Marco Vacante

L -Carnitine Supplementation to Diet: A New Tool in Treatment of Nonalcoholic Steatohepatitis — A Randomized and Controlled Clinical Trial

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is a known metabolic disorder of the liver. No treatment has been conclusively shown to improve NASH or prevent disease progression. The function of L-carnitine to modulate lipid profile, glucose metabolism, oxidative stress, and inflammatory responses has been shown. The aim of this study was to evaluate the effects of L-carnitines supplementation on regression of NASH.METHODS:In patients with NASH and control subjects, we randomly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen. We evaluated liver enzymes, lipid profile, fasting plasma glucose, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment (HOMA)-IR, body mass index, and histological scores.RESULTS:At the end of the study, L-carnitine-treated patients showed significant improvements in the following parameters: aspartate aminotransferase (P=0.000), alanine aminotransferase (ALT) (P=0.000), γ-glutamyl-transpeptidase (γ-GT) (P=0.000), total cholesterol (P=0.000), low-density lipoprotein (LDL) (P=0.000), high-density lipoprotein (HDL) (P=0.000), triglycerides (P=0.000), glucose (P=0.000), HOMA-IR (P=0.000), CRP (P=0.000), TNF-α (P=0.000), and histological scores (P=0.000).CONCLUSIONS:L-carnitine supplementation to diet is useful for reducing TNF-α and CRP, and for improving liver function, glucose plasma level, lipid profile, HOMA-IR, and histological manifestations of NASH.

Potential role of probiotics on colorectal cancer prevention

BackgroundColorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora.DiscussionProbiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention.SummarySeveral mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.

l-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes

BACKGROUND Patients with type 2 diabetes are under high oxidative stress, and levels of hyperglycemia correlate strongly with levels of LDL oxidation. Carnitine favorably modulates oxidative stress. OBJECTIVE This objective of this study was to evaluate the efficacy of L-carnitine on the reduction of oxidized LDL cholesterol in patients with type 2 diabetes. DESIGN Eighty-one patients with diabetes were randomly assigned to 1 of 2 treatment groups for 3 mo. The 2 groups received either 2 g L-carnitine once daily (n = 41) or placebo (n = 40). The following variables were assessed at baseline, after washout, and at 1, 2, and 3 mo of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B-100, oxidized LDL cholesterol, thiobarbituric acid-reactive substances, and conjugated dienes. RESULTS At the end of the study period, the L-carnitine-treated patients showed significant improvements compared with the placebo group in the following markers: oxidized LDL levels decreased by 15.1 compared with 3.0 U/L (P < 0.001); LDL cholesterol decreased by 0.45 compared with 0.16 mmol/L (P < 0.05); triglycerides decreased by 1.02 compared with 0.09 mmol/L (P < 0.001); apolipoprotein A1 concentrations decreased by 0.12 compared with 0.03 mg/dL (P < 0.05); apolipoprotein B-100 concentrations decreased by 0.13 compared with 0.04 mg/dL (P < 0.05); thiobarbituric acid-reactive substance concentrations decreased by 1.92 compared with 0.05 (P < 0.001), and conjugated diene concentrations decreased by 0.72 compared with 0.11 in the placebo group (P < 0.001). CONCLUSION Our study indicates that oral administration of L-carnitine reduces oxidized LDL cholesterol levels in patients with type 2 diabetes.

Neurotoxicity of Acrylamide in Exposed Workers

Acrylamide (ACR) is a water-soluble chemical used in different industrial and laboratory processes. ACR monomer is neurotoxic in humans and laboratory animals. Subchronic exposure to this chemical causes neuropathies, hands and feet numbness, gait abnormalities, muscle weakness, ataxia, skin and in some cases, cerebellar alterations. ACR neurotoxicity involves mostly the peripheral but also the central nervous system, because of damage to the nerve terminal through membrane fusion mechanisms and tubulovescicular alterations. Nevertheless, the exact action mechanism is not completely elucidated. In this paper we have reviewed the current literature on its neurotoxicity connected to work-related ACR exposure. We have analyzed not only the different pathogenetic hypotheses focusing on possible neuropathological targets, but also the critical behavior of ACR poisoning. In addition we have evaluated the ACR-exposed workers case studies. Despite all the amount of work which have being carried out on this topic more studies are necessary to fully understand the pathogenetic mechanisms, in order to propose suitable therapies.

Oral acetyl-l-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study

BACKGROUND Fatigue is frequently reported in hepatic encephalopathy (HE) and may be related to hyperammonemia. Acetyl-L-carnitine (ALC) offers neuroprotective benefits and improves mitochondrial energetics and function. OBJECTIVE This study evaluated the effect of exogenous ALC on physical and mental fatigue, fatigue severity, and physical activity in patients with mild and moderate hepatoencephalopathy (HE1 and HE2, respectively). DESIGN A total of 121 patients with overt HE were recruited to the study and were subdivided into 2 groups according to their initial HE grade [HE1 (n = 61) or HE2 (n = 60)]. Thirty-one patients with HE1 and 30 with HE2 received 2 g ALC, and 30 patients with HE1 and 30 patients with HE2 received placebo twice a day for 90 d. All patients underwent clinical and laboratory assessments and automated electroencephalogram analysis. RESULTS At the end of the study period, the ALC-treated patients in the HE1 group showed significantly better improvement than did the placebo group in mental fatigue score (-1.7 compared with -0.3; P < 0.05), the fatigue severity scale (-6.4 compared with 2.3; P < 0.001), 7-d Physical Activity Recall questionnaire score (17.1 compared with -2.5; P < 0.001), and Short Physical Performance Battery (2.1 compared with 0.2; P < 0.001); the HE2 group showed significantly better improvement in the fatigue severity scale (-8.1 compared with -5.1; P < 0.001) and 6-min walk test (19.9 compared with 2.3; P < 0.05). Significant decreases in NH(4)(+) were observed in both groups (P < 0.001). CONCLUSION Patients with HE treated with ALC showed a decrease in the severity of both mental and physical fatigue and an increase in physical activity. This trial was registered at clinicaltrials.gov as NCT01223742.

Probiotics in the gastrointestinal diseases of the elderly

Changes of the gut microflora in elderly appear to involve a reduction in numbers of healthy bacteria (lactobacilli and bifidobacteria) and an increase in numbers of potentially pathogenic species. These changes are generally described as gastrointestinal disorders and infections. This review analyses benefits of probiotics in old people, with particular interesting for the latest researches relevant to elderly people, e.g. trials examining enteric infections, antibiotic-associated diarrhea and Clostridium difficile associated diarrhea, functional bowel problems (constipation and irritable bowel syndrome), inflammatory bowel diseases, stimulation of the immune system and prevention of cancer. A growing number of researches indicates that some probiotic strains may help to maintain the health in old people, suggesting both health and cost-saving benefits in offering fermented dairy products. These benefits include: establishment of balanced intestinal microflora; improving colonization resistance and or prevention of diarrhea; reduction of fecal enzymes; reduction of serum cholesterol; reduction of potential mutagenes; reduction of lactose intolerance; synthesis of vitamins; predigestion of proteins.

Lipoprotein(a) in Cardiovascular Diseases

Lipoprotein(a) (Lp(a)) is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100)) particle attached by a disulphide bridge to apo(a). Many observations have pointed out that Lp(a) levels may be a risk factor for cardiovascular diseases. Lp(a) inhibits the activation of transforming growth factor (TGF) and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a) inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a) may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a) is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a) levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a) may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a)-lowering therapy might be beneficial in patients with high Lp(a) levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events.

A single dose of rasburicase in elderly patients with hyperuricaemia reduces serum uric acid levels and improves renal function

Aim: Given the relevance of hyperuricaemia in the development of several diseases, we evaluated rasburicase, generally used in tumor lysis syndrome for uric acid treatment. Our purpose was to evaluate the reduction of serum uric acid and the improvement in renal function. Methods: This is a pilot randomized clinical trial. The study was performed as an 8-week, placebo-controlled group comparison of rasburicase and placebo. Thirty-eight patients were randomly assigned to administration of a single dose of rasburicase (4.5 mg in 100-cc physiological solution versus only physiological solution in 15 min). Results: We observed in the first week a fast decrease in uric acid value. Two months after rasburicase administration we saw a significant reduction of urate (p < 0.05) and creatinine (p < 0.001) and an increase in creatinine clearance (p < 0.001) and urate clearance (p < 0.001). Conclusion: In hyperuricaemic elderly patients, a single dose of rasburicase is very effective in lowering serum uric acid levels. Moreover, in patients treated with rasburicase we noted an improvement of renal function. We conclude that rasburicase is an alternative resource for treating those patients who are allopurinol intolerant, have renal dysfunction or have multiple polypharmacy problems in which drug–drug interaction may be of concern.

Elevated serum levels of Chromogranin A in hepatocellular carcinoma

BackgroundDuring the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages.MethodsThe study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed.ResultsThe chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001).ConclusionsMolecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.

L-carnitine supplementation improves hematological pattern in patients affected by HCV treated with Peg interferon-α 2b plus ribavirin

AIM To evaluate the efficacy of L-carnitine on alleviating anemia, thrombocytopenia and leukopenia, and minimizing dose reductions in patients with chronic hepatitis C virus (HCV) in treatment with Interferon α (IFN-α) plus ribavirin. METHODS Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two groups. group A (n = 35) received Peg-IFN-α 2b plus ribavirin plus L-carnitine, and group B (n = 34) received Peg-IFN-α and ribavirin for 12 mo. All patients underwent laboratory investigations including: red cell count, hemoglobin, white cell count, platelets, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and viremia. RESULTS After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8 (IU/L; P < 0.001), ALT 137.9 vs 112.3 (IU/L; P < 0.001), viremia 4.04 vs 2.36 (× 10(6) copies/mL; P < 0.001), Hb 1 vs 3.5 (g/dL; P < 0.05), red blood cells 0.3 vs 1.1 (× 10(12)/L; P < 0.001), white blood cells 1.5 vs 3 (× 10(9)/L; P < 0.001) and platelets 86 vs 85 (× 10(9)/L; P < 0.001). The end treatment responders were 18 vs 12 (60% vs 44%) and the non responders were 12 vs 15 (40% vs 50%) [odds ratio (OR) 1.65, 95% CI = 0.65-5.37, P < 0.05]. In group A compared to group B there was a significant improvement of sustained virological response in 15 vs 7 patients (50% vs 25%), while the relapsers were 3 vs 5 (10% vs 18%) (OR 3.57, 95% CI = 0.65-19.3, P < 0.001). CONCLUSION L-carnitine supplementations modulate erythropoiesis, leucopoiesis and thrombocytopoiesis, and may be useful in patients treated for HCV. L-carnitine treatment offers the possibility of achieving a sustained virological response while preventing overtreatment.