Bretschneider Solution and Two Antianginal Drugs Protect Peripheral Tissue in an Animal Model of Hemorrhagic Shock.

ABSTRACT: Shock and subsequent resuscitation provoke ischemia-reperfusion injury. Trimetazidine (TMZ), allopurinol (ALO), and histidine-tryptophan-ketoglutarate (HTK) solution, can protect from ischemia-reperfusion injury in chronic coronary syndromes and in transplantation. The objective of the current study is to compare, in a hemorrhagic shock and standard resuscitation animal model, organ damage parameters between placebo and treatment with TMZ, ALO, or HTK. Shock was induced in Wistar rats by controlled arterial bleeding, maintaining mean arterial pressure between 38 and 42 mm Hg for 60 minutes; then, drawn blood was reinfused. Animals were divided into: Sham (n = 4), Control (n = 6), TMZ (n = 7), ALO (n = 9), and HTK (n = 7). At the end of the experiment, animals were sacrificed and tissue harvested. TMZ, ALO and HTK decreased histopathologic damage in heart [Control: 1.72 (1.7-1.77); TMZ: 1.75 (1.72-1.79); ALO: 1.75 (1.74-1.8); HTK: 1.82 (1.78-1.85); all P < 0.05], kidney [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1(1-1); all P < 0.05] and intestine [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1 (0-2); all P < 0.05]. Also, treatment with TMZ, ALO, and HTK increased immunohistochemical expression of thioredoxin-1 in heart [Control: 6.6 (5.6-7.4); TMZ: 9.5 (8.1-9.7); ALO: 9.1 (8.4-10.2); HTK: 14.2 (12.6-15); all P < 0.05]; and kidney [Control: 4.6 (4-5.1); TMZ: 9.7 (9.3-9.9); ALO: 9.6 (9-9.9); HTK: 16.7 (16.1-17); all P < 0.05]. In an experimental model of hemorrhagic shock, TMZ, ALO, and HTK solution attenuated cell damage in multiple parenchyma and increased antioxidant defenses.

Structural changes in endocrine pancreas of male Wistar rats due to chronic cola drink consumption. Role of PDX-1.

AIM: The objective of this work was to analyze the structural changes of the pancreatic islets in rats, after 6 month consuming regular and light cola for 6 months. Also, we have analyzed the possible role of PDX-1 in that process. Finally, with the available knowledge, we propose a general working hypothesis that explains the succession of phenomena observed. Previously, we reported evidence showing that chronic cola consumption in rats impairs pancreatic metabolism of insulin and glucagon and produces some alterations typically observed in the metabolic syndrome, with an increase in oxidative stress. Of note It is worth mentioning that no apoptosis nor proliferation of islet cells could be demonstrated. In the present study, 36 male Wistar rats were divided into three groups to and given free access to freely drink regular cola (C), light cola (L), or water (W, control). We assessed the impact of the three different beverages in on glucose tolerance, lipid levels, creatinine levels and immunohistochemical changes addressed for the expression of insulin, glucagon, PDX-1 and NGN3 in islet cells, to evaluate the possible participation of PDX-1 in the changes observed in α and ß cells after 6 months of treatment. Moreover, we assessed by stereological methods, the mean volume of islets (Vi) and three important variables: the fractional ß -cell area, the cross-sectional area of alpha (A α-cell) and beta cells (A ß-cell), and the number of ß and α cell per body weight. Data were analyzed by two-way ANOVA followed by Bonferroni's multiple t-test or by Kruskal-Wallis test, then followed by Dunn's test (depending on distribution). Statistical significance was set at p<0.05. Cola drinking caused impaired glucose tolerance as well as fasting hyperglycemia (mean:148; CI:137-153; p<0.05 vs W) and an increase of in insulin immunolabeling (27.3±19.7; p<0.05 vs W and L). Immunohistochemical expression for PDX-1 was significantly high in C group compared to W (0.79±0.71; p<0.05). In this case, we observed cytoplasmatic and nuclear localization. Likewise, a mild but significant decrease of in Vi was detected after 6 months in C compared to W group (8.2±2.5; p<0.05). Also, we observed a significant decrease of in the fractional ß cell area (78.2±30.9; p<0.05) compared to W. Accordingly, a reduced mean value of islet α and ß cell number per body weight (0.05±0.02 and 0.08±0.04 respectively; both p<0.05) compared to W was detected. Interestingly, consumption of light cola increased the Vi (10.7±3.6; p<0.05) compared to W. In line with this, a decreased cross-sectional area of ß-cells was observed after chronic consumption of both, regular (78.2±30.9; p<0.05) and light cola (110.5±24.3; p<0.05), compared to W. As for, NGN3, it was negative in all three groups. Our results support the idea that PDX-1 plays a key role in the dynamics of the pancreatic islets after chronic consumption of sweetened beverages. In this experimental model, the loss of islets cells might be attributed to autophagy, favored by the local metabolic conditions and oxidative stress.

Vitamin D deficiency among patients with pulmonary hypertension.

BACKGROUND: There is little information about vitamin D (Vit D) deficiency in patients with pulmonary hypertension (PH). The objective of this study was: 1) compare Vit D levels between patients with PH, left ventricular failure (LVF) and healthy subjects (HS); 2) correlate, in patients with PH, Vit D levels with prognosis-related variables, such as the 6-min walk test (6MWT). METHODS: Vitamin D levels were measured in a cross-sectional study in 126 patients from one of three groups: patients with PH (n = 53), patients with LVF (n = 42) and healthy subjects (n = 31). In all groups, 8-h fasting blood samples were obtained in the morning. In the PH and the LVF group, functional class (WHO criteria), metres covered in the 6MWT and echocardiographic parameters were analysed. In the PH group, plasma N terminal pro B type natriuretic peptide (NT-proBNP) level was analysed and a complete haemodynamic evaluation by right heart catheterisation was made. RESULTS: Mean Vit D levels were lower in PH than in both other groups (ng/ml, mean ± SD): PH 19.25 ± 10, LVF 25.68 ± 12, HS 28.8 ± 12 (PH vs LVF p = 0.017, PH vs HS p = 0.001 and HS vs LVF p = 0.46). Vit D deficiency prevalence was higher in PH as compared to the other groups (PH 53.8%, LVF 45.2%, HS 25%, p = 0.01). Patients with PH in functional class (FC; WHO criteria) III-IV had higher Vit D deficiency prevalence than those in FC I-II (86.7% vs 40.5%, p = 0.003). There was a significant linear correlation between the 6MWT and Vit D levels in PH (p < 0.01), but not in LVF (p = 0.69). CONCLUSIONS: Vit D levels were lower in patients with PH as compared to patients with LVF and HS and correlated directly with 6-min walk distance.

El déficit de hierro en pacientes con hipertensión arterial pulmonar es altamente prevalente / Iron Deficiency is Highly Prevalent in Patients with Pulmonary Arterial Hypertension

RESUMEN Objetivos: Evaluar la prevalencia del déficit de hierro en hipertensión pulmonar y compararlo con otras poblaciones de pacientes. Establecer su valor pronóstico. Material y métodos: Estudio prospectivo, observacional. Se midieron parámetros de hierro sérico en pacientes consecutivos con diagnóstico de hipertensión pulmonar. Se compararon con pacientes con insuficiencia cardíaca y con controles sanos. Se buscó correlación entre los valores séricos de hierro y la clase funcional, la distancia recorrida en TC6M y el NT-proBNP. Resultados: Participaron 107 pacientes: 60 con hipertensión pulmonar, 26 con insuficiencia cardíaca y 21 controles sanos. El déficit de hierro fue del 78,3% en los pacientes con hipertensión pulmonar; del 45,8%, en aquellos que presentaban insuficiencia cardíaca; y del 23,8% (p < 0,001) en los controles sanos. La prevalencia de anemia resultó del 25% en los pacientes con hipertensión pulmonar; del 26,9% en los que padecían insuficiencia cardíaca; y del 19% (p < 0,8) en los controles sanos. En el subgrupo de pacientes en clase funcional I-II, la prevalencia de DFe fue del 78% en los pacientes con hipertensión pulmonar vs. el 43,5% (p < 0,005) en los que tenían insuficiencia cardíaca, y la anemia resultó del 17,1%% vs. el 28%% (p < 0,2). Se halló correlación significativa entre ferremia y saturación de transferrina con distancia caminada en TC6M (r: 0,35; p < 0,01 y r: 0,34; p < 0,01) y no hubo correlación para ferritina y transferrina. No se encontró significancia estadística entre déficit de hierro y clase funcional o NT-proBNP. Conclusiones: El déficit de hierro en la hipertensión arterial es altamente prevalente y superior al observado en la insuficiencia cardíaca y en los sujetos control, y no se establece relación con prevalencia de anemia, la cual fue similar en los tres grupos. El hierro sérico tiene una clara relación con la distancia caminada, no así con clase funcional, lo que, tal vez, obedezca al bajo número de pacientes.

ABSTRACT Objective: The aim of this study was to assess the prevalence of iron deficiency in pulmonary hypertension, to compare it with other patient populations and to establish its prognostic value. Methods: This was a prospective, observational study. Serum iron parameters were measured in consecutive patients diagnosed with pulmonary hypertension and compared with heart failure patients and healthy controls. A correlation was sought between serum iron levels and functional class, distance walked in the 6-minute walk test and NT-proBNP. Results: A total of 107 patients were included in the study: 60 with pulmonary hypertension, 26 with heart failure and 21 healthy controls. Iron deficiency was 78.3% in patients with pulmonary hypertension, 45.8% in those with heart failure and 23.8% in healthy controls (p<0.001). The prevalence of anemia was 25% in pulmonary hypertension, 26.9% in heart failure and 19% in healthy controls (p<0.8). In patients with functional class I-II, iron deficiency was: 78% in pulmonary hypertension vs. 43.5% in heart failure (p<0.005), and anemia was 17.1% vs. 28%, respectively (p<0.2). A significant correlation was found between serum iron and transferrin saturation with the distance walked in the 6-minute walk test (r: 0.35; p<0.01 and r: 0.34; p<0.01, respectively) and no correlation was found for transferrin and ferritin. Also, no significant correlation was found between iron deficiency and functional class or NT-proBNP. Conclusions: Iron deficiency is highly prevalent in pulmonary hypertension, and superior to that found in heart failure patients and healthy controls. No relationship was established with anemia, which was similar in the three groups. Serum iron is clearly related with the distance walked, but not with functional class, a result which may be attributed to the limited number of patients.