Synaptosomal glutamate release induced by the fraction Bc2 from the venom of the sea anemone Bunodosoma caissarum

The effect of a fraction (Bc2) from the venom of the sea anemone Bunodosoma caissarum on [3H]glutamate release from rat cortical synaptosomes was investigated. Bc2 (2-20 microg/ml) provoked massive glutamate release without causing synaptosome disruption. Glutamate release stimulated by Bc2 was independent of extracellular Ca2+ and of voltage-sensitive Na+ channels, and it was completely abolished by the addition of sphingomyelin. No definitive evidence about the mechanism underlying the stimulatory effect of Bc2 is available as yet. However, a direct interaction with the exocytotic machinery cannot be ruled out.     

The long-term behavior of the valve bladder as a function of the initial treatment and its effect on early kidney failure

In approximately 25-40% of infants presenting with posterior urethral valves (PUV) renal insufficiency will develop before adolescence. In some these patients, renal dysplasia, bladder dysfunction and mismanagement may precipitate renal failure at even earlier age. The goals of this study were to determine whether long-term bladder dysfunction was more frequent in children who underwent early temporary pyelostomy than in those who underwent valve ablation, and to know if bladder dysfunction and mismanagement, in some patients, could be responsible of early renal failure. Urodynamic studies were performed in 59 boys with severe PUV divided into two groups based on initial treatment. A) Valve ablation (30 p.); B) Cutaneous pyeloureterostomy (29 p.). At the end of the study 22 boys had chronic renal failure. Of the 59 boys, 42% (25 p.) had bladders with overdistended or normal behaviour, 58% (34 p.) had bladder dysfunction (instability 37%, low compliance 15%, myogenic failure 5%). The 89% of low compliance bladders, 66% of myogenic failure and 23% of those with instability were in CRF. No difference at all was found in bladder function between boys treated as neonates by high diversion or valve ablation. Of the group in chronic renal failure (22 p.), only 7 patients (32%) had bladders with normal behaviour and in five of these patients a mismanagement was directly related with a quicker renal deterioration. The 58% of our boys with severe PUV have some type of bladder dysfunction. Neonatal pyelo-ureterostomy does not increase long-term bladder dysfunction. Surgical mismanagement should be added to bladder dysfunction as contributors to earlier renal failure.     

Modified therapeutic community for mentally ill chemical abusers: outcomes and costs.

Several studies have established that the personal and social consequences of substance abuse are extensive and costly. These consequences are frequently compounded by mental illness. Although interventions that target mentally ill chemical abusers (MICAs) present several challenges, the potential benefits of successful interventions are significant. This article presents outcomes and costs of a modified therapeutic community (TC) intervention for homeless MICAs. Outcomes at follow-up are compared with those for a control group of homeless MICAs receiving standard services in a "treatment-as-usual" (TAU) condition. Annual economic costs for the modified TC and the average weekly cost of treating a single client are estimated. Treatment and other health service costs at 12 months postbaseline are compared for modified TC and TAU clients. The results of this study indicate that, suitably modified, the TC approach is an effective treatment alternative for homeless MICAs, with the potential to be highly cost-effective relative to standard services.     

Cancer mortality in Russia and Ukraine: validity, competing risks and cohort effects

BACKGROUND: The dramatic increase in mortality in Russia and Ukraine in the late 1980s and 1990s has been due to increases in certain causes of death, particularly cardiovascular disease and accidents and violence. In contrast, there has been a slight fall in mortality from cancer. METHODS: This paper presents an analysis of trends and patterns in cancer mortality and examines four possible explanations for its recent fall: changes in data collection; cohort effects; competing mortality from other causes of death; and improvements in health care. RESULTS: All contribute to some extent to the observed changes, with each affecting predominantly different age groups. There is evidence of a significant underrecording of cancer deaths among the elderly especially in rural areas and of significant changes in coding practices in the early 1990s. Competing mortality from cardiovascular diseases and accidents can explain some reduction in male deaths from cancer in middle age. Birth cohort effects can explain some reduction among males after early middle age and among females at all ages. The impact of changes in health care are more difficult to identify with certainty but there is evidence of reduced deaths from childhood leukaemia. IMPLICATIONS: Recent changes in mortality in Russia are complex and their understanding will require a multidisciplinary approach embracing demography, epidemiology and health services research.     

Comparative effects of a glucocorticosteroid, theophylline and the peptido-leukotriene-antagonist CGP 45715A on antigen-induced early and late phase airway response and inflammatory cell influx in sensitised guinea pigs

A novel model of allergic early and late-phase reaction in the airways of conscious guinea pigs was developed and the effect of established and novel antiasthmatic drugs on peak of immediate response, late phase response and associated inflammatory cell influx investigated. Guinea pigs were sensitised twice in adjuvant (50 mg/kg silica + 0.1 ml/kg Bordetella pertussis). Under cover of 10 mg/kg i.p. mepyramine guinea pigs exhibited still a pronounced immediate reaction. During a screening phase about 75% of guinea pigs demonstrated a late phase reaction of decrease of tidal volume between 4-10 h after ovalbumin inhalation. In a cross over study theophylline at 50 mg/kg p.o. (-1 h before ovalbumin) tended to attenuate not only the peak of the immediate reaction by about 69% (P>0.05, n = 12), but inhibited the airway late phase response significantly (P<0.05, 5-10 h, n = 12). Methylprednisolone (40 mg/kg p.o. 1 h before ovalbumin) did not inhibit the immediate response, but the late phase response. In contrast the cysteinyl-leukotriene antagonist CGP 45715A (Iralukast; 30 mg/kg p.o. 2 h before ovalbumin) neither interfered with the peak of the immediate, nor with the late phase response. When bronchoalveolar lavage by orotracheal route was performed 24 h after ovalbumin inhalation, total cell count, eosinophils, neutrophils, macrophages and lymphocytes were significantly increased in ovalbumin-controls compared to sham (n = 5; P<0.05). Methylprednisolone reduced significantly the antigen-induced increase of total cell count and eosinophil number. Neither theophylline nor the cysteinyl-leukotriene receptor antagonist attenuated the antigen-associated cell influx. The results do not provide evidence for a major role of cysteinyl-leukotrienes in the late phase response and inflammatory cell influx in this model.     

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.     

Coping in thebarrio: Case studies of Mexican-American families

This paper reports preliminary findings of a study of coping abilities of Mexican-American families. The purpose of the study was to identify variables related to styles of behavior that can be characterized as adaptive. A complex of factors differentiated families who were judged to be dealing effectively with their environment (copers) from those who were not (noncopers). The factors included the health status of the children, various child-rearing attitudes and practices, and patterns of decision making as they related to a more general ability of parents to conceptualize and organize time.The authors wish to thank Bernard R. Cavazos and Maria Rosario de los Santos for their help in data collection and interpretation.     

Correlates of self-reported and objectively determined exposure to Agent Orange

The authors examined the relationship between 100 Viet Nam veterans' self-reported and objectively determined exposure to the herbicide Agent Orange and the relationship between self- or objective ratings and self-reported psychological and medical problems. Veterans who believed they had been exposed reported more psychological and medical problems than the other veterans but did not differ on "success at living" indices; the medical problems many reported suggested psychosomatic etiologies. Grouped according to objective ratings of herbicide exposure, the veterans did not show such differences in psychological or medical problems. No differences on neuropsychological testing appeared, no matter how the subjects were grouped.