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Hepatic angiotensin

Ryuichi Morishita
Recent research on vaccination has extended its scope from infectious diseases to chronic diseases, including Alzheimer disease, dyslipidemia, and hypertension. We have designed DNA vaccine for the treatment of high blood pressure (BP) toward to human vaccine therapy to treat hypertension. Plasmid vector encoding hepatitis B core-angiotensin II (Ang II) fusion protein was injected into spontaneously hypertensive rats (SHR) using needleless injection system. Anti-Ang II antibody was successfully produced in hepatitis B core-Ang II group, and antibody response against Ang II was sustained for at least 6 months...
September 2016: Journal of Hypertension
Laila Alawdah, Ahmad Nahari, Dayel Alshahrani, Musa Fagih, Shahid Ghazi, Abdulrahman Al-Hussaini
Gastrointestinal sarcoidosis is a rare disease with very limited data in children. Here we report the first pediatric case of successful treatment with infliximab. The first case was an 8-year-old Saudi girl who presented with fever, weight loss, and abdominal pain that was followed in a few months with hematemesis and development of hepatosplenomegaly. The second case was a 9-year-old Sudanese boy who manifested with vomiting, epigastric pain, and weight loss. On upper endoscopy, both cases demonstrated severe erosive nodular gastric mucosa...
September 2016: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
Kiyoshi Asada, Yosuke Aihara, Hiroaki Takaya, Ryuichi Noguchi, Tadashi Namisaki, Kei Moriya, Masakazu Uejima, Mitsuteru Kitade, Tsuyoshi Mashitani, Kosuke Takeda, Hideto Kawaratani, Yasushi Okura, Kosuke Kaji, Akitoshi Douhara, Yasuhiko Sawada, Norihisa Nishimura, Kenichiro Seki, Akira Mitoro, Junichi Yamao, Hitoshi Yoshiji
AIM: To clarify whether Agtr1a methylation is involved in the development of nonalcoholic steatohepatitis (NASH)-related liver fibrosis in adult rats. METHODS: A choline-deficient amino acid (CDAA) diet model was employed for methylation analysis of NASH-related liver fibrosis. Agtr1a methylation levels were measured in the livers of CDAA- and control choline-sufficient amino acid (CSAA)-fed rats for 8 and 12 wk using quantitative methylation-specific PCR. Hepatic stellate cells (HSCs) were isolated by collagenase digestion of the liver, followed by centrifugation of the crude cell suspension through a density gradient...
October 8, 2016: World Journal of Hepatology
Serena Pelusi, Salvatore Petta, Chiara Rosso, Vittorio Borroni, Anna Ludovica Fracanzani, Paola Dongiovanni, Antonio Craxi, Elisabetta Bugianesi, Silvia Fargion, Luca Valenti
BACKGROUND: The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD) are still under definition. AIM: To assess the clinical determinants of fibrosis progression rate (FPR) in NAFLD patients with baseline and follow-up histological evaluation, with a special focus on the impact of pharmacological therapy. METHODS: In an observational cohort of 118 Italian patients from tertiary referral centers, liver histology was evaluated according to Kleiner...
2016: PloS One
Ryuichi Morishita
Recent research on vaccination has extended its scope from infectious diseases to chronic diseases, including Alzheimer disease, dyslipidemia, and hypertension. We have designed DNA vaccine for the treatment of high blood pressure (BP) toward to human vaccine therapy to treat hypertension. Plasmid vector encoding hepatitis B core-angiotensin II (Ang II) fusion protein was injected into spontaneously hypertensive rats (SHR) using needleless injection system. Anti-Ang II antibody was successfully produced in hepatitis B core-Ang II group, and antibody response against Ang II was sustained for at least 6 months...
September 2016: Journal of Hypertension
Giovanni Sansoè, Manuela Aragno, Raffaella Mastrocola, Giulio Mengozzi, Erica Novo, Maurizio Parola
BACKGROUND: Tissue Angiotensin II (Ang-II), produced through local non ACE-dependent pathways, stimulates liver fibrogenesis, renal vasoconstriction and sodium retention. AIM: To highlight chymase-dependent pathway of Ang-II production in liver and kidney during cirrhosis development. METHODS: Liver histology, portal pressure, liver and kidney function, and hormonal status were investigated in rat liver cirrhosis induced through 13 weeks of CCl4, with or without chymase inhibitor SF2809E, administered between 4th and 13th CCl4 weeks; liver and kidney chymase immunolocation and Ang-II content were assessed...
2016: PloS One
M B Hilscher, L J Odell, L J Myhre, L Prokop, J Talwalkar
WHAT IS KNOWN AND OBJECTIVE: The presence of cirrhosis has a multifaceted impact on hepatic drug metabolism. An area of concern and uncertainty in the care of patients with cirrhosis is the safe use of both prescription and over-the-counter medications. COMMENT: Retrospective studies indicate a high incidence of adverse drug reactions (ADRs) among patients with cirrhosis related to use of certain medication classes including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and non-steroidal anti-inflammatory drugs...
August 31, 2016: Journal of Clinical Pharmacy and Therapeutics
G K Rangan, M C Tchan, A Tong, A T Y Wong, B J Nankivell
Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure...
August 2016: Internal Medicine Journal
Shu Li, Qinglan Wang, Yanyan Tao, Chenghai Liu
The rennin-angiotensin system (RAS) is crucial in hepatic fibrosis development, and therapies targeting this system may be a promising treatment for hepatic fibrosis. In this study, we investigated the effects of swertiamarin (Swe), an ethanol extract of Gentiana manshurica Kitag, on hepatic fibrosis and its underlying mechanisms through regulating RAS. Primary rat hepatic stellate cells (HSCs) were isolated and treated with angiotensin II (Ang II) with or without Swe and losartan. The proliferation and activation of HSCs were measured...
November 2016: Journal of Pharmacology and Experimental Therapeutics
Angelika Bickel, Irene Koneth, Annette Enzler-Tschudy, Jörg Neuweiler, Lukas Flatz, Martin Früh
BACKGROUND: Pembrolizumab is an anti- Programmed Death 1 (PD-1) antibody approved in melanoma, non-small cell lung cancer and investigated in malignant pleural mesothelioma. The most frequent immunotherapy related autoimmune reactions include dermatitis, pneumonitis, colitis, hypophysitis, uveitis, hypothyreodism, hepatitis and interstitial nephritis. CASE PRESENTATION: We describe a 62-year old patient diagnosed with malignant pleural mesothelioma who experienced ten days after the second dose of third line therapy with pembrolizumab sudden onset of generalized edema including legs and eyelids and weight gain of 15 kg resulting from nephrotic syndrome and acute renal failure...
2016: BMC Cancer
Devender Kodati, Harish Kaushik Kotakonda, Narsimhareddy Yellu
BACKGROUND: Olmesartan medoxomil is an orally given angiotensin II receptor antagonist indicated for the treatment of hypertension. OBJECTIVE: The aim of the study was to establish a population pharmacokinetic model for olmesartan, the active metabolite of olmesartan medoxomil, in Indian hypertensive patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of olmesartan. METHODS: The population pharmacokinetic model for olmesartan was developed using Phoenix NLME 1...
August 17, 2016: European Journal of Drug Metabolism and Pharmacokinetics
Zuo-Wei Ning, Xiao-Ying Luo, Guo-Zhen Wang, Yang Li, Miao-Xia Pan, Ren-Qiang Yang, Xu-Guang Ling, Shan Huang, Xiao-Xin Ma, Si-Yi Jin, Dan Wang, Xu Li
Aims Angiotensin II (AngII), a vasoconstrictive peptide of the renin-angiotensin system, promotes hepatic fibrogenesis and induces microRNA-21 expression. Angiotensin-(1-7) [Ang-(1-7)], which counter-regulates Ang II, has been evidenced to protect against hepatic fibrosis. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, which is activated by reactive oxygen species, was identified as a novel mechanism of liver fibrosis. However, it remains unclear how microRNA-21 mediates AngII-induced NLRP3 inflammasome activation...
August 8, 2016: Antioxidants & Redox Signaling
Makoto Harada, Yuji Kamijo, Takero Nakajima, Koji Hashimoto, Yosuke Yamada, Hisashi Shimojo, Frank J Gonzalez, Toshifumi Aoyama
Activation of renal peroxisome proliferator-activated receptor α (PPARα) is renoprotective, but there is no safe PPARα activator for patients with chronic kidney disease (CKD). Studies have reported that irbesartan (Irbe), an angiotensin II receptor blocker (ARB) widely prescribed for CKD, activates hepatic PPARα. However, Irbe's renal PPARα-activating effects and the role of PPARα signalling in the renoprotective effects of Irbe are unknown. Herein, these aspects were investigated in healthy kidneys of wild-type (WT) and Ppara-null (KO) mice and in the murine protein-overload nephropathy (PON) model respectively...
November 1, 2016: Clinical Science (1979-)
Jingjing Zhao, Juntian Liu, Xiaoming Pang, Xiaolu Zhang, Shuyue Wang, Di Wu
Inflammation plays a key role in many chronic diseases such as cardiovascular diseases and liver diseases. As a representative inflammatory molecule, C-reactive protein (CRP) is mainly produced in the liver. Hepatic CRP plays a direct role in the inflammatory hepatic diseases and in development of atherosclerosis when entering into the blood circulation. In the present study, we observed the effect of epigallocatechin-3-gallate (EGCG) on Ang II-induced CRP generation in hepatocytes and the molecular mechanism...
November 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
J S Possomato-Vieira, R A Khalil
Preeclampsia is a pregnancy-related disorder characterized by hypertension and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral, and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin, and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension, and other manifestation of preeclampsia...
2016: Advances in Pharmacology
Shuntarou Tsuchiya, Yuichiro Amano, Osamu Isono, Mayumi Imai, Fumi Shimizu, Mari Asada, Shigemitsu Imai, Ayako Harada, Yoshitaka Yasuhara, Ryuichi Tozawa, Hiroshi Nagabukuro
AIM: Low-density lipoprotein receptor knockout (LDLR-KO) mouse fed with modified choline-deficient and amino acid-defined (mCDAA) diet exhibits non-alcoholic steatohepatitis (NASH)-like pathophysiology. In order to pharmacologically benchmark this model, effects of pioglitazone, a thiazolidinedione and candesartan cilexetil, an angiotensin II type 1 receptor blocker (ARB) on steatosis and liver fibrosis were examined. METHODS: Pioglitazone (10 mg/kg) and candesartan cilexetil (3 mg/kg) were orally administered once daily to LDLR-KO mice under mCDAA diet for 7 weeks...
July 15, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Chad Hall, Keisaku Sato, Nan Wu, Tianhao Zhou, Tina Kyritsi, Fanyin Meng, Shannon Glaser, Gianfranco Alpini
BACKGROUND: Cholangiocytes, a small population of cells within the normal liver, have been the focus of a significant amount of research over the past two decades because of their involvement in cholangiopathies such as primary sclerosing cholangitis and primary biliary cholangitis. METHODS: This manuscript summarizes landmark studies in the field of cholangiocyte physiology and aims to provide an updated review of biliary pathogenesis. RESULTS: The historical approach of rodent extrahepatic bile duct ligation and the relatively recent utilization of transgenic mice have led to significant discoveries in cholangiocyte pathophysiology...
July 12, 2016: Gene Expression
Zakaria A Salama, Ahmed Sadek, Ahmed M Abdelhady, Samar Kamal Darweesh, Shereif Ahmed Morsy, Gamal Esmat
BACKGROUND: Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. METHODS: A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted...
June 2016: Hepatobiliary Surgery and Nutrition
Mina T Kelleni, Salwa A Ibrahim, Aly M Abdelrahman
Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid drug whose efficacy is limited by its hepatotoxicity. The aim of this study was to investigate the possible protective role of captopril (100 mg/kg/day, p.o. for seven days), an angiotensin converting enzyme inhibitor, and telmisartan (10 mg/kg/day p.o. for seven days), an angiotensin II receptor blocker with peroxisome proliferative receptor gamma (PPARγ) agonism, in a model of MTX (single dose 20 mg/kg i.p. at the fifth day) induced hepatotoxicity in rats...
June 2016: Toxicology Mechanisms and Methods
Jang Hoon Lee, Dong Heon Yang, Jin Yong Hwang, Seung Ho Hur, Tae Joon Cha, Ki-Sik Kim, Moo Hyun Kim, Kook Jin Chun, Gwang Soo Cha, Geu Ru Hong, Sang Gon Lee, Dong Soo Kim, Doo Il Kim, Shung Chull Chae
PURPOSE: A new antihypertensive drug that selectively blocks angiotensin II receptor type 1, fimasartan, has a potent and rapidly acting antihypertensive effect. We investigated the antihypertensive effects of fimasartan 60 and 120 mg and its safety in comparison to 8 mg of candesartan. METHODS: This clinical trial is a multicenter, randomized, double-blind, active comparator, and parallel group study. Three hundred sixty-two individuals were screened, and 290 patients aged 19 to 75 years with mild to moderate hypertension (diastolic blood pressure [DBP], 90-110 mm Hg) were randomly assigned to 60 to 120 mg/d of fimasartan or 8 mg/d of candesartan after a 2-week placebo run-in period...
June 2016: Clinical Therapeutics
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