Effects of oxytocin on in vitro ovarian contractility during the estrous cycle of the rat.
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Biomedical subjects
Publications and source records attributed to M Sala.
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The application into the rat conjunctiva of various phlogistic agents, such as croton oil, mustard oil and formaldehyde, elicits an increase of serum corticosterone linearly related to the log of the applied concentrations, so that from their parallelized regression lines it is possible to calculate the phlogistic potency of each tested agent in reference to croton oil. The time kinetic of such an increase (elicited by croton oil) is compared with that of two other parameters previously adopted as indirect quantitative indices of the phlogosis: the adrenal ascorbic acid depletion and the liver tyrosine-alpha-ketoglutarate transaminase increase. Serum corticosterone is shown to be the quickest and the most sensitive of the adopted indices, even if the phlogistic potency of the tested agents and the precision of these evaluations substantially coincides whatsoever the index adopted. Finally the pathways of adrenocortical activation are investigated and it is shown that the activation may be peripherally blocked by topical application of corticosteroids (but not of local anesthetics) and centrally by hypophysectomy or parenteral administration of pentobarbital plus morphine.
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Given that a number of the techniques used to test drug abuse liability are not free from criticism, a series of oral free-choice experimental procedures was adopted. When simultaneously offered as alternatives to glucose using the classical polydipsic procedure, no preference for buprenorphine (0.025 mg/ml), morphine (0.5 mg/ml) or fentanyl (0.005 mg/ml) solutions was shown by premedicated rats. The same result was obtained when the two-bottle procedure was used for at least one month to offer etonitazene (10 micrograms/ml), buprenorphine (60 micrograms/ml), cocaine (300 micrograms/ml) and haloperidol (25 micrograms/ml) solutions as simultaneous alternatives to aspartame. This absence of preference was maintained even when the rats showed evident pharmacological effects and, in the case of the opiates, tolerance and withdrawal syndrome. However, when a gustatory marker (quinine) was introduced into one of the two solutions, preference was always shown for the other. Finally, in a conditioned taste aversion (CTA) test, etonitazene (5 or 40 micrograms/kg, i.p.) and haloperidol (0.5 or 2 mg/kg, i.p.) did not induce any reduction in saccharin consumption, while morphine (40 mg/kg) did. Pretreatment with naloxone (120 micrograms/kg, i.c.v.) did not antagonize morphine-induced CTA, while it did antagonize morphine-induced analgesia.
Previous epidemiological studies have indicated an association between the ingestion of opium pyrolysates, dietary deficiencies, and a high incidence of oesophageal cancer in subjects in north-east Iran. Laboratory studies have shown that pyrolysates of opium and particularly of morphine, a major opium alkaloid, are highly mutagenic in bacteria and induce sister-chromatid exchanges in mammalian cells after metabolic activation. We now report the ability of these pyrolysates to transform Syrian hamster embryo cells in culture and present some evidence for their carcinogenicity in mice and hamsters following topical, subcutaneous, intratracheal and intragastric administration. 6 of the most abundant mutagenic compounds present in morphine pyrolysate were isolated and purified by high-performance liquid chromatography and characterized by gas chromatography/mass spectrometry and 1H-Fourier transform nuclear magnetic resonance spectroscopy. These hitherto unknown compounds, all containing a hydroxy-phenanthrene moiety, were identified as: 3-methyl-3H-naphth[1,2-e]indol-10-ol; 1,2-dihydro-3-methyl-3H-naphth[1,2-e]indol-10-ol; 6-methylaminophenanthren-3-ol; 2-methylphenanthro[3,4-d] [1,3]oxazol-10-ol; 2,3-dimethyl-3H-phenanthro[3,4-d]imidazol-10-ol and 2-methyl-3H-phenanthro[3,4-d]imidazol-10-ol. Mutagenicity in Salmonella typhimurium TA98 of these compounds increased in the order listed, the last compound being 35 times more active than benzo[a]pyrene. The mechanisms, by which these mutagens are formed and metabolically activated are discussed.
Dermorphin, injected intracerebroventricularly (ICV) to rats, provokes, like to morphine, an inhibition of intestinal propulsion linearly related to the log of the administered doses (in the range from 0.06 to 0.56 micrograms/rat), but it is 143 times more active than morphine. Naloxone, ICV or IP, antagonizes dermorphin less effectively than morphine. Quaternary naloxone ICV administered antagonizes the intestinal effect of ICV dermorphin, while IP administered it is not effective until 8 mg/kg. The dose of dermorphin maximally active by the ICV route (0.56 micrograms/rat) is completely inactive when injected IP. Increasing doses of dermorphin IP (from 12 to 6400 micrograms/kg) inhibit intestinal propulsion to the same extent irrespectively of the doses employed, but never by more than 50%. Only a high dose of naloxone (30 mg/kg/IP) antagonizes this IP effect. The central and peripheral components of this intestinal effect of dermorphin are discussed.
Hexachlorobenzene (HCB) is an organochlorine compound widespread in the environment, highly lipophilic, that accumulates in biological systems. It has been suggested that it should be classified as a dioxin-like compound. Newborns are exposed to organochlorine compounds across the placenta and through breastfeeding. Although HCB is one of the most common organochlorine compounds, the transplacental transference of HCB from mother to fetus during pregnancy has been scarcely documented. This study reports the levels of HCB, dichlorodiphenyl trichloroethane (DDT) and its metabolite p,p'DDE, polychlorinated biphenyls (PCBs), and beta-hexachlorocyclohexane (beta-HCH) in 72 maternal blood samples at delivery and in 69 cord blood samples, from which 62 corresponded to mother infant pairs born between May 1997 and September 1999 in a rural area highly exposed to HCB. Results show that all newborns presented detectable levels of HCB, PCBs, and p,p'DDE, and, to a lesser extent, of beta-HCH, the HCB levels being the highest. The geometric mean of HCB was 1.1 ng/ml, ranging from 0.3 to 5.7 ng/ml. Concentrations of HCB levels in cord blood (log ng/ml) were positively associated with concentrations in maternal blood (log ng/ml) (coefficient = 0.45, P < 0.01). Gestational age was not associated with the transplacental transfer of HCB. Maternal p,p'DDE and beta-HCH levels were also associated with newborn levels, but levels of PCBs were not. We conclude that HCB, similar to other organochlorinated compounds, has a transplacental transfer.
OBJECTIVE: [corrected] We describe a method for feasibility assessment of workplace health promotion (WHP) programs as a necessary prerequisite of any WHP program. METHODS: A total of 167 employees from five workplace communities participated in the study. A questionnaire on the basic components of feasibility (risk factors, attitudes to workplace health promotion interventions, and social-occupational context) was administered. RESULTS: Risk behaviours were common among the employees interviewed. Health promotion in the workplace was favorably viewed by 79% of subjects but reported participation would be lower. Interventions on diet and physical activity received the highest acceptance. Participation would be greatest among local administration employees. CONCLUSIONS: The method demonstrated its utility in obtaining useful data for designing workplace health promotion interventions.
The population of Flix (region of Ribera del Ebro, Tarragona) is highly exposed to hexachlorobenzene (HCB) due to the closeness of an electrochemical factory. Although the degree of HCB contamination in this population is still high, concentrations of HCB in the sera of women aged 18-40 years from 1997 to 1999 were 61% lower than those observed in 1994 (4.1 ng/ml vs. 10.6 ng/ml). Concentrations of dichlorodiphenyl dichloroethane (p,p'-DDE) and beta-hexachlorocyclohexane (beta-HCH) also decreased, although the difference was not statistically significant. In contrast, concentrations of polychlorinated biphenyls (PCB) in the period 1997-1999 showed a nonsignificant increase compared with those in 1994.
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The short-term (during tolerance to behavioural effects and withdrawal) and long-term (3, 6, 9 and 12 months after treatment) effects of morphine on mean total electroencephalographic spectral power (analysed by means of fast Fourier transform) and band distribution (delta, theta, alpha, beta) were studied in freely moving young rats implanted with chronic cortical bilateral recording electrodes. Morphine was administered i.p. daily for 1 month at weekly increasing doses of 20, 50, 100 and 200 mg kg-1, and the electroencephalogram was evaluated for 2 h at every change of dose. Treatment with 20, 50 and 100 mg kg-1 led to a significant increase in mean total spectral power 30-60 min from treatment. However, the dose of 100 mg kg-1 led to a smaller increase than that obtained with 50 mg kg-1 and no change was shown with the highest dose, suggesting the progressive development of tolerance. The modification observed for 100 mg kg-1 was accompanied by a relative increase in the delta and decrease in the theta and alpha power spectra. Between the last day of morphine and the first 3 days of abstinence, a progressive decrease in mean total spectral power accompanied by a significant increase in delta and beta and a decrease in theta and alpha frequency was observed. Long-term EEG activity and the counting of the pyramidal cells of the hippocampus failed to reveal any pathological findings after 3, 6, 9 and 12 months.
Hexachlorobenzene, an organochlorine compound that accumulates in humans, is widespread throughout the environment. In this study, we describe the health status of inhabitants of a rural village that surrounds an electrochemical factory characterized by high levels of hexachlorobenzene in the air. During 1994, we conducted a cross-sectional study of 1 800 inhabitants in the south of Catalonia, Spain, who were older than 14 y of age. We obtained information on lifestyles and occupational and medical histories via questionnaire. Self-reported health outcomes were validated against clinical records and cancer registry data. Serum levels of hexachlorobenzene were very high in males who worked in the electrochemical factory (geometric mean = 54.6 ng/ml in randomized participants). Levels were lower among subjects who had never worked in the electrochemical factory (females, 14.9 ng/ml; males, 9.0 ng/ml). Levels of other organochlorine compounds (i.e., beta-hexachlorocy-clohexane, 2,2-bis[p-chlorophenyl]-1,1-dichloroethylene) were in the same range found in other communities. Perceived health, prevalence of self-reported common chronic conditions, and porphyria cutanea tarda, thyroid pathology, Parkinson's disease, cancer, and reproductive outcomes were within the ranges observed in other studies. Employment in the plant, however, was associated with having any of the a priori selected health outcomes that were potentially related to exposure to hexachlorobenzene (odds ratio for cancer prevalence = 1.9; 95% confidence interval = 0.5, 7.6). Our population of workers and nonworkers had the highest levels of hexachlorobenzene ever described. The results suggest that exposure to hexachlorobenzene did not affect the general health status of the this population, but it was associated with specific health effects of the most highly exposed subjects.
A total of 60 children (mean age +/- SD 7.6 +/- 3.5 years, range 2 - 14.2 years) with recurrent respiratory infections were treated with bacterial wall extract plus bacterial ribosomes (Immucytal) or placebo sprayed into the nostrils and oropharynx three times a day for 1 or 2-week periods over 3.5 months. The treatment was completed by 58 subjects; two patients in the placebo-treated group were withdrawn, one for poor compliance and the other because of headaches. Respiratory symptoms improved from the first month in the Immucytal treated children, but not in the placebo group, with a reduction in the incidence of infections in the upper and lower airways. No changes were noted in respiratory function parameters. Treatment with Immucytal significantly increased serum immunoglobulin A (P less than 0.02) and immunoglobulin M (P less than 0.01) and enhanced skin response to the in vivo lymphocyte blastization test, but there was no significant change in the circulating lymphocyte subpopulations. Both physicians and the patients' parents judged the bacterial extract to be clinically better than the placebo. Immucytal, therefore, may provide a useful alternative therapy for recurrent respiratory infections in infancy.