mutagenic in the presence of nitrous oxide.

Anesthesia, Inhalation↗
PubMed1987

Inhibition of rat fetal methionine synthase by nitrous oxide. An in vitro study.

The effect of in vitro exposure to nitrous oxide on rat fetal and maternal methionine synthase activity was investigated. Enzyme solutions were prepared from livers of fetuses and mothers on day 19 of gestation and exposed to air, 50% oxygen or 50% nitrous oxide in oxygen for periods up to 24 h. Normal activity of methionine synthase in the fetus was about 65% of that in the mother. Activity decreased by about 25% over 24 h when the enzyme was incubated at 37 degrees C in the presence of either air or 50% oxygen. Nitrous oxide produced a time-dependent decrease in activity which generally was similar for both fetal and maternal enzyme. After 24 h exposure to nitrous oxide, activity has decreased to 14 and 17% of fetal and maternal control values, respectively.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1987

Halothane metabolism in cirrhotic rats.

A rat model was used to determine whether the metabolism of halothane is changed in the presence of cirrhosis and whether exacerbation of liver dysfunction is correlated with such a change. Cirrhosis was produced by gavaging enzyme-induced male Wistar rats with carbon tetrachloride in corn oil once weekly for 12 weeks. Control rats received corn oil only. After a 3-week period without treatment, blood and urine were collected from each rat for determination of background levels of inorganic fluoride, bromide, and trifluoroacetic acid (halothane metabolites) and for assessment of liver function. Rats were then anesthetized with 1.05% halothane in 50% oxygen for 3 h. Following anesthesia, serial blood and urine samples were taken to monitor halothane metabolism and liver function. No differences were observed between cirrhotic and non-cirrhotic rats in serum levels and urinary excretion of halothane metabolites. However, serum levels of SGOT and SGPT were significantly increased about 1.5-fold in the noncirrhotic group and about 2.5-fold in the cirrhotic group after anesthesia. The increased levels observed in the cirrhotic group were significantly greater than in the noncirrhotic group. The results imply that the exacerbation of liver dysfunction after halothane anesthesia is most likely related to an indirect effect, such as change in liver blood flow, rather than to toxic metabolites.

Animals↗
PubMed1987

Reproductive and teratogenic effects of nitrous oxide, isoflurane, and their combination in Sprague-Dawley rats.

The reproductive and teratogenic effects of nitrous oxide (N2O), isoflurane, and their combination were studied in 130 timed-pregnant rats. Rats were exposed to either air, 0.35% isoflurane (1/4 MAC), 50% N2O (a known teratogenic concentration), or 50% N2O plus 0.35% isoflurane for 24 h on day 8 of pregnancy. On day 20 of pregnancy, cesarean sections were performed; a total of 1268 offspring were delivered and immediately examined for external abnormalities. They were subsequently examined microscopically either for visceral or skeletal abnormalities. N2O caused significantly higher incidences of early and late resorptions, and major visceral malformations. The addition of isoflurane to N2O prevented the majority of these adverse effects. These results cast doubt on the methionine synthase inhibition theory of N2O teratogenicity.

Abnormalities, Drug-Induced↗
PubMed1986

Reproductive and teratogenic effects of nitrous oxide, halothane, isoflurane, and enflurane in Sprague-Dawley rats.

A total of 305 timed-pregnant Sprague-Dawley rats were exposed for 6 h a day on each of three consecutive days in one of three periods, i.e., pregnancy days 14-16, 11-13, or 8-10, either to 0.55 times the minimum alveolar concentration (MAC) of nitrous oxide (75%) or to 0.75 MAC of halothane (0.8%), isoflurane (1.05%) or enflurane (1.65%); an additional 232 positive-control (retinoic acid) and air control rats were studied. Reproductive indices were determined, and the 5178 offspring delivered at cesarean section were examined for external, internal, and skeletal abnormalities. There were no major or minor teratologic effects in anesthetic treated groups, although several developmental variants were observed in halothane- and enflurane-treated groups. Nitrous oxide exposure on days 14-16 resulted in a three-fold increase in fetal resorptions. The results suggest that the volatile anesthetics are not teratogenic and confirm that nitrous oxide may be associated with increased reproductive loss.

Abnormalities, Drug-Induced↗
PubMed1986

Carcinogen bioassay of nitrous oxide in mice.

A carcinogen bioassay of nitrous oxide (N2O) was performed in groups of male and female Swiss-Webster mice exposed to either air (n = 179), 10% N2O (n = 152), or 40% N2O (n = 151) for 4 h per day, 5 days per week. After 78 weeks of exposure, there was a 5-week period without treatment following which surviving mice were killed. Mice killed at this time or dying in extremis at other times were subjected to complete autopsy unless advanced autolysis or cannibalism precluded examination. Mean body weights for male and female mice in the 10% N2O group were the same as those in the air control group throughout the study, whereas they were 5% less in the 40% N2O group. Mean organ weights for N2O-treated mice were not statistically different from those of control mice. Gross and microscopic examination of tissues revealed a variety of neoplastic and nonneoplastic lesions; however, their presence was unrelated to treatment.

Adenoma↗
PubMed1985

Fetal development in mice exposed to isoflurane.

The developmental toxicity of trace (0.006%), subanesthetic (0.06%), and light anesthetic (0.6%) exposure to isoflurane was examined in Swiss/Webster mice. No adverse effects were demonstrated following exposure of dams to 0.006% (n = 26) and 0.06% (n = 27) isoflurane for 4 hr daily on days 6-15 of pregnancy. Exposure to 0.6% isoflurane (n = 23) for the same period resulted in significantly decreased fetal weight, decreased skeletal ossification, minor hydronephrosis, and increased renal pelvic cavitation. The incidence of cleft palate also was significantly increased, abnormalities occurring in 12.1% of fetuses and affecting 11 of 23 litters. This incidence was considerably higher than that of the combined treatment and colony control groups (0.75%) and those that we have found in previous experiments with this mouse strain following exposure to halothane (1.2%) or enflurane (1.9%).

Abnormalities, Drug-Induced↗
PubMed1985

Toxicity and teratogenicity of inhaled anesthetics in Drosophila melanogaster.

The toxic and teratogenic effects of inhaled anesthetics were assessed in an in vivo assay using the fruit fly Drosophila melanogaster. Eggs were exposed during development (metamorphosis) to enflurane, isoflurane or halothane at a vapor concentration of 0.1 or 0.2% (v/v), to fluroxene at 0.025 or 0.05% (v/v), or to nitrous oxide at 20 or 40% (v/v). Flies produced in each group were counted and were examined for morphological abnormalities within one day of hatching. All the anesthetics except nitrous oxide produced a dose-dependent increase in the duration of metamorphosis and a decrease in the number of flies. Despite these effects on development, no morphological abnormalities were observed in any fly.

Abnormalities, Drug-Induced↗