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.

Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology.

AIMS: To describe the outcomes of pregnancy in women with pulmonary hypertension. METHODS AND RESULTS: In 2007 the European Registry on Pregnancy and Heart Disease was initiated by the European Society of Cardiology. Consecutive patients with all forms of cardiovascular disease, presenting with pregnancy, were enrolled with the aim of investigating the pregnancy outcomes. This subgroup of the cohort included 151 women with pulmonary hypertension (PH) either diagnosed by right heart catheterization or diagnosed as possible PH by echocardiographic signs, with 26% having pulmonary arterial hypertension (PAH), in three subgroups: idiopathic (iPAH), associated with congenital heart disease (CHD-PAH), or associated with other disease (oPAH), and 74% having PH caused by left heart disease (LHD-PH, n = 112). Maternal mean age was 29.2 ± 5.6 years and 37% were nulliparous. Right ventricular systolic pressure was <50 mmHg in 59.6% of patients, 50-70 mmHg in 28.5% and >70 mmHg in 11.9%. In more than 75% of patients, the diagnosis of PH had been made before pregnancy. Maternal death up to 1 week after delivery occurred in five patients (3.3%), with another two out of 78 patients who presented for follow-up (2.6%), dying within 6 months after delivery. The highest mortality was found in iPAH (3/7, 43%). During pregnancy, heart failure occurred in 27%. Caesarean section was performed in 63.4% (23.9% as emergency). Therapeutic abortion was performed in 4.0%. Complications included miscarriage (5.6%), fetal mortality (2%), premature delivery (21.7%), low birth weight (19.0%), and neonatal mortality (0.7%). CONCLUSION: Mortality in this group of patients with various forms of PH was lower than previously reported as specialized care during pregnancy and delivery was available. However, maternal and fetal mortality remains prohibitively high in women with iPAH, although this conclusion is restricted by limited numbers. Early advice on contraception, pregnancy risk and fetal outcome remains paramount.

Leflunomide-induced pulmonary hypertension in a young woman with rheumatoid arthritis: a case report.

Leflunomide, a disease-modifying antirheumatic drug, has been shown to be effective in the management of rheumatoid arthritis (RA). Among other side effects, systemic hypertension has been described, and also a case of possible pulmonary hypertension (PH) has been reported. Symptomatic PH in RA is rare. We present a 28-year-old woman with a history of RA who consulted our hospital because of severe symptomatic pulmonary hypertension. Two years before admission, she was started on leflunomide. Due to previous evidence of the association of leflunomide with pulmonary hypertension, the drug was stopped. The patient became asymptomatic with normal pulmonary arterial pressure within a year. Given the poor prognosis of idiopathic pulmonary arterial hypertension, the recognition of potentially reversible causes is crucial. Until further evidence is available in a patient who develops pulmonary arterial hypertension, stopping leflunomide should be considered.

Pharmacologic reversion of persistent atrial fibrillation with amiodarone predicts long-term sinus rhythm maintenance.

OBJECTIVE: The study analyzed the role of different variables that determine long-term sinus rhythm maintenance in patients with persistent atrial fibrillation who are treated with amiodarone. BACKGROUND: It has been recognized that different factors influence long-term sinus rhythm preservation after the conversion of persistent atrial fibrillation. Although the duration of the arrhythmia appears to be the most important factor, consistent information regarding the role of the mode of arrhythmia conversion (pharmacologic or electric) is still lacking. METHODS: One hundred and forty one anticoagulated patients with persistent atrial fibrillation (median duration 8 months, percentiles 25 and 75: 2-24) were treated for 4 weeks with oral amiodarone (600 mg/day). Those in whom the arrhythmia persisted underwent electric cardioversion. After restoration of normal sinus rhythm (either pharmacologic or electric), all patients received a daily dose of amiodarone (200 mg) and were followed for a median of 19 months (percentiles 25 and 75: 8-34 months). RESULTS: Sixty eight patients (48.22%) regained sinus rhythm during the initial period of amiodarone treatment with 600 mg/day (Group I) and 73 (51.78%) required electric cardioversion (Group II). During the entire follow-up, atrial fibrillation relapsed in 63 patients: 17 (25%) in Group I and 46 (63%) in Group II. Recurrences of the arrhythmia were strikingly less frequent in patients whose atrial fibrillation lasted 12 months or less (33/103, 32.3%) than in those whose atrial fibrillation lasted more than 12 months (30/38, 78.94%). In the multivariate analysis, the mode of reversion (HR, 0.37; CI, 0.21-0.65) and the duration of the arrhythmia (HR, 2.55; CI, 1.54-4.20) were the determinants for long-term sinus rhythm maintenance. Age, sex, left atrium size, left ventricle diameter, and the shortening fraction did not significantly influence the rate of arrhythmia recurrence. Among the 141 patients included in the study, 113 patients were followed for at least 1 year, and cardiac rhythm was assessed at this time. Of these, only 1 of 48 patients (2.1%) in Group I was in atrial fibrillation, in marked contrast with 18 of 65 patients (27.8%) in Group II (RR, 0.075; 95% CI, 0.01-0.54). CONCLUSIONS: In patients with persistent atrial fibrillation, long-term preservation of sinus rhythm under chronic amiodarone treatment may be anticipated when the arrhythmia lasts 12 months or less and/or its reversion is obtained pharmacologically. We may confidently assume that these two factors have a beneficial additive influence on the outcome.