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Endozepine-4 levels are increased in hepatic coma

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World Journal of Gastroenterology 2015年第30期21卷 9103-9110页

作者： Giulia malaguarnera Marco Vacante Filippo Drago Gaetano Bertino Massimo Motta Maria Giordano michele malaguarnera Research Center "The Great Senescence" Hospital of Cannizzaro University of Catania Department of Clinical and Experimental Medicine University of Catania Department of Biomedical and Biotechnological Sciences Section of PharmacologySchool of MedicineUniversity of Catania Gerontology and Bone Metabolic Disease Section Department of Medical SciencesUniversity of Torino

AIM:To evaluate the serum levels of endozepine-4,their relation with ammonia serum levels,the grading of coma and the severity of cirrhosis,in patients with hepatic coma. METHODS:In this study we included 20 subjects with Hepatic coma,20 subjects with minimal hepatic encephalopathy(MHE) and 20 subjects control. All subjects underwent blood analysis,Child Pugh and Model for End- stage liver disease(MELD) assessment,endozepine-4 analysis. RESULTS:Subjects with hepatic coma showed significant difference in endozepine-4(P < 0.001) and NH3 levels(P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation(P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD(P = 0.017; Pearsoncorrelation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma,with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia(P < 0.001). In patients with grade Ⅳ hepatic coma,endozepine levels were significantly higher compared to other groups. CONCLUSION:This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion,data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.

关键词： Endozepine-4 Hepatic encephalopathy Hepatic coma Cirrhosis, Benzodiazepine Peripheralbenzodiazepine receptor Model for End - stage liverdisease Glutamate-related neurotoxicity which in turnmay alter the γ-aminobutyric acid

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

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World Journal of Gastroenterology 2011年第39期17卷 4414-4420页

作者： michele malaguarnera Marco Vacante Maria Giordano Massimo Motta Gaetano Bertino Manuela Pennisi Sergio Neri Mariano malaguarnera Giovanni Li Volti Fabio Galvano Department of Biological Chemistry Medical Chemistry and Molecular BiologyUniversity of Catania Department of Internal Medicine and Systemic Disease University of Catania Research Center"The Great Senescence" University of Catania

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 Interferonα（IFN-α）plus ***：Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two *** A（n=35）received Peg-IFN-α2b plus ribavirin plus L-carnitine,and group B（n=34）received Peg-IFN-αand ribavirin for 12 *** patients underwent laboratory investigations including：red cell count,he-moglobin,white cell count,platelets,bilirubin,alanineaminotransferase（ALT）,aspartate aminotransferase（AST）,and ***：After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8（IU/L;P0.001）,ALT *** 112.3（IU/L;P 0.001）,viremia 4.04 vs 2.36（106 copies/mL;P 0.001）,Hb 1 vs 3.5（g/dL;P0.05）,red blood cells 0.3 vs 1.1（1012/L;P0.001）,white blood cells 1.5 vs 3（10/L;P0.001）and platelets 86 vs 85（×10/L;P0.001）.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）1.65,5%CI =0.65-5.37,*** group A compared to group B there was a significant improvement of sustained vi-rological response in 15 vs 7 patients（50%vs25%）,while the relapsers were 3 vs 5（10%vs 18%）（OR 3.57,5%CI=0.65-1.3,P0.001）.CONCLUSION：L-carnitine supplementations modulate erythropoiesis,leucopoiesis and thrombocytopoiesis,and may be useful in patients treated for HCV.L-carni-tine treatment offers the possibility of achieving a sus-tained virological response while preventing overtreat-ment.

关键词： L-carnitine Chronic hepatitis C Anemia In-terferon

Comparison of YKL-39 and CHIT-1 expression during macrophages differentiation and polarization

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Modern Research in Inflammation 2013年第4期2卷 82-89页

作者： Michelino Di Rosa Daniele Tibullo michele malaguarnera michele Tuttobene Lucia malaguarnera Department of Bio-Medical Sciences University of Catania Catania Italy Department of Clinical and Molecular Biomedicine Division of Hematology University of Catania Catania Italy S. Immuno-Haemathology and Transfusional Medicine Transfusional Centre “Garibaldi” Hospital Catania Italy

The chitinase-like proteins YKL-39 (chitinase 3-like-2) and Chitortriosidase (CHIT-1) are members of the chitinases family. YKL-39 expression has been associated with osteoarthritis, whereas CHIT-1 activity is regarded as a biochemical marker of macrophage activation. So far, the physiological or pathological role of YKL-39 in the inflammation is still poorly understood. We compared YKL-39 and CHIT-1 modulation during monocyte to macrophage transition and polarization. Gene expression analysis was investigated by real-time PCR from mRNA of human monocytes obtained from buffy coat of healthy volunteers, from mRNA of polarized macrophages to classically activated macrophages (or M1), obtained by interferon-γ and lipopolysaccharide exposure, and from mRNA of alternatively activated macrophages (or M2) obtained by interleukin-4 exposure. We demonstrated different variations of YKL-39 and CHIT-1 production during macrophages polarization. CHIT-1 levels gradually increase in the course of the time with a peak of expression between the fifth and the seventh day of culture. In contrast, YKL-39 expression was unaltered in the diverse stage of HMMs differentiation, but increased significantly in M1 polarized macrophages and reverted to base levels in M2 polarized macrophages. These findings indicated that the function of YKL-39 is much more restricted and selective than that exerted by CHIT-1.

关键词： YKL-39 Chitotriosidase Human Monocyte/Macrophages Classically Activated Macrophages Alternatively Activated Macrophages

Chronic hepatitis C:This and the new era of treatment

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World Journal of Hepatology 2016年第2期8卷 92-106页

作者： Gaetano Bertino Annalisa Ardiri Maria Proiti Giuseppe Rigano Evelise Frazzetto Shirin Demma MariaIrene Ruggeri Laura Scuderi Giulia malaguarnera Nicoletta Bertino Venerando Rapisarda Isidoro Di Carlo Adriana Toro Federico Salomone Mariano malaguarnera Emanuele Bertino michele malaguarnera Hepatology Unit-Department of Clinical and Experimental Medicine University of Catania95123 CataniaItaly Internal Medicine Unit ARNAS Civic Hospital90142 PalermoItaly Research Centre“La Grande Senesce” University of Catania95100 CataniaItaly Department of Biomedical Sciences University of Catania95100 CataniaItaly Faculty of Pharmacy University of Catania95123 CataniaItaly Occupational Medicine Unit Department of Clinical and Experimental MedicineUniversity of Catania95100 CataniaItaly Department of Surgical Sciences Organ Transplantation and Advanced TechnologiesUniversity of Catania95100 CataniaItaly Gastroenterology Unit Acireale Hospital95024 AcirealeCataniaItaly

Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects.

关键词： Direct-acting antiviral agents Nucleosideinhibitors Boceprevir Sofosbuvir Telaprevir HepatitisC Simeprevir Daclatasvir Ledipasvir Faldaprevir Ritonavir Ombitasvir Dasabuvir

Hepatocellular carcinoma and the risk of occupational exposure

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World Journal of Hepatology 2016年第13期8卷 573-590页

作者： Venerando Rapisarda Carla Loreto michele malaguarnera Annalisa Ardiri Maria Proiti Giuseppe Rigano Evelise Frazzetto Maria Irene Ruggeri Giulia malaguarnera Nicoletta Bertino Mariano malaguarnera Vito Emanuele Catania Isidoro Di Carlo Adriana Toro Emanuele Bertino Dario Mangano Gaetano Bertino Occupational Medi-cine Unit Department of Clinical and Experimental MedicineUniversity of Catania Department of Biomedical Sciences Human Anatomy and Histology Section University of Catania Department of Biomedical Sciences University of Catania Hepatology Unit Department of Clinical and Experimental Medicine University of Catania Internal Medicine Unit ARNAS Civic Hospital Research Centre "La Grande Senescenza" University of Catania Faculty of Pharmacy University of Catania Department of Surgical Sciences Organ Transplantation and Advanced TechnologiesUniversity of Catania

Hepatocellular carcinoma(HCC)is the most common type of liver *** main risk factors for HCC are alcoholism,hepatitis B virus,hepatitis C virus,nonalcoholic steatohepatitis,obesity,type 2 diabetes,cirrhosis,aflatoxin,hemochromatosis,Wilson’s disease and *** exposure to chemicals is another risk factor for *** the relationship between occupational risk and HCC is unclear and the reports are fragmented and *** review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem.

关键词： Hepatocellular carcinoma Autophagy Epigenetic events Hepatitis B virus Hepatitis C virus Occupational exposure Chemical agents Mitophagy Arsenic Cadmium

Moro orange juice prevents fatty liver in mice

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World Journal of Gastroenterology 2012年第29期18卷 3862-3868页

作者： Federico Salamone Giovanni Li Volti Lucilla Titta Lidia Puzzo Ignazio Barbagallo Francesco La Delia Shira Zelber-Sagi michele malaguarnera Pier Giuseppe Pelicci Marco Giorgio Fabio Galvano Department of Internal Medicine University of Catania95123 CataniaItaly Department of Drug Sciences University of Catania95125 CataniaItaly Department of Experimental Oncology European Institute of Oncology20141 MilanItaly Department of Pathology University of Catania95123 CataniaItaly Department of Gastroenterology Tel Aviv Sourasky Medical CenterTel-Aviv 64239Israel

AIM:To establish if the juice of Moro,an anthocyaninrich orange,may improve liver damage in mice with diet-induced ***:Eight-week-old mice were fed a high-fat diet(HFD) and were administrated water or Moro juice for 12 *** morphology,gene expression of lipid transcription factors,and metabolic enzymes were ***:Mice fed HFD displayed increased body weight,insulin resistance and *** juice administration limited body weight gain,enhanced insulin sensitivity,and decreased serum triglycerides and total *** fed HFD showed liver steatosis associated with *** Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase,a key enzyme of lipid ***,Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase,and restored liver glycerol-3-phosphate acyltransferase 1 ***:Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

关键词： Liver steatosis Anthocyanins Lipogenesis Lipid oxidation

Responsibility of hepatitis C virus in the development of hepatocellular carcinoma:From molecular alterations to possible solutions

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World Journal of Hepatology 2018年第6期10卷 448-451页

作者： Gaetano Bertino Giulia malaguarnera Evelise Frazzetto Alice Sciuto Gaetano Inserra Guido Nicola Zanghì michele malaguarnera Hepatology Unit Department of Clinical and Experimental MedicineUniversity of CataniaPoliclinico“G.Rodolico”Catania 95123Italy Research Center“the Great Senescence” University of CataniaCatania 95100Italy Department of Biomedical and Biotechnological Science University of CataniaCatania 95100Italy Department of Clinical and Experimental Medicine University of CataniaCatania 95123Italy Department of Surgery Policlinico Vittorio Emanuele University HospitalUniversity of CataniaCatania 95100Italy

There are several causes of hepatocellular carcinoma(HCC), but certainly the hepatitis C virus(HCV) is one of the most common. The HCV is able to contribute, both directly and indirectly, to the development of HCC. Determining early HCV clearance before an advanced liver disease develops, is absolutely necessary as this prevents the initiation of the cascade of events induced by HCV that may result in the development of HCC. The early treatment of the infection and the clearance of HCV represents today, in the age of the direct antiviral agents(DAAs), an extraordinary opportunity for true prevention of the development of HCV-related HCC.

关键词： Hepatitis C virus Hepatocellular carcinoma Inflammation Fibrosis Insulin-resistance Oxidative stress Direct acting antivirals

Work Productivity and Activity Impairment in Colorectal Cancer Patients Treated with Capecitabine

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Journal of Cancer Therapy 2013年第7期4卷 1198-1202页

作者： Giulia malaguarnera Manuela Pennisi Giuseppe Grosso Marco Vacante Salvatore Salomone Filippo Drago michele malaguarnera Erdogan Ozyalcin Massimo Motta Valentina Raciti Mariano malaguarnera Department of Neurosciences University of Catania Catania Italy International PhD Programme in Neuropharmacology University of Catania Catania Italy Research Center “The Great Senescence” Cannizzaro Hospital University of Catania Catania Italy

Background: The employment status of workers with cancer has important implications for impairment of intimate and family relationships and for economic, social and psychological health. The aim of the present study was to evaluate the effect of chemotherapy with capecitabine in patients with colorectal cancer on work productivity and daily activity. Methods: 30 patients with primary diagnosis of stage III colorectal cancer were enrolled for our study. All patients received capecitabine twice daily at a cumulative dose of 2500 mg/m2 on days 1 -14 and repeated on day 22. Work productivity was determined using the WPAI questionnaire. Results: We observed a significant increase in absenteeism after 1 cycle, after 6 cycles of therapy and at follow-up (p 0.001). On the other hand, presenteeism, work productivity loss and daily activity impairment, increased after 1 cycle and 6 cycles of therapy, but we could not find statistically different significances. Conclusions: Colorectal cancer diagnosis and treatment are associated with frailty and vulnerability. Chemotherapy with capecitabine may result in negative consequences for job performance.

关键词： Capecitabine Colorectal Cancer Work Productivity Activity Impairment Absenteeism Presenteeism

Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of Methodology 2025年第1期15卷 20-25页

作者： Nadeesha R Samarasinghe Taniya S Nagpal michele L Barbeau Charys M Martin Division of General Surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada Department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary *** investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in PA based interventions to supplement MSK course *** with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： Medical education Musculoskeletal Anatomy Exercise Online learning