7-Nitro indazole, an inhibitor of neuronal nitric oxide synthase, attenuates pilocarpine-induced seizures

7-Nitro indazole (25–100 mg/kg i.p.), an inhibitor of neuronal nitric oxide (NO) synthase, attenuated the severity of pilocarpine (300 mg/kg i.p.)-induced seizures in mice. This indicates that the decreased neuroexcitability of the central nervous system (CNS) following administration of 7-nitro indazole may be due to inhibition of neuronal NO synthase, implying that NO acts as an excitatory and proconvulsant factor in the CNS

Prevalence of sleep disturbances among head and neck cancer patients:A systematic review and meta-analysis

This systematic review and meta-analysis aim to investigate the prevalence rates of various types of sleep disturbances among head and neck cancer (HNC) patients before, during, and after cancer treatment. We performed a systematic search on PubMed, Embase, CINAHL, and PsycINFO to find studies that reported the prevalence of any type of sleep disturbance among adult HNC patients. Meta-analyses of prevalence were performed using random effects models, with I2 values to indicate the extent of heterogeneity. In total, 29 studies of accumulatively 2315 HNC patients were included. The quality of the studies was fairly low and the heterogeneity was high. Studies on three types of sleep disturbances were found: insomnia (17 studies), hypersomnolence (12 studies), and sleep-related breathing disturbances (14 studies). The prevalence of insomnia was 29% (95% CI 20–41%) before treatment, 45% (95% CI 33–58%) during treatment, and 40% (95% CI 24–58%) after treatment, while for hypersomnolence the prevalence was 16% (95% CI 7–32%) before treatment and 32% (95% CI 20–48%) after treatment. The prevalence of sleep-related breathing disturbances before and after treatment was 66% (95% CI 44–82%) and 51% (95% CI 34–67%), respectively. These results imply that sleep disturbances are highly prevalent among HNC patients before, during, and after treatment

AT(2) receptor-mediated vasodilation in the heart: effect of myocardial infarction

To investigate the functional consequences of postinfarct cardiac angiotensin (ANG) type 2 (AT(2)) receptor upregulation, rats underwent coronary artery ligation or sham operation and were infused with ANG II 3-4 wk later, when scar formation is complete. ANG II increased mean arterial pressure (MAP) more modestly in infarcted animals than in sham animals. The AT(1) receptor antagonist ir

Implications of Brexit on EU Financial Services

This study, which is prepared by Policy Department A at the request of the ECON Committee, addresses the implications and economic impact of several scenarios of the UK leaving the EU in relation to financial services, ranging from a ‘hard Brexit’ without any arrangements concerning financial services to the current state of affairs under the terms of a full EU membership. Special focus is put on a peculiar variation of ‘hard Brexit’, which are the third-country regimes in the current EU secondary legal framework that allow partial access to the EU single market based on ‘equivalence’ on the basis of decisions by the European Commission or national authorities. The study presents these regimes and the extent to which they were already used in the past. The economic analysis looks at three variations of ‘hard Brexit’ (one, in which the access to the single market is closed, one with partial access based on equivalence and one, in which the City of London is transformed into an ‘offshore financial centre’) and at the scenario, in which the UK joins the EEA. The economic assessment is based on the current state of affairs in relation to the interwovenness of financial services in the EU28 including a closer look at the importance of UK-based clearing of Euro denominated trades

Beneficial effects of combined AT1 receptor/neprilysin inhibition (ARNI) versus AT1 receptor blockade alone in the diabetic eye

PURPOSE. Dysfunction of the renin-angiotensin system (RAS) contributes to pathogenesis of diabetic retinopathy (DR). Yet RAS blockers have only limited beneficial effects on progression of DR in clinical trials. The natriuretic peptide system offsets RAS, so that enhancing the activity of this system on top of RAS blockade might be beneficial. Neprilysin has an important role in the degradation of natriuretic peptides. Therefore, we hypothesize that dual angiotensin receptor-neprilysin inhibition (ARNI) may outperform angiotensin receptor blocker (ARB) in protection against DR. We tested this hypothesis in streptozotocininduced diabetic transgenic (mRen2)27 rats. METHODS. Adult male diabetic (mRen2)27 rats were followed for 5 or 12 weeks. Treatment with vehicle, irbesartan (ARB), or ARB combined with the neprilysin inhibitor thiorphan (irbesartan+thiorphan [ARNI]) occurred during the final 3 weeks. Retinal cell death, gliosis, and capillary loss were evaluated. Real-time polymerase chain reaction (RT-PCR) analyses were performed to quantify the retinal level of inflammatory cell markers. RESULTS. Both ARB-and ARNI-treated groups showed similarly reduced retinal apoptotic cell death, gliosis, and capillary loss compared to the vehicle-treated group in the 5-week study. Treatment with ARNI reduced the expression of inflammatory markers more than ARB treatment in the 5-week study. In the 12-week study, ARNI treatment showed significantly more reduction in apoptotic cell death (51% vs. 25% reduction), and capillary loss (68% vs. 43% reduction) than ARB treatment. CONCLUSIONS. Treatment with ARNI provides better protection against DR in diabetic (mRen2)27 transgenic rats, compared to ARB alone. This approach may be a promising treatment option for patients with DR

Methylation of migraine-related genes in different tissues of the rat

17β-Estradiol, an epigenetic modulator, is involved in the increased prevalence of migraine in women. Together with the prophylactic efficacy of valproate, which influences DNA methylation and histone modification, this points to the involvement of epigenetic mechanisms. Epigenetic studies are often performed on leukocytes, but it is unclear to what extent methylation is similar in other tissues. Therefore, we investigated methylation of migraine-related genes that might be epigenetically regulated (CGRP-ergic pathway, estrogen receptors, endothelial NOS, as well as MTHFR) in different migraine-related tissues and compared this to methylation in rat as well as human leukocytes. Further, we studied whether 17β-estradiol has a prominent role in methylation of these genes. Female rats (n = 35) were ovariectomized or shamoperated and treated with 17b-estradiol or placebo. DNA was isolated and methylation was assessed through bisulphite treatment and mass spectrometry. Human methylation data were obtained using the Illumina 450k genome-wide methylation array in 395 female subjects from a population-based cohort study. We showed that methylation of the Crcp, Calcrl, Esr1 and Nos3 genes is tissue-specific and that methylation in leukocytes was not correlated to that in other tissues. Interestingly, the interindividual variation in methylation differed considerably between genes and tissues. Furthermore we showed that methylation in human leukocytes was similar to that in rat leukocytes in our genes of interest, suggesting that rat may be a good model to study human DNA methylation in tissues that are difficult to obtain. In none of the genes a significant effect of estradiol treatment was observed