Manganese superoxide dismutase activity and incidence of hepatocellular carcinoma in patients with Child-Pugh class A liver cirrhosis: a 7-year follow-up study.

AIMS: To evaluate possible modifications in the manganese superoxide dismutase (MnSOD) activity during neoplastic transformation of a cirrhotic liver and to find out whether its assessment may have predictive value to identify cirrhotic patients at a higher risk of hepatocellular carcinoma (HCC). METHODS: Seventy-one consecutive subjects with Child-Pugh class A liver cirrhosis were recruited. At the time of enrolment, HCC was diagnosed in 20 cirrhotic patients. The 51 cirrhotic patients without HCC were followed up for the occurrence of tumour by 6-monthly screening for 7 years. During follow-up, 16 patients developed HCC. Seventy healthy subjects formed the control group. MnSOD activity was assayed spectrophotometrically. RESULTS: Serum MnSOD activity was significantly lower in 70 healthy subjects compared with 51 cirrhotic patients and 20 cirrhotic patients with HCC. Cirrhotic patients who developed HCC during follow-up showed significantly higher values of MnSOD activity than HCC-free patients. The best cut-off of MnSOD activity was 0.40 U/ml. At this cut-off, chi2 analysis revealed that MnSOD activity was significantly different between the HCC-free cirrhotic patients and cirrhotic patients who developed HCC. CONCLUSION: The present findings suggest that during neoplastic transformation of cirrhotic liver, an increase in MnSOD activity may occur already during the precancerous phase, making this enzyme a probable malignancy-associated parameter.     

Effect of chronic venous insufficiency on activities of daily living and quality of life: correlation of demographic factors with duplex ultrasonography findings

The study evaluates to what extent symptoms of chronic venous insufficiency (CVI) and functional venous incompetence as investigated using color-coded duplex ultrasonography may interfere with activities of daily living (ADLs). This study comprises a cross-sectional survey conducted in urban areas surrounding 24 Italian cities. A spontaneous sample of 5,187 subjects (4,457 women [mean age, 54 years] and 730 men [mean age, 61 years]), selected by advertising on television and in newspapers, underwent a clinical examination that included duplex ultrasonography in 3 vein segments in both legs to determine the presence and severity of venous reflux. Subjective perception of lower limb symptoms of CVI and the effect of leg problems on the ability to perform normal ADLs are assessed by means of a self-administered questionnaire. Most of the respondents have some CVI symptoms, with women being 1.5 to 3 times as likely as men to report leg symptoms. The risk of developing the most frequent subjective symptoms such as heaviness and tiredness in the legs is not statistically significantly different for younger subjects compared with older subjects. Advanced age is considered to be a relevant risk factor only for heat sensation and swollen legs. Persons living in southern Italy are at higher risk of almost all lower limb symptoms. Results of duplex ultrasonography performed on 3875 subjects show that fewer than 1 in 5 young persons, regardless of sex, manifest some degree of venous reflux (primarily mild symptoms). The risk of developing venous incompetence increases rapidly with age until it triples among subjects 50 years and older. Adjusting for all other factors, men are on average 1.5 times as likely as childless women to have venous reflux, and the risk increases in the case of family history of CVI or (among women) in the case of past pregnancies. More women than men report that their leg problems affect their ADLs. Pregnancy and living in the south contribute to a reduction in the ability to perform most heavy housework. Although milder lower limb symptoms such as evening heaviness and tiredness in the legs may begin early in life, venous reflux and related symptoms of heat sensation and swollen legs become more pronounced with age, and their severity can be disabling for those afflicted.     

Transmural electrical potential difference in the mammalian esophagus in vivo

A simple, safe, accurate, and reproducible technique for measuring the transmural electrical potential difference (PD) of the esophagus has been developed. This technique, a modification of those previously used, allows simultaneous correlation of the PD profile with the pressure profile obtained during routine manometry. With this technique, a subcutaneous reference bridge was shown to detect accurately a lumen-negative electrical orientation for the esophageal PD in three species: rabbit, opossum, and man. A characteristic and reproducible PD profile was present for each species. In the rabbit the gastric PD was low,--12 mv, relative to the body of the esophagus,--26 to -29 mv. In contrast, both opossum and man had relatively high gastric PD's ( -36 to -43 mv) when compared to esophageal PD's ( -12 to -25 mv). In the rabbit and opossum, the PD in the lower esophageal sphincter ( -5 to -6 mv) was less than both gastric or esophageal PD's, whereas in human beings the lower esophageal sphincter PD ( -22 mv) was between gastric and esophageal values. In vitro PD measurements and histological studies of opossum esophagus revealed differences in the epithelium which correlated with the different in vivo PD's.     

Evidence for a heritable predisposition to death due to influenza

Animal model studies and human epidemiological studies have shown that some infectious diseases develop primarily in individuals with an inherited predisposition. A heritable contribution to the development of severe influenza virus infection (i.e., that which results in death) has not previously been hypothesized or tested. Evidence for a heritable contribution to death due to influenza was examined using a resource consisting of a genealogy of the Utah population linked to death certificates in Utah over a period of 100 years. The relative risks of death due to influenza were estimated for the relatives of 4,855 individuals who died of influenza. Both close and distant relatives of individuals who died of influenza were shown to have a significantly increased risk of dying of influenza, consistent with a combination of shared exposure and genetic effects. These data provide strong support for a heritable contribution to predisposition to death due to influenza.     

Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric oxide synthesis

BACKGROUND: The arginine-degrading enzyme, arginine deiminase conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw), reduces extracellular arginine, has minimal toxicity, decreases tumor burden and improves liver function in patients with chronic hepatitis C virus infection (HCV) and inoperable hepatocellular carcinoma (HCC). Reduced extracellular arginine inhibits viral replication through unknown mechanisms. It is hypothesized that ADI-SS PEG 20,000 mw reduces HCV viral titers through nitric oxide (NO)-dependent effects. METHODS: The effects of ADI-SS PEG 20,000 mw (dose, 160 IU/m2; three cycles of four once-weekly i.m. injections) on HCV titers, serum NO and plasma arginine, were evaluated using archived plasma from patients with HCC and HCV and in vitro cell model measurements of HCV replication. RESULTS: ADI-SS PEG 20,000 mw selectively inhibited HCV replication in vitro (IC50 = 0.027 IU/mL). Fifteen HCC/HCV patients completed treatment. The HCV titers were reduced by up to 99% in five out of 10 (50%) HCV-serotype 1b patients (P = 0.0093). These patients also experienced significant improvements in liver function (P = 0.0091). There were concomitant reductions of plasma arginine and serum NO levels. The HCV titer was not reduced in HCV-type 2c patients. CONCLUSION: Reduction of extracellular arginine by ADI-SS PEG 20,000 mw in HCC patients reduces HCV viral titers and improves liver function, possibly through suppression of NO.     

Anti-inflammatory activity of Agaricus blazei in different basidiocarp maturation phases

Agaricus blazei Murrill ss. Heinemann (Agaricus brasiliensis Wasser et al.; Agaricus subrufescens Peck) has raised interest in the scientific community due to its therapeutic properties. Although there are numerous studies about this fungus a few of them study the anti-inflammatory activity and the relationship with basidiocarp development phases. Thus, the objective of this study was to evaluate the effect of A. blazei extracts of closed and opened basidiocarp on the cell migration of rats submitted to an inflammatory challenge. The basidiocarp extracts were administered by gavage at 55 or 110 mg/kg. The inflammatory challenge was performed by administering phlogistic agent (carrageenan 2%) in an air-pouch induced in the animal subcutaneous tissue. It was concluded that the extracts affect leukocyte mobilisation regulation; closed basidiocarp extract in doses of 55 and 110 mg/kg and opened basidiocarp extract in 110 mg/kg modulate the anti-inflammatory response.