Local inhibition of ornithine decarboxylase reduces vascular stenosis in a murine model of carotid injury

Objectives

Polyamines are organic polycations playing an essential role in cell proliferation and differentiation, as well as in cell contractility, migration and apoptosis. These processes are known to contribute to restenosis, a pathophysiological process often occurring in patients submitted to revascularization procedures. We aimed to test the effect of α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, on vascular cell pathophysiology in vitro and in a rat model of carotid arteriotomy-induced (re)stenosis.

Methods

The effect of DFMO on primary rat smooth muscle cells (SMCs) and mouse microvascular bEnd.3 endothelial cells (ECs) was evaluated through the analysis of DNA synthesis, polyamine concentration, cell viability, cell cycle phase distribution and by RT-PCR targeting cyclins and genes belonging to the polyamine pathway. The effect of DFMO was then evaluated in arteriotomy-injured rat carotids through the analysis of cell proliferation and apoptosis, RT-PCR and immunohistochemical analysis of differential gene expression.

Results

DFMO showed a differential effect on SMCs and on ECs, with a marked, sustained anti-proliferative effect of DFMO at 3 and 8 days of treatment on SMCs and a less pronounced, late effect on bEnd.3 ECs at 8 days of DFMO treatment. DFMO applied perivascularly in pluronic gel at arteriotomy site reduced subsequent cell proliferation and preserved smooth muscle differentiation without affecting the endothelial coverage. Lumen area in DFMO-treated carotids was 49% greater than in control arteries 4 weeks after injury.

Conclusions

Our data support the key role of polyamines in restenosis and suggest a novel therapeutic approach for this pathophysiological process.     

The contribution of risk factors to the higher incidence of invasive and in situ breast cancers in women with higher levels of education in the European prospective investigation into cancer and nutrition

The authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasive breast cancer. Reproductive history (age at first full-term pregnancy and parity), exposure to endogenous and exogenous hormones, height, and health behaviors were accounted for in the analyses. Relative indices of inequality (RII) for education were estimated using Cox regression models. A higher risk of invasive breast cancer was found among women with higher levels of education (RII = 1.22, 95% confidence interval (CI): 1.09, 1.37). This association was not observed among nulliparous women (RII = 1.13, 95% CI: 0.84, 1.52). Inequalities in breast cancer incidence decreased substantially after adjusting for reproductive history (RII = 1.11, 95% CI: 0.98, 1.25), with most of the association being explained by age at first full-term pregnancy. Each other risk factor explained a small additional part of the inequalities in breast cancer incidence. Height accounted for most of the remaining differences in incidence. After adjusting for all known risk factors, the authors found no association between education level and risk of invasive breast cancer. Inequalities in incidence were more pronounced for in situ breast cancer, and those inequalities remained after adjustment for all known risk factors (RII = 1.61, 95% CI: 1.07, 2.41), especially among nulliparous women.     

Phenolic content and antioxidant and antiacetylcholinesterase properties of honeys from different floral origins

Twenty-three honey samples of Apis mellifera L. forged on plants from northeastern Brazil were analyzed to determine total phenolic content, flavonoid content, antioxidant activity, and antiacetylcholinesterase activity. The total phenol content was determined by using the Folin-Ciocalteu method, and the flavonoid content was analyzed using by the aluminum chloride method. The antioxidant activity was evaluated using the diphenyl-1-picrylhydrazyl-scavenging test. Honey samples from Lippia sidoides Cham. (mean [±standard deviation] 50% inhibitory concentration [IC(50)], 4.20±1.07?mg/mL) and Myracrodruon urundeuva Fr. All. (IC(50), 28.27±1.41?mg/mL) showed better antioxidant activity and presented higher total phenol values (108.50±3.52?mg gallic acid equivalents/100?g for L. sidoides and 68.55±1.01?mg gallic acid equivalents/100?g for M. urundeuva). Several honey samples had relevant results on antiacetylcholinesterase assay. The biological activity of honeys is related to their floral origin, and medicinal plants constitute a useful resource for the generation of functional foods.     

An open randomized study of the treatment of escitalopram alone and combined with gamma-hydroxybutyric acid and naltrexone in alcoholic patients.

gamma-hydroxybutyric acid (GHB) and the selective serotonin reuptake inhibitor escitalopram are effective in inducing and maintaining abstinence in alcohol. Naltrexone (NTX), an opioid antagonist, may be effective in preventing relapse in alcohol-dependent subjects. To evaluate whether each drug and its combination help to maintain alcohol abstinence, we determined the relapse rate over 6 months in 3 groups of patients. Group 1 (11 patients) received escitalopram (20 mg/day) orally administered; group 2 (12 patients) received NTX (50 mg/day) and escitalopram (20 mg/day); group 3 (12 patients) received GHB (75 mg/kg body weight) and escitalopram (20 mg/day); and group 4 (12 patients) received NTX (50mg/day) plus GHB (75 mg/kg) and escitalopram (20 mg/day). All groups received psychological support and underwent urine tests for alcohol metabolites twice a week. In group 1 (escitalopram only), 6 patients relapsed within 3 months and 3 after 6 months; whereas 2 patients remained abstinent. In group 2 (SSRI+NTX), 5 patients relapsed after 3 months and 3 after 6 months; whereas 4 patients remained abstinent. In group 3 (GHB+SSRI), 3 patients relapsed after 3 months and 3 after 6 months; whereas 6 patients remained abstinent. Finally, in group 4 (NTX+GHB+SSRI), 1 patient relapsed after 3 months and 1 after 6 months, whereas 10 patients remain abstinent. In conclusion, the combination of NTX+GHB+SSRI was the most effective in preventing relapses.     

Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.

Methods:

We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.

Results:

After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83–1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74–0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.

Conclusion:

Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.     

A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape affects the epidemiology of tuberculosis

This study was aimed at determining the cause for the high incidence of tuberculosis (TB) reactivation occurring in males with a low body mass index (BMI). Current thinking about pulmonary TB describes infection in the lung apex resulting in cavitation after reactivation. A different hypothesis is put forward for TB infection, suggesting that this occurs in subclinical apical cavities caused by increased pleural stress due to a low BMI body habitus. A finite element analysis (FEA) model of a lung was constructed including indentations for the first rib guided by paramedian sagittal CT reconstructions, and simulations were conducted with varying antero‐posterior (AP) diameters to mimic chests with a different thoracic index (ratio of AP to the transverse chest diameters). A Pubmed search was conducted about gender and thoracic index, and the effects of BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung apex in low BMI chests, and a four‐fold increase with a low thoracic index, r² = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean thoracic index was statistically significantly lower in males, P = 0.001, and increased with age in both genders. This article is the first to suggest a possible mechanism linking pulmonary TB reactivation to low BMI due to the flattened thoracic wall shape of young male adults. The low thoracic index in young males may promote TB reactivation due to tissue destruction in the lung apex from high pleural stress levels. Clin. Anat. 28:614–620, 2015. © 2015 Wiley Periodicals, Inc.     

Yogurt consumption and risk of colorectal cancer in the Italian European prospective investigation into cancer and nutrition cohort

Fermented dairy products like yogurt have been suggested to protect against colorectal cancer (CRC). We conducted a prospective study on 45,241 (14,178 men; 31,063 women) volunteers of the EPIC-Italy cohort who completed a dietary questionnaire including specific questions on yogurt intake. During 12 years of follow-up, 289 volunteers were diagnosed with CRC. Hazard ratios (HRs) for the disease and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models, stratified by dietary questionnaire and adjusted for energy intake and other potential confounders. Yogurt intake was inversely associated with CRC risk. For the energy-adjusted model, HR for CRC in the highest versus lowest tertile of yogurt intake was 0.62 (95% CI, 0.46-0.83). In the full model adjusted for energy, simple sugar, calcium, fiber, animal fat, alcohol and red meat intake, as well as body mass index, smoking, education and physical activity, HR was 0.65 (95% CI, 0.48-0.89) in the highest versus lowest tertile. The protective effect of yogurt was evident in the entire cohort, but was stronger in men, although there was no interaction of sex with the yogurt-CRC association (p(interaction) 0.20, fully adjusted model). In our prospective study, high yogurt intake was significantly associated with decreased CRC risk, suggesting that yogurt should be part of a diet to prevent the disease. Investigation of larger cohorts is necessary to reveal any residual confounding of the association of yogurt intake with CRC risk.