NUTRITIONAL STATUS IN CHRONICALLY ALCOHOLIC MEN FROM THE MIDDLE SOCIOECONOMIC CLASS AND ITS RELATION TO ETHANOL INTAKE

Two-hundred and fifty chronically alcoholic men (mean age, 41± 11 years) entering an alcoholism treatment programwere studied. Detailed clinical history, nutritional assessmentand measurement of muscle strength by electronic myometer wereperformed in each case. In addition, hepatic ultrasonographyand liver biopsy, echocardiography and radionuclide cardiacscanning, and electrophysiological testing of peripheral nerveswere performed when there was clinical evidence of liver disease,cardiomyopathy or neuropathy, respectively. Alcoholic cirrhosiswas diagnosed in 20 cases, skeletal myopathy in 117, dilatedcardiomyopathy in 20 and peripheral neuropathy in 41 cases.No patients with chronic myopathy or cardiomyopathy showed eitherclinical or laboratory evidence of malnutrition. Patients withcirrhosis showed a significantly lower lean body mass than controls(P = 0.03) and significantly lower nutritional protein levelsthan those alcoholics without cirrhosis. Alcoholics with peripheralneuropathy had significantly lower anthropometric parametersand nutrition protein levels than their counter parts (P <0.001). However, in the multivariate analysis, the only independentfactor for developing these complications of alcoholism wasthe total lifetime dose of ethanol (P < 0.001). We concludethat alcohol-related diseases are common in asymptomatic alcoholicmen and these diseases appear to be due to an accumulative toxiceffect of ethanol. Age and nutritional status do not seem toplay a part in the development of such diseases     

Diabetes Mellitus as a Risk Factor for Development of Vulnerable (Unstable) Coronary Plaque: A Review of Possible Mechanisms

The prevalence of early and severe atherosclerotic coronary disease is much higher in diabetic patients than in their nondiabetic counterparts. The incidence of acute coronary syndrome is also disproportionately higher in this population. This difference has generally been attributed to a much higher prevalence of traditional risk factors such as hypertension and dyslipidemias in diabetic patients; however, a clear explanation is yet to be found. Vascular injury and growth factors are increased in these individuals. Metabolic and biochemical abnormalities such as glycosylation and oxidation of low density lipoprotein (LDL) and the formation of "large" very low density lipoprotein (VLDL) promote the accumulation of monocytes and macrophages, leading to the formation of foam cells. Glycosylation of high density lipoprotein (HDL) impairs its antiatherogenic action. These abnormalities may enhance the extracellular (core) lipid content of the atherosclerotic plaque, rendering it softer. An augmented inflammatory response also appears to take place in the atherosclerotic plaque of diabetic patients. There is a strong chemotaxis for monocytes and macrophages mediated by glycoxidation. These cells induce the secretion of interleukin-1 and cachectin/tumor necrosis factor, which in turn inhibit nitric oxide activity, leading to detrimental action of mast cells. Diabetic patients also have an enhanced vasoconstrictive response. Significant platelet, coagulation, and fibrinolytic abnormalities are also present in these individuals, which favor a relatively hypercoagulable state. Plaque stress due to enhanced tensile and compression forces appears to be increased in diabetic patients.     

ITRACONAZOLE IN THE TREAMENT OF CHROMOBLASTOMYCOSIS DUE TO FONSECAEA PEDROSOI

The efficacy and tolerability of itraconazole in chromoblastomycosis due to Fonsecaea pedrosoi were evaluated in a non-comparative open clinical trial in 19 Brazilian patients with histopathologically and mycologically proven active chromoblastomycosis. Patients were classified in terms of severity and received itraconazole at the dosage of 200 to 400 mg per day until previously described criteria of cure have been reached. Clinical, mycologic, histopathologic, and laboratory evaluations were performed before, during, and after therapy. The plasma levels of itraconazole and the in vitro susceptibility of the isolates were determined in 15 cases. Clinical and biologic cure were achieved by eight patients (42%) having mild to moderate disease, after a mean duration of therapy of 7.2 months (3.2-29.6 months). Sterile scarred lesions were observed in a post-therapy follow-up lasting on average 9.6 months that was carried out in this subgroup. Clinical cure alone occurred after a mean period of 25.1 months of treatment (16-30.5 months) in seven patients (36%) with moderate to severe disease. Finally, clinical improvement was obtained in four patients (21%) with severe lesions after a mean treatment time of 17.6 months (10.7-22.5 months). All patients responded favorably to itraconazole therapy. No significant side effects nor biochemical alteration during this trial were important enough to interrupt the treatment. Our results support those of previous trials, suggesting that itraconazole is an effective compound against chromoblastomycosis due to Fonsecaea pedrosoi.     

Immunohistochemical Localization of Gap Junction Protein Channels in Hamster Sinoatrial Node in Correlation with Electrophysiologic Mapping of the Pacemaker Region

Gap Junction Proteins in the Sinoatrial Node. Introduction: Gap junction proteins are thought to form the low resistance pathways that connect neighboring cells within the sinoatrial node, and to mediate pacemaker synchronization.
Methods and Results: We have carried out microelectrode mapping experiments of the hamster sinoatrial region to localize the primary pacemaker area for subsequent light, electron, and immunofluorescence microscopic studies aimed at testing the hypothesis that the major cardiac gap junction protein (connexin43) is present in such an area. The site of earliest activation is unifocal and the pattern of activation, obtained In multiple sequential microelectrode recordings of the Sinoatrial region, is qualitatively similar to that previously described for other species. However, quantitatively, the impulse transmission time from the primary pacemaker area to the crista (sulcus) terminal's in the hamster sinoatrial node is about 50% briefer than that of the guinea pig and five times faster than that of the rabbit. Immunolocalization studies in the hamster sinoatrial node using anti-connexin43 antisera demonstrated specific staining at the areas of cell-to-cell apposition and suggested that the apparently high degree of electrical coupling in this tissue is the result of abundant connexin43 expression. The immunofluorescence data were supported by light microscopic studies, which demonstrated the typical morphologic characteristics of sinus nodal cells in the pacemaker area. In addition, an electron microscopic study of the sinoatrial region revealed the presence of gap junctions in the junctional complex at areas of cell-to-cell contact.
Conclusion: Our results demonstrate that cells in the sinoatrial region of the hamster heart are electrically well coupled and strongly suggest that such coupling is mediated by gap junctional channels formed by connexin43.     

Comparative Analysis of the Vascular Actions of Diterpenes Isolated from Euphorbia canariensis

We have analysed the effects of 2,3-diepiingol 7,12-diacetate-8-isobutyrate (compound 1 ), ingenol-3-angelate-17-benzoate (compound 2 ), ingenol-3-angelate-17-benzoate-20-acetate (compound 3 ) and 3,5,7,8,9,15-hexahydroxyjatropha-6(17),11-dien-14-one-5,8-bis(2-methylbutyrate)-7-(2-methylpropionate) (compound 4 ), four diterpenes isolated from E. canariensis, on the isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to these compounds were obtained cumulatively in both arteries at resting tension and active tone (KCl, 50 mM). At resting tension a concentration-dependent contraction was induced by the four compounds. In the basilar artery the order of potency was 3 = 1 > 2 = 4 , without significant differences between E_max values. In the carotid artery the order of potency was 3 > 2 = 1 = 4 and there were no significant differences between the E_max (maximum effect) values of compounds 1–3 , all of which were higher than that of compound 4 . In pre-contracted basilar artery compounds 1–3 induced concentration-dependent relaxation and compound 4 was almost ineffective; the order of potency was 3 > 2 = 1 without significant differences between E_max values. In the carotid artery with active tone the four compounds tested induced further contractions; the order of potency was 3 > 2 = 4 > 1 without significant differences between E_max values. These results show that the four diterpenes are potent active substances in rabbit basilar and carotid arteries and that there are regional differences between their action. The four compounds tested contract basilar and carotid arteries at resting tension. Compounds 1–3 relax pre-contracted basilar artery but not carotid artery.     

Reproductive Toxicology of Aluminum in Male Mice

The reproductive toxicology of aluminum was studied in mice.Adult male mice were treated intraperitoneally with aluminumnitrate at doses of 0, 50, 100, and 200 mg/kg/day for 4 weeksbefore mating with untreated females. Decreased body weightwas seen in all aluminum-treated groups. Decreased pregnancyrate was observed in the females mated with males previouslytreated with 100 or 200 mg/kg/day of aluminum nitrate. High-dosemale mice showed significantly decreased testicular and epididymalweights, as well as significant decreases in testicular andspermatid counts and epididymal sperm counts. Spermatid countswere also reduced at 100 mg/kg/day. However, the sperm motilitywas unaffected, and the percentages of morphological normalspermatozoa in all mice exposed to aluminum were comparableto the values in control mice. Histological changes, includingnecrosis of spermatocytes/spermatids, were observed in the testesof male mice treated with 100 and 200 mg/kg/day of aluminumnitrate, whereas the tubu lar diameters were unaffected by aluminumadministration. The current study demonstrates adverse effectsof parenteral aluminum exposure on the mouse male reproductivesystem. The "no observable adverse effect level" (NOAEL) was50 mg/kg/day.