Patients with primary biliary cirrhosis do not show post-exercise depression of cortical excitability.

OBJECTIVE: Primary biliary cirrhosis (PBC), a female-predominant autoimmune liver disease, is commonly associated with fatigue, a sensation of weariness from physical activity. In healthy subjects, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) increase in amplitude during fatiguing exercise and decrease after the exercise due to post-contraction cortical excitability depression. TMS was utilized herein to investigate if unique cortical excitability changes discriminate women with PBC from healthy controls. METHODS: Twenty-two women (11 with PBC and 11 healthy controls) performed a voluntary submaximal tonic contraction of finger flexor muscles until exhaustion; MEPs were recorded before and during exercise as well as 10min after exercise discontinuation. All subjects completed questionnaires for quality of life and fatigue evaluation. RESULTS: During exercise an increase in MEPs amplitude was observed in all subjects, with no sign of altered peripheral fatigability. Following exercise women with PBC associated with high fatigability showed a significant lack of reduction of MEP size compared to the healthy controls. CONCLUSIONS: Women with PBC do not manifest post-exercise depression of cortical excitability. SIGNIFICANCE: We suggest that an impairment of neural mechanisms underlying physiological central fatigue could occur in PBC, possibly leading to the pathological fatigability lamented by some patients.

A short version of a HRQoL questionnaire for Italian and Japanese patients with Primary Biliary Cirrhosis.

BACKGROUND: The available self-report questionnaire for the quality of life in patients with primary biliary cirrhosis (PBC-40) is currently validated only in the British population but it lacks an evaluation of its dimensionality. AIMS: To validate the Italian and Japanese versions of PBC-40 and to assess the dimensionality of the original structure of PBC-40 by a confirmatory factor analysis. PBC-40 was translated to Italian and Japanese using the forward-backward method and then reviewed in focus groups in the framework of a large multicentric study. METHODS: A sample of 290 patients with PBC (125 Italian and 165 Japanese) was administered two questionnaires previously validated for PBC-specific (PBC-40) and general quality of life (SF-36). RESULTS: The confirmatory model failed to fit adequately the original hypothesized structure. A principal component analysis led to a seven-factor structure, with exclusion of 13 items characterized by lower load; PBC-27 questionnaire was the final instrument. The validity of the PBC-27 was supported by its strong correlation with the SF-36 scores. CONCLUSION: We here propose an alternative structure of the quality of life questionnaire for PBC, namely PBC-27, which appears to be effective in detecting the impact of PBC on quality of life in Italian and Japanese patients.

The chemical pathway to primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a female predominant chronic disease of autoimmune pathogenesis and unknown etiology, although data suggest that genetic predisposition and environmental factors concur to its onset. Among nongenetic factors, several lines of evidence spanning from geoepidemiology to experimental findings support the role of xenobiotics, i.e., chemicals that are capable to induce molecular mimicry through cross reactivity. Indeed, specific xenobiotics are hypothesized to substitute lipoic acid residues on PBC-specific autoepitopes thus triggering autoimmunity. This is supported by data obtained with patient sera reactivities as well as animal models. The scenario is further complicated by the possibility that xenobiotic-metabolizing bacteria might also play a role. We will review the available evidence in this intriguing and rapidly growing field of research and critically discuss its potential implications.

Chocolate at heart: the anti-inflammatory impact of cocoa flavanols.

Chronic and acute inflammation underlies the molecular basis of atherosclerosis. Cocoa-based products are among the richest functional foods based upon flavanols and their influence on the inflammatory pathway, as demonstrated by several in vitro or ex vivo studies. Indeed, flavanols modify the production of pro-inflammatory cytokines, the synthesis of eicosanoids, the activation of platelets, and nitric oxide-mediated mechanisms. A relative paucity of data still characterizes the in vivo implications of these findings albeit there have been studies suggesting that the regular or occasional consumption of cocoa-rich compounds exerts beneficial effects on blood pressure, insulin resistance, vascular damage, and oxidative stress. Accordingly, rigorous controlled human studies with adequate follow-up and with the use of critical dietary questionnaires are needed to determine the effects of flavanols on the major endpoints of cardiovascular health.

Environmental factors and the induction of autoimmunity in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease with an autoimmune pathogenesis and an unknown etiology, predominantly affecting postmenopausal women. The term PBC is a misnomer since most cases currently diagnosed have limited probability to develop cirrhosis. Antimitochondrial autoantibodies, elevated IgM and selective destruction of the intrahepatic bile ducts are the hallmarks of PBC. A permissive genetic background is critical in producing susceptibility despite limited associations with alleles within the MHC. The disease has incomplete concordance in monozygotic twins and its geoepidemiology suggests a role for environmental factors in the induction of PBC. This hypothesis is further supported by clinical (risk factors) and experimental evidence. Some of the factors incriminated model molecular mimicry by infectious agents and xenobiotic chemicals. Additional candidates are being proposed through large screening; all proposed associations ultimately require confirmation in animal models and clinical practice.