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Biomedical subjects

J Fishman

Publications and source records attributed to J Fishman.

At least 181 records · Page 10Linked to original sources
PubMed1976

An evaluation of the hot plate technique to study narcotic antagonists.

The mouse hot plate model, with slight differences from the way it is used to study narcotic analgesics, was evaluated as a method for determining the oral effectiveness, relative potency and duration of action of two standard narcotic antagonists, naloxone and naltrexone, and a new agent, 6-desoxy-6-methylene-naltrexone (ORF 11676). Naltrexone and ORF 11676 were found to be more effective orally than naloxone. Naltrexone and ORF 11676 were equipotent by 3 routes of administration and both were more potent than naloxone. Naloxone produced a significantly shorter duration of action than the other two drugs. It was concluded that the mouse hot plate method, used to detect and characterize the activity of narcotic antagonists, provides information compatible with that obtained in other species, including man.

Animals↗
PubMed1975

Narcotic antagonists. 4. Carbon-6 derivatives of N-substituted noroxymorphones as narcotic antagonists.

A series of new narcotic antagonists has been synthesized by modifying the C-6 carbonyl group in naloxone (Ia) and naltrexone (Ib). New functional units were introduced by reaction with various phosphorus and sulfur ylides and alkyllithium reagents. The activity of the new compounds were measured by the hot-plate and tail-clip tests after oral administration to mice. The majority of the new narcotic antagonists exhibited oral potencies considerably superior to the parent compounds, with 6-methylene derivatives IIa and IIb showing the most impressive increases.

Analgesia↗
PubMed1975

Psychiatric complications following coronary bypass surgery.

Previous studies of psychiatric complications following open heart surgery have included few if any patients who had coronary bypass surgery. This experiment reports the relative incidence of psychiatric complications in a sample of 97 open heart surgery patients of whom 51 patients (53 per cent) had coronary bypass surgery. The results suggest that the incidence of psychiatric symptoms following coronary bypass surgery is significantly lower (16 per cent) than that following cardiac valvular surgery (41 per cent). Several possible reasons for this large discrepancy in incidence of psychiatric complications are considered.

Age Factors↗
PubMed1975

Preparation and evaluation of a sustained naloxone delivery system in rats.

The use of a non-biodegradable polymer system to provide a sustained release of the narcotic antagonist naloxone in rats is described. The kinetics of morphine analgesia (measured by the hot-plate test) in the presence of the naloxone implant, and the urinary excretion of radiolabeled naloxone were measured. The shift of the morphine dose-response curve to the right is expressed in terms of dose ratios, which were calculated from the ED50 values for morphine obtained 9 days before, and 1, 8, 15, 22 and 29 days after implantation of the polymer. Our experiments indicate that effective levels of antagonist were maintained for 3-4 weeks after implantation of a polymer system containing 16 mg of naloxone. After 29 days, more than 95% of the absorbed drug had been released, with 16% of the implanted radioactivity appearing in the urine. These results demonstrate the feasibility of using a sustained release form of a narcotic antagonist to block the effects of morphine.

Animals↗
PubMed1975

Catechol estrogen formation in the central nervous system of the rat.

Conversion of estradiol and estrone to catechol estrogens by rat hypothalamic tissue but not by the cerebral cortex was demonstrated from the incubation of these tissues with estradiol-2-3H and estrone-2-3H and monitoring the incorporation of tritium into water. Direct evidence for this transformation was obtained by isolating the labelled phenazine derivative of 2-hydroxyestrone after hypothalamic incubation with estrone-4-14C.

Animals↗
PubMed1975

The affinity of catechol estrogens for estrogen receptors in the pituitary and anterior hypothalamus of the rat.

The purpose of these experiments was to evaluate the potential for interaction between 2-hydroxyestrone and 2-hydroxyestradiol and estrogen receptors in rat pituitary and anterior hypothalamus. The 150,000 X g supernatant fractions of these tissues were prepared, the estrogen receptor-site concentration was measured, and the relative abilities of unlabelled estradiol, estrone, 2-hydroxyestradiol and 2-hydroxyestrone to compete with [3H]estradiol for estrogen binding sites was determined. From these results, and the previously determined association constant for [3H]estradiol, 10(10)M-1, the association constants of the other estrogens were calculated. The introduction of the 2-hydroxy group caused only a modest reduction in the affinity of these estrogens for the receptors. The association constants of the 2-hydroxy derivatives were within one order of magnitude of those of the parent compounds. These results demonstrate the potential for interaction between catechol estrogens and estrogen receptor in rat brain and pituitary of a magnitude which could be biologically significant.

Animals↗
PubMed1975

Plasma estetrol as an index of fetal well-being.

Estetrol (15alpha-hydroxyestriol or E4) is considered to be a specific product of fetal liver and has been suggested as a good indicator of fetal well-being. The concentration of unconjugated estetrol (E4) was measured by rapid and specific radioimmunoassay in 1 ml of maternal plasma. E4 levels prior to the 18th week of pregnancy were often undetectable (smaller than 50 pg/ml). The mean plasma E4 level at term of 1.2 ng/ml was 7-fold higher than that observed at 24 weeks of gestation, and no diurnal variations were found. E4 levels in fetal plasma at term were 12-fold higher than those in maternal plasma and no fetal arterial venous differences were found. Umbilical vein but not maternal plasma levels of patients undergoing vaginal delivery were higher than those undergoing cesarean section (P smaller than 0.05) suggesting increased adrenal output of E4 precursors during labor. In patients with severe Rh-isoimmune disease plasma E4 levels were not helpful in assessing fetal well-being. However, in patients with chronic hypertension or pre-eclampsia, subnormal plasma E4 concentrations always preceded intrauterine fetal death. Plasma E4 appears to be a good indicator of fetal well-being in patients with hypertensive disease of pregnancy.

Amniotic Fluid↗
PubMed1975

Influence of body weight on estradiol metabolism in young women.

The metabolism of estradiol in girls with anorexia nervosa was compared with obese subjects and normal weight, age and sex matched controls. Increasing body weight was accompanied by a sharp decrease in 2-hydroxylation of estradiol and an increase in 16alpha-hydroxylation. These metabolic changes are discussed in terms of the biological activity of 2-hydroxyestrone and estriol.

Adolescent↗
PubMed1975

Changes in estradiol and cortisol production rates in men under the influence of narcotics.

The production rates of estradiol and cortisol in two male opiate addicts while on narcotic maintenance, were in the low normal or subnormal range. There was a sharp several-fold increase upon withdrawal with a subsequent fall to normal values after a period of abstinence. The changes in estradiol production rates were proportionally greater than those of cortisol and suggest that they were due to changes in testicular secretion of the precursor testosterone.

Adrenal Glands↗
PubMed1975

Hormone profiles in hormone-dependent cancers.

Studies on the relationship of urinary excretion of androgen metabolites and estrogens to the natural history of breast cancer are reviewed. The importance of distinguishing between "within-population" studies (i.e., cancer patients versus normal controls) and "between populations" studies (i.e., low-risk versus high-risk populations) is emphasized, and it is pointed out that "qualitative" agreement (i.e. the same direction of differences) between the two types of studies must be present in order to implicate a hormonal parameter as a determinant of the natural history of breast cancer. For reasons detailed in this paper, it is concluded that the reported relationship of low urinary androgen metabolite excretion to increased risk of developing breast cancer and poor response to adrenalectomy or hypophysectomy and the validity of the "estriol hypothesis," namely, that a high urinary ratio of estriol to estrone-plus-estradiol in early life is protective against subsequent development of breast cancer, are both dubious. A new hypothesis concerning the relationship of estrogens to breast cancer risk is presented: "A period of of time, prior to age 30, during which the amount of biological availability of active estrogens' (i.e., estrone and estradiol) is diminished, protects against subsequent development of cancer." This hypothesis is shown to be compatible with the epidemiological and biochemical data. Reports concerning the influence of nutrition on endocrine parameters are reviewed. Inanition and obesity have been shown to alter steroid metabolism but it is not known whether nutritional "microdifferences" (i.e., differences between populations or individuals that are due to cultural, geographic, or socioeconomic factors, but that fall within the range of "normal" or adequate nutrition) can also alter steroid metabolism.

Adrenalectomy↗