Hypothalamic expression of inflammatory mediators in an animal model of binge eating

Binge eating episodes are characterized by uncontrollable, distressing eating of a large amount of highly palatable food and represent a central feature of bingeing related eating disorders. Research suggests that inflammation plays a role in the onset and maintenance of eating-related maladaptive behavior. Markers of inflammation can be selectively altered in discrete brain region where they can directly or indirectly regulate food intake. In the present study we measured expression levels of different components of cytokine systems (IL-1, IL-6, IL-18, TNF-\uf061 and IFN-&3) and related molecules (iNOS and COX2) in the preoptic and anterior-tuberal parts of the hypothalamus of a validated animal model of binge eating. In this animal model, based on the exposure to both food restriction and frustration stress, binge-like eating behavior for highly palatable food is not shown when animals are exposed to the frustration stress during the estrus phase. We found a characteristic down-regulation of the IL-18/ IL-18 receptor system (with increased expression of the inhibitor of the pro-inflammatory cytokine IL18, IL-18BP, together with a decreased expression of the binding chain of the IL-18 receptor) and a three-fold increase in the expression of iNOS specifically in the anterior- tuberal region of the hypothalamus of animals that develop a binge-like eating behavior. Differently, when food restricted animals were stressed during the estrus phase IL-18 expression increased while iNOS expression was not significantly affected. Considering the role of this region of the hypothalamus in controlling feeding related behavior, this can be relevant in eating disorders and obesity. Our data suggest that by targeting centrally selected inflammatory markers, we may prevent that disordered eating turns into a full blown eating disorder

Brain Alterations in High Fat Diet Induced Obesity: Effects of Tart Cherry Seeds and Juice

Evidence suggests that obesity adversely affects brain function. High body mass index, hypertension, dyslipidemia, insulin resistance, and diabetes are risk factors for increasing cognitive decline. Tart cherries (Prunus Cerasus L.) are rich in anthocyanins and components that modify lipid metabolism. This study evaluated the effects of tart cherries on the brain in diet-induced obese (DIO) rats. DIO rats were fed with a high-fat diet alone or in association with a tart cherry seeds powder (DS) and juice (DJS). DIO rats were compared to rats fed with a standard diet (CHOW). Food intake, body weight, fasting glycemia, insulin, cholesterol, and triglycerides were measured. Immunochemical and immunohistochemical techniques were performed. Results showed that body weight did not differ among the groups. Blood pressure and glycemia were decreased in both DS and DJS groups when compared to DIO rats. Immunochemical and immunohistochemical techniques demonstrated that in supplemented DIO rats, the glial fibrillary acid protein expression and microglial activation were reduced in both the hippocampus and in the frontal cortex, while the neurofilament was increased. Tart cherry intake modified aquaporin 4 and endothelial inflammatory markers. These findings indicate the potential role of this nutritional supplement in preventing obesity-related risk factors, especially neuroinflammation

Progressive myoclonus epilepsies due to SEMA6B mutations. New variants and appraisal of published phenotypes

Variants of SEMA6B have been identified in an increasing number of patients, often presenting with progressive myoclonus epilepsy (PME), and to lesser extent developmental encephalopathy, with or without epilepsy. The exon 17 is mainly involved, with truncating mutations causing the production of aberrant proteins with toxic gain of function. Herein, we describe three adjunctive patients carrying de novo truncating SEMA6B variants in this exon (c.1976delC and c.2086C > T novel; c.1978delC previously reported). These subjects presented with PME preceded by developmental delay, motor and cognitive impairment, worsening myoclonus, and epilepsy with polymorphic features, including focal to bilateral seizures in two, and non-convulsive status epilepticus in one. The evidence of developmental delay in these cases suggests their inclusion in the “PME plus developmental delay” nosological group. This work further expands our knowledge of SEMA6B variants causing PMEs. However, the data to date available confirms that phenotypic features do not correlate with the type or location of variants, aspects that need to be further clarified by future studie

A multidisciplinary approach to study the brain injury in Diet-Induced Obesity (DIO) rats

Obesity represents an independent risk factor for the development of cerebrovascular disease and cognitive impairment. The systemic effects, such as increased fat mass, hypertension, insulin resistance and general metabolic dysfunction, have been identified as factors that may lead to impaired cognitive function. To clarify the possible relationships between obesity and nervous system changes, high-caloric Diet-Induced Obesity (DIO) rats 7 weeks-old, were studied after 17 weeks of hypercaloric diet compared to control rats with not fat diet (Chow) or to rats not developing obesity (DIO-resistant DR). Food consumption, fat mass content, blood pressure and blood parameters were assessed. Different behavioural tests were used to estimate cognitive performance. RT-qPCR, immunochemical and immunohistochemical analysis were performed to evaluate neuronal, glial and vascular markers. The obese phenotype developd after 5 weeks of high fat diet exposure and body weight values remained higher in DIO rats compared to the control group and DR rats during the treatment. Systolic blood pressure, glycaemia and insulin were higher in DIO rats only after 17 weeks. No differences in values of total cholesterol and triglycerides were observed. Furthermore increase of thiobarbituric reactive substances and increase of oxidated proteins, was observed in the serum of DIO rats compared to Chow rats. The open-field test revealed, in the older DIO rats, a decrease of cumulative distance travelled and in the number of rearings and an increase of total immobility time. Older DIO rats only, showed a reduction of retention latency time in the passive avoidance test. RT-qPCR, immunochemical and immunohistochemical analysis showed an increased expression of the glial-fibrillary acid protein in the frontal cortex and hippocampus of older DIO rats compared to age-matched Chow and DR rats. A decrease of neurofilament expression was found in the hippocampus of older DIO rats without changes in the number of neurons. A modulation in the Transient Receptor Potential (TRP) channels and synaptic components was highlighted in cerebral areas. These results indicate that obesity in rats, in addition to the development of correlate cerebrovascular risk factors, causes brain injury characterized by astrogliosis, neurodegeneration and impaired learning and memory tasks. The identification of neurodegenerative changes in DIO rats may represent the first step to better characterize the neuronal modifications occurring in the obesity and propose pharmacological treatments or food strategies to counter them

Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial

<p>Abstract</p> <p>Background</p> <p>In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment.</p> <p>Methods</p> <p>Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment.</p> <p>Results</p> <p>At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse.</p> <p>Conclusion</p> <p>In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR.</p> <p>Trial registration</p> <p>Trial number ISRCTN29259563</p

Obesity-related nervous system injury: preliminary evidences in diet induced obesity (DIO) rats.

Increased food intake, reduced physical activity and altered metabolic processes are the variables that affect energy balance inducing obesity. Obesity is now considered an increas-ingly medical challenge. Actually, the prevalence of obesity has increased dramatically worldwide over the last decades and has now reached epidemic proportions. On the other hand, obesity is associated with the development of chronic diseases such as cerebrovascu-lar disease promoting the cognitive decline. Caloric-dense diet induced obesity (DIO), provides a useful animal model sharing several common features with human obesity. DIO rats of 7 weeks of age are expose to high fat (45 %) diet ad libitum and after 5 weeks the obese phenotype starts to be develop. To clarify the possible relationships between obesity and nervous system changes, DIO rats were studied after 5 weeks and 17 weeks of hypercaloric diet compared to the control rats with not fat diet (Chow). Memory performance were measured using different cognitive tests. Moreover, ultrasonographic (US) and computed tomography (CT) evaluations were per-formed to detect adipose tissue changes. Magnetic resonance imaging (MRI) to highlight brain morphological alterations was used. Morphological changes of brain areas (frontal cor-tex, hippocampus) were evaluated by immunohistochemical analysis. The results confirmed the developed of obesity after 5 weeks of fat diet. At long-term (17 weeks) high fat diet exposure, rats increased significantly their body weight in comparison to the control group and the youngest DIO rats. The US and CT analysis indicated an increase of deposition of both visceral and subcutaneous adipose tissue and evidences a decrease of hepatic attenuation in the older DIO rats.MRI images did not show vascular and morphologi-cal alterations in brain. Instead, immuhistochemical and immunochemical analysis, revealed an increase expression of glial-fibrillary acidic protein (GFAP) in the older DIO rats compared to the age- matched Chow rats both in frontal cortex and in hippocampus. DIO rats showed a reduction of retention latency time in the emotional learning task. These preliminary findings indicate that the development of obesity, does not determined gross anatomy alteration in brain, but the occurrence of injury characterized by astrogliosis. The identification of neurodegenerative changes in DIO may represent the first insight to better characterize the neuronal involvement in obesity

Factors related to the development of health-promoting community activities in Spanish primary healthcare: two case-control studies

Atenció Primària de Salut; Salut Comunitària; Promoció de la SalutAtención Primaria de Salud; Salud Comunitaria; Promoción de la SaludPrimary Health Care; Community Health; Health PromotionOBJECTIVE: Spanish primary healthcare teams have the responsibility of performing health-promoting community activities (CAs), although such activities are not widespread. Our aim was to identify the factors related to participation in those activities. DESIGN: Two case-control studies. SETTING: Performed in primary care of five Spanish regions. SUBJECTS: In the first study, cases were teams that performed health-promoting CAs and controls were those that did not. In the second study (on case teams from the first study), cases were professionals who developed these activities and controls were those who did not. MAIN OUTCOME MEASURES: Team, professional and community characteristics collected through questionnaires (team managers/professionals) and from secondary sources. RESULTS: The first study examined 203 teams (103 cases, 100 controls). Adjusted factors associated with performing CAs were percentage of nurses (OR 1.07, 95% CI 1.01 to 1.14), community socioeconomic status (higher vs lower OR 2.16, 95% CI 1.18 to 3.95) and performing undergraduate training (OR 0.44, 95% CI 0.21 to 0.93). In the second study, 597 professionals responded (254 cases, 343 controls). Adjusted factors were professional classification (physicians do fewer activities than nurses and social workers do more), training in CAs (OR 1.9, 95% CI 1.2 to 3.1), team support (OR 2.9, 95% CI 1.5 to 5.7), seniority (OR 1.06, 95% CI 1.03 to 1.09), nursing tutor (OR 2.0, 95% CI 1.1 to 3.5), motivation (OR 3.7, 95% CI 1.8 to 7.5), collaboration with non-governmental organisations (OR 1.9, 95% CI 1.2 to 3.1) and participation in neighbourhood activities (OR 3.1, 95% CI 1.9 to 5.1). CONCLUSIONS: Professional personal characteristics, such as social sensitivity, profession, to feel team support or motivation, have influence in performing health-promoting CAs. In contrast to the opinion expressed by many professionals, workload is not related to performance of health-promoting CAs