Rat visual cortical neurones express TrkA NGF receptor

In this study we report the expression of TrkA receptor within the rat visual cortex during postnatal development and in adulthood, using a specific monoclonal antibody which recognizes the extracellular domain of TrkA receptor. TrkA was not detected by immunohistochemistry at postnatal day 13 (P13), i.e. before eye opening. At P22 TrkA was mostly localised in cortical fibre-like processes. At P39 and P90, TrkA-positive neuronal cell bodies in supragranular and infragranular layers were found. Using double immunohistochemistry, labelled cells were identified as intrinsic cholinergic neurones, and as interneurones expressing calbindin and neuropeptide Y. We conclude that TrkA is expressed in visual cortical neurones during postnatal development and in adulthood and that its pattern of expression is developmentally regulated.     

Comparison of different infratentorial-supracerebellar approaches to the posterior and middle incisural space: a cadaveric study

OBJECT: The purpose of this investigation was to describe and compare through cadaveric dissection the microsurgical exposure afforded by the median, paramedian, and extreme-lateral infratentorial-supracerebellar approaches to the posterior and middle incisural space. METHODS: The median, paramedian, and extreme-lateral infratentorial-supracerebellar approaches were performed in 10 embalmed cadaveric heads by using standard microneurosurgical methods; each approach was executed a minimum of five times. The dissections were performed in a stepwise fashion, comparing the exposure afforded by each surgical route and highlighting the relationships among the targeted neurovascular structures. Exposure of the dural sinuses and transection of the tentorium were also evaluated in relation to the degree of exposure achieved. The median infratentorial-supracerebellar route provides direct exposure of the posterior incisural space, although the culmen represents a relative obstacle to exposure of the lower quadrigeminal plate. The paramedian variant allows a more lateral perspective on the posterolateral brainstem surface at the level of the middle incisural space, in addition to exposing the homolateral collicular plate. The extreme-lateral corridor widens the exposure of the paramedian approach to include the anterolateral brainstem surface, offering a complete view of the cisternal space surrounding the middle incisural space. Complete, constant exposure and retraction of the dural sinuses facilitated the surgical exposure. CONCLUSIONS: The infratentorial-supracerebellar approaches allow safe circumferential exposure of the posterior and middle incisural space. Choosing among different variants allows the surgeon to reach selected areas, with the midline variant being best for exposure of the posterior incisural space, and the paramedian and extreme-lateral variants being best for reaching the posterior and the anterior part of the middle incisural space, respectively. The more lateral the approach, the more anterior and multiangled the exposure gained. Complete, constant exposure and retraction of the dural sinuses improves the exposure. Accurate knowledge of the regional anatomy is mandatory.     

Plasma total and free fatty acids composition in human non-alcoholic steatohepatitis

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH), the association of steatosis with an inflammatory response, is a novel liver disease of unknown pathogenesis and prognosis. Triacylglycerols and their precursors, the fatty acids, are the likely candidates to accumulate in the hepatocyte. Disturbed fatty acid metabolism can be involved in the pathogenesis of NASH but there is no information concerning its plasma fatty acid profile. The aim of this study was to evaluate plasma total (esterified plus free) and free fatty acids concentrations to assess the association of NASH with plasma fatty acid accumulation. MATERIALS AND METHODS: Overnight fasting blood samples from 22 biopsy-proven NASH patients and of 6 matched age healthy controls were studied. RESULTS: NASH patients had significantly higher concentration of total and free fatty acids than controls (P<0.05), higher total saturated and monounsaturated levels in both studied lipid fractions (P<0.05), mainly due to the increase of hexadecanoic, hexadecenoic and octadecenoic acids. Absolute polyunsaturated fatty acids (PUFA) concentrations were similar in both groups. The C20:4/C18:2 and the C18:1/C18:0 ratios as well as the peroxidability index were not significantly different. CONCLUSION: In overweight/obese patients NASH is associated with deranged fatty acid metabolism which may be involved in its pathogenesis and/or progression.     

Income inequality,residential poverty clustering and infant mortality: a study in Rio de Janeiro,Brazil

In this paper, we propose an approach to investigate the hypothesis that the residential concentration of poverty affects health status more deeply than when poverty is randomly scattered in a given geographical area. To characterize the geographic pattern of poverty in the city of Rio de Janeiro, Brazil, an index that measures the heterogeneity of poverty concentration among sub-areas was proposed. We used census data and defined poverty by means of the household head monthly income. The 153 neighborhoods that compose the city were used as the geographic units, and the census tracts as the sub-areas. The proposed index measures differences of poverty concentration across census tracts within a neighborhood. The effects of geographic poverty clustering on infant mortality related variables (early neonatal mortality rate; post-neonatal mortality rate; proportion of adolescent mothers; and fertility rate among adolescents) were estimated by partial correlation coefficients, controlling for the neighborhood poverty rate. Our study revealed that intra-city variations of the post-neonatal mortality rate are associated with geographic patterns of poverty, and that pregnancy in adolescence is strongly and contextually correlated with intra-neighborhood poverty clustering, even after adjustment for the poverty rate. The evidence of relevant health differences associated with the spatial concentration of poverty supports the hypothesis that properties of the environment of residence contextually influence health. Our findings suggest that prevention of some infant mortality related problems has to be focused directly on features of communities, considering their physical, cultural and psychosocial characteristics, being of particular concern the health of communities segregated from the society at large by extreme poverty.     

Nutritional characteristics of a rural Southern Italy population: the Ventimiglia di Sicilia Project

OBJECTIVE: Knowledge of alimentary habits among populations permits a better definition of appropriate public health interventions. We designed the epidemiological project "Ventimiglia di Sicilia" to characterize the risk profile in a rural village with low total cholesterol levels and low early cardiovascular mortality but with a large prevalence of overweight and obesity, which previously have been significantly associated with total mortality. METHODS: 488 individuals of age 20 to 69 years were included in the dietary survey conducted by a seven-day food record. RESULTS: Alimentary habits were characterized by high consumption of total and complex carbohydrates (respectively 52.5 +/- 7.6% and 46.6 +/- 8.2% of daily energy) and by a low cholesterol intake (92.5 +/- 35.0 mg/1000 kcal/day). Fat intake was 34.7 +/- 7.7% of daily energy due to a higher consumption of monounsaturated fats in respect to saturated fats (respectively 20.5 +/- 5.1% and 10.2 +/- 2.9% of daily energy). In particular, in this population there was a large consumption of bread, pasta, fresh vegetables, olive oil and fruits. We also observed an excess of total calories (about 2900 kcal/day in men and 2100 kcal/day in women) not balanced by a high degree of physical activity levels. Furthermore we found a significant higher total and saturated fat consumption in the youngest individuals and in people with higher educational levels. CONCLUSIONS: Dietary habits of Ventimiglia di Sicilia still follow the nutritional characteristics typical of the Mediterranean diet. The high total calorie intake indicates a quantitative more than qualitative problem, which may account the large prevalence of overweight and obesity and may represent a public health issue that needs to be corrected in such a rural population.     

Evaluation of HER-2/NEU protein expression in breast cancer by immunohistochemistry: an interlaboratory study assessing the reproducibility of HER-2/NEU testing

This study investigated the degree of interlaboratory agreement when HER-2/neu was evaluated by immunohistochemistry (IHC) on archival primary breast cancer samples. IHC for HER-2/neu was performed on the same archival tissue sections from 394 invasive primary breast cancers in two different laboratories. Both laboratories used the primary antibody NCL-CB11; however, different methods of immunostaining (antigen retrieval procedure and manual processing or no antigen retrieval and autostainer processing) as well as different scoring systems were used. Fluorescence in situ hybridization (FISH), considered as the correlation method for HER-2/neu status determination, was performed using the PathVysion kit and compared to the IHC results. Forty-eight of 394 analyzed tumors (12.2%) were scored as HER-2/neu positive in one laboratory, and 109 (27.7%) in the other laboratory where antigen retrieval was performed. Complete concordance in categorization of HER-2/neu status between the two laboratories was achieved in 333 of 394 cases (84.5%). FISH performed in 248 formalin-fixed samples revealed HER-2/neu gene amplification in 55/248 (22.2%). Concordance of FISH and IHC was found in 211/248 cases (85.1%) and 220/248 cases (88.7%) when the CB11 antibody was used without and with antigen retrieval, respectively. Both IHC methods generated similar rates of false results, but with different positive predictive values. Our data demonstrate that HER-2/neu evaluation by IHC is not a reproducible technique if there is no standardization of the procedure.     

The diet,prostate inflammation,and the development of prostate cancer

Evidence that somatic inactivation of GSTP1, encoding the human -class glutathione S-transferase, may initiate prostatic carcinogenesis is reviewed along with epidemiological evidence implicating several environment and lifestyle factors, including the diet and sexually transmitted diseases, as prostate cancer risk factors. An integrated model is presented featuring GSTP1 function as a 'caretaker' gene during the pathogenesis of prostate cancer, in which the early loss of GSTP1 activity renders prostate cells vulnerable to genome damage associated with chronic prostatic inflammation and repeated exposure to carcinogens. The model predicts that the critical prostate carcinogens will be those that are substrates for GSTP1 detoxification and are associated with high prostate cancer risk diet and lifestyle habits.     

Effects of cyclosporine on hematopoietic and immune functions in patients with hypoplastic myelodysplasia: in vitro and in vivo studies

BACKGROUND: Immunosuppression may benefit some patients with hypoplastic myelodysplasia (HMDS) and refractory anemia (RA), but its mechanism of action is still obscure. METHODS: Using flow cytometry, we studied Fas-receptor (Fas-R), Fas-ligand (Fas-L), and interferon-gamma (IFN-gamma) expression in CD34(+) cells and lymphocytes obtained from 11 HMDS and 20 RA patients. In colony assays and long-term cultures, the effects of Fas triggering, IFN-gamma blockade, or cyclosporine(CsA) on the growth of hematopoietic progenitors (colony-forming cells [CFC]) were determined. The effects of CsA at daily doses of 1-3 mg/kg for at least 3 months in HMDS patients were also studied. RESULTS: In basal conditions, committed and immature progenitor cells were found decreased in myelodysplastic (MDS) patients. No significant differences between HMDS and RA patients were detected. IFN-gamma-expressing CD4(+) cells were significantly increased in HMDS patients, whereas intracytoplasmic Fas-L expression was only borderline elevated in CD3(+) MDS cells. Increased numbers of CD34(+) cells expressing Fas-R were found in HMDS and RA patients. CFC and secondary CFC showed higher susceptibility to Fas-L-mediated inhibition and the blockade of IFN-gamma improved marrow primary, but not secondary, CFC growth. CsA added in vitro to patient's lymphocytes significantly decreased the number of IFN-gamma-expressing CD4(+) cells, but not Fas-L production. These effects were associated with increased colony formation. Similar to IFN-gammablockade, production of secondary CFC was not enhanced by CsA. Administration of CsA to patients resulted in prolonged partial hematologic improvement in 8 of 11 HMDS patients. CONCLUSIONS: Increased frequency of IFN-gamma producing CD4(+) cells supports the involvement of lymphocyte-mediated suppression of hematopoiesis in the development of cytopenia in MDS patients. The ability of CsA to decrease in vitro IFN-gamma production may improve hematopoietic function, explaining the beneficial effect of this agent in HMDS patients.