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https://www.readbyqxmd.com/read/29792708/nonalcoholic-fatty-liver-disease-and-diabetes-is-associated-with-decreased-cyp3a4-protein-expression-and-activity-in-human-liver
#1
Rohitash Jamwal, Suzanne M de la Monte, Ken Ogasawara, Sravani Adusumalli, Benjamin B Barlock, Fatemeh Akhlaghi
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease in Western population. We investigated the effect of nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus on CYP3A4 activity in human liver tissue from brain dead donors (N=74). Histopathologically graded livers were grouped into normal (n=24), nonalcoholic fatty liver (NAFL, n=26) and nonalcoholic steatohepatitis (NASH, n=24) categories. The rate of conversion of midazolam to its 1-hydroxy metabolite was used to assess in vitro CYP3A4 activity in human liver microsomes (HLM)...
May 24, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29787859/design-and-rationale-of-the-insyte-study-a-randomised-placebo-controlled-study-to-test-the-efficacy-of-a-synbiotic-on-liver-fat-disease-biomarkers-and-intestinal-microbiota-in-non-alcoholic-fatty-liver-disease
#2
Eleonora Scorletti, Paul R Afolabi, Elizabeth A Miles, Debbie E Smith, Amal Almehmadi, Albandri Alshathry, Helen E Moyses, Geraldine F Clough, Mark Wright, Janisha Patel, Laure Bindels, Nathalie M Delzenne, Philip C Calder, Christopher D Byrne
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. OBJECTIVES: In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp...
May 19, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29778254/long-term-liver-disease-treatment-and-mortality-outcomes-among-17-000-persons-diagnosed-with-chronic-hepatitis-c-virus-infection-current-chronic-hepatitis-cohort-study-status-and-review-of-findings
#3
REVIEW
Anne C Moorman, Loralee B Rupp, Stuart C Gordon, Yuna Zhong, Jian Xing, Mei Lu, Joseph A Boscarino, Mark A Schmidt, Yihe G Daida, Eyasu H Teshale, Philip R Spradling, Scott D Holmberg
Chronic Hepatitis Cohort Study (CHeCS) publications using data from "real-world" patients with hepatitis C virus (HCV) have described demographic disparities in access to care; rates of advanced liver disease, morbidity, and mortality (2.5%-3.5% per year during 2006-10, although only 19% of all CHeCS decedents, and just 30% of those with deaths attributed to liver disease, had HCV listed on death certificate); substantial comorbidities, such as diabetes, advanced liver fibrosis (29% prevalence), renal disease, and depression, and partial reversal of all these with successful antiviral therapy; patient risk behaviors; and use of noninvasive markers to assess liver disease...
June 2018: Infectious Disease Clinics of North America
https://www.readbyqxmd.com/read/29769061/five-traditional-nigerian-polyherbal-remedies-protect-against-high-fructose-fed-streptozotocin-induced-type-2-diabetes-in-male-wistar-rats
#4
O E Kale, O B Akinpelu, A A Bakare, F O Yusuf, R Gomba, D C Araka, T O Ogundare, A C Okolie, O Adebawo, O Odutola
BACKGROUND: This present study sought to assess the modulatory effects of five Nigerian traditional polyherbal in high fructose-fed, streptozotocin-induced (HF-STZ) Type 2 diabetes (T2D) in rats. T2D was achieved via fructose feeding (20%W/V ) ad libitum for 2 weeks and streptozotocin (STZ, 40 mg/kg) (15th Day) intraperitoneally. METHODS: Seventy-two hours after STZ injection, fourty-eight diabetic rats were divided into eight of 6 rats/group: Diabetic normal untreated, glibenclamide (GBLI, 0...
May 16, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29761171/coding-variants-in-pnpla3-and-tm6sf2-are-risk-factors-for-hepatic-steatosis-and-elevated-serum-alanine-aminotransferases-caused-by-a-glucagon-receptor-antagonist
#5
Cristina B Guzman, Suman Duvvuru, Anthony Akkari, Pallav Bhatnagar, Chakib Battioui, Wendra Foster, Xiaotian Michelle Zhang, Sudha S Shankar, Mark A Deeg, Naga Chalasani, Thomas A Hardy, Christof M Kazda, Sreekumar G Pillai
LY2409021 is a glucagon receptor antagonist that was associated with hepatic steatosis and elevated aminotransferases in phase 2 diabetes studies. We investigated the relationship between selected genetic variants and hepatic steatosis and elevated alanine aminotransferases (ALTs) associated with LY2409021. Patients participated in a 6-week placebo-controlled trial (I1R-MC-GLDI [GLDI], n = 246) and a 52-week placebo- and active comparator-controlled trial (I1R-MC-GLDJ [GLDJ], n = 158). GLDJ had endpoints at 6 months, including measures of hepatic fat fraction (HFF) by magnetic resonance imaging...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29755645/hepatic-steatosis-in-chronic-hepatitis-b-a-study-of-metabolic-and-genetic-factors
#6
Michael O Baclig, Karen G Reyes, Veni R Liles, Cynthia A Mapua, Mark Pierre S Dimamay, Juliet Gopez-Cervantes
Hepatic steatosis is a common finding in liver biopsy and may co-exist with chronic hepatitis B (CHB) infection. The aims of this study were to determine the prevalence of steatosis in CHB patients among Filipinos; determine the factors related to the presence of steatosis among individuals with and without CHB infection; and to investigate the possible association between steatosis and polymorphism in interleukin 28B (IL28B) gene. The presence of steatosis was correlated with clinical, biochemical and histological parameters...
2018: International Journal of Molecular Epidemiology and Genetics
https://www.readbyqxmd.com/read/29752759/metformin-targets-brown-adipose-tissue-in-vivo-and-reduces-oxygen-consumption-in-vitro
#7
Peter Breining, Jonas B Jensen, Elias I Sundelin, Lars C Gormsen, Steen Jakobsen, Morten Busk, Lars Rolighed, Peter Bross, Paula Fernandez-Guerra, Lasse K Markussen, Nanna E Rasmussen, Jacob B Hansen, Steen B Pedersen, Bjørn Richelsen, Niels Jessen
Metformin is the most widely prescribed oral antidiabetic drug worldwide. Despite well-documented beneficial effects on health outcomes in diabetic patients, the target organs that mediate the effects of metformin remain to be established. In adult humans, brown adipose tissue (BAT) can influence basic metabolic rate, making BAT an attractive target for treatment of type 2 diabetes. Under the hypothesis that BAT is a metformin target tissue, we investigated in vivo uptake of [11 C]-metformin tracer in mice and studied in vitro effects of metformin on cultured human brown adipocytes...
May 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29752333/the-endocrinology-of-male-breast-cancer
#8
REVIEW
Ian S Fentiman
Male breast cancer (MBC) is a rare disease but, as a result of epidemiological collaborations, there is now greater clarity concerning endocrine risk factors. The significant rise in global age-standardised mean BMI in men is likely to lead to increases in incidence of maturity-onset diabetes and MBC. The metabolic changes accompanying obesity decrease androgens and sex hormone-binding globulin (SHBG), thereby increasing available oestrogens. The higher rates of MBC in North and Equatorial Africa are largely due to liver damage from endemic bilharziasis and hepatitis B causing elevated oestradiol (E2 ) levels from hepatic conversion of androgen...
June 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29745909/a-young-adult-with-generalized-lipodystrophy-and-diabetes-mellitus-case-report
#9
E Çelo, B Kalari, F Toti
Lipodystrophies are a group of heterogeneous disorders characterized by varying degrees of body fat loss and predisposition to insulin resistance and its metabolic complications. Lipodystrophy associated metabolic abnormalities include insulin resistance, that often lead to diabetes mellitus and its complications, hypertriglyceridemia that may be severe enough to cause acute pancreatitis, and hepatic steatosis that may lead to cirrhosis. We present the case of an 18-year-old female who was hospitalized as an inaugural Diabetes Mellitus...
April 2018: Georgian Medical News
https://www.readbyqxmd.com/read/29734463/diabetes-plasma-glucose-and-incidence-of-fatty-liver-cirrhosis-and-liver-cancer-a-prospective-study-of-0-5-million-people
#10
Yuanjie Pang, Christiana Kartsonaki, Iain Turnbull, Yu Guo, Robert Clarke, Yiping Chen, Fiona Bragg, Ling Yang, Zheng Bian, Iona Y Millwood, Juanzhi Hao, Xianyong Han, Yajing Zang, Junshi Chen, Liming Li, Michael V Holmes, Zhengming Chen
The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We aimed to examine the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults, and to assess the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow-up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalised non-alcoholic fatty liver disease (NAFLD), and 244 hospitalised alcoholic liver disease (ALD) were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline...
May 7, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29733999/discovery-and-structure-activity-relationships-study-of-thieno-2-3-b-pyridine-analogues-as-hepatic-gluconeogenesis-inhibitors
#11
Fei Ma, Jian Liu, Tingting Zhou, Min Lei, Jing Chen, Xiachang Wang, Yinan Zhang, Xu Shen, Lihong Hu
Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC50  = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC50  = 16...
April 24, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29729445/emerging-role-of-il-35-in-inflammatory-autoimmune-diseases
#12
REVIEW
Lin-Chong Su, Xiao-Yan Liu, An-Fang Huang, Wang-Dong Xu
Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis...
May 3, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29729383/ameliorative-potential-of-lavandula-stoechas-in-metabolic-syndrome-via-multitarget-interactions
#13
S S Kulabas, H Ipek, A R Tufekci, S Arslan, I Demirtas, R Ekren, U Sezerman, T B Tumer
ETHNOPHARMACOLOGICAL IMPORTANCE: Decoction and infusion prepared from aerial parts of Lavandula stoechas L. (L. stoechas) have been traditionally used as remedy against several components of metabolic syndrome (MetS) and associated disorders including type II diabetes and cardiovascular diseases by Anatolian people. AIM OF THE STUDY: The aim is to elucidate the potential ameliorative effects of L. stoechas aqueous extracts on insulin resistance and inflammation models through multitarget in vitro approaches and also to elucidate mechanism of action by analyzing transcriptional and metabolic responses...
May 2, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29727379/severe-liver-failure-rather-than-cirrhosis-is-associated-with-mortality-in-patients-with-infectious-endocarditis-a-retrospective-case-control-study
#14
Manon Allaire, Jean-François D Cadranel, Christophe Bureau, Salah Zerkly, Thierry Thévenot, Armand Garioud, Patrice Cacoub, Gilles Macaigne, Laurent Alric, Vincent Jouannaud, Hortensia Lison, Carine Chagneau-Derrode, Alexandre Pariente, Agne Combining Grave Accent S Pe Combining Acute Accent Laquier, Marc Bourlie Combining Grave Accent Re, Xavier Causse, Jean-Baptiste Nousbaum, Je Combining Acute Accent Rôme Dumortier, Alexandre Louvet, Isabelle Rosa-He Combining Acute Accent Zode, Nathalie Ganne-Carrie Combining Acute Accent, Ryme Chentouh, Anis Sfaxi, Je Combining Acute Accent Rome Gournay, He Combining Acute Accent le Combining Grave Accent Ne Blasco-Perrin, Teresa Antonini, Laurent Spahr, Jean-Pierre Bronowicki, Christine Silvain, Vincent Di Martino, Jean-Didier Grange, Jacques Denis, Karine Dupont, Pierre Iaria, Isabelle Ollivier-Hourmand, Thong Dao
BACKGROUND: Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC. PATIENTS AND METHODS: Overall, 101 patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013. RESULTS: Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively...
May 3, 2018: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29723527/inhibitory-effect-of-fasiglifam-on-hepatitis-b-virus-infections-through-suppression-of-the-sodium-taurocholate-cotransporting-polypeptide
#15
Yasunori Nio, Yuichi Akahori, Hitomi Okamura, Koichi Watashi, Takaji Wakita, Makoto Hijikata
Fasiglifam is a selective partial agonist of G-protein-coupled receptor 40 (GPR40), which was developed for the treatment of type 2 diabetes mellitus. However, the clinical development of fasiglifam was voluntarily terminated during phase III clinical trials due to adverse liver effects. Fasiglifam showed an inhibitory effect on sodium taurocholate cotransporting polypeptide (NTCP) in human and rat hepatocytes. Recently, NTCP was reported to be a functional receptor for human hepatitis B virus (HBV) infections...
April 30, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29723161/metreleptin-improves-insulin-sensitivity-independent-of-food-intake-in-humans-with-lipodystrophy
#16
Rebecca J Brown, Areli Valencia, Megan Startzell, Elaine Cochran, Peter J Walter, H Martin Garraffo, Hongyi Cai, Ahmed M Gharib, Ronald Ouwerkerk, Amber B Courville, Shanna Bernstein, Robert J Brychta, Kong Y Chen, Mary Walter, Sungyoung Auh, Phillip Gorden
BACKGROUND: Recombinant leptin (metreleptin) ameliorates hyperphagia and metabolic abnormalities in leptin-deficient humans with lipodystrophy. We aimed to determine whether metreleptin improves glucose and lipid metabolism in humans when food intake is held constant. METHODS: Patients with lipodystrophy were hospitalized for 19 days with food intake held constant by controlled diet in an inpatient metabolic ward. In a non-randomized cross-over design, previously metreleptin-treated patients (n= 8) were continued on-metreleptin for five days, and off-metreleptin for the next 14 days (withdrawal cohort)...
May 3, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29720370/association-of-25-hydroxyvitamin-d-with-liver-cancer-incidence-and-chronic-liver-disease-mortality-in-finnish-male-smokers-of-the-atbc-study
#17
Gabriel Y Lai, Jian-Bing Wang, Stephanie J Weinstein, Dominick Parisi, Ronald L Horst, Katherine A McGlynn, Satu Männistö, Demetrius Albanes, Neal D Freedman
BACKGROUND: Although circulating 25-hydroxyvitamin D [25(OH)D] concentrations were linked to liver cancer and chronic liver disease (CLD) in laboratory studies, few epidemiologic studies have addressed the associations. METHODS: Within the ATBC Study, we measured 25(OH)D in baseline serum of 202 incident liver cancer cases and 225 CLD deaths that occurred during nearly 25 years of follow-up, and 427 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression...
May 2, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29718992/analysis-of-risk-factors-associated-with-hepatocellular-carcinoma-in-black-south-africans-2000-2012
#18
Daniel Mak, Chantal Babb de Villiers, Charles Chasela, Margaret I Urban, Anna Kramvis
OBJECTIVE: The aims of this study were to determine the prevalence of risk factors associated with hepatocellular carcinoma (HCC) in black adult South Africans and to estimate the size of the associated risks. METHODS: A case-control analysis of 150 black South African patients (aged 18-75 years) with HCC-who were a subset of patients recruited for the Johannesburg Cancer Case Control Study 2000 to 2012-was undertaken. The association between this tumour and hepatitis B/C virus infections, and human immunodeficiency virus (HIV) mono- and co-infections was investigated...
2018: PloS One
https://www.readbyqxmd.com/read/29710658/guava-leaf-inhibits-hepatic-gluconeogenesis-and-increases-glycogen-synthesis-via-ampk-acc-signaling-pathways-in-streptozotocin-induced-diabetic-rats
#19
Ramachandran Vinayagam, Muthukumaran Jayachandran, Stephen Sum Man Chung, Baojun Xu
Psidium guajava (PG) is a short shrub or tree cultivated in tropical and subtropical regions around the world. The leaf extract of PG (guava leaf) has been used historically to cure many ailments. However, mechanisms of action of guava leaf in treating diabetes are not fully understood. Effects and underlying mechanisms of guava leaf on gluconeogenesis and glycogenesis in hepatocytes, insulin signaling proteins, liver function markers, and lipid profile in streptozotocin (STZ) injected diabetic Wistar rats were investigated within the current study...
April 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29703790/impact-of-sustained-virological-response-on-the-extrahepatic-manifestations-of-chronic-hepatitis-c-a-meta-analysis
#20
Patrice Cacoub, Anne Claire Desbois, Cloe Comarmond, David Saadoun
BACKGROUND AND AIMS: Extrahepatic manifestations of HCV are responsible for morbidity and mortality in many chronically infected patients. New, interferon-free antiviral treatment regimens, which present the opportunity to treat all HCV-infected patients, call for a better understanding of the benefits of treating non-cirrhotic chronically infected individuals. METHODS: A systematic review was conducted. Identified studies from targeted database searches on Embase and Medline were screened...
April 27, 2018: Gut
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