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https://www.readbyqxmd.com/read/29785143/pilot-study-of-the-antifibrotic-effects-of-the-multikinase-inhibitor-pacritinib-in-a-mouse-model-of-liver-fibrosis
#1
Suliman Al-Fayoumi, Taishi Hashiguchi, Yuka Shirakata, John Mascarenhas, Jack W Singer
Background: Fibrotic diseases result from an exuberant response to chronic inflammation. Myelofibrosis is the end result of inflammation in bone, caused by an inflammatory process triggered by production of abnormal myeloid cells driven by mutations affecting the JAK-STAT pathway. Inflammatory cytokine overproduction leads to increased mesenchymal cell proliferation, culminating in fibrosis. Although JAK2 inhibitors, such as the JAK1/2 inhibitor ruxolitinib and the JAK2/FLT3/CSF1R/IRAK1 inhibitor pacritinib suppress abnormal clone expansion in myelofibrosis, ruxolitinib does not appear to prevent or reverse bone-marrow fibrosis in most patients...
2018: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/29747582/the-renal-manifestations-of-type-4-familial-partial-lipodystrophy-a-case-report-and-review-of-literature
#2
Ru-Xuan Chen, Lei Zhang, Wei Ye, Yu-Bing Wen, Nuo Si, Hang Li, Ming-Xi Li, Xue-Mei Li, Ke Zheng
BACKGROUND: Lipodystrophy syndromes are rare disorders of variable body fat loss associated with potentially serious metabolic complications. Familial partial lipodystrophy (FPLD) is mostly inherited as an autosomal dominant disorder. Renal involvement has only been reported in a limited number of cases of FPLD. Herein, we present a rare case of proteinuria associated with type 4 FPLD, which is characterized by a heterozygous mutation in PLIN1 and has not been reported with renal involvement until now...
May 10, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29701171/risk-factors-for-rhabdomyolysis-with-hmg-coa-reductase-inhibitors-identified-using-a-postmarketing-surveillance-database-in-japan
#3
Masayuki Hashiguchi, Jun Hakamata, Mikiko Shimizu, Junya Maruyama, Tsuyoshi Shiga, Mayumi Mochizuki
OBJECTIVE: To investigate quantitatively the risk factors for rhabdomyolysis or related symptoms associated with HMG-CoA reductase inhibitors (statins), we used the lipid-lowering drug database (32,157 patients) developed by the RAD-AR Council, Japan, based on the postmarketing surveillance (PMS) data of pharmaceutical companies to perform a nested case-control study. MATERIALS AND METHODS: Of 26,849 patients taking statins, the case group was composed of 51 patients who experienced rhabdomyolysis or related symptoms while taking statins, and the control group was 1,020 patients randomly selected from patients who did not experience rhabdomyolysis or related symptoms while taking statins...
April 27, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29670841/effect-of-onopordon-acanthium-l-as-add-on-antihypertensive-therapy-in-patients-with-primary-hypertension-taking-losartan-a-pilot-study
#4
Roshanak Ghods, Manouchehr Gharouni, Massoud Amanlou, Niusha Sharifi, Ali Ghobadi, Gholamreza Amin
Purpose: Onopordon acanthium L. is known for its medicinal properties. Our recent study showed that its seed extract is a novel natura angiotensin-converting-enzyme inhibitor (ACEI). This study was carried out to investigate its possible antihypertensive effects in patients receiving losartan. Methods: This uncontrolled clinical trial was carried out among 20 patients (30-60y) with uncontrolled hypertension despite receiving 50 mg losartan (stage I & II) in two hospitals in Iran. After completing informed consent, patients were treated by 2 capsules [each 1g of Onopordon acanthium seed extract (OSE)] as add-on therapy, two times per day...
March 2018: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29614743/protective-effect-of-polyphenol-rich-extract-from-bee-pollen-in-a-high-fat-diet
#5
Anna Rzepecka-Stojko, Agata Kabała-Dzik, Robert Kubina, Krzysztof Jasik, Maciej Kajor, Dorota Wrześniok, Jerzy Stojko
We have studied a preventive effect of polyphenol-rich bee pollen ethanol extract (EEP) against histological changes in the liver and cardiac blood vessels, abnormalities of lipid profile, and the levels of oxidized low density lipoproteins (ox-LDL), asymmetric dimethylarginine (ADMA), angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) caused by a high-fat diet in C57 BL₆ mice. Supplementing the diet with EEP in the doses of 0.1 g/kg body mass (BM) and 1 g/kg BM resulted in a decrease of total cholesterol by 31% and 35%, respectively...
March 31, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29609847/angiotensin-iv-improves-subnormothermic-machine-perfusion-preservation-of-rat-liver-graft
#6
Donia Tabka, Mohamed Bejaoui, James Javellaud, Jean-Michel Achard, Hassen Ben Abdennebi
This study aims to determine whether Angiotensin IV (Ang IV) addition to Celsior preservation solution could improve hepatic endothelium function and provide better liver protection during subnormothermic machine preservation (SMP). Two experimental models were used: In the first part of the study, rings isolated from rat hepatic artery were preserved in Celsior solution (6 h, 20 °C) with and without Ang IV (10-9  M), then, endothelium-dependent relaxation (EDR) and the concentration of acetylcholine inducing half-maximal relaxation of pre-contracted rings (EC50) were measured...
March 30, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29564328/maternal-high-fat-and-high-salt-diets-have-differential-programming-effects-on-metabolism-in-adult-male-rat-offspring
#7
Stephanie A Segovia, Mark H Vickers, Claudia J Harrison, Rachna Patel, Clint Gray, Clare M Reynolds
Maternal high-fat or high-salt diets can independently program adverse cardiometabolic outcomes in offspring. However, there is a paucity of evidence examining their effects in combination on metabolic function in adult offspring. Female Sprague Dawley rats were randomly assigned to either: control (CD; 10% kcal from fat, 1% NaCl), high-salt (SD; 10% kcal from fat, 4% NaCl), high-fat (HF; 45% kcal from fat, 1% NaCl) or high-fat and salt (HFSD; 45% kcal from fat, 4% NaCl) diets 21 days prior to mating and throughout pregnancy and lactation...
2018: Frontiers in Nutrition
https://www.readbyqxmd.com/read/29524604/altered-global-microrna-expression-in-hepatic-stellate-cells-lx-2-by-angiotensin-1-7-and-mirna-1914-5p-identification-as-regulator-of-pro-fibrogenic-elements-and-lipid-metabolism
#8
Brenda de Oliveira da Silva, Luciane Carla Alberici, Letícia Ferreira Ramos, Caio Mateus Silva, Marina Bonfogo da Silveira, Carlos R P Dechant, Scott L Friedman, Kumiko Koibuchi Sakane, Letícia Rocha Gonçalves, Karen C M Moraes
The development of new therapeutic strategies to control or reverse hepatic fibrosis requires thorough knowledge about its molecular and cellular basis. It is known that the heptapeptide angiotensin-(1-7) [ang-(1-7)] can reduce hepatic fibrosis and steatosis in vivo; therefore, it is important to uncover the mechanisms regulating its activity and cellular model of investigation. Ang-(1-7) is a peptide of the renin-angiotensin system (RAS), and here we investigated its modulatory effect on the expression pattern of microRNAs (miRNAs) in hepatic stellate cells (HSCs) LX-2, which transdifferentiate into fibrogenic and proliferative cells...
May 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29515450/chymase-inhibitor-as-a-novel-therapeutic-agent-for-non-alcoholic-steatohepatitis
#9
REVIEW
Shinji Takai, Denan Jin
Non-alcoholic steatohepatitis (NASH) is characterized by inflammation and fibrosis, in addition to steatosis, of the liver, but no therapeutic agents have yet been established. The mast cell protease chymase can generate angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β, all of which are associated with liver inflammation or fibrosis. In animal models of NASH, augmented chymase has been observed in the liver. In histological analysis, chymase inhibitor prevented hepatic steatosis, inflammation, and fibrosis...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29501845/acetone-fraction-from-sechium-edule-jacq-s-w-edible-roots-exhibits-anti-endothelial-dysfunction-activity
#10
Celeste Trejo-Moreno, Gabriela Castro-Martínez, Marisol Méndez-Martínez, Jesús Enrique Jiménez-Ferrer, José Pedraza-Chaverri, Gerardo Arrellín, Alejandro Zamilpa, Omar Noel Medina-Campos, Galia Lombardo-Earl, Gerardo Joel Barrita-Cruz, Beatriz Hernández, Christian Carlos Ramírez, María Angélica Santana, Gladis Fragoso, Gabriela Rosas
ETHNOPHARMACOLOGICAL RELEVANCE: A recent ethnomedical survey on medicinal plants grown in Mexico revealed that Sechium edule (Jacq.) Sw. (Cucurbitaceae) is one of the most valued plant species to treat cardiovascular diseases, including hypertension. Fruits, young leaves, buds, stems, and tuberous roots of the plant are edible. Considering that endothelial dysfunction induced by Angiotensin II plays an important role in the pathogenesis of hypertension and is accompanied by a prooxidative condition, which in turn induces an inflammatory state, vascular remodeling, and tissue damage, and that S...
June 28, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29478818/ace-phenotyping-in-gaucher-disease
#11
Sergei M Danilov, Victoria E Tikhomirova, Roman Metzger, Irina A Naperova, Tatiana M Bukina, Ozlem Goker-Alpan, Nahid Tayebi, Nurshat M Gayfullin, David E Schwartz, Larisa M Samokhodskaya, Olga A Kost, Ellen Sidransky
BACKGROUND: Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. METHODS: ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes...
April 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29470765/angiotensin-ii-receptor-blockers-for-the-treatment-of-portal-hypertension-in-patients-with-liver-cirrhosis-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#12
Huijing Yao, Chunqing Zhang
BACKGROUND: Randomized controlled trials (RCTs) showed inconsistent results regarding the efficacy of angiotensin II receptor blockers (ARBs) on portal pressure as indicated by hepatic venous pressure gradient (HVPG). METHODS: A meta-analysis of RCTs was performed to evaluate the influence of ARBs treatment on HVPG. PubMed, Embase, and Cochrane's Library were searched for relevant RCTs. A fixed or a randomized effect model was used to pool the results according the heterogeneity...
February 22, 2018: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29462546/role-of-the-renin-angiotensin-system-in-hepatic-fibrosis-and-portal-hypertension
#13
REVIEW
Kwang Yong Shim, Young Woo Eom, Moon Young Kim, Seong Hee Kang, Soon Koo Baik
The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang-(1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension...
May 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29449808/suppressive-effects-of-clerodendrum-volubile-p-beauv-labiatae-methanolic-extract-and-its-fractions-on-type-2-diabetes-and-its-complications
#14
Ochuko L Erukainure, Rahman M Hafizur, Nurul Kabir, M Iqbal Choudhary, Olubunmi Atolani, Priyanka Banerjee, Robert Preissner, Chika I Chukwuma, Aliyu Muhammad, Eric O Amonsou, Md Shahidul Islam
Type 2 diabetes is the most prominent of all diabetes types, contributing to global morbidity and mortality. Availability and cost of treatment with little or no side effect especially in developing countries, remains a huge burden. This has led to the search of affordable alternative therapies especially from medicinal plants. In this study, the antidiabetic effect of the methanolic extract, dichloromethane (DCM), butanol (BuOH) and aqueous fractions of Clerodendrum volubile leaves were investigated in type 2 diabetic rats for their effect on glucose homeostasis, serum insulin level and hepatic biomarkers, lipid profile, pancreatic redox balance and Ca2+ levels, and β-cell distribution and function...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29427823/contribution-of-diagnostic-tests-for-the-etiological-assessment-of-uveitis-data-from-the-ulisse-study-uveitis-clinical-and-medicoeconomic-evaluation-of-a-standardized-strategy-of-the-etiological-diagnosis
#15
REVIEW
Pierre Grumet, Laurent Kodjikian, Audrey de Parisot, Marie-Hélène Errera, Neila Sedira, Emmanuel Heron, Laurent Pérard, Pierre-Loïc Cornut, Christelle Schneider, Sophie Rivière, Priscille Ollé, Grégory Pugnet, Pascal Cathébras, Pierre Manoli, Bahram Bodaghi, David Saadoun, Stéphanie Baillif, Nathalie Tieulie, Marc Andre, Frédéric Chiambaretta, Nicolas Bonin, Philip Bielefeld, Alain Bron, Frédéric Mouriaux, Boris Bienvenu, Stéphanie Vicente, Sylvie Bin, Marc Labetoulle, Christiane Broussolle, Yvan Jamilloux, Evelyne Decullier, Pascal Sève
PURPOSE: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. METHODS: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis...
April 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29425464/renin-angiotensin-system-inhibition-ameliorates-ccl4-induced-liver-fibrosis-in-mice-through-the-inactivation-of-nuclear-transcription-factor-kappa-b
#16
Sameh Saber, Amr A A Mahmoud, Noha Said Helal, Eman El-Ahwany, Rasha Abdelghany
Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl4-induced liver fibrosis. Mice were treated with silymarin (30 mg kg-1), perindopril (1 mg kg-1), fosinopril (2 mg kg-1), or losartan (10 mg kg-1). The administration RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline...
February 9, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29404501/effect-of-combined-farnesoid-x-receptor-agonist-and-angiotensin-ii-type-1-receptor-blocker-on-hepatic-fibrosis
#17
Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Yasushi Okura, Naotaka Shimozato, Shinya Sato, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Yasuhiko Sawada, Takemi Akahane, Soichiro Saikawa, Keisuke Nakanishi, Takuya Kubo, Masanori Furukawa, Ryuichi Noguchi, Kiyoshi Asada, Koh Kitagawa, Takahiro Ozutsumi, Yuki Tsuji, Daisuke Kaya, Yukihisa Fujinaga, Hitoshi Yoshiji
The farnesoid X receptor (FXR) agonist, a bile acid-activated nuclear receptor, has been shown to improve the histologic features of nonalcoholic steatohepatitis (NASH); however, a satisfactory effect on hepatic fibrosis has not been achieved. We aimed to investigate the combined effect of FXR agonist and angiotensin II type 1 receptor blocker on hepatic fibrogenesis in rat models of NASH. For 8 weeks, two rat models of NASH were developed. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were administered intraperitoneal injections of 1 mL/kg pig serum (PS) twice a week, whereas Fischer-344 rats were fed a choline-deficient, L-amino acid-defined diet (CDAA)...
November 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29393446/angiotensin%C3%A2-1%C3%A2-7-prevents-lipopolysaccharide%C3%A2-induced-hepatocellular-inflammatory-response-by-inhibiting-the-p38mapk-ap%C3%A2-1-signaling-pathway
#18
Hongli Xiao, Xiaoya Liu, Yan Wang, Guoxing Wang, Chenghong Yin
The pathological mechanism of lipopolysaccharide (LPS)‑induced liver injury involves a number of inflammatory mediators and cytokines. Angiotensin (Ang)‑(1‑7), a ligand for the proto‑oncogene Mas (Mas) receptor, antagonizes the actions of Ang II in the renin angiotensin system and exerts an anti‑inflammatory effect on LPS‑induced macrophages. The present study investigated the potential role of Ang‑(1‑7) in the regulation of inflammatory responses in LPS‑induced hepatocytes using the rat liver BRL cell line...
April 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29374184/creating-a-mouse-model-resistant-to-induced-ischemic-stroke-and-cardiovascular-damage
#19
Qing-Lan Ling, Anita J Mohite, Emma Murdoch, Hironari Akasaka, Qun-Ying Li, Shui-Ping So, Ke-He Ruan
Vascular prostanoids, isomerized from an intermediate prostaglandin (PG), H2 , produced by cyclooxygenase (COX), exert various effects on the vascular system, both protective and destructive. During endothelial dysfunction, vascular protector prostacyclin/prostaglandin I2 (PGI2 ) is decreased, while inflammatory PGE2 and thrombotic TXA2 are increased. Therefore, our research aim was to reverse the event by controlling PGH2 metabolism by generating an in vivo model via enzymatic engineering of COX-1 and prostacyclin synthase (PGIS)...
January 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29358853/serum-levels-of-angiotensin-converting-enzyme-as-a-biomarker-of-liver-fibrosis
#20
EDITORIAL
Aline Silva Miranda, Ana Cristina Simões E Silva
The renin angiotensin system (RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues, including the liver, pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-Ang type 1 (AT1) receptor mediates pro-inflammatory, pro-thrombotic, and pro-fibrotic processes...
December 28, 2017: World Journal of Gastroenterology: WJG
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