Antigenic cross-reactivity between sixteen venoms from scorpions belonging to six genera.

Venoms of 15 scorpion species from Venezuela and one from Brazil were compared in their antigenic cross-reactivity with specific F(ab')2 against Tityus discrepans (Td-antibodies), using the method of King and collaborators (1). Our results show that Tityus venoms cross-reactivity (shared epitopes) with the venoms of other species within the genus tended to be less for a greater distance between the habitat of the species. A nonparametric linear regression of free Td-antibody binding to T. discrepans venom immobilized to a solid phase in the presence of other Tityus venoms versus distance showed binding = a + b x log10 (distance) where: median (95% confidence interval) for a = 0.92 (7.43, 9.80) and b = 17.20 (4.15, 22.57) binding/log10(Km); Spearman rS = 0.783 with associated P = 0.006. Our results show that toxins from different Tityus species, targeting mammalian Na+ and K+ channels, are antigenically very similar. Venoms from species from other genera such as Centruroides, Broteas, Diplocentrus, Chactas, and Rhopalurus did not cross-react with Td-antibodies.

Relationship between plasmatic levels of various cytokines, tumour necrosis factor, enzymes, glucose and venom concentration following Tityus scorpion sting.

A sandwich enzyme-linked immunosorbent assay was developed for measuring Tityus venom levels in plasma. The method proved capable of distinguishing patients with only local symptoms from controls, and was used to quantify venom in 205 accidental human envenomations. Our results show that the severity of envenoming is related to the patient plasma venom concentration. This depends on time elapsed between the sting and when the plasma was drawn. We observed that 46 and 49% of patients with moderate to severe symptoms (MS, n=41) showed hyperamylasemia and hyperglycemia, respectively. In addition, 39% of cases with MS symptoms had partial thromboplastin time values prolonged or shorted and 6.5% of patients with local symptoms (LS, n=164) had only prolonged prothrombin time values. Interleukin 6 (IL6) increased significantly in patients with MS symptoms. IL6 values increased with hyperamylasemia, envenoming severity and time hyperamylasemia.

Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation.

This study was aimed at assessing the effects of long-term exposure to NO of respiratory activities in mitochondria from different tissues (with different ubiquinol contents), under conditions that either promote or prevent the formation of peroxynitrite. Mitochondria and submitochondrial particles isolated from rat heart, liver and brain were exposed either to a steady-state concentration or to a bolus addition of NO. NO induced the mitochondrial production of superoxide anions, hydrogen peroxide and peroxynitrite, the latter shown by nitration of mitochondrial proteins. Long-term incubation of mitochondrial membranes with NO resulted in a persistent inhibition of NADH:cytochrome c reductase activity, interpreted as inhibition of NADH:ubiquinone reductase (Complex I) activity, whereas succinate:cytochrome c reductase activity, including Complex II and Complex III electron transfer, remained unaffected. This selective effect of NO and derived species was partially prevented by superoxide dismutase and uric acid. In addition, peroxynitrite mimicked the effect of NO, including tyrosine nitration of some Complex I proteins. These results seem to indicate that the inhibition of NADH:ubiquinone reductase (Complex I) activity depends on the NO-induced generation of superoxide radical and peroxynitrite and that Complex I is selectively sensitive to peroxynitrite. Inhibition of Complex I activity by peroxynitrite may have critical implications for energy supply in tissues such as the brain, whose mitochondrial function depends largely on the channelling of reducing equivalents through Complex I.

Los pacientes de escorpionismo con sintomatología local tiene niveles importantes de veneno en plasma / The scorpionism patients with local symptomatology have important venoms levels in plasma

Se desarrolló un método de inmunoensayo (Enzime-Linked Imunosorbent Assay) sensible y específico para cuantificar veneno de T. discrepans en plasma de pacientes de escorpionismo. Los casos se clasificaron como: asintomáticos (Clasificación del Hospital "Dr. Leopoldo Manrique Terrero", Caracas, D.F.) equivalente a sintomatología local (Clasificación del Hospital "Victorino Santaella", Los Teques, Edo. Miranda), o con sintomatología sistemática: leve, moderada o grave. Se analizó el plasma de 82 pacientes, de los cuales 23 fueron niños. La venenemia en 58 pacientes con sintomatología local estuvo entre 0,01 y 17,2 ng/ml con una mediana e intervalos de confianza de 95 por ciento (entre paréntesis) de 0,5 (0,2 - 2)ng/ml. La venenemia en 13 pacientes con sintomatología leve o moderada flactuó desde 0,1 hasta 202 ng/ml [11,2 (0,5 - 80,4) ng/ml]. Sólo se obtuvo plasma de un paciente con sintomatología grave el cual presentó una venenemia de 31,8 ng/ml. El nivel de falsos positivos del ensayo se determinó con el plasma de 10 personas no emponzoñadas en las cuales el ensayo indicó una venenemia aparente de 0,13 (0,5 - 0,25) ng/ml. Las concentraciones más altas y después de aplicar antiveneno (n= 7) demostró que éste hace desaparecer el veneno del plasma. Se observaron alteraciones en el tiempo parcial de tromboplastina prevalentemente en pacientes con sintomatología local. Alteraciones en amilasa y glicemia sólo se observaron en pacientes con clínica sistémica. El 14 por ciento de 58 pacientes con sintomatología local presentaron alteraciones del tiempo parcial de tromboplastina indicativas de anticoagulación en algunos, o procoagulación en otros casos; estos coincide con resultados in vitro de nuestro laboratorio donde se identificaron fracciones pro y anticoagulantes en el veneno de Tityus discrepans (D'Suze y col., 2000). En 63 por ciento de los pacientes con sintomatología local se detectó veneno en el plasma, 24 por ciento de ellos en concentraciones entre 1 y 4 ng/ml y 9 por ciento por encima de ese rango, estas concentraciones de veneno se correlacionan en otros estudios con aumentos de citokinas, factores de necrosis tumoral y de agregación plaquetaria. Este trabajo indica que la ausencia de clínica no es equivalente a ausencia de veneno en plasma ni a ausencia de daño. Este trabajo fue financiado por el proyecto aplicado IVIC-Silanes

[Role of nitric oxide in cell respiration]. / Papel del óxido nítrico en la respiración celular.

Nitric oxide (NO) synthesized in a constitutive manner by a cell, acts on effector cells as a physiological regulator of the vascular tone, of platelet inhibition and of neuron-neuron interaction. By contrast, the release for longer periods of time of higher amounts of inducible NO, transforms NO from a physiological mediator into a cytostatic and cytotoxic molecule. The presence of NO synthetase in mitochondria suggests that physiological small amounts of NO could be involved in cellular respiration regulation by inhibition of cytochrome oxidase. Long exposure of cells to NO results in an irreversible inhibition of cellular respiration not dependent on a generalized superoxide or peroxynitrite formation. Cellular respiration inhibition could be reverted by either analyzing complex IV alone, by blocking Complex I or by the addition of gluthation. Therefore, our hypothesis is that suppression of complex IV is a normal physiological effect dependent on NO concentration. When cells are exposed to NO for longer periods of time, thiol groups are nitrosilated in complex I while gluthation transnitrosilates until its level drops to critical values. At this point, cellular respiration is blocked and this could be the pathway by which NO is transformed from a physiological mediator into a pathological molecule. We also believe that thiol nitrosilation and transnitrosilation by gluthation is a critical mechanism involved in oxidative stress prevention.

[Occupational accidents in Barcelona (Spain), from 1992 to 1993]. / Acidentes de trabalho em Barcelona (Espanha), no período de 1992-1993.

INTRODUCTION: The statistics related to labor accidents as with any other notification system ought to be the basis for programs and policies with a view to the adoption of preventive measures. In order to establish preventive norms, however, the health system needs data from researchers focussing on the dynamics of and the pitfalls revealed by specific events. Within this context the main objective of this study is to proceed with an in-depth analysis of the labor accidents verified in Barcelona (Spain) using for this purpose a descriptive statistics model to test variables such as type of accident, economic sector, economic enterprise and type of labor contract. METHOD: The data source utilized was the notification system for labor accidents with grave consequences such as death of the victim registered in Barcelona during the period 1992-1993. Labor accidents registered for male workers numbered 848. A log-linear model was applied to this data base. RESULTS AND CONCLUSIONS: The results show a positive association between traumatic accidents with the construction, traffic and services sectors. A positive association was also found between traumatic accidents and the size of the company concerved the small ones being the worse type in terms of worker's injuries. Regarding the nontraumatic accidents, the study showed a positive correlation between large-sized enterprises and type of temporary worker and the civil construction sector as compared to workers with long term work contracts within industry and services. There was some evidence, also, of a positive association between small and medium sized companies and temporary work and the occurrence of work accidents.

Calcium supplementation prevents pregnancy-induced hypertension by increasing the production of vascular nitric oxide.

Pregnancy-induced hypertension (PIH) remains a common cause of maternal and fetal morbidity and mortality. During the past 7 years, some progress has been made in the prevention of PIH. Specifically, clinical studies have shown that supplementation with calcium can significantly reduce the frequency of PIH, specially in populations with a low calcium intake. We have suggested that, in such a population, calcium supplementation is a safe and effective measure for reducing the frequency of PIH. Thus, the purpose of this article is to advance a hypothesis about the mechanism by which calcium supplementation reduces the risk of PIH. We propose that dietary calcium supplementation reduces the frequency of PIH by maintaining the serum ionized calcium level which is crucial for the production of endothelial nitric oxide, the increased generation of which maintains the vasodilatation that is characteristic of normal pregnancy.

Chlorpromazine inhibits both the constitutive nitric oxide synthase and the induction of nitric oxide synthase after LPS challenge.

The effects of chlorpromazine on either the activity of mouse brain nitric oxide synthase or the induction of lung nitric oxide synthase in mice and rats were studied. Chlorpromazine inhibited the nitric oxide synthase activity in mouse brain cytosol. This effect could be reversed by adding an excess of calmodulin. In addition, chlorpromazine was able to inhibit the induction of lung nitric oxide synthase, in both species, after LPS administration. Furthermore, chlorpromazine also inhibited arginase activity in mouse lung cytosol.

[Transthoracic and transesophageal echocardiography in the study of young adults with a cerebral ischemic event]. / Ecocardiografia transtorácica y transesofágica en el estudio de adultos jóvenes con evento isquémico cerebral.

The aim of this study was the evaluation of transesophageal echocardiography (TEE) in the detection of potential emboli sources of cardiac origin in a young population with cerebrovascular events, and to compare this study with transthoracic echocardiography (TE). We have studied 24 young subjects (average 33 years) and detected a potential cardiac source in 9 subjects, with transthoracic approach only in 4. We concluded that TEE is superior than TE to detect potential cardiac source of cerebral embolism. The most frequently abnormality was mitral valve prolapse.

Role of nitric oxide pathway in the protection against lethal endotoxemia afforded by low doses of lipopolysaccharide.

Survival after lipopolysaccharide challenge (LD80, 20 mg.kg-1, i.p.) was significantly enhanced by previous treatment with a microdose of LPS (50 micrograms.kg-1, i.v.). When NG-monomethyl-L-arginine, a specific inhibitor of the formation of nitric oxide from L-arginine, was given 30 minutes before microdose, survival was significantly reduced. When we monitored the serum Tumor Necrosis Factor (TNF) levels in both groups a significant reduction of TNF level after the microdose was observed in mice previously treated with L-NMMA. The ability of L-NNMA to reduce TNF release was dose dependent.

[Premature atherosclerosis in a 17-year-old male with diabetes mellitus and familial dyslipoproteinemia]. / Aterosclerosis prematura en un joven de 17 años con diabetes mellitus y una dislipoproteinemia familiar.

A 17-year-old male was admitted with an acute myocardial infarction. A coronarography showed 90% occlusion in of the descendent anterior artery. A coronary angioplasty was done with excellent response. As coronary risk factors he had diabetes mellitus for 5 years and dyslipidemia with a phenotype IIb and hypo-alpha-lipoproteinemia. The case is discussed in regard to the possible etiopathogenic causes for his premature atherosclerosis.