Lisa Cammalleri

Acetyl-L-Carnitine Treatment in Minimal Hepatic Encephalopathy

Minimal hepatic encephalopathy (MHE) is characterized by disturbance of mental state and neuromuscular function. To assess the clinical efficacy of acetyl-l-carnitine (ALC) in the treatment of MHE, we performed a randomized, double-blind, placebo-controlled study administering ALC in cirrhotic patients with this disease and evaluating their cognitive functions. One hundred and twenty-five cirrhotic patients, of whom 21 were infected by hepatitis B virus, 75 by hepatitis C virus and 29 with cryptogenic cirrhosis, were enrolled in our study. Patients were randomly divided into two groups, and using double-blind administration, group A was treated with ALC and group B with placebo for 90xa0days. The two groups were similar in demographic characteristics, aetiology of cirrhosis, duration and Child-Pugh grade. Minimal hepatic encephalopathy was diagnosed with the Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT) and Auditory Verbal Learning Test (AVL) and cognitive function with the Mini Mental State Examination (MMSE). After 90xa0days in group A treated with ALC, we observed a significant decrease in prothrombin time (Pxa0<xa00.001), bilirubin serum levels (Pxa0<xa00.01), AST (Pxa0<xa00.001), fasting NH4 serum levels (Pxa0<xa00.001), Trail Making Test-A (Pxa0<xa00.001) and Trail Making Test-B (Pxa0<xa00.001), and a significant increase in albumin serum levels (Pxa0<xa00.005), MMSE test (Pxa0<xa00.001), Symbol Digit Modalities Test (Pxa0<xa00.001), BDT (Pxa0<xa00.001), AVL long-term test (Pxa0<xa00.001) and AVL total test (Pxa0<xa00.001). No significant differences were observed in EEG in either group of patients treated with ALC or placebo. The benefits of ALC in comparison with placebo are demonstrated in greater reductions in serum ammonia levels, as well as in improvements of neuropsychological functioning.

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

BACKGROUNDnPatients 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.nnnOBJECTIVEnThis 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.nnnDESIGNnEighty-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.nnnRESULTSnAt 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).nnnCONCLUSIONnOur study indicates that oral administration of L-carnitine reduces oxidized LDL cholesterol levels in patients with type 2 diabetes.

Elevated chromogranin A (CgA) serum levels in the patients with advanced pancreatic cancer

The neuroendocrine differentiation in PC could potentially represent a new finding with diagnostic, prognostic and therapeutic implications. This study aimed at evaluating the clinical usefulness of CgA as a neuroendocrine (NE) serum-marker. We investigated the role of the serum concentration of CgA in a study group of patients with PC. CgA was significantly higher in the patients affected by PC as compared with the group of healthy subjects (HS) and those with chronic pancreatitis (CHP) (p<0.001). Also the HS group differed significantly from the CHP control group in the serum CgA levels (p<0.001). The serum carbohydrate antigen (CA19-9) level displayed a significant difference (p<0.001) between the PC and the HS group. The PC and CHP groups, as well as the HS and CHP groups showed also significant differences in the CA19-9 levels (p<0.001). One can conclude that the patients with higher CgA levels had poorer prognosis and survival, as compared to those with lower CgA levels. These results support the notion that the determination of serum CgA level before treatment may be a potential prognostic factor for PC.

L-Carnitine Treatment Reduces Steatosis in Patients with Chronic Hepatitis C Treated with α-Interferon and Ribavirin

AbstractBackground Hepatic steatosis is a common presentation in patients with chronic hepatitis C. Interferon α exerts both antiviral and immunomodulating actions, and influences on lipid metabolism. The aim of our study was to test whether l-carnitine reduces steatosis in patients treated with interferon and ribavirin. Patients and methods A total of 70 patients were randomly assigned to receive either leucocyte IFN alpha at a dose of 3xa0MIU thrice a week plus 1,000xa0mg ribavirin per day for 12xa0months n(group A) or IFN alpha and ribavirin at the same dose plus 2xa0g carnitine per day (group B). Results Comparison of the two treatments showed significant differences between the mean values of the following parameters at the end of the treatment: ALT −68 vs −95xa0IU/ml (Pxa0<xa00.05), total cholesterol 0.08 vs −0.91xa0mmol/l (Pxa0<xa0n0.05) and triglycerides +0.25 vs −20xa0mmol/l (Pxa0<xa00.05); and at the follow-up: AST −35xa0vs −65xa0IU/ml (Pxa0<xa00.05) nand ALT −55 vs −84xa0IU/ml (Pxa0<xa00.05). All values were lower in group B (IFNxa0+xa0Ribavirinxa0+xa0Carnitine) than in group A n(IFN plus Ribavirin). When comparing those patients treated with IFNxa0+xa0ribavirin with those treated with IFN plus ribavirin plus carnitine, the response at the end of the treatment was 48% vs 56%, and the sustained response 39% vs 46%, respectively. Conclusions Combined treatment with l-carnitine, ribavirin and IFN alpha resulted in greater antihyperlipidaemic effects and than with ribavirin and IFN alpha alone. The results of this study suggest that l-carnitine may have a role among the reduction of steatosis strategies in patients with hepatitis C treated with IFN alpha and ribavirin.

Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study.

Objective Our earlier study has demonstrated that the administration of L-acetylcarnitine (LAC) improves neurological symptoms and serum parameters in hepatic coma. The aim of this work has been to evaluate the efficacy of the LAC and branched chain amino acids (BCAA) versus BCAA, administered in intravenous infusion, in patients with cirrhotic hepatic coma. Methods Forty-eight highly selected patients were enrolled in the study and, after randomization, received blindly LAC+BCAA (n=24) versus BCAA (n=24). The two groups were similar in age, sex, pathogenesis of cirrhosis, and severity of liver disease. The comparison between values before and after LAC planned treatment showed statistical significant differences in neurological findings, evaluated by the Glasgow Scale, ammonia serum levels, blood urea nitrogen, and EEG. Results After 60u2009min of the study period, the LAC+BCAA treated patients compared with BCCA treated showed a significant decrease of ammonia serum levels: 41.20 versus 10.40u2009μmol P<0.05. After 1 day of the study period, the LAC+BCAA treated patients compared with BCCA treated patients showed a significant increase of Glasgows score: 3.60 versus 1.50 score P<0.05; a significant decrease of ammonia serum levels: 63.30 versus 27.00u2009μmol P<0.01; a significant improvement of EEG cps/s: 2.70 versus 0.6 P<0.001. No side-effects were observed in our study series. Conclusion Our study demonstrated that the administration of BCAA supplemented with LAC might improve neurological symptoms and serum ammonium levels in selected cirrhotic patients with hepatic coma.

Egg white injury

A 66-year-old man was admitted to our Department for a sudden loss of consciousness, tonic–clonic movement and psychomotor agitation. During the previous 4 months the patient had complained of drowsiness, fatigue, lack of appetite, and nausea. During the prior 2 months he had experienced hair loss, coating of the tongue, and skin flaking with pruritus. Two hours prior to admission, the patient had experienced loss of spacio-temporal orientation, dizziness, cold sweats, postural instability, and sudden loss of muscle tone in the lower limbs causing a collapse on the ground. On physical examination the skin was dry, greyish, markedly flaky; and the tongue was pale. There was a circumoral dermatitis, as well as a skin rash described as scaly (seborrhoic) and red (eczematous) distributed around the eyes, nose and mouth, along with alopecia and thinning hair. The vital signs were: rate 75 beats/min, blood pressure 145/90 mmHg, and normal respirations. The social history revealed that during the previous year the patient had established a chicken farm, and that each morning, when he had gone to collect the newly laid eggs, he had ingested some of the eggs whose shell was broken. For 3 months, he had eaten daily a mean 6 g of albumen. Laboratory evaluation revealed a minor elevation of the serum cholesterol level. Complete blood count, thyroxine, vitamin B12 and folic acid levels were within reference range. Computerized tomography and magnetic resonance imagining of the brain and spinal cord were normal. No lesions were observed in the temporo-mandibular joint. The audiometric, vestibular and tilt-test examinations, together with electronystagmogram, electroencephalography, electrocardiogram (ECG) and carotid Doppler studies were unrevealing. Additional investigations ruled out infective and autoimmune causes, as well as malignancies. Because of the inability to reach a diagnosis, despite the use of sophisticated technologies, we decided to investigate and review the history of the patient. Much to our surprise, we discovered that at admission, the laboratory determination of biotin was low (98 pmol/L), confirming the diagnosis of egg white injury syndrome (Table 1). Although data are lacking to effectively guide the frequency of follow-up and the specific testing warranted, a reasonable strategy is to follow a patient and re-evaluate him, after biotin supplementation for 1 month, including measurement of biotin status. Our patient was treated with 5 mg 9 3 for 1 month of diathynil neobiotin. Neurologic signs disappeared after 24 h, and the skin lesions after 10 days. The patient has been followed up monthly for 6 months, without clinical and serum alterations. Neurologic and cutaneous manifestations are related to ‘‘egg white injury’’, a cause of biotin deficiency. Biotin (also called vitamin H or coenzyme R) is a watersoluble vitamin of the B complex. ‘‘H’’ is the initial of ‘‘haut’’, the German word for skin, because of the skin involvement in deficiency states [1]. The mechanism by which ingestion of raw egg whites leads to biotin deficiency is the irreversible binding of biotin by avidin, a glyco-protein present in the albumen of raw eggs. The resulting compound renders this vitamin non-absorbable by the human gastro-intestinal tract [2]. Cooking denatures avidin, rendering it susceptible to L. Cammalleri P. Bentivegna M. Malaguarnera (&) Department of Senescence, Urological and Neurological Sciences, University of Catania, Via Messina 829, 95125 Catania, Italy e-mail: malaguar@unict.it

Losartan vs. amlodipine treatment in elderly oncologic hypertensive patients: A randomized clinical trial

Elderly neoplastic patients frequently may show hypertension and hyperuricemia, before and after chemotherapeutic treatments. The purpose of this study was to evaluate the efficacy of losartan which is an antihypertensive drug with uricosuric properties vs. amlodipine in hypertensive neoplastic elderly patients. This was an open-labeled, randomized, comparative trial. The study was performed as a 30-day study. Seventy patients with cancer were randomly assigned to receive losartan or amlodipine. Blood pressure (BP), blood urea nitrogen (BUN) levels, creatinine, serum and urinary uric acid, creatinine and uric acid clearance were determined before and after chemotherapy. One day after chemotherapy in losartan group vs. amlodipine group we observed a significant difference in urinary uric acid (p<0.001) of 18 mg/24 h vs. 40 mg/24 h. Thirty days after chemotherapy we observed a significant difference in azotemia of 0.0 mg/dl vs. 3.8 mg/dl (p<0.001), serum uric acid of 0.05 mg/dl vs. 0.49 mg/dl (p<0.001), urinary uric acid (p<0.001) of 23 mg/24 h vs. 0.0 mg/24 h, GFR of 2 ml/min/1.73 m(2) vs. -8 ml/min/1.73 m(2) (p<0.05) and systolic BP (SBP) of 3.6 mmHg vs. 0.8 mmHg (p<0.05). The findings of the present study support the effective role of losartan compared to amlodipine in treating hypertension and hyperuricemia in elderly patients under chemotherapeutic treatment.