A sensitive period for environmental regulation of eating behavior and leptin sensitivity

Western lifestyle contributes to body weight dysregulation. Leptin down-regulates food intake by modulating the activity of neural circuits in the hypothalamic arcuate nucleus (ARC), and resistance to this hormone constitutes a permissive condition for obesity. Physical exercise modulates leptin sensitivity in diet-induced obese rats. The role of other lifestyle components in modulating leptin sensitivity remains elusive. Environmentally enriched mice were used to explore the effects of lifestyle change on leptin production/action and other metabolic parameters. We analyzed adult mice exposed to environmental enrichment (EE), which showed decreased leptin, reduced adipose mass, and increased food intake. We also analyzed 50-d-old mice exposed to either EE (YEE) or physical exercise (YW) since birth, both of which showed decreased leptin. YEE mice showed no change in food intake, increased response to leptin administration, increased activation of STAT3 in the ARC. The YW leptin-induced food intake response was intermediate between young mice kept in standard conditions and YEE. YEE exhibited increased and decreased ratios of excitatory/inhibitory synapses onto α-melanocyte-stimulating hormone and agouti-related peptide neurons of the ARC, respectively. We also analyzed animals as described for YEE and then placed in standard cages for 1 mo. They showed no altered leptin production/action but demonstrated changes in excitatory/inhibitory synaptic contacts in the ARC similar to YEE. EE and physical activity resulted in improved insulin sensitivity. In conclusion, EE and physical activity had an impact on feeding behavior, leptin production/action, and insulin sensitivity, and EE affected ARC circuitry. The leptin-hypothalamic axis is maximally enhanced if environmental stimulation is applied during development.     

TrkA activation in the rat visual cortex by antirat trkA IgG prevents the effect of monocular deprivation

It has been recently shown that intraventricular injections of nerve growth factor (NGF) prevent the effects of monocular deprivation in the rat. We have tested the localization and the molecular nature of the NGF receptor(s) responsible for this effect by activating cortical trkA receptors in monocularly deprived rats by cortical infusion of a specific agonist of NGF on trkA, the bivalent antirat trkA IgG (RTA-IgG). TrkA protein was detected by immunoblot in the rat visual cortex during the critical period. Rats were monocularly deprived for 1 week (P21–28) and RTA-IgG or control rabbit IgG were delivered by osmotic minipumps. The effects of monocular deprivation on the ocular dominance of visual cortical neurons were assessed by extracellular single cell recordings. We found that the shift towards the ipsilateral, non-deprived eye was largely prevented by RTA-IgG. Infusion of RTA-IgG combined with antibody that blocks p75^NTR (REX), slightly reduced RTA-IgG effectiveness in preventing monocular deprivation effects. These results suggest that NGF action in visual cortical plasticity is mediated by cortical TrkA receptors with p75^NTR exerting a facilitatory role.     

Membrane and capillary blood components of diffusion capacity of the lung for carbon monoxide in pulmonary sarcoidosis: relation to exercise gas exchange

BACKGROUND: Resting pulmonary diffusing capacity of the lung for carbon monoxide (DLCO) is known to be the best predictor of arterial desaturation during exercise in patients with sarcoidosis. However, the relative contribution of each of the two components of DLCO-alveolar membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc)-remains unclear. STUDY OBJECTIVES: To evaluate which component is responsible for the decrease of resting DLCO in patients with sarcoidosis, and to determine which resting pulmonary function test, including Dm and Vc, is the best predictor of gas exchange abnormalities during submaximal exercise. DESIGN: Prospective analysis of patients referred to our department of respiratory medicine. PATIENTS: Twenty four patients with pulmonary sarcoidosis were separated into two groups according to chest radiographic findings: group 1, stages 2 and 3 (n = 15); group 2, stage 4 (n = 9). All the patients completed pulmonary function tests (flows, volumes, single-breath DLCO, transfer coefficient [Ka], Dm, Vc) and submaximal exercise (two steady-state levels of mild and moderate exercise corresponding respectively to a target oxygen consumption of approximately 10 to 15 mL/min/kg). RESULTS: DLCO was reduced in the two groups (group 1, 63 +/- 16% of predicted; group 2, 64 +/- 16% of predicted). Dm was severely decreased (group 1, 58 +/- 24% of predicted; group 2, 51 +/- 15% of predicted), whereas Vc was unchanged or only mildly decreased (group 1, 81 +/- 18% of predicted; group 2, 85 +/- 28% of predicted). Whatever the group of patients and the exercise level, Dm and DLCO were the strongest predictors (p < 0.001) of gas exchange abnormalities. Ka or volumes were weak predictors, and Vc or flows were not related with exercise gas exchange. CONCLUSIONS: This study demonstrates that a decrease in Dm mostly accounts for resting DLCO reduction, and that Dm as well as DLCO are highly predictive of gas exchange abnormalities at exercise in patients with sarcoidosis.     

(In)accuracy of blood pressure measurement in 14 Italian hospitals

OBJECTIVES:: The diagnosis and control of hypertension depend on accurate measurement of blood pressure (BP). The literature on the accuracy of BP recording by health professionals is, however, limited, and no study directly interviewed patients in the hospital setting. This multicenter cross-sectional study aimed at evaluating the compliance to current recommendations on BP measurement by health professionals directly from patients and to investigate potential predictors of higher quality in BP recording. METHODS:: A trained nurse interviewed a random sample of adult patients hospitalized for an ordinary admission (except in the emergency room) lasting more than one night, without mental disorder, who had their BP routinely measured by the hospital personnel less than 3?h before. The questionnaire contained 15 items on the main procedures that are common to current guidelines. RESULTS:: Fourteen public hospitals from seven regions of Italy participated, and 1334 questionnaires were collected. Nine of the recommended practices were followed in the majority (>70%) of BP recordings, whereas some others were infrequent or rare: in 98.6, 82.2 and 81.1% of the participants, respectively, the arm circumference was never recorded, BP was measured only once, and BP was never recorded in both arms. Overall, 10 or more recommended procedures were followed during 33.4% recordings. At multivariate analysis, physicians were less likely than nurses to provide a more accurate BP measurement. CONCLUSIONS:: The operator's compliance to some recommendations in BP measurement is unacceptably low. This survey provides detailed indications for medical directors on the procedures and settings to prioritize in educational programs, which are definitely needed.     

Role of protein synthesis in the protection conferred by ozone-oxidative-preconditioning in hepatic ischaemia/reperfusion

The liver is damaged by sustained ischaemia during liver transplantation, and the reperfusion after ischaemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischaemia/reperfusion (I/R) injury through different mechanisms. The aim of this study was to investigate the influence of the inhibition of protein synthesis on the protective actions conferred by OzoneOP in hepatic I/R. Rats were treated with cycloheximide (CHX) in order to promote protein synthesis inhibition after OzoneOP treatment. Plasma transaminases, malondialdehyde and 4-hydroxyalkenals and morphological characteristics were measured as an index of hepatocellular damage; Cu/Zn-superoxide dismutase (SOD), Mn-SOD, catalase, total hydroperoxides and glutathione levels as markers of endogenous antioxidant system. OzoneOP increased Mn-SOD isoform and ameliorated mitochondrial damage. CHX abrogated the protection conferred by OzonoOP and decreased Mn-SOD activity. Cellular redox balance disappeared when CHX was introduced. Protein synthesis is involved in the protective mechanisms mediated by OzoneOP. Ozone treatment preserved mitochondrial functions and cellular redox balance.     

The unresponsive regions of visual cortical receptive fields

We have recorded from simple and complex cells in area 17 of the cat cortex. Around the classical receptive field (regions within which a moving or flashing bar can elicit a response from a cell) there are large regions which dramatically influence the cell's responsiveness. In some cells these regions are facilitatory, in others, inhibitory. Since these regions do not respond in isolation to moving or flashing bars, we called them unresponsive regions of the receptive field. Both the inhibitory and facilitatory unresponsive regions show spatial-frequency selectivity. All the facilitatory unresponsive regions show orientation selectivity, while most of the inhibitory unresponsive regions are not orientation selective. Both the facilitatory and the inhibitory unresponsive regions contribute to the size-selectivity of the cell. The facilitatory unresponsive regions show a great influence on the orientation selectivity of the cell, in that they sharpen the orientation channel of the cell. The inhibitory unresponsive regions, on the contrary, have not such an effect.     

Endodermal sinus tumor of the omentum: case report

We report a case of primary endodermal sinus tumor of the omentum in a 46-year-old woman. The patient had been referred to our hospital for pain in the right abdomen. CT scan revealed a right-sided abdominal mass. At laparotomy, a large omental tumor extending to the bowel, uterus, ovaries and peritoneum was found, and it was totally resected. The tumor displayed the typical histological patterns observed in endodermal sinus tumor, and the immunohistochemical findings confirmed the diagnosis. Serum AFP level was 21.550 ng/ml prior to laparotomy, and decreased to 13.845 ng/mL after surgery, whereas the level of serum beta human chorionic gonadotropin was normal. Post-surgery, the patient received combination chemotherapy consisting of cisplatin, etoposide and bleomycin every 3 weeks for a total of 6 cycles. At the end of the treatment, all the findings, including AFP level, were normal.     

Osteonecrosis in human immunodeficiency virus (HIV)-infected patients: a multicentric case�Ccontrol study

Osteonecrosis (ON) is a rare disabling complication occurring in patients with human immunodeficiency virus (HIV) infection at a higher frequency than in the general population despite effective combination antiretroviral therapy being made available, as recently documented by several retrospective studies. We designed a multicentric case-control study among HIV-infected patients cared for at institutions in the Italian CISAI group (Italian Study Group for Adverse Events in HIV Infection) to search for additional predictors of ON in this special population. All centers which observed at least one case of ON were requested to report data for central re-evaluation. Parallel HIV-positive, ON-free controls were randomly selected and matched with confirmed cases of ON for sex, age and CD4 T-cell counts at the time of HIV diagnosis. Fifteen cases and controls were included in the final sample. Univariate statistical analyses revealed a significant association between ON and exposure to steroids (P?=?0.001), exposure to one or more drugs in addition to HAART (Highly Active Anti-Retroviral Therapy) (P?=?0.03), high titers of total serum IgE (P?=?0.02), loss of working ability (P?=?0.03), triglycerides levels over 200?mg/dL before antiretrovirals (P?=?0.03) and cholesterol levels over 200?mg/dL before and after antiretrovirals (P?=?0.03 and 0.05, respectively). High serum IgE levels and loss of working ability in advance of ON appeared for the first time as possible predictors of ON in HIV patients, while long-term exposure to steroids, combined hyperlipemia and chronic treatment with other drugs in addition to antiretrovirals were confirmed. Predicting and preventing ON in the individual HIV-infected patient is therefore a clinically challenging opportunity.     

High seroprevalence of HCV in the Abruzzo Region,Italy: results on a large sample from opt-out pre-surgical screening

Purpose

Available estimates of the prevalence of chronic HCV infection in Italy are quite conflicting, varying from 1.5 to 22.5 %, with an apparent north to south gradient. As Direct Acting Antivirals are expensive, both National and local governmental Agencies are in urgent need of detailed and reliable estimates of HCV patients to be treated, nationwide and in each district. We investigated the prevalence of anti-HCV antibodies in a large unselected sample of surgical patients providing consent to in-hospital opt-out pre-surgical HCV screening, at two hospitals from the Abruzzo Region, Italy.

Methods

Data were retrieved for 55,533 screened patients (4.1 % of the total population in the Abruzzo Region), admitted in the Orthopedic and General Surgery wards of Pescara and Teramo Hospitals from 1999 to 2014.

Results

The prevalence of anti-HCV antibodies was 4.4 % in the total sample. HCV-positive patients had a mean age of 63.8 ± 19.9 years; 49.2 % were males. From 1999 to 2014, the prevalence of HCV antibodies decreased from 5.4 % to 4.1 %; at both sites, however, two age-related-peaks were evidenced, the first among patients aged 30–49 years, the second among those older than 70 years. Statistical analyses confirmed a significant trend to decrease over time and a higher prevalence in Pescara and among males (all p < 0.01).

Conclusions

Data retrieved from opt-out pre-surgical screening programs may allow inexpensive and easy-to-perform estimates of HCV seroprevalence from large samples of unselected patients with a well-defined provenience, which may turn useful for future treatment resource allocation.