The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor ␣ (TNF-␣) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-␣ and their p55 and p75-receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and (2) the relationship between TNF-␣, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF-␣ was found in patients with NASH in hepatic tissue (0.65 ؎ 0.54) and in peripheral fat (0.43 ؎ 0.45); in the control samples, the mRNA expression was 0.28 ؎ 0.32, P < .007, and 0.26 ؎ 0.22, P < .018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 ؎ 1.81 vs. 1.56 ؎ 1.17; P < .05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF-␣ in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF-␣ mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF-␣ system may be involved in the pathogenesis of NASH.

The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.

NAFLD patients have elevated plasma levels of LBP and they are further increased in patients with NASH. This increase is related to a rise in TNF-alpha gene expression in the hepatic tissue which supports a role for endotoxemia in the development of steatohepatitis in obese patients.

Since only age was a predictor of moderate or severe fibrosis, and no clinical or biochemical abnormalities detected slowly progressive hepatic fibrosis, liver biopsy is the only means of detecting progression to more advanced liver disease in a NASH patient.

One of the most important recent observations in traumatic brain injury (TBI) relates to the potential role of apoptosis in secondary brain injury. We aimed to analyze the presence of apoptosis and the expression of apoptosis-related proteins in brain samples from patients with TBI. We also tried to find any association between the in situ results and the in vitro observations in a neuronal model of induced-apoptosis. Brain tissue from the pericontusional zone (PCZ) of patients with traumatic contusions and from post-mortem samples was analyzed. Immunohistochemical analyses of apoptosis-related proteins and the terminal deoxynucleotide transferase-mediated nick end labeling (TUNEL) method to determine the presence of apoptotic cells were performed. Apoptotic rates on neuronal cells induced by jugular bulb vein sera was determined by flow cytometry. TUNEL-positive cells were detected in all PCZ of traumatic contusions and in most of PCZ in post-mortem specimens (none in control; p = 0.026). In vivo samples showed higher expression of antiapoptotic proteins Bcl-2 (p = 0.027) and Bcl-XL (p = 0.014) than post-mortem samples. In autopsies, the expression of Fas and Bim (p < 0.05) were higher in PCZ than in the zone distal from the contusion. In vitro studies showed that apoptotic rate was an independent factor associated with mortality at 6 months (p = 0.014). In the receiving operator curve (ROC) curve, a cut-off point of 66.5% showed a sensitivity of 89.5% and specificity of 66.7% in the prediction of patients' death. Cerebral apoptosis is a prominent form of cell death in the PCZ of human traumatic cerebral contusions, and high rates of in vitro apoptosis are associated with a poorer prognosis after TBI.

Liver disease resulting from heart failure (HF) has generally been referred as “cardiac hepatopathy”. One of its main forms is congestive hepatopathy (CH), which results from passive venous congestion in the setting of chronic right-sided HF. The current spectrum of CH differs from earlier reports with HF, due to ischemic cardiomyopathy and congenital heart disease having surpassed rheumatic valvular disease. The chronic passive congestion leads to sinusoidal hypertension, centrilobular fibrosis, and ultimately, cirrhosis (“cardiac cirrhosis”) and hepatocellular carcinoma after several decades of ongoing injury. Contrary to primary liver diseases, in CH, inflammation seems to play no role in the progression of liver fibrosis, bridging fibrosis occurs between central veins to produce a “reversed lobulation” pattern and the performance of non-invasive diagnostic tests of liver fibrosis is poor. Although the clinical picture and prognosis is usually dominated by the underlying heart condition, the improved long-term survival of cardiac patients due to advances in medical and surgical treatments are responsible for the increased number of liver complications in this setting. Eventually, liver disease could become as clinically relevant as cardiac disease and further complicate its management.

The results of the study demonstrate for the first time increased leptin receptor expression in liver tissue and its relationship with overexpression of TGF-beta1 and the degree of hepatic fibrosis.

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