Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.

Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.     

Action of antiestrogens on the (Ca2+ + Mg2+)-ATPase and Na+/Ca2+ exchange of brain cortex membranes

The effect of tamoxifen (TAM) and other antiestrogens on the Ca2+ transport activity of synaptic plasma membranes (SPM) and microsomal membranes isolated from sheep brain cortex was investigated. The maximal (Ca2+ + Mg2+)-ATPase activity of SPM, which is reached at a pCa of about 6.0-6.5, is decreased by about 30% in the presence of 50 microM TAM, whereas the (Ca2+ + Mg2+)-ATPase activity of microsomes, which is maximal at a pCa of about 5.0, is decreased by about 90% by 50 microM TAM. In parallel experiments, we observed that the ATP-dependent Ca2+ uptake is also affected differently by TAM in the two membrane preparations. We found that 50 microM TAM inhibits SPM Ca2+ uptake by about 25-30%, whereas the ATP-dependent Ca2+ uptake by the microsomal fraction is inhibited by about 60%. No significant effect of TAM was observed on the Na+/Ca2+ exchange of either membrane system. The results indicate that TAM is a more potent inhibitor of the active, calmodulin-independent Ca2+ transport system of the intracellular membranes than of that of the plasma membranes, which is calmodulin-dependent. It appears that TAM inhibits calmodulin-mediated reactions, probably through its binding to calmodulin, as we showed previously. However, the Ca2+ transport system of microsomes, which does not depend on calmodulin, is also particularly sensitive to TAM.     

Neuquen,Argentina: Provincial Health Policies and Their Results*

ABSTRACT: A case study of the creation and implementation of a four-tier, integrated system of health care services in a sparsely populated, rural province in Argentina is described and discussed. Begun in 1970 in a diverse geographical area with a tradition of poor health status and inadequate health care resources, the provincial government set out to develop the human, physical and technological resources needed to provide a system of preventive and curative services appropriate to the health care needs of its residents. Innovative programs included training in management techniques, and epidemiological perspective of high risk, an emphasis on personnel development through a rural general medicine residency and an expanded nursing program as well as programs to attack infectious diseases, poor sanitation and dental problems were all developed in response to the distinctive features of the physical and social environment of the province. Improvements in traditional health indicators are reviewed and attributed to the program and administrative structures that were developed.     

Maternal syphilis and congenital syphilis in Latin America: big problem, simple solution]

From the data submitted to the Pan American Health Organization (PAHO) by nationwide programs against sexually transmitted diseases (STD), HIV infection, and AIDS (2002), one can estimate the overall prevalence of syphilis among pregnant women to be 3.1% and to range from 1.00% in Peru to 6.21% in Paraguay. According to these data, the incidence of congenital syphilis ranges from 1.4 per 1000 live births in El Salvador to 12.0 per 1000 live births in Honduras. Among men who engage in sex with other men, who often classify themselves as heterosexual, as well as in female sex workers, the prevalence of syphilis ranged from 5% to 15%. Factors that determine the persistence of congenital syphilis as public health problem include a lack of awareness of the seriousness of the problem among politicians, health officials, and health care providers, difficult access to prenatal care, and screening services, a low demand for the test among users, and the stigma and discrimination that surround sexually transmitted diseases (STD). This paper seeks to focus the attention of health professionals on maternal and congenital syphilis so they will undertake actions, using an interprogrammatic approach, to eliminate congenital syphilis from Latin America and the Caribbean. Eliminating congenital syphilis will only become possible if interventions targeting vulnerable groups are also implemented. PAHO's role in eliminating congenital syphilis includes determining the baseline situation in the Region as a whole and in each country, developing communication and procurement strategies, supporting nationwide programs, promoting operational research, and facilitating interprogrammatic coordination.     

Elevated concentrations of TNF-alpha are related to low serum magnesium levels in obese subjects.

The aim of this study was to determine the relationship between serum magnesium and TNF-alpha levels in obese subjects. A cross-sectional population based study that included 192 non-diabetic, non-hypertensive subjects allocated in three categories of body mass index (BMI) <25; > or =25 to <30 kg/m2; and > or =30 kg/m2. Elevation of TNF-alpha levels was defined by serum levels > or =3.5 pg/mL, and low serum magnesium by levels < or = 0.74 mmol/L. Multivariate odds ratios (OR) adjusted by age, HOMA-IR index, and glucose tolerance status are presented. Obese subjects exhibited higher serum concentration of TNF-alpha (p = 0.002) and lower serum magnesium levels (p < 0.0001) than lean and overweight subjects. Ninety-one (47.4%) subjects showed elevated levels of TNF-alpha, of them 7 (10.9%), 31 (48.4%), and 43 (67.2%) in the groups with BMI <25, > or = 25 to < 0, and > or =0 kg/m2, respectively. Multivariate OR between low serum magnesium and TNF-alpha levels in obese subjects was of 1.8, Cl95% 1.2-9.1, P = 0.001, whereas in the lean and overweight individuals of 1.1, Cl95% 0.7-8.7, P = 0.12, and 1.3, Cl95% 0.9-10.8, P = 0.09, respectively. These data shows that low serum magnesium levels and elevated TNF-alpha are related in the obese subjects. It will be necessary to conduct more studies in order to add new data on this issue.     

Sleep complaints and their relation with drug treatment in patients suffering from Parkinson's disease.

The aim of this research was to quantify sleep problems in patients suffering from Parkinson's disease by means of the new Parkinson's Disease Sleep Scale (PDSS) and to correlate such problems with the possible influence of current drug treatment. A total of 70 patients (36 men and 34 women) with a diagnosis of Parkinson's disease were enrolled. Their mean age was 69.7 +/- 8.2 years, and duration of disease was 7.4 +/- 4.8 years. All patients completed the PDSS and the Unified Parkinson's Disease Rating Scale (UPDRS Parts I-IV). Drug consumption and doses were registered. The mean score on the PDSS scale was 109.23 +/- 19.75 and on the UPDRS III scale was 25.24 +/- 11.35. The lowest scores were obtained in Item 3 (sleep fragmentation): 5.53 (2.46); and in Item 8 (nocturia): 5.75 (2.91). There was a weak correlation between the PDSS and UPDRS III (cc = -0.355, P = 0.003), PDSS and UPDRS I (cc = -0.272, P = 0.02), and PDSS and UPDRS IV (cc = -0.416, P < 0.001). Motor conditions, mental state, and drug complications influence sleep quality. Although this effect was significant, it was not of a great magnitude. Dopaminergic drugs did not increase daytime sleepiness. As a whole, sleep quality in patients who took dopaminergic agonists did not differ from that of patients who took levodopa in monotherapy.     

Two deaths from intravenous nifedipine abuse

Summary An incident is reported in which 2 intravenous drug abusers died as the result of uncontrolled experimentation with intravenous injection of the common anti-hypertensive and anti-anginal drug Nifedipine (Adalatt.m. Bayer), probably in mistake for the commonly abused short-acting benzodiazepine drug Temazepam. Large quantities of Nifedipine were identified in the blood of both deceased men by gas chromatography. Apart from intense gastric mucosal congestion, pulmonary oedema and general visceral congestion, the autopsy findings were entirely nonspecific. The similarity in colour, shape and texture between capsules of Nifedipine and those of Temazepam is likely to have prompted the mistake.