Alfredo Coviello

Estado protrombótico en estadios tempranos de la enfermedad de Chagas crónica

La etiopatogenia de esta enfermedad es multi-factorial, sin que ninguno de los factores involu-crados expliquen por si mismos el inicio y pro-gresion de las lesiones organicas. Actualmentese postula que el dano cardiaco dependeria delbalance que se establece entre los mecanismosinmunitarios que controlan el parasito y los me-canismos inmunitarios que inducen patologia.

Alcohol Drinking and Blood Pressure Among Adolescents

The purpose of this study was to evaluate alcohol consumption among adolescents from Tucuman, Argentina, and to determine its possible relationship with increased levels of blood pressure. Three hundred fifty-six students aged 13-18 included in the study were asked to answer questionnaires anonymously. Two blood pressures measures were then taken. Differences between both sexes were found in quantity and frequency of alcohol consumption. Enjoyment was determined to be the main reason for drinking. There was an association between frequency and alcohol-related problems, and smoking habits. There were also differences in blood pressure among males and females. A weak, but significant, relationship between quantity/frequency index and diastolic blood pressure was found. A greater prevalence of hypertension in male heavy drinkers was noted as well. Because this addiction implies multiple social problems and it also accounts for a hypertension risk factor, the importance of aiming at developing prevention strategies for alcohol abuse among adolescents is stressed.

Angiotensin converting enzyme in the toad Bufo arenarum

Angiotensin converting enzyme activity (ACEA) was determined in serum, kidney, whole skin and isolated epithelia homogenates of the South American toad Bufo arenarum. ACEA was present in the tissues and serum of the toad. The activity was higher in the kidney, as compared to that of the whole skin or isolated epithelium. Captopril, teprotide and EDTA, caused a significant decrease in the ACEA. Possible physiological roles for the presence of ACEA in the toad are discussed.

Angiotensin-(1-7) increases osmotic water permeability in isolated toad skin

Angiotensin-(1-7) (Ang-(1-7)) increased osmotic water permeability in the isolated toad skin, a tissue with functional properties similar to those of the distal mammalian nephron. Concentrations of 0.1 to 10 microM were effective, with a peak at 20 min. This effect was similar in magnitude to that of frog skin angiotensin II (Ang II) and oxytocin but lower than that of human Ang II and arginine-vasotocin. The AT2 angiotensin receptor antagonist PD 123319 (1.0 microM) fully inhibited the response to 0.1 microM Ang-(1-7) but had no effect on the response to Ang II at the same concentration. The specific receptor antagonist of Ang-(1-7), A-779, was ineffective in blocking the response to Ang-(1-7) and to frog skin Ang II. The AT1 receptor subtype antagonist losartan, which blocked the response to frog skin Ang II, was ineffective in blocking the response to Ang-(1-7). The present results support the view of an antidiuretic action of Ang-(1-7) in the mammalian nephron.

Reversed short-circuit current across isolated skin of the toadBufo arenarum

Short-circuit current (SCC) aross isolated pelvic skin of the toadBufo arenarum has been shown to be reflected by the algebraic sum of net sodium and chloride transport. After the animals had been maintained in tap water, amiloride — an apical sodium channel blockerled to a reversal of potential difference (rPD) across this preparation, to which corresponded a reversed short-circuit current (rSCC). Both rSCC and rPD were abolished by dermal treatment of skins with the metabolic inhibitor dinitrophenol, or by omission of chloride ion from the Ringer solution bathing both sides of the skin. There was a significant positive correlation between rSCC and isotopically determined net chloride transport after amiloride. An inhibitory action of amiloride on unidirectional chloride fluxes was detected, but only early after drug addition. rSCC was absent in skins of toads exposed to 110 mmol/l NaCl in tap water during 10 days. Together, our results suggest that amiloride addition —by inhibiting active sodium movement — can in certain conditions reveal the existence of an inward active chloride transport.

Comparative effects of angiotensin II on osmotic water permeability in the toad (Bufo arenarum)

The possible relationship between the renin-angiotensin system and water balance in the toad Bufo arenarum has been indirectly explored. A positive correlation was found between the hydrosmotic response of ventral pelvic toad skin to angiotensin II (A II) and some age indicators (body weight, snout-urostyle length or head width). A different hydrosmotic response for oxytocin and isoproterenol (but not for A II) was found between four cutaneous regions of toad body. We conclude that A II may not be directly involved in the regulation of water balance mediated by water absorption across the skin of Bufo arenarum toads.

Structural Changes in the Renal Vasculature in Streptozotocin-Induced Diabetic Rats without Hypertension

Background/Aim: We evaluated in diabetic-streptozotocin rats (STZR) the structural changes of glomeruli, preglomerular vessels, glomerular tuft and renal parenchyma in order to determine the degree of renal injury and the presence of remodeling in afferent arterioles developed by diabetes without overimposed hypertension. Methods: Renal mass index and histological score (glomerular number, density, tubular lesions and degree of arteriosclerosis) were estimated. In afferent arterioles the ratio of wall thickness/lumen was obtained by stereological methods. Results: STZR developed diabetes without hypertension; renal mass index increased and matched changes in glomeruli (decrease of capillary number and enlargement of mesangium and basement capillary membrane). Both glomerular number and density as well as afferent arteriole number were diminished. Degenerative changes in both proximal (glycogenic and hyaline degeneration) and distal tubules (hyaline casts) were also observed. At variance with preglomerular vessels, the efferent arterioles only presented initial arteriosclerosis. Finally, the stereological study of afferent arterioles showed a significantly lower arteriolar lumen area and arteriolar wall thickness in STZR, resulting in a remodeling without modification of wall/lumen ratio. Conclusion: Diabetes, uncomplicated by hypertension, is associated with (1) a reduction in glomerular number; (2) degeneration in parenchyma and renal tubules, and (3) a specific pattern of remodeling in preglomerular vessels different from that induced by hypertension. Although this work demonstrated that these changes are not triggered by hypertension, further investigations are required in order to determine which mediators are involved in diabetic-vascular renal dysfunction.

Inflammatory and prothrombotic activation with conserved endothelial function in patients with chronic, asymptomatic Chagas disease.

Previously, our group showed a prothrombotic state in asymptomatic patients with chronic Chagas disease. The current paper studies the inflammatory status and endothelial function in these patients. Methods: In 40 patients and 40 healthy volunteers, we evaluated prothrombotic state, blood parasitemia (molecular biology: polymerized chain reaction [PCR]-amplification), tissue factor pathway inhibitor antibodies (aTFPI), interleukin 6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1). Endothelial function was determined by reactive hyperemia (pulse plethysmography). Results: In patients, prothrombin fragment 1 + 2, d-dimer, PAI-1, and fibrinogen were higher. Amplification of 121/122 primers (Trypanosoma cruzi) was positive in 45% of the patients. Patients presented higher values of aTFPI- immunoglobulin G (IgG; P < .05), aTFPI-IgM (P < .001), IL-6 (P = .004), and VCAM-1 (P = .00001). In both groups, endothelial function was preserved. Conclusions: We found that asymptomatic patients with chronic Chagas disease presented a prothrombotic/inflammatory status. The fact that endothelial function is still preserved suggests that prothrombosis and inflammation are primarily implicated in the beginning of cardiovascular damage.

Internal mammary artery grafts reactivity in hypertensive patients : Role of stretching in extraendothelial nitric oxide

Background. The internal mammary artery (IMA) used in bypass coronary surgery remains efficient for a longer time than other grafts, such as saphenous veins; however, its biological characteristics are incompletely defined. Objective. To compare in IMA grafts from hypertensive (HT) and normotensive (NT) patients the presence of endothelium and their functionability, the response to passive stretching and basal tone, the reactivity to exogenous vasoconstrictors, the role of stretching in NO release, and the possible extraendothelial NO source. Methods and Results. IMA rings contractility, presence of endothelium, and nitrite release were studied. An endothelial dysfunction associated with hypertension was found. IMA rings from HT had an impaired response to passive stretching, resulting in a decreased relaxation. All IMA grafts had an increased basal tone demonstrated by relaxation to SNP; however, a lesser response was found in HT. Interestingly, it was demonstrated that NO release was present in IMA grafts, despite an endothelial dysfunction and that stretching increased NO release. This effect was inhibited by Ca2+-free media, L-NAME and a specific neuronal NO synthase (nNOS) inhibitor. Furthermore, the demonstration of the presence of nNOS in smooth muscle cells by immunohistochemistry supports a role of extraendothelial NO. Conclusion. We demonstrate the impact of hypertension in IMA grafts producing increased endothelial dysfunction, reduced response to passive stretching, increased basal tone, and impaired responsiveness to exogenous vasoconstrictors and NO release. A specific role of stretching in extraendothelial NO release was demonstrated, which may have an important role in the outcome of IMA grafts due to the protective actions of NO, even in the absence of the endothelium.

Trypsin affects basal and stimulated osmotic water permeability in isolated toad skin.

1. We investigated the effect of trypsin (Tryp) on basal, stimulated and fluphenazine (FPZ)-inhibited net water flow (Jw) through isolated toad skin (Bufo arenarum). 2. Epidermal Tryp (20 min) promoted an increase in basal Jw which was dose-dependent (maximal with 0.5 mg/ml) and was prevented by a Tryp inhibitor (SBTI). 3. Tryp treatment inhibited the subsequent response to substances known to act before (oxytocin, Oxy) or after cyclic AMP (cAMP) generation (theophylline). 4. Tryp-induced Jw was not additive with the maximal response to Oxy or theophylline and did not modify FPZs inhibitory effect on stimulated Jw. 5. Dermal Tryp (0.5 mg/ml, 20 min) did not modify basal, but inhibited Oxy and isoproterenol-stimulated Jw, without altering the response to theophylline or db-cAMP. 6. Collectively, our results show a differential action for epidermal and dermal Tryp. Tryps side-selective action enables its use as a pharmacological tool in the functional dissection of Jw across toad skin.