Professional Educational Opportunities

Sexuality and Disability -     

From the Editor of Sexuality and Disability: The More We Listen to What is Being Said,the More We Can Learn

Sexuality and Disability -     

Phospholipase A2-catalyzed conversion of hepatic cytochrome P450 to P420 in microsomal membranes prepared from young and old rats

Previous studies from this Laboratory have revealed few significant age-related changes in either hepatic microsomal cytochrome P₄₅₀ content or NADPH-cytochrome P₄₅₀ reductase activity, prompting the suggestion that the nearly ubiquitous age-associated decline in the hepatic metabolism of xenobiotics by the mixed-function oxidases is a result of alterations in the lipid matrix in which the macromolecular components are organized. In order to examine this postulate, the membrane microenvironment surrounding hepatic microsomal cytochrome P₄₅₀ was enzymatically digested with snake venom phospholipase A₂, and the kinetics of conversion of cytochrome P₄₅₀ to cytochrome P₄₂₀ determined for preparations obtained from rats of varying age. There were no significant differences in the kinetics of conversion of cytochrome P₄₅₀ to cytochrome P₄₂₀, suggesting that there are no significant age-related changes in the lipid microenvironment immediately adjacent to cytochrome P₄₅₀. However, there was a slight difference, independent of age, in the rate of conversion of cytochrome P₄₅₀ to cytochrome P₄₂₀ between smooth and rough microsomes. The results are discussed in terms of general experimental approaches toward understanding drug metabolism in senescent organisms.     

Neurobiology of Bipolar Illness: Implications for Future Study and Therapeutics

Many findings implicating prefrontal cortical and limbic areas of the brain and endocrine systems in the neuropathology and pathophysiology of bipolar illness have greatly increased our understanding of the neurobiology of the illness. New imaging techniques such as PET, MRI, SPECT, and MRS have detailed more evidence of specific regional alterations in the brains of bipolar patients than was thought possible just 20 years ago. These methods are beginning to be used to help predict response to treatment. Examining the mechanisms of action of mood stabilizers (such as lithium, carbamazepine, and valproate) has provided clues to potential underlying neurobiological abnormalities in the illness. Recent studies of postmortem brain tissue have begun to confirm prefrontal cortical and limbic neurochemical and microstructural alterations in patients with bipolar illness compared with controls. It is postulated that it is the balance between primary pathological versus secondary adaptive alterations in gene expression in the illness and their enhancement or dampening by pharmacotherapy, that may determine the episodic course of mood fluctuations and remissions. Further examination of the pathophysiology and neurobiology of bipolar illness should lead to both more effective treatments and, potentially, secondary and even primary episode prevention.     

The need for a standard national immunization record

Perhaps the most significant link in achieving the nation's immunization objectives is the extent of parental knowledge. Admittedly, this is a weak link. The 1990 federal objectives calling for an official format using common guidelines for completion of immunizations, though well-conceived, has not been used exclusively by health care givers. The lack of accord has permitted the proliferation of many different immunization records that are not only confusing to parents, but also to health care providers at times. A standard national immunization record could be an essential element in strengthening the weak link of parental knowledge of immunizations and stressing the importance of preserving such a record for a lifetime.     

Potentiation of 2-deoxy-D-glucose antinociception, but not hyperphagia by zolantidine, a histamine (H2) receptor antagonist.

Antagonism of the histamine (H2) receptor reduces antinociception induced by naloxone-resistant foot-shock, naloxone-sensitive foot-shock, and morphine with a rank-order potency similar to their H2 antagonism. The antimetabolic glucose analog 2-deoxy-D-glucose (2DG) produces antinociceptive and hyperphagic responses that dissociate from each other and are in part mediated by opioid systems. The present study determined the effects of the brain-penetrating H2 receptor antagonist zolantidine (ZOL) on 2DG antinociception on the tail-flick and jump tests, as well as on 2DG hyperphagia, in rats. ZOL (0.01-1 mg/kg) potentiated the antinociceptive responses induced by a moderate (450 mg/kg) dose of 2DG, but had lesser effects upon antinociception induced by a lower (100 mg/kg) 2DG dose. ZOL itself slightly increased jump thresholds, but not tail-flick latencies. Combinations of ZOL and 2DG produced supraadditive antinociception, even though ZOL failed to significantly shift the 2DG dose-response curve to the left. In contrast, ZOL failed to alter basal intake or 2DG hyperphagia, supporting previous evidence implicating the H1 but not the H2 receptor in these effects. These results further dissociate the antinociceptive and hyperphagic effects of 2DG, and also support previous results indicating both pro- and antinociceptive roles for H2 receptors.     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Acculturation and the probability of use of health services by Mexican Americans.

How does level of acculturation affect the probability that Mexican Americans use general health, mental health, and human social services? We studied this question using data from a general population sample of Mexican Americans (N = 1,055). Data were elicited in face-to-face interviews. After controlling for sociodemographic and economic factors, health status, and insurance coverage, Mexican Americans who were less acculturated had significantly lower probabilities of an outpatient medical visit for physical health problems and of a visit to a mental health specialist or human service provider for emotional problems. The less acculturated with good perceived general health were especially unlikely to receive outpatient medical care. Having Medicaid coverage was associated with a larger increase in the probability of an inpatient medical admission for the more acculturated than for the less acculturated. Other individual characteristics had generally similar effects on use of medical and mental health services for both the more and the less acculturated Mexican Americans.