Influence of different hemodialysis membranes on red blood cell susceptibility to oxidative stress

Oxidative stress is crucial in red blood cell (RBC) damage induced by activated neutrophils in in vitro experiments. The aim of the study was to evaluate whether the bioincompatibility phenomena occurring during hemodialysis (HD) (where neutrophil activation with increased free radical production is well documented) may have detrimental effects on RBC. We evaluated RBC susceptibility to oxidative stress before and after HD in 15 patients using Cuprophan, cellulose triacetate, and polysulfone membrane. RBC were incubated with t-butyl hydroperoxide as an oxidizing agent both in the presence and in the absence of the catalase inhibitor sodium azide. The level of malonaldehyde (MDA), a product of lipid peroxidation, was measured at 0, 5, 10, 15, and 30 min of incubation. When Cuprophan membrane was used, the MDA production was significantly higher after HD, indicating an increased susceptibility to oxidative stress in comparison to pre-HD. The addition of sodium azide enhanced this phenomenon. Both cellulose triacetate and polysulfone membranes did not significantly influence RBC susceptibility to oxidative stress. Neither the level of RBC reduced glutathione nor the RBC glutathione redox ratio changed significantly during HD with any of the membranes used. The RBC susceptibility to oxidative stress was influenced in different ways according to the dialysis membrane used, being increased only when using the more bioincompatible membrane Cuprophan, where neutrophil activation with increased free radical production is well documented. The alterations found in this study might contribute to the reduced RBC longevity of HD patients where a bioincompatible membrane is used.     

GM2 gangliosidosis variant B1

Variant B1 is a rare type of GM2 gangliosidosis. Clinically, it shows a wide spectrum of forms ranging from infantile to juvenile. We report the first magnetic resonance imaging (MRI) findings from three patients affected by GM2 gangliosidosis variant B1, two presenting with the infantile form and one with the juvenile form. The MRI appearances of the two patients with the infantile form disease are congruent with those reported for the early-onset type of both Tay-Sachs and Sandhoff diseases, and are characterized by early involvement of the basal ganglia and thalamus with cortical atrophy appearing later. In contrast, the patient with the juvenile form of variant B1 showed progressive cortical and white-matter atrophy of the supratentorial structures and, to a lesser extent, the infratentorial structures. No basal ganglia or thalamic anomalies were observed. Because in the adult forms of both Tay-Sachs and Sandhoff diseases a progressive cerebellar atrophy represents the only abnormality detectable, it appears that an MRI pattern peculiar to GM2 gangliosidosis can be defined. This pattern ranges from the basal ganglia injury associated with the early and severe demyelination process noted in the infantile form of the disease, to cerebellar atrophy with no supratentorial anomalies in the adult form. An “intermediate” MRI picture, with cortical atrophy and mild cerebellar atrophy, but without basal ganglia impairment, can be observed in the juvenile form. In addition, our investigations suggest that MRI abnormalities in GM2 gangliosidosis correlate with the clinical form of the disease rather than with the biochemical variant of the enzymatic defect. Received: 9 January 2002, Received in revised form: 26 June 2002, Accepted: 8 July 2002 Correspondence to Paolo Balestri, M. D.     

Is cholangiocarcinoma another complication of insulin resistance: a report of three cases

Background: Cholangiocarcinoma is the second most common primary liver cancer, and the number of cases of intrahepatic cholangiocarcinoma (ICC) have been steadily increasing worldwide. Although the reasons for this surge are unknown, insulin resistance (IR) could be a risk factor, similar to what has been reported for other cancers. Case Report: We report on 3 cases of ICC arising in subjects sharing IR as an underlying risk factor. Case 1 was an obese and dyslipidemic patient with NAFLD. The second and the third patients were affected by type 2 diabetes. Conclusions: Evidence for a link between IR and onset of cholangiocarcinoma in our patients rests on three lines of evidence: epidemiological, biological, and exclusion of others risk factors. Studies are needed to confirm our hypothesis that IR is a risk factor for the development of ICC.     

Is nonalcoholic steatohepatitis associated with a high-though-normal thyroid stimulating hormone level and lower cholesterol levels?

Hypothyroidism is associated with the risk of development of the metabolic syndrome (MS) and hypercholesterolemia. Direct evidence that hypothyroidism might be associated with advanced chronic liver disease via nonalcoholic steatohepatitis (NASH) is limited. We studied the relationship between thyroid hormones, thyroid stimulating hormone (TSH), cholesterol, and NASH. In consecutive euthyroid patients with biopsy-proven nonalcoholic fatty liver disease, TSH and thyroid hormone (FT3 and FT4) concentrations were compared in 25 patients with steatosis and 44 non-cirrhotic NASH patients featuring concurrent ballooning, lobular inflammation and steatosis. The MS was diagnosed according to ATP III criteria. A meta-analysis of previously published studies was performed to evaluate whether NASH, compared to simple steatosis, is associated with lower cholesterol levels. At univariate analysis, compared to those with steatosis, patients with NASH have a wider waist, elevated levels of BMI, ALT, AST, fasting insulin, HOMA-IR, ferritin, TSH and a lower serum cholesterol. At stepwise multivariable logistic regression analysis, the independent predictors of NASH are high HOMA and TSH and lower total cholesterol (Model 1); MS and high TSH (Model 2). At meta-analysis, serum total cholesterol levels are significantly lower in predominantly non-cirrhotic NASH than in simple steatosis. This study provides cross-sectional and meta-analytic evidence that, in euthyroid patients, high-though-normal TSH values are independently associated with NASH. Further work is needed to ascertain the role, if any, of lower cholesterol serum levels in assisting in the diagnosis of NASH.     

Fatty liver, carotid disease and gallstones： A study of age-related associations

INTRODUCTIONAtherothrombosis (AT), fatty liver (FL) and gallstone disease (GD) represent a clinically heterogeneous group of disorders which commonly occur in the general population and impose a heavy economic burden for direct and indirect health expendi…     

Dialysate flow distribution in hollow fiber hemodialyzers with different dialysate pathway configurations

The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, since this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different dialysate compartment designs on dialysate flow distribution and urea clearances. Eighteen hollow fiber 1.3 m2 hemodialyzers were studied, 6 each of 3 designs: Type A--standard fiber bundle (PAN 65DX Asahi Medical, Tokyo, Japan); Type B--spacing filaments external to the fibers (PAN 65SF Asahi Medical, Tokyo, Japan); Type C--fibers waved to give Moiré structure (FB130 Nissho-Nipro, Osaka, Japan). In vitro studies: 3 dialyzers of each type were studied following dye injection into the dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer were undertaken, using a new generation helical CT scanner (X-Press/HS1 Toshiba Corporation, Tokyo, Japan). In vivo studies: 3 dialyzers of each type were studied, in randomized sequence, in 3 different patients under standardized dialysis conditions. Blood- and dialysate-side urea clearances were measured at 30 and 150 minutes of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with Moiré structure (Type C) and least homogeneous in the standard dialyzer (Type A). Space yarns (Type B) gave an intermediate dialysate flow distribution. Significantly increased urea clearances (p<0.001) were seen with Types B and C, compared to the standard dialyzer. Type C (Moiré) had the highest clearances although these were not significantly greater than Type B (space yarns). In conclusion, more homogeneous dialysate flow distribution and improved small solute clearances can be achieved by use of spacing yarns or waved (Moiré structure) patterns of fiber packing in the dialyzer. These effects are achieved probably as a result of reduced dialysate channeling resulting in a lower degree of mismatch between blood and dialysate flows. The new radiological technique using the helical CT scanner allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design.     

Cellulose triacetate: another membrane for continuous renal replacement therapy.

The evolution of technology and biomaterials has permitted a parallel development of renal replacement therapies in the acute, critically ill patient. From the original continuous artero-venous hemofiltration method new techniques such as continuous veno-venous hemofiltration, hemodiafiltration and high-flux dialysis have been developed and are clinically used. Similar progress has been made with artificial membranes. We investigated the possibility of using a modified cellulosic membrane for continuous therapies, assessing the hydraulic characteristics and clearance performances of high-flux cellulose triacetate hemodiafilter (0.7 m2) in vitro and in vivo. The flowdynamic characteristics of the filter suggest its optimal use in veno-venous pump-drive techniques. Efficiency was excellent, with urea daily clearances as high as 50 liters or more. The high permeability and porosity of the membrane also increased the clearances of larger solutes such as creatinine and inulin. No side effects occurred during treatment and we conclude that cellulose triacetate may be considered a good alternative to synthetic membranes in continuous renal replacement therapies.     

Nonalcoholic fatty liver disease and aging: Epidemiology to management

Nonalcoholic fatty liver disease(NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic(nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications(cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment(diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients.     

Clinical relevance of liver histopathology and different histological classifications of NASH in adults

Introduction: Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis and steatohepatitis (NASH) with or without fibrosis/cirrhosis and hepatocellular carcinoma. NAFLD occurs epidemically in most areas of the world, contributes to cardiovascular events and liver-related mortality and therefore exacts a major economic toll.

Areas covered: Here we summarize what clinicians should know about NAFLD histopathology in adults. We report on the individual histological features and scoring systems of NAFLD: the NAFLD activity score (NAS) introduced by the NASH-Clinical Research Network, the ‘Fatty Liver Inhibition of Progression’ algorithm and Steatosis, Activity, and Fibrosis (SAF) score. Pros and cons of histological classifications in NASH are discussed. Special emphasis is given to liver histopathology in some high-risk patient groups, such as those with severe obesity and type 2 diabetes. Moreover, we also examine the relationship between liver histopathology and clinical features, and the impact of liver histopathology on the long-term prognosis of NAFLD. Finally, we propose an integrated diagnostic approach which utilizes both non-invasive tools and liver biopsy in those individual patients with suspected NAFLD.

Expert commentary: Based on expert opinions, we conclude with a research agenda on NAFLD which focuses on the most burning topics to be addressed over the next five years.