Positive and negative interactions in the behavioural expression of D1 and D2 receptor stimulation in a model of Parkinsonism: role of priming.

Previous exposure to a dopaminergic agonist (priming) strongly potentiates contralateral turning behaviour in response to D1 and D2 agonists in unilaterally 6-hydroxydopamine-lesioned rats. In order to study the influence of priming on the behavioural interaction of D1 and D2 receptors, we examined the effect of selective D1 and D2 receptor blockade on the contralateral turning induced by the mixed D2/D2 agonist apomorphine in drug-naive and primed 6-hydroxydopamine-lesioned rats. In drug-naive rats, apomorphine induced a dose-related, apparently monophasic rotation curve. Administration of selective D1 (SCH 23390) or D2 (raclopride) antagonists abolished the contralateral turning induced by 0.1 mg/kg of apomorphine and partially inhibited that induced by 0.5 mg/kg. In primed rats low doses of apomorphine (0.05 mg/kg) induced an apparently monophasic contralateral turning which was reduced by D1 receptor blockade and completely abolished by D2 receptor blockade; a higher dose of apomorphine (0.1 mg/kg) instead elicited a biphasic (two-peak) pattern of rotation. After this dose of the agonist, blockade of D1 or D2 receptors abolished the second peak of rotation but, while D1 blockade reduced the total number of turns, D2 blockade failed to do so. Quantitative analysis of the interaction between D1 and D2 receptors in the overall turning effect, as well as in the time-course of turning behaviour, indicates that D1 and D2 receptors interact not only positively but also negatively. After higher doses of apomorphine, both negative and positive interactions take place sequentially during the time-course of apomorphine action and provide a clue for explaining the two-peak pattern of rotation observed after apomorphine in rats previously exposed to the drug.     

Cytoskeletal alterations might account for the phylogenetic vulnerability of the human brain to Alzheimer's disease

A theory is presented here in the attempt to explain why Alzheimer's disease (AD) primarily affects areas of the human brain that have been acquired recently in phylogenesis. Disturbances in cytoskeletal function are proposed to play a fundamental role in triggering the sequence of pathologic events leading to the occurrence of AD-related histopathological markers and to the degeneration and death of neurons. These deficits are supposed to occur more likely in neuronal populations that possess a high degree of plasticity, the substrate of memory functions, and that constitute, in fact, the phylogenetically new telencephalic regions of the human brain.     

Daily nutrient intake represents a modifiable determinant of nutritional status in chronic haemodialysis patients.

BACKGROUND: In maintenance haemodialysis patients, daily food intake is changeable; however, its relationship with nutritional status is unexplored. This study aimed to evaluate the isolated, long-term effect of daily nutrient intake on nutritional status in haemodialysis patients. METHODS: We performed a prospective 1-year controlled study in 27 chronic haemodialysis patients, without recognized risk factors for malnutrition. Each day for 1 week, four times in the year, we measured protein nitrogen appearance, and assessed dietary protein (DPI) and energy (DEI) intake from dietary diaries. We compared the nutritional outcome of patients spontaneously reducing nutrient intake below the threshold of 0.8 g/kg body weight/day for DPI and 25 kcal/kg body weight/day for DEI during the week (LOW, n = 8), with controls at adequate nutrient intake (CON, n = 19). An interventional 6-month study was then carried out in LOW to verify the cause-effect relationship. RESULTS: All patients showed a day-by-day reduction of whole nutrient intake during interdialytic period, which was mostly relevant in the third interdialytic day (L3). During the 1-year study, even in the presence of adequate dialysis dose and normal inflammatory indexes, body weight (68.0 +/- 5.5 to 65.8 +/- 5.9 kg), serum albumin (3.96 +/- 0.07 to 3.66 +/- 0.06 g/dl) and creatinine (9.2 +/- 1.1 to 8.1 +/- 0.7 mg/dl) significantly decreased in LOW but not in CON. Diaries evidenced in LOW a reduced number of meals at L3 that was explained by the fear of excessive interdialytic weight gain. During the interventional study, daily DPI and DEI increased at L3; this was associated with a significant increment of body weight, and serum albumin and creatinine levels. CONCLUSIONS: In maintenance haemodialysis patients the persistent, marked reduction of daily nutrient intake, even if limited to a single day of the week, is an independent determinant of reversible impairment of nutritional status.     

Phosphatidylcholine does not affect peritoneal transport of intact rabbits

Ultrafiltration and solute transport during 60-min peritoneal dialyses of normal rabbits with intraperitoneal administration of phosphatidylcholine were compared to control values. The ultrafiltration rate of 0.27 mL/Kg/min did not increase when phosphatidylcholine was added. This agent had no effect on the ultrafiltration coefficient, sodium mass transport or solute clearances. Previously reported beneficial results with this agent could be due to repletion of a deficiency or an effect of the organic solvent. More studies of safety and efficacy of phosphatidylcholine are warranted before widespread clinical use.     

Stopping a medical research project for financial reasons

Sir, We are writing to provide some clarifications on the EditorialComment by Drüeke et al. [1]. We would have been happyto provide these very same clarifications had we been fairlyinvited to do so before the publication of the article. First of all, we would like to     

Esthesioneuroblastoma: endonasal endoscopic treatment.

Objectives: To illustrate endoscopic techniques used in the treatment of esthesioneuroblastoma and to advocate this method of management followed by radiation therapy in selected cases. Methods: A retrospective case series of 10 patients with esthesioneuroblastomas treated between 1999 and 2004 at a tertiary referral center using endonasal techniques. Results: Mean age of patients at presentation was 56.2 years (median 57 years). Seven patients were female and 3 patients were male. Kadish staging at presentation was: A - 3 patients, B - 5 patients, C - 2 patients. Dulguerov stage at presentation was: T1 - 4 patients, T2 - 4 patients, T3 - 2 patients. The period of follow-up ranged from 11 months to 74 months (mean 38.1 months, median 39 months). To date no recurrence has developed in any patient. Conclusions: Our experience suggests that endoscopic surgery can be an effective method of management. Strict attention to selection criteria, careful surgical techniques, and regular follow-up are key elements for success.