Effects of low doses of transdermal 17 beta-estradiol on carbohydrate metabolism in postmenopausal women.

The impact of a 3-month continuous administration of transdermal estradiol (E2-TTS 50; 50 micrograms/day) or oral conjugated estrogen (CE; 0.625 mg/day) on glucose and lipid metabolism was investigated in two groups (n = 15/group) of postmenopausal women. Fasting levels of glucose, insulin, and C-peptide; C-peptide/insulin ratio (index of hepatic insulin clearance); and their responses to a 75-g oral glucose tolerance test (OGTT) were evaluated before and after 3 months of continuous estrogen administration. E2-TTS 50 modified carbohydrate metabolism, decreasing fasting insulin levels (P less than 0.01) and increasing the pancreatic islet response to glucose challenges, as indicated by an increased integrated value of the C-peptide curve associated with OGTT (P less than 0.05). Despite greater C-peptide secretion, integrated peripheral insulin after OGTT was decreased (P less than 0.05). The resulting increase in the integrated curve of the molar C-peptide/insulin ratio (P less than 0.01) indicated elevated hepatic insulin clearance after E2-TTS 50 administration. CE treatment did not modify carbohydrate metabolism, except for reducing fasting glucose levels (P less than 0.01). Neither therapy modified lipid metabolism, but a slight increase in circulating triglycerides (P less than 0.01) was observed during CE administration. Our data show that the addition of low doses of natural estrogens does not negatively influence glucose and lipid metabolism in postmenopausal women. By contrast, reversal of postmenopausal hypoestrogenism to early follicular phase estrogenic values with E2-TTS 50 administration seems to exert a beneficial effect on glucose metabolism by increasing hepatic insulin clearance.     

Long-term neurological assessment of the post-resuscitative effects of flunarizine, verapamil and nimodipine in a new model of global complete ischaemia

In anesthetized rats, global complete ischaemia lasting for 9 min was induced by controlled hydraulic compression of the chest. A neurological score, based on cranial and spinal reflexes, postural tone, gait, movement and limb placement, was determined at 2 hr and 1, 2, 3, 7, 14, 21 and 28 days after resuscitation. Three doses of three calcium antagonists, flunarizine, verapamil and nimodipine and their respective solvents, were given intravenously during the resuscitation. The total neurological score was significantly better than solvent with 0.16 and 0.63 mg/kg of flunarizine and 0.04 and 0.16 mg/kg of verapamil; it was significantly better with solvent (10% ethanol) than with 0.04 and 0.16 mg/kg of nimodipine. The deficiency in tactile placing reactions of the hindpaws was the most resistant to therapy. This non-invasive model of global ischaemia in rats seems useful for the evaluation of drugs, since it requires minimal anesthesia and allows assessment of neurological recovery over an extended period of time.     

Neuroendocrine evaluation in catamenial epilepsy

The hypothesis that catamenial epilepsy depends on abnormal rhythmic hormone activity in the hypothalamus-pituitary-gonadal axis has never been critically tested. No significant modifications in the secretory pattern of pituitary hormones, both basally and in response to stimulatory tests, were found in a group of catamenial epileptic women. On the contrary, our data showed a reduction of luteal phase progesterone secretion. These findings indicate that an imbalanced secretion of ovarian steroids plays a role in the catamenial exacerbation of epilepsy.     

Improved short-term neurological recovery with flunarizine in a canine model of cardiac arrest

A 10-minute cardiac arrest was produced in dogs by electrical fibrillation of the heart. Recovery of cerebral function was monitored by estimating the cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow (CBF), electroencephalograph (EEG) and extent of neurological deficit. The study group received flunarizine (0.1 mg/kg intravenously) at the beginning of resuscitation, while control animals were given the drug vehicle. By four hours after resuscitation, CMRO2 in flunarizine-treated dogs was 121 +/- 43% of pre-arrest baseline, as compared with 37 +/- 9% in control animals (P less than 0.02). In the flunarizine group, CBF was 83 +/- 21% of baseline, while it was only 31 +/- 8% in controls (P less than 0.01). As compared with the control group, no other significant changes were detected in electrocardiographic, hemodynamic, or biochemical parameters in the flunarizine-treated dogs. A significant improvement in the visual EEG score (P less than 0.001) and neurological deficit (P less than 0.05) was seen in flunarizine-treated dogs six hours after ischemic insult.     

Involvement of ovarian factors magnified by pharmacological induction of multiple follicular development (MFD) in the increase in Ca125 occurring during the luteal phase and the first 12 weeks of induced pregnancies

Objective To evaluate the relationship of ovarian activity on Ca125 production, we studied whether Ca125 production varies during the menstrual cycle both in normal ovulatory women and in women whose ovarian factors are significantly stimulated by multiple follicular development (MFD). Furthermore, since the first 12 weeks of pregnancy is characterized by the enhancement of corpus luteum function mainly in MFD-induced pregnancies, Ca125 levels were also evaluated in the first quarter of pregnancy both in spontaneous and in MFD-induced pregnancies.Subjects Subjects were normal ovulatory women in the late follicular phase (FP) (N =20) and in the luteal phase (LP) (N =20), 32 infertile women submitted to MFD with pure FSH, and 40 pregnant women in which pregnancy occurred spontaneously (N =20) or after induction of MFD (N =20).Results and Conclusions In regularly cycling women plasma Ca125 levels were constant during the menstrual cycle. In contrast, in stimulated cycles Ca125 levels were significantly higher (P < 0.0008) in the LP than in the FP. In addition, in these subjects Ca125 levels in the LP were significantly correlated (P < 0.0001, r = 0.686) with E₂ plasma levels. These data strongly suggest that an increase in corpus luteum function could be involved in Ca125 production. Since granulosa cells have not been demonstrated to produce Ca125, it can be hypothesized that endometrial or peritoneal cells submitted to exaggerated stimulation by ovarian activity are the source of increased Ca125 secretion. In agreement with this hypothesis, Ca125 levels were significantly higher in the first weeks of spontaneous pregnancies than in the luteal phase and they were also higher in MFD-induced pregnancies than in spontaneous pregnancies (P < 0.001).     

Involvement of the renal parenchyma in acute urinary tract infection: The contribution of99mTc dimercaptosuccinic acid scan

Summary We performed^99mTc dimercaptosuccinic acid (DMSA) scan and ultrasonography in 146 children during the acute phase of a proven urinary tract infection (UTI). In 99 a micturating cysto-urethrography and in 83 an intravenous urography was also done. The occurrence of fever and increased WBC count, CRP and ESR were also studied. It appeared from this retrospective study that 47% of the kidneys had a cortical or patchy pattern of decreased uptake of^99mTc DMSA, as compared to 23% with abnormal findings on US. Vesico-ureteral reflux was present in 38% of the kidneys with parenchymal involvement on^99mTc DMSA scan. Although fever, leucocytosis and elevated CRP and ESR were significantly correlated with abnormal^99mTc DMSA scan, they were also observed in children without renal parenchymal involvement. Our results suggest that^99mTc DMSA scan is a sensitive method for the detection of parenchymal involvement during acute UTI. The exact nature of these lesions and their relation with scars need, however, to be defined.     

Italian experience regarding the prevention of Duchenne and Becker muscular dystrophies

The indirect approach to carrier detection and prenatal diagnosis of Duchenne and Becker muscular dystrophies based on the study of DNA polymorphisms closely linked to this gene has been followed by five Italian laboratories in the study of 106 pedigrees. Out of 354 women studied up to 1 May 1987, 147 were identified as carriers because of pedigree information and/or of increased creatine phosphokinase (CPK) values. Of the remaining 207, 184 could be assigned to three arbitrarily defined risk categories (low, intermediate and high) using linkage analysis. This disaggregation of women at risk is clearly more useful than that defined before DNA analysis, in which the same 184 women could be assigned only to the low or intermediate risk categories. Prenatal diagnosis was theoretically possible in 90% of carrier women, and was actually performed in 14 pregnancies, which led to the identification of four affected male foetuses, one also having Down syndrome.Abbreviations DMD Duchenne muscular dystrophy - BMD Becker muscular dystrophy - CPK creatine phosphokinase - PND prenatal diagnosis     

Cyclo-oxygenase-inhibitors increase morphine effects on mesolimbic dopamine neurons

The effect of cyclo-oxygenase inhibitors, indomethacin and nimesulide, on the action of i.v. morphine on dopamine neurons projecting to the nucleus Accumbens was studied using standard extracellular recording techniques coupled with antidromic identification in unanesthetized rats. The i.v. administration of either nimesulide (3 mg/kg) or indomethacin (3.5 mg/kg) per se did not affect the firing rate of mesolimbic dopamine cells. In contrast, the subsequent administration of morphine (0.25-2 mg/kg i.v.) potently increased the firing rate of mesolimbic dopamine neurons in cyclo-oxygenase inhibitor-pretreated rats as compared with saline-pretreated rats. The maximal enhancement of basal firing rate at the highest dose of morphine tested was 92%, 80% and 47%, for nimesulide-, indomethacin-, and saline-treated rats, respectively. Our results indicate that the effect of morphine on mesolimbic dopamine cells is potentiated by blocking cyclo-oxygenase activity and suggest that the modulation of cyclo-oxygenase pathway in dopamine cells might be involved in the cellular mechanisms of the rewarding actions of morphine.