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Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil

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World Journal of Hepatology 2022年第1期14卷 195-208页

作者： Mariana Sandoval Lourenço Patricia Momoyo Y Zitelli Marlone Cunha-Silva Arthur Ivan N Oliveira Cláudia P Oliveira Tiago Sevá-Pereira Flair JoséCarrilho mario g pessoa Daniel F Mazo Division of gastroenterology Department of Internal MedicineSchool of Medical SciencesUniversity of CampinasSao Paulo 13083-878Brazil Division of Clinical gastroenterology and Hepatology Department of GastroenterologyUniversity of São Paulo School of MedicineSao Paulo 05403-900Brazil

BACKgROUND Hepatitis C virus(HCV)treatment has undergone major changes in recent *** interferon-based therapies have been replaced by oral direct-acting antivirals(DAA)regimens,with high sustained virologic response(SVR)rates,and a lower incidence of adverse events(AEs).AIM To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in *** This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C(CHC),undergoing treatment with interferon-free regimens from November 2015 to November *** therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of ***,anthropometric,clinical,and laboratory variables were *** were assessed at 12 to 24 wk after therapy by intention-to-treat(ITT),and modified ITT(m-ITT)*** and serious adverse events(SAEs)were *** the statistical analysis,a P value ofge was 56.88 years,with 415(78.5%)being HCV genotype 1,followed by genotype 3(20.1%).Moreover,306(57.5%)subjects had cirrhosis,and a third of them had decompensated ***(SOF)plus daclatasvir±ribavirin was the most frequently used treatment(66.9%),followed by SOF plus simeprevir(21.2%).The overall ITT SVR was 92.6%(493/532),while the m-ITT SVR was 96.8%(493/509).Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy(OR:4.320;95%CI:1.920-9.721,P=0.0004),presence of esophageal varices(OR:2.381;95%CI:1.137-4.988,P=0.0215),previous portal hypertensive bleeding(OR:2.756;95%CI:1.173-6.471,P=0.02),higher model for end-stage liver disease scores(OR:1.143,95%CI:1.060–1.233,P=0.0005),lower serum albumin levels(OR:0.528,95%CI:0.322-0.867,P=0.0115),higher serum creatinine(OR:1.117,95%CI:1.056-1.312,P=0.0033),and international normalized ratio(INR)levels(OR:5.542,95%CI:2.023-15.182,P=0.0009).AEs were reported

关键词： Chronic hepatitis C Antiviral agents Hepatitis C virus Sustained virologic response Liver cirrhosis Safety

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Overcoming mitochondrial dysfunction in neurodegenerative diseases

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Neural Regeneration Research 2023年第7期18卷 1486-1488页

作者： João pessoa Ana I.Duarte CNC-Center for Neuroscience and Cell Biology CIBB-Center for Innovative Biomedicine and BiotechnologyUniversity of CoimbraCoimbraPortugal

Due to their intense electrical activity,neurons have high energy *** requirement makes them particularly sensitive to mitochondrial *** all eukaryotic cells,neurons have intrinsic mechanisms to mitigate the impact of mitochondrial dysfunction and its consequent production of toxic *** such(neuro)protective mechanisms,mitochondrial autophagy(mitophagy)is responsible for the removal of dysfunctional *** inhibition of mitophagy,together with insufficient mitochondrial activity,results in a shortage of adenosine triphosphate(ATP)and the accumulation of reactive oxygen species(ROS)(Simmons et al.,2020).

关键词： protective dysfunction intense

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Induced pluripotent stem cells throughout the animal kingdom:Availability and applications

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World Journal of Stem Cells 2019年第8期11卷 491-505页

作者： Lais Vicari de Figueiredo pessoa Fabiana Fernandes Bressan Kristine Karla Freude group of Stem Cell Models for Studies of Neurodegenerative Diseases Section for Pathobiological Sciences Department of Veterinary and Animal Sciences Faculty of Health and Medical Sciences University of Copenhagen Frederiksberg 1870 Denmark Department of Veterinary Medicine Faculty of Animal Science and Food Engineering University of Sao Paulo Pirassununga 13635-000 Sao Paulo Brazil

Up until the mid 2000s, the capacity to generate every cell of an organism was exclusive to embryonic stem cells. In 2006, researchers Takahashi and Yamanaka developed an alternative method of generating embryonic-like stem cells from adult cells, which they coined induced pluripotent stem cells (iPSCs). Such iPSCs possess most of the advantages of embryonic stem cells without the ethical stigma associated with derivation of the latter. The possibility of generating “custom-made” pluripotent cells, ideal for patient-specific disease models, alongside their possible applications in regenerative medicine and reproduction, has drawn a lot of attention to the field with numbers of iPSC studies published growing exponentially. IPSCs have now been generated for a wide variety of species, including but not limited to, mouse, human, primate, wild felines, bovines, equines, birds and rodents, some of which still lack well-established embryonic stem cell lines. The paucity of robust characterization of some of these iPSC lines as well as the residual expression of transgenes involved in the reprogramming process still hampers the use of such cells in species preservation or medical research, underscoring the requirement for further investigations. Here, we provide an extensive overview of iPSC generated from a broad range of animal species including their potential applications and limitations.

关键词： Pluripotency Embryonic Stem cell Reprogramming Animal Wild Induced pluripotency

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Promises and pitfalls of immune-based strategies for Huntington's disease

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Neural Regeneration Research 2017年第9期12卷 1422-1425页

作者： gabriela Delevati Colpo Erin Furr Stimming Natalia pessoa Rocha Antonio Lucio Teixeira Neuropsychiatry Program Department of Psychiatry and Behavioral Sciences Mc Govern Medical School The University of Texas Health Science Center at Houston Department of Neurology McGovern Medical School The University of Texas Health Science Center at Houston

Huntington＇s disease （HD） is an autosomal-dominant neurodegenerative disease characterized by the selec- tive loss of neurons in the striatum and cortex, leading to progressive motor dysfunction, cognitive decline and behavioral symptoms. HD is caused by a trinucleotide （CAg） repeat expansion in the gene encoding for huntingtin. Several studies have suggested that inflammation is an important feature of HD and it is already observed in the early stages of the disease. Recently, new molecules presenting anti-inflammatory and/or immunomodulatory have been investigated for HD. The objective of this review is to discuss the data obtained so far on the immune-based therapeutic strategies for HD.

关键词： Huntington's disease treatment disease modifying therapy inflammation

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Effective and simple recovery of 1,3-propanediol from a fermented medium by liquid–liquid extraction system with ethanol and K_3PO_4

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Chinese Journal of Chemical Engineering 2018年第1期26卷 104-108页

作者： Daiana Wischral Hongxin Fu Fernando L.Pellegrini pessoa Nei Pereira Jr Shang-Tian Yang School of Chemistry Department of Biochemical EngineeringFederal University of Rio de Janeiro William g.Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University School of Chemistry Department of Chemical EngineeringFederal University of Rio de Janeiro

1,3-Propanediol,traditionally obtained from fossils,has numerous industrial applications,including use in the production of high performance *** microbial production of 1,3-propanediol presents several opportunities,and the final purity grade determines its price and commercial *** development of novel separation technology could improve the economic viability of the bioproduction of 1,***,we investigated salting-out extraction as a novel process for 1,3-propanediol recovery from fermentation ***,a screening for the best salt/solvent combination was conducted and then optimized using the response surface *** solvents studied were methanol,ethanol,isopropanol and acetone,and the salts examined were K_2HPO_4,Na_2CO_3,K_2CO_3,(NH_4)_2SO_4,NaHPO_4,K_3PO_4 and C_6H_5NaO_*** optimal extraction system consisted of 34 wt%K_3PO_4,28 wt% ethanol,and 38 wt% fermentation broth containing 23.0 g·L^(-1)1,3-propanediol,which gave the highest partition coefficient of 33 and recovery yield of 97%.The results demonstrated that salting-out extraction was a promising method for 1,3-propanediol recovery from fermentation broth.

关键词： Fermentation Downstream process 1 3-Propanediol Clostridium beijerinckii Liquid-liquid extraction Salting-out extraction

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Mechanisms and consequences of COVID-19 associated liver injury: What can we affirm?

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World Journal of Hepatology 2020年第8期12卷 413-422页

作者： Carlos Antunes Brito Fabio Marinho Barros Edmundo pessoa Lopes Department of Internal Medicine Center of Medical Sciences of Federal University of PernambucoRecifePernambuco 50740600Brazil Clinical Hospital of Federal University of Pernambuco RecifePernambuco 50740900Brazil Post-graduation Program of Tropical Medicine of Federal University of Pernambuco RecifePernambuco 50670901Brazil Autoimmune Research Institute RecifePernambuco 52011010Brazil Português Hospital of Pernambuco RecifePernambuco 52010075Brazil

Since the first reports of coronavirus disease 2019(COVID-19)cases in December 2019 in China,numerous papers have been published describing a high frequency of liver injury associated with severe acute respiratory syndrome coronavirus 2 infection,many of them proposing a link between these findings and patient *** in serum aminotransferase levels(ranging from 16%to 62%)and bilirubin levels(ranging from 5%to 21%)have been reported and seem to be more often observed in patients with severe forms of *** absolute changes in these parameters are frequently seen,other variables,such as the ratio above the upper limit of normal,the onset of liver injury as a complication in severe cases and histopathological findings,reinforce that liver changes are of dubious clinical relevance in the course of this *** factors must also be considered in these analyses,such as the repercussions of hemodynamic changes,the presence of thrombotic events,and,mainly,the possible drug-induced liver injury with the current,yet off-label,*** paper aimed to analyze the currently available data on liver injury in patients with COVID-19.

关键词： COVID-19 SARS-CoV-2 Liver injury Liver enzymes Drug induced liver injury Pandemic

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Unusual cause of gastrointestinal bleeding in a cirrhotic patient:hepatocellular carcinoma with gastric invasion

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Hepatobiliary & Pancreatic Diseases International 2009年第4期8卷 431-433页

作者： Marcos Vinicius Perini Paulo Herman Rodrigo pessoa Willian Abraao Saad Luiz Augusto Carneiro D’Albuquerque University of So Paulo School of Medicine Department of GastroenterologyDigestive Surgery DivisionSo PauloSPBrazil

BACKgROUND:Upper gastrointestinal(gI)bleeding is a common complication of portal hypertension in cirrhotic patients,and hepatocellular carcinoma(HCC)is the most common tumor in cirrhotic *** from tumor erosion into the gI tract is very rare.A patient with HCC and gastric tumor invasion was described and the previously reported cases were reviewed. METHOD:A patient with upper gI bleeding was treated in a tertiary hospital. RESULTS:A cirrhotic patient with a HCC invading the stomach leading to upper gI bleeding was treated by left lateral segmentectomy and sub-total *** bleeding was controlled and a good surgical outcome was achieved. CONCLUSIONS:HCC with gastric invasion should be differentially diagnosed from upper gI bleeding in cirrhotic *** can be controlled and symptomatic relief marked in selected cases.

关键词： hepatocellular carcinoma gastintestinal hemorrhage surgery bleeding

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Antifungal activity and antidiarrheal activity via antimotility mechanisms of (-)-fenchone in experimental models

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World Journal of gastroenterology 2020年第43期26卷 6795-6809页

作者： Michelle Liz de Souza pessoa Leiliane Macena Oliveira Silva Maria Elaine Cristina Araruna Catarina Alves de Lima Serafim Edvaldo Balbino Alves Junior Alessa Oliveira Silva Matheus Marley Bezerra pessoa Hermes Diniz Neto Edeltrudes de Oliveira Lima Leonia Maria Batista Department of Pharmaceutical Sciences IPeFarMFederal University of ParaibaJoao Pessoa 58051-970ParaibaBrazil Health Sciences Center Federal University of ParaibaJoaoPessoa 58051-970ParaibaBrazil Postgraduate Program in Natural and Synthetic Bioactive Products Universidade Federal da ParaibaJoão Pessoa 58051-900Brazil

BACKgROUND(-)-Fenchone is a bicyclic monoterpene present in essential oils of plant species,such as Foeniculum vulgare and Peumus boldus,used to treatment of gastrointestinal *** studies report its anti-inflammatory,antioxidant,and antinociceptive *** To investigate antidiarrheal activity related to gastrointestinal motility,intestinal secretion and antimicrobial *** A castor oil-induced diarrhea model was used to evaluate antidiarrheal *** transit and gastric emptying protocols were used to assess a possible antimotility *** receptors,presynaptic α2-adrenergic and tissue adrenergic receptors,KATP channels,nitric oxide were investigated to uncover antimotility mechanisms of action and castor oil-induced enteropooling to elucidate antisecretory *** antimicrobial activity was evaluated in the minimum inhibitory concentration model,the fractional inhibitory concentration index using the(-)-fenchone association method with standard antifungal ***(-)-Fenchone(75,150 and 300 mg/kg)showed antidiarrheal activity,with a significant decrease in the evacuation *** activity is possibly related to a percentage of reduced intestinal transit(75,150 and 300 mg/kg).The antimotility effect of(-)-fenchone decreased in the presence of pilocarpine,yohimbine,propranolol,L-Ng-nitroarginine methyl ester or *** the enteropooling model,no reduction in intestinal fluid weight was observed.(-)-Fenchone did not show antibacterial activity;on the other hand,inhibits the growth of strains of fungi with a minimum fungicide concentration of 32μg/***,when it was associated with amphotericin B,no synergism was *** The antidiarrheal effect of(-)-fenchone in this study involves antimotility effect and not involve antisecretory mechanisms.(-)-Fenchone presents antifungal activity;however,it did not show antibacterial activity.

关键词： (-)-Fenchone Monoterpenes Diarrhea Motility Antifungal

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Noninvasive diagnosis of periportal fibrosis in schistosomiasis mansoni:A comprehensive review

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World Journal of Hepatology 2022年第4期14卷 696-707页

作者： Joelma Carvalho Santos Caroline Louise Diniz Pereira Ana Lúcia Coutinho Domingues Edmundo pessoa Lopes Postgraduate Program in Tropical Medicine Center of Health SciencesUniversidade Federal de PernambucoRecife 50670-901PernambucoBrazil gastroenterology Division Department of Internal Medicine of Center of Health SciencesHospital das Clínicas-Universidade Federal de PernambucoRecife 50670-901PernambucoBrazil

Schistosomiasis mansoni is a neglected disease and key public health problem,mainly due to its high prevalence,the scarcity of public policies,and the severity of some clinical *** fibrosis(PPF)is the commonest complication of chronic schistosomiasis mansoni and its diagnosis requires different *** though wedge biopsy of the liver is considered the gold standard,it is not justified in non-surgical patients,and percutaneous liver biopsy may be informative but does not have sufficient *** PPF tests mostly include biological(serum biomarkers or combined scores)or physical assessments(imaging assessment of fibrosis pattern or tissue stiffness).Moreover,imaging techniques,such as ultrasound,computed tomography,magnetic resonance imaging,and elastography are applied not only to support the diagnosis of schistosomiasis,but also to assess and detect signs of portal hypertension and organ damage due to chronic schistosomiasis.A combination between a comprehensive history and physical examination with biomarkers for liver fibrosis and imaging methods seems to offer the best approach for evaluating these *** addition,understanding their strengths and limitations will allow a more accurate interpretation in the clinical context and can lead to greater accuracy in estimating the degree of fibrosis in patients with Schistosomiasis mansoni(***)*** review will discuss the different noninvasive methods that are currently available for the evaluation of PPF in *** infection,and their application,advantages,and limitations in clinical practice.

关键词： Schistosoma mansoni Parasitic liver diseases Liver fibrosis Biomarkers Elasticity imaging techniques Ultrasonography

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An Innovative Approach for Attribute Reduction in Rough Set Theory

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Intelligent Information Management 2014年第5期6卷 223-239页

作者： Alex Sandro Aguiar pessoa Stephan Stephany National Institute for Space Research (INPE) Sao Jose dos Campos Brazil

The Rough Sets Theory is used in data mining with emphasis on the treatment of uncertain or vague information. In the case of classification, this theory implicitly calculates reducts of the full set of attributes, eliminating those that are redundant or meaningless. Such reducts may even serve as input to other classifiers other than Rough Sets. The typical high dimensionality of current databases precludes the use of greedy methods to find optimal or suboptimal reducts in the search space and requires the use of stochastic methods. In this context, the calculation of reducts is typically performed by a genetic algorithm, but other metaheuristics have been proposed with better performance. This work proposes the innovative use of two known metaheuristics for this calculation, the Variable Neighborhood Search, the Variable Neighborhood Descent, besides a third heuristic called Decrescent Cardinality Search. The last one is a new heuristic specifically proposed for reduct calculation. Considering some databases commonly found in the literature of the area, the reducts that have been obtained present lower cardinality, i.e., a lower number of attributes.

关键词： Rough Set Theory Reducts Attribute Reduction Metaheuristics

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