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Renin angiotensin system in liver diseases: Friend or foe?

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World Journal of Gastroenterology 2017年第19期23卷 3396-3406页

作者： ana cristina simoes e silva Aline S Miranda Natália P Rocha Antonio L Teixeira Department of Pediatrics Faculty of MedicineFederal University of Minas Gerais Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineUFMG Laboratory of Neurobiology Department of MorphologyInstitute of Biological SciencesUFMG Neuropsychiatry Program Department of Psychiatry and Behavioral SciencesMcGovern Medical SchoolUniversity of Texas Health Science Center at Houston

In the last three decades,the understanding of the renin angiotensin system(RAS)has been changed by the discoveries of functional local systems,novel biologically active peptides,additional specific receptors,alternative pathways of angiotensin(Ang)?Ⅱ?generation,and new roles for enzymes and precursor components other than those in Ang?Ⅱ?*** this regard,the discovery that Ang-(1-7)opposes the pressor,proliferative,pro-fibrotic,and pro-inflammatory effects mediated by Ang?Ⅱ?has contributed to the realization that the RAS is composed of two *** first axis consists of the angiotensin-converting enzyme(ACe),with Ang?Ⅱ?as the end product,and the angiotensin type 1(AT1)receptor as the main effector mediating the biological actions of Ang?Ⅱ.The second axis results from ACe2-mediated hydrolysis of Ang?Ⅱ,leading to the production of Ang-(1-7),with the Mas receptor as the main effector conveying the vasodilatory,antiproliferative,anti-fibrotic,and anti-inflammatory effects of Ang-(1-7).experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver *** this manuscript,we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications,including hemodynamic changes and hepatorenal *** therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.

关键词： Renin angiotensin system Angiotensin Ⅱ Angiotensin-(1-7) Hepatic cirrhosis Liver fibrosis Hepatorenal syndrome

Bartter's syndrome:clinical findings,genetic causes and therapeutic approach

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World Journal of Pediatrics 2021年第1期17卷 31-39页

作者： Flavia cristina Carvalho Mrad Sílvia Bouissou Morais Soares Luiz Alberto Wanderley de Menezes silva Pedro Versiani dos Anjos Menezes ana cristina simoes-e-silva Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineFederal University of Minas Gerais(UFMG)Av.Alfredo Balena190Room#281Belo HorizonteMG 30130-100Brazil Pediatric Nephrology Unit Faculty of MedicineUFMGBelo HorizonteBrazil

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 *** sources Literature reviews and original research articles were collected from database,including PubMed and *** According to the time of onset and symptoms,BS can be classified into antenatal and classic *** studies have identified different subtypes of *** 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),***-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type Ⅳ*** mutations of CLCNKB and CLCNKA cause BS type Ⅳ*** type Ⅴ consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGe family member *** gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of *** 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 *** 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 *** early diagnosis and treatment of BS may prevent long-term consequences such as growth failure,nephrocal-cinosis and end-stage renal disease.

关键词： Bartter's syndrome Hypercalciuria Hypokalemia Metabolic alkalosis Nephrocalcinosis

Renin-angiotensin system in the pathogenesis of liver fibrosis

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World Journal of Gastroenterology 2009年第21期15卷 2579-2586页

作者： Regina Maria Pereira Robson Augusto Souza dos Santos Filipi Leles da Costa Dias Mauro Martins Teixeira ana cristina simoes e silva Department of Pediatrics Faculty of MedicineFederal University of Minas Gerais Laboratory of Hypertension Department of Physiology and BiophysicsInstitute of Biological SciencesFederal University of Minas Gerais Laboratory of Immunopharmacology Department of Biochemistry and ImmunologyInstitute of Biological SciencesFederal University of Minas Gerais

Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACe2-Ang-（1-7）- Mas receptor axis.

关键词： Hepatic fibrosis Renin angiotensin system Angiotensin II Angiotensin-(1-7) Receptor Mas Angiotensin converting enzyme 2

Autoimmune hepatitis in childhood: The role of genetic and immune factors

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World Journal of Gastroenterology 2013年第28期19卷 4455-4463页

作者： Priscila Menezes Ferri Liu Débora Marques de Miranda eleonora Druve Tavares Fagundes Alexandre Rodrigues Ferreira ana cristina simoes e silva Department of Pediatrics Interdisciplinary Laboratory of Medical Investigation Federal University of Minas Gerais Belo Horizonte Minas Gerais 30130-100 Brazil National Institute of Science and Technology of Molecular Medicine (INCT-MM) CNPq-FAPEMIG Federal University of Minas Gerais Belo Horizonte Minas Gerais 30130-100 Brazil

Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.

关键词： Autoimmune hepatitis Genetics Clinical practice Immunophenotype

Current knowledge on esophageal atresia

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World Journal of Gastroenterology 2012年第28期18卷 3662-3672页

作者： Paulo Fernando Martins Pinheiro ana cristina simoes e silva Regina Maria Pereira Department of Pediatric Surgery Odilon Behrens HospitalAvenida JoséBonifácioSão CristovãoBelo Horizonte31210-690 Minas GeraisBrazil Department of Pediatrics Faculty of MedicineFederal University of Minas GeraisBelo Horizonte30130-100 Minas GeraisBrazil

esophageal atresia (eA) with or without tracheoesophageal fistula (TeF) is the most common congenital anomaly of the esophagus. The improvement of survival observed over the previous two decades is multifactorial and largely attributable to advances in neonatal intensive care, neonatal anesthesia, ventilatory and nutritional support, antibiotics, early surgical intervention, surgical materials and techniques. Indeed, mortality is currently limited to those cases with coexisting severe life-threatening anomalies. The diagnosis of eA is most commonly made during the first 24 h of life but may occur either antenatally or may be delayed. The primary surgical correction for eA and TeF is the best option in the absence of severe malformations. There is no ideal replacement for the esophagus and the optimal surgical treatment for patients with long-gap eA is still contro-versial. The primary complications during the postoperative period are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal dysmotility, fistula recurrence, respiratory disorders and deformities of the thoracic wall. Data regarding long-term outcomes and follow-ups are limited for patients following eA/TeF repair. The determination of the risk factors for the complicated evolution following eA/TeF repair may positively impact long-term prognoses. Much remains to be studied regarding this condition. This manuscript provides a literature review of the current knowledge regarding eA.

关键词： esophageal atresia Tracheoesophageal fistula esophageal stenosis Long-gap Gastro-esophageal reflux

Relationship between angiotensin-(1-7) and angiotensin Ⅱ correlates with hemodynamic changes in human liver cirrhosis

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World Journal of Gastroenterology 2009年第20期15卷 2512-2519页

作者： Walkíria Wingester Vilas-Boas Antnio Ribeiro-Oliveira Jr Regina Maria Pereira Renata da Cunha Ribeiro Jerusa Almeida ana Paula Nadu ana cristina simoes e silva Robson Augusto Souza dos Santos Laboratory of Hypertension Department of Physiology Biological Sciences institute Federal University of Minas Gerais Av. Antonio Carlos 6627 Belo Horizonte MG 31270-901 Brazil Laboratory of endocrinology Department of Medicine Faculty of Medicine Federal University of Minas Gerais Av. Alfredo Balena 190 Belo Horizonte MG 30130-100 Brazil Hospitalar Foundation of the State of Minas Gerais FHEMIG Belo Horizonte MG Brazil Department of Pediatrics Faculty of Medicine Federal University of Minas Gerais Av.Alfredo Balena 190 Belo Horizonte MG 30130-100 Brazil

AIM： To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system （RAS） components and hemodynamic changes. MeTHODS： Patients were allocated into 4 groups： mild-to-moderate liver disease （MLD）, advanced liver disease （ALD）, patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity （PRA）, angiotensin （Ang） Ⅰ, Ang Ⅱ, and Ang-（1-7） levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components. ReSULTS： PRA and angiotensins were elevated in ALD when compared to MLD and controls （P 〈 0.05）. In contrast, Ang Ⅱ was significantly reduced in MLD. Ang-（1-7）/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-（1-7）/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation （0.52 ± 0.08 vs 0.38 ±0.04, P 〈 0.02）, whereas the peripheral circulating Ang Ⅱ/Ang Ⅰ ratio was elevated in comparison to splanchnic levels （0.18 ±0.02 vs 0.13 ±0.02, P 〈 0.04）. Ang-（1-7）/ Ang Ⅱ ratios positively correlated with cardiac output （r = 0.66） and negatively correlated with systemic vascular resistance （r = -0.70）. CONCLUSION： Our findings suggest that the relationship between Ang-（1-7） and Ang Ⅱ may play a role in the hemodynamic changes of human cirrhosis.

关键词： Renin-angiotensin system Liver cirrhosis Angiotensin-(1-7) Angiotensin Ⅱ Splanchnic circulation Angiotensin converting enzyme 2

Inherited Fanconi syndrome

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World Journal of Pediatrics 2023年第7期19卷 619-634页

作者： Anna Luiza Braga Albuquerque Rafael dos Santos Borges ana Flavia Conegundes erika emmylaine dos Santos Frederico Moreira Man Fu Clara Tavares Araujo Pedro Alves Soares Vaz de Castrol ana cristina simoes e silva Interdisciplinary Laboratory of Medical Investigation Unit of Pediatric NephrologyFaculty of MedicineFederal University of Minas Gerais(UFMG)Belo HorizonteBrazil Department of Pediatrics Faculty of MedicineUFMGAlfredo Balena Avenue1902Nd FloorRoom#281Belo HorizonteMG 30130-100Brazil

Background Fanconi-Debré-de Toni syndrome(also known as Fanconi renotubular syndrome,or FRST)profoundly increased the understanding of the functions of the proximal convoluted tubule(PCT)and provided important insights into the pathophysiology of several kidney diseases and drug *** sources We searched Pubmed and Scopus databases to find relevant articles about *** review article focuses on the physiology of the PCT,as well as on the physiopathology of FRST in children,its diagnosis,and *** FRST encompasses a wide variety of inherited and acquired PCT alterations that lead to impairment of PCT *** children,FRST often presents as a secondary feature of systemic disorders that impair energy supply,such as Lowe's syndrome,Dent's disease,cystinosis,hereditary fructose intolerance,galactosemia,tyrosinemia,Alport syndrome,and Wilson's *** rare,congenital causes of FRST greatly impact the morbidity and mortality of patients and impose diagnostic ***,its treatment is diverse and considers the ability of the clinician to identify the correct etiology of the *** The early diagnosis and treatment of pediatric patients with FRST improve the prognosis and the quality of life.

关键词： Cystinosis Fanconi syndrome Fanconi renotubular syndrome Fanconi-Debre-de Toni syndrome Proximal tubule Renal tubular transport-Rickets

Synthesis and applications of lanthanoid complexes of pentadentate and hexadentate N_(5) and N_(6) macrocycles:A review

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Journal of Rare earths 2024年第1期42卷 1-15,I0001页

作者： Julio Corredoira-Vázquez cristina González-Barreira Paula Oreiro-Martínez ana M.García-Deibe Jesús Sanmartín-Matalobos Matilde Fondo Departamento de Química Inorganica Facultade de QuímicaUniversidade de Santiago de CompostelaCampus Vida15782Santiago de CompostelaSpain Phantom-g CICECO-Aveiro Institute of MaterialsDepartment of PhysicsUniversity of Aveiro3810-193AveiroPortugal Institute of Materials(iMATUS) Universidade de Santiago de Compostela15782Santiago de CompostelaSpain

In this paper,the lanthanoid complexes of N_(5) and N_(6) macrocycle ligands,without pendant arms or additional heteroatoms,are *** review covers the period from 2015 to the current date,since in 2014 Schiff base macrocyclic ligands incorporating the pyridine moiety,and their complexes,were revised,and in 2015 the chemistry of pentaaza macrocycle ligands with rare earth metals was also *** and phthalocyanine ligands are not included in this review,which primarily focuses on complexes with Schiff bases and amines without pendant arms or any additional donor other than *** synthetic methods,structural characterization,based on single X-ray crystal data,and properties of the lanthanoid complexes,with special attention to magneto-structural correlations,are presented herein.

关键词： Lanthanoid N_(5),N_(6)macrocycle Coordination chemistry Chirality Biological activity Molecule magnet

MicroRNAs in inflammatory bowel disease:What do we know and what can we expect?

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World Journal of Gastroenterology 2024年第16期30卷 2184-2190页

作者： ellen cristina Souza de Oliveira ana elisa Valencise Quaglio Thais Gagno Grillo Luiz Claudio Di Stasi Ligia Yukie Sassaki Department of Internal Medicine Medical SchoolSão Paulo State University(Unesp)Botucatu 18618-686São PauloBrazil Verum Ingredients Botucatu Technology ParkBotucatu 18605-525São PauloBrazil Department of Biophysics and Pharmacology Institute of BiosciencesSão Paulo State University(Unesp)Botucatu 18618-689São PauloBrazil

MicroRNAs(miRNAs),small non-coding RNAs composed of 18–24 nucleotides,are potent regulators of gene expression,contributing to the regulation of more than 30%of protein-coding *** that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells,there is an interest in exploring their importance in inflammatory bowel disease(IBD).IBD is a chronic and multifactorial disease of the gastrointestinal tract;the main forms are Crohn's disease and ulcerative *** studies have investigated the dysregulated expression of miRNAs in IBD,demonstrating their important roles as regulators and potential biomarkers of this *** editorial presents what is known and what is expected regarding miRNAs in *** the important regulatory roles of miRNAs in IBD are clearly established,biomarkers for IBD that can be applied in clinical practice are lacking,emphasizing the importance of further *** regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.

关键词： MicroRNAs Inflammatory bowel disease Crohn’s disease Ulcerative colitis Biomarker Therapy