Role of retinol in protecting epithelial cell damage induced by Clostridium difficile toxin A

Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage.     

二甲双胍在多囊卵巢综合征的作用

生殖及代谢异常是多囊卵巢综合征(PCOS)的特征性表现。已证实高胰岛素血症及胰岛素抵抗,导致血中雄激素水平过高,是PCOS的重要发病机制。二甲双胍(metformin)称为胰岛素增敏剂,用于治疗PCOS后,可减轻高雄激素血症,使月经周期规律,改善卵巢对诱导排卵的反应,提高妊娠率,降低早孕流产率,且能减低发展为II型糖尿病及心血管疾病的危险性。本文就国外近年有关metformin运用于PCOS的进展作一综述。     

Enhanced dispersion of atrial refractoriness as an electrophysiological substrate for vulnerability to atrial fibrillation in patients with paroxysmal atrial fibrillation.

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.     

Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

Modulation of arterial stiffness with intensive competitive training.

BACKGROUND: Aerobic exercise training has been associated with beneficial effects on the cardiovascular system, improving arterial compliance, possibly related to a positive impact on the endothelium. The effects of competitive aerobic exercise are not so well documented. This prompted us to evaluate the possible modulation of arterial properties in a group of athletes and their response to the aging process. METHODS: 423 healthy males were enrolled in a cross-sectional study, 212 of whom were competitive athletes and 211 were controls. All underwent carotid-femoral pulse wave velocity (PWV) evaluation, and casual blood pressure and other relevant anthropometric data were evaluated. RESULTS: To control the effects of age, each group was divided into two subgroups with an age cut-point of 20 years. PWV was 6.3 +/- 0.9 m/s (athletes) vs. 7.0 +/- 1.0 m/s (controls) for ages <20 years, and 7.6 +/- 1.2 m/s (athletes) vs. 8.1 +/- 0.9 m/s (controls) for ages >20 years, with statistically significant differences in both comparisons. A linear regression model with logarithmic tendency analysis with age as the independent determinant of PWV revealed a different progression of age-related deterioration of aortic compliance between the two groups (athletes and controls). CONCLUSIONS: Our data documented better compliance indices in competition athletes compared with controls, which may reflect optimization of endothelial function. This improvement was age-dependent, being less pronounced as the athletes grow older, which could be due partially to sustained stretching effects on the arterial walls in long-term competitors.