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| 1 | Bartter's syndrome:clinical findings,genetic causes and therapeutic approach显示文摘Backgound Bartter's syndrome(BS)is a rare group of salt losing tubulopathies due to the impairment of transport mecha-nisms at the thick ascending limb of the Henle's loop.Data sources Literature reviews and original research articles were collected from database,including PubMed and Scopus.Results According to the time of onset and symptoms,BS can be classified into antenatal and classic BS.Molecular studies have identified different subtypes of BS.BS types Ⅰ,Ⅱ and Ⅲ are caused by mutations on genes encoding the luminal Na^(+)-K^(+)-2Cl^(-) co-transporter,the luminal K+ channel ROMK,and the basolateral chloride channel ClC-Kb(CLCNKB),respectively.Loss-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type Ⅳa.Simultaneous mutations of CLCNKB and CLCNKA cause BS type Ⅳb.BS type Ⅴ consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGE family member D2.Severe gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of BS.Main clinical and biochemical alterations in BS include polyuria,dehydration,hypokalemia,hypochloremic metabolic alka-losis,hyperreninemia,high levels of prostaglandins,normal or low blood pressure,hypercalciuria and failure to thrive.Treatment focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria,including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 production.Conclusions Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure,nephrocal-cinosis and end-stage renal disease. | Flavia Cristina Carvalho Mrad Sílvia Bouissou Morais Soares Luiz Alberto Wanderley de Menezes Silva Pedro Versiani dos Anjos Menezes Ana Cristina Simoes-e-Silva | 2021 | World Journal of Pediatrics2021，17，1： | 10 |
| 2 | Associations of sense of coherence with psychological distress and quality of life in inflammatory bowel disease显示文摘AIM:To investigate the relationship between sense of coherence,psychological distress and health related quality of life in inflammatory bowel disease(IBD).METHODS:This cross-sectional study enrolled a consecutive sample of 147 IBD(aged 45.1 ± 14.1 years; 57.1% female) patients recruited from a tertiary gastroenterology service.Sixty-four participants met diagnostic criteria for Crohn's disease,while eightythree patients had ulcerative colitis.Socio-demographic data(education,age,race,gender,gross monthly income and marital status),disease-related variables(illness activity,relapse rate in past 2 years,history of surgery and time since diagnosis),sense of coherence(Antonovsky's SOC scale),psychological distress symptoms(Hospital Anxiety and Depression Scale) and health-related quality of life(HRQo L; WHOQOLBref) were assessed.Hierarchical multiple regression analyses were performed to identify factors that are independently associated with psychological distress and HRQo L in patients with IBD and to provide indications for possible moderating or mediating effects.In addition,formal moderation and mediation analyses(Sobel tests) were performed to confirm potential moderators/mediators of the relationship between SOC,psychological distress symptoms and HRQoL.RESULTS:Lower SOC scores(std beta=-0.504; P < 0.001),female gender(std beta = 0.176; P = 0.021) and White race(std beta = 0.164; P = 0.033) were independently associated with higher levels of depressive symptoms,while lower levels of SOC(std beta =-0.438; P < 0.001) and higher relapse rate(std beta = 0.161; P = 0.033) were independently associated with more severe anxiety symptoms.A significant interaction between time since diagnosis and SOC was found with regard to the severity of depressive or anxiety symptoms,as the interaction term(time since diagnosis X SOC) had beta coefficients of-0.191(P = 0.009) and-0.172(P = 0.026),respectively.Lower levels of anxiety symptoms(std beta =-0.369; P < 0.001),higher levels of SOC(std beta = 0.231; P = 0.016) and non-White race(std beta =-0.229; P = 0.006),i.e.,mixed-race,which represented the reference category,were independently associated with higher levels of overall HRQoL.Anxiety symptoms were the most potent independent correlate of most aspects of HRQoL.In addition,anxiety mediated the association between SOC and satisfaction with health,as well as its relationship with physical,mental,and social relations HRQo L.Depressive symptoms also mediated the association between SOC and mental HRQoL.CONCLUSION:Our data indicated that SOC is an important construct,as it influences psychological distress and has significant albeit indirect effects on several HRQoL domains in IBD. | Thiago H Freitas Elias Andreoulakis Gilberto S Alves Hesley LL Miranda Lúcia LBC Braga Thomas Hyphantis André F Carvalho | 2015 | World Journal of Gastroenterology2015，21，21： | 10 |
| 3 | Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide显示文摘Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential. | Emanuel Monteiro Candeias Inês Carolina Sebastio Susana Maria Cardoso Sónia Catarina Correia Cristina Isabel Carvalho Ana Isabel Plácido Maria Sancha Santos Catarina Resende Oliveira Paula Isabel Moreira Ana Isabel Duarte | 2015 | World Journal of Diabetes2015，6，6： | 9 |
| 4 | Personalizing therapies for gastric cancer: Molecular mechanisms and novel targeted therapies显示文摘Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in 2008.In the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong survival.Moreover,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)therapies.Trastuzumab,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy.Further,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field.Thus,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved. | Michael Luis Ana Tavares Liliana S Carvalho Lúcio Lara-Santos António Araújo Ramon Andrade de Mello | 2013 | World Journal of Gastroenterology2013，19，38： | 6 |
| 5 | Helicobacter pylori and EBV in gastric carcinomas:Methylation status and microsatellite instability显示文摘AIM:To verify the methylation status of CDH1, DAPK, COX2, hMLH1 and CDKN2A genes and to evaluate their association with Helicobacter pylori (H. pylori)-cagA+ and Epstein Barr virus (EBV) infections in gastric adenocarcinomas.METHODS: Methylation-specific PCR (MSP) assay was performed in 89 primary gastric carcinomas (intestinal and diffuse types). Microsatellite instability (MSI) analysis was performed using the BAT26 primer set and PCR products were analyzed with the ABI PRISM 3100 Genetic Analyzer using Genescan 3.7 software (Applied Biosystems). Detection of H. pylori and genotyping were performed by PCR, using specifi c primers for ureaseC and cagA genes. The presence of EBV was assessed by in situ hybridization. Statistical analyses were performed using the χ2 or Fisher's exact test.RESULTS: The most frequent hypermethylated gene was COX-2 (63.5%) followed by DAPK (55.7%), CDH1 (51%), CDKN2A (36%) and hMLH1 (30.3%). Intestinal and diffuse adenocarcinomas showed different methylation profiles and there was an association between methylation of E-CDH1 and H. pylori-cagA+ in the intestinal adenocarcinoma type. MSI was correlated with hMLH1 methylation. There was an inverse correlation between DAPK hypermethylation and MSI.CONCLUSION: We found a strong association between CDH1 methylation and H. pylori-cagA+ in intestinal-type gastric cancer, association of MSI and better prognosis and an heterogeneous COX-2 overexpression. | Adriana Camargo Ferrasi Nídia Alice Pinheiro Silvia Helena Barem Rabenhorst Otávia Luisa Caballero Maria Aparecida Marchesan Rodrigues Fabrício de Carvalho Celso Vieira de Souza Leite Marcia Valéria Pitombeira Ferreira Marcos Aurélio Pessoa Barros Maria Inês de Moura Campos Pardini | 2010 | World Journal of Gastroenterology2010，16，3： | 6 |
| 6 | Embolization of splenorenal shunt associated to portal vein thrombosis and hepatic encephalopathy显示文摘Hepatic encephalopathy(HE)is a cognitive disturbance characterized by neuropsychiatric alterations.It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts.The presence of these portosystemic shunts allows the passage of nitrogenous substances from the intestines through systemic veins without liver depuration.Therefore,the embolization of these shunts has been performed tocontrol HE manifestations,but the presence of portal vein thrombosis is considered a contraindication.In this presentation we show a cirrhotic patient with severe HE and portal vein thrombosis who was submitted to embolization of a large portosystemic shunt.Case report:a 57 years-old cirrhotic patient who had been hospitalized many times for persistent HE and hepatic coma,even without precipitant factors.She had a wide portosystemic shunt and also portal vein thrombosis.The abdominal angiography confirmed the splenorenal shunt and showed other shunts.The larger shunt was embolized through placement of microcoils,and the patient had no recurrence of overt HE.There was a little increase of esophageal and gastric varices,but no endoscopic treatment was needed.Since portosystemic shunts are frequent causes of recurrent HE in cirrhotic patients,portal vein thrombosis should be considered a relative contraindication to perform a shunt embolization.However,in particular cases with many shunts and severe HE,we found that one of these shunts can be safely embolized and this procedure can be sufficient to obtain a good HE recovery.In conclusion,we reported a case of persistent HE due to a wide portosystemic shunt associated with portal vein thrombosis.As the patient had other shunts,she was successfully treated by embolization of the larger shunt. | Letícia de Campos Franzoni Fábio Cardoso de Carvalho Rafael Gomes de Almeida Garzon Fábio da Silva Yamashiro Laís Augusti Lívia Alves Amaral Santos Mariana de Souza Dorna Júlio Pinheiro Baima Talles Bazeia Lima Carlos Antonio Caramori Giovanni Faria Silva Fernando Gomes Romeiro | 2014 | World Journal of Gastroenterology2014，20，42： | 6 |
| 7 | Lymphocyte subsets in alcoholic liver disease显示文摘AIM:To compare lymphocyte subsets between healthy controls and alcoholics with liver disease.METHODS:The patient cohort for this study included individuals who were suspected to have alcoholic liver disease(ALD) and who had undergone liver biopsy(for disease grading and staging,doubts about diagnosis,or concurrent liver disease;n = 56).Normal controls included patients who were admitted for elective cholecystectomy due to non-complicated gallstones(n = 27).Formalin-fixed,paraffin-embedded liver biopsy specimens were sectioned and stained with hematoxylin and eosin and Perls' Prussian blue.The non-alcoholic steatohepatitis score was used to assess markers of ALD.Lymphocyte population subsets were determined by flow cytometry.T lymphocytes were identified(CD3+),and then further subdivided into CD4+ or CD8+ populations.B lymphocytes(CD19+) and natural killer(NK) cell numbers were also measured.In addition to assessing lymphocyte subpopulation differences between ALD patients and controls,we also compared subsets of alcoholic patients without cirrhosis or abstinent cirrhotic patients to normal controls.RESULTS:The patient cohort primarily consisted of older men.Active alcoholism was present in 66.1%.Reported average daily alcohol intake was 164.9 g and the average lifetime cumulative intake was 2211.6 kg.Cirrhosis was present in 39.3% of the patients and 66.1% had significant fibrosis(perisinusoidal and portal/periportal fibrosis,bridging fibrosis,or cirrhosis) in their liver samples.The average Mayo end-stage liver disease score was 7.6.No hereditary hemochromatosis genotypes were found.ALD patients(n = 56) presented with significant lymphopenia(1.5 × 109/L ± 0.5 × 109/L vs 2.1 × 109/L ± 0.5 × 109/L,P < 0.0001),due to a decrease in all lymphocyte subpopulations,except for NK lymphocytes:CD3+(1013.0 ± 406.2/mm3 vs 1523.0 ± 364.6/mm3,P < 0.0001),CD4+(713.5 ± 284.7/mm3 vs 992.4 ± 274.7/mm3,P < 0.0001),CD8+(262.3 ± 140.4/mm3 vs 478.9 ± 164.6/mm3,P < 0.0001),and CD19+(120.6 ± 76.1/mm3 vs 264.6 ± 88.0/mm3,P < 0.0001).CD8+ lymphocytes suffered the greatest reduction,as evidenced by an increase in the CD4+/CD8+ ratio(3.1 ± 1.3 vs 2.3 ± 0.9,P = 0.013).This ratio was associated with the stage of fibrosis on liver biopsy(rs = 0.342,P = 0.01) and with Child-Pugh score(rs = 0.482,P = 0.02).The number of CD8+ lymphocytes also had a positive association with serum ferritin levels(rs = 0.345,P = 0.009).Considering only patients with active alcoholism but not cirrhosis(n = 27),we found similar reductions in total lymphocyte counts(1.8 × 109/L ± 0.3 × 109/L vs 2.1 × 109/L ± 0.5 × 109/L,P = 0.018),and in populations of CD3+(1164.7 ± 376.6/mm3 vs 1523.0 ± 364.6/mm3,P = 0.001),CD4+(759.8 ± 265.0/mm3 vs 992.4 ± 274.7/mm3,P = 0.003),CD8+(330.9 ± 156.3/mm3 vs 478.9 ± 164.6/mm3,P = 0.002),and CD19+(108.8 ± 64.2/mm3 vs 264.6 ± 88.0/mm3,P < 0.0001).In these patients,the CD4+/CD8+ ratio and the number of NK lymphocytes was not significantly different,compared to controls.Comparing patients with liver cirrhosis but without active alcohol consumption(n = 11),we also found significant lymphopenia(1.3 × 109/L ± 0.6 × 109/L vs 2.1 × 109/L ± 0.5 × 109/L,P < 0.0001) and decreases in populations of CD3+(945.5 ± 547.4/mm3 vs 1523.0 ± 364.6/mm3,P = 0.003),CD4+(745.2 ± 389.0/mm3 vs 992.4 ± 274.7/mm3,P = 0.032),CD8+(233.9 ± 120.0/mm3 vs 478.9 ± 164.6/mm3,P < 0.0001),and CD19+(150.8 ± 76.1/mm3 vs 264.6 ± 88.0/mm3,P = 0.001).The NK lymphocyte count was not significantly different,but,in this group,there was a significant increase in the CD4+/CD8+ ratio(3.5 ± 1.3 vs 2.3 ± 0.9,P = 0.01).CONCLUSION:All patient subsets presented with decreased lymphocyte counts,but only patients with advanced fibrosis presented with a significant increase in the CD4+/CD8+ ratio. | Luís Costa Matos Paulo Batista Nuno Monteiro Joo Ribeiro Maria A Cipriano Pedro Henriques Fernando Giro Armando Carvalho | 2013 | World Journal of Hepatology2013，5，2： | 4 |
| 8 | Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients显示文摘AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IBD)patients from southeastern Brazil.METHODS:A total of 219 consecutive patients with IBD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IBD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among Brazilian patients.Variants genes*2and*3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population. | Ana Teresa P Carvalho Barbara C Esberard Renata S B Fróes Davy C M Rapozo Ana B Grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza | 2014 | World Journal of Gastroenterology2014，20，12： | 3 |
| 9 | Lack of microRNA‐101 causes E‐cadherin functional deregulation through EZH2 up‐regulation in intestinal gastric cancer显示文摘 | Joana Carvalho Nicole C van Grieken Patricia M Pereira Sónia Sousa Marianne Tijssen Tineke E Buffart Bego?a Diosdado Heike Grabsch Manuel AS Santos Gerrit Meijer Raquel Seruca Beatriz Carvalho Carla Oliveira | 2012 | J Pathol2012，，1： | 3 |
| 10 | Respiratory physiotherapy in gastroesophageal reflux disease:A review article显示文摘Gastroesophageal reflux disease(GERD) is a frequen disorder which is expensive to diagnose and treat Initiating therapy with empiric trial of proton-pump inhibitor is a well established strategy; however symptoms of GERD do often persist regardless of effective medication. Nowadays, increasing interest concerning the efficacy and safety of chronic acid suppression with proton-pump inhibitors(PPIs), prompts a consideration fo GERD treatment strategies related to the basic physiology of the lower esophageal sphincter, including modulationof its tone and ending of spontaneous transient lower esophageal sphincter relaxation, which contributes to reflux. Together, the lower esophageal sphincter and the crural diaphragm represent the major antireflux barrier, protecting the esophagus from reflux of gastric content. In order to prevent the need for enduring PPIs therapy or surgical procedures, substitute therapeutics approaches are being researched. Recently, studies have focused on the response of the respiratory muscles to inspiratory muscle training. As a result, inspiratory muscle training has emerged as a potential alternative for treatment of gastroesophageal reflux. The present report reviews the physiologic factors contributing to GERD, and presents the newly developed therapies that can be applied either alone or in association with available efficient GERD therapy. | Renata Carvalho de Miranda Chaves Tomás Navarro-Rodriguez | 2015 | World Journal of Respirology2015，5，1： | 2 |
| 11 | Full survival of paraquat-exposed rats after treatment with sodium salicylate显示文摘 | R.J. Dinis-Oliveira C. Sousa F. Remi?o J.A. Duarte A. Sánchez Navarro M.L. Bastos F. Carvalho | 2007 | Free Radical Biology and Medicine2007，，7： | 2 |
| 12 | Paraquat Poisonings: Mechanisms of Lung Toxicity, Clinical Features, and Treatment显示文摘 | R. J. Dinis-Oliveira J. A. Duarte A. Sánchez-Navarro F. Remi?o M. L. Bastos F. Carvalho | 2008 | CRC Critical Reviews in Toxicology2008，，1： | 2 |
| 13 | Contrasted effect of biochar and earthworms on rice growth and resource allocation in different soils显示文摘 | Diana Noguera Marco Rondón Kam-Rigne Laossi Valerio Hoyos Patrick Lavelle Maria Helena Cruz de Carvalho Sébastien Barot | 2010 | Soil Biology and Biochemistry2010，，7： | 2 |
| 14 | Helicobacter pylori Induces Increased Expression of Toll‐Like Receptors and Decreased Toll‐Interacting Protein in Gastric Mucosa that Persists Throughout Gastric Carcinogenesis显示文摘 | Pedro Pimentel‐Nunes Nádia Gon?alves Inês Boal‐Carvalho Luís Afonso Paula Lopes Roberto Roncon‐Albuquerque Rui Henrique Luís Moreira‐Dias Adelino F. Leite‐Moreira Mário Dinis‐Ribeiro | 2012 | Helicobacter2012，，1： | 2 |
| 15 | Transmission capacity: availability, maximum, transfer and reliability显示文摘 | Leite da S A M de Carvalho C J G da Fonseca M L A | 2002 | IEEE Transactions on Power Systems2002，17，3： | 1 |
| 16 | Using interpretive structural modelling to identify and rank performance measures: an application supply chain显示文摘 | AZEVEDO S CARVALHO H CRUZ-MACHADO V | 2013 | Baltic Journal of Management2013，8，2： | 1 |
| 17 | Central role of brown adipose tissue thyroxine 5 ' -deiodinase on thyroid hormone-dependent thermogenic response to cold显示文摘 | CARVALHO S D KIMURA E T BIANCO A C | 1991 | Endocrinology1991，128，4： | 1 |
| 18 | Metformin protectsthe brain against the oxidative imbalance promoted by type 2diabetes显示文摘 | Correia S Carvalho C Santos MS | 2008 | Med Chem2008，4，4： | 1 |
| 19 | 2-Fluorophenol degradation by aerobic granular sludge in a sequencing batch reactor显示文摘 | Duque A F Bessa V S Carvalho M F | 2011 | Water Research2011，45，20： | 1 |
| 20 | Microstructure,mechanical Properties and wearresistance of high speedsteel rolls for hot rolling mills 显示文摘 | Carvalho M A De Xavier R R Filho C S P | 2002 | I& SM2002，29，1： | 1 |
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