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Biomedical subjects

R George

Publications and source records attributed to R George.

At least 181 records · Page 10Linked to original sources

Thermoregulation in hyperthyroid rats: mechanism underlying the lack of hypothermic response to morphine in hyperthyroid animals.

Previous experiments in our laboratory demonstrated that morphine, at doses which produced pronounced hypothermia in normal rats, not only failed to decrease but instead increased body temperature in thyroxine-treated animals. The present studies were undertaken to further investigate these initial findings. In animals treated chronically with subcutaneous thyroxine, basal body temperatures were elevated and morphine induced only hyperthermia whether given subcutaneously (10 mg/kg) or centrally (30 micrograms) into the anterior hypothalamus. Basal oxygen consumption, which reflects metabolic heat production, was significantly elevated when compared to controls. In response to morphine, control animals showed decreased oxygen consumption while thyroxine-treated animals showed a slight increase. In both groups of animals, changes in core temperatures reflected changes in oxygen consumption. These results indicate that hyperthyroid animals fail to decrease body temperature in response to morphine because they are unable to decrease metabolic heat production. Morphine, acting at central hypothalamic sites, reduces heat production in normal animals, but in thyroxine-treated animals morphine cannot overcome the increased thermogenesis.

Animals↗

Polyphosphoinositide activation of cholesterol side chain cleavage with purified cytochrome P-450scc.

Highly purified beef adrenal cytochrome P-450 specific for cholesterol side chain cleavage (P-450-scc) has been reconstituted with sonicated vesicles containing cholesterol and either dimyristoyl phosphatidylcholine (DMPC) or dioleoyl phosphatidylcholine (DOPC). When cholesterol was present in DMPC vesicles at 1:15 molar ratio, cardiolipin and L-alpha-phosphatidylinositol 4-monophosphate (DPI) increased side chain cleavage by at least 5-fold (0.7 min-1-3.5 min-1). In DOPC vesicles, a smaller increase was observed (2.8 min-1-5.0 min-1). Activator phospholipids increased the rate of transference of cholesterol both to and from the cytochrome when, respectively, cholesterol-free P-450scc and cholesterol-P-450scc complex are combined with either DMPC or DOPC vesicles. Transfer of cholesterol to and from cytochrome P-450 occurred with similar first order rate constants and was also independent of the concentrations of cholesterol vesicles and P-450. It is suggested that transfer in both directions is limited by the rate of insertion of P-450scc into the membrane. Phospholipid stimulatory effects for both cholesterol transfer and for activation of side chain cleavage occurred with the same ranking, even though cholesterol transfer, following reconstitution, was 5-10 times slower than the turnover of side chain cleavage. DPI increased Vmax for side chain cleavage in both DMPC and DOPC vesicles to the same rate (12 min-1) without effect on the Km for cholesterol, while cardiolipin both produced a similar increase in Vmax and decreased Km (cholesterol). This activation by DPI is attributed to more favorable incorporation of P-450scc in these membranes and is consistent with previously reported effects of acidic phospholipids on other mitochondrial proteins.

Adrenal Cortex↗

A comparison of definable traits in women requesting reversal of sterilization and women satisfied with sterilization.

More women of reproductive age are being sterilized. Some of these women regret the decision and subsequently request a reversal of sterilization, whereas others do not. This study was undertaken to develop a profile of easily definable traits of 159 women who requested a reversal of sterilization and compare it with that of 160 women who apparently were satisfied with sterilization. Statistically significant differences were found. Remarriage was the most common cause for regret among women in the group which requested reversal of sterilization. Women in this group married younger, completed their family earlier, and were sterilized at a younger age. These women had significantly fewer live children and had undergone more therapeutic abortions (p less than 0.005).

Abortion, Therapeutic↗

Endocrine influences on the actions of morphine. III. Responses to hypothalamic hormones.

As part of an assessment of endocrine influences on the actions of morphine, we have studied the effects of intracerebroventricular administration of somatostatin and thyrotropin releasing hormone (TRH) on the antinociceptive, temperature and cataleptic responses to subcutaneous morphine in both intact and hypophysectomized rats. Somatostatin significantly antagonized morphine-induced antinociception in intact, but not in hypophysectomized, animals. TRH, on the other hand, had no effect on antinociceptive response to morphine in either intact or hypophysectomized animals. Neither hormone altered hyperthermic response to morphine but TRH antagonized the hypothermic response. Similarly, TRH antagonized the cataleptic actions of morphine whereas somatostatin had no effect. These results indicate that somatostatin and TRH can attenuate certain actions of morphine in vivo and suggest that specific opiate actions may be modulated by specific hypothalamic hormones.

Animals↗

Endocrine influences on the actions of morphine. I. Alteration of target gland hormones.

There are few data concerning the effects of hormones on opiate actions. Consequently, we have studied the influences of peripheral endocrine systems upon sensitivity and tolerance to three major morphine effects: antinociception, hypothermia and catalepsy. It was found that in opiate naive animals adrenalectomy increased morphine-induced antinociception, hypothermia and catalepsy, whereas dexamethasone treatment decreased all three opiate effects. Thyroidectomy decreased the antinociceptive and cataleptic actions of morphine, but had no effect on the hypothermic response. Thyroxine treatment markedly altered the temperature response to morphine without affecting the other two actions. Control animals showed both hyperthermia and hypothermia after morphine, but animals treated chronically with thyroxine showed only hyperthermia. Alterations of the gonadal axis in males had no pronounced effects upon the actions of morphine. Further investigations demonstrated that morphine, when administered i.c.v. to thyroidectomized animals, produced responses similar to those seen after s.c. administration. During chronic studies, the only notable effects of endocrine alterations on the development of tolerance to morphine were trends toward suppression with dexamethasone treatment and trends toward augmentation after adrenalectomy. These results indicate that the actions of morphine are influenced by endocrine status. Adrenal hormones exert their effects upon the actions of morphine via peripheral metabolic alterations, whereas the effects of thyroid hormones are mediated at central sites. These results also indicate that the development of tolerance to morphine is not significantly influenced by any of the endocrine systems studied.

Adrenalectomy↗

Endocrine influences on the actions of morphine. II. Responses to pituitary hormones.

Studies have been made on the hypophysectomy-induced changes in antinociceptive and temperature responses to morphine and the effects various anterior pituitary hormones have on these altered responses under both acute and chronic conditions. Hypophysectomy altered the slope of the dose-response curve for morphine antinociception without significantly changing the ED50. It also induced an upward shift in the temperature-response curve. Treatment of hypophysectomized animals with s.c. adrenocorticotropic hormone decreased responsiveness to the antinociceptive and the hyperthermic actions of morphine. Administration of triiodothyronine increased the antinociceptive response and normalized the upward shift in the temperature response; however, these effects required approximately 3 weeks of hormone treatment. Both of these treatments normalized the altered antinociceptive dose-response curve slope. Growth hormone, luteinizing hormone and prolactin had no effects on acute morphine responses. Further experiments examined the effects of anterior pituitary hormones during chronic treatment with morphine. Adrenocorticotropic hormone, when administered 30 min before morphine, showed reproducible but statistically nonsignificant suppression of tolerance development. Growth hormone, which had no effects on acute morphine responses, was more effective than adrenocorticotropic hormone at suppressing tolerance. In studies with animals bearing growth hormone/prolactin secreting tumors, significant suppression of tolerance was seen for both responses to morphine. These results add further support to previous findings from our laboratory that the adrenal and thyroid systems are involved in modulation of acute opiate actions and also indicate that growth hormone can inhibit the development of opiate tolerance.

Analgesia↗

Domperidone elevates rat plasma beta-endorphin-immunoreactivity when administered peripherally but not intracerebroventricularly.

Domperidone, a dopamine receptor antagonist which apparently does not penetrate the blood-brain barrier in rats was administered to adult males. Domperidone 500 micrograms and 100 micrograms, given through intracarotid cannula, significantly elevated plasma beta-endorphin-immunoreactivity (beta-EP-I) at +15 min. To show that only a peripheral site(s) of action is implicated, domperidone was given to rats by cannulae implanted into both lateral ventricles. Plasma beta-EP-I was unaffected by this route of administration. These results suggest that plasma beta-EP-I is tonically inhibited by dopamine acting at site(s) outside of the blood-brain barrier.

Animals↗

Differential diagnosis and treatment planning of the surgical orthodontic class III malocclusion.

The decision to reposition the mandible posteriorly or the maxilla anteriorly in the treatment of Class III malocclusions depends upon multiple clinical, cephalometric, and biomedical considerations. In each case the decision must be made on teh basis of frontal and profile treatment objectives, occlusion, and the needs of the patient. In many instances, depending upon the magnitude of the disharmony, the treatment plan will be based upon the clinical judgment and experience of the surgeon and orthodontist. Surgery for the Class III patient is equally predictable and stable, whether the maxilla or the mandible is moved. This article discusses the diagnostic criteria by which one might evaluate and plan treatment for a patient with a Class III malocclusion and facial disharmony.

Adult↗

Bleeding manifestations of dengue haemorrhagic fever in Malaysia.

Analysis of the bleeding manifestations of 130 cases of dengue haemorrhagic fever admitted into the Children's ward of the General Hospital, Kuala Lumpur from May 1973 to September 1978 has been done. Petechial skin rash, epistaxis and gum bleeding were seen most commonly in mild and moderately severe cases. However, blood stained gastric aspirates, and severe haematemesis were seen in severe or very severe cases. Though with better vector control and preventive measures, a marked reduction in the incidence of the cases has been noted, severe cases were seen with symptoms of shock and gastrointestinal bleeding. These symptoms carried a bad prognosis. Among 15 children that died 10 had gastrointestinal bleeding and 2 had a disseminated intravascular coagulation defect. Lymphocytosis with atypical lymphocytes, low platelet count, low reticulocyte count and raised packed cell volume were the main haematological features seen in all these cases. All these features reverted to normal within a week. Mild evidence of disseminated intravascular coagulation was seen in a number of cases, but severe features were seen only in four. Two cases improved as a result of heparin therapy.

Age Factors↗

A comparison of serum phenytoin determination by the substrate-labeled fluorescent immunoassay with gas chromatography, liquid chromatography, radioimmunoassay and "EMIT".

Patients' sera were analyzed for phenytoin by the Substrate-Labeled Fluorescent Immunoassay (SLFIA), gas chromatography (GC), liquid chromatography (LC), Radioimmunoassay (RIA) and EMIT and the results were compared. The EMIT assay was performed using a "PACER Analyzer". All assay results compared favorably. The correlation coefficients were: SLFIA vs GC, 0.995 (n = 45); SLFIA vs. LC, 0.993 (n = 37); SLFIA vs. EMIT, 0.965 (n = 67); SLFIA vs. RIA, 0.977 (n = 34). These results show that phenytoin levels determined by the SLFIA compare well with those obtained by the other four assay techniques.

Chromatography, Gas↗