Serum levels of alpha-tocopherol (vitamin E) in Parkinson's disease.

To elucidate the possible role of vitamin E in the pathogenesis of Parkinson's disease (PD), we compared serum levels of alpha-tocopherol (vitamin E), measured by high-performance liquid chromatography, and the vitamin E/cholesterol ratio of 42 Parkinson's disease (PD) patients using their spouses as the control group. The serum levels of vitamin E did not differ significantly between the groups (13.84 +/- 0.56 micrograms/ml for PD and 14.80 +/- 0.57 micrograms/ml for controls), nor did the vitamin E/cholesterol ratio (0.64 +/- 0.03 for both groups). There was no influence of antiparkinsonian therapy on vitamin E or the vitamin E/cholesterol ratio. Serum levels of the vitamin E and vitamin E/cholesterol ratio did not correlate with age, age at onset, scores of the Unified Parkinson's Disease Rating Scale or the Hoehn and Yahr staging in the PD group. These results suggest that serum vitamin E concentrations do not play a role in the pathogenesis of PD.     

Micro1-opioid antagonist naloxonazine alters ethanol discrimination and consumption.

The endogenous opioid system is implicated in excessive ethanol-drinking behavior. However, the role of individual opioid receptor subtypes in the mechanism underlying excessive ethanol-drinking behavior is not yet well understood. Therefore, we investigated the ability of a selective micro1-opioid antagonist, naloxonazine, to modulate ethanol-drinking behavior and ethanol discrimination in a rat model with the use of ethanol self-administration and drug discrimination paradigms. The effects of naloxonazine (0.001-10 mg/kg) on ethanol intake were examined in Sprague-Dawley rats under conditions of limited access to 10% (wt./vol.) ethanol and ad libitum access to food and water. Pretreatment with high doses of naloxonazine (1-10 mg/kg) significantly reduced ethanol consumption. When the effects of naloxonazine on food intake in free-feeding male rats were examined, naloxonazine (1.8-10 mg/kg) significantly suppressed 24-h food intake. Another group of rats was trained to discriminate ethanol (1.25 g/kg, i.p.) from saline on a fixed-ratio schedule (FR 10), and ethanol dose-response tests were conducted once rats had acquired ethanol-saline discrimination. Injections were given 15 min before ethanol dose-response tests were conducted, and after characterization of the ethanol dose-response curve, the effects of naloxonazine on ethanol discrimination were assessed by administering naloxonazine (0.001-10 mg/kg, i.p.) 15 min before ethanol administration. Treatment with naloxonazine (0.001-1.8 mg/kg, i.p.) before the ED(100) dose of ethanol partially antagonized the discriminative stimulus of ethanol without having any effect on the response rate. The results support the suggestion of involvement of micro1-opioid receptors in the discriminative effects of ethanol and ethanol-drinking behavior.     

Acetylator polymorphism in multiple sclerosis

To elucidate whether any relationship exists between genetic polymorphic acetylation and the risk for multiple sclerosis (MS), we determined this polymorphism, using sulphamethazine, in 71 patients with definite MS and in 268 age-matched controls. Thirty-seven patients (52.1%) and 151 controls (56.3%) were classified as slow acetylators (not significant difference). No relation was found between acetylator polymorphism and age at onset of disease in MS patient's group. Our results do not support the existence of any relationship between acetylator polymorphism and the risk for MS.     

Mortality rate after hip hemiarthroplasty: analysis of risk factors in 299 consecutives cases

Abstract The femoral neck fracture is actually the most important traumatic event in the elderly, because of its high rate and terrible complications. We reviwed clinical records of 314 patients treated in our institution with a bipolar implant for femoral neck fracture. At a mean follow-up of 5 years, 15 patients (4.8%) were lost to followup so data for 299 patients was studied to identity factors associated with mortality. Ten predictor variables were examined: age, sex, waiting time for surgery, pulmonary dysfunction, fracture etiology, and comorbidity with ischemic heart disease, and heart failure, hypertension, cerebrovascular disease, and chronic renal failure. Cumulative mortality rate during the first 6 months was 19% (55 of 299 patients) and in the first year it was 25% (76 of 299). At logistic regression analysis, mortality was associated with age, male gender, waiting period for surgery and presence of neoplastic disease or pathological fracture. Waiting for surgery was a significant factor for mortality at 6, 12 and 24 months: patients surgically treated in the first 24 hours had lower mortality than those who waited longer. The risk of mortality in the first 6 months doubled for an age increase of 12 years, while mortality within 2 years doubled for an age increase of 9 years. Although the motality rate after surgery for femoral neck fracture was high in the first year (25%), it dropped off in successive years to levels observed in a healthy population. Thus, we agree with the literature that femoral fracture is a risk factor for survival only in the first year after trauma, above all in the elderly.     

Morphine-3-glucuronide: hyperglycemic and neuroendocrine potentiating effects

The greater potency of morphine-6-glucuronide (M6G) as well as the inactivity of morphine-3-glucuronide (M3G) with respect to the antinociceptive effects of the parent molecule, morphine (MOR), have been well established. It has been suggested that M3G is an antagonist of MOR's antinociceptive and respiratory depressive effects. The present study addressed the central nervous system (CNS) interaction of these opiate metabolites on their metabolic and hormonal effects. Whole body glucose kinetics were assessed on conscious, chronically catheterized, unrestrained rats. M3G (5 μg) or H₂O (5 μl) was injected intracerebroventricularly (i.c.v.) 15 min prior to the bolus administration of H₂O (5 μl), M6G (1 μg), or MOR (80 μg). i.c.v. M3G (5 μg) resulted in behavioral excitation, hyperglycemia (+50%), stimulation of glucose rate of appearance (R_a; +100%), glucose rate of disappeaance (R_d; +70%), and metabolic clearance rate (MCR; +33%) within 30 min after injection with no alterations in hormone concentrations. i.c.v. M6G and MOR produced progressive hyperglycemia with significantly high catecholamine and corticosterone levels. M3G pretreatment resulted in enhanced elevations in plasma glucose levels (+52% and +18%), plasma lactate (+138% and +108%), norepinephrine (+96% and +30%), and epinephrine (+62% and +67%) in response to both i.c.v. MOR and M6G administration. These findings suggest a non-opiate and non-hormonal mechanism for M3G-induced hyperglycemia. In contrast, the metabolic and hormonal responses to i.c.v. M6G and MOR are associated with elevations in catecholamine and corticosterone levels, which are remarkably enhanced by M3G pretreatment, most likely through accelerated catecholamine release. Our findings suggest a modulatory role for MOR glucuronidation, not only by rendering it inactive, as in the case of M3G, but by an interplay of the metabolic effects of the parent molecule and its metabolite