Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats

<p>Abstract</p> <p>Background</p> <p>Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation.</p> <p>Methods</p> <p>Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days) and controls were sensitized by s.c. injection of ovalbumin (OA) in aluminium hydroxide 14 days before OA (1 mg/0.4 mL) or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a) quantification of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage fluid (BALF) by Enzyme-Linked Immunosorbent Assay, b) expression of E- and P- selectins on lung vessels by immunohistochemistry, and c) inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c.) was given i.v. 2 hours before antigen challenge.</p> <p>Results</p> <p>Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1β (30%) and TNF-α (45%), and in the lung expression of P-selectin (30%) compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1β, TNF-α and P-selectin, and neutrophil migration.</p> <p>Conclusion</p> <p>Data presented suggest that insulin modulates the production/release of TNF-α and IL-1β, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction.</p

Changes in histological criteria lead to different prevalences of nonalcoholic steatohepatitis in severe obesity

The worldwide obesity epidemic contributes to the increasing incidence of a number of diseases, as nonalcoholic fatty-liver disease (NAFLD) and its most severe form, the nonalcoholic steatohepatitis (NASH). Data on the prevalence of NASH has varied from 18.5%4 to 69%43 in obesity, an unacceptable wide range. The aim of our study was to evaluate how prevalence of NASH is influenced by the different diagnostic histological criteria. Consecutive assessment of 325 obese patients referred for bariatric surgery (BMI ≥ 35 kg/m2), 146 of whose were submitted to histological analysis of the liver allowed the evaluation of the prevalence of NAFLD. Steatohepatitis was diagnosed histologically using 3 types of criteria: a) broad criteria, where steatosis was associated with at least 2 of the following parameters: any degree of lobular inflammatory infiltrate, hepatocellular ballooning and perisinusoidal/ perivenular fibrosis; b) restricted criteria, where the hepatocellular ballooning was of moderate or severe intensity; c) ultrarestricted criteria, which required perisinusoidal and/or perivenular fibrosis. NAFLD was present in 111 (76%) of the patients, and the prevalence of NASH was 25.3% when ultrarestricted criteria were used, 41.1% with restricted criteria and 55.5% with broad criteria. In conclusion, more accurate definition of the criteria for histological diagnosis of NASH should be required, so that further clinico-pathological studies may define the long-term progression of the disease and evaluate therapeutic strategies

CONGENITAL HEPATIC FIBROSIS AND OBLITERATIVE PORTAL VENOPATHY WITHOUT PORTAL HYPERTENSION - A REVIEW OF LITERATURE BASED ON AN ASYMPTOMATIC CASE

ABSTRACT The disease and the case reported here are relevant especially because of their varied clinical presentation, possibility of being associated with other disorders affecting several organs and possible differential diagnoses. Congenital Hepatic Fibrosis is an autosomal recessive disease due to mutation in the PKHD1 gene, which encodes the fibrocystin/polyductine protein. It is a cholangiopathy, characterized by varying degrees of periportal fibrosis and irregular proliferation of bile ducts. Affected patients are typically diagnosed in childhood, but in some cases the disease may remain asymptomatic for many years. The exact prevalence and incidence of the disease are not known, but it is consider a rare disease, with a few hundred cases described worldwide. It can affect all ethnic groups and occur associated with various hereditary and non-hereditary disorders. The clinical presentation is quite variable, with melena and hematemesis being initial symptoms in 30%-70% of the cases. More rarely, they may present episodes of cholangitis. The disease has been classified into four types: portal hypertension, cholestasis / cholangitis, mixed and latent. Diagnosis begins with imaging tests, but the definition is made by the histopathological sample. So far, there is no specific therapy that can stop or reverse the pathological process. Currently, the therapeutic strategy is to treat the complications of the disease

Prognostic factors for progression of liver structural lesions in chronic hepatitis C patients

AIM: To evaluate the epidemiological, clinical, laboratory and histological variables capable of predicting the progression of hepatic structural disturbances in chronic hepatitis C patients during the time interval between two liver biopsies