PYY-Tag transgenic mice displaying abnormal (H+-K+)ATPase activity and gastric mucosal barrier impairment

The mechanism by which the gastrointestinal hormones peptide YY and glucagon inhibit gastric acid secretion is largely unknown. PYY-Tag transgenic mice develop endocrine tumors in the colon that are composed mainly of peptide YY/enteroglucagon-producing L type cells. Therefore we studied the functional activity of such tumors and the gastric functions of PYY-Tag mice. Fasting and fed PYY-Tag transgenic mice and CD1 controls were assayed for circulating levels of peptide YY, glucagon, insulin, and gastrin. The gastric pH was determined and gastric samples were examined for (a) histologic appearance; (b) K(+)-stimulated p-nitrophenylphosphatase activity and [(14)C]aminopyrine accumulation of apical and tubulovesicle membranes; (c) adherent mucus determination by Alcian blue recovery; and (d) DNA/RNA/protein epithelial content and in vivo incorporation of [(3)H]thymidine into DNA. Transgenic mice showed high serum levels of peptide YY and glucagon, increased gastric pH, and a high incidence of gastric ulcers after fasting. p-Nitrophenylphosphatase activity, [(14)C] aminopyrine accumulation, and proton pump redistribution from cytoplasmic tubulovesicles to apical membranes were significantly lower in the gastric mucosa of transgenic mice compared with the controls. In addition, the adherent mucus was thinner, and [(3)H]thymidine incorporation into the DNA was decreased. The abnormal and unregulated levels of circulating peptide YY and glucagon led to gastric acid inhibition and an impairment of gastric barrier function as a result of a striking reduction in epithelial proliferation

Preliminary Evaluation of Sedentary Lifestyle in Italian Children after Solid Transplant: What Role Could Physical Activity Play in Health? It Is Time to Move

Background: Advances in the medical–surgical field have significantly increased survival after solid organ transplantation in the pediatric population. However, these patients are predisposed to the development of long-term complications (e.g., cardiovascular disease). The therapeutic role of physical activity (PA) to counteract these complications is well known. The purpose of the study was to investigate the level of PA in a pediatric population after solid organ transplantation. Methods: In the first 4 weeks at the beginning of the school year, the Physical Activity Questionnaire for Older Children and Adolescents was administered to young patients who had previously undergone solid transplants at our institute. Results: Questionnaires of 49 patients (57.1% female, mean age 13.2 ± 3.5 years) were analyzed and 32.7% of subjects did not perform any exercise during school physical education classes. Only 24% practiced a moderate quantity of exercise in the previous week (2–3 times/week) and 72% engaged in sedentary behaviors during weekends. Conclusions: Preliminary data confirmed that young recipients are still far from meeting the minimum indications of the World Health Organization on PA and sedentary behavior. It will be necessary to increase their involvement in PA programs in order not only to increase their life expectancy but also to improve their quality of life

RELATIONSHIPS BETWEEN NAFLD BIOCHEMICAL SCORES AND LEFT VENTRICULAR GEOMETRIC PATTERN IN NAÏVE ESSENTIAL HYPERTENSIVE PATIENTS

OBJECTIVE: The not alcoholic fatty liver disease (NAFLD) is associated with an increased cardiovascular mortality and morbidity. An hypothesis for this association could be the left ventricular (LV) geometric alteration sometime found in hypertension that is a known prognostic factor for cardiovascular events in hypertension. We searched for a relationship between biochemical scores of NAFLD and left ventricular (LV) hypertrophy (LVH) or LV geometric patterns changes in a large group of never treated essential hypertensive (EH) patients. DESIGN AND METHOD: In 434 naïve (49 ± 14 years, 234 males) we evaluated BMI, waist circumference, liver steatosis at abdominal echography, the biochemical scores of liver steatosis: Liver Fat Score (LFS), Fatty Liver Index (FLI), Hepatic Steatosis Index (NAÏVE), and the fibrosis scores: NAFLD Fibrosis Score (NFS), APRI, FIB-4, parameters of glucose and insulin homeostasis, liver blood tests, lipids, platelets count, glomerular filtration rate (GFR), reactive C protein. LV mass and relative wall thickness was calculated with echocardiography. Patients were classified in 4 groups of LV geometry: 1 = LV normal geometry, 2 = LV concentric remodeling, 3 = concentric LVH, 4 = eccentric LVH. RESULTS: A LVH was present in 17.3% of patients, and these patients had higher LFS (P < 0.001), FLI (P = 0.008), NAÏVE (P = 0.004) and NFS (P = 0.011) scores than patients without LVH. LVH was independently associated with the FLI score but not with fibrosis scores. The steatosis scores (LFS, NAÏVE, FLI) linearly increased across the four LV geometric patterns (P = 0.007, P = 0.001, P = 0.003, respectively). The fibrosis score NFS was significantly higher in subjects with concentric LVH (P = 0.041). The LFS was independently associated with BMI, GAUC, G120, and triglycerides levels. The NFS was independently associated with waist circumference, GFR and weakly with fasting glucose level. Ultrasound steatosis was not different among the four LV geometric patterns. CONCLUSIONS: In naïve EH patients the biochemical steatosis scores show a relationship with LVH and LV geometric changes, while fibrosis is associated with concentric LVH. An accurate investigation to reveal a NAFLD should be done in EH patients with altered LV geometry and to better understanding of mechanisms linking the two conditions

Diagnostic approach to neonatal and infantile cholestasis: A position paper by the SIGENP liver disease working group

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life