Reproductive Function in Epilepsy

Summary: : The hypothalamic-pituitary-gonadal axis is a complex system within which both positive and negative feedback occur among its elements and higher brain systems. The occurrence of seizures and changes in the secretion of pituitary hormones can affect the feedback loop. Both seizures and antiepileptic drugs can affect the hypothalamic-pituitary-gonadal axis of males and females and cause changes in hormones and sexuality. Reproductive dysfunction has a social impact because of reduced fertility. Once conception occurs, live birth rates are not diminished. Prospective studies of men and women with epilepsy are needed.     

Hypothalamic lesions in rats with long-term streptozotocin-induced diabetes mellitus

Summary Sixteen male Wistar rats, 1 year after injection of streptozotocin or vehicle, were fixed by whole-body perfusion, the brains were removed and processed for light and electron microscopy. Study of semithin sections from the hypothalamic area revealed changes in the arcuate nucleus and median eminence. The lesions, in comparison with controls, were subjected to a blind semiquantitative evaluation. The following changes were observed by light microscopy in diabetic rats: accumulation of glycogen (P<0.01), degeneration of neurons (P<0.05), hypotrophy of tanycytes (P<0.01), and axonal changes. Electron microscopy of diabetic rats revealed that glycogen was increased in neuronal bodies and processes (axons, synapses), also in tanycytes, and glia cells. In neurons were seen: dilated and fragmented endoplasmic reticulum, degranulated ergastoplasm, loss of organelles, increased number of microtubuli, myelin figures, irregulatities in the form of nuclei, and appearance of chromatin. The tanycytes in diabetic animals were reduced in volume, had an increased nuclear cytoplasmic ratio, a reduced number of organelles, short basal processes, and almost complete loss of the apical processes. These changes demonstrate the existance, under experimental conditions, of an encephalopathy pathogenetically related to streptozotocin-induced diabetes.Supported by the Schweizer Nationalfonds grant No. 3. 198-0.77     

Central calcitonin exerts anoretic effects via the hypothalamus in chicks

Calcitonin (CT) causes satiety in mammals, but the mechanisms that mediate this effect are poorly understood. Additionally, there are no reports on CT-induced satiety within the avian class. Therefore, the purpose of this study was to elucidate some of the central mechanisms regulating CT-induced satiety in a non-mammalian vertebrate, the chick. Broiler-type chicks, at 4 days of age, responded to central CT (0.3, 1.0 and 3.0 nmol) with both reduced food and water intake. The effect on water intake was secondary to that of food. An increased number of c-Fos immunoreactive cells were found in hypothalamic nuclei associated with satiety including the arcuate nucleus, dorsomedial nucleus and ventromedial hypothalamus after central CT injection. Increased jumps, distance traveled and time spent perching on food containers were also observed, and these behaviors are likely not competitive with ingestion. Also, central CT injection was associated with reduced food pecks, but increased pecking efficiency. Blockage of corticotrophin releasing factor receptors did not prevent central CT-induced satiety. Central CT appears to be a regulator of satiety in chicks and this effect is likely mediated via interactions within the hypothalamus.     

Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions

BACKGROUND: Melatonin exerts oncostatic effects on different kinds of tumors, especially on endocrine-responsive breast cancer. The most common conclusion is that melatonin reduces the incidence and growth of chemically induced mammary tumors, in vivo, and inhibits the proliferation and metastatic behavior of human breast cancer cells, in vitro. Both studies support the hypothesis that melatonin oncostatic actions on hormone-dependent mammary tumors are mainly based on its anti-estrogenic actions. METHODS AND RESULTS: Two different mechanisms have been proposed to explain how melatonin reduces the development of breast cancer throughout its interactions with the estrogen-signaling pathways: (a) the indirect neuroendocrine mechanism which includes the melatonin down-regulation of the hypothalamic-pituitary reproductive axis and the consequent reduction of circulating levels of gonadal estrogens and (b) direct melatonin actions at tumor cell level. Melatonin's direct effect on mammary tumor cells is that it interferes with the activation of the estrogen receptor, thus behaving as a selective estrogen receptor modulator. Melatonin also regulates the activity of the aromatases, the enzymes responsible for the local synthesis of estrogens, thus behaving as a selective estrogen enzyme modulator. CONCLUSIONS: The same molecule has both properties to selectively neutralize the effects of estrogens on the breast and the local biosynthesis of estrogens from androgens, one of the main objectives of recent antitumor pharmacological therapeutic strategies. It is these action mechanisms that collectively make melatonin an interesting anticancer drug in the prevention and treatment of estrogen-dependent tumors, since it has the advantage of acting at different levels of the estrogen-signaling pathways.     

Rigidity,hyperpyrexia and coma following fluphenazine enanthate

Beginning one day after receiving fluphenazine enanthate (Prolixin Enanthate®), 25 mg, subcutaneously, an acute schizophrenic girl with mixed schizoaffective and excited catatonic symptomatology became mute and withdrawn, then developed severe muscular rigidity and hyperpyrexia, and finally became comatose. The patient developed large increases in serum creatine phosphokinase (CPK) activity by the third day of this syndrome. The previously described symptoms, which have been labeled the neuroloptic malignant syndrome (Delay and Deniker, 1968), diminished with supportive treatment and intravenous benztropine mesylate (Cogentin®). Because of renewed psychotic behavior, phenothiazine treatment was eventually restarted, including treatment with fluphenazine enanthate, without recurrence of the extrapyramidal or hypothalamic symptoms. The difficulty in distinguishing between the neuroleptic malignant syndrome and Stauder's acute lethal catatonia is emphasized. The relationship between these syndromes and malignant hyperpyrexia is discussed. Possible causes of the increased serum CPK activity are discussed.     

Localization of an isoform of car☐ylesterase in rat brain differs from that in human brain

Liver car☐ylesterase (CE) is an enzyme capable of metabolizing drugs, and may also function as a regulator of lipid metabolism. We examined two isoforms of CE (RH1 and RL1) by immunohistochemistry in rat brain. The anti-RL1 antibody did not stain any brain structures. Teh anti-RH1 antibody, however, stained oligodendrocytes in all brain tissues and tanycytes, as well as some neurons in the deep cingulate gyrus, various hypothalmic nuclei and the spinal trigeminal nucleus. In the central nervous system, rat CE may function as a protective factor against foreign chemicals in these glial and neuronal cells. The distribution differed from that of the homologous human isoform which has been previously found only in endothelial cells in human brain. A possible relation between RH1 positive neurons and the medial pain system is discussed.