Galloway, Chad A; Lee, Hakjoo; Brookes, Paul S; Yoon, Yisang
Mitochondria produce the majority of cellular ATP through oxidative phosphorylation, and their capacity to do so is influenced by many factors. Mitochondrial morphology is recently suggested as an important contributor in controlling mitochondrial bioenergetics. Mitochondria divide and fuse continuously, which is affected by environmental factors, including metabolic alterations. Underscoring its bioenergetic influence, altered mitochondrial morphology is reported in tissues of patients and in animal models of metabolic dysfunction. In this study, we found that mitochondrial fission plays a vital role in the progression of nonalcoholic fatty liver disease (NAFLD). The development of hepatic steatosis, oxidative/nitrative stress, and hepatic tissue damage, induced by a high-fat diet, were alleviated in genetically manipulated mice suppressing mitochondrial fission. The alleviation of steatosis was recapitulated in primary hepatocytes with the inhibition of mitochondrial fission. Mechanistically, our study indicates that fission inhibition enhances proton leak under conditions of free fatty acid incubation, implicating bioenergetic change through manipulating mitochondrial fission. Taken together, our results suggest a mechanistic role for mitochondrial fission in the etiology of NAFLD. The efficacy of decreasing mitochondrial fission in the suppression of NAFLD suggests that mitochondrial fission represents a novel target for therapeutic treatment of NAFLD. Copyright © 2014 the American Physiological Society.
Full Text Available The Amaryllidaceae family is well known for the presence of an exclusive group of alkaloids with a wide range of biological activities. Narcissus serotinus L. is a plant belonging to this family and its geographical distribution is mainly located along the Mediterranean coast. In the present work, specimens collected near Casablanca (Morocco were used to study the alkaloid content of this species. Starting with 350 g of the whole plant we used standard extraction and purification procedures to obtain fractions and compounds for GC-MS and NMR analysis. As well as five known alkaloids, we isolated two new compounds: 1-O-(3´-acetoxybutanoyllycorine and narseronine. The latter has been previously published, but with an erroneous structure.
Choi, Ha-Neul; Jang, Yang-Hee; Kim, Min-Joo; Seo, Min Jeong; Kang, Byoung Won; Jeong, Yong Kee; Kim, Jung-In
BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free...
Choi, Ha-Neul; Jang, Yang-Hee; Kim, Min-Joo; Seo, Min Jeong; Kang, Byoung Won; Jeong, Yong Kee; Kim, Jung-In
Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.
Tobita, Hiroshi; Sato, Shuichi; Yazaki, Tomotaka; Mishiro, Tsuyoshi; Ishimura, Norihisa; Ishihara, Shunnji; Kinoshita, Yoshikazu
Pioglitazone (PIO) has been reported to be effective for nonalcoholic fatty liver disease (NAFLD) and alogliptin (ALO) may have efficacy against NAFLD progression in patients with type 2 diabetes mellitus (T2DM). The present study examined the effectiveness of ALO in a rodent model of NAFLD and diabetes mellitus. KK‑Ay mice were used to produce an NAFLD model via administration of a choline‑deficient (CD) diet. To examine the effects of alogliptin, KK‑Ay mice were provided with a CD diet with 0.03% ALO and/or 0.02% PIO orally for 8 weeks. Biochemical parameters, pathological alterations and hepatic mRNA levels associated with fatty acid metabolism were assessed. Severe hepatic steatosis was observed in KK‑Ay mice fed with a CD diet, which was alleviated by the administration of ALO and/or PIO. ALO administration increased the hepatic carnitine palmitoyltransferase 1a (CPT1a) mRNA expression level and enhanced the Thr172 phosphorylation of AMP‑activated protein kinase α (AMPKα) in the liver. PIO administration tended to decrease the hepatic fatty acid synthase mRNA expression level and increase the serum adiponectin level. Homeostasis model of assessment‑insulin resistance values tended to improve with ALO and PIO administration. ALO and PIO alleviated hepatic steatosis in KK‑Ay mice fed with a CD diet. ALO increased hepatic mRNA expression levels associated with fatty acid oxidation. In addition, the results of the present study suggested that ALO promotes CPT1a expression via Thr172 phosphorylation of AMPKα.
Petrželková, Klára Judita; Zukal, Jan
Roc. 51, č. 4 (2001), s. 395-414 ISSN 0028-2960 R&D Projects: GA AV ČR IAC6087502; GA AV ČR KSK6005114 Institutional research plan: CEZ:AV0Z6093917 Keywords : Eptesicus serotinus * emergence * predation risk Subject RIV: EG - Zoology Impact factor: 0.509, year: 2001
Full Text Available The aim of this study was to investigate the effect of different concentrations of sorbitol on the development of the in vitro culture of D. serotinus in the multiplication phase. The obtained results showed that sorbitol generally had a positive effect, depending on its concentration and explant type. In addition, the presence of sorbitol affected the change of pH value of the media after autoclaving and after 25 days of in vitro culture, which could affect the availability of certain ions to plants. Therefore, the obtained results indicate that sorbitol can be used as an energy source for the in vitro culture of D. serotinus, but this should be further investigated. [Projekat Ministarstva nauke Republike Srbije, br. 43007
Garcimartín, Alba; López-Oliva, M Elvira; Sántos-López, Jorge A; García-Fernández, Rosa A; Macho-González, Adrián; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J
Background: Lipoapoptosis has been identified as a key event in the progression of nonalcoholic fatty liver disease (NAFLD), and hence, antiapoptotic agents have been recommended as a possible effective treatment for nonalcoholic steatohepatitis (NASH). Silicon, included in meat as a functional ingredient, improves lipoprotein profiles and liver antioxidant defenses in aged rats fed a high-saturated fat, high-cholesterol diet (HSHCD). However, to our knowledge, the antiapoptotic effect of this potential functional meat on the liver has never been tested. Objective: This study was designed to evaluate the effect of silicon on NASH development and the potential antiapoptotic properties of silicon in aged rats. Methods: One-year-old male Wistar rats weighing ∼500 g were fed 3 experimental diets containing restructured pork (RP) for 8 wk: 1 ) a high-saturated fat diet, as an NAFLD control, with 16.9% total fat, 0.14 g cholesterol/kg diet, and 46.8 mg SiO 2 /kg (control); 2 ) the HSHCD as a model of NASH, with 16.6% total fat, 16.3 g cholesterol/kg diet, and 46.8 mg SiO 2 /kg [high-cholesterol diet (Chol-C)]; and 3 ) the HSHCD with silicon-supplemented RP with amounts of fat and cholesterol identical to those in the Chol-C diet, but with 750 mg SiO 2 /kg (Chol-Si). Detailed histopathological assessments were performed, and the NAFLD activity score (NAS) was calculated. Liver apoptosis and damage markers were evaluated by Western blotting and immunohistochemical staining. Results: Chol-C rats had a higher mean NAS (7.4) than did control rats (1.9; P silicon substantially affects NASH development in aged male Wistar rats fed an HSHCD by partially blocking apoptosis. These results suggest that silicon-enriched RP could be used as an effective nutritional strategy in preventing NASH. © 2017 American Society for Nutrition.
Full Text Available Background/Aims: Non-alcoholic fatty liver disease (NAFLD is the most common cause of chronic liver disease. This study aims to investigate whether chloride channel 2 (ClC-2 is involved in high fat diet (HFD-induced NAFLD and possible molecular mechanisms. Methods: ClC-2 expression was liver-specifically downregulated using adeno-associated virus in C57BL/6 mice treated with a chow diet or HFD for 12 weeks. Peripheral blood and liver tissues were collected for biochemical and pathological estimation respectively. Western blotting was applied to detect the protein expressions of lipid synthesis-related enzymes and the phosphorylated level of IRS-1, Akt and mTOR. Results: ClC-2 mRNA level was significantly increased in patients with non-alcoholic steatohepatitis, which positively correlated with the plasma levels of alanine transaminase (ALT, aspartate transaminase (AST and insulin. Knockdown of ClC-2 in liver attenuated HFD-induced weight gain, obesity, hepatocellular ballooning, and liver lipid accumulation and fibrosis, accompanied by reduced plasma free fatty acid (FFA, triglyceride (TG, total cholesterol (TC, ALT, AST, glucose and insulin levels and homeostasis model of insulin resistance (HOMA-IR value. Moreover, HFD-treated mice lacking ClC-2 showed inhibited hepatic lipid accumulation via regulating lipid metabolism through decreasing sterol regulatory element binding protein (SREBP-1c expression and its downstream targeting enzymes such as fatty acid synthase (FAS, HMG-CoA reductase (HMGCR and acetyl-Coenzyme A carboxylase (ACCα. In addition, in vivo and in vitro results demonstrated that ClC-2 downregulation in HFD-treated mice or HepG2 cells increased the sensitivity to insulin via activation of IRS-1/Akt/mTOR signaling pathway. Conclusion: Our present study reveals a critical role of ClC-2 in regulating metabolic diseases. Mice lacking ClC-2 are associated with a remarkably beneficial metabolic phenotype, suggesting that decreasing Cl
Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V
The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities. Copyright Â© 2010 Elsevier GmbH. All rights reserved.
Raghdaa Hamdan Al Zarzour
Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri. NAFLD was induced in male Sprague–Dawley rats using a special high-fat diet (HFD. A 50% methanolic extract (50% ME exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16% and visceral fat weight (22%, decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC (48%, low-density lipoprotein (LDL (65%, free fatty acids (FFAs (25%, alanine aminotransferase (ALT (45%, alkaline phosphatase (ALP (38%, insulin concentration (67%, homeostatic model assessment of insulin resistance (HOMA-IR (73%, serum atherogenic ratios TC/high-density lipoprotein (HDL (29%, LDL/HDL (66% and (TC–HDL/HDL (64%, hepatic content of cholesterol (43%, triglyceride (29% and malondialdehyde (MDA (40% compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.
Zhu, Chong-Gui; Liu, Ya-Xin; Wang, Hao; Wang, Bao-Ping; Qu, Hui-Qi; Wang, Bao-Li; Zhu, Mei
The purpose of this study was to determine whether treatment using the active form of vitamin D (1,25(OH) 2 D 3 ) could protect against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats and ameliorate oxidative stress. Male Sprague-Dawley rats were divided into three groups and treated with standard chow, HFD, or HFD plus intraperitoneal injection of 1,25(OH) 2 D 3 (5 μg/kg body weight, twice per week), respectively, for 16 weeks. Serum lipid profiles, hepatic function, intrahepatic lipid, and calcium levels were determined. Hepatic histology was examined using hematoxylin/eosin, Masson's trichrome, and Oil Red O staining. Oxidative stress was assessed by measuring hepatic malondialdehyde (MDA) and F2α-isoprostane content. Expression of nuclear factor-erythroid-2-related factor 2 (Nrf2) and downstream target genes was analyzed using quantitative RT-PCR. 1,25(OH) 2 D 3 treatment improved the serum lipid profile, reduced intrahepatic lipid levels, and attenuated hepatic steatosis and inflammation in HFD rats. Furthermore, MDA and F2α-isoprostane levels in liver tissue were reduced by 1,25(OH) 2 D 3 administration. Although 1,25(OH) 2 D 3 did not regulate the expression of Nrf2 mRNA, it did induce Nrf2 nuclear translocation. The expression of Nrf2 target genes, including Gclc, Nqo1, Sod2, and Cat, was up-regulated by 1,25(OH) 2 D 3 . We conclude that 1,25(OH) 2 D 3 protects against HFD-induced NAFLD by attenuating oxidative stress, inducing NRF2 nuclear translocation, and up-regulating the expression of genes encoding antioxidant enzymes.
Yuan, Fahu; Wang, Hualin; Tian, Yu; Li, Qi; He, Lei; Li, Na; Liu, Zhiguo
Intake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD. Ten male Sprague-Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR). The consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genes per2 and per3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such as Srebf1, Fasn, Scd1, Insig2, Cd36, Cyp7a1, Abcg5, Abcg8 and Pcsk9. Moreover, the expression levels of pro-inflammation genes Mcp1, Socs2, Sema4a, and Cd44 in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation. The present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD.
Verboom, B.; Huitema, H.
The relation between two species of bats, the pipistrelle (Pipistrellus pipistrellus (Schreber, 1774)) and the serotine (Eptesicus serotinus (Schreber, 1774)) and linear landscape elements such as hedgerows, tree lines and tree lanes was studied in an agricultural area in The Netherlands. The
Jansen, P. L. M.
Nonalcoholic steatohepatitis (NASH) is an underdiagnosed liver disease characterised by steatosis, necroinflammation and fibrosis. This disease may eventually develop into cirrhosis and hepatocellular carcinoma. NASH is highly prevalent among obese individuals and among patients with diabetes
Freuling, C; Vos, A; Johnson, N; Kaipf, I; Denzinger, A; Neubert, L; Mansfield, K; Hicks, D; Nuñez, A; Tordo, N; Rupprecht, C E; Fooks, A R; Müller, T
The serotine bat (Eptesicus serotinus) accounts for the vast majority of bat rabies cases in Europe and is considered the main reservoir for European bat lyssavirus type 1 (EBLV-1, genotype 5). However, so far the disease has not been investigated in its native host under experimental conditions. To assess viral virulence, dissemination and probable means of transmission, captive bats were infected experimentally with an EBLV-1a virus isolated from a naturally infected conspecific from Germany. Twenty-nine wild caught bats were divided into five groups and inoculated by intracranial (i.c.), intramuscular (i.m.) or subcutaneous (s.c.) injection or by intranasal (i.n.) inoculation to mimic the various potential routes of infection. One group of bats was maintained as uninfected controls. Mortality was highest in the i.c.-infected animals, followed by the s.c. and i.m. groups. Incubation periods varied from 7 to 26 days depending on the route of infection. Rabies did not develop in the i.n. group or in the negative-control group. None of the infected bats seroconverted. Viral antigen was detected in more than 50% of the taste buds of an i.c.-infected animal. Shedding of viable virus was measured by virus isolation in cell culture for one bat from the s.c. group at 13 and 14 days post-inoculation, i.e. 7 days before death. In conclusion, it is postulated that s.c. inoculation, in nature caused by bites, may be an efficient way of transmitting EBLV-1 among free-living serotine bats.
Świerczyńska, Joanna; Kozieradzka-Kiszkurno, Małgorzata; Bohdanowicz, Jerzy
Chalazal endosperm haustorium in Rhinanthus serotinus consists of a single large binucleate cell. It originates from the primary endosperm cell dividing transversely into two unequal cells: a smaller micropylar cell and a larger chalazal cell. The chalazal cell undergoes a single mitotic division, then lengthens significantly during development and functions as a chalazal endosperm haustorium. In this paper, immunofluorescent techniques, rhodamine phalloidin assay, and electron microscopy were used to examine the actin and tubulin cytoskeleton during the development of the chalazal haustorium. During the differentiation stage, numerous longitudinally oriented bundles of microfilaments ran along the axis of transvacuolar strands in haustorium. Microtubules formed intensely fluorescent areas near the nuclear envelope and also formed radial perinuclear microtubule arrays. In the fully differentiated haustorium cell, the actin cytoskeleton formed dense clusters of microfilaments on the chalazal and micropylar poles of the haustorium. Numerous microfilament bundles occurred near wall ingrowths on the chalazal wall. There were numerous clusters of microfilaments and microtubules around the huge lobed polytenic haustorial nuclei. The microfilaments were oriented longitudinally to the long axis of the haustorium cell and surrounded both nuclei. The microtubules formed radial perinuclear systems which were appeared to radiate from the surface of the nuclear envelope. The early stage of degeneration of the chalazal haustorium was accompanied by the degradation of microtubules and disruption of the parallel orientation of microtubules in the chalazal area of the cell. The degree of vacuolization increased, autophagous vacuoles appeared and the number of vesicles decreased.
Moussy, C; Atterby, H; Griffiths, A G F; Allnutt, T R; Mathews, F; Smith, G C; Aegerter, J N; Bearhop, S; Hosken, D J
Understanding of the movements of species at multiple scales is essential to appreciate patterns of population connectivity and in some cases, the potential for pathogen transmission. The serotine bat (Eptesicus serotinus) is a common and widely distributed species in Europe where it frequently harbours European bat lyssavirus type 1 (EBLV-1), a virus causing rabies and transmissible to humans. In the United Kingdom, it is rare, with a distribution restricted to south of the country and so far the virus has never been found there. We investigated the genetic structure and gene flow of E. serotinus across the England and continental Europe. Greater genetic structuring was found in England compared with continental Europe. Nuclear data suggest a single population on the continent, although further work with more intensive sampling is required to confirm this, while mitochondrial sequences indicate an east-west substructure. In contrast, three distinct populations were found in England using microsatellite markers, and mitochondrial diversity was very low. Evidence of nuclear admixture indicated strong male-mediated gene flow among populations. Differences in connectivity could contribute to the high viral prevalence on the continent in contrast with the United Kingdom. Although the English Channel was previously thought to restrict gene flow, our data indicate relatively frequent movement from the continent to England highlighting the potential for movement of EBLV-1 into the United Kingdom.
Klapper, Gilbert; Vodrážková, Stanislava
Klapper, G. and Vodražkova, S. 2013. Ontogenetic and intraspecific variation in the late Emsian - Eifelian (Devonian) conodonts Polygnathus serotinus and P. bultyncki in the Prague Basin (Czech Republic) and Nevada (western U.S.). Acta Geologica Polonica, 63 (2), 153-174, Warszawa. Samples from populations of Polygnathus serotinus Telford 1975 and P. bultyncki Weddige 1977 from the Prague Basin and Nevada display normal variation for Devonian conodont species. A considerable number of previous authors, however, have proposed unnecessary synonyms of these two species, primarily because they have not recognized ontogenetic variation. In contrast, we interpret the variation as ontogenetic as well as intraspecific and present detailed synonymies as a result. A third species, P. praetrigonicus Bardashev 1992, which has been carried in open nomenclature for many years, is an important indicator of the basal costatus Zone in the Prague Basin, New York, and Nevada. We review the stratigraphic distribution of these three species and the conodont zonation across the Emsian-Eifelian (Lower-Middle Devonian) boundary. Polygnathus pseudocostatus sp. nov. (partitus-costatus zones, central Nevada) is described herein. We have observed a decrease in the pit size during ontogeny in P. bultyncki although we have not measured enough specimens to rule out intraspecific versus ontogenetic variation.
... Eating, Diet, & Nutrition Clinical Trials Wilson Disease Nonalcoholic Fatty Liver Disease & NASH View or Print All Sections Definition & Facts Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat ...
Patrick-Melin, A J; Kalinski, M I; Kelly, K R
Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage...... that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...
Zhu, Wenhua; Chen, Siwen; Chen, Ronggui; Peng, Zhiqing; Wan, Jun; Wu, Benyan
Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease, for which there is currently no safe and effective drug for therapy. In this study, we explored the effects of taurine, tea polyphenols (TPs), or a combination thereof, on NASH rats. Rats were divided into a normal group, a high-fat diet induced model group and a treatment group (including taurine, TPs, or taurine + TPs treatment for 8 weeks). Twelve weeks later, all rats were sacrificed, and serum transaminase, lipid and lipopolysaccharide levels and hepatic oxidative stress levels were determined. Histological changes were evaluated. In NASH rats, hepatocyte damage, lipid disturbance, oxidative stress and elevated lipopolysaccharide levels were confirmed. Taurine treatment alleviated hepatocyte damage and oxidative stress. TPs treatment improved lipid metabolism and increased hepatic antioxidant activity. The therapeutic effects of taurine + TPs treatment on hepatocyte damage, lipid disturbance, and oxidative stress were superior to those of taurine and TPs treatment, respectively. Taurine, TPs and their combination all decreased serum lipopolysaccharide levels in NASH rats, but the combination of the compounds caused these levels to decrease more significantly than taurine or TPs treatment alone. Taurine combined with TPs treatment could relieve NASH by alleviating hepatocyte damage, decreasing oxidative stress and improving lipid metabolism and gut flora disturbance partly. Taurine and TPs combination may act as a new effective medicine for treating NASH patients.
Full Text Available Psoralea corylifolia L. (PC is a traditional Chinese herb used to treat yang deficiency of the spleen and kidney in pediatric disease. Recent studies have shown its liver protection and anti-oxidative effects. The aim of this study was to explore the effect and mechanism of PC on nonalcoholic steatohepatitis in juvenile mice. The juvenile mouse model of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH was established by being fed a high-fat diet in maternal-offspring manner. PC granules were prepared and the quality was assessed. The main components were identified by high performance liquid chromatography. Then, different dosages of PC were administered for 6 weeks. Homeostatic model assessment of insulin resistance, plasma liver enzymes, hepatic morphology, hepatic superoxide anion, and triglyceride/total cholesterol levels were examined. The changes of nuclear factor-κB (NF-κB activity phosphatidylinositol 3 kinase (PI3K/protein kinase B (Akt and protein kinase C-α (PKC-α/nicotinamide-adenine dinucleotide phosphate (NADPH oxidase signaling pathways in hepatic tissues were also determined. Our data demonstrated that PC significantly improved liver dysfunction, liver triglyceride/total cholesterol accumulation and insulin resistance in juvenile NAFLD/NASH mice. PC also alleviated hepatic steatosis, inflammatory cell infiltration, and fibroplasia in the portal area. Additionally, PC inhibited the activation of NF-κB and the mRNA expression of inflammatory factors while enhancing PI3K/Akt signaling in hepatic tissues. PC could also reduce hepatic superoxide anion levels, and NADPH oxidase activity as well as p47phox protein expression and PKCα activation in hepatic tissues. The results suggest that PC is effective in the treatment of NASH in juvenile mice. The mechanism may be related to the attenuation of hepatic oxidative stress through the PKC-α/NADPH oxidase signaling pathway.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is increasing in pediatric age group parallel to the growing prevalence of obesity and overweight all around the world. So changing in life style and interventions on obesogenic environment is cornerstone of NAFLD therapy in obese children. Some experts recommend that children and adolescents be encouraged to follow a low-fat, low-glycemic-index diet that includes eating a minimum of 5 servings of vegetables and fruits daily, engaging in physical activity for at least 1 hour daily, and minimizing television/computer time to 2 hours daily. In spite of effectiveness of weight loss and exercise in improvement NAFLD, this goal is very difficult to be achieved and pharmacological approaches have become necessary. Pharmacologic therapies against one or more specific factors and/or molecules involved in the development of NAFLD (i.e., insulin resistance, free fatty acid lipid toxicity, and oxidative stress also might slow the progression of NAFLD to NASH or cirrhosis. On this basis, insulin sensitizers, antioxidants, cytoprotective agents, and dietary supplementations have been evaluated in pediatric clinical trials but there is no approved pharmacologic therapy for NAFLD or NASH. Not all obese children affected by NAFLD. Diet modification and regular exercise beside to serial medical follow up highly suggested for this group of children. Normal weight and thin children with NAFLD or NASH should be investigated appropriately in a logical manner based on causes of primary liver steatosis in children and treatment of underlying disease can cause improvement fatty liver in these patients. Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Children; Steatosis; Treatment
Wu, Sheng-di; Li, Lei; Wang, Ji-yao
The aim of this study was to evaluate the effects of ursodeoxycholic acid on patients with nonalcoholic steatohepatitis using meta-analysis. PubMed, EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Databases, and article references were searched. We included randomized controlled trials using liver biopsy as a reference standard. We identified three eligible studies. Among histological responses, only lobular inflammation improved in the high-dose ursodeoxycholic acid subgroup compared with the control group [mean deviation (MD): -0.23 (-0.40, -0.06), P=0.008]. However, fibrosis may tend to increase [MD: 0.08 (-0.04, 0.20), P=0.17]. Among biochemical responses, γ-glutamyl transpeptidase reduction was significantly greater in the ursodeoxycholic acid group than in the placebo group, and the reduction tendency was only shown in the high-dose subgroup [MD: -35.58 (-52.60, -18.56), Pursodeoxycholic acid subgroup compared with the control group [MD: 0.43 (0.14, 0.72), P=0.004]. Ursodeoxycholic acid-treated patients did not differ significantly from control patients with regard to alanine transaminase, aspartate aminotransferase, and alkaline phosphatase activities. Adverse events were nonspecific and considered of no major clinical relevance. Ursodeoxycholic acid in monotherapy has no substantial positive effect on nonalcoholic steatohepatitis.
Bragg, Marie A; Miller, Alysa N; Roberto, Christina A; Sam, Rachel; Sarda, Vishnudas; Harris, Jennifer L; Brownell, Kelly D
Food and nonalcoholic beverage companies spend millions of dollars on professional sports sponsorships, yet this form of marketing is understudied. These sponsorships are valuable marketing tools but prompt concerns when unhealthy products are associated with popular sports organizations, especially those viewed by youth. This descriptive study used Nielsen audience data to select 10 sports organizations with the most 2-17 year old viewers of 2015 televised events. Sponsors of these organizations were identified and assigned to product categories. We identified advertisements promoting food and/or nonalcoholic beverage sponsorships on television, YouTube, and sports organization Web sites from 2006 to 2016, and the number of YouTube advertisement views. The nutritional quality of advertised products was assessed. Youth watched telecasts associated with these sports organizations over 412 million times. These organizations had 44 food and/or nonalcoholic beverage sponsors (18.8% of sponsors), second to automotive sponsors ( n = 46). The National Football League had the most food and/or nonalcoholic beverage sponsors ( n = 10), followed by the National Hockey League ( n = 7) and Little League ( n = 7). We identified 273 advertisements that featured food and/or nonalcoholic beverage products 328 times and product logos 83 times (some advertisements showed multiple products). Seventy-six percent ( n = 132) of foods had unhealthy nutrition scores, and 52.4% ( n = 111) of nonalcoholic beverages were sugar-sweetened. YouTube sponsorship advertisements totaled 195.6 million views. Sports sponsorships are commonly used to market unhealthy food and nonalcoholic beverages, exposing millions of consumers to these advertisements. Copyright © 2018 by the American Academy of Pediatrics.
Longitudinal survey of two serotine bat (Eptesicus serotinus maternity colonies exposed to EBLV-1 (European Bat Lyssavirus type 1: Assessment of survival and serological status variations using capture-recapture models.
Full Text Available This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 (EBLV-1 antibodies in serotine bat (Eptesicus serotinus maternity colonies located in the North-East of France. This species is currently considered as the main EBLV-1 reservoir. Multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. Considering the period of study, analyses revealed that survival and recapture probabilities were not affected by the serological status of individuals, confirming the capacity of bats to be exposed to lyssaviruses without dying. Five bats have been found with EBLV-1 RNA in the saliva at the start of the study, suggesting they were caught during virus excretion period. Among these bats, one was interestingly recaptured one year later and harbored a seropositive status. Along the survey, some others bats have been observed to both seroconvert (i.e. move from a negative to a positive serological status and serorevert (i.e. move from a positive to a negative serological status. Peak of seroprevalence reached 34% and 70% in site A and B respectively. On one of the 2 sites, global decrease of seroprevalence was observed all along the study period nuanced by oscillation intervals of approximately 2-3 years supporting the oscillation infection dynamics hypothesized during a previous EBLV-1 study in a Myotis myotis colony. Seroprevalence were affected by significantly higher seroprevalence in summer than in spring. The maximum time observed between successive positive serological statuses of a bat demonstrated the potential persistence of neutralizing antibodies for at least 4 years. At last, EBLV-1 serological status transitions have been shown driven by age category with higher seroreversion frequencies in adults than in juvenile. Juveniles and female adults seemed indeed acting as distinct drivers
Longitudinal survey of two serotine bat (Eptesicus serotinus) maternity colonies exposed to EBLV-1 (European Bat Lyssavirus type 1): Assessment of survival and serological status variations using capture-recapture models.
Robardet, Emmanuelle; Borel, Christophe; Moinet, Marie; Jouan, Dorothée; Wasniewski, Marine; Barrat, Jacques; Boué, Franck; Montchâtre-Leroy, Elodie; Servat, Alexandre; Gimenez, Olivier; Cliquet, Florence; Picard-Meyer, Evelyne
This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 (EBLV-1) antibodies in serotine bat (Eptesicus serotinus) maternity colonies located in the North-East of France. This species is currently considered as the main EBLV-1 reservoir. Multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. Considering the period of study, analyses revealed that survival and recapture probabilities were not affected by the serological status of individuals, confirming the capacity of bats to be exposed to lyssaviruses without dying. Five bats have been found with EBLV-1 RNA in the saliva at the start of the study, suggesting they were caught during virus excretion period. Among these bats, one was interestingly recaptured one year later and harbored a seropositive status. Along the survey, some others bats have been observed to both seroconvert (i.e. move from a negative to a positive serological status) and serorevert (i.e. move from a positive to a negative serological status). Peak of seroprevalence reached 34% and 70% in site A and B respectively. On one of the 2 sites, global decrease of seroprevalence was observed all along the study period nuanced by oscillation intervals of approximately 2-3 years supporting the oscillation infection dynamics hypothesized during a previous EBLV-1 study in a Myotis myotis colony. Seroprevalence were affected by significantly higher seroprevalence in summer than in spring. The maximum time observed between successive positive serological statuses of a bat demonstrated the potential persistence of neutralizing antibodies for at least 4 years. At last, EBLV-1 serological status transitions have been shown driven by age category with higher seroreversion frequencies in adults than in juvenile. Juveniles and female adults seemed indeed acting as distinct drivers of the rabies
Ionică Floriana Elvira
Full Text Available Background and aims: Nonalcoholic fatty liver disease (NAFDL is a multifactorial condition with a wide spectrum of histological severities, from asymptomatic hepatic steatosis to nonalcoholic steatohepatitis (NASH with or without fibrosis. NAFLD is highly common and potentially serious in children and adolescents and affects approximately one third of the general population. It is closely associated with obesity, insulin resistance and dyslipidemia. NASH is a histological diagnosis and has a great significance because it can progress to cirrhosis, liver failure, and hepatocellular carcinoma (HCC, and is associated with both increased cardiovascular and liver related mortality. The purpose of this review is to summarize the evidence for current potential therapies of NAFLD.
Brent A Neuschwander-Tetri
Full Text Available Nonalcoholic steatohepatitis (NASH is a histological diagnosis applied to a constellation of liver biopsy findings that develop in the absence of alcohol abuse. Steatosis, a mixed cellular inflammatory infiltrate across the lobule, evidence of hepatocyte injury and fibrosis are the findings that can be seen. This entity is often identified during evaluation of elevated aminotransferases after exclusion of viral, metabolic and other causes of liver disease. Obesity is a major risk factor for NASH. The role of diabetes is less certain, although evidence is accumulating that hyperinsulinism may play an important pathophysiological role. Patients sometimes suffer from right upper quadrant abdominal pain and fatigue; examination may reveal centripetal obesity and hepatomegaly. Although patients are often discovered because of persistent aminotransferase elevations, these enzymes can be normal in NASH. When they are elevated, the alanine aminotransferase level is typically significantly greater than the aspartate aminotransferase level. This can be particularly helpful for excluding occult alcohol abuse. Imaging studies identify hepatic steatosis when the amount of fat in the liver is significant; however, imaging does not distinguish benign steatosis from NASH. Ultimately a liver biopsy is needed to diagnose NASH. The biopsy may be useful for establishing prognosis based on the presence or absence of fibrosis and for excluding other unexpected causes of liver enzyme elevations. Weight loss is the mainstay of treatment for obese patients. About 15% to 40% of NASH patients develop fibrosis; how many of these cases progress to cirrhosis is unknown, but about 1% of liver transplants are performed with a pretransplant diagnosis of NASH.
Macías, Juan; Pineda, Juan A; Real, Luis M
Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.
Energy services play an important role in human welfare. India faces acute energy poverty indicating lack of access of clean energy fuels. Access to electricity is limited to 56% households in India and about 89% of rural households depend on polluting energy sources. Energy poverty impacts income poverty as poor find it difficult to acquire high priced cleaner fuels. It also adversely impacts the socio economic conditions of women. The paper highlights the linkage of energy poverty with income poverty and gender inequality. It analyses measures taken to alleviate energy poverty and recommends regulatory and policy measures as way forward.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin.
Full Text Available To establish a versatile means for screening and management of nonalcoholic steatohepatitis (NASH, shear wave velocity was measured in 20 normal controls and 138 consecutive nonalcoholic fatty liver disease (NAFLD cases. Referencing biochemical properties in 679 healthy volunteers, a formula to distinguish NASH suspects was established and validated in another cohort of 138 histologically proven NAFLD cases. NASH and simple steatosis (SS suspects were selected based on a plot of shear wave velocity against age. A formula consisting of five factors (γ-glutamyl transpeptidase, alkaline phosphatase, platelet counts, body mass index, and presence/absence of type 2 diabetes mellitus distinguished NASH suspects from SS suspects with area under the receiver operating characteristic curve values of 86% and 84% in the development and validation cohorts. Among 25 NAFLD cases in which shear wave velocity was repeatedly measured, 8 and 9 cases revealed an increase or decrease, respectively, of shear wave velocity in the entire liver, and the corresponding change in shear wave velocity was primarily observed in the right lobe or the left lateral segment, respectively. These results suggest that the new formula and sequential shear wave velocity measurements at each segment enable high throughput screening of NASH suspects and noninvasive assessment of pathophysiological alleviation/aggravation in cases of NASH.
Miyake, Teruki; Matsuura, Bunzo; Furukawa, Shinya; Todo, Yasuhiko; Yamamoto, Shin; Yoshida, Osamu; Imai, Yusuke; Watanabe, Takao; Yamamoto, Yasunori; Hirooka, Masashi; Tokumoto, Yoshio; Kumagi, Teru; Abe, Masanori; Seike, Hirotaka; Miyauchi, Shozo; Hiasa, Yoichi
3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.
Wright, M H; Obitz, F W
Alcoholic and nonalcoholic subjects rated the degree of control that they and others possess over future life events. Alcoholics attributed less personal control over events to themselves than nonalcoholics did. Alcoholics also attributed less control to themselves than to others, whereas nonalcoholics attributed more control to themselves than to others. These differences prevailed despite the similar socioeconomic and demographic characteristics, recent life experiences and beliefs concerning the general controllability of events of both alcoholics and nonalcoholics. The attributions of alcoholics were consistent with others' notions of self-handicapping. The attributions of nonalcoholics were consistent with control motivation. Alcoholics who attributed less control to themselves than to others more frequently failed to complete treatment than did alcoholics who attributed more control to themselves.
In it, we have argued that past poverty alleviation policies and programmes have been elitist and non-participatory, especially by the target population. In most cases the designs for poverty alleviations are characterized by improper conceptualization, grandiosity and lack of social justice even in implementation. Based on ...
Küçükazman, Metin; Ata, Naim; Dal, Kürşat; Yeniova, Abdullah Özgür; Kefeli, Ayşe; Basyigit, Sebahat; Aktas, Bora; Akin, Kadir Okhan; Ağladioğlu, Kadir; Üre, Öznur Sari; Topal, Firdes; Nazligül, Yaşar; Beyan, Esin; Ertugrul, Derun Taner
OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver ...
Full Text Available The syndrome of spatial neglect results from the combination of a number of deficits in attention, with patients demonstrating both spatially lateralised and non-lateralised impairments. Previous reports have hinted that there may be a motivational component to neglect and that modulating this might alleviate some of the debilitating symptoms. Additionally, recent work on the effects of reward on attention in healthy participants has revealed improvements across a number of paradigms. As the primary deficit in neglect has been associated with attention, this evidence for reward’s effects is potentially important. However, until very recently there have been few empirical studies addressing this potential therapeutic avenue. Here we review the growing body of evidence that attentional impairments in neglect can be reduced by motivation, for example in the form of preferred music or anticipated monetary reward, and discuss the implications of this for treatments for these patients. Crucially these effects of positive motivation are not observed in all patients with neglect, suggesting that the consequences of motivation may relate to individual lesion anatomy. Given the key role of dopaminergic systems in motivational processes, we suggest that motivational stimulation might act as a surrogate for dopaminergic stimulation. In addition, we consider the relationship between clinical post stroke apathy and lack of response to motivation.
Noureddin, Mazen; Zhang, Alice; Loomba, Rohit
Introduction Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60–80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). A subset of patients with hepatic steatosis progress to NASH, while 15–20% of patients with NASH develop cirrhosis. This progression is thought to be multifactorial, and there are currently no FDA-approved medications for the treatment of NASH. Areas covered We review drugs currently in Phase II and III clinical trials for treatment of NAFLD and NASH, including their mechanisms of action, relationship to the pathophysiology of NASH, and rationale for their development. Expert opinion The treatment of NASH is complex and necessitates targeting a number of different pathways. Combination therapy, preferably tailored toward the disease stage and severity, will be needed to achieve maximum therapeutic effect. With multiple agents currently being developed, there may soon be an ability to effectively slow or even reverse the disease process in many NAFLD/NASH patients. PMID:27501374
Full Text Available Abstract: With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the actual pathophysiology of NAFLD is complex and involves multiple pathways. Moreover, NAFLD is not always benign, and patients with non-alcoholic steatohepatitis (NASH are at increased risk of developing advanced stages of liver disease. It has also been shown that NAFLD is not only a liver disease, but is also associated with multiple extrahepatic manifestations, including cardiovascular diseases, type 2 diabetes, and low bone mineral density. Although the data is scarce in the pediatric population, some studies have suggested that long-term mortality and the requirement of liver transplantation will continue to increase in patients with NAFLD. More studies are needed to better understand the natural history of NAFLD, especially in the pediatric age group.
Full Text Available Tropical Calcific Pancreatitis (TCP is a type of chronic calcific nonalcoholic pancreatitis. Similar to nonalcoholic chronic pancreatitis, it presents in the second and third decades of life; however this type is reported mostly in the developing tropical and subtropical countries. It is associated with the formation of pancreatic calculi and a high probability of developing insulin-dependent diabetes mellitus. Epidemiologic studies have shown that these patients have an increased risk of developing pancreatic carcinoma. The etiology of TCP remains uncertain, with the current consensus suggesting genetics as well as possible toxicity from consuming large amounts of cassava, a tuber. Definite diagnosis of TCP requires younger age of onset, history of malnutrition, and presence of diabetes mellitus along with extensive pancreatic calcification and ductal calculi. When patients meet most but not all of these conditions the term Idiopathic Chronic Pancreatitis (ICP is used. This is a case of a 44-year-old man who presented with most features seen in TCP, and however, was diagnosed with ICP.
Poverty Alleviation Programmes and Economic Development in Nigeria: A Comparative Assessment of Asa and Ilorin West Local ... Journal Home > Vol 3, No 4 (2009) > ... and worst hit income inequality group with about 84percent of total
Exercise alleviates depression related systemic inflammation in chronic obstructive pulmonary disease patients. ... African Health Sciences ... Currently, physical activity is an important lifestyle factor that has the potential to modify inflammatory ...
... individual is considered to have a fatty liver (hepatic steatosis) if the liver contains more than 5 to ... Resources Genetic Testing (2 links) Genetic Testing Registry: Fatty liver disease, nonalcoholic 1 Genetic Testing Registry: Fatty liver ...
Development and Quality Evaluation of a Non-Alcoholic Beverage from Cocoyam ( Xanthosoma sagittifolium and Colocasia esculenta ) ... Nigerian Food Journal ... evaluation were conducted on the products to assess the highest preference.
affect NAFLD development and progression besides dyslip- idaemia. .... analysis adjusted for gender, age, smoking status and BMI. Two-sided P ... Smokers (%). 10.0. 15.2 .... 2009 Metabolic syndrome and non-alcoholic fatty liver disease.
Reddy, Srinevas K; Hyder, Omar; Marsh, J Wallis; Sotiropoulos, Georgios C; Paul, Andreas; Alexandrescu, Sorin; Marques, Hugo; Pulitano, Carlo; Barroso, Eduardo; Aldrighetti, Luca; Geller, David A; Sempoux, Christine; Herlea, Vlad; Popescu, Irinel; Anders, Robert; Rubbia-Brandt, Laura; Gigot, Jean-Francois; Mentha, Giles; Pawlik, Timothy M
The objective of this report was to determine the prevalence of underlying nonalcoholic steatohepatitis in resectable intrahepatic cholangiocarcinoma. Demographics, comorbidities, clinicopathologic characteristics, surgical treatments, and outcomes from patients who underwent resection of intrahepatic cholangiocarcinoma at one of eight hepatobiliary centers between 1991 and 2011 were reviewed. Of 181 patients who underwent resection for intrahepatic cholangiocarcinoma, 31 (17.1 %) had underlying nonalcoholic steatohepatitis. Patients with nonalcoholic steatohepatitis were more likely obese (median body mass index, 30.0 vs. 26.0 kg/m(2), p < 0.001) and had higher rates of diabetes mellitus (38.7 vs. 22.0 %, p = 0.05) and the metabolic syndrome (22.6 vs. 10.0 %, p = 0.05) compared with those without nonalcoholic steatohepatitis. Presence and severity of hepatic steatosis, lobular inflammation, and hepatocyte ballooning were more common among nonalcoholic steatohepatitis patients (all p < 0.001). Macrovascular (35.5 vs. 11.3 %, p = 0.01) and any vascular (48.4 vs. 26.7 %, p = 0.02) tumor invasion were more common among patients with nonalcoholic steatohepatitis. There were no differences in recurrence-free (median, 17.0 versus 19.4 months, p = 0.42) or overall (median, 31.5 versus 36.3 months, p = 0.97) survival after surgical resection between patients with and without nonalcoholic steatohepatitis. Nonalcoholic steatohepatitis affects up to 20 % of patients with resectable intrahepatic cholangiocarcinoma.
Noto, Haruka; Tokushige, Katsutoshi; Hashimoto, Etsuko; Taniai, Makiko; Shiratori, Keiko
Lack of exercise and excessive food intake are known to be the important causes of nonalcoholic steatohepatitis (NASH). To elucidate the relationship between lifestyle and NASH, we surveyed exercise and dietary habits, comparing them among 171 biopsy-proven NASH patients, 29 nonalcoholic fatty liver (NAFL) patients and 49 normal subjects. Dietary habits including the duration of dinner time, amount of rice at dinner, and weekly frequencies of meat, fries, Chinese noodles, sweets, and instant ...
Ma, Xiaoqing; Du, Wenhua; Shao, Shanshan; Yu, Chunxiao; Zhou, Lingyan; Jing, Fei
Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27%) and liver triglycerides (314.75%) compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.
Full Text Available Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD, high fat diet (HFD, and HFD administered with vildagliptin (50 mg/Kg (V-HFD. After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27% and liver triglycerides (314.75% compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.
Mindy C.W. Lam
Full Text Available Familial hypobetalipoproteinemia (FHBL is a rare genetic disorder of lipid metabolism that is associated with abnormally low serum levels of low-density lipoprotein (LDL cholesterol and apolipoprotein B. It is an autosomal co-dominant disorder, and depending on zygosity, the clinical manifestations may vary from none to neurological, endocrine, hematological or liver dysfunction. Nonalcoholic fatty liver disease is common in persons with FHBL, however progression to nonalcoholic steatohepatitis is unusual. We describe here a patient with a novel APOB mutation, V703I, which appears to contribute to the severity of the FHBL phenotype. He had liver enzyme abnormalities, increased echogenicity of the liver consistent with steatosis, very low LDL cholesterol at 0.24 mmol/l (normal 1.8–3.5 mmol/l and an extremely low apolipoprotein B level of 0.16 g/l (normal 0.6–1.2 g/l. APOB gene sequencing revealed him to be a compound heterozygote with two mutations (R463W and V703I. APOB R463W has previously been reported to cause FHBL. Genetic sequencing of his first-degree relatives identified the APOB V703I mutation in his normolipidemic brother and father and the APOB R463W mutation in his mother and sister, both of whom have very low LDL cholesterol levels. These results suggest that the APOB V703I mutation alone does not cause the FHBL phenotype. However, it is possible that it has a contributory role to a more aggressive phenotype in the presence of APOB R463W.
Lee, Seung Soo; Park, Seong Ho
Nonalcoholic fatty liver disease (NAFLD) is a frequent cause of chronic liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH)-related liver cirrhosis. Although liver biopsy is still the gold standard for the diagnosis of NAFLD, especially for the diagnosis of NASH, imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy. Ultrasonography is a well-established and cost-effective imaging technique for the diagnosis of hepatic steatosis, especially for screening a large population at risk of NAFLD. Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis, operator-dependent, and rather qualitative. Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard. However, computed tomography may be effective in specific clinical situations, such as evaluation of donor candidates for hepatic transplantation. Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice, especially for longitudinal follow-up of patients with NAFLD. Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis. This article will review current imaging methods used to evaluate hepatic steatosis, including the diagnostic accuracy, limitations, and practical applicability of each method. It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD. PMID:24966609
Nonalcoholic fatty liver disease (NAFLD), formerly called nonalcoholic steatohepatitis, is characterized by hepatic steatosis and abnormal triglyceride accumulation in liver cells. Its etiology, pathophysiology, and pathogenesis are still poorly understood. Some have suggested that the increased in...
Lake, A.D.; Novák, Petr; Hardwick, R.N.; Flores-Keown, B.; Zhao, F.; Klimecki, W. T.; Cherrington, N.J.
Roč. 137, č. 1 (2014), s. 26-35 ISSN 1096-6080 Institutional support: RVO:60077344 Keywords : nonalcoholic fatty liver disease * lipotoxicity * nonalcoholic steatohepatitis Subject RIV: CE - Biochemistry Impact factor: 3.854, year: 2014
Feng, Simin; Gan, Ling; Yang, Chung S; Liu, Anna B; Lu, Wenyun; Shao, Ping; Dai, Zhuqing; Sun, Peilong; Luo, Zisheng
To study the effects of stigmasterol and β-sitosterol on high-fat Western diet (HFWD)-induced nonalcoholic fatty liver disease (NAFLD), lipidomic analyses were conducted in liver samples collected after 33 weeks of the treatment. Principal component analysis showed these phytosterols were effective in protecting against HFWD-induced NAFLD. Orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and S-plots showed that triacylglycerols (TGs), phosphatidylcholines, cholesteryl esters, diacylglycerols, and free fatty acids (FFAs) were the major lipid species contributing to these discriminations. The alleviation of NAFLD is mainly associated with decreases in hepatic cholesterol, TGs with polyunsaturated fatty acids, and alterations of free hepatic FFA. In conclusion, phytosterols, at a dose comparable to that suggested for humans by the FDA for the reduction of plasma cholesterol levels, are shown to protect against NAFLD in this long-term (33-week) study.
Setji, Tracy L; Holland, Nicole D; Sanders, Linda L; Pereira, Kathy C; Diehl, Anna Mae; Brown, Ann J
Nonalcoholic fatty liver disease and polycystic ovary syndrome (PCOS) are both associated with insulin resistance. Thus, women with PCOS may have an increased prevalence of nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH). The objective of the study was to determine the prevalence and characteristics of NASH and abnormal aminotransferase activity in women with PCOS. The study is a retrospective chart review. The setting is an academic endocrinology clinic. Patients were 200 women with PCOS, defined as irregular menses and hyperandrogenism. Biopsy-documented NASH and aminotransferase levels were the main outcome measures. Fifteen percent (29 of 200) had aspartate aminotransferase and/or alanine aminotransferase more than 60 U/liter. Women with aminotransferase elevations had lower high-density lipoprotein (HDL) (41 vs. 50 mg/dl, P = 0.006), higher triglycerides (174 vs. 129 mg/dl, P = 0.024), and higher fasting insulin (21 vs. 12 microIU/ml, P = 0.036) compared with women with normal aminotransferases. Six women (mean age 29 yr) with persistent aminotransferase elevations underwent liver biopsy. All six had NASH with fibrosis. Compared with the 194 of 200 PCOS women who did not undergo biopsy, women with biopsy-documented NASH had lower HDL (median 34 vs. 50 mg/dl, P PCOS. Low HDL, high triglycerides, and high fasting insulin were associated with abnormal aminotransferase activity. Some women already had evidence of NASH with fibrosis. Further studies are needed to evaluate whether to screen PCOS women for liver disease at an earlier age than is currently recommended for the general population.
Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. Alleviating gizzard erosion with Hepasan® - Provisional Communication. K Boa-Amponsem, A Osei-Somuah. Full Text:.
The paper concludes that well-articulated vocational education policy and programmes will assist in employment generations and poverty reduction in Nigeria. Keywords: Alleviating Poverty, Vocational Education, Nigerian Experience Journal of Technology and Education in Nigeria Vol. 10 (2) 2005: pp. 10-14 ...
Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women hence Chinese herbal medicine (CHM) has been chosen by many clinicians and patients as alternative treatment for PCOS. The present study was to explore the effects of CHM in alleviating hyperandrogenism of PCOS ...
Anbazhagan, Arivarasu N; Thaqi, Mentor; Priyamvada, Shubha; Jayawardena, Dulari; Kumar, Anoop; Gujral, Tarunmeet; Chatterjee, Ishita; Mugarza, Edurne; Saksena, Seema; Onyuksel, Hayat; Dudeja, Pradeep K
The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1β, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate that GLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD). Published by Elsevier Inc.
Chow, Monica D; Lee, Yi-Horng; Guo, Grace L
Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is marked by the presence of macrosteatosis on liver histology but is often clinically asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is a more severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism by which simple steatosis progresses to steatohepatitis is not entirely clear. However, multiple pathways have been proposed. A common link amongst many of these pathways is disruption of the homeostasis of bile acids. Other than aiding in the absorption of lipids and lipid-soluble vitamins, bile acids act as ligands. For example, they bind to farnesoid X receptor, which is critically involved in many of the pathways responsible for maintaining bile acid, glucose, and lipid homeostasis. Alterations to these pathways can lead to dysregulation of energy balance and increased inflammation and fibrosis. Repeated insults over time may be the key to development of steatohepatitis. For this reason, current drug therapies target aspects of these pathways to try to reduce and halt inflammation and fibrosis. This review will focus on the role of bile acids in these various pathways and how changes in these pathways may result in steatohepatitis. While there is no approved pharmaceutical treatment for either hepatic steatosis or steatohepatitis, this review will also touch upon the multitude of potential therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available As the etiology of hepatocellular carcinoma (HCC has been changing, the incidence of HCC related to nonalcoholic fatty liver disease (NAFLD is gradually increasing in developed countries in Europe and America and some countries in Asia. This article introduces the close association between NAFLD and HCC, risk factors, clinicopathological features, and prevention and screening, and points out that although the incidence of NAFLD is not as high as that of hepatitis B- or hepatitis C-related HCC, there are a large absolute number of NAFLD patients, especially the high-risk patients with diabetes and obesity, or liver fibrosis/cirrhosis, due to a huge base number of NAFLD patients. NAFLD-related HCC is commonly seen in the elderly with various comorbidities and a poor prognosis. This article also points out that the prevention should focus on the effective treatment of NAFLD. The strict screening of high-risk population is the strategy for the diagnosis of early-stage HCC. At present, the sensitivity of alpha-fetoprotein is relatively low, and imaging examinations including computed tomography are the main screening methods; however, there are no measures for early warning of NAFLD-related HCC.
Carrascosa, J M; Bonanad, C; Dauden, E; Botella, R; Olveira-Martín, A
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.
Marino, Laura; Jornayvaz, François R
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.
Ma, Hong; Cui, Fan; Dong, Jing-Jing; You, Guo-Ping; Yang, Xiang-Jiu; Lu, Hua-Dong; Huang, Yan-Ling
To explore the therapeutic role of globular adiponectin (gAd) in high-fat diet/streptozotocin (STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease (NAFLD). Seven rats were fed a basic diet (normal control group; NC) during the experiment. Experimental rats (14 rats) were given a high-fat diet for 4 wk and were then injected with STZ to induce type 2 diabetes mellitus (T2DM) and NAFLD. Half of the T2DM/NAFLD rats were randomly injected intraperitoneally with gAd for 7 d (gAd-treated group), while the other 7 rats (T2DM/NAFLD group) received 0.9% saline. Plasma biochemical parameters and insulin concentrations were measured. Liver histopathology was examined by hematoxylin-eosin staining. Insulin receptor expression in the liver was analyzed by immunohistochemical staining, Western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Compared to the control group, the T2DM/NAFLD group had increased levels of glucolipid and decreased levels of insulin. Plasma glucose and lipid levels were decreased in the gAd-treated group, while serum insulin levels increased. The expression of insulin receptor in the T2DM/NAFLD group increased compared with the NC group, and gAd downregulated insulin receptor expression in the livers of T2DM/NAFLD rats. Steatosis of the liver was alleviated in the gAd-treated group compared to the T2DM/NAFLD group (NAS 1.39 ± 0.51 vs 1.92 ± 0.51, P Globular adiponectin exerts beneficial effects in T2DM rats with NAFLD by promoting insulin secretion, mediating glucolipid metabolism, regulating insulin receptor expression and alleviating hepatic steatosis.
Kappus, Matthew; Abdelmalek, Manal
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developing countries. Approximately 25% of patients with NAFLD develop nonalcoholic steatohepatitis (NASH). NASH-related cirrhosis is now a leading listing indication for liver transplantation in the United States. Although posttransplant survival for NASH-related cirrhosis is comparable with that of other liver diseases, many patients have features of metabolic syndrome, which can contribute to a recurrence of NAFLD or NASH. This article reviews the epidemiology, pathophysiology, and treatment of de novo and recurrence of NASH after liver transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.
Liu, Xiaofei; Yang, Fan; Song, Tao; Zeng, Anrong; Wang, Qi; Sun, Zhong; Shen, Jun
O-Carboxymethyl chitosan (O-CMCs) and N-((2-hydroxy-3-N,N-dimethylhexadecylammonium)propyl)chitosan chloride (N-CQCs) were synthesized for nonalcoholic fatty liver disease (NAFLD) treatment. The weight-average weight and substitution degree of O-CMCs and N-CQCs were 6.5 × 10(4) and 0.72 and 7.9 × 10(4) and 0.21, respectively. O-CMCs was negatively charged with a zeta-potential value of -31.82 mV, whereas that of N-CQCs was +36.1 mV, and both showed low cytotoxcity. Serum lipid level and liver fat accumulation were reduced with chitosan and its two derivatives. Furthermore, mRNA and protein expression assay of hepatic lipid metabolism enzymes and low-density lipoprotein receptor (LDL-R) were observed by RT-PCR and Western blot. Results showed that N-CQCs exhibited a more evident desired effect than chitosan and O-CMCs, indicating that amphiphilicity, solubility, and surface charge of chitosan and its two derivatives played roles in the expression of hepatic lipid metabolism enzymes and LDL-R. Therefore, dietary supplementation of O-CMCs and N-CQCs can alleviate the high fat diet induced aberrations related to NAFLD by their antilipidemic property.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR, a natural plant product, has beneficial effects on NAFLD, though the mechanisms are not completely known. In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD. Increase of insulin sensitivity, regulation of adenosine monophosphate-activated protein kinase (AMPK pathway, improvement of mitochondrial function, alleviation of oxidative stress, LDLR mRNA stabilization, and regulation of gut microenvironment are the major targets of BBR in the treatment of NAFLD. Additionally, reduction of proprotein convertase subtilisin/kexin 9 (PCSK9 expression and DNA methylation are also involved in pharmacological mechanisms of berberine in the treatment of NAFLD. The immunologic mechanism of BBR in the treatment of NAFLD, development of berberine derivative, drug combinations, delivery routes, and drug dose can be considered in the future research.
Lonardo, Amedeo; Nascimbeni, Fabio; Maurantonio, Mauro; Marrazzo, Alessandra; Rinaldi, Luca; Adinolfi, Luigi Elio
In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. PMID:29085206
Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija
Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470
The Chinese Communist Central Committee and the State Council aim to solve food and clothing problems among impoverished rural people by the year 2000. This goal was a priority on the agenda of the recent October 1996 National Conference on Poverty Alleviation and Development and the 1996 National Conference of the State Family Planning Commission. Poverty is attributed to rapid population growth and underdevelopment. Poverty is concentrated in parts of 18 large provinces. These provinces are characterized by Family Planning Minister Peng as having high birth rates, early marriage and childbearing, unplanned births, and multiple births. Overpopulation is tied to overconsumption, depletion of resources, deforestation, soil erosion, pollution, shortages of water, decreases in shares of cultivated land, degraded grasslands, and general destruction of the environment. Illiteracy in poor areas is over 20%, compared to the national average of 15%. Mortality and morbidity are higher. Family planning is harder to enforce in poor areas. Pilot programs in Sichuan and Guizhou provinces are promoting integration of family planning with poverty alleviation. Several conferences have addressed the integrated program strategies. Experience has shown that poverty alleviation occurs by controlled population growth and improved quality of life. Departments should "consolidate" their development efforts under Communist Party leadership at all levels. Approaches should emphasize self-reliance and public mobilization. The emphasis should be on women's participation in development. Women's income should be increased. Family planning networks at the grassroots level need to be strengthened simultaneously with increased poverty alleviation and development. The government strategy is to strengthen leadership, mobilize the public, and implement integrated programs.
Poverty alleviation is a long and painstaking process. It involves knowing what poverty is, its causes and means of alleviating it. Poverty is one of the scourges including disease and ignorance a combination of which deprives humanity of the basic needs for living. Among the strategies to alleviate poverty is effective ...
The case of rural tourism and community development has been made in general terms with less focus on poverty alleviation and more emphasis on economic modernisation. Recently, a link between rural tourism and poverty alleviation has been emphasised in the contemporary tourism and poverty alleviation literature.
Carducci, Bernardo J.; McNeely, Judith A.
Several researchers have explored the role of alcohol in domestic violence and attributions of blame. To compare the amount of blame attributed to an incident of wife abuse, alcoholic (N=52) and nonalcoholic (N=159) subjects read an account of wife abuse and distributed a percentage of the blame to the man, the woman, and the situation.…
Sargenti, Konstantina; Prytz, Hanne; Bertilsson, Sara
.001), this relationship was not significant after adjustment for confounders in Cox regression analysis (P=0.056). Resistance to piperacilin-tazobactam and carbapenems was more common in infections occurring in alcoholic versus nonalcoholic cirrhosis (13 vs. 5%, P=0.057 and 12 vs. 2%, P=0.009). Alcoholic etiology...
Full Text Available BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA in the treatment of NASH.
ter Horst, Kasper W.; Serlie, Mireille J.
Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be
de Knegt, RJ
Non-alcoholic steatohepatitis (NASH) is a form of liver disease resembling alcoholic liver disease in a patient who does not consume significant amounts of alcohol. Since its first description in 1980 it has been recognized with increasing frequency. The natural course is relatively benign, but
It was found that Burn®, XL energy drink® and Red Bull® had the highest amount of caffeine. It was however noted that though most of the non-alcoholic beverages had high caffeine content they had no label claim. Key Words: Reverse Phase High Performance Liquid chromatography (HPLC), Ultra violet visible (UV/VIS), ...
Kelly, B; King, L; Baur, L; Rayner, M; Lobstein, T; Monteiro, C; Macmullan, J; Mohan, S; Barquera, S; Friel, S; Hawkes, C; Kumanyika, S; L'Abbé, M; Lee, A; Ma, J; Neal, B; Sacks, G; Sanders, D; Snowdon, W; Swinburn, B; Vandevijvere, S; Walker, C
Food and non-alcoholic beverage marketing is recognized as an important factor influencing food choices related to non-communicable diseases. The monitoring of populations' exposure to food and non-alcoholic beverage promotions, and the content of these promotions, is necessary to generate evidence to understand the extent of the problem, and to determine appropriate and effective policy responses. A review of studies measuring the nature and extent of exposure to food promotions was conducted to identify approaches to monitoring food promotions via dominant media platforms. A step-wise approach, comprising 'minimal', 'expanded' and 'optimal' monitoring activities, was designed. This approach can be used to assess the frequency and level of exposure of population groups (especially children) to food promotions, the persuasive power of techniques used in promotional communications (power of promotions) and the nutritional composition of promoted food products. Detailed procedures for data sampling, data collection and data analysis for a range of media types are presented, as well as quantifiable measurement indicators for assessing exposure to and power of food and non-alcoholic beverage promotions. The proposed framework supports the development of a consistent system for monitoring food and non-alcoholic beverage promotions for comparison between countries and over time. © 2013 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of the International Association for the Study of Obesity.
Jan 1, 2018 ... ABSTRACT. BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic ...
Pavlides, Michael; Banerjee, Rajarshi; Tunnicliffe, Elizabeth M; Kelly, Catherine; Collier, Jane; Wang, Lai Mun; Fleming, Kenneth A; Cobbold, Jeremy F; Robson, Matthew D; Neubauer, Stefan; Barnes, Eleanor
The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease. Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed. Magnetic resonance success rate was 95% vs 59% for transient elastography (Pliver inflammation and fibrosis (r s =.51, Pliver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (Pliver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) (PLiver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively (Pliver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0.89. Multiparametric magnetic resonance is a promising technique with good diagnostic accuracy for non-alcoholic fatty liver disease histological parameters, and can potentially identify patients with non-alcoholic steatohepatitis and cirrhosis. © 2017 The Authors Liver International Published by John Wiley & Sons Ltd.
Hsu, Ching-Sheng; Kao, Jia-Horng
Non-alcoholic fatty liver disease (NAFLD) has become the most overwhelming liver disease in Asia. In consideration of its increasing medical and economic impact on Asian people, it is time for us to review the update data in Asian countries and formulate strategies to cope with this emerging health problem in Asia. Moreover, growing data indicates that NAFLD may be a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with several extra-hepatic manifestations, such as cardiovascular diseases, chronic renal diseases, and malignancy. As the co-occurrence of NAFLD and viral hepatitis is common in Asia, issues related to the impact of NAFLD on the clinical outcomes and management of viral hepatitis remain to be elucidated. Areas covered: In this article, a narrative review was conducted, searching for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database till August 2016. Studies relevant to the emerging data of NAFLD in Asia, including the diagnosis, risk factors, the assessment and management of Asian NAFLD patients were examined and discussed. Expert commentary: Collaboration in Asian countries to develop an effective and practical measurement to assess the severity of NAFLD is urgently required.
Full Text Available Nonalcoholic steatohepatitis (NASH is a severe form of nonalcoholic fatty liver disease (NAFLD. The prevalence and clinical significance of NAFLD/NASH have been increasingly recognized in Western countries but much less known in Asian countries, including Taiwan. Here, we report the case of a 43-year-old man who had abnormal liver tests for 18 years. Retrospective evaluation of his initial clinical, laboratory and histologic findings indicated that the hepatic disorder was compatible with the diagnosis of NASH. Although his liver biochemical tests improved after taking lipid-lowering agents, a liver biopsy 17 years later demonstrated histologic progression of intralobular necroinflammation and perivenular fibrosis. These facts suggest that NASH, albeit mild and slowly progressive, indeed exists in Taiwan. After the control of chronic hepatitis B and C and westernization of the lifestyle in Taiwan, an increasing burden of NAFLD/NASH is anticipated and active prophylactic measures should be implemented.
Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.
Klementina Fon Tacer
Full Text Available Obesity with associated comorbidities is currently a worldwide epidemic and among the most challenging health conditions in the 21st century. A major metabolic consequence of obesity is insulin resistance which underlies the pathogenesis of the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of obesity and metabolic syndrome. It comprises a disease spectrum ranging from simple steatosis (fatty liver, through nonalcoholic steatohepatitis (NASH to fibrosis, and ultimately liver cirrhosis. Abnormality in lipid and lipoprotein metabolism accompanied by chronic inflammation is the central pathway for the development of metabolic syndrome-related diseases, such as atherosclerosis, cardiovascular disease (CVD, and NAFLD. This paper focuses on pathogenic aspect of lipid and lipoprotein metabolism in NAFLD and the relevant mouse models of this complex multifactorial disease.
LISBOA, QUELSON COELHO; COSTA, SILVIA MARINHO FEROLLA; COUTO, CLÁUDIA ALVES
SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic infla...
Full Text Available Nonalcoholic fatty liver disease (NAFLD has been developing rapidly in recent years and has become one of the most common liver diseases. However, its pathogenesis remains unclear, and there are no widely accepted therapeutic regimens. NAFLD has a complex pathogenesis with multiple factors involved, including insulin resistance, oxidative stress, bile acid metabolic disorders, and autophagy. This article reviews the pathogenesis of NAFLD in order to provide a reference for further research and clinical treatment in the future.
Widodo, B.; Prinzand, D.; Malik, A.H.
Too little water and too much water can be as devastating as well. Drought usually does not show up instantly like flood, but it creeps slowly. Drought that is less popular than flood has impact more serious than flood. It is difficult to be identified when it comes and when it goes away. However, it is suddenly understood when water becomes scare, or no more water is available in wells, rivers and reservoirs. Managing flood and drought has to be at an integrated basis. Rainwater harvesting (RWH) combined with water conservation methods can be developed to alleviate drought disaster as well as flood disaster in the same time. RWH and water conservation must be an integral part of integrated water resources management. Preventing drought could be automatically reducing the extent of flood that means preventing people and the environment from the disasters. (author)
Full Text Available The demand for cellular data service has been skyrocketing since the debut of data-intensive smart phones and touchpads. However, not all data are created equal. Many popular applications on mobile devices, such as email synchronization and social network updates, are delay tolerant. In addition, cellular load varies significantly in both large and small time scales. To alleviate network congestion and improve network performance, we present a set of opportunistic trough filling schemes that leverage the time-variation of network congestion and delay-tolerance of certain traffic in this paper. We consider average delay, deadline, and clearance time as the performance metrics. Simulation results show promising performance improvement over the standard schemes. The work shed lights on addressing the pressing issue of cellular overload.
Wang, Yunxia; Zhu, Kongxi; Yu, Weihua; Wang, Hongjuan; Liu, Lan; Wu, Qiong; Li, Shuai; Guo, Jianqiang
Non-alcoholic fatty liver diseases (NAFLD) is one of the leading cause of chronic liver diseases in the world. However, the pathogenesis of NAFLD is still unclear. Emerging studies have demonstrated that microRNAs (miRs) are profoundly involved in NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-181b influences NAFLD via direct targeting SIRT1. The expression of miR181b was up-regulated while SIRT1 was down-regulated in both human NAFLD patients and high fat diet (HFD) induced NAFDL mice model. And palmitic acid (PA) treatment increased the miR-181b expression while decreased SIRT1 expression in HepG2 cells. Further, we identified that SIRT1 is a direct downstream target of miR-181b. Ectopic expression of miR-181b significantly repressed the 3'-UTR reporter activities of SIRT1 in a dose-dependent manner, while the effect of miR-181b was interrupted when the binding site of miR-181b within the SIRT1 3'-UTR was mutated. And overexpression of miR-181b reduced both the mRNA and protein levels of SIRT1 in HepG2 cells. We also found that inhibition of miR-181b expression alleviates hepatic steatosis both in vitro and in vivo. And the effect of miR-181b on steatosis was blocked by SIRT1 overexpression. Taken together, our data indicated that increased expression of miR-181b potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target SIRT1. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available ObjectiveTo investigate the prevalence, natural history, and causes of death of nonalcoholic fatty liver disease (NAFLD, as well as related influencing factors. MethodsA total of 833 retired cadres and staff members who underwent physical examination in Shanghai Changzheng Hospital and Shanghai 85 Hospital of the PLA from January 1 to December 31, 2011 and received follow-up visits in either hospital every year since 2011 were enrolled as study subjects, and were divided into NAFLD group (459 patients who were diagnosed with NAFLD before December 31, 2011 and control group (374 patients without liver or biliary diseases. The patients′ clinical data were collected, including body height, body weight, systolic pressure, diastolic pressure, blood biochemical parameters, presence or absence of diabetes, hyperlipidemia, cerebrovascular and cardiovascular diseases, and malignant tumor, and smoking and drinking, and the death time and causes of death were clarified for the patients who died. The prevalence and natural course of NAFLD and related risk factors and prognostic factors were analyzed in this population. The t-test was applied for comparison of continuous data between groups, the chi-square test was applied for comparison of categorical data between groups, the multivariate binary logistic regression was applied to analyze the risk factors for the pathogenesis of NAFLD, and the multinomial logistic regression was applied to analyze the influencing factors for aggravation or alleviation of NAFLD. ResultsThe patients in NAFLD group accounted for 55.1% of all subjects, and the proportion of male patients was higher than that of female patients (58.0% vs 46.7%, χ2=4.962, P=0.026. Compared with the control group, the NAFLD group had significantly higher body mass index (BMI, systolic pressure, diastolic pressure, alanine aminotransferase (ALT, fasting blood glucose, serum uric acid, and triglyceride (TG, a significantly higher proportion of
Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH
Full Text Available Meir Mizrahi,1 Yehudit Shabat,1 Ami Ben Ya'acov,1 Gadi Lalazar,1 Tomer Adar,1 Victor Wong,2 Brian Muller,2 Grant Rawlin,2 Yaron Ilan11Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel; 2Immuron Limited, North Melbourne, AustraliaBackground: Nonalcoholic steatohepatitis (NASH is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. Imm124-E (Immuron Ltd, Melbourne, Australia, containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of NASH. The aim of our study was to determine the safety and efficacy of oral administration of Imm124-E to patients with insulin resistance and NASH.Methods: In an open-label trial, ten patients with biopsy-proven NASH and insulin resistance were orally treated with Imm124-E for 30 days.Results: Oral administration of Imm124-E was safe, and no side effects were noted. Alleviation of insulin resistance was reflected by significantly improved hemoglobin A1c (HbA1c values in all ten treated patients. For between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (OGGT and homeostatic model assessment insulin resistance (HOMA scores; and alleviation in lipid profile. These effects were accompanied by increased serum levels of glucagon-like peptide 1 (GLP-1, adiponectin and T regulatory cells.Conclusion: Hyperimmune colostrum alleviates NASH.Keywords: NASH, anti-LPS, diabetes, adipokines, regulatory T cells
Lake, A.D.; Novák, Petr; Shipkova, P.; Aranibar, N.; Robertson, D.G.; Reily, M.D.; Lehman-McKeeman, L.D.; Vaillancourt, R.R.; Cherrington, N.J.
Roč. 47, č. 3 (2015), s. 603-615 ISSN 0939-4451 Institutional support: RVO:60077344 Keywords : Branched chain amino acid * nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * metabolomics and transcriptomics Subject RIV: CE - Biochemistry Impact factor: 3.196, year: 2015
Clarke, D. J.; Novák, Petr; Lake, A.D.; Shipkova, P.; Aranibar, N.; Robertson, D.; Severson, P.L.; Reily, M.D.; Futscher, B. W.; Lehman-McKeeman, L.D.; Cherrington, N.J.
Roč. 59, č. 2 (2014), s. 365-374 ISSN 0163-2116 Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * hepatocellular carcinoma * metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.613, year: 2014
Gaemers, Ingrid C.; Stallen, Jan M.; Kunne, Cindy; Wallner, Christian; van Werven, Jochem; Nederveen, Aart; Lamers, Wouter H.
The major risk factors for non-alcoholic fatty liver disease (NAFLD) are obesity, insulin resistance and dyslipidemia. The cause for progression from the steatosis stage to the inflammatory condition (non-alcoholic steatohepatitis (NASH)) remains elusive at present. Aim of this study was to test
van Best, Niels; Jansen, Peter L.; Rensen, Sander S.
The role of intestinal bacteria in the pathogenesis of nonalcoholic fatty liver disease is increasingly acknowledged. Recently developed microbial profiling techniques are beginning to shed light on the nature of gut microbiota alterations in nonalcoholic fatty liver disease. In this review, we
Anderson R. Meda
Full Text Available A laboratory experiment was conducted to evaluate the effects of water soluble plant extracts on soil acidity. The plant materials were: black oat, oil seed radish, white and blue lupin, gray and dwarf mucuna, Crotalaria spectabilis and C. breviflora, millet, pigeon pea, star grass, mato grosso grass, coffee leaves, sugar cane leaves, rice straw, and wheat straw. Plant extracts were added on soil surface in a PVC soil column at a rate of 1.0 ml min-1. Both soil and drainage water were analyzed for pH, Ca, Al, and K. Plant extracts applied on the soil surface increased soil pH, exchangeable Ca ex and Kex and decreased Al ex. Oil seed radish, black oat, and blue lupin were the best and millet the worst materials to alleviate soil acidity. Oil seed radish markedly increased Al in the drainage water. Chemical changes were associated with the concentrations of basic cations in the plant extract: the higher the concentration the greater the effects in alleviating soil acidity.Foram conduzidos experimentos de laboratórios para avaliar os efeitos de extratos de plantas solúveis em água na acidez do solo. Os materiais de plantas foram: aveia preta, nabo, tremoço branco e azul, mucuna cinza e anã, Crotalaria spectabilis e C. breviflora, milheto, guandu, grama estrela, grama mato grosso, folhas de café, folhas de cana-de-açúcar, palhada de arroz e palhada de trigo. Foi utilizado o seguinte procedimento para o extrato da planta solúvel em água: pesar 3g de material de planta, adicionar 150 ml de água, agitar por 8h e filtrar. Os extratos de plantas foram adicionados na superfície do solo em uma coluna de PVC (1 ml min-1. Após, adicionou-se água deionizada em quantidade equivalente a três volumes de poros. Os extratos de plantas aumentaram o pH, Ca e K trocável e diminuíram Al. Nabo, aveia preta e tremoço azul foram os melhores e milheto o pior material para amenizar a acidez do solo. Nabo aumentou Al na água de drenagem. As altera
Despite these programmes, poverty still exists among Nigerians especially the youth. This study therefore examines the impact of government poverty alleviation programmes on the youth. The population of the study comprised of all youths who have benefited from government poverty alleviation programmes. The Random ...
Kragh, Knud Abildgaard; Hansen, Morten Hartvig; Henriksen, Lars Christian
As the size of wind turbines increases, the load alleviating capabilities of the turbine controller are becoming increasingly important. Load alleviating control schemes have traditionally been based on feedback from load sensor; however, recent developments of measurement technologies have enabled...... control on the basis of preview measurements of the inflow acquired using, e.g., light detection and ranging. The potential of alleviating load variations that are caused by mean wind speed changes through feed-forward control have been demonstrated through both experiments and simulations in several...... studies, whereas the potential of preview control for alleviating the load variations caused by azimuth dependent inflow variations is less described. Individual or cyclic pitch is required to alleviate azimuth dependent load variations and is traditionally applied through feedback control of the blade...
Sagar, Ambuj D.
Improving energy services for poor households in developing countries remains one of the most pressing challenges facing the development community. The dependence of these households on traditional forms of energy leads to significant health impacts as well as other major disbenefits, yet there has been little progress in meeting this challenge. This viewpoint argues for an 'energy-poverty alleviation' fund to help provide modern energy services to these households. It also proposes an approach through which to create such a fund, namely by introducing an incremental levy on petroleum. Notably, this scheme does not need a global agreement since a levy could be introduced by major oil-exporting countries. The implementation of this mechanism would result in a climate-friendly outcome (even before taking into account the elimination of products of incomplete combustion resulting from the traditional household use of biomass-based fuels) while providing immense socio-economic benefits to the world's poor. Such an approach would allow significant progress on the sustainable development front while reducing global greenhouse gas emissions, and therefore is very much consistent with the United Nations Framework Convention on Climate Change
Yu, Leilei; Zhai, Qixiao; Liu, Xiaoming; Wang, Gang; Zhang, Qiuxiang; Zhao, Jianxin; Narbad, Arjan; Zhang, Hao; Tian, Fengwei; Chen, Wei
Aluminium (Al) is the most abundant metal in the earth's crust. Al exposure can cause a variety of adverse physiological effects in humans and animals. Our aim was to demonstrate that specific probiotic bacteria can play a special physiologically functional role in protection against Al toxicity in mice. Thirty strains of lactic acid bacteria (LAB) were tested for their aluminium-binding ability, aluminium tolerance, their antioxidative capacity, and their ability to survive the exposure to artificial gastrointestinal (GI) juices. Lactobacillus plantarum CCFM639 was selected for animal experiments because of its excellent performance in vitro. Forty mice were divided into four groups: control, Al only, Al plus CCFM639, and Al plus deferiprone (DFP). CCFM639 was administered at 10(9) CFU once daily for 10 days, followed by a single oral dose of aluminium chloride hexahydrate at 5.14 mg aluminium (LD50) for each mouse. The results showed that CCFM639 treatment led to a significant reduction in the mortality rates with corresponding decrease in intestinal aluminium absorption and in accumulation of aluminium in the tissues and amelioration of hepatic histopathological damage. This probiotic treatment also resulted in alleviation of hepatic, renal, and cerebral oxidative stress. The treatment of L. plantarum CCFM639 has potential as a therapeutic dietary strategy against acute aluminium toxicity.
Perumpail, Brandon J; Khan, Muhammad Ali; Yoo, Eric R; Cholankeril, George; Kim, Donghee; Ahmed, Aijaz
Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. PMID:29307986
Kim, Jeongjun; Lee, Hyunghee; Lim, Jonghoon; Lee, Haerim; Yoon, Seolah; Shin, Soon Shik; Yoon, Michung
Increasing evidence indicates that angiogenesis inhibitors regulate obesity. This study aimed to determine whether the lemon balm extract ALS-L1023 inhibits diet-induced obesity and nonalcoholic fatty liver disease (NAFLD) in female ovariectomized (OVX) mice. OVX mice received a low fat diet (LFD), a high fat diet (HFD) or HFD supplemented with ALS-L1023 (ALS-L1023) for 15 weeks. HFD mice exhibited increases in visceral adipose tissue (VAT) angiogenesis, body weight, VAT mass and VAT inflammation compared with LFD mice. In contrast, all of these effects were reduced in ALS-L1023 mice compared with HFD mice. Serum lipids and liver injury markers were improved in ALS-L1023 mice. Hepatic lipid accumulation, inflammatory cells and collagen levels were lower in ALS-L1023 mice than in HFD mice. ALS-L1023 mice exhibited a tendency to normalize hepatic expression of genes involved in lipid metabolism, inflammation and fibrosis to levels in LFD mice. ALS-L1023 also induced Akt phosphorylation and increased Nrf2 mRNA expression in livers of obese mice. Our results indicate that the angiogenesis inhibitor ALS-L1023 can regulate obesity, hepatic steatosis and fibro-inflammation, in part through improvement of VAT function, in obese OVX mice. These findings suggest that angiogenesis inhibitors may contribute to alleviation of NAFLD in post-menopausal women with obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ampuero, Javier; Sánchez-Torrijos, Yolanda; Aguilera, Virginia; Bellido, Francisco; Romero-Gómez, Manuel
Management of non-alcoholic steatohepatitis is focused on restitution of metabolic derangement, weight loss and drugs able to improve steatosis, ballooning and fibrosis. Life-style interventions based on Mediterranean diet and increasing physical activity are the first line therapy. In patients with unsuccessful life-style intervention several drugs are under development: agonist PPAR, agonist GLP-1R and agonist FXR together with drugs focussing on inflammation, ballooning, apoptosis and fibrosis. Bariatric surgery or advanced endoscopy are reserved for morbid obese without response to life-style intervention and weighting loss drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
Full Text Available Berberine (BBR, an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonalcoholic fatty liver disease (NAFLD. The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials. This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD.
Cacioppo, S; Cacioppo, J T
Impaired biosynthesis of Allopregnanolone (ALLO), a brain endogenous neurosteroid, has been associated with numerous behavioral dysfunctions, which range from anxiety- and depressive-like behaviors to aggressive behavior and changes in responses to contextual fear conditioning in rodent models of emotional dysfunction. Recent animal research also demonstrates a critical role of ALLO in social isolation. Although there are likely aspects of perceived social isolation that are uniquely human, there is also continuity across species. Both human and animal research show that perceived social isolation (which can be defined behaviorally in animals and humans) has detrimental effects on physical health, such as increased hypothalamic pituitary adrenal (HPA) activity, decreased brain-derived neurotrophic factor (BDNF) expression, and increased depressive behavior. The similarities between animal and human research suggest that perceived social isolation (loneliness) may also be associated with a reduction in the synthesis of ALLO, potentially by reducing BDNF regulation and increasing HPA activity through the hippocampus, amygdala, and bed nucleus of the stria terminalis (BNST), especially during social threat processing. Accordingly, exogenous administration of ALLO (or ALLO precursor, such as pregnenolone), in humans may help alleviate loneliness. Congruent with our hypothesis, exogenous administration of ALLO (or ALLO precursors) in humans has been shown to improve various stress-related disorders that show similarities between animals and humans i.e., post-traumatic stress disorders, traumatic brain injuries. Because a growing body of evidence demonstrates the benefits of ALLO in socially isolated animals, we believe our ALLO hypothesis can be applied to loneliness in humans, as well. Copyright © 2015 Elsevier Ltd. All rights reserved.
Gu, Yuan; Sun, Xiao-xiao; Ye, Ji-ming; He, Li; Yan, Shou-sheng; Zhang, Hao-hao; Hu, Li-hong; Yuan, Jun-ying; Yu, Qiang
Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5 and 10 μmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 μmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 μmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 μmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 μmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 β cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. PMID:22705729
Full Text Available Abstract Background Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of nonalcoholic steatohepatitis. We aimed to investigate the total antioxidant response using a novel automated method in nonalcoholic steatohepatitis subjects. As a reciprocal measure, we also aimed to determine total peroxide level in the same plasma samples. Methods Twenty-two subjects with biopsy proven nonalcoholic steatohepatitis and 22 healthy controls were enrolled. Total antioxidant response and total peroxide level measurements were done in all participants. The ratio percentage of total peroxide level to total antioxidant response was regarded as oxidative stress index. Results Total antioxidant response of subjects with nonalcoholic steatohepatitis was significantly lower than controls (p In subjects with nonalcoholic steatohepatitis, fibrosis score was significantly correlated with total peroxide level, total antioxidant response and oxidative stress index (p 0.05. Conclusion Nonalcoholic steatohepatitis is associated with increased oxidant capacity, especially in the presence of liver fibrosis. The novel automated assay is a reliable and easily applicable method for total plasma antioxidant response measurement in nonalcoholic steatohepatitis.
Full Text Available OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005, uric acid (p = 0.001, aspartate aminotransferase (p<0.001, alanine aminotransferase (p<0.001, γ-glutamyltransferase (p<0.0001, alkaline phosphatase (p = 0.028, HbA1c (p<0.001, ferritin (p<0.001, insulin (p = 0.016, C-peptide (p = 0.001, HOMA-IR (p = 0.003, total cholesterol (p = 0.001, triglyceride (p = 0.001 and white blood cell (p = 0.04 levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OHD levels (12.3±8.9 ng/dl, p<0.001 compared with those of the control group (20±13.6 ng/dl. CONCLUSIONS: In this study, we found lower serum 25(OHD levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.
Noto, Haruka; Tokushige, Katsutoshi; Hashimoto, Etsuko; Taniai, Makiko; Shiratori, Keiko
Lack of exercise and excessive food intake are known to be the important causes of nonalcoholic steatohepatitis (NASH). To elucidate the relationship between lifestyle and NASH, we surveyed exercise and dietary habits, comparing them among 171 biopsy-proven NASH patients, 29 nonalcoholic fatty liver (NAFL) patients and 49 normal subjects. Dietary habits including the duration of dinner time, amount of rice at dinner, and weekly frequencies of meat, fries, Chinese noodles, sweets, and instant food consumption were significantly different in male NASH patients compared to normal male subjects. In women, differences were seen in the amount of rice at dinner, frequency of eating out, and proclivity for sweets. In male NASH patients, the frequency of physical exercise was significantly lower. The lifestyle tendencies of NASH were almost similar to those of NAFL. In the comparison between obese NASH and non-obese NASH, no clear lifestyle differences were found. In conclusion, the most striking result of this survey was that the lifestyle of males contributed significantly to the development of NASH. These results point to treatment of NASH in males. In female NASH patients, lifestyle differences were minimal, and the effects of other factors such as genetic background will need to be investigated.
Pan, Jen-Jung; Fallon, Michael B
Due to the worldwide epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of elevated liver enzymes. NAFLD represents a spectrum of liver injury ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may progress to advanced fibrosis and cirrhosis. Individuals with NAFLD, especially those with metabolic syndrome, have higher overall mortality, cardiovascular mortality, and liver-related mortality compared with the general population. According to the population-based studies, NAFLD and NASH are more prevalent in males and in Hispanics. Both the gender and racial ethnic differences in NAFLD and NASH are likely attributed to interaction between environmental, behavioral, and genetic factors. Using genome-wide association studies, several genetic variants have been identified to be associated with NAFLD/NASH. However, these variants account for only a small amount of variation in hepatic steatosis among ethnic groups and may serve as modifiers of the natural history of NAFLD. Alternatively, these variants may not be the causative variants but simply markers representing a larger body of genetic variations. In this article, we provide a concise review of the gender and racial differences in the prevalence of NAFLD and NASH in adults. We also discuss the possible mechanisms for these disparities.
Full Text Available Nonalcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1 inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in the Western world (it affects 30% of the general adult population. The NAFLD encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH, defined by steatosis, hepatocellular damage, and lobular inflammation in individuals without significant alcohol consumption and negative viral, congenital, and autoimmune liver disease markers. Currently, NAFLD is considered an emerging epidemic in light of the dramatic increase in obesity rates. With the progressive nature of NASH and its rising prevalence there is a significant need for a specific and targeted treatments since to date there has not been any validated therapies for NAFLD other than weight loss, which is well known to have a poor long-term success rate. In recent years, visceral adipose tissue has taken an important role in NAFLD pathogenesis, and current therapeutic approaches aim at reducing visceral obesity and free fatty acid overflow to the liver. This paper is focused on the treatments used for NAFLD and the potential new therapy.
Younossi, Zobair M; Baranova, Ancha; Stepanova, Maria; Page, Sandra; Calvert, Valerie S; Afendy, Arian; Goodman, Zachary; Chandhoke, Vikas; Liotta, Lance; Petricoin, Emanuel
The progression of nonalcoholic fatty liver disease (NAFLD) has been linked to deregulated exchange of the endocrine signaling between adipose and liver tissue. Proteomic assays for the phosphorylation events that characterize the activated or deactivated state of the kinase-driven signaling cascades in visceral adipose tissue (VAT) could shed light on the pathogenesis of nonalcoholic steatohepatitis (NASH) and related fibrosis. Reverse-phase protein microarrays (RPMA) were used to develop biomarkers for NASH and fibrosis using VAT collected from 167 NAFLD patients (training cohort, N = 117; testing cohort, N = 50). Three types of models were developed for NASH and advanced fibrosis: clinical models, proteomics models, and combination models. NASH was predicted by a model that included measurements of two components of the insulin signaling pathway: AKT kinase and insulin receptor substrate 1 (IRS1). The models for fibrosis were less reliable when predictions were based on phosphoproteomic, clinical, or the combination data. The best performing model relied on levels of the phosphorylation of GSK3 as well as on two subunits of cyclic AMP regulated protein kinase A (PKA). Phosphoproteomics technology could potentially be used to provide pathogenic information about NASH and NASH-related fibrosis. This information can lead to a clinically relevant diagnostic/prognostic biomarker for NASH.
Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L'Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal
Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development.
Bashar M. Attar
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common cause of liver dysfunction worldwide. NAFLD may progress to nonalcoholic steatohepatitis (NASH and in turn cirrhosis. Importantly, hepatic cancer can occur in NASH in the absence of cirrhosis. The cardinal histologic feature of NAFLD is the presence of an excessive accumulation of triacylglycerols and diacylglycerols in hepatocytes. The presence of obesity and insulin resistance lead to an increased hepatic-free fatty acid (FFA flux creating an environment appropriate for the development of NAFLD. The generation of toxic reactive oxygen species with the production of hepatic injury and inflammation as a consequence of FFA oxidation will ultimately lead to the initiation and progression of fibrosis. Lifestyle modifications specifically weight loss, physical exercise, and cognitive behavior therapy have been recommended as treatments for NASH. Dietary fructose is an independent risk factor for the development of NAFLD. Pioglitazone can be used to treat biopsy-proven NASH; however, its safety risks should be considered carefully. Greater consumption for coffee, independent of its caffeine component, has been associated with a significant reduced risk of advanced fibrosis in NASH. Additional data are needed before recommending bariatric surgery as an established option for the specific treatment of NASH.
AlShaalan, Rasha; Aljiffry, Murad; Al-Busafi, Said; Metrakos, Peter; Hassanain, Mazen
Hepatic steatosis is the buildup of lipids within hepatocytes. It is the simplest stage in nonalcoholic fatty liver disease (NAFLD). It occurs in approximately 30% of the general population and as much as 90% of the obese population in the United States. It may progress to nonalcoholic steatohepatitis, which is a state of hepatocellular inflammation and damage in response to the accumulated fat. Liver biopsy remains the gold standard tool to diagnose and stage NAFLD. However, it comes with the risk of complications ranging from simple pain to life-threatening bleeding. It is also associated with sampling error. For these reasons, a variety of noninvasive radiological markers, including ultrasound, computed tomography, magnetic resonance spectroscopy, and the controlled attenuation parameter using transient elastography and Xenon-133 scan have been proposed to increase our ability to diagnose NAFLD, hence avoiding liver biopsy. The aim of this review is to discuss the utility and accuracy of using available noninvasive diagnostic modalities for fatty liver in NAFLD. PMID:25843191
Full Text Available Metabolic syndrome that represents a totality of interrelated carbohydrate metabolism and lipid disorders, as well as a mechanism regulating arterial tension and endothelium function is one of the critical issues in pediatrics. In recent years, children with metabolic syndrome are increasingly diagnosed with liver injuries symptoms that are associated with a fatty transformation of the liver [1–3]. In this case, non-alcoholic fatty liver disease (NAFLD, a liver manifestation of metabolic syndrome is diagnosed. The diagnosis is confirmed in the absence of alcohol abuse in the past medical history, virus and autoimmune liver disease markers, elimination of toxic and drug influence, as wells as disorders of copper and iron exchange in the patient’s system. One of the key risk factors for developing NAFLD in children is overeating and reduced physical activities. It was believed in the past that NAFLD is relatively benign, however, there is evidence in current literature that this is a pathological condition that may develop and result in extreme fibrotic alterations in the liver parenchymatous tissue all the way to cirrhosis and hepatocellular carcinoma . Early-stage identification and timely launch of therapy for NAFLD in children represents one of the most important objectives in modern healthcare. Key words: metabolic syndrome, non-alcoholic fatty liver disease, children, steatohepatosis. (Pediatric Pharmacology. – 2010; 7(6:68-72
Verbeek, Jef; Jacobs, Ans; Spincemaille, Pieter; Cassiman, David
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non-genetically manipulated C57BL6/J mice a 'Western style' high-fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.
Full Text Available Adipokines and ghrelin play role in insulin resistance, the key pathophysiological abnormality in patients with nonalcoholic fatty liver diseases. In the present study, relationship between nonalcoholic steatohepatitis (NASH and serum adipokine and ghrelin levels was investigated. Thirty seven patients with biopsy-proven NASH and 25 age- and sex-matched controls were enrolled. Ten of NASH patients (27% had diabetes mellitus (n=5 or impaired glucose tolerance (n=5. Body mass index (BMI was less than 30 kg/m2 in 67.6% of patients, while in the remaining 32.4% it was more than 30 kg/m2. Serum adiponectin, leptin, TNF-α, and ghrelin were determined. Serum leptin (15.49±4.84 vs 10.31±2.53 and TNF-α (12.1±2.7 vs 10.31±2.56 levels were significantly higher in the NASH group compared to in the control group (P30 or glucose tolerance was impaired or not (P>.05. Additionally, neither adipokines nor ghrelin was correlated with histopathological grade and stage (P>.05. In conclusion; there is a significant relationship between NASH and adipokines and ghrelin independent from BMI and status of the glucose metabolism. These cytokines that appear to have role in the pathogenesis of NASH, however, do not have any effect upon the severity of the histopathology.
Mutter, J. C.
essential and could hold the key to making gains toward alleviating the burden of global poverty.
Effect of Dry Season Tomato Farming on Poverty Alleviation among Women ... their major sources of resources for tomato farming, marketing and marketing ... and the effect of dry season tomato farming as strategy for poverty reduction; ...
Aqueous extract of Hibiscus sabdarrifa calyx alleviates anemia and organ damage in Trypanosoma brucei brucei infected rats. IA Umar, E Daikwo, NG Maryoms, A Gidado, LB Buratai, FS Saka, MA Ibrahim ...
Phosphorus and humic acid application alleviate salinity stress of pepper seedling. ... It consequently affects plant growth and yield and ameliorates the deleterious effects of salt stress. The objective of the study ... from 32 Countries: Algeria (5) ...
Yan, Jie; Yu, Yang; Kang, Jeon Woong; Tam, Zhi Yang; Xu, Shuoyu; Fong, Eliza Li Shan; Singh, Surya Pratap; Song, Ziwei; Tucker Kellogg, Lisa; So, Peter; Yu, Hanry
We combined Raman micro-spectroscopy and machine learning techniques to develop a classification model based on a well-established non-alcoholic steatohepatitis (NASH) mouse model, using spectrum pre-processing, biochemical component analysis (BCA) and logistic regression.
Full Text Available Alba Berlanga,1,* Esther Guiu-Jurado,1,* José Antonio Porras,1,2 Teresa Auguet1,21Group GEMMAIR (AGAUR and Applied Medicine Research Group, Department of Medicine and Surgery, Universitat Rovira i Virgili (URV, IISPV, Hospital Universitari Joan XXIII, Tarragona, Spain; 2Department of Internal Medicine, Hospital Universitari Joan XXIII Tarragona, Tarragona, Spain *These authors contributed equally to this workAbstract: Non-alcoholic fatty liver disease (NAFLD is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA
Full Text Available Sandra Milic,1 Ivana Mikolasevic,1,2 Irena Krznaric-Zrnic,1 Marija Stanic,3 Goran Poropat,1 Davor Stimac,1 Vera Vlahovic-Palcevski,4 Lidija Orlic2 1Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia; 2Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia; 3Department of Hematology, UHC Rijeka, Rijeka, Croatia; 4Department for Clinical Pharmacology, University of Rijeka Medical School, UHC Rijeka, Rijeka, Croatia Abstract: Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD. NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only
Rambaldi, A; Gluud, C
Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine...... evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis....
Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Fusun F; Sabuncu, Tevfik; Aslan, Mehmet; Sarifakiogullari, Serpil; Gunaydin, Necla; Erel, Ozcan
Abstract Background Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of nonalcoholic steatohepatitis. We aimed to investigate the total antioxidant response using a novel automated method in nonalcoholic steatohepatitis subjects. As a reciprocal measure, we also aimed to determine total peroxide level in the same plasma samples. Methods Twenty-two subjects with biopsy proven nonalco...
Canet, Mark J.; Hardwick, Rhiannon N.; Lake, April D.; Dzierlenga, Anika L.; Clarke, John D.; Cherrington, Nathan J.
Nonalcoholic fatty liver disease is a prevalent form of chronic liver disease that can progress to the more advanced stage of nonalcoholic steatohepatitis (NASH). NASH has been shown to alter drug transporter regulation and may have implications in the development of adverse drug reactions. Several experimental rodent models have been proposed for the study of NASH, but no single model fully recapitulates all aspects of the human disease. The purpose of the current study was to determine whic...
Semb, Synne; Dam-Larsen, Sanne; Mogensen, Anne Mellon
Non-alcoholic fatty liver disease encompasses a spectrum of histological lesions ranging from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Simple steatosis is generally benign, while NASH can progress to severe liver disease. The aim of the present study was to quantify...... the number of patients with NASH and assess the prognosis associated with the condition in a large Danish referral centre for liver disease....
Yamamoto, Takaya; Nakade, Yukiomi; Yamauchi, Taeko; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sato, Ken; Fukuzawa, Yoshitaka; Yoneda, Masashi
To investigate whether a glucagon-like peptide-1 (GLP-1) analogue inhibits nonalcoholic steatohepatitis (NASH), which is being increasingly recognized in Asia, in non-obese mice. A methionine-choline-deficient diet (MCD) along with exendin-4 (20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice (non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride (TG) and free fatty acid (FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry. Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fatty acid transport protein 4 (FATP4), a hepatic FFA influx-related gene; macrophage recruitment; and the level of malondialdehyde (MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) mRNA (lipogenesis-related gene) and acyl-coenzyme A oxidase 1 (ACOX1) mRNA (β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein mRNA (a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 mRNA level. These results suggest that GLP-1 inhibits hepatic steatosis and
Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Fusun F; Sabuncu, Tevfik; Aslan, Mehmet; Sarifakiogullari, Serpil; Gunaydin, Necla; Erel, Ozcan
Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of nonalcoholic steatohepatitis. We aimed to investigate the total antioxidant response using a novel automated method in nonalcoholic steatohepatitis subjects. As a reciprocal measure, we also aimed to determine total peroxide level in the same plasma samples. Twenty-two subjects with biopsy proven nonalcoholic steatohepatitis and 22 healthy controls were enrolled. Total antioxidant response and total peroxide level measurements were done in all participants. The ratio percentage of total peroxide level to total antioxidant response was regarded as oxidative stress index. Total antioxidant response of subjects with nonalcoholic steatohepatitis was significantly lower than controls (p total peroxide level and mean oxidative stress index were higher (all p total peroxide level, total antioxidant response and oxidative stress index (p 0.05). Nonalcoholic steatohepatitis is associated with increased oxidant capacity, especially in the presence of liver fibrosis. The novel automated assay is a reliable and easily applicable method for total plasma antioxidant response measurement in nonalcoholic steatohepatitis.
Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu
Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454
Full Text Available In recent years, the incidence of nonalcoholic fatty liver disease (NAFLD has increased gradually along with the rising prevalence of obesity, type 2 diabetes, and hyperlipidemia, and NAFLD has become one of the most common chronic liver diseases in the world and the second major liver disease after chronic viral hepatitis in China. However, its pathogenesis has not yet been clarified. Animal models are playing an important role in researches on NAFLD due to the facts that the development and progression of NAFLD require a long period of time, and ethical limitations exist in conducting drug trials in patients or collecting liver tissues from patients. The animal models with histopathology similar to that of NAFLD patients are reviewed, and their modeling principle, as well as the advantages and disadvantages, are compared. Animal models provide a powerful tool for further studies of NAFLD pathogenesis and drug screening for prevention and treatment of NAFLD.
Nobili, Valerio; Socha, Piotr
Non-alcoholic fatty liver disease (NAFLD), an increasingly prevalent paediatric disorder is diagnosed and managed by both paediatric gastroenterologists / hepatologists but also frequently by the general paediatrician. This paper updates recent advances in diagnostic and therapeutic approach which may be applied to everyday practice. Diagnosis of NAFLD takes into account the risk factor profile and is a diagnosis of exclusion. Techniques such as transient elastography and specific biomarkers aimed at improving diagnosis and monitoring of NAFLD need further validation in the paediatric population. Defining the risk to develop cirrhosis seems to be of primary importance already in childhood and a combination of genetic, clinical and environmental factors can help in monitoring and making decisions on therapy. Weight reduction therapy should be the aim of treatment approach but the compliance is poor and pharmacological treatment would be helpful- DHA, some probiotics, vitamin E are to be considered but evidence is not sufficient to recommend widespread use.
Zhan, Yu-Tao; Su, Hai-Ying; An, Wei
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized. PMID:26937136
Claudia P. Oliveira
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM, but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD.
Full Text Available Non-alcoholic steatohepatitis (NASH is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. Obesity is considered a chronic low-grade inflammatory state and the liver has been recognized as being an “immunological organ”. The complex role of the immune system in the pathogenesis of NASH is currently raising great interest, also in view of the possible therapeutic potential of immunotherapy in NASH. This review focuses on the disturbances of the cells constituting the innate and adaptive immune system in the liver and in adipose tissue.
Timon E. Adolph
Full Text Available Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD. Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.
Full Text Available Introduction. Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2 and non-alcoholic steatohepatitis (NASH and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD, and controls.
Full Text Available Nonalcoholic fatty liver disease (NAFLD occurs frequently in a setting of obesity, dyslipidemia and insulin resistance, but the etiology of the disease, particularly the events favoring progression to nonalcoholic steatohepatitis (NASH as opposed to simple steatosis (SS, are not fully understood. Based on known zonation patterns in protein, glucose and lipid metabolism, coupled with evidence that phosphatidylcholine may play a role in NASH pathogenesis, we hypothesized that phospholipid zonation exists in liver and that specific phospholipid abundance and distribution may be associated with histologic disease. A survey of normal hepatic protein expression profiles in the Human Protein Atlas revealed pronounced zonation of enzymes involved in lipid utilization and storage, particularly those facilitating phosphatidylcholine (PC metabolism. Immunohistochemistry of obese normal, SS and NASH liver specimens with anti-phosphatidylethanomine N-methyltransferase (PEMT antibodies showed a progressive decrease in the zonal distribution of this PC biosynthetic enzyme. Phospholipid quantitation by liquid chromatography mass spectrometry (LC-MS in hepatic extracts of Class III obese patients with increasing NAFLD severity revealed that most PC species with 32, 34 and 36 carbons as well as total PC abundance was decreased with SS and NASH. Matrix assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS imaging revealed strong zonal distributions for 32, 34 and 36 carbon PCs in controls (minimal histologic findings and SS that was lost in NASH specimens. Specific lipid species such as PC 34:1 and PC 36:2 best illustrated this phenomenon. These findings suggest that phospholipid zonation may be associated with the presence of an intrahepatic proinflammatory phenotype and thus have broad implications in the etiopathogenesis of NASH.
Bragg, Marie A; Miller, Alysa N; Elizee, Juleen; Dighe, Shatabdi; Elbel, Brian D
Food and beverage marketing has been associated with childhood obesity. We quantified the number and type of food or beverage brands promoted by music celebrities, assessed the nutritional quality of the products, and examined Teen Choice Award data to assess the celebrities' popularity among adolescents. This was a descriptive study. A list of music celebrities associated with the 2013 and 2014 Billboard Hot 100 Chart, which ranks songs according to sales and radio impressions, was compiled. Data on celebrity endorsements were gathered from official company Web sites, YouTube commercials, an advertising database, and media reports. Nutritional quality of foods was assessed according to the Nutrient Profile Index, whereas nonalcoholic beverages were evaluated based on calories from added sugar. Teen Choice Award nominations were used to measure the celebrities' popularity among adolescents. Of the 590 endorsements made by the 163 celebrities in the sample, consumer goods (eg, fragrances, makeup) represented the largest endorsement category (26%), followed by food and beverage (18%) and retail (11%). Sixty-five celebrities were collectively associated with 57 different food and beverage brands owned by 38 parent companies. Of these 65 celebrities, 53 (81.5%) had ≥1 Teen Choice Award nomination. Forty-nine (71%) of the 69 nonalcoholic beverage references promoted sugar-sweetened beverages. Twenty-one (80.8%) of the 26 endorsed foods were energy dense and nutrient poor. Baauer, will.i.am, Justin Timberlake, Maroon 5, and Britney Spears had the most food and beverage endorsements. This study demonstrates that music celebrities who are popular among adolescents endorse energy-dense, nutrient-poor products. Copyright © 2016 by the American Academy of Pediatrics.
Li, Songtao; Liao, Xilu; Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying; Sun, Changhao
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.
Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA, an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD-induced obese non-alcoholic fatty liver disease (NAFLD rat model. METHODOLOGY/PRINCIPAL FINDINGS: Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.
Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan
Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.
Hua, Yinan; Clark, Suzanne; Ren, Jun; Sreejayan, Nair
Type 2 diabetes is often associated with obesity, dyslipidemia, and cardiovascular anomalies and is a major health problem approaching global epidemic proportions. Insulin resistance, a prediabetic condition, precedes the onset of frank type 2 diabetes and offers potential avenues for early intervention to treat the disease. Although lifestyle modifications and exercise can reduce the incidence of diabetes, compliance has proved to be difficult, warranting pharmacological interventions. However, most of the currently available drugs that improve insulin sensitivity have adverse effects. Therefore, attractive strategies to alleviate insulin resistance include dietary supplements. One such supplement is chromium, which has been shown reduce insulin resistance in some, but not all, studies. Furthermore, the molecular mechanisms of chromium in alleviating insulin resistance remain elusive. This review examines emerging reports on the effect of chromium, as well as molecular and cellular mechanisms by which chromium may provide beneficial effects in alleviating insulin resistance. PMID:22423897
Espeland, Erin K; Kettenring, Karin M
Ecosystem-based adaptation (EbA) uses biodiversity and ecosystem services to reduce climate change impacts to local communities. Because plants can alleviate the abiotic and biotic stresses of climate change, purposeful plant choices could improve adaptation. However, there has been no systematic review of how plants can be applied to alleviate effects of climate change. Here we describe how plants can modify climate change effects by altering biological and physical processes. Plant effects range from increasing soil stabilization to reducing the impact of flooding and storm surges. Given the global scale of plant-related activities such as farming, landscaping, forestry, conservation, and restoration, plants can be selected strategically-i.e., planting and maintaining particular species with desired impacts-to simultaneously restore degraded ecosystems, conserve ecosystem function, and help alleviate effects of climate change. Plants are a tool for EbA that should be more broadly and strategically utilized. Copyright © 2018. Published by Elsevier Ltd.
Full Text Available Driving fatigue is more likely to bring serious safety trouble to traffic. Therefore, accurately and rapidly detecting driving fatigue state and alleviating fatigue are particularly important. In the present work, the electrical stimulation method stimulating the Láogóng point (劳宫PC8 of human body is proposed, which is used to alleviate the mental fatigue of drivers. The wavelet packet decomposition (WPD is used to extract θ, α, and β subbands of drivers’ electroencephalogram (EEG signals. Performances of the two algorithms (θ+α/(α+β and θ/β are also assessed as possible indicators for fatigue detection. Finally, the differences between the drivers with electrical stimulation and normal driving are discussed. It is shown that stimulating the Láogóng point (劳宫PC8 using electrical stimulation method can alleviate driver fatigue effectively during longtime driving.
Hepatocellular injury resulting from increased lipid peroxidation products and oxidative stress is considered a potential mechanism driving the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitsis (NASH). To test the significance of lipid peroxidation and protein...
Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean P; Loomba, Rohit; Brunt, Elizabeth M; Chen, Yii-Der Ida; Goodarzi, Mark O; Taylor, Kent D; Yates, Katherine P; Tonascia, James; Rotter, Jerome I
To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7 -07 ). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9 -07 ). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies. Copyright © 2017 Elsevier Inc. All rights reserved.
Bilek, Maciej; Rybakowa, Maria
Increase the intake of sugars among the inhabitants of developed countries is related to, among others, increasing consumption of non-alcoholic beverages, for which the relationship with the epidemic of obesity, particularly among children and adolescents, has been proven. The most frequently cited are non-alcoholic beverages, sweetened glucose-fructose syrup, ie. colas, tonics, ice teas, lemonades. Fruit drinks, fruit juices and nectars are commonly cited as a healthy alternative to non-alcoholic beverages and, however, we do not pay attention to the high content of sugars in these products. Determine the content of sugars in non-alcohollic beverages popular among children and adolescents. 80 non-alcoholic beverages such as cola, tonic, lemonade, ice tea, flavored waters, fruit juices, fruit nectars and fruit drinks. Evaluation of the content of monosaccharides and sucrose was performed by high performance liquid chromatography method (HPLC). In the tested non-alcohollic beverages, monosaccharides ie. glucose and fructose and the disaccharide sucrose were detected in different proportions. The product with the lowest content of the total sugars content was flavored water with lemon flavor based on the mineral water (2.72 g/100 ml). In the group of fruit juices, fruit nectars and fruit drinks highest sugars content have been reported (12.94 g/100 ml for aronia nectar and 12.76 g/100ml for the juice of pomegranate and grapes). Significant monosaccharides and sucrose content in the tested non-alcohollic beverages tends to claim that their manufacturers should be obliged to place warnings on the labels addressed to patients suffering from disorders of carbohydrate metabolism. Educational programs for children and adolescents with diabetes should include information about the content of a large amount of sugars in fruit products: fruit juices, fruit drinks and fruit nectar. © Polish Society for Pediatric Endocrinology and Diabetology.
Kitajima, Yoichiro; Eguchi, Yuichiro; Ishibashi, Eriko
Although nonalcoholic fatty liver disease (NAFLD) is associated with visceral obesity, the relationship between visceral fat accumulation and skeletal muscle steatosis in patients with NAFLD has not been established. We evaluated: the relationship between multifidus muscular tissue steatosis, visceral fat accumulation, and biochemical data in a cross-sectional study, and the influence of weight reduction on multifidus muscular tissue steatosis in a longitudinal study. Three hundred thirty-three NAFLD patients were enrolled. Hepatic steatosis, visceral fat area, and the multifidus muscle/subcutaneous fat attenuation ratio (MM/F ratio) were evaluated by computed tomography. To evaluate how weight reduction produced by diet and exercise affected the MM/F ratio, changes in the MM/F ratio were compared between weight reduction and non-weight reduction groups. There was a gender difference in MM/F ratios. The MM/F ratio was significantly correlated with age (male r=0.613, P<0.01; female r=0.440, P<0.01). The MM/F ratio was positively correlated with visceral fat area (male: r=0.262, P<0.01; female: r=0.214, P<0.01). A decrease in the MM/F ratio, concomitant with reduced visceral fat accumulation, led to alleviation of hepatic steatosis in 20 patients with weight reduction, but not in 22 patients without weight reduction. The MM/F ratio was closely related to aging and visceral fat accumulation. The MM/F ratio was improved by weight reduction, indicating that fat accumulation in the multifidus muscle evaluated by computed tomography might be a therapeutic indicator of NAFLD. (author)
Liu, Yanjun; Shi, Di; Tian, Yingying; Liu, Yuntao; Zhan, Qiping; Xu, Jie; Wang, Jingfeng; Xue, Changhu
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Disturbed cholesterol metabolism plays a crucial role in the development of NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on liver steatosis and cholesterol metabolism in NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group, lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model rats were established by administering a diet containing 1% orotic acid. To determine the possible cholesterol metabolism promoting mechanism of EPA-PC, we analyzed the transcription of key genes and transcriptional factors involved in hepatic cholesterol metabolism. EPA-PC dramatically alleviated hepatic lipid accumulation, reduced the serum TC concentration, and elevated HDLC levels in NAFLD rats. Fecal neutral cholesterol excretion was also promoted by EPA-PC administration. Additionally, EPA-PC decreased the mRNA expression of hydroxymethyl glutaric acid acyl (HMGR) and cholesterol 7α-hydroxylase (CYP7A), and increased the transcription of sterol carrying protein 2 (SCP2). Moreover, EPA-PC stimulated the transcription of peroxisome proliferators-activated receptor α (PPARα) and adenosine monophosphate activated protein kinase (AMPK) as well as its modulators, liver kinase B1 (LKB1) and Ca 2+ /calmodulin-dependent kinase kinase (CAMKK). Based on the results, the promoting effects of EPA-PC on NAFLD may be partly associated with the suppression of cholesterol synthesis via HMGR inhibition and the enhancement of fecal cholesterol excretion through increased SCP2 transcription. The underlying mechanism may involve stimulation of PPARα and AMPK.
Liu, Y T; Li, Y Q; Wang, Y Z
Objective: To investigate the protective effect of Saccharomyces boulardii against intestinal mucosal barrier injury in rats with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 36 healthy male Sprague-Dawley rats with a mean body weight of 180±20 g were randomly divided into control group, model group, and treatment group, with 12 rats in each group, after adaptive feeding for 1 week. The rats in the control group were given basic feed, and those in the model group and treatment group were given high-fat feed. After 12 weeks of feeding, the treatment group was given Saccharomyces boulardii (75×10 8 CFU/kg/d) by gavage, and those in the control group and model group were given isotonic saline by gavage. At the 20th week, blood samples were taken from the abdominal aorta to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), intestinal fatty acid binding protein (IFABP), tumor necrosis factor-α (TNF-α), and endotoxins. The liver pathological changes, intestinal histopathological changes, and expression of occludin in the intestinal mucosa were observed. Fecal samples were collected to measure the changes in Escherichia coli and Bacteroides. A one-way analysis of variance and the SNK test were used for comparison between multiple groups, and the rank sum test was used as the non-parametric test. Results: Compared with the control group, the model group had significantly higher body weight, liver mass, and liver index ( P 0.05). Compared with the control group, the model group had significant increases in the levels of endotoxin, TNF-α, and IFABP ( P Saccharomyces boulardii can reduce body weight and improve hepatocyte steatosis. Saccharomyces boulardii can reduce endotoxemia in NAFLD rats and thus alleviate inflammatory response. Saccharomyces boulardii can also adjust the proportion of Escherichia coli and Bacteroides in the intestine of NAFLD rats.
Full Text Available Although Japanese herbal medicines (JHMs are widely used in Japan, only a few studies have investigated their effects on nonalcoholic steatohepatitis (NASH. In the present study, we examined the effect of 4 kinds of JHMs [sho-saiko-to (TJ-9, inchin-ko-to (TJ-135, juzen-taiho-to (TJ-48, and keishi-bukuryo-gan (TJ-25] on a mouse model of NASH. Db/db mice were divided into 6 groups: control diet (control, methionine- and choline-deficient diet (MCD, and MCD diet supplemented with TJ-9, TJ-135, TJ-48, and TJ-25 (TJ-9, TJ-135, TJ-48, and TJ-25, respectively. All mice were sacrificed after 4 weeks of treatment, and biochemical, pathological, and molecular analyses were performed. Serum alanine aminotransferase levels and liver histology, including necroinflammation and fibrosis, were significantly alleviated in the TJ-9 and TJ-48 groups compared with the MCD group. The expression level of transforming growth factor (TGF-β1 mRNA in the liver was significantly suppressed by TJ-48. Although the differences were not statistically significant, the expression levels of tumor necrosis factor (TNF-α and interleukin (IL-6 were lower, and those of peroxisome proliferators-activated receptor (PPARγ were higher in the TJ-9 and/or TJ-48 groups than in the MCD group. Similarly, even though the results were not statistically significant, malondialdehyde levels in liver tissues were lower in the TJ-9 and TJ-48 groups than in the MCD group. We showed that JHMs, especially TJ-9 and TJ-48, inhibited the necroinflammation and fibrosis in the liver of a mouse model of NASH, even though the mechanisms were not fully elucidated. Further studies are needed in the future to investigate the possibility of clinical application of these medicines in the treatment for NASH.
Alam, Kazi Rafiqul
Ganokendras (people's learning centers) employ a literacy-based approach to alleviating poverty in Bangladesh. They give special attention to empowering rural women, among whom poverty is widespread. The present study reviews the Ganokendra-approach to facilitating increased political and economic awareness and improving community conditions in…
poverty alleviation on the inhabitants of Nigeria with special reference to. Asa and Ilorin West Local ... poverty is defined as a state of deprivation in terms of both economic and social indicators such as income ..... Source Book. The World Bank ...
The occasional paper studies the role of zakat and awqaf in mitigating poverty in Muslim communities. The study addresses the issue by studying the institutional set-up and mechanisms of using zakat and awqaf for poverty alleviation. It discusses how these institutions can be implemented successfully to achieve the results in contemporary times using theoretical arguments and empirical support.
It will help the planners and the policy makers to determine the best methods to tackle poverty in order to alleviate youth employment. The study made use of descriptive research design for the investigation. All the local government in Ogun State constitutes the population for the study. Out of these, two local governments ...
Rogerson, Christian M.
Growing international attention has focussed on the potential role of urban agriculture in poverty alleviation. The aim in this paper is to analyse the existing challenge of urban poverty in South Africa and examine the potential role of urban agriculture as a component of a pro-poor urban development strategy.
Nigeria is facing serious poverty and hunger despite her enormous resources. Recent statistics reveal that poverty and hunger are increasing despite successive governments and non–governmental organizations alleviation programmes. Unless, these twin problems are tacked urgently, they are likely to undermine the ...
Lade, Steven J; Haider, L Jamila; Engström, Gustav; Schlüter, Maja
The poverty trap concept strongly influences current research and policy on poverty alleviation. Financial or technological inputs intended to "push" the rural poor out of a poverty trap have had many successes but have also failed unexpectedly with serious ecological and social consequences that can reinforce poverty. Resilience thinking can help to (i) understand how these failures emerge from the complex relationships between humans and the ecosystems on which they depend and (ii) navigate diverse poverty alleviation strategies, such as transformative change, that may instead be required. First, we review commonly observed or assumed social-ecological relationships in rural development contexts, focusing on economic, biophysical, and cultural aspects of poverty. Second, we develop a classification of poverty alleviation strategies using insights from resilience research on social-ecological change. Last, we use these advances to develop stylized, multidimensional poverty trap models. The models show that (i) interventions that ignore nature and culture can reinforce poverty (particularly in agrobiodiverse landscapes), (ii) transformative change can instead open new pathways for poverty alleviation, and (iii) asset inputs may be effective in other contexts (for example, where resource degradation and poverty are tightly interlinked). Our model-based approach and insights offer a systematic way to review the consequences of the causal mechanisms that characterize poverty traps in different agricultural contexts and identify appropriate strategies for rural development challenges.
Despite South Africa's economic growth having been accelerated considerably in the country, poverty levels have not decreased as one would have experienced. Food Security Projects initiated by the government of South Africa in order to help alleviate poverty within Limpopo Province have proved unsustainable and ...
The study investigated the Role of Information Technology (IT) in thecreation of wealth and poverty alleviation in Nigeria. The design of the studywas a descriptive survey, carried out at Nwafor Orizu College of Education,Nsugbe in Anambra State of Nigeria. One hundred and ninety three (193)respondents formed the ...
Lade, Steven J.; Haider, L. Jamila; Engström, Gustav; Schlüter, Maja
The poverty trap concept strongly influences current research and policy on poverty alleviation. Financial or technological inputs intended to “push” the rural poor out of a poverty trap have had many successes but have also failed unexpectedly with serious ecological and social consequences that can reinforce poverty. Resilience thinking can help to (i) understand how these failures emerge from the complex relationships between humans and the ecosystems on which they depend and (ii) navigate diverse poverty alleviation strategies, such as transformative change, that may instead be required. First, we review commonly observed or assumed social-ecological relationships in rural development contexts, focusing on economic, biophysical, and cultural aspects of poverty. Second, we develop a classification of poverty alleviation strategies using insights from resilience research on social-ecological change. Last, we use these advances to develop stylized, multidimensional poverty trap models. The models show that (i) interventions that ignore nature and culture can reinforce poverty (particularly in agrobiodiverse landscapes), (ii) transformative change can instead open new pathways for poverty alleviation, and (iii) asset inputs may be effective in other contexts (for example, where resource degradation and poverty are tightly interlinked). Our model-based approach and insights offer a systematic way to review the consequences of the causal mechanisms that characterize poverty traps in different agricultural contexts and identify appropriate strategies for rural development challenges. PMID:28508077
At first glance, Asia seems to have all the organizations, skills, policies and facilities essential for bio-innovation. However, these are not generally put to the service of the millions of poor who lack access to technology. This project aims to stimulate research on bio-innovation for poverty alleviation, sustainable employment ...
The prospects and challenges of this strategy in the context of the Nigerian situation are articulated and the conclusion of the paper is that poverty alleviation in contemporary Nigeria requires both economic policy and educational reforms. To enhance the human capital of the poor in particular, the priorities for educational ...
Occupational stress in not a new phenomenon in the working population. However, in the helping professions it has only recently attracted attention. The survey reported here was carried out in order to assess the extent of occupational stress, identify its causes, and suggest ways in which occupational stress can be alleviated. Field social…
Raszeja-Wyszomirska, Joanna; Lawniczak, Małgorzata; Marlicz, Wojciech; Miezyńska-Kurtycz, Joanna; Milkiewicz, Piotr
Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others
de Campos Mazo, Daniel Ferraz; Mattar, Rejane; Stefano, José Tadeu; da Silva-Etto, Joyce Matie Kinoshita; Diniz, Márcio Augusto; Duarte, Sebastião Mauro Bezerra; Rabelo, Fabíola; Lima, Rodrigo Vieira Costa; de Campos, Priscila Brizolla; Carrilho, Flair José; Oliveira, Claudia P
AIM To assess lactase gene (LCT)-13910C>T polymorphisms in Brazilian non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients in comparison with healthy controls. METHODS This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clínicas, São Paulo, Brazil. The polymorphism of lactase non-persistence/lactase persistence (LCT-13910C>T) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients (steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher’s exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were performed. RESULTS No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients (66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls (59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism (LCT-13910C>T) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase non-persistence (low lactase activity or hypolactasia) phenotype was associated with higher insulin levels (23.47 ± 15.94 μU/mL vs 15.8 ± 8.33 μU/mL, P = 0.027) and a higher frequency of insulin resistance (91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes (P = 0
Benetolo, Patrícia O; Fernandes, Maria I M; Ciampo, Ieda R L Del; Elias-Junior, Jorge; Sawamura, Regina
To determine the frequency of nonalcoholic fatty liver disease using nuclear magnetic resonance as a noninvasive method. This was a cross-sectional study conducted on 50 children and adolescents followed up at an outpatient obesity clinic. The subjects were submitted to physical examination, laboratory tests (transaminases, liver function tests, lipid profile, glycemia, and basal insulin) and abdominal nuclear magnetic resonance (calculation of hepatic, visceral, and subcutaneous fat). Nonalcoholic fatty liver disease was diagnosed in 14 (28%) participants, as a severe condition in eight (percent fat >18%), and as non-severe in four (percent fat from 9% to 18%). Fatty liver was associated with male gender, triglycerides, AST, ALT, AST/ALT ratio, and acanthosis nigricans. Homeostasis model assessment of insulin resistance and metabolic syndrome did not show an association with fatty liver. The frequency of nonalcoholic fatty liver disease in the present population of children and adolescents was lower than that reported in the international literature. It is suggested that nuclear magnetic resonance is an imaging exam that can be applied to children and adolescents, thus representing an effective noninvasive tool for the diagnosis of nonalcoholic fatty liver disease in this age range. However, further national multicenter studies with longitudinal design are needed for a better analysis of the correlation between nonalcoholic fatty liver disease and its risk factors, as well as its consequences. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
Nikolakaros, Georgios; Ilonen, Tuula; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G; Vataja, Risto
Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy. Copyright © 2016 Elsevier B.V. All rights reserved.
S A Butrova
Full Text Available The mechanism of action of metformin is realized through activation of cAMP-dependent protein kinase, leading to a decrease hepatic glucose production as well as to decrease the synthesis of triglycerides and an increase in fat oxidation. Several studies have demonstrated the positive effect of the drug in non-alcoholic fatty liver disease, manifested in reducing the activity of enzymes, reducing the size of the liver and insulin resistance. The aim of our study was to evaluate the effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease. The study found that the use Siofor 850 mg 2 times a day in conjunction with a reduced-calorie nutrition in patients with metabolic syndrome and nonalcoholic fatty liver disease leads to a significant reduction in insulin resistance associated with decreased activity of transaminases, improvement of metabolic parameters. The therapy Siofor majority of patients (60% with metabolic syndrome and nonalcoholic fatty liver disease achieved a clinically significant weight loss and improved body composition. Application Siofor improves lifestyle changes in obese patients with non-alcoholic liver disease dirovoy and metabolic disorders.
Hagymási, Krisztina; Reismann, Péter; Rácz, Károly; Tulassay, Zsolt
The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.
Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been show...
Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a
Nguyen, Vi; George, Jacob
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities that can range from bland liver fat (steatosis), to hepatic inflammation and liver injury (steatohepatitis). It is estimated that NAFLD will become the principal cause of liver disease in Western nations and the leading indication for liver transplantation. Advancements in disease recognition and management are therefore paramount. Although the development of new, reliable drug therapies is vital, lifestyle interventions remain the most effective treatment modality. In addition to weight loss as a primary measure of treatment success, there is growing recognition that other endpoints, including the prevention or delay of diabetes onset, reduced cardiovascular events, prevention of cancer, and improved overall mortality, are equally important outcomes that can be independently modified by lifestyle change. Moreover, NAFLD is inextricably part of a complex, systemic disease process that is linked with deeply entrenched maladaptive lifestyle behaviors. Thus, a holistic, multidisciplinary, and individualized approach to disease management will be the key to achieving any realistic population-level change. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Full Text Available Objective:Nonalcoholic fatty liver disease (NAFLD which is strongly correlated with obesity; has been a common worldwide health problem with the improvements in social status. Body composition studies are accepted as a simple follow-up tool for treatment of obesity. Since the correlation of body mass index (BMI with the hepatosteatosis (HS is well known; the aim of this study was to assess the usefulness of body composition parameters (BCP to determine HS on NAFLD patients; using dual bioimpedance analyzer (BIA. Methods:A total of 253 patients with diagnosis of NAFLD were included into the study. The demographic parameters such as age, sex and BMI were collected; and the ultrasonographic (US evolution was performed to determine the HS stages. The BCP, such as amount and the percentage of total body fat, fat free mass, and total body water were assessed with the dual bioimpedance analyzer. Results:There were strong significant correlations between BMI and HS, between BCP and HS (p0.05. Conclusion: According to our results, it can be concluded that BCP values may have a diagnostic value on diagnosis of NAFLD.
Te Sligte, K.; Bourass, I.; Sels, J.P.; Driessen, A.; Stockbrugger, R.W.; Koek, G.H.
Non-alcoholic steatohepatitis (NASH) is a metabolic liver disorder that is seen in 2-6% of the general population. It manifests itself by elevated liver enzymes, frequently without symptoms. The histological findings include steatosis, inflammation, fibrosis, and cirrhosis. Three case reports are presented to illustrate features of NASH. A two-hit model has been proposed in the pathogenesis of NASH. The first hit is hepatic steatosis. A hypercaloric diet with high levels of carbohydrates and saturated fatty acids results in elevated plasma free fatty acids (FFA) and expands the adipose tissue. Insulin resistance develops and augments steatosis. Oxidation of FFA yields toxic free radicals, resulting in lipid peroxidation. They cause the second hits: increased oxidative stress on hepatocytes and induction of pro-inflammatory cytokines. When the antioxidant capacities of the liver are insufficient, mitochondrial dysfunction and tumor necrosis factor alpha (TNF-alpha) cause inflammation and fibrosis. Treatment consists of life style modifications, particularly weight loss and exercise. Many drugs have been tried in the treatment of NASH. The insulin-sensitizing drugs metformin, rosiglitazone, and pioglitazone, and the antioxidant vitamin E show promising results. Further investigation of therapeutic options is needed to direct the choice of therapy in the future.
Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical determinant of this process. However, there is evidence that portal venous pressure may begin to rise in the earliest stages of NAFLD when fibrosis is far less advanced or absent. The biological and clinical significance of these early changes in sinusoidal homeostasis remains unclear. Experimental and human observations indicate that sinusoidal space restriction due to hepatocellular lipid accumulation and ballooning may impair sinusoidal flow and generate shear stress, increasingly disrupting sinusoidal microcirculation. Sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells are key partners of hepatocytes affected by NAFLD in promoting endothelial dysfunction through enhanced contractility, capillarization, adhesion and entrapment of blood cells, extracellular matrix deposition, and neovascularization. These biomechanical and rheological changes are aggravated by a dysfunctional gut-liver axis and splanchnic vasoregulation, culminating in fibrosis and clinically significant portal hypertension. We may speculate that increased portal venous pressure is an essential element of the pathogenesis across the entire spectrum of NAFLD. Improved methods of noninvasive portal venous pressure monitoring will hopefully give new insights into the pathobiology of NAFLD and help efforts to identify patients at increased risk for adverse outcomes. In addition, novel drug candidates targeting reversible components of aberrant sinusoidal circulation may prevent progression in NAFLD.
Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore
In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964
Non-alcoholic fatty liver disease (NAFLD) has been known as the hepatic feature of metabolic syndrome. Extra fat depots, especially in visceral areas, develop insulin resistance as a result of mild oxidation and inflammation. Insulin resistance induces lipolysis and releases free fatty acids into the circulation, where they are transported to the liver. In the liver, free fatty acids are converted to triglycerides and accumulate, causing simple steatosis that, if left untreated, can lead to steatohepatitis, and subsequently liver necrosis and cirrhosis.Flavonoids, a group of plant compounds with incredible biological characteristics, have shown advantages in pathological conditions. Beneficial effects of flavonoids against NAFLD and its related disorders have been observed in both animal and human studies. Various mechanisms have been found for their protection. Flavonoids prevent hepatosteatosis by increasing fatty acid oxidation in the liver. They can also reduce caloric intake and decrease body weight and fat deposition in visceral tissues. Flavonoids are unique antioxidants that exert their beneficial effects through inhibition of nuclear factor κB, thereby attenuating release of inflammatory cytokines, which are triggers of insulin resistance. Finally, flavonoids have shown to increase adiponectin, improve insulin sensitivity and glucose tolerance, correct dyslipidemia, and reduce blood pressure in patients with NAFLD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Henning, Justin R; Graffeo, Christopher S; Rehman, Adeel; Fallon, Nina C; Zambirinis, Constantinos P; Ochi, Atsuo; Barilla, Rocky; Jamal, Mohsin; Deutsch, Michael; Greco, Stephanie; Ego-Osuala, Melvin; Bin-Saeed, Usama; Rao, Raghavendra S; Badar, Sana; Quesada, Juan P; Acehan, Devrim; Miller, George
Nonalcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DCs) are antigen-presenting cells with an emerging role in hepatic inflammation. We postulated that DCs are important in the progression of NASH. We found that intrahepatic DCs expand and mature in NASH liver and assume an activated immune phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibroinflammation. Our mechanistic studies support a regulatory role for DCs in NASH by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. We found that DCs limit CD8(+) T-cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Our findings support a role for DCs in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. Copyright © 2013 American Association for the Study of Liver Diseases.
Sid, Victoria; Siow, Yaw L; O, Karmin
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.
Full Text Available Nonalcoholic steatohepatitis has become one of the most common liver-related health problems. This condition has been linked to an unhealthy diet and weight gain, but it can also be observed in nonobese people. The standard of care is represented by the lifestyle intervention. However, because this approach has several limitations, such as a lack of compliance, the use of many drugs has been proposed. The first-line pharmacological choices are vitamin E and pioglitazone, both showing a positive effect on transaminases, fat accumulation, and inflammation. Nevertheless, vitamin E has no proven effect on fibrosis and on long-term morbidity and mortality and pioglitazone has a negative impact on weight. Other drugs have been studied such as metformin, ursodeoxycholic acid, statins, pentoxiphylline, and orlistat with only partially positive results. Among the emerging treatments, telmisartan is particularly interesting as it seems to have an impact on insulin resistance, liver steatosis, inflammation, and fibrosis. However, the pathogenesis of steatohepatitis is highly complex and is determined by different parallel hits; indeed, the association of different drugs that act on various levels has been suggested. In conclusion, lifestyle intervention should be optimised and the associations of different drugs should be tested in large studies with long-term outcomes.
Issa, Danny; Wattacheril, Julia; Sanyal, Arun J
There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered: This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis. Expert opinion: Current therapies continue to remain suboptimal. Weight loss is effective but hard to achieve. Traditional and endoscopic bariatric procedures are promising although more randomized trials are needed and the long-term safety remains to be established. Clinical trials have demonstrated the efficacy of several drugs for the treatment of NASH. Of these, there remains some uncertainty about the long-term safety of vitamin E. Pioglitazone is associated with osteopenia, fluid retention and weight gain. Obeticholic acid causes pruritus in a substantial proportion of subjects and elafibranor has been associated with transient rises in creatinine. Several exciting therapies are under development and results of clinical and post-marketing trials will help elucidate their safety.
Della Corte, Claudia; Liccardo, Daniela; Ferrari, Federica; Alisi, Anna; Nobili, Valerio
In the past decade, nonalcoholic fatty liver disease (NAFLD) had rapidly become one of the most common liver diseases. If efficient therapeutic strategies will not reduce the prevalence of NAFLD in children soon, serious deleterious effects on the quality of life of these patients in adulthood are expected. Lifestyle modification is the current first-line therapy for pediatric NAFLD, even though it is difficult to obtain and to maintain. Therefore, lifestyle changes are usually ineffective and long-lasting improvement of the NAFLD-associated liver damage is rarely observed. As guidelines for the management of NAFLD in children are still lacking, the identification of effective treatments represents a challenge for pediatric hepatologists in the near future. Here, we review the existing therapeutic approaches for treating NAFLD in children and overview all ongoing clinical trials for new promising drugs in pediatric setting. Considering the multifactorial pathogenesis and the wide spectrum of histological and clinical features of NAFLD, we believe that a drug mix, containing agents that are effective against the principal pathogenetic factors, associated with lifestyle modification, could represent the winning choice of treatment for pediatric NAFLD.
Ter Horst, Kasper W; Serlie, Mireille J
Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be used for gluconeogenesis and de novo lipogenesis (DNL). Fructose-derived precursors also act as nutritional regulators of the transcription factors, including ChREBP and SREBP1c, that regulate the expression of hepatic gluconeogenesis and DNL genes. In support of these mechanisms, fructose intake increases hepatic gluconeogenesis and DNL and raises plasma glucose and triglyceride levels in humans. However, epidemiological and fructose-intervention studies have had inconclusive results with respect to liver fat, and there is currently no good human evidence that fructose, when consumed in isocaloric amounts, causes more liver fat accumulation than other energy-dense nutrients. In this review, we aim to provide an overview of the seemingly contradicting literature on fructose and NAFLD. We outline fructose physiology, the mechanisms that link fructose to NAFLD, and the available evidence from human studies. From this framework, we conclude that the cellular mechanisms underlying hepatic fructose metabolism will likely reveal novel targets for the treatment of NAFLD, dyslipidemia, and hepatic insulin resistance. Finally, fructose-containing sugars are a major source of excess calories, suggesting that a reduction of their intake has potential for the prevention of NAFLD and other obesity-related diseases.
Papanastasiou, Labrini; Fountoulakis, Stelios; Vatalas, Ioannis-Anastasios
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5α/5β-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.
Benedict, Mark; Zhang, Xuchen
Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the “magic bullet” in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients. PMID:28652891
Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B
Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.
Full Text Available ObjectiveTo investigate the collection and preservation of blood specimens from patients with nonalcoholic fatty liver disease (NAFLD and the establishment and information management of biobank. MethodsWhole blood samples were collected from 1226 patients who were diagnosed with NAFLD based on B-mode ultrasound and blood tests from October 2009 to October 2013. Biochemical parameters were measured. Plasma and whole-blood genomic DNA was extracted from the samples, and the purity and concentration of DNA were determined. Specimens were preserved in a refrigerator (-80℃. An information management system for NAFLD biobank was established. ResultsSpecimens of 1226 NAFLD patients, including those of 83 twins and 100 families, were collected. The success rate was 100% for extraction of plasma and whole-blood genomic DNA. One hundred DNA samples were randomly selected for testing, and the results showed that the collected specimens met the requirements of following experiments. ConclusionThe NAFLD Biobank has been successfully established in this study. It has the standard information management system and enables the quality control and information management of specimens, laying a solid foundation for further research on NAFLD.
Doaa A. Ghareeb
Full Text Available Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL. The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE and amyloid beta precursor protein (AβPP. These changes were significantly correlated with decreased insulin degrading enzyme (IDE and beta-amyloid40 (Aβ40 and increased beta-amyloid42 (Aβ42 in the hippocampal region. Daily administration of berberine (50 mg/kg for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.
Kim, Ja Kyung; Lee, Kwan Sik; Lee, Dong Ki; Lee, Su Yeon; Chang, Hye Young; Choi, Junjeong; Lee, Jung Il
Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen α1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor α showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.
Full Text Available BACKGROUND Cardiovascular dysfunction is the major component of morbidity in patients of liver cirrhosis and a cardinal prognostic indicator in patients undergoing liver transplantation. The constellation of hyperdynamic circulation, peripheral vasodilation and volume overload alters the systolic and diastolic dysfunction leading to cirrhotic cardiomyopathy (CCM. In this study, we evaluated and compared the diastolic dysfunction among alcoholic and non-alcoholic cirrhotic patients. AIMS 1 To Study the Prevalence of Diastolic Dysfunction in Alcoholic & Non-Alcoholic Cirrhotics and Controls. 2 To Compare the Diastolic functional status between alcoholic and non-alcoholic cirrhosis patients. MATERIALS AND METHODS A cross-sectional case control study was conducted in 100 male cirrhotic patients consisting of alcoholic and non-alcoholic cirrhotic subjects with age matched 50 controls in Pt. JNM Medical College & Dr. BRAM Hospital, Raipur. Left ventricular diastolic dysfunction was assessed using echocardiographic parameters. STATISTICAL ANALYSIS The range, median, standard deviation and statistical significance were calculated. Most of the data is analysed by Student Ttest, Mann Whitney U test, while the data with frequency distribution is analysed by Fisher’s exact. With p value 1. CONCLUSION Our study showed that patients with alcoholic and non-alcoholic cirrhosis have higher occurrence of DD (49% and 46% respectively than controls owing to alterations in the myocardial contractile and relaxation function. It also shows that although DD is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There were no significant differences in diastolic parameters between alcoholic and non-alcoholic cirrhosis concluding that alcohol likely plays a non-significant role in cardiovascular dysfunction in cirrhotics.
Yang, Jia-Yao; Tao, Dong-Qing; Liu, Song; Zhang, Shu; Ma, Wei; Shi, Zhao-Hong
To investigate the effects of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang on the cell proliferation and apoptosis of nonalcoholic fatty liver cells through the nonalcoholic fatty liver cell model established by inducing L02 cells with oleic acid. Different concentrations of oleic acid were added into L02 cells to induce the nonalcoholic fatty liver cell model. Oil red O staining was used to observe fatty droplets of fatty liver cells. Automatic biochemical analyzer was used to detect the levels of aspartic transaminase(AST), alanine aminotransferase(ALT), total cholesterol(TC), and triglyceride(TG) in the cell supernatants. There were five groups, namely normal group, model group, model and Sijunzi Tang group, model and Lizhong Tang group, and model and Fuzi Lizhong Tang group. The cell proliferation and apoptosis of the five groups were detected by MTT colorimetry test and flow cytometer. The expressions of PCNA, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax and Bcl-2 proteins of the five groups were detected by Western blot. The oil red O staining results showed that the optimum concentration of oleic acid that was used to induce nonalcoholic fatty liver cell models was 80 mg•L-1. The levels of AST, ALT, TC and TG in the nonalcoholic fatty liver cell supernatants were higher than that in normal liver cell supernatants(PTang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells(PTang showed the best effect. Western blot results showed that Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could down-regulate the expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and Bax proteins, and up-regulate the expressions of PCNA and Bcl-2 proteins of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang showed the best effect. In conclusion, all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell
Haga, Yuki; Kanda, Tatsuo; Sasaki, Reina; Nakamura, Masato; Nakamoto, Shingo; Yokosuka, Osamu
Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review, the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed.
Keating, Shelley E; George, Jacob; Johnson, Nathan A
As exercise is now an established therapy for the management of non-alcoholic fatty liver disease (NAFLD), recent investigations have sought to identify the optimal dose (type, intensity and amount) of exercise for hepatic benefit. Here, the authors discuss the following: the role of aerobic exercise for the modulation of hepatic steatosis; the limited evidence for the role of resistance training in reducing liver fat; the lack of evidence from clinical trials on the role of exercise in non-alcoholic steatohepatitis; and the benefits of exercise for patients with NAFLD, beyond steatosis. Based on current evidence, the authors provide recommendations for exercise prescription for patients with NAFLD.
Leth, Torben; Jensen, U.; Fagt, Sisse
In 2005, 76 out of 177 analysed samples of non-alcoholic beverages were found to contain the intense sweeteners cyclamate, acesulfame-K, aspartame, and saccharin. The content of cyclamate did not exceed the now permitted maximum level in the European Union of 250 mg l(-1) in soft drinks. The esti......In 2005, 76 out of 177 analysed samples of non-alcoholic beverages were found to contain the intense sweeteners cyclamate, acesulfame-K, aspartame, and saccharin. The content of cyclamate did not exceed the now permitted maximum level in the European Union of 250 mg l(-1) in soft drinks...
Kragh, Knud Abildgaard; Hansen, Morten Hartvig
Vertical wind shear is one of the dominating causes of load variations on the blades of a horizontal axis wind turbine. To alleviate the varying loads, wind turbine control systems have been augmented with sensors and actuators for individual pitch control. However, the loads caused by a vertical...... wind shear can also be affected through yaw misalignment. Recent studies of yaw control have been focused on improving the yaw alignment to increase the power capture at below rated wind speeds. In this study, the potential of alleviating blade load variations induced by the wind shear through yaw...... misalignment is assessed. The study is performed through simulations of a reference turbine. The study shows that optimal yaw misalignment angles for minimizing the blade load variations can be identified for both deterministic and turbulent inflows. It is shown that the optimal yaw misalignment angles can...
Roziana Ainul Hidayati
Full Text Available Poverty is a multidimensional problem that the approach to eradicate poverty must also be multidimensional. The study aims to formulate a model of poverty alleviation in coastal fishing in the North Coast of East Java. Grounded research approach used to determine the causes, impacts and implications of poverty fishermen. The results showed that the main cause of poverty that occurred in the three districts in East Java's north coast is different from one another. In Gresik district, the major cause of poverty is law enforcements that do not support fishermen and overfishing. While Lamongan more due to low fish prices and capital problems. While in Tuban fishermen due to limited infrastructure and lazy and extravagant lifestyle of the fishermen. These differences lead to different coping strategies so that later can form a concept model of poverty alleviation North Coast fishermen in East Java.
Amit Kumar Chakrabarty
Full Text Available This theoretical paper deals with Islamic microfinance and its rationality in Indian context as a panacea of Muslim poverty. Conventional microfinance system is very effective to alleviate poverty of developing countries. But it could not touch all community of people because of ‘interest’ component in debt and high degree of interest. Muslims dislike that microfinance which is based on ‘interest’ as it is strictly prohibited in Islam. Therefore the motto of financial inclusion is out of reach through conventional microfinance. An alternative interest free microfinance model has been developed in some part of world to include all Muslim poor people within the banking system. India is yet to adopt Islamic microfinance though 20% of total population is Muslim. The author strongly opines that India should adopt Islamic microfinance as a tool for poverty alleviation of Muslims as well as other communities.
Kjær, Katrine Heinsvig; Rosenqvist, Eva S. K.; Ottosen, Carl-Otto
Title: The alleviating effect of elevated CO2 on heat stress susceptibility of two wheat (Triticum aestivum L.) cultivars Session: Plant response and adaptation to abiotic stress Sindhuja Shanmugam1, Katrine Heinsvig Kjaer2*, Carl-Otto Ottosen2, Eva Rosenqvist3, Dew Kumari Sharma3 and Bernd...... Wollenweber4 1Department of Bioenergy, Tamilnadu Agricultural University, Coimbatore, India. 2Department of Food Science, Aarhus University, Kirstinebjergvej 10, 5792 Årslev, Denmark 3Institute of Agricultural Sciences and Ecology, University of Copenhagen, Hojbakkegaard Allé 9, 2630 Taastrup, Denmark 4......Institute for Agroecology, Aarhus University, Forsøgsvej 1, 4200 Slagelse, Denmark *Presenting author This study analysed the alleviating effect of elevated CO2 on stress-induced decreases in photosynthesis and changes in carbohydrate metabolism in two wheat cultivars (Triticum aestivum L.) of different...
Wiersum, K.F.; Ros-Tonen, Mirjam A.F.
This policy brief summarises the present state of scientific understanding of the potential contribution of tropical forests to poverty alleviation and highlights the implications of this knowledge for forest-based poverty alleviation policies
Jurado-Ruiz, Enrique; Varela, Lourdes M; Luque, Amparo; Berná, Genoveva; Cahuana, Gladys; Martinez-Force, Enrique; Gallego-Durán, Rocío; Soria, Bernat; de Roos, Baukje; Romero Gómez, Manuel; Martín, Franz
We evaluated the protective effect of extra virgin olive oil (EVOO) in high-fat diets (HFDs) on the inflammatory response and liver damage in a nonalcoholic fatty liver disease (NAFLD) mouse model. C57BL/6J mice were fed a standard diet or a lard-based HFD (HFD-L) for 12 wk to develop NAFLD. HFD-fed mice were then divided into four groups and fed for 24 wk with the following: HFD-L, HFD-EVOO, HFD based on phenolics-rich EVOO, and reversion (standard diet). HFD-L-induced metabolic disorders were alleviated by replacement of lard with EVOO. EVOO diets improved plasma lipid profile and reduced body weight, plasma and epididymal fat INF-γ, IL-6 and leptin levels, and macrophage infiltration. Moreover, NAFLD activity scores were reduced. The liver lipid composition showed an increase in MUFAs, especially oleic acid, and a decrease in saturated fatty acids. Hepatic adiponutrin and Cd36 gene expression was upregulated in the EVOO groups. Liver ingenuity pathway analysis revealed in EVOO groups regulation of proteins involved in lipid metabolism, small molecule biochemistry, gastrointestinal disease, and liver regeneration. Dietary EVOO could repair HFD-induced hepatic damage, possibly via an anti-inflammatory effect in adipose tissue and modifications in the liver lipid composition and signaling pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Rashid Amjad; A.R. Kemal
The paper provides a consistent time-series of poverty estimates for the period 1963- 64 to 1992-93 for both the rural as well as the urban areas, examines the influence of macroeconomic policies on the poverty levels, analyses the impact of Structural Adjustment Programmes on the levels of poverty, and suggests a strategy for poverty alleviation in Pakistan. The paper explores in particular the influence on poverty of such factors as economic growth, agricultural growth, terms of trade for t...
Arp, Frithjof; Ardisa, Alvin
Debate persists about the effectiveness of microcredit for poverty alleviation. We argue that much of this debate is due to discipline-specific research approaches and methodological complexities obscuring fundamental issues. Microfinance organisations do not operate in a vacuum: other forms of collateral-free lending must be taken into account. We illustrate our argument with a study of formal and informal collateral-free lending in the Yogyakarta region of Indonesia. Focused on the fundame...
Two control schemes designed to alleviate gust-induced vibration are analytically investigated for a helicopter with four articulated blades. One is an individual blade pitch control scheme. The other is an adaptive blade pitch control algorithm based on linear optimal control theory. In both controllers, control inputs to alleviate gust response are superimposed on the conventional control inputs required to maintain the trim condition. A sinusoidal vertical gust model and a step gust model are used. The individual blade pitch control, in this research, is composed of sensors and a pitch control actuator for each blade. Each sensor can detect flapwise (or lead-lag or torsionwise) deflection of the respective blade. The acturator controls the blade pitch angle for gust alleviation. Theoretical calculations to predict the performance of this feedback system have been conducted by means of the harmonic method. The adaptive blade pitch control system is composed of a set of measurements (oscillatory hub forces and moments), an identification system using a Kalman filter, and a control system based on the minimization of the quadratic performance function.
Mavhungu Abel Mafukata
Full Text Available The main objective of this paper is to investigate the factors having the most influence on the alleviation of poverty amongst the households adopting microfinance in Zambia. Ninety nine (n=99 respondents were randomly and purposively selected from amongst 340 microfinance adopters of the so-called Micro Bankers Trust programme operating a microfinance business in the Makululu Compound of Kabwe, Zambia. Socio-demographic primary data were collected through face-to-face interviews based on a semi-structured questionnaire instrument. The data were entered into an excel spreadsheet for analysis. The descriptive data were thereafter exported and fitted to an empirical model. The descriptive results revealed that the majority of the respondents were married, unemployed, fairly educated younger women from larger-sized poor households who drew their household income mainly from microfinance activities. The majority of the respondents thought microfinance had improved their well-being in some crucial areas. The results of the empirical model found that some respondents were indeed alleviated from poverty through microfinance. Conclusion drawn in this paper is that microfinance does alleviate poverty of the poor.
Airon José da Silva
Full Text Available Arsenic is a metalloid highly toxic to plants and animals, causing reduced plant growth and various health problems for humans and animals. Silicon, however, has excelled in alleviating stress caused by toxic elements in plants. The aim of this study was to investigate the effects of Si in alleviating As stress in maize plants grown in a nutrient solution and evaluate the potential of the spectral emission parameters and the red fluorescence (Fr and far-red fluorescence (FFr ratio obtained in analysis of chlorophyll fluorescence in determination of this interaction. An experiment was carried out in a nutrient solution containing a toxic rate of As (68 μmol L-1 and six increasing rates of Si (0, 0.25, 0.5, 1.0, 1.5, and 2.0 mmol L-1. Dry matter production and concentrations of As, Si, and photosynthetic pigments were then evaluated. Chlorophyll fluorescence was also measured throughout plant growth. Si has positive effects in alleviating As stress in maize plants, evidenced by the increase in photosynthetic pigments. Silicon application resulted in higher As levels in plant tissue; therefore, using Si for soil phytoremediation may be a promising choice. Chlorophyll fluorescence analysis proved to be a sensitive tool, and it can be successfully used in the study of the ameliorating effects of Si in plant protection, with the Fr/FFr ratio as the variable recommended for identification of temporal changes in plants.
Bogue, Rodney K.; Ehernberger, L. J.; Soreide, David; Bagley, Hal
Atmospheric turbulence adversely affects operation of commercial and military aircraft and is a design constraint. The airplane structure must be designed to survive the loads imposed by turbulence. Reducing these loads allows the airplane structure to be lighter, a substantial advantage for a commercial airplane. Gust alleviation systems based on accelerometers mounted in the airplane can reduce the maximum gust loads by a small fraction. These systems still represent an economic advantage. The ability to reduce the gust load increases tremendously if the turbulent gust can be measured before the airplane encounters it. A lidar system can make measurements of turbulent gusts ahead of the airplane, and the NASA Airborne Coherent Lidar for Advanced In-Flight Measurements (ACLAIM) program is developing such a lidar. The ACLAIM program is intended to develop a prototype lidar system for use in feasibility testing of gust load alleviation systems and other airborne lidar applications, to define applications of lidar with the potential for improving airplane performance, and to determine the feasibility and benefits of these applications. This paper gives an overview of the ACLAIM program, describes the lidar architecture for a gust alleviation system, and describes the prototype ACLAIM lidar system.
K Yesudian, C A
The review highlights the poverty alleviation programmes of the government in the post-economic reform era to evaluate the contribution of these programmes towards reducing poverty in the country. The poverty alleviation programmes are classified into (i) self-employment programmes; (ii) wage employment programmes; (iii) food security programmes; (iv) social security programmes; and (v) urban poverty alleviation programmes. The parameter used for evaluation included utilization of allocated funds, change in poverty level, employment generation and number or proportion of beneficiaries. The paper attempts to go beyond the economic benefit of the programmes and analyzes the social impact of these programmes on the communities where the poor live, and concludes that too much of government involvement is actually an impediment. On the other hand, involvement of the community, especially the poor has led to better achievement of the goals of the programmes. Such endeavours not only reduced poverty but also empowered the poor to find their own solutions to their economic problems. There is a need for decentralization of the programmes by strengthening the panchayat raj institutions as poverty is not merely economic deprivation but also social marginalization that affects the poor most.
Full Text Available Abstract Background Fundamental questions in evolutionary genetics, including the possible advantage of sexual reproduction, depend critically on the effects of deleterious mutations on fitness. Limited existing experimental evidence suggests that, on average, such effects tend to be aggravated under environmental stresses, consistent with the perception that stress diminishes the organism's ability to tolerate deleterious mutations. Here, we ask whether there are also stresses with the opposite influence, under which the organism becomes more tolerant to mutations. Results We developed a technique, based on bioluminescence, which allows accurate automated measurements of bacterial growth rates at very low cell densities. Using this system, we measured growth rates of Escherichia coli mutants under a diverse set of environmental stresses. In contrast to the perception that stress always reduces the organism's ability to tolerate mutations, our measurements identified stresses that do the opposite – that is, despite decreasing wild-type growth, they alleviate, on average, the effect of deleterious mutations. Conclusions Our results show a qualitative difference between various environmental stresses ranging from alleviation to aggravation of the average effect of mutations. We further show how the existence of stresses that are biased towards alleviation of the effects of mutations may imply the existence of average epistatic interactions between mutations. The results thus offer a connection between the two main factors controlling the effects of deleterious mutations: environmental conditions and epistatic interactions.
Wytiaz, Victoria; Homko, Carol; Duffy, Frank; Schey, Ron; Parkman, Henry P
Nutritional counseling for gastroparesis focuses on reduction of meal size, fiber, and fat to control symptoms. The tolerance of gastroparesis patients for particular foods is largely anecdotal. The aim of this study was to identify and characterize foods provoking or alleviating gastroparesis symptoms. Gastroparesis patients completed: (1) Demographic Questionnaire; (2) Patient Assessment of Upper GI Symptoms; (3) Food Toleration and Aversion survey asking patients about experiences when eating certain foods utilizing a scale from -3 (greatly worsening symptoms) to +3 (greatly improving symptoms). Descriptive qualities (acidic, fatty, spicy, roughage-based, bitter, salty, bland, and sweet) were assigned to foods. Forty-five gastroparesis patients participated (39 idiopathic gastroparesis). Foods worsening symptoms included: orange juice, fried chicken, cabbage, oranges, sausage, pizza, peppers, onions, tomato juice, lettuce, coffee, salsa, broccoli, bacon, and roast beef. Saltine crackers, jello, and graham crackers moderately improved symptoms. Twelve additional foods were tolerated by patients (not provoking symptoms): ginger ale, gluten-free foods, tea, sweet potatoes, pretzels, white fish, clear soup, salmon, potatoes, white rice, popsicles, and applesauce. Foods provoking symptoms were generally fatty, acidic, spicy, and roughage-based. The foods shown to be tolerable were generally bland, sweet, salty, and starchy. This study identified specific foods that worsen as well as foods that may help alleviate symptoms of gastroparesis. Foods that provoked symptoms differed in quality from foods that alleviated symptoms or were tolerable. The results of this study illustrate specific examples of foods that aggravate or improve symptoms and provide suggestions for a gastroparesis diet.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD. PMID:25024594
Cave, Matthew C.; Clair, Heather B.; Hardesty, Josiah E.; Falkner, K. Cameron; Feng, Wenke; Clark, Barbara J.; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A.; McClain, Craig J.; Prough, Russell A.
Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic
Pagadala, Mangesh R.; Zein, Claudia O.; Dasarathy, Srinivasan; Yerian, Lisa; Lopez, Rocio; McCullough, Arthur J.
Background A possible association between nonalcoholic fatty liver disease (NAFLD) and hypothyroidism has been suggested. Possible explanations for this association are the recognized links between hypothyroidism and various elements of the metabolic syndrome which is often present in NAFLD. To further explore this association, we determined the prevalence of hypothyroidism in a cohort of patients with NAFLD and analyzed the potential factors associated with hypothyroidism in this patient population. Methods Two hundred and forty six patients with biopsy proven NAFLD attending hepatology clinics at the Cleveland Clinic between October 2006 to June 2009 and 430 age, gender, race and BMI matched control subjects seen in the general internal medicine clinic were included. Patients with a clinical diagnosis of hypothyroidism who were on thyroid replacement therapy were considered to be hypothyroid. Results Hypothyroidism was more frequent among patients with NAFLD (21%vs 9.5%.; Phypothyroidism were 2.1 (95% CI: 1.1, 3.9,P=0.02)) and 3.8 (95% CI:2,6.9, Phypothyroidism. NAFLD subjects who reported mild alcohol consumption were less likely to have hypothyroidism compared to those who reported complete abstinence (OR 0.37, P=0.008). Conclusions A higher prevalence of hypothyroidism was demonstrated in patients with NAFLD compared to controls. Patients with hypothyroidism were more likely to have NASH. Among subjects with NALFD, female gender, increased BMI and history of abstinence from alcohol were associated with hypothyroidism. Further studies are needed in order to confirm and better characterized these findings as well as the described associations and their pathogenesis. PMID:22183820
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD.
Full Text Available Physical activity improves various metabolic disturbances. The effect of physical activity on non-alcoholic fatty liver disease (NAFLD has not been defined, particularly in athletes who are able to consume a diet to increase body mass. The aim of this study was to evaluate the prevalence of NAFLD and associated factors of NAFLD among male university rugby football players [n = 69, 37 forwards (FW and 32 backs (BK], relative to age-matched controls (CON; n = 29. For FW players exercise consists of physical contact play, such as ruck, mall, scrum, and tackle. For BK players exercise consists of sprints and endurance running. Liver function tests and bioimpedance analysis to assess body composition were performed. Subjects consuming ≤ 20 g/day of ethanol and exhibiting an aspartate transaminase (AST level ≥ 33 U/L, and/or alanine transaminase (ALT level ≥ 43 U/L, were considered to have NAFLD. The PNPLA3 and MTP genotypes were determined using real-time polymerase chain reaction (PCR. The body mass index, body fat mass, and lean body mass were significantly higher in the FW group than in the BK and CON groups (P < 0.05. The total cholesterol, low-density lipoprotein cholesterol, triglyceride, AST, ALT, and alkaline phosphatase levels were significantly higher in the FW group than in the CON group (P < 0.05. The prevalence of NAFLD was significantly higher in the FW group than in the BK group and CON group (18.9, 8.6, and 0.0%, respectively, whereas there were non-significant between-group differences in the frequency of the PNPLA3 and MTP genotypes. These findings indicate that rugby football players, especially those in the FW position, are at higher risk of developing NAFLD, which emphasizes the role of diet and exercise in the development of NAFLD.
Gutiérrez-Grobe, Ylse; Chávez-Tapia, Norberto; Sánchez-Valle, Vicente; Gavilanes-Espinar, Juan Gabriel; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez-Sánchez, Nahum
Some phytochemicals present in coffee have a potential antioxidant role which seems to protect the human body against cardiovascular diseases, liver disease and malignancies. Nonalcoholic fatty liver disease is a common disease with limited therapeutic options. This study investigated the antioxidant effect of coffee by measuring antioxidant enzymes and lipid peroxidation markers in patients with nonalcoholic fatty liver disease. We performed a case-control study at the University Hospital, Mexico City. Anthropometric, metabolic, dietary and biochemical variables of all patients were determined and compared. The presence of nonalcoholic fatty liver disease was established by ultrasonography. All patients completed a dietary questionnaire in order to determine their of coffee consumption. Catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured in all of the patients. Seventy-three subjects with and 57 without nonalcoholic fatty liver disease were included. Patients with nonalcoholic fatty liver disease had significantly higher body mass index, blood glucose, homeostasis model of assessment-insulin resistance and insulin values in comparison to patients without nonalcoholic fatty liver disease. On the one hand, there was a significant difference in coffee intake between the groups (p coffee has a protective effect against nonalcoholic fatty liver disease however there was no significant difference in the antioxidant variables analyzed.
Ding, Shibin; Jiang, Jinjin; Zhang, Guofu; Bu, Yongjun; Zhang, Guanghui; Zhao, Xiangmei
Studies have demonstrated that resveratrol (a natural polyphenol) and caloric restriction activate Sirtuin-1 (SIRT1) and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD) development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy. Eight-week-old male Wistar rats (40) were divided into four groups: the STD group, which was fed a standard chow diet; the HFD group, which was fed a high-fat diet; HFD-RES group, which was fed a high-fat diet plus resveratrol (200 mg/kg.bw); and the HFD-CR group, which was fed a high-fat diet in portions containing 70% of the mean intake of the HFD group rats. The groups were maintained for 18 weeks. Metabolic parameters, Oil Red O and hematoxylin-eosin staining of the liver, and the mRNA and protein expression of SIRT1, autophagy markers and endoplasmic reticulum(ER) stress-associated genes in the liver were assessed after the 18-week treatment. We found that resveratrol (200 mg/kg bw) and caloric restriction (30%) partially prevented hepatic steatosis and hepatocyte ballooning, increased the expression of SIRT1 and autophagy markers while decreasing ER stress markers in the liver and alleviated lipid metabolism disorder. Moreover, caloric restriction provided superior protection against HFD-induced hepatic fatty accumulation compared with resveratrol and the effects were associated with decreased total energy intake and body weight. We conclude that the SIRT1-autophagy pathway and decreased ER stress are universally required for the protective effects of moderate caloric restriction (30%) and resveratrol (a pharmacological SIRT1 activator) supplementation
Full Text Available Studies have demonstrated that resveratrol (a natural polyphenol and caloric restriction activate Sirtuin-1 (SIRT1 and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy.Eight-week-old male Wistar rats (40 were divided into four groups: the STD group, which was fed a standard chow diet; the HFD group, which was fed a high-fat diet; HFD-RES group, which was fed a high-fat diet plus resveratrol (200 mg/kg.bw; and the HFD-CR group, which was fed a high-fat diet in portions containing 70% of the mean intake of the HFD group rats. The groups were maintained for 18 weeks. Metabolic parameters, Oil Red O and hematoxylin-eosin staining of the liver, and the mRNA and protein expression of SIRT1, autophagy markers and endoplasmic reticulum(ER stress-associated genes in the liver were assessed after the 18-week treatment. We found that resveratrol (200 mg/kg bw and caloric restriction (30% partially prevented hepatic steatosis and hepatocyte ballooning, increased the expression of SIRT1 and autophagy markers while decreasing ER stress markers in the liver and alleviated lipid metabolism disorder. Moreover, caloric restriction provided superior protection against HFD-induced hepatic fatty accumulation compared with resveratrol and the effects were associated with decreased total energy intake and body weight.We conclude that the SIRT1-autophagy pathway and decreased ER stress are universally required for the protective effects of moderate caloric restriction (30% and resveratrol (a pharmacological SIRT1 activator
Zimmermann, Esther; Anty, Rodolphe; Tordjman, Joan
Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH), but th......Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH...
word “elegant” refers to the presentation of the cocktail, as defined in the choice of .... a thin layer in the mouth and is perceived as less fresh. For example ... be used in marketing non-alcoholic cocktails, because they are. Table 1: The basic ...
We established a mouse model of developmental nonalcoholic steatohepatitis (NASH) by feeding a high polyunsaturated fat liquid diet to female glutathione-S-transferase 4-4 (Gsta4-/-)/peroxisome proliferator activated receptor a (Ppara-/-) double knockout 129/SvJ mice for 12 weeks from weaning. We us...
Cabrera, Daniel; Wree, Alexander; Povero, Davide; Solís, Nancy; Hernandez, Alejandra; Pizarro, Margarita; Moshage, Han; Torres, Javiera; Feldstein, Ariel E; Cabello-Verrugio, Claudio; Brandan, Enrique; Barrera, Francisco; Arab, Juan Pablo; Arrese, Marco
Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-kB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the
Rambaldi, A; Gluud, C
Alcohol and hepatotropic viruses cause the majority of liver cirrhosis cases in the Western World. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic or non-alcoholic...
Radek Toušek; Jaroslava Pechová
The article is focused on optimization of logistic operations in food stuff industry with emphasis on non-alcoholic drinks form the point of view of the usage of common applied wrapping technologies potential. Especially the attention is paid to the influence of used packages over the level of logistic costs including the influence of used packages over the transport intensity of logistic operations.
Pruis, M. G. M.; Lendvai, A.; Bloks, V. W.; Zwier, M. V.; Baller, J. F. W.; de Bruin, A.; Groen, A. K.; Plosch, T.
AimMetabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver
Lauridsen, Bo Kobberø; Stender, Stefan; Kristensen, Thomas Skårup
Aims: In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. Methods and results: In a cohort study...
Obese Hispanic adolescents (OHAs) with dysglycemia have increased cardiovascular disease risk burden. To investigate if nonalcoholic fatty liver disease (NAFLD) confers added risk for endothelial dysfunction in these youth. Cross-sectional study. Academic institution. Thirty-six OHAs (15.360.4 years...
Hoffmann, Anika; Bootsveld, Klaus; Gebhardt, Ursel; Daubenbuchel, Anna M. M.; Sterkenburg, Anthe S.; Muller, Hermann L.
Objective: Hypothalamic obesity in childhood craniopharyngioma (CP) patients carries a high risk for development of metabolic syndrome. In metabolic syndrome, the development of nonalcoholic fatty liver disease (NAFLD) is known. The aim of this study is to detect the risk for NAFLD in
Banasik, Karina; Justesen, Johanne M.; Hornbak, Malene
Objective: Candidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes. Research Design and Methods: By integrating public database text mining, trans-organism protein...
Zhang, Jian; Wang, Chunying; Wang, Ji; Zhang, Fengchi
This study was conducted to analyze the change in intestinal flora of patients with nonalcoholic steatohepatitis and its correlation to the levels of the inflammatory cytokines interleukin-10 (IL-10) and IL-17. We selected 90 patients that were diagnosed with and treated for nonalcoholic steatohepatitis as the patient group and 80 healthy cases as the control group. We then compared the intestinal flora in the subject feces and the intestinal colonization resistance (B/E, Bifidobacterium to Enterobacter ) of both groups. Using RT-PCR, we also detected IL-10 and IL-17 mRNA levels in the peripheral blood mononuclear cells of both groups. Furthermore, we used the ELISA method to determine serum IL-10 and IL-17 levels in order to explore the correlation between IL-10, IL-17 and B/E. The number of Bifidobacterium and Lactobacillus were significantly lower in the patient group than the control group (Pflora in the patients group were negatively correlated with serum IL-10 (r=-0.546, Pflora in patients with nonalcoholic steatohepatitis are closely related to the changes of serum IL-10 and IL-17 levels, and they are involved in the development of nonalcoholic steatohepatitis.
Overload of nutrients can lead to diet-induced inflammation, also called metabolic inflammation, which is thought to play an important role in many metabolic diseases, including the development of nonalcoholic fatty liver disease (NAFLD). NAFLD encompasses a spectrum of pathologies that range from
Gaemers, Ingrid C.; Groen, Albert K.
PURPOSE OF REVIEW: The hallmark of non-alcoholic fatty liver disease is hepatic steatosis. This is mostly a benign condition, but for largely unknown reasons it progresses to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma in about 10% of patients. In this review we discuss recent
Schneider, Claudia; Thierauf, Annette; Kempf, Jürgen; Auwärter, Volker
During lactation, the consumption of ethanol is discussed controversially. After women drink alcoholic beverages, ethanol can be found in breastmilk with a time lag. To abstain from ethanol, but not from the taste of alcoholic beverages, in particular, non-alcoholic beer has become popular in recent years. According to regulations in the United States and most European countries, these "alcohol-free" beverages may still contain ethanol up to 1.2% by volume. To determine how much of this ethanol may reach the breastfed child, a drinking experiment with non-alcoholic beer was performed. Fifteen healthy breastfeeding women participated in the study. After at least 5 days of abstinence from ethanol and the donation of a void breastmilk sample, they were asked to drink 1.5 L of non-alcoholic beer within 1 hour. Breastmilk samples were collected using electronic breast pumps immediately after the end of drinking as well as 1 and 3 hours later. The milk was analyzed for ethanol by headspace-gas chromatography-flame ionization detection using a fully validated method. In two women, trace amounts of ethanol (up to 0.0021 g/L) were found in the samples gained immediately after the drinking period. In the other samples ethanol could not be detected (limit of detection=0.0006 g/L). The mother's consumption of non-alcoholic beer is likely innocuous for the breastfed infant.
Epidemiological and experimental studies provide supportive evidence that lycopene (LY), a major carotenoid from tomatoes and tomato products, may act as a chemopreventive agent against certain types of cancers. We recently showed that high-fat diet (HFD)-induced nonalcoholic steatohepatitis (NASH) ...
Wouters, Kristiaan; van Bilsen, Marc; van Gorp, Patrick J.; Bieghs, Veerle; Luetjohann, Dieter; Kerksiek, Anja; Staels, Bart; Hofker, Marten H.; Shiri-Sverdlov, Ronit
Hepatic inflammation is the key factor in non-alcoholic steatohepatitis (NASH) and promotes progression to liver damage. We recently identified dietary cholesterol as the cause of hepatic inflammation in hyperlipidemic mice. We now show that hepatic transcriptome responses are strongly dependent on
Bocca, Gianni; Stolk, R.P.; Scheenstra, R.; Sauer, P.J.
Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases from simple steatosis to steatohepatitis and cirrhosis with liver failure. In children, NAFLD is mainly associated with obesity and metabolic syndrome, the results of an unhealthy lifestyle. Insulin resistance and
Full Text Available BACKGROUND AND AIMS: A major impediment to establishing new treatments for non-alcoholic steatohepatitis is the lack of suitable animal models that accurately mimic the biochemical and metabolic characteristics of the disease. The aim of this study was to explore a unique polygenic animal model of metabolic disease as a model of non-alcoholic steatohepatitis by determining the effects of 2% dietary cholesterol supplementation on metabolic and liver endpoints in Psammomys obesus (Israeli sand rat. METHODS: P. obesus were provided ad libitum access to either a standard rodent diet (20% kcal/fat or a standard rodent diet supplemented with 2% cholesterol (w/w for 4 weeks. Histological sections of liver from animals on both diets were examined for key features of non-alcoholic steatohepatitis. The expression levels of key genes involved in hepatic lipid metabolism were measured by real-time PCR. RESULTS: P. obesus fed a cholesterol-supplemented diet exhibited profound hepatomegaly and steatosis, and higher plasma transaminase levels. Histological analysis identified extensive steatosis, inflammation, hepatocyte injury and fibrosis. Hepatic gene expression profiling revealed decreased expression of genes involved in delivery and uptake of lipids, and fatty acid and triglyceride synthesis, and increased expression of genes involved in very low density lipoprotein cholesterol synthesis, triglyceride and cholesterol export. CONCLUSIONS: P. obesus rapidly develop non-alcoholic steatohepatitis when fed a cholesterol-supplemented diet that appears to be histologically and mechanistically similar to patients.
Leth, Torben; Fabricius, N.; Fagt, Sisse
In 1999, 116 samples of non-alcoholic beverages were analysed for the intense sweeteners cyclamate, acesulfame-K, aspartame and saccharin. High contents of cyclamate close to the maximum permitted level in 1999 of 400 mgl(-1) were found in many soft drinks. The estimated intake of the sweeteners...
Mejía-Díaz, Diana Margarita; Carmona-Garcés, Isabel Cristina; Giraldo-López, Paula Andrea; González-Zapata, Laura
To describe the nutritional content of foods and non-alcoholic beverages advertised in the children's frame vs. the general frame in two national, private, free-access, television channels in Colombia. Cross-sectional, descriptive study. The recording was performed in July of 2012, for four days randomly chosen from 6:00 am to 12:30 pm. The nutritional content was classified according to the nutritional profiles criteria of the Food Standards Agency for risk-indicating nutrients, the Health Pan-American Organization for trans fat, and the 333 Colombian Resolution of 2011 that classifies foods as source of protecting nutrients. Descriptive statistics were used, the Kolmogorov-Smirnov test to establish the normality, and the Chi square test for variables comparison. A p value foods and beverages, of which 56.3% were shown within the children's frame. Regarding the nutritional content, a high percentage of foods and non-alcoholic beverages classified as "rich" in sugar, sodium, saturated fat was observed within the children's' frame (69.0%, 56.0%, 57.1%), as compared to the general frame. By contrast, the percentage of foods and nonalcoholic beverages classified as "rich" in total fat was higher in the general frame as compared to the children's frame (70.4% vs. 29.6%, respectively). Higher exposure to advertising of foods and non-alcoholic beverages was observed within the children's' frame, characterized by high content of risk-indicating nutrients and low content of foods and non-alcoholic beverages with protective nutrients. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
Milić, Sandra; Mikolasević, Ivana; Radić, Mladen; Hauser, Goran; Stimac, Davor
Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as apart of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We retrospectively analyzed 241 patients (176 men and 65 women) with liver cirrhosis and anemia, defined as a hemoglobin value reference range is 11-15%. Alcoholic liver cirrhosis had 204 patients (85%) while non-alcoholic cirrhosis had 37 patients (15%). In group of alcoholic cirrhosis the average RDW was 16.8%. In relation to severity of disease the average RDW for Child-Pugh A was 16.80%, for Child-Pugh B was 16.92%, for Child-Pugh C was 17.10%. In the group of non-alcoholic cirrhosis the average RDW was 16.73% and in relation to severity of disease for Child-Pugh A was 16.25%, for Child-Pugh B 17.01% and for Child-Pugh C was 16.87%. We didn't find statistically significant difference of RDW between alcoholic and non alcoholic cirrhosis (p > 0.05) and we didn't proved any statistically significant increase of RDW in relation to severity of disease in group of alcoholic cirrhosis (p = 0.915) nor in group of patients with non-alcoholic cirrhosis (p = 0.697). Our study showed that RDW had not any clinical value in differentiation of anemia neither in alcoholic and non-alcoholic liver cirrhosis nor in severity of liver disease.
Full Text Available Background: Non-alcoholic Wernicke's encephalopathy and Korsakoff syndrome are greatly underdiagnosed. There are very few reported cases of neuropsychologically documented non-alcoholic Korsakoff syndrome, and diffusion tensor imaging (DTI data are scarce.Methods: We report clinical characteristics and neuropsychological as well as radiological findings from three psychiatric patients (one woman and two men with a history of probable undiagnosed non-alcoholic Wernicke's encephalopathy and subsequent chronic memory problems.Results: All patients had abnormal neuropsychological test results, predominantly in memory. Thus, the neuropsychological findings were compatible with Korsakoff syndrome. However, the neuropsychological findings were not uniform. The impairment of delayed verbal memory of the first patient was evident only when the results of the memory tests were compared to her general cognitive level. In addition, the logical memory test and the verbal working memory test were abnormal, but the word list memory test was normal. The second patient had impaired attention and psychomotor speed in addition to impaired memory. In the third patient, the word list memory test was abnormal, but the logical memory test was normal. All patients had intrusions in the neuropsychological examination. Executive functions were preserved, except for planning and foresight, which were impaired in two patients. Conventional MRI examination was normal. DTI showed reduced fractional anisotropy values in the uncinate fasciculus in two patients, and in the corpus callosum and in the subgenual cingulum in one patient.Conclusions: Non-alcoholic Korsakoff syndrome can have diverse neuropsychological findings. This may partly explain its marked underdiagnosis. Therefore, a strong index of suspicion is needed. The presence of intrusions in the neuropsychological examination supports the diagnosis. Damage in frontotemporal white matter tracts, particularly in the
Nikolakaros, Georgios; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G; Vataja, Risto; Ilonen, Tuula
Background: Non-alcoholic Wernicke's encephalopathy and Korsakoff syndrome are greatly underdiagnosed. There are very few reported cases of neuropsychologically documented non-alcoholic Korsakoff syndrome, and diffusion tensor imaging (DTI) data are scarce. Methods: We report clinical characteristics and neuropsychological as well as radiological findings from three psychiatric patients (one woman and two men) with a history of probable undiagnosed non-alcoholic Wernicke's encephalopathy and subsequent chronic memory problems. Results: All patients had abnormal neuropsychological test results, predominantly in memory. Thus, the neuropsychological findings were compatible with Korsakoff syndrome. However, the neuropsychological findings were not uniform. The impairment of delayed verbal memory of the first patient was evident only when the results of the memory tests were compared to her general cognitive level. In addition, the logical memory test and the verbal working memory test were abnormal, but the word list memory test was normal. The second patient had impaired attention and psychomotor speed in addition to impaired memory. In the third patient, the word list memory test was abnormal, but the logical memory test was normal. All patients had intrusions in the neuropsychological examination. Executive functions were preserved, except for planning and foresight, which were impaired in two patients. Conventional MRI examination was normal. DTI showed reduced fractional anisotropy values in the uncinate fasciculus in two patients, and in the corpus callosum and in the subgenual cingulum in one patient. Conclusions: Non-alcoholic Korsakoff syndrome can have diverse neuropsychological findings. This may partly explain its marked underdiagnosis. Therefore, a strong index of suspicion is needed. The presence of intrusions in the neuropsychological examination supports the diagnosis. Damage in frontotemporal white matter tracts, particularly in the uncinate
Hirase, Shotaro; Takeshima, Hirohiko; Nishida, Mutsumi; Iwasaki, Wataru
Reliably rooted phylogenetic trees play irreplaceable roles in clarifying diversification in the patterns of species and populations. However, such trees are often unavailable in phylogeographic studies, particularly when the focus is on rapidly expanded populations that exhibit star-like trees. A fundamental bottleneck is known as the random rooting effect, where a distant outgroup tends to root an unrooted tree "randomly." We investigated whether parallel mitochondrial genome (mitogenome) sequencing alleviates this effect in phylogeography using a case study on the Sea of Japan lineage of the intertidal goby Chaenogobius annularis Eighty-three C. annularis individuals were collected and their mitogenomes were determined by high-throughput and low-cost parallel sequencing. Phylogenetic analysis of these mitogenome sequences was conducted to root the Sea of Japan lineage, which has a star-like phylogeny and had not been reliably rooted. The topologies of the bootstrap trees were investigated to determine whether the use of mitogenomes alleviated the random rooting effect. The mitogenome data successfully rooted the Sea of Japan lineage by alleviating the effect, which hindered phylogenetic analysis that used specific gene sequences. The reliable rooting of the lineage led to the discovery of a novel, northern lineage that expanded during an interglacial period with high bootstrap support. Furthermore, the finding of this lineage suggested the existence of additional glacial refugia and provided a new recent calibration point that revised the divergence time estimation between the Sea of Japan and Pacific Ocean lineages. This study illustrates the effectiveness of parallel mitogenome sequencing for solving the random rooting problem in phylogeographic studies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Beaudin, Stephane A.; Strupp, Barbara J.; Uribe, Walter; Ysais, Lauren; Strawderman, Myla; Smith, Donald R.
Recent studies from our lab have demonstrated that postnatal manganese (Mn) exposure in a rodent model can cause lasting impairments in fine motor control and attention, and that oral methylphenidate (MPH) treatment can effectively treat the dysfunction in fine motor control. However, it is unknown whether MPH treatment can alleviate the impairments in attention produced by Mn exposure. Here we used a rodent model of postnatal Mn exposure to determine whether (1) oral MPH alleviates attention and impulse control deficits caused by postnatal Mn exposure, using attention tasks that are variants of the 5-choice serial reaction time task, and (2) whether these treatments affected neuronal dendritic spine density in the medial prefrontal cortex (mPFC) and dorsal striatum. Male Long-Evans rats were exposed orally to 0 or 50 mg Mn/kg/d throughout life starting on PND 1, and tested as young adults (PND 107 – 115) on an attention task that specifically tapped selective attention and impulse control. Animals were treated with oral MPH (2.5 mg/kg/d) throughout testing on the attention task. Our findings show that lifelong postnatal Mn exposure impaired impulse control and selective attention in young adulthood, and that a therapeutically relevant oral MPH regimen alleviated the Mn-induced dysfunction in impulse control, but not selective attention, and actually impaired focused attention in the Mn group. In addition, the effect of MPH was qualitatively different for the Mn-exposed versus control animals across a range of behavioral measures of inhibitory control and attention, as well as dendritic spine density in the mPFC, suggesting that postnatal Mn exposure alters catecholaminergic systems modulating these behaviors. Collectively these findings suggest that MPH may hold promise for treating the behavioral dysfunction caused by developmental Mn exposure, although further research is needed with multiple MPH doses to determine whether a dose can be identified that
Pulzi Fernanda BU
Full Text Available Abstract Background Nonalcoholic fatty liver disease (NAFLD is the most frequent disease associated with abnormal liver tests that is characterized by a wide spectrum of liver damage, ranging from simple macro vesicular steatosis to steatohepatitis (NASH, cirrhosis or liver carcinoma. Liver biopsy is the most precise test to differentiate NASH from other stages of NAFLD, but it is an invasive and expensive method. This study aimed to create a clinical laboratory score capable of identify individual with NASH in severely obese patients submitted to bariatric surgery. Methods The medical records from 66 patients submitted to gastroplasty were reviewed. Their chemistry profile, abdominal ultrasound (US and liver biopsy done during the surgical procedure were analyzed. Patients were classified into 2 groups according to liver biopsy: Non-NASH group - those patients without NAFLD or with grade I, II or III steatosis; and NASH group - those with steatohepatitis or fibrosis. The t-test was used to compare each variable with normal distribution between NASH and Non-NASH groups. When comparing proportions of categorical variables, we used chi-square or z-test, where appropriate. A p-value Results 83% of patients with obesity grades II or III showed NAFLD, and the majority was asymptomatic. Total Cholesterol (TC≥200 mg/dL, alanine aminotransferase (ALT ≥30, AST/ALT ratio (AAR≤ 1, gammaglutaril-transferase (γGT≥30 U/L and abdominal US, compatible with steatosis, showed association with NASH group. We proposed 2 scores: Complete score (TC, ALT, AAR, γGT and US and the simplified score, where US was not included. The combination of biochemical and imaging results improved accuracy to 84.4% the recognition of NASH (sensitivity 70%, specificity 88.6%, NPV 91.2%, PPV 63. 6%. Conclusion Alterations in TC, ALT, AAR, γGT and US are related to the most risk for NASH. The combination of biochemical and imaging results improved accuracy to 84.4% the
Hansen, Jesper Melchior
are limited. Anecdotal reports have shown partial or complete resolution of NSF following successful renal transplantation early in the course of NSF. In this report, we describe alleviation of NSF symptoms in two women following successful renal transplantation more than 3 years after onset of NSF.......Nephrogenic systemic fibrosis (NSF) is a rare, serious, and life-threatening disease of patients with severe renal impairment. Gadolinium-containing contrast agents have been shown to be the crucial trigger. There is no proven medical cure for the disease, and symptomatic treatment options...
Wouters, Kristiaan; van Gorp, Patrick J.; Bieghs, Veerle; Gijbels, Marion J.; Duimel, Hans; Luetjohann, Dieter; Kerksiek, Anja; van Kruchten, Roger; Maeda, Nobuyo; Staels, Bart; van Bilsen, Marc; Shiri-Sverdlov, Ronit; Hofker, Marten H.
Nonalcoholic steatohepatitis (NASH) involves liver lipid accumulation (steatosis) combined with hepatic inflammation. The transition towards hepatic inflammation represents a key step in pathogenesis, because it will set the stage for further liver damage, culminating in hepatic fibrosis, cirrhosis,
Wouters, Kristiaan; van Gorp, Patrick J.; Bieghs, Veerle; Gijbels, Marion J.; Duimel, Hans; Lütjohann, Dieter; Kerksiek, Anja; van Kruchten, Roger; Maeda, Nobuyo; Staels, Bart; van Bilsen, Marc; Shiri-Sverdlov, Ronit; Hofker, Marten H.
Nonalcoholic steatohepatitis (NASH) involves liver lipid accumulation (steatosis) combined with hepatic inflammation. The transition towards hepatic inflammation represents a key step in pathogenesis, because it will set the stage for further liver damage, culminating in hepatic fibrosis, cirrhosis,
Full Text Available Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.
Shroder, J. F.
Mineral and water resources in Afghanistan may be the best means by which redevelopment of the country can be used to alleviate future terrorism. Remote-sensing analysis of snow, ice, resources, and topography in Afghanistan, and development of digital elevation models with ASTER imagery and previously classified, large scale topographic maps from the Department of Defense enable better assessment and forecasting resources in the country. Adequate resource assessment and planning is viewed as critical to alleviation of one cause of the problems associated with the fertilization of terrorism in Afghanistan. Long-term diminution of meltwater resources in Afghanistan is exemplified by the disastrous and famine-inducing droughts of the present time and three decades prior, as well as by the early Landsat assessment of glacier resources sponsored by USGS and now brought up-to-date with current imagery. Extensive cold-war projects undertaken by both the USSR and USA generated plentiful essential mineral, hydrocarbon, hydrogeological, and hydrological data, including an extensive stream gauging and vital irrigation network now adversly affected or destroyed entirely by decades of war. Analysis, measurement, prediction, rehabilitation, and reconstruction of critical resource projects are regarded as most critical elements in the war on terrorism in this portion of the world. The GLIMS (Global Land Ice Measurements from Space) Project, initially sponsored by USGS, has established our group as the Regional Center for Afghanistan and Pakistan, in which the above concepts serve as guiding research precepts.
In medicine, we have historically been better at learning about the body and disease than we have at understanding the human beings who come to us with the ailments. We have acted to relieve pain, consoling patients and families as a complement, but done little to understand and alleviate suffering as a fundamental part of our practice. In fact, only in more recent decades has "suffering" been conceptualized as something apart from pain, associated with distress and its causes. It was Eric T. Cassell, in his ground-breaking work in the 1980s, who posed the need to consider alleviation of suffering and treatment of illness as twin-and equally important-obligations of the medical profession. Suffering is defined as a negative, complex emotional and cognitive state, characterized by feeling under constant threat and powerless to confront it, having drained the physical and psycho-social resources that might have made resistance possible. This unique depletion of personal resources is key to understanding suffering.
Liu, Ming; Liao, Kaijun; Yu, Changxi; Li, Xuejun; Liu, Suhuan; Yang, Shuyu
Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4-100 nM) for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB) and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.
Dharmasena, Senarath; Capps, Oral, Jr.; Bessler, David A.
The non-alcoholic beverage market in the U.S. is a multi-billion dollar industry growing steadily over the past decade. Also, non-alcoholic beverages are among the most heavily advertised food and beverage groups in the United States. Several studies pertaining to non-alcoholic beverages including the incorporation of advertising effects have been conducted, but most of these have centered attention on milk consumption. Some studies have considered demand interrelationships for several bevera...
Beaudin, Stephane A; Strupp, Barbara J; Uribe, Walter; Ysais, Lauren; Strawderman, Myla; Smith, Donald R
Recent studies from our lab have demonstrated that postnatal manganese (Mn) exposure in a rodent model can cause lasting impairments in fine motor control and attention, and that oral methylphenidate (MPH) treatment can effectively treat the dysfunction in fine motor control. However, it is unknown whether MPH treatment can alleviate the impairments in attention produced by Mn exposure. Here we used a rodent model of postnatal Mn exposure to determine whether (1) oral MPH alleviates attention and impulse control deficits caused by postnatal Mn exposure, using attention tasks that are variants of the 5-choice serial reaction time task, and (2) whether these treatments affected neuronal dendritic spine density in the medial prefrontal cortex (mPFC) and dorsal striatum. Male Long-Evans rats were exposed orally to 0 or 50Mn/kg/d throughout life starting on PND 1, and tested as young adults (PND 107-115) on an attention task that specifically tapped selective attention and impulse control. Animals were treated with oral MPH (2.5mg/kg/d) throughout testing on the attention task. Our findings show that lifelong postnatal Mn exposure impaired impulse control and selective attention in young adulthood, and that a therapeutically relevant oral MPH regimen alleviated the Mn-induced dysfunction in impulse control, but not selective attention, and actually impaired focused attention in the Mn group. In addition, the effect of MPH was qualitatively different for the Mn-exposed versus control animals across a range of behavioral measures of inhibitory control and attention, as well as dendritic spine density in the mPFC, suggesting that postnatal Mn exposure alters catecholaminergic systems modulating these behaviors. Collectively these findings suggest that MPH may hold promise for treating the behavioral dysfunction caused by developmental Mn exposure, although further research is needed with multiple MPH doses to determine whether a dose can be identified that ameliorates the
Camila Gastelumendi Gonçalves
Full Text Available This study explores the relationship between coping styles and strategies, and personality styles in a sample of 41 young volunteers of an institution that alleviates poverty in Lima. Peruvian adaptations of COPE and MIPS scales were administered. The results show that volunteers have higher scores on adaptive coping strategies. High scores in some particular personality styles were reported, which allowed to establish a personality profile of this group. According with theoretical framework, most coping strategies correlated with most personality styles, revealing four particular tendencies in these volunteers: they wish to have contact with other people, they usually see positive aspects of situations, they look forward for challenges, and they developed adaptive coping strategies.
Full Text Available Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration.
Mitchell, Gary; Agnelli, Joanne
Distress is one of the most common clinical manifestations associated with dementia. Pharmacological intervention may be appropriate in managing distress in some people. However, best practice guidelines advocate non-pharmacological interventions as the preferred first-line treatment. The use of non-pharmacological interventions encourages healthcare professionals to be more person-centred in their approach, while considering the causes of distress. This article provides healthcare professionals with an overview of some of the non-pharmacological approaches that can assist in alleviating distress for people living with dementia including: reminiscence therapy, reality orientation, validation therapy, music therapy, horticultural therapy, doll therapy and pet therapy. It provides a summary of their use in clinical practice and links to the relevant literature.
Kurishita, A.; Ono, T.
Radiation induced hematopoietic and gastro-intestinal damages in mice were tried to alleviate experimentally by post-treatment. Combined treatment of OK-432 and aztreonam clearly prevented the radiation induced sepsis and elevated the survival rate in mice; the survival was 80% in the OK-432 plus aztreonam group while it was 55% in the group treated with OK-432 alone and 0% with saline. Irsogladine maleate, an anti-ulcer drug, increased the survival rate of jejunal crypt stem cells with a clear dose-related trend. The D 0 for irsogladine maleate was 2.8 Gy although it was 2.3 Gy for saline, These findings suggest that some conventional drugs are effective for radiation induced hematopoietic and gastro-intestinal damages and the possibility that they can be applied for people exposed to radiation accidentally. (author)
Miguel Ángel Sánchez-Martos
Full Text Available The effect of an individualized exercise programme on a non-alcoholic steatohepatitis case is presented. Before entering the programme the patient was treated with conventional recommendations on diet plus aerobic exercise during fourteen years, without major improvements of his analytical parameters. Two years after including him in a tailored exercise programme, aimed to fulfil the recommendations of the American College of Sports Medicine, his blood markers of liver dysfunction and cardio-metabolic risk tended to improve. Consequently, our data support the idea that in non-alcoholic steatohepatitis the exercise-based therapeutic interventions should be individualized taking into account the cardio-respiratory and muscular fitness of the patient, rather than using generic behavioural recommendations.
Becker, U; Gluud, C; Farholt, S
In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were...... and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded....... significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations...
When dealing with the treatment of obesity-linked illnesses - in particular nonalcoholic fatty liver disease - beyond diet, various nutritional ingredients are reported to be useful as silymarin, spirulina, choline, folic acid, methionine and vitamin E, all of them showing promising but not definite results. An emerging field of study is represented by prebiotics/probiotics and restoration of normal gut flora, which could play a fundamental role diet and various its components. It is noteworthy to point out that both improving or reducing the severity of nonalcoholic fatty liver disease bear a positive consequence on evolution of atherosclerosis and its cardiovascular-associated disease, such as coronary artery disease, even though the involved immunologic mechanisms are gaining greater credit in the most recent literature, without excluding the role of nutrition in modulating the acquired immunity in this condition.
Han, Eugene; Lee, Yong Ho
As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged. Copyright © 2017 Korean Diabetes Association.
Silvia M. Ferolla
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease worldwide. It is a progressive disorder involving a spectrum of conditions that include pure steatosis without inflammation, nonalcoholic steatohepatitis (NASH, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes, which may be followed by lipid peroxidation, production of reactive oxygen species and consequent inflammation. Recent studies suggest that the characteristics of the gut microbiota are altered in NAFLD, and also, that small intestinal bacterial overgrowth (SIBO contributes to the pathogenesis of this condition. This review presents the chief findings from all the controlled studies that evaluated SIBO, gut permeability and endotoxemia in human NAFLD. We also discuss the possible mechanisms involving SIBO, lipid accumulation and development of NASH. The understanding of these mechanisms may allow the development of new targets for NASH treatment in the future.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is an emerging global health concern. It is the most common form of chronic liver disease in Western countries, affecting both adults and children. NAFLD encompasses a broad spectrum of fatty liver disease, ranging from simple steatosis (NAFL to nonalcoholic steatohepatitis (NASH, and is strongly associated with obesity, insulin resistance, and dyslipidemia. First-line therapy for NAFLD includes weight loss achieved through diet and physical activity. However, there is a lack of evidenced-based dietary recommendations. The American Diabetes Association’s (ADA recommendations that aim to reduce the risk of diabetes and cardiovascular disease may also be applicable to the NAFLD population. The objectives of this review are to: (1 provide an overview of NAFLD in the context of insulin resistance, and (2 provide a rationale for applying relevant aspects of the ADA recommendations to the nutritional management of NAFLD.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is prevalent in 20–25% of the general population and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. Histologically, NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH, fibrosis, and cirrhosis. As NASH develops in only 10–15% of patients with NAFLD, it is not practical to biopsy all patients who present with NAFLD. Noninvasive fibrosis tests have been extensively developed recently and offer alternatives for staging fibrosis. Despite their increasing use, such tests cannot adequately differentiate simple steatosis from NASH. At present, such tests can be used as first line tests to rule out patients without advanced fibrosis and thus prevent unnecessary secondary care referrals in a significant number of patients. In this review we present the evidence for the use of noninvasive fibrosis tests in patients with NAFLD.
Full Text Available Non-alcoholic fatty liver disease (NAFLD is a spectrum of diseases ranging from simple steatosis without inflammation or fibrosis to nonalcoholic steatohepatitis (NASH. Despite the strong association between dietary factors and NAFLD, no dietary animal model of NAFLD fully recapitulates the complex metabolic and histological phenotype of the disease, although recent models show promise. Although animal models have significantly contributed to our understanding of human diseases, they have been less successful in accurate translation to predict effective treatment strategies. We discuss strategies to overcome this challenge, in particular the adoption of big data approaches combining clinical phenotype, genomic heterogeneity, transcriptomics, and metabolomics changes to identify the ideal NAFLD animal model for a given scientific question or to test a given drug. We conclude by noting that novel big data approaches may help to bridge the translational gap for selecting dietary models of NAFLD.
Wang, Chaoyi; Guo, Dunwei; Wang, Qiang; You, Song; Qiao, Zhongpeng; Liu, Yong; Dai, Hang; Tang, Hua
To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia‑associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia‑induced activation of the renin‑angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy‑lysosome as well as ubiquitin‑proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti‑cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin-proteasome pathway (UPP).
de la Monte, Suzanne M; Longato, Lisa; Tong, Ming; Wands, Jack R
Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neu...
Full Text Available The Japanese success rate for alcoholism treatment is approximately 30%, indicating high relapse rates. Although “difficulty in life” is thought to contribute to alcoholics’ relapse, the characteristics of the phenomenon are unknown. This study examined the factors contributing to alcoholics’ difficulty in life. Alcoholic self-help group members, who indicated the extent of their difficulty in life and described the factors that contributed to this difficulty, completed a self-administered questionnaire. Participants’ hypersensitivity/grandiosity traits were also examined. A control group of nonalcoholic men also completed the questionnaire. Simple tabulation, descriptive statistics, Mann-Whitney U tests, and multivariate analyses were used to compare data between groups. Ultimately, 574 and 512 valid responses were received from the alcoholic (response rate: 27.1% and nonalcoholic (response rate: 33.1% groups, respectively. The proportion of alcoholics (54% who indicated that they found life difficult was significantly higher relative to that of nonalcoholics (39.9%. Alcoholics’ mean hypersensitivity score was significantly higher (2.67 relative to that observed for nonalcoholics (2.44. Significant between-group differences were observed for the following factors: building and maintaining relationships, satisfaction with life, self-distrust, cognitive bias, loneliness, empathic understanding, and self-acceptance. Multivariate logistic regression identified cognitive bias and building and maintaining relationships as factors contributing to alcoholics’ difficulty in life. Alcoholics’ social contexts, including broken families, social instability, and cross addiction, also contributed to this difficulty. Personal characteristics, such as hypersensitive-type narcissistic tendencies, relationship problems, and cognitive bias, were also associated with alcoholics’ difficulty in life.
Full Text Available Miwa Kawanaka,1 Ken Nishino,1 Takahito Oka,1 Noriyo Urata,1 Jun Nakamura,1 Mitsuhiko Suehiro,1 Hirofumi Kawamoto,1 Yasutaka Chiba,2 Gotaro Yamada1 1Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan; 2Clinical Research Center, Kinki University Hospital, Sayama, Japan Objective: Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH. Methods: In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA, tyrosine (Tyr, and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index, biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin, and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid. Results: Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion: Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels
Silva, Ana Patricia; Jager, Gerry; Bommel, Roelien van; Zyl, Hannelize van; Voss, Hans-Peter; Hogg, Tim; Pintado, M. E.; Graaf, Cees de
Non-alcoholic beer (NAB) may be a healthier alternative to wine and beer consumption, however has little appeal to consumers. Conceptualisations, i.e. functional and emotional associations that consumers have with foods/beverages, were explored to understand how NAB consumption is perceived, and compared to beer and wine conceptualisations in the Netherlands and Portugal. A qualitative study was performed using a focus group approach with moderate consumers of both countries (n = ...
Chen, Yu-Jung; Chen, Kai-Wen; Shih, Yu-Leung; Su, Fang-Ying; Lin, Yen-Po; Meng, Fan-Chun; Lin, Felicia; Yu, Yun-Shun; Han, Chih-Lu; Wang, Chih-Hung; Lin, Jia-Wei; Hsieh, Tsai-Yuan; Li, Yi-Hwei; Lin, Gen-Min
To investigate the association of chronic hepatitis B and nonalcoholic steatohepatitis with physical fitness in a Taiwanese military male cohort. We made a cross-sectional examination of this association using 3669 young adult military males according to cardiorespiratory fitness and hospitalization events recorded in the Taiwan Armed Forces study. Cases of chronic hepatitis B ( n = 121) were defined by personal history and positive detection of hepatitis B surface antigen. Cases of nonalcoholic steatohepatitis ( n = 129) were defined by alanine transaminase level > 60 U/L, liver ultrasound finding of steatosis, and absence of viral hepatitis A, B or C infection. All other study participants were defined as unaffected ( n = 3419). Physical fitness was evaluated by performance in 3000-m run, 2-min sit-ups, and 2-min push-ups exercises, with all the procedures standardized by a computerized scoring system. Multiple linear regression analysis was used to determine the relationship. Chronic hepatitis B negatively correlated with 2-min push-up numbers (β = -2.49, P = 0.019) after adjusting for age, service specialty, body mass index, systolic and diastolic blood pressures, current cigarette smoking, alcohol intake status, serum hemoglobin, and average weekly exercise times. Nonalcoholic steatohepatitis was borderline positively correlated with 3000-m running time (β = 11.96, P = 0.084) and negatively correlated with 2-min sit-up numbers (β = -1.47, P = 0.040). Chronic hepatitis B viral infection and nonalcoholic steatohepatitis affects different physical performances in young adult military males, and future study should determine the underlying mechanism.
Zheng, Yuqing; Kaiser, Harry M.
We propose a regime-switching model that allows demand to respond asymmetrically to upward and downward advertising changes. With the introduction of a smooth transition function, the model features smooth rather than abrupt parameter changes between regimes. We apply the model to nonalcoholic beverage data in the United States for 1974 through 2005 to investigate asymmetric advertising response. Results indicate that a decrease in milk advertising had a more profound impact on milk demand th...
Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD). The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iro...
Li, Hui; Clarke, John D.; Dzierlenga, Anika L.; Bear, John; Goedken, Michael J.; Cherrington, Nathan J.
Nonalcoholic steatohepatitis (NASH) has been identified as a source of significant interindividual variation in drug metabolism. A previous ex vivo study demonstrated significant changes in hepatic Cytochrome P450 (CYP) activity in human NASH. This study evaluated the in vivo activities of multiple CYP isoforms simultaneously in prominent diabetic NASH mouse models. The pharmacokinetics of CYP selective substrates: caffeine, losartan, and omeprazole changed significantly in a diabetic NASH mo...
Mônica Rodrigues de Araújo Souza
Full Text Available CONTEXT: Non-alcoholic fatty liver disease (NAFLD, hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS to non-alcoholic steatohepatitis (NASH. The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1 recognize patients with metabolic syndrome at high risk for NAFLD, 2 elucidate pathways common to other co-morbidities, 3
Silvia Marinho Ferolla
Full Text Available OBJECTIVE: Recent evidence suggests that non-alcoholic fatty liver disease is associated with diet. Our aim was to investigate the dietary patterns of a Brazilian population with this condition and compare them with the recommended diet. METHODS: A cross-sectional study was conducted on 96 non-alcoholic fatty liver disease patients before any dietetic counseling. All patients underwent abdominal ultrasound, biochemical tests, dietary evaluations, and anthropometric evaluations. Their food intake was assessed by a semi-quantitative food-frequency questionnaire and 24-hour food recall. RESULTS: The median patient age was 53 years, and 77% of the individuals were women. Most (67.7% participants were obese, and a large waist circumference was observed in 80.2% subjects. Almost 70% of the participants had metabolic syndrome, and 62.3% presented evidence of either insulin resistance or overt diabetes. Most patients (51.5, 58.5, and 61.7%, respectively exceeded the recommendations for energy intake, as well as total and saturated fat. All patients consumed less than the amount of recommended monounsaturated fatty acids, and 52.1 and 76.6% of them consumed less polyunsaturated fatty acids and fiber, respectively, than recommended. In most patients, the calcium, sodium, potassium, pyridoxine, and vitamin C intake did not meet the recommendations, and in 10.5-15.5% of individuals, the tolerable upper limit intake for sodium was exceeded. The patients presented a significantly high intake of meats, fats, sugars, legumes (beans, and vegetables and a low consumption of cereals, fruits, and dairy products compared with the recommendations. CONCLUSIONS: Although patients with non-alcoholic fatty liver disease exhibited high energy and lipid consumption, most of them had inadequate intake of some micronutrients. The possible role of nutrient-deficient intake in the development of non-alcoholic fatty liver disease warrants investigation.
Betancourt, Angela M.; King, Adrienne L.; Fetterman, Jessica L.; Millender-Swain, Telisha; Finley, Rachel D.; Oliva, Claudia R.; Crowe, David Ralph; Ballinger, Scott W.; Bailey, Shannon M.
Nonalcoholic fatty liver disease (NAFLD) involves significant changes in liver metabolism characterized by oxidative stress, lipid accumulation, and fibrogenesis. Mitochondrial dysfunction and bioenergetic defects also contribute to NAFLD. Herein, we examined whether differences in mtDNA influence NAFLD. To determine the role of mitochondrial and nuclear genomes in NAFLD, Mitochondrial-Nuclear eXchange (MNX) mice were fed an atherogenic diet. MNX mice have mtDNA from C57BL/6...
Khurram, M.; Mushraf, M.
To describe clinical and biochemical features of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). Fifty patients of either and of all ages were included, who had ultrasound evidence of fatty liver, deranged liver enzymes, and negative history of alcohol uptake. Serological/biochemical tests/markers of other liver diseases were negative. Each subject underwent liver biopsy reported by a single histopathologist. Clinical (symptoms, hypertension, hepatomegaly, and obesity) and biochemical evaluation (for diabetes, lipid abnormalities, and aspartate to alanine aminotransferase ratio (AST/ALT)) of each subject was done. Chi-square and t-tests were used for p-value calculation for finding significant difference between fatty liver and non-alcoholic steato-hepatitis groups. Thirty three (66%) patients were female and 34% were male. Mean age was 45.50+-11.50 years. Histopathologically, 62% subjects had fatty liver alone, while 38% had nonalcoholic steatohepatitis (NASH). Fatigue (100%), hypertriglyceridemia (80%), hepatomegaly (72%), AST/ALT ratio <1 (72%), and obesity/overweight (54%) were common NAFLD-related features. Except for hypertriglycedemia (p-value 0.008), no statistically significant association was noted between these features and histopathological subtypes of NAFLD. NAFLD-related clinical and biochemical features included fatigue, obesity, hepatomegaly, AST/ALT ratio <1, and hypertriglycedemia. Significant relationship existed between hypertriglyceridemia and NASH. (author)
Full Text Available The phenomenon that the same syndrome turns up in different diseases appears in the sight of people around the world, which raises the thought for possibility of “Same Treatment for Different Diseases.” Actually, treatment based on ZHENG classification in Traditional Chinese Medicine could bring revelation for the former finding. The dampness-heat syndrome in chronic hepatitis B and nonalcoholic fatty liver is regarded as the breakthrough point. We discussed the molecular mechanism of similar connotation that exists in chronic hepatitis B and nonalcoholic fatty liver by metabonomics to give the modern understanding of dampness-heat syndrome. Both urine and serum metabolic profiling revealed that obvious differences existed between dampness-heat syndrome and non-dampness-heat syndrome but the commonality was proved to appear in chronic hepatitis B and nonalcoholic fatty liver patients with dampness-heat syndrome. Furthermore, disorder of body fluid metabolism, decline in digestive capacity, and imbalance of intestinal flora were found to be the new guiding for treatment, with the hope to provide the basis for Chinese personalized medicine.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL to nonalcoholic steatohepatitis (NASH and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning, inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future.
Bonfiglioli, Catriona; Hattersley, Libby; King, Lesley
This study aimed to analyse the contribution of Australian print news coverage to the public profile of sweet, non-alcoholic beverages. News media portrayal of health contributes to individuals' decision-making. The focus on sugar-sweetened beverages reflects their contribution to excessive energy intake. One year's coverage of sweet, non-alcoholic beverages by major Australian newspapers was analysed using content and frame analysis. Research questions addressed which sweet drinks are most prominently covered, what makes sweet drinks newsworthy and how are the health aspects of sweet drinks framed? Fruit juice was the most widely covered sweet drink, closely followed by carbonated, sugar-sweetened soft drinks. Overall coverage was positively oriented towards sweet drinks, with fruit juice primarily portrayed as having health benefits. Some coverage mentioned risks of sweet drinks, such as obesity, tooth decay, metabolic syndrome and heart attack. Sweet drinks often enjoy positive coverage, with their health benefits and harms central to their ability to attract journalists' attention. However, the mix of coverage may be contributing to consumer confusion about whether it is safe and/or healthy to consume sweet non-alcoholic drinks. Framing of sweet drinks as healthy may undermine efforts to encourage individuals to avoid excess consumption of energy-dense drinks which offer few or minimal health benefits. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.
Full Text Available Nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH are increasingly common cause of chronic liver disease worldwide. The diagnosis of NASH is challenging as most affected patients are symptom-free and the role of routine screening is not clearly established. Most patients with severe obesity who undergo bariatric surgery have NAFLD, which is associated insulin resistance, type 2 diabetes mellitus (T2DM, hypertension, and obesity-related dyslipidemia. The effective treatment for NAFLD is weight reduction through lifestyle modifications, antiobesity medication, or bariatric surgery. Among these treatments, bariatric surgery is the most reliable method for achieving substantial, sustained weight loss. This procedure is safe when performed by a skilled surgeon, and the benefits include reduced weight, improved quality of life, decreased obesity-related comorbidities, and increased life expectancy. Further research is urgently needed to determine the best use of bariatric surgery with NAFLD patients at high risk of developing liver cirrhosis and its role in modulating complications of NAFLD, such as T2DM and cardiovascular disease. The current evidence suggests that bariatric surgery for patients with severe obesity decreases the grade of steatosis, hepatic inflammation, and fibrosis. However, further long-term studies are required to confirm the true effects before recommending bariatric surgery as a potential treatment for nonalcoholic steatohepatitis.
Full Text Available The aim of this paper is to investigate household spending by income deciles. Only the most important one among the expenditure categories was considered, food and non-alcoholic beverages. Research and analysis were based on the results of the Questionnaire on Household Expenditure in the Republic of Croatia. Adequate mathematical and statistical models of expenditure for food and non-alcoholic beverages by income deciles were established. The defined models were used in further research to calculate the coefficient of elasticity. The research showed that expenditure for food and non-alcoholic beverages is non-elastic, thus confirming the first Engel’s law. The obtained results can be used in planning household expenditure also in future periods, considering the fact that the model of expenditure by income deciles referring to the period 200 – 2009 was developed. A model for measuring elasticity was constructed as well. It refers to a 10-year period and can be used to forecast future coefficients of elasticity.
Full Text Available Non-alcoholic fatty liver disease (NAFLD covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL to non-alcoholic steatohepatitis (NASH and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD. Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%–23% fat and 57%–65% carbohydrate lower liver fat compared to diets with 43%–55% fat and 27%–38% carbohydrate. Diets rich in saturated (SFA as compared to monounsaturated (MUFA or polyunsaturated (PUFA fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.
Giuseppe Della Pepa
Full Text Available Non-alcoholic fatty liver disease (NAFLD incorporates an extensive spectrum of histologic liver abnormalities, varying from simple triglyceride accumulation in hepatocytes non-alcoholic fatty liver (NAFL to non-alcoholic steatohepatitis (NASH, and it is the most frequent chronic liver disease in the industrialized world. Beyond liver related complications such as cirrhosis and hepatocellular carcinoma, NAFLD is also an emerging risk factor for type 2 diabetes and cardiovascular disease. Currently, lifestyle intervention including strategies to reduce body weight and to increase regular physical activity represents the mainstay of NAFLD management. Total caloric intake plays a very important role in both the development and the treatment of NAFLD; however, apart from the caloric restriction alone, modifying the quality of the diet and modulating either the macro- or micronutrient composition can also markedly affect the clinical evolution of NAFLD, offering a more realistic and feasible treatment alternative. The aim of the present review is to summarize currently available evidence from randomized controlled trials on the effects of different nutrients including carbohydrates, lipids, protein and other dietary components, in isocaloric conditions, on NAFLD in people at high cardiometabolic risk. We also describe the plausible mechanisms by which different dietary components could modulate liver fat content.
Full Text Available Objective: To observe the clinical effects of Qianggan capsule and silibinin capsule in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia. Methods: A total of 112 patients with non-alcoholic fatty liver disease were included in the study and divided into the control group (n=50 and the observation group (n=62. The patients in the control group were given silibinin capsule, while the patients in the observation group were given Qianggan capsule. The patients in the two groups were treated for 24 weeks. The liver/ spleen CT was performed before and after treatment. BMI was measured. The liver function, serum lipid, and leptin were detected. Results: TG, LDL-C, BMI, and liver/spleen CT ratio in the observation group were significantly reduced when compared with the control group. The levels of HDL-C and adiponectin in the observation group were significantly elevated when compared with the control group. The differences of ALT, GGT, and AST after treatment between the two groups were not statistically significant. Conclusions: Qianggan capsule and silibinin capsule has an accurate efficacy and high safety in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia.
Guo, Jun; Zhou, Yuan; Cheng, Yafen; Fang, Weiwei; Hu, Gang; Wei, Jie; Lin, Yajun; Man, Yong; Guo, Lixin; Sun, Mingxiao; Cui, Qinghua; Li, Jian
Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention. The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention. Liver samples from three groups of mice were harvested for transcriptome profiling, which covered mRNA, lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray technique. A systematic alleviation of high-fat diet (HFD)-induced transcriptome alterations by metformin was observed. The metformin treatment largely reversed the correlations with diabetes-related pathways. Our analysis also suggested interaction networks between differentially expressed lncRNAs and known hepatic disease genes and interactions between circRNA and their disease-related miRNA partners. Eight HFD-responsive lncRNAs and three metformin-responsive lncRNAs were noted due to their widespread associations with disease genes. Moreover, seven miRNAs that interacted with multiple differentially expressed circRNAs were highlighted because they were likely to be associated with metabolic or liver diseases. The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD. © 2018 The Author(s). Published by S. Karger AG, Basel.
Kim, Sera; Hong, Jihye; Jeon, Raok; Kim, Hyun-Sook
Nonalcoholic fatty liver disease (NAFLD) is a simple steatosis, in which fat accumulates more than 5% in the liver, and regarded as most common liver diseases worldwide. Because NAFLD can be developed to severe liver disease and correlated with metabolic disease, its importance is currently emphasized. Occurrence of NAFLD is strongly related to dietary patterns and lifestyles; therefore, the suggestion of physiologically beneficial food is essential. Based on these, adzuki beans containing anthocyanin, catechin, and adzukisaponin are suggested as a health-beneficial food. Moreover, the effects of adzuki beans on metabolic improvement are not well established through the in vivo studies. Therefore, this study hypothesized that adzuki beans can alleviate lipid accumulation and oxidative stress-mediated inflammation in high-cholesterol and high-fat diet-induced NALFD mice. To demonstrate its effects, 6-week-old C57BL/6 male mice were allocated into 4 groups and fed a normal diet (ND), a high-cholesterol and high-fat diet (HCD), and HCD with 10% and 20% adzuki bean for 10 weeks. The result shows that fasting blood glucose, serum and hepatic triglyceride and cholesterol levels, and antioxidative enzyme activity ameliorated in the adzuki bean groups (P hepatic lipogenesis, such as adiponectin, AMP-activated protein kinase α, sterol regulatory element-binding protein 1c, fatty acid synthase, carnitine palmitoyltransferase 1, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and apolipoprotein B, as well as proinflammatory mediators, such as tumor necrosis factor α, nuclear factor κB, and caspase-3, improved in both experimental groups (P hepatic messenger RNA expression of lipogenic and inflammatory mediators in NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.
Alam, Mushfiqul; Hromcik, Martin; Hanis, Tomas
Lightweight flexible blended-wing-body (BWB) aircraft concept seems as a highly promising configuration for future high capacity airliners which suffers from reduced stiffness for disturbance loads such as gusts. A robust feedforward gust load alleviation system (GLAS) was developed to alleviate ...
Lee, Young Ku [Korea Energy Economics Institute, Euiwang (Korea)
For alleviating domestic oil price when the international oil crisis happens, the government has been reacted directly such as using stored oil or alleviation fund. Although the release of stored oil works for short-term depending on the type of crisis, concerning that most of oil crisis had been resulted in temporary supply reduction rather than long-term supply suspension, utilizing the domestic alleviation fund is regarded more economical than storing oil. However, it has been suggested to compare efficiencies of alleviation fund and a futures market regarding the perspectives that using alleviation fund is more inefficient than utilizing a futures market. Moreover, the direct management by government is less efficient than indirect management. As an efficient way to alleviate domestic oil price at international oil crisis, this study presents an effective utilization of trading in futures of crude oil. There is a high probability of occurrence of this kind of oil crisis by judging from the world political situation and the trend of oil market. In such a case, the government as a crude oil importer should minimize the stored oil and utilize a futures market effectively. The subject of alleviating oil price by trading in futures is an oil supplier, such as oil refining companies or oil importers not the government as a prerequisite. Furthermore, the government should approve to include appropriate cost for preparing oil price alleviation in the oil price and it is required that such a government policy should be consistent. (author). 41 refs., 3 figs., 15 Tabs.
Fedorova, T E; Efimenko, N V; Kaĭsinova, A S
The objective of the present work was to estimate the effectiveness of combined spa-and-resort treatment with the use of the Essentuki-type drinking mineral waters for the patients presenting with non-alcoholic fatty liver disease. A total of 40 patients presening with non-alcoholic fatty liver disease (NOFLD) were available for the examination. The study has demonstrated positive dynamics of clinical symptoms and results of liver functional tests, characteristics of intrahepatic dynamics, lipid metabolism, antioxidant hemostais, and the hormonal status of the patients with non-alcoholic fatty liver disease. The intake of the Essentuki-type drinking mineral waters promoted normalization of adiponectin and leptin levels in conjunction with the reduction in the degree of insulin resistance, i.e., the key pathogenetic factors responsible for hepatic steatosis and non-alcoholic steatohepatitis. It is concluded that the Essentuki-type drinking mineral waters may be recommended for the inclusion in the combined treatment and prevention of the progression of non-alcoholic fatty liver disease.
Full Text Available Extracts from deer bones, called nok-gol in Korean, have long been used to invigorate Qi. While neutropenia is not well detected in normal physiological condition, it could be a cause of severe problems to develop diseases such as infectious and cancerous diseases. Thus, a prevention of neutropenia in normal physiology and pathophysiological states is important for maintaining Qi and preventing disease progress. In cell biological aspects, activated macrophages are known to prevent neutropenia. In this study, we demonstrate that water extract of deer bone (herein, NG prevents neutropenia by activating macrophages. In mouse neutropenia model system in vivo where ICR mice were treated with cyclophosphamide to immunosuppress, an oral administration of NG altered the number of blood cells including lymphocytes, neutrophils, basophils, and eosinophils. This in vivo effect of NG was relevant to that of granulocyte colony stimulating factor (G-CSF that was known to improve neutropenia. Our in vitro studies further showed that NG treatment increased intracellular reactive oxygen species (ROS and promoted macrophagic differentiation of mouse monocytic Raw264.7 cells in a dose-dependent manner. In addition, NG enhanced nitric oxide (NO synthesis and secretions of cytokines including IL-6 and TNF-α. Consistently, NG treatment induced phosphorylation of ERK, JNK, IKK, IκBα, and NF-κB in Raw264.7 cells. Thus, our data suggest that NG is helpful for alleviating neutropenia.
Mavhungu Abel Mafukata
Full Text Available The main objective of this paper is to explore the factors having the most significance on the probability of the adopters of microfinance moving out of poverty in Zambia. Ninety nine (n=99 respondents were randomly and purposively selected from amongst 340 microfinance adopters of the so-called Micro Bankers Trust programme operating a microfinance business in the Makululu Compound of Kabwe, Zambia. Primary data were collected through face-to-face interviews based on a semi-structured questionnaire. The data were entered into an excel spreadsheet for analysis. The descriptive data were thereafter exported and fitted to an empirical model. The descriptive results revealed that the majority of the respondents were married, unemployed, fairly educated younger women from larger-sized poor households who drew their household income mainly from microfinance activities. The majority of the respondents thought microfinance had improved their well-being in some crucial areas. The results of the empirical model found that some respondents indeed had improved their probabilities to move out of poverty. Conclusion drawn in this paper is that microfinance does alleviate poverty of the poor.
M Carme Coll Ferrer
Full Text Available Lysozyme dextran nanogels (NG have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with "stealth" properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab directed to Intercellular Adhesion Molecule-1(ICAM-NG, whereas IgG conjugated NG (IgG-NG are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG; and, ii DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation.
Schrey, Aleksi; Airas, Laura; Jokela, Manu; Pulkkinen, Jaakko
Oropharyngeal dysphagia is a disabling and undertreated symptom that often occurs in patients with sporadic inclusion body myositis (s-IBM). In this study, we examined the effect of botulinum neurotoxin A (BoNT-A) injections to the cricopharyngeus muscle (CPM) of patients with s-IBM and dysphagia. A single-center retrospective study involving 40 biopsy-proven s-IBM-patients treated in the District of Southwest Finland from 2000 to 2013. The incidence of dysphagia, rate of aspirations, rate of aspiration pneumonias and treatment results of dysphagia were analyzed. Patients treated for dysphagia were evaluated before and after surgery by video-fluoroscopy and/or using a questionnaire. Twenty-five of the 40 s-IBM patients (62.5%) experienced dysphagia. BoNT-A was injected a median of 2 times (range 1-7) in 12 patients with dysphagia. Before the injections 7 patients reported aspiration, none afterwards. The corresponding figures for aspiration pneumonia were 3 and 0. All of these patients had normal swallowing function 12months (median, range 2-60) after the last injection. BoNT-A injections to the CPM alleviate the dysphagia of s-IBM patients reversibly and appear to reduce the rate of aspiration effectively. Copyright © 2017 Elsevier B.V. All rights reserved.
Qiu, Tian; Wang, Tian-Tian; Zhang, Zi-Ke; Zhong, Li-Xin; Chen, Guang
Recommendation bias towards objects has been found to have an impact on personalized recommendation, since objects present heterogeneous characteristics in some network-based recommender systems. In this article, based on a biased heat conduction recommendation algorithm (BHC) which considers the heterogeneity of the target objects, we propose a heterogeneous heat conduction algorithm (HHC), by further taking the heterogeneity of the source objects into account. Tested on three real datasets, the Netflix, RYM and MovieLens, the HHC algorithm is found to present better recommendation in both the accuracy and diversity than two benchmark algorithms, i.e., the original BHC and a hybrid algorithm of heat conduction and mass diffusion (HHM), while not requiring any other accessorial information or parameter. Moreover, the HHC algorithm also elevates the recommendation accuracy on cold objects, referring to the so-called cold-start problem. Eigenvalue analyses show that, the HHC algorithm effectively alleviates the recommendation bias towards objects with different level of popularity, which is beneficial to solving the accuracy-diversity dilemma.
Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang
Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.
Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua
L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. Copyright © 2016 Elsevier B.V. All rights reserved.
Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B
Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.
Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li
In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H₂O₂) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H₂O₂and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-α and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury.
Su, Weihua; Reich, Gregory W.
Artificial hair sensors (AHS) have been recently developed in Air Force Research Laboratory (AFRL) using carbon nanotube (CNT). The deformation of CNT in air flow causes voltage and current changes in the circuit, which can be used to quantify the dynamic pressure and aerodynamic load along the wing surface. AFRL has done a lot of essential work in design, manufacturing, and measurement of AHSs. The work in this paper is to bridge the current AFRL's work on AHSs and their feasible applications in flight dynamics and control (e.g., the gust alleviation) of highly flexible aircraft. A highly flexible vehicle is modeled using a strain-based geometrically nonlinear beam formulation, coupled with finite-state inflow aerodynamics. A feedback control algorithm for the rejection of gust perturbations will be developed. A simplified Linear Quadratic Regulator (LQR) controller will be implemented based on the state-space representation of the linearized system. All AHS measurements will be used as the control input, i.e., wing sectional aerodynamic loads will be defined as the control output for designing the feedback gain. Once the controller is designed, closed-loop aeroelastic simulations will be performed to evaluate the performance of different controllers with the force feedback and be compared to traditional controller designs with the state feedback. From the study, the feasibility of AHSs in flight control will be assessed. The whole study will facilitate in building a fly-by-feel simulation environment for autonomous vehicles.
Liang, Bowen; Li, Cuiying; Ma, Changqing; Wei, Zhiwei; Wang, Qian; Huang, Dong; Chen, Qi; Li, Chao; Ma, Fengwang
Dopamine mediates many physiological processes in plants. We investigated its role in regulating growth, root system architecture, nutrient uptake, and responses to nutrient deficiencies in Malus hupehensis Rehd. Under a nutrient deficiency, plants showed significant reductions in growth, chlorophyll concentrations, and net photosynthesis, along with disruptions in nutrient uptake, transport, and distribution. However, pretreatment with 100 μM dopamine markedly alleviated such inhibitions. Supplementation with that compound enabled plants to maintain their photosynthetic capacity and development of the root system while promoting the uptake of N, P, K, Ca, Mg, Fe, Mn, Cu, Zn, and B, altering the way in which those nutrients were partitioned throughout the plant. The addition of dopamine up-regulated genes for antioxidant enzymes involved in the ascorbate-glutathione cycle (MdcAPX, MdcGR, MdMDHAR, MdDHAR-1, and MdDHAR-2) but down-regulated genes for senescence (SAG12, PAO, and MdHXK). These results indicate that exogenous dopamine has an important antioxidant and anti-senescence effect that might be helpful for improving nutrient uptake. Our findings demonstrate that dopamine offers new opportunities for its use in agriculture, especially when addressing the problem of nutrient deficiencies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Full Text Available Herbal medicines have been used in preventing and treating skin disorders for centuries. It has been demonstrated that systemic administration of chrysanthemum extract exhibits anti-inflammatory properties. However, whether topical applications of apigenin, a constituent of chrysanthemum extract, influence cutaneous inflammation is still unclear. In the present study, we first tested whether topical applications of apigenin alleviate cutaneous inflammation in murine models of acute dermatitis. The murine models of acute allergic contact dermatitis and acute irritant contact dermatitis were established by topical application of oxazolone and phorbol 12-myristate 13-acetate (TPA, respectively. Inflammation was assessed in both dermatitis models by measuring ear thickness. Additionally, the effect of apigenin on stratum corneum function in a murine subacute allergic contact dermatitis model was assessed with an MPA5 physiology monitor. Our results demonstrate that topical applications of apigenin exhibit therapeutic effects in both acute irritant contact dermatitis and allergic contact dermatitis models. Moreover, in comparison with the vehicle treatment, topical apigenin treatment significantly reduced transepidermal water loss, lowered skin surface pH, and increased stratum corneum hydration in a subacute murine allergic contact dermatitis model. Together, these results suggest that topical application of apigenin could provide an alternative regimen for the treatment of dermatitis.
Full Text Available Gust load alleviation (GLA tests are widely conducted to study the effectiveness of the control laws and methods. The physical parameters of models in these tests are aeroelastic scaled, while the scaling of GLA control system is always unreached. This paper concentrates on studying the scaling laws of GLA control system. Through theoretical demonstration, the scaling criterion of a classical PID control system has been come up and a scaling methodology is provided and verified. By adopting the scaling laws in this paper, gust response of the scaled model could be directly related to the full-scale aircraft theoretically under both open-loop and closed-loop conditions. Also, the influences of different scaling choices of an important non-dimensional parameter, the Froude number, have been studied in this paper. Furthermore for practical application, a compensating method is given when the theoretical scaled actuators or sensors cannot be obtained. Also, the scaling laws of some non-linear elements in control system such as the rate and amplitude saturations in actuator have been studied and examined by a numerical simulation.
Shi, Li-Juan; Song, Guang-Yao
With the increased morbidity of Nonalcoholic fatty liver disease, the pathogenesis of which has become one of the focuses for researchers. Many details need to be clarified. The hepatic steatosis has been taken as the clinical pathological characters and the "golden standard of diagnosis" for the nonalcoholic fatty liver disease. More and more studies have shown that the hepatic steatosis (mainly as triglycerides) is the consequence of hepatic lipid metabolism disequilibrium. Generally, the related metabolism pathways including lipid input, lipid uptake, de novo lipogenesis, fatty acid oxidation, fatty acid reesterification, and lipid secretion etc. In this review, we focused on the progress of some key enzymes involved in these pathways in order to clarify the possible molecular mechanisms and the effective targets so that to broad our vision about the prevention and treatment of non-alcoholic fatty liver disease.
Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki
For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (PBCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.
Lădaru, Anca; Bălănescu, Paul; Stan, Mihaela; Codreanu, Ioana; Anca, Ioana Alina
Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. Medline and Embase databases were searched from inception to December 2014. A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.
Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan
Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.
Liu, Yun; She, Weimin; Wang, Fuping; Li, Jing; Wang, Jiyao; Jiang, Wei
This study was designed to discuss the effects of 3, 3'-diindolylmethane (DIM) on methionine-choline-deficient (MCD)-diet induced mouse nonalcoholic steatohepatitis (NASH) and the potential mechanisms. NASH mice were administrated with or without DIM at different concentrations for 8 weeks. Both the in-vivo and in-vitro effects of DIM on Treg/Th17 imbalance during NASH progression were analyzed. The in-vivo blocking of CD25 or IL-17 was performed to respectively deplete respective function of Treg or Th17 subset. Besides, with the assistance of AhR antagonist CH223191 and anti-TLR4 neutralizing antibody, we designed the in-vitro DIM-incubation experiments to discuss the roles of aryl hydrocarbon receptor (AhR) (CYP1A1, CYP1B1) and toll-like receptor 4 (TLR4) on DIM's effects when shifting Treg/Th17 imbalance. Notably, in NASH mouse models, DIM alleviated hepatic steatosis and inflammation, and shifted the Treg/Th17 imbalance from MCD diet-induced Th17 dominance to Treg dominance. In-vitro, DIM not only significantly up-regulated the mRNAs of Foxp3 (Treg-specific) in purified spleen CD4(+) T cells, but also enhanced the immunosuppressive function of these Treg cells. Besides, DIM significantly up-regulated the proteins of CYP1A1 and CYP1B1 whereas down-regulated those of TLR4 on CD4(+) T cells from MCD-diet mice. Moreover, blocking AhR attenuated while blocking TLR4 enhanced the effects of DIM when regulating Treg/Th17 imbalance. Conclusively, DIM could be used as a potential therapeutic candidate to treat NASH based on its dramatic induction of Treg dominance to alleviate intra-hepatic inflammation, suggesting us a clue that the dietary cruciferous vegetables (containing abundant DIM) might exist as a protective factor for patients with NASH-related liver diseases. Copyright © 2014 Elsevier B.V. All rights reserved.
Belcaro, G; Cesarone, M R; Genovesi, D; Ledda, A; Vinciguerra, G; Ricci, A; Pellegrini, L; Gizzi, G; Ippolito, E; Dugall, M; Cacchio, M; Di Renzo, A; Stuard, S
A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology. Specific medications exist to target individual side effects. The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient's quality of life. Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition, both physically and psychologically, were recruited for this study and divided into two groups. These patients received their first cycle of radiotherapy or chemotherapy, which lasted from 10 days up to 1 month. Then one group of patients received 150 mg Pycnogenol, the control group comparable placebo in a single-blinded fashion. The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy, respectively. Twenty five radiotherapy patients receiving Pycnogenol showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo, though in many categories the difference was limited. The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes. A decreased incidence of nausea /vomiting, diarrhoea, edema and weakness was noticed, which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group. Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group (2.9% vs 10%). Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30
Roberts, Leanne; Ahmed, Irshad; Hall, Steve; Davison, Andrew
Prayer is amongst the oldest and most widespread interventions used with the intention of alleviating illness and promoting good health. Given the significance of this response to illness for a large proportion of the world's population, there has been considerable interest in recent years in measuring the efficacy of intercessory prayer for the alleviation of ill health in a scientifically rigorous fashion. The question of whether this may contribute towards proving or disproving the existence of God is a philosophical question lying outside the scope of this review of the effects of prayer. This revised version of the review has been prepared in response to feedback and to reflect new methods in the conduct and presentation of Cochrane reviews. To review the effects of intercessory prayer as an additional intervention for people with health problems already receiving routine health care. We systematically searched ten relevant databases including MEDLINE and EMBASE (June 2007). We included any randomised trial comparing personal, focused, committed and organised intercessory prayer with those interceding holding some belief that they are praying to God or a god versus any other intervention. This prayer could be offered on behalf of anyone with health problems. We extracted data independently and analysed it on an intention to treat basis, where possible. We calculated, for binary data, the fixed-effect relative risk (RR), their 95% confidence intervals (CI), and the number needed to treat or harm (NNT or NNH). Ten studies are included in this updated review (7646 patients). For the comparison of intercessory prayer plus standard care versus standard care alone, overall there was no clear effect of intercessory prayer on death, with the effect not reaching statistical significance and data being heterogeneous (6 RCTs, n=6784, random-effects RR 0.77 CI 0.51 to 1.16, I(2) 83%). For general clinical state there was also no significant difference between groups (5
Buytaert, W.; Baez, S.; Cuesta, F.; Veliz Rosas, C.
Over the last decades, near real-time environmental observation, technical advances in computer power and cyber-infrastructure, and the development of environmental software algorithms have increased dramatically. The integration of these evolutions, which is commonly referred to as the establishment of a virtual observatory, is one of the major challenges of the next decade for environmental sciences. Worldwide, many coordinated activities are ongoing to make this integration a reality. However, far less attention is paid to the question of how these developments can benefit environmental services management in a poverty alleviation context. Such projects are typically faced with issues of large predictive uncertainties, limited resources, limited local scientific capacity. At the same time, the complexity of the socio-economic contexts requires a very strong bottom-up oriented and interdisciplinary approach to environmental data collection and processing. In this study, we present three natural resources management cases in the Andes and the Amazon basin, and investigate how "virtual observatory" technology can improve ecosystem management. Each of these case studies present scientific challenges in terms of model coupling, real-time data assimilation and visualisation for management purposes. The first project deals with water resources management in the Peruvian Andes. Using a rainfall-runoff model, novel visualisations are used to give farmers insight in the water production and regulation capacity of their catchments, which can then be linked to land management practices such as conservation agriculture, wetland protection and grazing density control. In a project in the Amazonian floodplains, optimal allocation of the nesting availability and quality of the giant freshwater turtle are determined using a combined hydraulic model and weather forecasts. Finally, in the rainforest of the Yasuní Biosphere Reserve, Ecuador, biodiversity models are used to
Martin, Elizabeth A.; Barresi, Rita; Byrne, Barry J.; Tsimerinov, Evgeny I.; Scott, Bryan L.; Walker, Ashley E.; Gurudevan, Swaminatha V.; Anene, Francine; Elashoff, Robert M.; Thomas, Gail D.; Victor, Ronald G.
Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates local α-adrenergic vasoconstriction thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. Here, we report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled cross-over trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation fully restored in the muscles of men with BMD by boosting NO-cGMP signaling with a single dose of the drug tadalafil, a phosphodiesterase (PDE5A) inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD. PMID:23197572
Studies were undertaken in Malawi from 1995 to 1997 and 2007 to 2008 to estimate the supply and demand of household energy. Because little is known about the supply chain for biomass, surveys were carried out for urban areas on its production, transport and trade as well as sustainable supply. Also, because biomass is used by all people for a multitude of purposes, a complete picture was made of regional and urban biomass supply and demand. The results indicated that biomass is not only the principal energy, accounting for 89 percent of demand, but also the main traded energy in the two time periods accounting for 56-59 percent of commercial demand. Petroleum products supplied 26-27 percent, electricity 8-12 percent and coal 6-10 percent. The market value of traded woodfuel was US$ 48.8 million and US$ 81.0 million in 1996 and 2008 respectively, about 3.5 percent of gross domestic product (GDP). The study found that in 1996 and 2008 respectively, the equivalent of 93,500 and 133,000 full-time people was employed in the biomass supply chain, approximately 2 percent of the potential workforce. In contrast, about 3400 and 4600 people were employed in the supply chain of other fuels in these years. If the Malawi findings are applied to the current estimated wood energy consumption in sub-Saharan Africa, then approximately 13 million people could be employed in commercial biomass energy; this highlights its importance as a means to assist with sustainable development and poverty alleviation. (author)
Yu, Jing; Xu, Wen-Hua; Sun, Wei; Sun, Yi; Guo, Zhi-Li; Yu, Xiao-Ling
Curcumin is a natural polyphenol extracted from the turmeric rhizome, which has a wide range of biological activities, but until now the effects of curcumin on the gastrointestinal peristalsis have not been fully understood. In vivo study, we observed the effects of curcumin on gastric emptying and intestinal propulsion rates of mice in normal state and in delayed state by atropine (ATR) or nitric oxide precursor L-arginine (L-Arg). An in vitro study explored the direct effects of curcumin on the intestinal contractility, but were studied through measuring spontaneous contraction of isolated jejunum of mice. Our results showed that intragastric administration of curcumin (200 mg/kg/day) for 10-20 days significantly improved gastric emptying and intestinal propulsion rates of mice delayed by ATR. Moreover, intragastric administration of curcumin (200 mg/kg/day) for 15 days also significantly improved mice gastric emptying and intestinal propulsion rates delayed by L-Arg. There was no significant effect on normal gastrointestinal propulsion of mice after intragastric administration of curcumin (200 mg/kg/day) for 1-20 days. When normal isolated jejunum of mice were incubated with curcumin in vitro, the amplitude of the spontaneous contractile waves of jejunum was reduced in a concentration-dependent manner. Moreover, curcumin reduced the amplitude of the contractile waves of jejunum in both contracted and relaxed state induced by acetylcholine or ATR individually. Taken together, our results suggest that curcumin has quite different effects on gastrointestinal peristalsis in vivo and in vitro. Moderate dose of curcumin by intragastric administration for more than 10 days can alleviate the functional gastrointestinal disorders of mice, but cannot affect normal gastrointestinal propulsion.
Full Text Available Each step of the seed-to-seed cycle of plant development including seed germination is characterized by a specific set of proteins. The continual renewal and/or replacement of these biomolecules are crucial for optimal plant adaptation. As proteins are the main effectors inside the cells, their levels need to be tightly regulated. This is partially achieved by specific proteolytic pathways via multicatalytic protease complexes defined as 20S and 26S proteasomes. In plants, the 20S proteasome is responsible for degradation of carbonylated proteins, while the 26S being a part of ubiquitin-proteasome pathway (UPP is known to be involved in proteolysis of phytohormone signaling regulators. On the other hand, the role of translational control of plant development is also well documented, especially in the context of pollen tube growth and light signaling. Despite the current progress that has been made in seed biology, the sequence of cellular events that determine if the seed can germinate or not are still far from complete understanding. The role and mechanisms of regulation of proteome composition during processes occurring in the plant’s photosynthetic tissues have been well characterized since many years, but in nonphotosynthetic seeds it has emerged as a tempting research task only since the last decade. This review discusses the recent discoveries providing insights into the role of protein turnover in seed dormancy alleviation, and germination, with a focus on the control of translation and proteasomal proteolysis. The presented novel data of translatome profiling in seeds highlighted that post-transcriptional regulation of germination results from a timely regulated initiation of translation. In addition, the importance of 26S proteasome in the degradation of regulatory elements of cellular signaling and that of the 20S complex in proteolysis of specific carbonylated proteins in hormonal- and light-dependent processes occurring in seeds is
Zakaria, Esraa M; El-Bassossy, Hany M; El-Maraghy, Nabila N; Ahmed, Ahmed F; Ali, Abdelmoneim A
Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out. Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia. Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms. Copyright © 2016. Published by Elsevier B.V.
Malouff, John M; Noble, William; Schutte, Nicola S; Bhullar, Navjot
The present study examined the efficacy of bibliotherapy in assisting individuals experiencing distress related to tinnitus. One hundred sixty-two tinnitus sufferers from Australia participated in a study designed to examine the effectiveness of a cognitive-behaviorally based self-help book in reducing distress. To maximize the ecological validity of the findings, we excluded no individuals interested in treatment for tinnitus-related distress. The experimental condition lost 35% of participants at postassessment, compared to 10% in the control group. In an analysis of participants who completed postintervention assessment, those assigned to the intervention condition, who received a tinnitus self-help book, showed significantly less tinnitus-related distress and general distress 2 months later compared to those assigned to the waiting list control condition. The intervention group's reduction in tinnitus-related distress and general distress from preintervention to postintervention 2 months later was significant, and these participants maintained a significant reduction in distress on follow-up 4 months after they received the tinnitus self-help book. A long-term follow-up of all participants, who at that time had received the book at least a year previously, showed a significant reduction in tinnitus distress. Although these group differences and pre-post changes were significant, effect sizes were small. Intention-to-treat analyses showed no significant effect for between-groups analyses, but did show a significant effect for the 1-year follow-up pre-post analysis. Information on the effectiveness of using a self-help book, without therapist assistance, in alleviating distress is important, as bibliotherapy can provide inexpensive treatment that is not bound by time or place. Copyright 2010 Elsevier Inc. All rights reserved.
Berman-Kishony, Talia; Shvarts, Shifra
Disruptive behavior among hospital staff can negatively affect quality of care. Motivated by a standard on disruptive behavior issued by The Joint Commission (LD 3.10), as well as the desire to improve patient care, minimize liability, and improve staff retention, hospitals are setting policies to prevent and resolve disruptive behaviors. However, it is unknown whether uniform conflict management tools are equally effective among different hospital settings. We surveyed residents and nurses to identify similarities and differences among hospital departments in the antecedents, characteristics, and outcomes of disruptive behaviors, and in the effectiveness of conflict management tools. We used a quantitative questionnaire-based assessment to examine conflict perceptions in eight different hospital departments at Rambam Medical Center in Haifa, Israel. Most participants (89 %) reported witnessing disruptive behavior either directly or in other parties; the most significant causes were identified as intense work, miscommunication, and problematic personalities. The forms of these behaviors, however, varied significantly between departments, with some more prone to expressed conflicts, while others were characterized by hidden disruptive behaviors. These outcomes were correlated by the antecedents to disruptive behavior, which in turn affected the effectiveness of alleviating strategies and tools. Some tools, such as processes for evaluating complaints, teamwork and conflict management courses, and introducing a behavioral mission statement, are effective across many antecedents. Other tools, however, are antecedent-specific, falling into two principal categories: tools directly removing a specific problem and tools that offer a way to circumvent the problem. Conflict resolution tools and strategies, based on residents and nurse perceptions, may be more effective if tailored to the specific situation, rather than using a "one-size-fits-all" approach.
Hasan, Saam N.; Rossiter, J. A.
Despite the fact that several Air Traffic Management (ATM) complexity metrics have been proposed in the past few years, very few of these studies incorporate a control independent intrinsic approach to the problem with the aim of sustaining trajectory flexibility. This paper proposes the introduction of novel decision making metrics for sustaining user trajectory flexibility. The hypothesis is, if all aircraft apply a flexibility preservation function, complexity may reduce automatically. The functions proposed combine concepts of adaptability, robustness and intrinsic traffic complexity metrics based on Lyapunov exponents. Adaptability is defined as a measure of the ability of the aircraft to change its planned trajectory in response to the occurrence of a disturbance that renders the current planned trajectory infeasible. The Robustness metric is defined as the ability of the aircraft to keep its planned trajectory unchanged in response to the occurrence of disturbances. An Intrinsic complexity measure is used to evaluate the level of disorder with regards to the aircraft trajectory; disorder is defined in this context as the level of consistency in the flow patterns of aircraft and their proximity. A point mass model for multiple aircraft(s) is used to extract the trajectories and computing a form of characterisation of sensitivity and interdependencies of a set of aircraft trajectories. Lyapunov exponents are used to compute this measure. The main contribution of this paper will be to test the hypothesis by combining the complexity metrics described above. Different operational scenarios are simulated using a airspace environment developed in MATLAB which shows how well the traffic is structured by varying the metrics defined. The simulation shows the efficacy of the metrics to alleviate complexity in a heavily congested airspace.
Ürge-Vorsatz, Diana; Tirado Herrero, Sergio
Even though energy poverty alleviation and climate change mitigation are inextricably linked policy goals, they have remained as relatively disconnected fields of research inquiry and policy development. Acknowledging this gap, this paper explores the mainstream academic and policy literatures to provide a taxonomy of interactions and identify synergies and trade-offs between them. The most important trade-off identified is the potential increase in energy poverty levels as a result of strong climate change action if the internalisation of the external costs of carbon emissions is not offset by efficiency gains. The most significant synergy was found in deep energy efficiency in buildings. The paper argues that neither of the two problems – deep reductions in GHG emissions by mid-century, and energy poverty eradication – is likely to be solved fully on their own merit, while joining the two policy goals may provide a very solid case for deep efficiency improvements. Thus, the paper calls for a strong integration of these two policy goals (plus other key related benefits like energy security or employment), in order to provide sufficient policy motivation to mobilise a wide-scale implementation of deep energy efficiency standards. - Highlights: ► A taxonomy of interactions between climate change and energy poverty is offered. ► Energy poverty levels may increase as a result of strong climate change action. ► However, strong synergies are offered by deep improvements of energy efficiency. ► Access to modern energy carriers is a key requirement in developing countries. ► Sufficiently solving both problems requires the integration of policy goals.
Highlights from an interview with Benjamin D. de Leon, who was appointed Presidential Assistant for Social Development in the Philippines in September 1992, are presented. Mr. de Leon's concern for the marginal sectors of society in health, employment, housing, social welfare, and manpower training as well as his goals of poverty alleviation and people empowerment account for this appointment. Duties include formulating a social development agenda; assisting the Social Development Committee of the Cabinet and the National Economic Development Authority (NEDA) in program implementation; and providing weekly information packages about family planning (FP), health, children, women, and the environment. The social development agenda of the Philippine Medium-term Plan (1992-1998) includes employment, income, wages; population, health and nutrition, and family planning; and housing, education, manpower development, social welfare, and community development. The Plan recognizes that poverty is aggravated by rapid population growth, and it strives to ensure that adolescents, military males, high-risk women, and young unmarried couples receive FP information and services from government agencies and nongovernmental organizations. Adequate resources for population and FP as well as recognizing the relationship among population, resources, and the environment are essential to meet the goals of the plan. The present population and FP policy is based on the 1987 Constitution, which spells out responsible parenthood but also rejects abortion as a method of contraception. The official FP program calls for child survival and safe motherhood and accessible, available, and affordable FP services. The Roman Catholic Church opposes the program, since the Church promotes only the rhythm method, but the other religions approve of the program. Some priests and nuns did not object to the promotion of FP. Sufficient financial support from the international community for the Philippine
Martin, Elizabeth A; Barresi, Rita; Byrne, Barry J; Tsimerinov, Evgeny I; Scott, Bryan L; Walker, Ashley E; Gurudevan, Swaminatha V; Anene, Francine; Elashoff, Robert M; Thomas, Gail D; Victor, Ronald G
Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.
Eric R Kallwitz; Alan McLachlan; Scott J Cotler
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisorne proliferators- activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPARγ to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.
Clint L. Miller, PhD
Full Text Available Nonalcoholic steatohepatitis is a common disease involving chronic accumulation of fat and inflammation in the liver, often leading to advanced fibrosis, cirrhosis, and cancer. It is known that nonalcoholic steatohepatitis shares many features with atherosclerosis; however, there are still no effective therapeutics. In a recent study published in Nature, investigators demonstrated that mice lacking a high-density lipoprotein–associated gene were surprisingly protected from both steatohepatitis and atherosclerosis through the stabilization of the liver X receptor. This work reveals a timely candidate target for 2 highly prevalent cardiovascular diseases.
Lin, Connie; Rountree, Carl B.; Methratta, Sosamma; LaRusso, Salvatore; Kunselman, Allen R.; Spanier, Adam J.
Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. Aims: To investigate the association of secondhand tobacco exposure with NAFLD in children. Methods: We surveyed parents/guardians of 304 children aged 3–12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed the ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. Results: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). Conclusion: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts. - Highlights: • We evaluated the relation of tobacco exposure with nonalcoholic fatty liver disease. • Tobacco smoke exposure was associated with nonalcoholic fatty liver disease. • Tobacco smoke exposure may be an addressable risk factor
Kawanaka, Miwa; Nishino, Ken; Oka, Takahito; Urata, Noriyo; Nakamura, Jun; Suehiro, Mitsuhiko; Kawamoto, Hirofumi; Chiba, Yasutaka; Yamada, Gotaro
Objective Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. PMID:26082668
Ou, Rongying; Liu, Jia; Lv, Mingfen; Wang, Jingying; Wang, Jinmeng; Zhu, Li; Zhao, Liang; Xu, Yunsheng
Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.
Full Text Available Background: Prevalence of non-alcoholic fatty liver disease (NAFLD is more common worldwide and no certain treatment apart from lifestyle modification has been established yet. Available data consistently show that energy intake is significantly higher in patients with NAFLD than in individuals with no evidence of fatty liver. Changing nutritional behaviors seems to be the primary approach for treatment, simultaneously addressing all the clinical and biochemical defects. This study was aimed to examine the effects of two different composition of low energy diet (diet I vs. diet II on non-alcoholic fatty liver disease patients.Methods: In this double-blind randomized controlled trial, 44 ultrasonography-proven overweight non-alcoholic fatty liver disease patients were divided into two groups and received two low-energy diets (-500 kcal less than energy requirement individually inc. diet I (Carbohydrate: Fat: Protein: 55:25:20 and diet II (Carbohydrate: Fat: Protein: 40:40:20 for six weeks. Anthropometric and biochemical measures as well as liver enzymes were assessed after 12 hours fasting.Results: After diet I and diet II, weight decreased significantly (%1.82 and %2.45, respectively. Liver enzymes and echogenicity decreased significantly by both diet I and diet II. Mean of triglyceride concentration decreased (%18.09 after diet II (P=0.023, while there was no significant change after diet I. Significant correlations were found between changes in aspartate aminotransferase with triglyceride and LDL-C diet I.Conclusion: Low energy diets can decrease liver enzymes regardless of their composition, while diet II seems to be more effective than diet I in reduction of weight and triglyceride level.
Elliott, Simon P; Fais, Paolo
GHB has been implicated in many cases of suspected surreptitious administration with the purpose of increasing victim vulnerability to sexual assault. Low amounts of endogenous (or naturally occurring) GHB, which do not reach pharmacologically active levels, have been detected in alcoholic and non-alcoholic beverages. Due to the continued requirement to obtain data on the presence of endogenous GHB in various beverage types, GHB concentrations were measured in a series of non-alcoholic beverages. Tonic water and lemon flavoured tonic water beverages were analysed at 0, 24 and 96h after the bottle opening using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) on an Agilent 6890/7000C Triple Quadrupole. GHB was detected in all beverages at very low amounts ranging from 89 to 145ng/mL (0.089-0.145mg/L) and did not demonstrate a general trend of variation for concentration along the tested time span (96h). The presented data provide additional evidence for the endogenous nature of GHB in non-alcoholic beverages at very low concentrations, which are many orders of magnitude lower than those described to produce any pharmacological effect on the subject. However, when considering a case of alleged drug-facilitated sexual assault, a low level of GHB detected in a drink may be related both to a surreptitiously GHB administration with subsequent dilution for concealment or to the presence of endogenous GHB. On this basis, a comprehensive analysis of all the available information, including circumstantial data demonstrating possible attempts to conceal GHB administration and an assessment of levels of endogenous GHB in the suspected beverage type, is of the utmost importance for a proper interpretation of the toxicological results. Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available INTRODUCTION: The hop (Humulus lupulus L., a component of beer, is a sedative plant whose pharmacological activity is principally due to its bitter resins, in particular to the α-acid degradation product 2-methyl-3-buten-2-ol. The mechanism of action of hop resin consists of raising the levels of the neurotransmitter γ-aminobutyric acid (GABA, an inhibitory neurotransmitter acting in the central nervous system (CNS. OBJECTIVES: To analyze the sedative effect of hops as a component of non-alcoholic beer on the sleep/wake rhythm in a work-stressed population. METHODS: The experiment was conducted with healthy female nurses (n = 17 working rotating and/or night shifts. Overnight sleep and chronobiological parameters were assessed by actigraphy (Actiwatch® after moderate ingestion of non-alcoholic beer containing hops (333 ml with 0.0% alcohol with supper for 14 days (treatment. Data were obtained in comparison with her own control group without consumption of beer during supper. RESULTS: Actigraphy results demonstrated improvement of night sleep quality as regards the most important parameters: Sleep Latency diminished (p≤0.05 in the Treatment group (12.01±1.19 min when compared to the Control group (20.50±4.21 min, as also did Total Activity (p≤0.05; Treatment group = 5284.78±836.99 activity pulses vs Control = 7258.78±898.89 activity pulses. In addition, anxiety as indexed by the State-Trait Anxiety Inventory (STAI decreased in the Treatment group (State Anxiety 18.09±3.8 vs Control 20.69±2.14. CONCLUSION: The moderate consumption of non-alcoholic beer will favour night-time rest, due in particular to its hop components, in addition to its other confirmed benefits for the organism.
Franco, Lourdes; Sánchez, Cristina; Bravo, Rafael; Rodríguez, Ana B.; Barriga, Carmen; Romero, Eulalia; Cubero, Javier
Introduction The hop (Humulus lupulus L.), a component of beer, is a sedative plant whose pharmacological activity is principally due to its bitter resins, in particular to the α-acid degradation product 2-methyl-3-buten-2-ol. The mechanism of action of hop resin consists of raising the levels of the neurotransmitter γ-aminobutyric acid (GABA), an inhibitory neurotransmitter acting in the central nervous system (CNS). Objectives To analyze the sedative effect of hops as a component of non-alcoholic beer on the sleep/wake rhythm in a work-stressed population. Methods The experiment was conducted with healthy female nurses (n = 17) working rotating and/or night shifts. Overnight sleep and chronobiological parameters were assessed by actigraphy (Actiwatch®) after moderate ingestion of non-alcoholic beer containing hops (333 ml with 0,0% alcohol) with supper for 14 days (treatment). Data were obtained in comparison with her own control group without consumption of beer during supper. Results Actigraphy results demonstrated improvement of night sleep quality as regards the most important parameters: Sleep Latency diminished (p≤0.05) in the Treatment group (12.01±1.19 min) when compared to the Control group (20.50±4.21 min), as also did Total Activity (p≤0.05; Treatment group = 5284.78±836.99 activity pulses vs Control = 7258.78±898.89 activity pulses). In addition, anxiety as indexed by the State-Trait Anxiety Inventory (STAI) decreased in the Treatment group (State Anxiety 18.09±3.8 vs Control 20.69±2.14). Conclusion The moderate consumption of non-alcoholic beer will favour night-time rest, due in particular to its hop components, in addition to its other confirmed benefits for the organism. PMID:22815680
Massart, Julie; Begriche, Karima; Moreau, Caroline; Fromenty, Bernard
Background Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. Aim The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity. For this purpose, we performed a data-mining analysis using different queries including drug-induced liver injury (or DILI), drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or NAFLD), steatosis and obesity. The main data from the collected articles are reported in this review and when available, some pathophysiological hypotheses are put forward. Relevance for patients Drugs that could pose a potential risk in obese patients include compounds belonging to different pharmacological classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine and tamoxifen. For some of these drugs, experimental investigations in obese rodents confirmed the clinical observations and unveiled different pathophysiological mechanisms which could explain why these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifylline, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver background or induce NAFLD worsening
Golabi, Pegah; Locklear, Cameron T; Austin, Patrick; Afdhal, Sophie; Byrns, Melinda; Gerber, Lynn; Younossi, Zobair M
To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients. Ovid-Medline, PubMed, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "non-alcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy (H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. Eight studies met selection criteria (6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared the two interventions. The beneficial effects of exercise on intrahepatic triglyceride (IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents. Prescribed exercise in subjects with NAFLD reduces IHTG independent of
Lin, Connie [College of Medicine, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Rountree, Carl B. [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Pediatrics, Bon Secour St. Mary' s Hospital, 5801 Bremo Rd, Richmond, VA 23226 (United States); Methratta, Sosamma [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Radiology, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); LaRusso, Salvatore [Department of Radiology, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Kunselman, Allen R. [Department of Public Health Sciences, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Spanier, Adam J., E-mail: firstname.lastname@example.org [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Public Health Sciences, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States)
Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. Aims: To investigate the association of secondhand tobacco exposure with NAFLD in children. Methods: We surveyed parents/guardians of 304 children aged 3–12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed the ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. Results: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). Conclusion: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts. - Highlights: • We evaluated the relation of tobacco exposure with nonalcoholic fatty liver disease. • Tobacco smoke exposure was associated with nonalcoholic fatty liver disease. • Tobacco smoke exposure may be an addressable risk factor.
María Serrano Iglesias
Full Text Available The aim of this study was to draw an updated map of the nutrition facts in the different categories of non-alcoholic beverages in the Spanish market based on the information declared on the labels of these products; we expect this first step to justify the need for the coordination and harmonization of food composition tables in Spain so that there will be an updated database available to produce realistic scientific nutrient intake estimates in accordance with the actual market scenario. Materials and Methods: The nutrition facts declared on the labels of non-alcoholic beverages by manufacturers in Spain were compiled and studied. Results: The database included 211 beverages classified in 7 groups with energy/carbohydrate content per 100 mL ranging from 0–55 kcal/0–13 g for soft drinks; 2–60 kcal/0–14.5 g for energy drinks; 24–31 kcal/5.8–7.5 g for sports drinks; 1–32 kcal/0–7.3 g for drinks containing mineral salts in their composition; 14–69 kcal/2.6–17 g for fruit juice, nectar, and grape musts; 43–78 kcal/6.1–14.4 g for vegetable drinks; and 33–88 kcal/3.6–14 g for dairy drinks. Conclusion: The current non-alcoholic beverage market is a dynamic, growing, and highly innovative one, allowing consumers to choose according to their preferences, needs, or level of physical activity at any moment of the day.
Full Text Available Abstract Non-alcoholic fatty liver disease (NAFLD is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD, the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS, genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13 may promote the development of NAFLD.
Full Text Available In recent years, extensive studies have been conducted on the pathogenesis of nonalcoholic fatty liver disease (NAFLD, and the action of mechanism of traditional Chinese medicine (TCM in NAFLD has become a new research topic. TCM has achieved good clinical efficacy in the treatment of NAFLD, with the advantages of specific, flexible, multilevel, and multi-target treatment. This article introduces the role of TCM in improving insulin, regulating lipid metabolism, preventing lipid peroxidation, regulating cytokines, regulating and maintaining the dynamic balance of factors involved in lipid metabolism, and maintaining the balance of intestinal microflora, and analyzes the major problems in TCM research.
Hannah, William N; Harrison, Stephen A
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD is the most common liver disease in developed countries. Weight reduction of 3% to 5% is associated with improved steatosis; reductions of 5% to 7% are necessary for decreased inflammation; with 7% to 10%, individuals may experience NAFLD/NASH remission and regression of fibrosis. No specific dietary intervention has proven beneficial beyond calorie restriction. Physical activity without weight loss seems to decrease hepatic steatosis. Bariatric surgery is associated with decreased cardiovascular risk and improved overall mortality in addition to reduction in hepatic steatosis, inflammation, and fibrosis. Published by Elsevier Inc.
Hassan, Kareem; Bhalla, Varun; Ezz El Regal, Mohammed; A-Kader, H Hesham
Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD. PMID:25232245
Milić, Sandra; Mikolašević, Ivana; Radić, Mladen; Hauser, Goran; Štimac, Davor
Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as a part of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We re...
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the leading cause of chronic liver disease, with prevalence increasing in parallel with the rising incidence in obesity. Believed to be a “multiple-hit” disease, several factors contribute to NAFLD initiation and progression. Of these, the gut microbiome is gaining interest as a significant factor in NAFLD prevalence. In this paper, we provide an in-depth review of the progression of NAFLD, discussing the mechanistic modes of hepatocyte injury and the potential role for manipulation of the gut microbiome as a therapeutic strategy in the prevention and treatment of NAFLD.
Kawakami, Sakura; Han, Kyu-Ho; Nakamura, Yumi; Shimada, Ken-ichiro; Kitano, Tomoko; Aritsuka, Tsutomu; Nagura, Taizo; Ohba, Kiyoshi; Nakamura, Kimihide; Fukushima, Michihiro
The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation, there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HFB) group was significantly (pNASH model mice.
Anna Di Sessa
Full Text Available The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.
Chu, Irma Giovanna Llamosas
Ceramic membranes are a strong prospect as an advanced treatment in the drinking water domain. But their high capital cost and the lack of specific research on their performance still discourage their application in this field. Thus, knowing that fouling is the main drawback experienced in filtration processes, this bench-scale study was aimed to assess the impact of an ozonation pre-treatment on the alleviation of the fouling of UF ceramic membranes. Preozonation and filtration steps were performed under two different pH and ozone doses. Chosen pH values were at the limits of natural surface waters range (6.5 and 8.5) to keep practicability. Raw water from the Thousand Isle's river at Quebec-Canada was used for the tests. The filtration setup involved an unstirred dead-end filtration cell operated at constant flux. Results showed that pre-oxidation by ozone indeed reduced the fouling degree of the membranes according to the dose applied (up to 60 and 85% for membranes 8 and 50 kDa, respectively). Direct NOM oxidation was found responsible for this effect as the presence of molecular ozone was not essential to achieve these results. In the context of this experiment, however, pH showed to be more effective than the ozonation pre-treatment to keep fouling at low levels: 70% lower at pH 6.5 than at pH 8.5 for un-ozonated waters, which was contrary to most of the literature found on the topic (Changwon, 2013; De Angelis & Fidalgo, 2013; Karnik et al., 2005; S. Lee & Kim, 2014). This behaviour results mainly from the operation mode used in the experiment, the electrical repulsions between MON molecules at basic pH that led to the accumulation of material on the feed side of the membranes (concentration polarisation) and ulterior cake formation. In addition, solution pH showed an influence in the definition of fouling mechanisms. At solution pH 6.5, which was precisely the isoelectric point of the membranes (+/-6.5), the blocking fouling mode was frequently detected
Qiu, Ao-Wang; Liu, Qing-Huai; Wang, Jun-Ling
Interleukin (IL)-17A, a proinflammatory cytokine, has been implicated in several autoimmune diseases. However, it is unclear whether IL-17A is involved in diabetic retinopathy (DR), one of the most serious complications of autoimmune diabetes. This study aimed to demonstrate that IL-17A exacerbates DR by affecting retinal Müller cell function. High glucose (HG)-treated rat Müller cell line (rMC-1) was exposed to IL-17A, anti-IL-17A-neutralizing monoclonal antibody (mAb) or/and anti-IL-17 receptor (R)A-neutralizing mAb for 24 h. For in vivo study, DR was induced by intraperitoneal injections of streptozotocin (STZ). DR model mice were treated with anti-IL-17A mAb or anti-IL-17RA mAb in the vitreous cavity. Mice that were prepared for retinal angiography were sacrificed two weeks after intravitreal injection, while the rest were sacrificed two days after intravitreal injection. IL-17A production and IL-17RA expression were increased in both HG-treated rMC-1 and DR retina. HG induced rMC-1 activation and dysfunction, as determined by the increased GFAP, VEGF and glutamate levels as well as the downregulated GS and EAAT1 expression. IL-17A exacerbated the HG-induced rMC-1 functional disorders, whereas either anti-IL-17A mAb or anti-IL-17RA mAb alleviated the HG-induced rMC-1 disorders. Intravitreal injections with anti-IL-17A mAb or anti-IL-17RA mAb in DR model mice reduced Müller cell dysfunction, vascular leukostasis, vascular leakage, tight junction protein downregulation and ganglion cell apoptosis in the retina. IL-17A aggravates DR-like pathology at least partly by impairing retinal Müller cell function. Blocking IL-17A is a potential therapeutic strategy for DR. © 2017 The Author(s)Published by S. Karger AG, Basel.
. Conclusion: The isolated chromone derivatives (1–2 from V. negundo are able to alleviate nociception and inflammation and the findings corroborated that V. negundo may be used as a potential source of antinociceptive and anti-inflammatory candidates. Keywords: chromone derivatives, Vitex negundo, Verbenaceae, antinociceptive, anti-inflammatory
Moses, Robert W.
The capability of modern fighter airplanes to sustain flight at high angles of attack and/or moderate angles of sideslip often results in immersion of part of such an airplane in unsteady, separated, vortical flow emanating from its forebody or wings. The flows from these surfaces become turbulent and separated during flight under these conditions. These flows contain significant levels of energy over a frequency band coincident with that of low-order structural vibration modes of wings, fins, and control surfaces. The unsteady pressures applied to these lifting surfaces as a result of the turbulent flows are commonly denoted buffet loads, and the resulting vibrations of the affected structures are known as buffeting. Prolonged exposure to buffet loads has resulted in fatigue of structures on several airplanes. Damage to airplanes caused by buffeting has led to redesigns of airplane structures and increased support costs for the United States Air Force and Navy as well as the armed forces of other countries. Time spent inspecting, repairing, and replacing structures adversely affects availability of aircraft for missions. A blend of rudder-control and piezoelectric- actuator engineering concepts was selected as a basis for the design of a vertical-tail buffet-load-alleviation system for the F/A-18 airplane. In this system, the rudder actuator is used to control the response of the first tail vibrational mode (bending at a frequency near 15 Hz), while directional patch piezoelectric actuators are used to control the second tail vibrational mode (tip torsion at a frequency near 45 Hz). This blend of two types of actuator utilizes the most effective features of each. An analytical model of the aeroservoelastic behavior of the airplane equipped with this system was validated by good agreement with measured results from a full-scale ground test, flight-test measurement of buffet response, and an in-flight commanded rudder frequency sweep. The overall performance of the
Xu, Jiangping; Khan, Kamran; El Sayed, Tamer S.
with the reported experimental results. We also propose a novel method of redesigning the rim geometry of the workpiece to alleviate the flash-line defects which also shows good agreement with experiments. © 2012 Elsevier Inc. All rights reserved.
Full Text Available ABSTRACTWe studied the effects of seed storage on germination and dormancy alleviation in three species of Fabaceae endemic to campo rupestrein southeastern Brazil. Fresh seeds of Collaea cipoensis, Mimosa maguirei and Mimosa foliolosawere set to germinate and germination of seeds after four, five and 13 years of storage was tested. Seed viability was maintained for all species after the full storage period. Seed storage significantly increased germination percentage and decreased germination time for C. cipoensisand M. foliolosa, suggesting the alleviation of physical dormancy with storage. However, we did not find evidence of dormancy alleviation in M. maguirei since stored seeds showed a decrease in germination in comparison to that of fresh seeds. Our data indicate species-specific storage-mediated dormancy alleviation, which will have important implications for restoration of campo rupestre.
E-Skill Information Acquisition Software: A Key to Poverty Alleviation Or Self Reliance. ... has not helped matters. This project is about developing an e-skill transfer using software. ... Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT
Manning, Robert M.
The work presented here will be a review of a NASA effort to provide a method to transmit and receive RF communications and telemetry through a re-entry plasma thus alleviating the classical RF blackout phenomenon.
Escamilla, M; Kurtycz, A; van der Helm, R
The construction of small water reservoirs has been used in an effort to alleviate poverty in Messeta Purépecha region in Mexico. The programme's rationale can be characterised as incentive-based participation, using both local employment and shared risks concepts. The programme so far has been a relative success. However, in the light of poverty alleviation questions have to be raised about the isolated nature of the programme as well as the role of the incentives used.
Di Lorenzo Chiara
Full Text Available Vine is widely cultivated due to the economic value of wine and other grape derivatives. The grape berry is character- ized by the presence of a wide variety of flavonoids, which have been investigated for their health promoting properties. Several epidemiological studies have shown that a moderate consumption of wine is associated with a J-shaped effect on some risk fac- tors for chronic diseases. On the other hand, the wine market has shown a decreasing trend due to the frequent abuse of alcoholic beverages also by young people, as denounced by WHO. Accordingly, the scientific research in the field of non-alcoholic grape products has been further stimulated. The aim of this paper was a preliminary collection of data on human studies supporting the beneficial properties of unfermented grape products. The most convincing positive effects, observed in humans, consisted in the reduction of risk factors for cardiovascular diseases, such as hypertension and oxidative stress. Other human trials have been published in the area of: immune system, diabetes, cognitive functions, oral health, and cancer. Generally speaking, the findings listed in this review support the use of non-alcoholic grape derivatives, as a source of beneficial compounds for the human diet, even though further studies are necessary.
Joo Ho Lee
Full Text Available Non-alcoholic fatty liver disease (NAFLD is defined as a pathologic accumulation of fat in the form of triglycerides (TG in the liver (steatosis that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis, which is referred to as non-alcoholic steatohepatitis (NASH. Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC. NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications.
Cole, Banumathi K; Feaver, Ryan E; Wamhoff, Brian R; Dash, Ajit
The progressive disease spectrum of non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is a rapidly emerging public health crisis with no approved therapy. The diversity of various therapies under development highlights the lack of consensus around the most effective target, underscoring the need for better translatable preclinical models to study the complex progressive disease and effective therapies. Areas covered: This article reviews published literature of various mouse models of NASH used in preclinical studies, as well as complex organotypic in vitro and ex vivo liver models being developed. It discusses translational challenges associated with both kinds of models, and describes some of the studies that validate their application in NAFLD. Expert opinion: Animal models offer advantages of understanding drug distribution and effects in a whole body context, but are limited by important species differences. Human organotypic in vitro and ex vivo models with physiological relevance and translatability need to be used in a tiered manner with simpler screens. Leveraging newer technologies, like metabolomics, proteomics, and transcriptomics, and the future development of validated disease biomarkers will allow us to fully utilize the value of these models to understand disease and evaluate novel drugs in isolation or combination.
Gallego-Durán, Rocío; Romero-Gómez, Manuel
Non-alcoholic fatty liver disease (NAFLD) is an emerging health concern in both developed and non-developed world, encompassing from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Incidence and prevalence of this disease are increasing due to the socioeconomic transition and change to harmful diet. Currently, gold standard method in NAFLD diagnosis is liver biopsy, despite complications and lack of accuracy due to sampling error. Further, pathogenesis of NAFLD is not fully understood, but is well-known that obesity, diabetes and metabolic derangements played a major role in disease development and progression. Besides, gut microbioma and host genetic and epigenetic background could explain considerable interindividual variability. Knowledge that epigenetics, heritable events not caused by changes in DNA sequence, contribute to development of diseases has been a revolution in the last few years. Recently, evidences are accumulating revealing the important role of epigenetics in NAFLD pathogenesis and in NASH genesis. Histone modifications, changes in DNA methylation and aberrant profiles or microRNAs could boost development of NAFLD and transition into clinical relevant status. PNPLA3 genotype GG has been associated with a more progressive disease and epigenetics could modulate this effect. The impact of epigenetic on NAFLD progression could deserve further applications on therapeutic targets together with future non-invasive methods useful for the diagnosis and staging of NAFLD.
Hartung P. A. D.
Full Text Available The objective of this present article is to understand the regulation of food and non-alcoholic beverage advertising aimed at children in Brazil. It is argued that this discussion must be contextualized within the broader debate on advertising that targets children of less than 12 years of age, of any product, service or brand, given that the advertising of food and drinks to children is a species of the broader commercial practice of advertising, which is considered abusive and therefore illegal under Brazilian rules and by the recommendations of interna-tional organizations. Advertising directly to children utilizes their hyper-vulnerability and their unfinished development to persuade them to consume, violating their rights guaran-teed by law, such as the right to respect comprising physical, mental and moral inviolability. Specifically, advertising of food and non-alcoholic beverages with low nutritional value to children, in addition to leveraging children’s vulnerability, directly impacts increasing rates of childhood and weight, therefore becoming an important public health issue to be regulated. In Brazil, the regulation of this commercial activity takes place within the broader context of restricting marketing communication directed at children under 12 years of age,, which has been discussed extensively at various state levels, including through lawsuits that generated a historical precedent in the Brazilian Superior Court of Justice, which considered ins his decision this practice to be abusive and, therefore, illegal.
Full Text Available Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.
Chen, Yi; Xu, Chengfu; Yan, Tianlian; Yu, Chaohui; Li, Youming
The aim of this study was to evaluate the effect of ω-3 fatty acids on nonalcoholic fatty liver disease concerning hepatocyte lipid accumulation as well as apoptosis induced by free fatty acids (FFAs) and to explore the underlying mechanism involving autophagy. Hepatocytes were incubated with a mixture of free fatty acids (FFAs) to mimic in vitro lipotoxicity in the pathogenesis of nonalcoholic fatty liver disease, presented by lipid accumulation and cellular apoptosis. Chemical inhibitor or inducer of autophagy and genetic deficit cells, as well as ω-3 fatty acids were used as intervention. The autophagic role of ω-3 fatty acids was investigated using Western blot and immunofluorescence. The underlying mechanism of ω-3 fatty acids involving autophagy was preliminarily explored by quantitative real-time polymerase chain reaction and Western blot. FFAs induce lipid accumulation and apoptosis in hepatocytes. Inhibition or genetic defect of autophagy increases lipid accumulation induced by FFA, whereas induction acts inversely. ω-3 Fatty acids reduced lipid accumulation and inhibited apoptosis induced by FFA. ω-3 Fatty acids induced autophagy by downregulating stearoyl-CoA desaturase 1 expression in hepatocytes. ω-3 Fatty acids exert protective effects on hepatocytes against lipotoxicity through induction of autophagy, as demonstrated by inhibition of lipid accumulation and apoptosis. Copyright © 2015 Elsevier Inc. All rights reserved.
Machado, Mariana Verdelho; Cortez-Pinto, Helena
Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. PMID:25278691
Cho, Jin Young; Ye, Soo Young
There is a need for aggressive diagnosis and treatment in middle-aged and high-risk individuals who are more likely to progress from nonalcoholic fatty liver to hepatitis. In this study, nonalcoholic fatty liver was divided into severe, moderate, and severe, and classified by quantitative method using computer analysis of GLCM algorithm. The purpose of this study was to evaluate the characteristics of ultrasound images in the local fat avoidance region. Normal, mild, moderate, severe fatty liver, and focal fat sparing area, 80 cases, respectively. Among the parameters of the GLCM algorithm, the values of the Autocorrelation, Square of the deviation, Sum of averages and Sum of variances with high recognition rate of the liver ultrasound image were calculated. The average recognition rate of the GLCM algorithm was 97.5%. The result of local fat avoidance image analysis showed the most similar value to the normal parenchyma. Ultrasonography can be easily accessed by primary screening, but there may be differences in the accuracy of the test method or the correspondence of results depending on proficiency. GLCM algorithm was applied to quantitatively classify the degree of fatty liver. Local fat avoidance region was similar to normal parenchyma, so it could be predicted to be homogeneous liver parenchyma without fat deposition. We believe that GLCM computer image analysis will provide important information for differentiating not only fatty liver but also other lesions
Fallo, F; Dalla Pozza, A; Sonino, N; Lupia, M; Tona, F; Federspil, G; Ermani, M; Catena, C; Soardo, G; Di Piazza, L; Bernardi, S; Bertolotto, M; Pinamonti, B; Fabris, B; Sechi, L A
Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography. The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P 220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis. Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.
Maria Catalina Hernandez-Rodas
Full Text Available Non-alcoholic fatty liver disease (NAFLD is the main cause of liver disease worldwide. NAFLD is linked to circumstances such as type 2 diabetes, insulin resistance, obesity, hyperlipidemia, and hypertension. Since the obesity figures and related comorbidities are increasing, NAFLD has turned into a liver problem that has become progressively more common. Currently, there is no effective drug therapy for NAFLD; therefore, interventions in lifestyles remain the first line of treatment. Bearing in mind that adherence rates to this type of treatment are poor, great efforts are currently focused on finding novel therapeutic agents for the prevention in the development of hepatic steatosis and its progression to nonalcoholic steatohepatitis and cirrhosis. This review presents a compilation of the scientific evidence found in the last years showing the results of interventions in lifestyle, diet, and behavioral therapies and research results in human, animal and cell models. Possible therapeutic agents ranging from supplementation with vitamins, amino acids, prebiotics, probiotics, symbiotics, polyunsaturated fatty acids and polyphenols to interventions with medicinal plants are analyzed.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is a chronic liver condition that can progress to nonalcoholic steatohepatitis, cirrhosis and cancer. It is considered an emerging health problem due to malnourishment or a high-fat diet (HFD intake, which is observed worldwide. It is well known that the hepatocytes’ apoptosis phenomenon is one of the most important features of NAFLD. Thus, this review focuses on revealing, through a proteomics approach, the complex network of protein interactions that promote fibrosis, liver cell stress, and apoptosis. According to different types of in vitro and murine models, it has been found that oxidative/nitrative protein stress leads to mitochondrial dysfunction, which plays a major role in stimulating NAFLD damage. Human studies have revealed the importance of novel biomarkers, such as retinol-binding protein 4, lumican, transgelin 2 and hemoglobin, which have a significant role in the disease. The post-genome era has brought proteomics technology, which allows the determination of molecular pathogenesis in NAFLD. This has led to the search for biomarkers which improve early diagnosis and optimal treatment and which may effectively prevent fatal consequences such as cirrhosis or cancer.
Liu, Feng; Zhao, Jing-Min; Rao, Hui-Ying; Yu, Wei-Miao; Zhang, Wei; Theise, Neil D; Wee, Aileen; Wei, Lai
Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: email@example.com
Machado, Mariana Verdelho; Michelotti, Gregory Alexander; Xie, Guanhua; de Almeida, Thiago Pereira; Boursier, Jerome; Bohnic, Brittany; Guy, Cynthia D.; Diehl, Anna Mae
Background and aims Non-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD) diet and Western diet. Methods Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose) for 16 weeks. Liver pathology and metabolic profile were compared. Results The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation) was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation. Conclusion Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH. PMID:26017539
Laron, Zvi; Ginsberg, Shira; Webb, Muriel
There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.
Chen, Shaohua; Teoh, Narci C; Chitturi, Shiv; Farrell, Geoffrey C
Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non-alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti-inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so-far limited data supporting such effects will be discussed, and the need for further study is highlighted. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Franco, L; Bravo, R; Galán, C; Rodríguez, A B; Barriga, C; Cubero, Javier
Sleep deprivation affects the homeostasis of the physiological functions in the human organism. Beer is the only beverage that contains hops, a plant which has a sedative effect. Our objective is to determine the improvement of subjective sleep quality using the Pittsburgh Sleep Quality Index (PSQI). The sample was conducted among a population of 30 university students. The study took place during a period of 3 weeks, the first 7 days were used for the Control, and during the following 14 days the students ingested beer (were asked to drink non-alcoholic beer) while having dinner. The results revealed that Subjective Sleep Quality improved in the case of those students who drank one beer during dinner compared to the Control, this is corroborated by the fact that Sleep Latency decreased (p < 0.05) compared to their Control. The overall rating Global Score of Quality of Sleep also improved significantly (p < 0.05). These results confirm that the consumption of non-alcoholic beer at dinner time helps to improve the quality of sleep at night.
Bhanji, Rahima A; Narayanan, Praveena; Allen, Alina M; Malhi, Harmeet; Watt, Kymberly D
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Up to one third of individuals with NAFLD will develop nonalcoholic steatohepatitis (NASH), which is associated with progression to cirrhosis and is rapidly becoming the leading indication for liver transplantation. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass, strength, and function. It is observed in up to 60% of patients with end-stage liver disease and portends a poor prognosis. Recent studies have shown that sarcopenia is a novel risk factor for developing NAFLD. Pathophysiological mechanisms relating sarcopenia and NASH may include insulin resistance (IR) and increased inflammation. IR leads to accumulation of triglycerides in both muscle tissue and the liver. It also exacerbates proteolysis and leads to muscle depletion. Chronic inflammation leads to liver injury and progression of fibrosis. The inflammatory milieu also stimulates protein catabolism. Viewing skeletal muscle as an endocrine organ that secretes various salutary myokines may help us understand its role in the development of steatosis. A better understanding of the pathophysiology will aid in developing physical and pharmacological therapeutic interventions. In this review, we will explore the complex inter-relationships between sarcopenia and NASH. We will discuss the impact of sarcopenia in patients with NASH and therapeutic options for the management of sarcopenia. (Hepatology 2017;66:2055-2065). © 2017 by the American Association for the Study of Liver Diseases.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is now the most common liver disease in the world. NAFLD can progress to nonalcoholic steatohepatitis (NASH, cirrhosis and eventually hepatocellular carcinoma. Acquired hepatic iron overload is seen in a number of patients with NAFLD; however, its significance in the pathology of NAFLD is still debated. Here, we investigated the role of dietary iron supplementation in experimental steatohepatitis in rats. Rats were fed a control, high-fat (HF, high-fat high-iron (HFHI and high-iron (HI diet for 30 weeks. Blood biochemical, histopathological and gut microbiota analyses were performed. Rats in HF and HFHI groups showed an ALT-dominant elevation of serum transaminases, hepatic steatosis, hepatic inflammation, and upregulation of proinflammatory cytokines. The number of large inflammatory foci, corresponding to lobular inflammation in NASH patients, was significantly higher in HFHI than in HF group; within the lesion, macrophages with intense iron staining were observed. Hepatic expression of TNFα was higher in HFHI than that in HF group. There was no significant change in hepatic oxidative stress, gut microbiota or serum endotoxin levels between HF and HFHI groups. These results suggested that dietary iron supplementation enhances experimental steatohepatitis induced by long-term high-fat diet feeding in rats. Iron-laden macrophages can play an important role in the enhancement of hepatic inflammation.
Liu, Yan; Chen, Hongen; Wang, Jingjing; Zhou, Wenjing; Sun, Ruifang; Xia, Min
Retinoic acid (RA), an active metabolite of vitamin A (retinol), has been implicated in the regulation of lipid metabolism and hepatic steatosis in animal models. However, the relation between RA and liver histology in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is unknown. This study aimed at examining the association of RA with NAFLD and NASH in Chinese subjects. Serum RA concentration was determined by ELISA in 41 control subjects, 45 patients with NAFLD, and 38 patients with NASH. The associations of RA with adiposity, serum glucose, lipid profiles, and markers of liver damage were studied. Moreover, both mRNA and protein levels of retinoic X receptor α (RXRα) in the liver were analyzed in subjects with different degrees of hepatic steatosis. Serum RA concentrations in patients with NAFLD (1.42 ± 0.47 ng/mL) and NASH (1.14 ± 0.26 ng/mL) were significantly lower than those in control subjects (2.70 ± 0.52 ng/mL) (P hepatic steatosis. Both serum RA concentrations and RXRα mRNA levels were inversely correlated with intrahepatic triglyceride content (r = -0.700, P hepatic lipid metabolism and insulin resistance. This trial was registered at clinicaltrials.gov as NCT01940263. © 2015 American Society for Nutrition.
Kajor, Maciej; Kukla, Michał; Waluga, Marek; Liszka, Łukasz; Dyaczyński, Michał; Kowalski, Grzegorz; Żądło, Dominika; Berdowska, Agnieszka; Chapuła, Mateusz; Kostrząb-Zdebel, Anna; Bułdak, Rafał J; Sawczyn, Tomasz; Hartleb, Marek
The aim of this study was to investigate hepatic chemerin mRNA, serum chemerin concentration, and immunohistochemical staining for chemerin and and chemokine receptor-like 1 (CMKLR1) in hepatic tissue in 56 morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to search for a relationship with metabolic and histopathological features. Chemerin mRNA was assessed by quantitative real-time PCR, chemerin, and CMKLR1 immunohistochemical expression with specific antibodies, while serum chemerin concentration was assessed with commercially available enzyme-linked immunosorbent assays. Serum chemerin concentration reached 874.1 ±234.6 ng/ml. There was no difference in serum chemerin levels between patients with BMI steatosis, and definite nonalcoholic steatohepatitis (NASH). Liver chemerin mRNA was observed in all included patients and was markedly, but insignificantly, higher in those with BMI ≥ 40 kg/m2, hepatocyte ballooning, greater extent of steatosis, and definite NASH. Hepatic chemerin mRNA might be a predictor of hepatic steatosis, hepatocyte ballooning, and NAFLD activity score (NAS) but seemed not to be a primary driver regulating liver necroinflammatory activity and fibrosis. The lack of association between serum chemerin and hepatic chemerin mRNA may suggest that adipose tissue but not the liver is the main source of chemerin in morbidly obese women.
Tang, An; Tan, Justin; Sun, Mark; Hamilton, Gavin; Bydder, Mark; Wolfson, Tanya; Gamst, Anthony C; Middleton, Michael; Brunt, Elizabeth M; Loomba, Rohit; Lavine, Joel E; Schwimmer, Jeffrey B; Sirlin, Claude B
To evaluate the diagnostic performance of magnetic resonance (MR) imaging-estimated proton density fat fraction (PDFF) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) by using centrally scored histopathologic validation as the reference standard. This prospectively designed, cross-sectional, internal review board-approved, HIPAA-compliant study was conducted in 77 patients who had NAFLD and liver biopsy. MR imaging-PDFF was estimated from magnitude-based low flip angle multiecho gradient-recalled echo images after T2* correction and multifrequency fat modeling. Histopathologic scoring was obtained by consensus of the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network Pathology Committee. Spearman correlation, additivity and variance stabilization for regression for exploring the effect of a number of potential confounders, and receiver operating characteristic analyses were performed. Liver MR imaging-PDFF was systematically higher, with higher histologic steatosis grade (P steatosis grade (ρ = 0.69, P steatosis grade 0 (n = 5) from those with grade 1 or higher (n = 72), 0.825 (95% confidence interval: 0.734, 0.915) to distinguish those with grade 1 or lower (n = 31) from those with grade 2 or higher (n = 46), and 0.893 (95% confidence interval: 0.809, 0.977) to distinguish those with grade 2 or lower (n = 58) from those with grade 3 (n = 19). MR imaging-PDFF showed promise for assessment of hepatic steatosis grade in patients with NAFLD. For validation, further studies with larger sample sizes are needed. © RSNA, 2013.
Hsu, Christine C; Ness, Erik; Kowdley, Kris V
Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches to Stop Hypertension diet, a sodium-restricted diet, has been associated with less prevalence of NAFLD and has been shown to improve NAFLD. In addition, the Mediterranean diet has been promising in improving hepatic steatosis, and a larger randomized controlled trial is currently enrolling subjects. For those who are unable to pursue weight loss through dietary approaches, bariatric surgery has been shown to improve hepatic steatosis and steatohepatitis. This method has been variable in improving hepatic fibrosis. In conclusion, weight loss is crucial to the improvement of NAFLD and NASH, and patients should attempt various diets in an attempt to achieve weight loss. © 2017 American Society for Nutrition.
Hsu, Christine C; Ness, Erik; Kowdley, Kris V
Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5–10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches to Stop Hypertension diet, a sodium-restricted diet, has been associated with less prevalence of NAFLD and has been shown to improve NAFLD. In addition, the Mediterranean diet has been promising in improving hepatic steatosis, and a larger randomized controlled trial is currently enrolling subjects. For those who are unable to pursue weight loss through dietary approaches, bariatric surgery has been shown to improve hepatic steatosis and steatohepatitis. This method has been variable in improving hepatic fibrosis. In conclusion, weight loss is crucial to the improvement of NAFLD and NASH, and patients should attempt various diets in an attempt to achieve weight loss. PMID:28298270
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of metabolic syndrome and a serious health burden worldwide which increases risk of cirrhosis, type 2 diabetes mellitus (T2DM, and cardiovascular complications. Current epidemics of obesity, unhealthy dietary patterns, and sedentary lifestyles, all contribute to the high prevalence of NAFLD. Dietary patterns and nutrients are important contributors to the development, progression, and treatment of NAFLD. A healthy diet is beneficial for all NAFLD patients beyond weight reduction. Generally, hypercaloric diets, especially rich in trans/saturated fat and cholesterol, high consumption of red and processed meat, and fructose-sweetened beverages seem to increase the risk of progression toward nonalcoholic steatohepatitis (NASH, whereas reducing caloric intake and high-glycemic index (GI foods, increasing consumption of monounsaturated fatty acids, omega-3 fatty acids, fibers, and specific protein sources such as fish and poultry have preventive and therapeutic effects. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation. In this review, the evidence linking macronutrients to NAFLD are discussed.
Full Text Available To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ, phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK, phosphorylated acetyl-CoA carboxylase (p-ACC, malonyl-CoA decarboxylase (MCD, medium chain acyl-CoA dehydrogenase (MCAD, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α, and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1, fatty acid synthase (FAS, and tumor necrosis factor-alpha (TNF-α. Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660. Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway.
Ip, Blanche C.; Wang, Xiang-Dong
Increased prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the consequences of the current obesity epidemic. NAFLD is a major form of chronic liver disease that is highly prevalent in obese and overweight adults and children. Nonalcoholic steatohepatitis (NASH) is the severe form of NAFLD, and uncontrolled inflammation as displayed in NASH has been identified as one of the key events in enhancing hepatic carcinogenesis. Lycopene is a non-provitamin A carotenoid and the pigment principally responsible for the characteristic deep-red color of ripe tomato and tomato products, as well as some fruits and vegetables. Lycopene’s innate antioxidant and anti-inflammatory properties have generated research interests on its capacity to protect against human diseases that are associated with oxidative stress and inflammation. In addition, differential mechanisms of lycopene metabolism including endogenous cleavage by carotenoid cleavage oxygenases (BCOs), generate lycopene metabolites that may also have significant impact on human disease development. However, it remains to be elucidated as to whether lycopene or its metabolites apolycopenoids have protective effects against obesity-related complications including inflammation and tumorigenesis. This article summarizes the in vivo experiments that elucidated molecular mechanisms associated with obesity-related hepatic inflammation and carcinogenesis. This review also provides an overview of lycopene metabolism, and the molecular pathways involved in the potential beneficial properties of lycopene and apolycopenoids. More research is clearly needed to fully unravel the importance of BCOs in tomato carotenoid metabolism and the consequence on human health and diseases. PMID:24379011
Mariana Verdelho Machado
Full Text Available Non-alcoholic steatohepatitis (NASH, the potentially progressive form of nonalcoholic fatty liver disease (NAFLD, is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD diet and Western diet.Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose for 16 weeks. Liver pathology and metabolic profile were compared.The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation.Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH.
Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the most common causes of chronic liver disease in adults and children worldwide. NAFLD has become a severe health issue and it can progress towards a more severe form of the disease, the non-alcoholic steatohepatitis (NASH. A combination of environmental factors, host genetics, and gut microbiota leads to excessive accumulation of lipids in the liver (steatosis, which may result in lipotoxicity and trigger hepatocyte cell death, liver inflammation, fibrosis, and pathological angiogenesis. NASH can further progress towards liver cirrhosis and cancer. Over the last few years, cell-derived extracellular vesicles (EVs have been identified as effective cell-to-cell messengers that transfer several bioactive molecules in target cells, modulating the pathogenesis and progression of NASH. In this review, we focused on recently highlighted aspects of molecular pathogenesis of NASH, mediated by EVs via their bioactive components. The studies included in this review summarize the state of art regarding the role of EVs during the progression of NASH and bring novel insight about the potential use of EVs for diagnosis and therapeutic strategies for patients with this disease.
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the commonest liver condition in the world, accounting for 20-30% of the adult population, and encompasses a spectrum of liver disorders characterized by fat accumulation within the liver, associated or not with varying degrees of hepatic inflammation and liver fibrosis through to cirrhosis. The prevalence of NAFLD increases significantly in the presence of obesity (60-80% and type 2 diabetes (60%. NAFLD is associated with metabolic disorders (type 2 diabetes, obesity and hyperlipidemia grouped together as the metabolic syndrome (MetS. It is now regarded as the hepatic manifestation of this syndrome and is closely linked to insulin resistance (IR.The presence of NAFLD predicts the development of type 2 diabetes independent of established risk factors. NAFLD patients should therefore be screened for diabetes, including by the Oral Glucose Tolerance Test (OGTT if there any abnormalities of fasting blood glucose (FBG and given appropriate lifestyle advice. Early diagnosis with the institution of lifestyle measures could help prevent or retard the onset of these metabolic disorders. Type 2 diabetes causes more severe non-alcoholic steatohepatitis (NASH, and patients with diabetes have an increased risk for cirrhosis and the development of hepatocellular carcinoma (HCC
Full Text Available Currently nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH are medical problems associated with the increasing prevalence of diabetes mellitus, obesity, hypertension and hypertriglyceridemia, usually designated as the metabolic syndrome associated with insulin resistance. One study demonstrated an increase in NAFLD prevalence of around 17-33% and in NASH prevalence of 5.7-16.5%. NAFLD comprises a range of mild to severe conditions, from simple steatosis to steatohepatitis, hepatic fibrosis and cirrhosis. The diagnosis of hepatic fibrosis is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. Ultrasonography (USG is a simple method for detecting fatty infiltrates in the liver. USG has a sensitivity of 82-89% and a specificity of 93%, but cannot differentiate between hepatic steatosis and fibrosis. The gold standard for evaluation of hepatic fibrosis is liver biopsy, which however is a painful and invasive procedure. Currently determination of serum type IV collagen has been suggested as an alternative to liver biopsy among the non-invasive methods for evaluation of hepatic fibrosis, as its serum concentration is closely correlated with advanced hepatic fibrosis in NASH. Type IV collagen is one of the components of basement membrane and its serum concentration is indicative of degradation of the extracellular matrix.
Full Text Available Currently nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH are medical problems associated with the increasing prevalence of diabetes mellitus, obesity, hypertension and hypertriglyceridemia, usually designated as the metabolic syndrome associated with insulin resistance. One study demonstrated an increase in NAFLD prevalence of around 17-33% and in NASH prevalence of 5.7-16.5%. NAFLD comprises a range of mild to severe conditions, from simple steatosis to steatohepatitis, hepatic fibrosis and cirrhosis. The diagnosis of hepatic fibrosis is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. Ultrasonography (USG is a simple method for detecting fatty infiltrates in the liver. USG has a sensitivity of 82-89% and a specificity of 93%, but cannot differentiate between hepatic steatosis and fibrosis. The gold standard for evaluation of hepatic fibrosis is liver biopsy, which however is a painful and invasive procedure. Currently determination of serum type IV collagen has been suggested as an alternative to liver biopsy among the non-invasive methods for evaluation of hepatic fibrosis, as its serum concentration is closely correlated with advanced hepatic fibrosis in NASH. Type IV collagen is one of the components of basement membrane and its serum concentration is indicative of degradation of the extracellular matrix.
Kelley, Carly E; Brown, Ann J; Diehl, Anna Mae; Setji, Tracy L
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases. PMID:25339805
Hendy, Olfat M; Elsabaawy, Maha M; Aref, Mona M; Khalaf, Fatma M; Oda, Abdel Moaty A; El Shazly, Helmy M
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested. Liver function tests, serum glucose, fasting insulin, C peptide, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR), IL-6, and circulating zonulin were performed to all subjects. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), triglycerides, HDL-c, fasting insulin, C peptide, HOMA-IR, IL-6, and serum zonulin were higher in NAFLD group than in controls (p Zonulin was positively correlated with body mass index (BMI), ALT, triglycerides, fasting insulin, HOMA-IR, liver histopathology, and serum IL-6 (p zonulin was found to be of diagnostic value of NASH occurrence with 100% sensitivity and specificity (AUR = 1.000, p-value = zonulin levels in NAFLD patients with steep rise in NASH group denotes a possible role in pathogenesis of NAFLD occurrence and progression. This could open a new avenue of implicating zonulin antagonists as targeted therapies in NAFLD prevention. © 2017 APMIS. Published by John Wiley & Sons Ltd.
Nonalcoholic fatty liver disease (NAFLD) represents one of the most common liver diseases. It is strongly associated with obesity and insulin resistance and is thought to be a part of the metabolic syndrome. It can progress from simple fatty liver to steatohepatitis, cirrhosis and liver failure. Adipocytokines, synthesized in adipose tissue, are involved in the pathophysiology of many acute and chronic liver diseases. The aim of this study was to investigate the role of Tumor Necrosis Factor-alpha (TNF-alpha) and resistin in the pathogenesis of NAFLD and their correlation to the severity of the disease. Serum concentration of TNF-alpha and resistin were measured in 20 patients with NAFLD and 20 healthy controls with ELISA method. The results of this study revealed that serum levels of both adipokines were significantly elevated in NAFLD patients than controls (P<0.01). Moreover, they were significantly higher in patients with nonalcoholic steatohepatitis than in patients with simple fatty liver. There was a significant positive correlation between TNF-alpha, resistin and each of AST, ALT and HOMA. Similarly, the results showed a significant positive correlation between the two studied adipokines, TNF-alpha and resistin (P<0.001). We conclude that TNF-alpha and resistin have a role in the pathogenesis of NAFLD and they may be promising markers for the progressin to steatohepatitis and inhibition of their activities by drugs may be a new approach for the treatment of NAFLD
Cho, Jin Young [Dept. of Radiological Science, Graduate School of Catholic University of Pusan, Busan (Korea, Republic of); Ye, Soo Young [Dept. of Radiological Science, Catholic University of Pusan, Busan (Korea, Republic of)
There is a need for aggressive diagnosis and treatment in middle-aged and high-risk individuals who are more likely to progress from nonalcoholic fatty liver to hepatitis. In this study, nonalcoholic fatty liver was divided into severe, moderate, and severe, and classified by quantitative method using computer analysis of GLCM algorithm. The purpose of this study was to evaluate the characteristics of ultrasound images in the local fat avoidance region. Normal, mild, moderate, severe fatty liver, and focal fat sparing area, 80 cases, respectively. Among the parameters of the GLCM algorithm, the values of the Autocorrelation, Square of the deviation, Sum of averages and Sum of variances with high recognition rate of the liver ultrasound image were calculated. The average recognition rate of the GLCM algorithm was 97.5%. The result of local fat avoidance image analysis showed the most similar value to the normal parenchyma. Ultrasonography can be easily accessed by primary screening, but there may be differences in the accuracy of the test method or the correspondence of results depending on proficiency. GLCM algorithm was applied to quantitatively classify the degree of fatty liver. Local fat avoidance region was similar to normal parenchyma, so it could be predicted to be homogeneous liver parenchyma without fat deposition. We believe that GLCM computer image analysis will provide important information for differentiating not only fatty liver but also other lesions.
Ni, Yinhua; Zhuge, Fen; Nagashimada, Mayumi; Ota, Tsuguhito
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.
Full Text Available The aim of this study is to develop a new technology for making traditional Lithuanian non-alcoholic beverage kvass from fermented cereals by extending the spectrum of raw materials (extruded rye and applying new biotechnological resources (xylanolytic enzymes and lactic acid bacteria (LAB to improve its functional properties. Arabinoxylans in extruded rye were very efficiently hydrolysed into oligosaccharides by xylanolytic complex Ceremix Plus MG. Using Ceremix Plus MG and LAB fermentation, the yield of arabinoxylooligosaccharides and xylooligosaccharides in beverage was increased to 300 and 1100 mg/L, respectively. Beverages fermented by LAB had lower pH values and ethanol volume fraction compared to the yeast-fermented beverage. The acceptability of the beverage fermented by Lactobacillus sakei was higher than of Pediococcus pentosaceus- or yeast-fermented beverages and similar to the acceptability of commercial kvass made from malt extract. The results showed that extruded rye, xylanolytic enzymes and LAB can be used for production of novel and safe high-value non-alcoholic beverages.
Orešic, Matej; Hyötyläinen, Tuulia; Kotronen, Anna
We examined whether analysis of lipids by ultra-performance liquid chromatography (UPLC) coupled to MS allows the development of a laboratory test for non-alcoholic fatty-liver disease (NAFLD), and how a lipid-profile biomarker compares with the prediction of NAFLD and liver-fat content based...
Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa
Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591
Poulsen, Marianne K; Nellemann, Birgitte; Bibby, Bo Martin
The present study assess long-term effects of high-dose Resveratrol (RSV) on basal and insulin-mediated very low-desity lipoprotein triglyceride (VLDL-TG), palmitate and glucose kinetics, and liver fat content in men with nonalcoholic fatty liver disease (NAFLD). Participants (n=16) were non...
Kim, Hee Yeon; Kim, Chang Wook; Choi, Jong Young; Lee, Chang Don; Lee, Sae Hwan; Kim, Moon Young; Jang, Byoung Kuk; Wo, Hyun Young
Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade. We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis. Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods. The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.
Koot, B. G. P.; van der Baan-Slootweg, O. H.; Vinke, S.; Bohte, A. E.; Tamminga-Smeulders, C. L. J.; Jansen, P. L. M.; Stoker, J.; Benninga, M. A.
Lifestyle intervention is the only established therapy for non-alcoholic fatty liver disease (NAFLD). The optimal treatment schedule and predictors of response of this treatment have not been established in children. We aimed to evaluate the 2-year efficacy of an inpatient versus ambulatory
Li, Wei; Guan, Zheng; Brisset, Jean C.; Shi, Qiaojuan; Lou, Qi; Ma, Yue; Suriguga, Su; Ying, Huazhong; Sa, Xiaoying; Chen, Zhenwen; Quax, Wim J.; Chu, Xiaofeng
Nonalcoholic fatty liver disease (NAFLD) usually takes decades to develop into cirrhosis, which limits the longitudinal study of NAFLD. This work aims at developing a NAFLD-caused cirrhosis model in gerbil and examining the dynamic relationship between hepatic lipid metabolism and cirrhosis. We fed
Full Text Available Background: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD. We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics.
Bechmann, Lars P.; Gastaldelli, Amalia; Vetter, Diana; Patman, Gillian L.; Pascoe, Laura; Hannivoort, Rebekka A.; Lee, Ursula E.; Fiel, Isabel; Munoz, Ursula; Ciociaro, Demetrio; Lee, Young-Min; Buzzigoli, Emma; Miele, Luca; Hui, Kei Y.; Bugianesi, Elisabetta; Burt, Alastair D.; Day, Christopher P.; Mari, Andrea; Agius, Loranne; Walker, Mark; Friedman, Scott L.; Reeves, Helen L.
The polymorphism, KLF6-IVS1-27A, in the Kruppel-like factor 6 (KLF6) transcription factor gene enhances its splicing into antagonistic isoforms and is associated with delayed histological progression of nonalcoholic fatty liver disease (NAFLD). To explore a potential role for KLF6 in the development
Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: "non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver". Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.
Van Den Berg, Eline; van Tienhoven-Wind, Lynnda; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, H.; Dullaart, Robin P.F.
Background: Non-alcoholic fatty live disease (NAFLD) is becoming the leading cause of chronic liver disease in de Western world. The liver plays a crucial role in the metabolism of cholesterol and triglycerides and thyroid hormones interact on hepatic lipid homeostasis. Given the importance of
van den Berg, Eline H.; van Tienhoven-Wind, Lynnda J. N.; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P. F.
Objective. Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a
Surya Prakash Bhatt
Full Text Available Background: Genetics of non-alcoholic fatty liver (NAFLD in Asian Indians has been inadequately investigated. This study aims to determine the association of the 1784G > C polymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India.
Shiri-Sverdlov, Ronit; Wouters, Kristiaan; van Gorp, Patrick J.; Gijbels, Marion J.; Noel, Benoit; Buffat, Laurent; Staels, Bart; Maeda, Nobuyo; van Bilsen, Marc; Hofker, Marten H.
The molecular mechanisms leading to Non-Alcoholic Steatohepatitis (NASH) are not fully understood. In mice, NASH can be inhibited by fenofibrate, a synthetic agonist for the nuclear receptor peroxisome proliferator activated receptor alpha, which regulates hepatic triglyceride metabolism. This study
Duval, C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, S.; Müller, M.
OBJECTIVE - Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction between adipose tissue and liver in NAFLD and identify potential early plasma markers
Duval, C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, S.; Muller, M.
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction between adipose tissue and liver in NAFLD and identify potential early plasma markers that
Duval, C.N.C.; Thissen, Uwe; Keshtkar, Shohreh; Accard, Bertrand; Stienstra, Rinke; Boekschoten, Mark; Roskams, Tania; Kersten, Sander; Muller, Michael
Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that
Duval, C.N.C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, A.H.; Müller, M.R.
Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that
Full Text Available ObjectiveTo investigate the incidence rates and features of non-alcoholic fatty liver (NAFL and nonalcoholic steatohepatitis (NASH, and to provide a theoretical basis for health management and development of intervention and preventive measures in the health management department. MethodsPhysical examination reports in 2016 were obtained from a large IT company to analyze the incidence rates of NAFL and NASH in different age and sex groups, as well as the correlation with the indices including overweight (or obesity, triglyceride, fasting blood glucose, blood uric acid, and blood pressure. The chi-square test was used for comparison of rates. Results In all employees, the incidence rates of NAFL and NASH were 4.51% and 17.64%, respectively, and the overall incidence rate of these two diseases was 22.15%. The NAFL-NASH group had significantly higher incidence rates of overweight (or obesity (91.20% vs 12.68%, χ2=7571.9, P＜0.001, hyperlipidemia (95.06% vs 9.27%, χ2=9373.8, P＜0.001, and hyperuricemia (40.02% vs 10.51%, χ2=1591.90, P＜0.001 than the non-NAFL-NASH group. Compared with female employees, male employees had significantly higher incidence rates of NAFL (6.78% vs 1.81%, χ2=190.35, P＜0.001 and NASH (25.04% vs 5.06%, χ2=991.90, P＜0.001, as well as significantly higher incidence rates of overweight (or obesity (40.90% vs 12.97%, χ2=1319.10, P＜0.001, hyperlipidemia (36.00% vs 16.07%, χ2=696.22, P＜0.001, hyperglycemia (2.17% vs 0.64%, χ2=53.82, P＜0.01, hyperuricemia (2676% vs 1.69%, χ2=1581.10, P＜0.001, and hypertension (6.21% vs 1.22%, χ2=170.94, P＜0.001. Compared with those aged ＜35 years, the employees aged ≥35 years had significantly higher incidence rates of NAFL (8.13% vs 4.47%, χ2=41.56, P＜0.001 and NASH (21.73% vs 16.76%, χ2=24.72, P＜0.001, as well as significantly higher incidence rates of hyperglycemia (2.79% vs 143%, χ2=17.26, P＜0.001 and hypertension (6.33% vs 4.03%, χ2=18.56, P＜0
Miele, Luca; Cammarota, Giovanni; Vero, Vittoria; Racco, Simona; Cefalo, Consuelo; Marrone, Giuseppe; Pompili, Maurizio; Rapaccini, Gianlodovico; Bianco, Alessandro; Landolfi, Raffaele; Gasbarrini, Antonio; Grieco, Antonio
Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease. Cross-sectional, case-control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication. The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16-4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24-5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12-3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76-6.36). Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Shanab, Ahmed Abu
Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS).
Cavalcante, Lourianne Nascimento; Stefano, Jose Tadeu; Machado, Mariana V; Mazo, Daniel F; Rabelo, Fabiola; Sandes, Kiyoko Abe; Carrilho, Flair José; Cortez-Pinto, Helena; Lyra, Andre Castro; de Oliveira, Claudia P
To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S
Jamali, Raika; Razavizade, Mohsen; Arj, Abbas; Aarabi, Mohammad Hossein
To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. Certain adipokines may
Cavalcante, Lourianne Nascimento; Stefano, Jose Tadeu; Machado, Mariana V; Mazo, Daniel F; Rabelo, Fabiola; Sandes, Kiyoko Abe; Carrilho, Flair José; Cortez-Pinto, Helena; Lyra, Andre Castro; de Oliveira, Claudia P
AIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH
Full Text Available Abstract Background and Purpose Recent research in the field of hematology indicate that among the many pathogenic mechanisms of development and progression of nonalcoholic steatohepatitis NASH which occurs on the background of the metabolic syndrome an important role is played by endothelial dysfunction and violations of haemocoagulation. The aim of this research was to study the effectiveness of L-arginine as it corrects endothelial dysfunction and disorders of homeostasis haemocoagulation link in patients with NASH associated with the metabolic syndrome. Subjects and Methods 128 patients with nonalcoholic steatohepatitis associated with metabolic syndrome were examined. Some patients 63 persons received standard treatment according to national guidelines. To another group 65 patients on the background of basic therapy L-arginine hydrochloride followed by transition to oral form of L-arginine aspartate was administered. Blood levels of stable nitrogen monoxide metabolites nitrites nitrates endothelin-1 and plasma recalcification time prothrombin time thrombin time activated partial thromboplastin time fibrinogen plasma level activity of antithrombin III and coagulation factor XIII potential activity of plasminogen plasma fibrinolytic blood activity were studied. Results Originally significantly increased levels of endothelin-1 decreased after the therapy in all studied groups but more noticeable changes in the group with L-arginine appointment were observed p0.05. In the studied groups normalization of stable nitrogen monoxide metabolites after treatment was also noticed. Significant p0.05 increase in all haemocoagulation time characteristics and activities of antithrombin-III and factor XIII was found. The positive effect of L-arginine on blood fibrinolytic activity was noted. Discussion and Conclusion Combined therapy of nonalcoholic steatohepatitis associated with metabolic syndrome with a differentiated degreeal L-arginine assignment by
Jamali, Raika; Arj, Abbas; Razavizade, Mohsen; Aarabi, Mohammad Hossein
Abstract Considering limitations of liver biopsy for diagnosis of nonalcoholic liver disease (NAFLD), biomarkers’ panels were proposed. The aims of this study were to establish models based on serum adipokines for discriminating NAFLD from healthy individuals and nonalcoholic steatohepatitis (NASH) from simple steatosis. This case-control study was conducted in patients with persistent elevated serum aminotransferase levels and fatty liver on ultrasound. Individuals with evidence of alcohol consumption, hepatotoxic medication, viral hepatitis, and known liver disease were excluded. Liver biopsy was performed in the remaining patients to distinguish NAFLD/NASH. Histologic findings were interpreted using “nonalcoholic fatty liver activity score.” Control group consisted of healthy volunteers with normal physical examination, liver function tests, and liver ultrasound. Binary logistic regression analysis was applied to ascertain the effects of independent variables on the likelihood that participants have NAFLD/NASH. Decreased serum adiponectin and elevated serum visfatin, IL-6, TNF-a were associated with an increased likelihood of exhibiting NAFLD. NAFLD discriminant score was developed as the following: [(−0.298 × adiponectin) + (0.022 × TNF-a) + (1.021 × Log visfatin) + (0.709 × Log IL-6) + 1.154]. In NAFLD discriminant score, 86.4% of original grouped cases were correctly classified. Discriminant score threshold value of (−0.29) yielded a sensitivity and specificity of 91% and 83% respectively, for discriminating NAFLD from healthy controls. Decreased serum adiponectin and elevated serum visfatin, IL-8, TNF-a were correlated with an increased probability of NASH. NASH discriminant score was proposed as the following: [(−0.091 × adiponectin) + (0.044 × TNF-a) + (1.017 × Log visfatin) + (0.028 × Log IL-8) − 1.787] In NASH model, 84% of original cases were correctly classified. Discriminant score threshold value of (−0.22) yielded a
Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed
Full Text Available Nonalcoholic fatty liver disease (NAFLD combines with a variety of liver pathologies, including hepatic steatosis, nonalcoholic steatohepatitis, fibrosis and cirrhosis, and acts as hepatic manifestation of metabolic syndrome. Not only the liver is a target organ in the formation of metabolic syndrome: also exist a possibility of gallbladder, pancreas and biliary tract steatosis. Fatty infiltration of the pancreatobiliary system associates with disturbance of digestive processes that promotes dysbiotic changes and intestinal disorders. Changes in intestinal microbiota, in turn, may induce systemic inflammatory response and promote NAFLD development and progression. Objective: to explore the structural and functional state of the pancreatobiliary system and changes of the enteric microflora in children with NAFLD. Methods. In 34 children with disorders of the gastrointestinal tract, we have determined controlled attenuation parameter by means of FibroScan. Assessment of functional status of biliary tract was performed using an ultrasound examination of the abdominal organs with test meal in order to determine gallbladder contractility and the sphincter of Oddi function. To characterize the state of the enteric microbiota, there was carried out a hydrogen breath test with glucose or lactose loading. Children were divided into groups according to the the transient elastography of the liver (FibroScan: the control group was represented by 21 patients without liver steatosis, the main group — 13 patients with liver steatosis. Results. Children with nonalcoholic fatty liver disease had signs of not only liver pathology, but also of the bile ducts and the pancreas. Biliary tract dysfunction in patients with NAFLD more often manifested as hypotension of the sphincter of Oddi and the gallbladder hypokinesia. Lesions of the pancreas function in children with NAFLD can be explained by the sphincter of Oddi disorders and manifestations of pancreatic
Berlanga Bustos, Alba
Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH), with the latter being more frequently progressive. Due to lipid accumulation in the human liver seems to be a crucial mechanism in the NAFLD pathogenesis, an improved understanding of the underlying mechanisms leading to the initial hepatic lipid accumulation could be of great interest for controlling the progression of NAFLD. It has also been repor...
Full Text Available Wenxi He,1 Yanjiao Xu,1 Chengliang Zhang,1 Jingli Lu,2 Juan Li,1 Dong Xiang,1 Jinyu Yang,1 Mujun Chang,3 Dong Liu1 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; 2Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; 3Center for Translational Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China Abstract: Calculus bovis (CB, niu-huang is a high-class therapeutic drug that is often used in traditional Chinese medicine. CB helps to eliminate heat and toxic components, and prevents the accumulation of phlegm and blood stasis in the liver. In Asian countries, CB Sativus (CBS, an ideal substitute for natural CB, is presently extensively used for long-term treatment of chronic liver diseases. The present study aimed to evaluate the effects and potential mechanism(s of action of CBS on mice with fructose-induced nonalcoholic fatty liver disease (NAFLD. The NAFLD model was established in C57BL/6 mice by exclusively feeding fluids containing 30% fructose for 8 consecutive weeks. After these 8 weeks, mice were given CBS (50 mg/kg/day or 100 mg/kg/day for 2 consecutive weeks. Treatment with CBS reversed the fructose-induced impaired glucose tolerance. Compared with the model group, in which mice received 8 weeks of high-fructose diet and 2 weeks of 0.5% sodium carboxymethyl cellulose, CBS treatment significantly decreased the levels of fasting serum glucose, fasting insulin, triglyceride, and total cholesterol, and increased levels of high-density lipoprotein-cholesterol. CBS treatment also significantly decreased the levels of triglyceride, total cholesterol, and free fatty acid in the liver. The activity of superoxide dismutase in the liver was increased after treatment with CBS, however, levels of malondialdehyde and reactive oxygen species decreased
Thoms, B.; Wackernagel, W.
Ultraviolet-induced restriction alleviation is an SOS function which partially relieves the K-12-specific DNA restriction in Escherichia coli. Restriction alleviation is determined by observing elevated survival of unmodified phage lambda in cells irradiated with ultraviolet prior to infection. The authors demonstrate that restriction of lambda is also relieved when log-phase cells are irradiated as late as 50 min after adsorption of lambda. At this time more than 60% of the lambda DNA is already released as acid-soluble material from the cells. Experiments involving reextraction of lambda DNA from infected cells and a mild detergent treatment removing adsorbed phages from the cellular surface showed that only a small specific fraction of all lambda infections is destined to escape restriction due to restriction alleviation. This fraction (10-20%) has a retarded mode of DNA injection (60 min or longer) after adsorption which allows the expression of the restriction alleviation function before the phage DNA is exposed to restriction endonucleases. This behaviour of a fraction of lambda phages explains why the SOS function restriction alleviation could initially be discovered. The authors show that the retarded mode of DNA injection is not required for another SOS function acting on lambda DNA, the increased repair of ultraviolet-irradiated DNA (Weigle reactivation). (Auth.)
Lwalaba, Jonas Lwalaba Wa; Zvobgo, Gerald; Fu, Liangbo; Zhang, Xuelei; Mwamba, Theodore Mulembo; Muhammad, Noor; Mundende, Robert Prince Mukobo; Zhang, Guoping
Cobalt (Co) contamination in soils is becoming a severe issue in environment safety and crop production. Calcium (Ca) , as a macro-nutrient element, shows the antagonism with many divalent heavy metals and the capacity of alleviating oxidative stress in plants. In this study, the protective role of Ca in alleviating Co stress was hydroponically investigated using two barley genotypes differing in Co toxicity tolerance. Barley seedlings exposed to 100µM Co showed the significant reduction in growth and photosynthetic rate, and the dramatic increase in the contents of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG), and the activities of anti-oxidative enzymes, with Ea52 (Co-sensitive) being much more affected than Yan66 (Co-tolerant). Addition of Ca in growth medium alleviated Co toxicity by reducing Co uptake and enhancing the antioxidant capacity. The effect of Ca in alleviating Co toxicity was much greater in Yan66 than in Ea52. The results indicate that the alleviation of Co toxicity in barley plants by Ca is attributed to the reduced Co uptake and enhanced antioxidant capacity. Copyright © 2017 Elsevier Inc. All rights reserved.
Gentile, S; Guarino, G; Strollo, F; Romano, M; Genovese, S; Masarone, M; Ceriello, A
To compare metabolic control under lispro and recombinant regular human insulin (RHI) in people with diet-unresponsive type 2 diabetes mellitus (T2DM) and compensated non-alcoholic liver disease (CLD). 108 people with T2DM and CLD were randomly allocated to RHI or lispro according to a 12+12 week cross-over protocol. A 1-week continuous glucose monitoring (CGM) session was performed at the end of each treatment period followed by a standard meal test with a 12IU lispro or RHI shot ahead. CGM showed higher glycemic excursions under RHI than under lispro (pliver glucose output expected from its earlier hepatic distribution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Abenavoli, Ludovico; Milic, Natasa; Peta, Valentina; Alfieri, Francesco; De Lorenzo, Antonino; Bellentani, Stefano
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The mechanisms of the underlying disease development and progression are awaiting clarification. Insulin resistance and obesity-related inflammation status, among other possible genetic, dietary, and lifestyle factors, are thought to play the key role. There is no consensus concerning the pharmacological treatment. However, the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy. On the basis of its components, the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases, including obesity and diabetes. New evidence supports the idea that the Mediterranean diet, associated with physical activity and cognitive behaviour therapy, may have an important role in the prevention and the treatment of NAFLD. PMID:25492997
Awai, Hannah I; Yu, Elizabeth L; Ellis, Linda S; Schwimmer, Jeffrey B
The prevalence of obesity and related morbidities such as nonalcoholic fatty liver disease (NAFLD) is high among adolescents. Current treatment recommendations for NAFLD focus on lifestyle optimization via nutrition and exercise. After encouraging exercise, many adolescents choose to participate in organized sports, which may lead to use of illicit substances such as anabolic androgenic steroids (AAS) to boost athletic performance. Approximately 3,000,000 individuals use non-therapeutic AAS at supra-physiologic doses in the United States.1 In 2012, 5.9% of adolescent boys reported steroid use in the previous year.2 We anticipate adolescents with pre-existing liver disease are at increased risk for AAS induced hepatotoxicity. We present such a case with IRB approval and written individual patient consent. PMID:23568051
Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Lockwood, Alan H; Weissenborn, Karin; Bokemeyer, Martin; Tietge, U; Burchert, Wolfgang
Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical-physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.
Kim, Kyoung Yeon [Dept. of Radiology, Anseong Hanju Clinic, Anseong (Korea, Republic of); Lim, Hyun Soo [Dept. of Biomedical Engineering, Chungnam University, Daejeon (Korea, Republic of)
Nonalcoholic fatty liver disease (NAFLD) is accumulation state of fat in liver cells without excessive alcohol intake, and it has been studied that is closely related to obesity. The purpose of this study is to identify risk factors for NAFLD and may prevent or to manage risk factors. This study was in progress for six months (2011 May 1 to October 31), of the 83 people who underwent abdominal ultrasound 11 people eventually were selected. Research results was as follows : First, the decreased body weight and body mass index (BMI), and the second, a decrease of the deepening of fatty liver in ultrasound diagnosis, and the third, steady movement reduces the deepening of fatty liver regardless of calories. Thus, the implication of this research is that long-term exercise programs have positive effects in the treatment of fatty liver.
Rix, Iben; Steen Pedersen, Julie; Storgaard, Heidi
PURPOSE: Non-alcoholic fatty liver disease (NAFLD) affects about 25% of the population worldwide. NAFLD may be viewed as the hepatological manifestation of metabolic syndrome. Patients with metabolic syndrome due to diabetes or obesity have an increased risk of cardiovascular disease....... This narrative review describes cardiometabolic effects of antidiabetic drugs in NAFLD. METHODS: We conducted a systematic search in PubMed and manually scanned bibliographies in trial databases and reference lists in relevant articles. RESULTS: Heart disease is the leading cause of death in NAFLD. Conversely......, NAFLD is an independent cardiovascular risk factor in patients suffering from metabolic syndrome. NAFLD is associated with markers of atherosclerosis, and patients have increased risk of ischaemic heart disease. Additionally, patients with NAFLD have increased risk of cardiac dysfunction and heart...
Full Text Available Currently the incidence of nonalcoholic fatty liver disease (NAFLD is increasing, and the age of onset is getting younger worldwide, resulting in a heavy economic burden for both individuals and the society. Since NAFLD is closely related to heredity, metabolism, and the environment, genetic factors play an important role in the development and progression of NAFLD. With the development and wide application of the techniques from the genome-wide association studies, new research advances have been achieved in the susceptibility genes of NAFLD. This review summarizes the related research findings at home and abroad, and investigates the pathogenic factors for NAFLD and related mechanisms with a focus on the polymorphisms of susceptibility genes.
Nobili, V; Alisi, A; Newton, Kimberly P.; Schwimmer, Jeffrey B.
Nonalcoholic fatty liver disease (NAFLD) is one of the main chronic non-communicable diseases in westernized societies; its worldwide prevalence has doubled during the last 20 years. NAFLD has serious health implications not only for adults, but also for children. However, pediatric NAFLD is not only an important global problem in itself, but it is likely to be associated with increases in comorbidities such as metabolic syndrome and cardiovascular diseases. There are several differences between NAFLD in children and adults and it is not clear whether the disease observed in children is the initial phase of a process that progresses with age. The increasing prevalence of pediatric NAFLD has serious implications for the future adult population requiring appropriate action. Studies of NAFLD progression, pathogenesis, and management should evaluate disease phenotypes in children and follow these over patient lifetimes. We review the similarities and differences of NAFLD between children and adults. PMID:27003600
Anavi, Sarit; Madar, Zecharia; Tirosh, Oren
Nonalcoholic fatty liver diseases (NAFLD) is one of the most common chronic liver disease in Western countries. Oxygen is a central component of the cellular microenvironment, which participate in the regulation of cell survival, differentiation, functions and energy metabolism. Accordingly, sufficient oxygen supply is an important factor for tissue durability, mainly in highly metabolic tissues, such as the liver. Accumulating evidence from the past few decades provides strong support for the existence of interruptions in oxygen availability in fatty livers. This outcome may be the consequence of both, impaired systemic microcirculation and cellular membrane modifications which occur under steatotic conditions. This review summarizes current knowledge regarding the main factors which can affect oxygen supply in fatty liver. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Kim, Kyoung Yeon; Lim, Hyun Soo
Nonalcoholic fatty liver disease (NAFLD) is accumulation state of fat in liver cells without excessive alcohol intake, and it has been studied that is closely related to obesity. The purpose of this study is to identify risk factors for NAFLD and may prevent or to manage risk factors. This study was in progress for six months (2011 May 1 to October 31), of the 83 people who underwent abdominal ultrasound 11 people eventually were selected. Research results was as follows : First, the decreased body weight and body mass index (BMI), and the second, a decrease of the deepening of fatty liver in ultrasound diagnosis, and the third, steady movement reduces the deepening of fatty liver regardless of calories. Thus, the implication of this research is that long-term exercise programs have positive effects in the treatment of fatty liver.
Asadzadeh-Aghdaee, Hamid; Mansouri, Vahid; Peyvandi, Ali Asghar; Moztarzadeh, Fathollah; Okhovatian, Farshad; Lahmi, Farhad; Vafaee, Reza; Zali, Mohammad Reza
Aim: The corresponding proteins are important for network mapping since the interaction analysis can provide a new interpretation about disease underlying mechanisms as the aim of this study. Backgroud: Nonalcoholic steatohepatitis (NASH) is one of the main causes of liver disease in the world. It has been known with many susceptible proteins that play essential role in its pathogenesis. Methods: In this paper, protein-protein interaction (PPI) network analysis of fatty liver disease retrieved from STRING db by the application of Cytoscape Software. ClueGO analyzed the associated pathways for the selected top proteins. Results: INS, PPARA, LEP, SREBF1, and ALB are the introduced biomarker panel for fatty liver disease. Conclusion: It seems that pathways related to insulin have a prominent role in fatty liver disease. Therefore, investigation in this case is required to confirm the possible linkage of introduced panel and involvement of insulin pathway in the disease. PMID:28224024
Full Text Available Diabetes mellitus (DM type 2 in clinical practice is often associated with non-alcoholic fatty liver disease (NAFLD, which has a number of clinical and morphological forms and develops in patients who do not abuse alcohol. The combination of DM type 2 and NAFLD is associated not only with a high risk of developing liver cirrhosis and hepatocellular carcinoma in these patients. Although all aspects of the etiology of NAFLD is not fully known, it is points to the role of insulin resistance in its development. This concept has facilitated a number of clinical studies using metformin as the insulin sensitizer in insulin-resistant patients with NAFLD. The findings emphasize the importance of metformin in the treatment of NAFLD in combination with a hypocaloric diet and the control of body weight. It is also reported about other tissue effects of metformin in NAFLD.
Full Text Available This report describes a case of liver failure secondary to pancreatoduodenectomy and rapid recovery following treatment. A 68-year-old woman with cancer on the ampulla of Vater underwent surgery for pancreatoduodenectomy. The patient developed liver failure 3 months postsurgically. She was hospitalized after presenting with jaundice, hypoalbuminemia and decreased serum zinc. Computed tomography (CT of the abdomen showed a reduction in CT attenuation values postoperatively. We suspected fatty liver due to impaired absorption caused by pancreatoduodenectomy. We initiated treatment with branched-chain amino acids and a zinc formulation orally. Trace elements were administered intravenously. Two months after treatment, there was a noticeable improvement in CT findings. The patient’s jaundice and hypoalbuminemia prompted a liver biopsy, which led to a diagnosis of non-alcoholic steatohepatitis.
Full Text Available Helicobacter pylori (H. pylori which colonizes the stomach can cause a wide array of gastric disorders, including chronic gastritis, peptic ulcer, and gastric cancer. Recently, accumulating evidence has implicated H. pylori infection in extragastrointestinal diseases such as cardiovascular diseases, neurological disorders, and metabolic diseases. At the same time, many scholars have noted the relationship between H. pylori infection and non-alcoholic fatty liver disease (NAFLD. Despite the positive association between H. pylori and NAFLD reported in some researches, there are opposite perspectives denying their relationship. Due to high prevalence, unclear etiology and difficult treatment of NAFLD, confirming the pathogenicity of H. pylori infection in NAFLD will undoubtedly provide insights for novel treatment strategies for NAFLD. This paper will review the relationship between H. pylori infection and NAFLD and the possible pathogenic mechanisms.
Full Text Available With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.
Full Text Available The gut microbiota plays critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD, type 2 diabetes(T2D, and insulin resistance(IR, highlighting the potential of gut microbiota-targeted therapies in these diseases. There are various ways that gut microbiota can be manipulated, including through use of probiotics, prebiotics, synbiotics, antibiotics, and some active components from herbal medicines. In this review, we review the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies for NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.
O. A. Pavlenko
Full Text Available Non-alcoholic fatty liver disease (NAFLD is a highly prevalent disorder associated with obesity and metabolic syndrome. The main pathophysiological factor of liver steatosis is insulin resistance that may lead to development of type 2 diabetes mellitus. Overcoming of insulin resistance by means of body weight reduction and administration of insulin sensitizers is considered to be a promising approach to NAFLD treatment. In accordance with the Russian guidelines on diagnostics and treatment of NAFLD, sibutramine is the drug of choice for medical treatment of obesity. As for insulin sensitizers, metformin (biguanide class is widely used for treatment of NAFLD in everyday clinical practice. Treatment of NAFLD as a component of metabolic syndrome should be multifactorial and aimed at different aspects of the disease pathophysiology.
Fujita, Nobuhiro; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Shirabe, Ken; Yoshizumi, Tomoharu; Kotoh, Kazuhiro; Furusyo, Norihiro; Hida, Tomoyuki; Oda, Yoshinao; Fujioka, Taisuke; Honda, Hiroshi
To evaluate the diagnostic performance of computed tomography (CT) volumetry for discriminating the fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). A total of 38 NAFLD patients were enrolled. On the basis of CT imaging, the volumes of total, left lateral segment (LLS), left medial segment, caudate lobe, and right lobe (RL) of the liver were calculated with a dedicated liver application. The relationship between the volume percentage of each area and fibrosis stage was analyzed using Spearman's rank correlation coefficient. A receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of CT volumetry for discriminating fibrosis stage. The volume percentages of the caudate lobe and the LLS significantly increased with the fibrosis stage ( r = 0.815, P volumetry is a useful diagnostic parameter for staging fibrosis in NAFLD patients.
Cai, Jingjing; Zhang, Xiao-Jing; Li, Hongliang
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets. © 2018 Wiley Periodicals, Inc.
Full Text Available Norwegian fluid milk consumption has declined steadily over the last twenty years, despite the dairy industry spending increasing amounts of money on advertising. Using a two-stage model, we investigate whether advertising has increased the demand for milk. No effect of advertising on the demand for non-alcoholic beverages is found in the first stage. In the second stage, an almost ideal demand system including advertising expenditures on competing beverages is estimated. The effects of generic advertising within the beverage group are positive and significant for whole milk and negative and significant for lower fat milk. The own-advertising elasticity for the combined fluid milk group is 0.0008. This highly inelastic elasticity suggests that increased advertising will not be profitable for the producers. Several cross-advertising effects are statistically significant, emphasizing the usefulness of a demand system approach.
Scalera, Antonella; Di Minno, Matteo Nicola Dario; Tarantino, Giovanni
Non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are two very common diseases in the general population. To date, there are no studies that highlight a direct link between NAFLD and IBS, but some recent reports have found an interesting correlation between obesity and IBS. A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD, leading to an increased cardiovascular risk, and IBS, leading to microbial dysbiosis, impaired intestinal barrier and altered intestinal motility. It is not known when considering local and systemic inflammation/immune system activation, which one has greater importance in NAFLD and IBS pathogenesis. Also, the nervous system is implicated. In fact, inflammation participates in the development of mood disorders, such as anxiety and depression, characteristics of obesity and consequently of NAFLD and, on the other hand, in intestinal hypersensitivity and dysmotility.
Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.
Poulsen, Mette Buch; Jakobsen, Johannes Klitgaard; Andersen, Henning
Chronic alcohol abuse has adverse effects on skeletal muscle, and reduced muscle strength is frequently seen in chronic alcoholics. In this study the acute effects of moderate alcohol intoxication on motor performance was evaluated in 19 non-alcoholic healthy subjects (10 women, 9 men......). A randomised double-blinded placebo controlled design was applied to subjects receiving alcohol in juice and pure juice at two separate test periods. Isokinetic and isometric muscle strength and endurance were determined before, during, 24 and 48 h after the ingestion of alcohol in juice and juice (placebo......). To detect a reduced activation of the central motor pathways superimposed external electrical stimulations during voluntary contractions were applied. Creatine kinase (CK) was measured to detect any alcohol-induced changes in sarcolemmal integrity. No change was seen in isokinetic as well as in isometric...
Vazquez-Chantada, Mercedes; Gonzalez-Lahera, Aintzane; Martinez-Arranz, Ibon
,414 type 2 diabetes mellitus (T2DM) cases and 4,567 controls were genotyped. Liver expression of the associated gene was measured and the effect of its potential role was studied by silencing the gene in vitro. Whole genome expression, oxidative stress (OS), and the consequences of oleic acid (OA......Susceptibility to develop nonalcoholic fatty liver disease (NAFLD) has genetic bases, but the associated variants are uncertain. The aim of the present study was to identify genetic variants that could help to prognose and further understand the genetics and development of NAFLD. Allele frequencies...... association with NAFLD, but not with T2DM, being the haplotype containing the minor allele of SLC2A1 sequence related to the susceptibility to develop NAFLD. Gene-expression analysis demonstrated a significant down-regulation of SLC2A1 in NAFLD livers. Enrichment functional analyses of transcriptome profiles...
Tveden-Nyborg, Pernille; Birck, Malene Muusfeldt; Ipsen, David Højland
Chronic dyslipidemia imposed by a high-fat and high-caloric dietary regime leads to debilitating disorders such as obesity, nonalcoholic fatty liver disease (NAFLD), and insulin resistance. As disease rates surge, so does the need for high validity animal models to effectively study the causal...... and either 15% or 20% sucrose) compared with isocaloric standard chow in adult guinea pigs. Biochemical markers confirmed dyslipidemia in agreement with dietary regimens; however, both high-fat groups displayed a decreased tissue fat percentage compared with controls. Macroscopic appearance, histopathologic....... Evaluation of glucose tolerance showed no indication of insulin resistance. The 5% increase in sucrose between the 2 high-fat diets did not lead to significant differences between groups. In conclusion, we find the dyslipidemic guinea pig to be a valid model of diet imposed dyslipidemia, particularly...
Mato, José M; Lu, Shelly C
Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide affecting over one-third of the population in the U.S. It has been associated with obesity, type 2 diabetes, hyperlipidemia, and insulin resistance and is initiated by the accumulation of triglycerides in hepatocytes. Isolated hepatic steatosis (IHS) remains a benign process, while a subset develops superimposed inflammatory activity and progression to nonalcoholic steatohepatitis (NASH) with or without fibrosis. However, the molecular mechanisms underlying NAFLD progression are not completely understood. Liver biopsy is still required to differentiate IHS from NASH as easily accessible noninvasive biomarkers are lacking. In terms of treatments for NASH, pioglitazone, vitamin E, and obeticholic acid have shown some benefit. All of these agents have potential complications associated with long-term use. Nowadays, a complex hypothesis suggests that multiple parallel hits are involved in NASH development. However, the ‘key switch’ between IHS and NASH remains to be discovered. We have recently shown that knocking out enzymes involved in S-adenosylmethionine (SAMe) metabolism, the main biological methyl donor in humans that is abundant in the liver, will lead to NASH development in mice. This could be due to the fact that a normal SAMe level is required to establish the proper ratio of phosphatidylethanolamine to phosphatidylcholine that has been found to be important in NAFLD progression. New data from humans have also suggested that these enzymes play a role in the pathogenesis of NAFLD and that some of SAMe cycle metabolites may serve as noninvasive biomarkers of NASH. In this review, we discuss the evidence of the role of SAMe in animal models and humans with NAFLD and how studying this area may lead to the discovery of new noninvasive biomarkers and possibly personalized treatment for NASH. PMID:25873078
Hiroshi Sakugawa; Fukunori Kinjo; Atsushi Saito; Tomofumi Nakayoshi; Kasen Kobashigawa; Tsuyoshi Yamashiro; Tatsuji Maeshiro; Satoru Miyagi; Joji Shiroma; Akiyo Toyama; Tomokuni Nakayoshi
AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease.However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type Ⅵ collagen 7S domain and hyaluronic acid.METHODS: One hundred and twelve patients with histologically proven NAFLD were studied.RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type Ⅵ collagen 7S domain ≥5.0 ng/mL, hyaluronic acid ≥43 ng/mL. Both markers had a high positive predictive value: type Ⅵ collagen 7S domain, 86% and hyaluronic acid,92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type Ⅵ collagen 7S domain (≥5.0 ng/mL),84% and hyaluronic acid (≥50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis.CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis.
Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.
Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids
Full Text Available Miwa Kawanaka,1 Ken Nishino,1 Jun Nakamura,1 Mitsuhiko Suehiro,1 Daisuke Goto,1 Noriyo Urata,1 Takahito Oka,1 Hirofumi Kawamoto,1 Hajime Nakamura,2 Junji Yodoi,3 Keisuke Hino,4 Gotaro Yamada11Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, 2Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, 3Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, 4Department of Hepatology and Pancreatology, Kawasaki Medical School, Okayama, JapanBackground: Nonalcoholic steatohepatitis (NASH is a common liver disease that can progress to cirrhosis. Oxidative stress is one of the central mechanisms causing hepatocellular injury in the disease. In this study, antioxidant therapy using both vitamins C and E was conducted in patients with NASH.Methods: Vitamin E 300 mg/day and vitamin C 300 mg/day were administered orally to 23 patients with NASH for 12 months. Body mass index was measured during therapy. Serum levels of alanine aminotransferase, thioredoxin (an oxidative stress marker, and high-sensitivity C-reactive protein were measured before treatment and after 12 months in all patients. Ten of the 23 patients underwent liver biopsy before and after treatment.Results: Body mass index remained unchanged during treatment with vitamins C and E. Serum alanine aminotransferase, thioredoxin, and high-sensitivity C-reactive protein levels were decreased significantly at 12 months compared with pretreatment. Liver biopsies showed improved necroinflammatory activity in eight cases and improved fibrosis staging in 4.Conclusion: Serum alanine aminotransferase, thioredoxin, and high-sensitivity C-reactive protein levels, and liver histology were clearly improved with vitamin C and E therapy. These findings suggest that combination therapy using these vitamins may be useful in patients with NASH to minimize damage from oxidative stress and slow
Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro
Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended
Fargion, Silvia; Porzio, Marianna; Fracanzani, Anna Ludovica
Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular
Abulizi, Abudukadier; Perry, Rachel J; Camporez, João Paulo G; Jurczak, Michael J; Petersen, Kitt Falk; Aspichueta, Patricia; Shulman, Gerald I
Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes. After 4 wk of oral CRMP (2 mg/kg body weight per day) or vehicle treatment, mice underwent hyperinsulinemic-euglycemic clamps combined with radiolabeled glucose to assess liver and muscle insulin responsiveness and tissue lipid measurements. CRMP treatment reversed hypertriglyceridemia and insulin resistance in liver and skeletal muscle. Reversal of insulin resistance could be attributed to reductions in diacylglycerol content and reduced PKC-ε and PKC-θ activity in liver and muscle respectively. CRMP treatment also reversed NASH as reflected by reductions in plasma aspartate aminotransferase and alanine aminotransferase concentrations; hepatic steatosis; and hepatic expression of IL-1α, -β, -2, -4, -6, -10, -12, CD69, and caspase 3 and attenuated activation of the IRE-1α branch of the unfolded protein response. Taken together, these results provide proof of concept for the development of liver-targeted mitochondrial uncoupling agents as a potential novel therapy for lipodystrophy-associated hypertriglyceridemia, NASH and diabetes.-Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., Shulman, G. I. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. © FASEB.
Hossain, Noreen; Afendy, Arian; Stepanova, Maria; Nader, Fatema; Srishord, Manirath; Rafiq, Nila; Goodman, Zachary; Younossi, Zobair
Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We investigated factors associated with advanced fibrosis in NAFLD. The study included 432 patients with histologically proven NAFLD (26.8% with nonalcoholic steatohepatitis [NASH] and 17.4% with moderate-to severe fibrosis). NASH was defined as steatosis, lobular inflammation, and ballooning degeneration with or without Mallory-Denk bodies and/or fibrosis. Fibrosis was classified into 2 groups: those with no or minimal fibrosis and those with moderate-to-severe fibrosis. Groups were compared using Mann-Whitney and chi-square method analyses. A model was constructed using a stepwise bidirectional method; its predictive power was measured using a 10-fold cross-validation technique. Patients with NASH were more likely to be male (P < .0001); have lower hip-to-waist ratios (P = .03); were less likely to be African American (P = .06); have higher levels of alanine aminotransferase (ALT; P < .0001), aspartate aminotransferase (AST; P < .0001), and serum triglycerides (P = .0154), but lower levels of high-density lipoprotein cholesterol (P < .0001). Patients with moderate-to-severe fibrosis were older (P = .0245); more likely to be male (P = .0189), Caucasian (P = .0382), have diabetes mellitus (P = .0238), and hypertension (P = .0375); and have a lower hip-to-waist ratio (P = .0077) but higher serum AST (P < .0001) and ALT (P < .0001) levels. The multivariate analysis model to predict moderate-to-severe fibrosis included male sex, Caucasian ethnicity, diabetes mellitus, and increased AST and ALT levels (model P value < .0001). In patients with NAFLD, diabetes mellitus and aminotransferase levels are independent predictors of moderate-to-severe fibrosis. They can be used to identify NAFLD patients at risk for advanced fibrosis.
Younossi, Zobair M; Jarrar, Mohammed; Nugent, Clare; Randhawa, Manpreet; Afendy, Mariam; Stepanova, Maria; Rafiq, Nila; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha
Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH. The aim of this study was to develop a noninvasive diagnostic biomarker for NASH. The study included 101 patients with liver biopsies who were tested with enzyme-linked immunosorbent assay (ELISA)-based assays. Of these, 69 were included in the biomarker development set and 32 were included in the biomarker validation set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum samples were assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, cytokeratin CK-18 (M65 antigen), and caspase-cleaved CK-18 (M30 antigen). Data analysis revealed that the levels of M30 antigen (cleaved CK-18) predicted histological NASH with 70% sensitivity and 83.7% specificity and area under the curve (AUC) = 0.711, p < 10(-4), whereas the predictive value of the levels of intact CK-18 (M65) was higher (63.6% sensitivity and 89.4% specificity and AUC = 0.814, p < 10(-4)). Histological NASH could be predicted by a combination of Cleaved CK-18, a product of the subtraction of Cleaved CK-18 level from intact CK-18 level, serum adiponectin, and serum resistin with a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10(-4)). Blinded validation of this model confirmed its reliability for separating NASH from simple steatosis. Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.
Mishra, Poonam; Nugent, Clarke; Afendy, Arian; Bai, Chunhong; Bhatia, Priya; Afendy, Mariam; Fang, Yun; Elariny, Hazem; Goodman, Zachary; Younossi, Zobair M
Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnoea are associated with metabolic syndrome and atherosclerotic heart disease. This study evaluates the potential association between the NAFLD subtypes and a number of polysomnographical (PSG) parameters. This study included patients undergoing bariatric surgery with extensive clinical and histological data for whom complete PSG data before surgery were also available. Excess alcohol intake and other causes of liver disease were excluded. Apnoea, hypopnoea and apnoea-hypopnoea index (AHI) were calculated as described previously. In this study, a total of 101 patients [77 nonalcoholic steatohepatitis (NASH) and 22 non-NASH controls] with PSG data were included (age 42.9 +/- 11.4 years, body mass index 51.6 +/- 9.5 kg/m(2), fasting serum glucose 117.4 +/- 53.4 mg/dl, fasting serum triglycerides 171.3 +/- 82.9 mg/dl, 58% hypertension and 33% diabetes mellitus). Subjects with histological NASH had significantly lower lowest desaturation (77 vs. 85%, P=0.006), lower mean nocturnal oxygen saturation (91 vs. 93%, P=0.05), higher AHI (35 vs. 22, P=0.03), higher respiratory disturbance index (46 vs. 21, P=0.02) and higher alanine aminotransferase/aspartate aminotransferase ratio (1.4 vs. 1.3, P=0.05) compared with non-NASH controls. In multivariate analysis, the lowest desaturation (P=0.04) was independently associated with histological NASH. Lowest desaturation and mean nocturnal oxygen saturation were significantly lower in subjects with fibrosis (76 vs. 85%, P=0.004 and 90.4 vs. 93.0%, P=0.02). Our results suggest that the frequent nocturnal hypoxic episodes in NAFLD patients may be a risk factor for developing NASH. Additional studies are needed to study the effect of optimizing sleep apnoea management on the outcomes of patients with NAFLD.
Mells, Jamie E; Fu, Ping P; Kumar, Pradeep; Smith, Tekla; Karpen, Saul J; Anania, Frank A
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). Up to a third of NAFLD subjects are at risk for developing nonalcoholic steatohepatitis (NASH). Many rodent models fail to replicate both MetS and NASH. The purpose of this study was to develop a reliable mouse model of NASH and MetS using a diet containing cholesterol, saturated fat and carbohydrate that is reflective of Western diets of North Americans. We used adult male C57BL/6 J 4- to 5-week-old mice and administered a solid diet containing 0.2% cholesterol, 45% of its calories from fat, with 30% of the fat in the form of partially hydrogenated vegetable oil. We also provided carbohydrate largely as high-fructose corn syrup equivalent in water. In a separate cohort, we gave the identical diet in the absence of cholesterol. Glucose and insulin tolerance testing was conducted throughout the feeding period. The feeding was conducted for 16 weeks, and the mice were sacrificed for histological analysis, markers of MetS, liver inflammation, circulating lipids, as well as liver staining for fibrosis and alpha smooth muscle actin (α-SMA). We found that cholesterol significantly increased serum leptin, interleukin-6, liver weight and liver weight/body weight ratio, fibrosis and liver α-SMA. Mice administered a diet accurately reflecting patterns associated with humans afflicted with MetS can reliably replicate features of MetS, NASH and significant liver fibrosis. The model we describe significantly reduces the time by several months for development of stage 3 hepatic fibrosis. Copyright © 2015 Elsevier Inc. All rights reserved.
Dasarathy, Jaividhya; Varghese, Rony; Feldman, Abram; Khiyami, Amer; McCullough, Arthur J; Dasarathy, Srinivasan
Background: Hypovitaminosis D is associated with an increased severity of nonalcoholic fatty liver disease (NAFLD), but reports on the response to cholecalciferol (vitamin D 3 ) supplementation are conflicting. Objective: The objective of this study was to determine if standard vitamin D 3 supplementation is effective in NAFLD with hypovitaminosis D. Methods: Sixty-five well-characterized adults [age (mean ± SD): 51.6 ± 12.3 y] with biopsy-proven NAFLD were screened. Forty-two patients (the ratio of men to women was 13:29) had hypovitaminosis D (plasma 25-hydroxyvitamin D [25(OH)D] D treated with 2000 IU cholecalciferol (vitamin D 3 ) daily for 6 mo per clinical practice. Plasma 25(OH)D, hepatic and metabolic panels, and metabolic syndrome components were assessed before and after cholecalciferol supplementation. Body composition was measured by using bioelectrical impedance analysis. The primary outcome measure was plasma 25(OH)D ≥30 ng/mL at the end of the study. Secondary outcomes included change in serum transaminases, fasting plasma glucose, and insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Chi-square, Student's t tests, correlation coefficient, and multivariate analysis were performed. Results: Twenty-six (61.9%) patients had nonalcoholic steatohepatitis (NASH), and 16 (38.1%) had hepatic steatosis. After 6 mo of cholecalciferol supplementation, plasma 25(OH)D ≥30 ng/mL was observed in 16 subjects (38.1%; responders) whereas the remaining 26 patients (61.9%) were nonresponders with plasma 25(OH)D D in the majority of patients with NASH. Further studies are needed to determine if higher doses are effective. This trial was registered at clinicaltrials.gov as 13-00153. © 2017 American Society for Nutrition.
Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.
Full Text Available During the last decade, pediatric nonalcoholic liver disease has reached epidemic proportions, becoming one of the most frequent chronic liver diseases in the global child population. Purpose: to study the relationship of the functional state of the gallbladder with structural changes in the liver in children with nonalcoholic fatty liver disease. Materials and methods. We examined 34 children aged from 8 to 17 years old. Hepatic steatosis was determined using the FibroScan® 502 touch with controlled attenuation parameter (CAP. According to the results of transient elastometry and ultrasound of the abdomen with the gallbladder function study, patients were divided into 4 groups: the 1st group consisted of 7 patients with steatosis and hypofunction of gallbladder (20.5 %, group 2 included 6 patients with steatosis and gallbladder normofunction (17.65 %, group 3 consisted of 11 patients without hepatic steatosis with hypofunction of gallbladder (32.35 %, group 4 included 10 patients without hepatic steatosis with gallbladder normofunction (29.4 %. Results. The sonographic studies demonstrated children of the 1st group (steatosis with gallbladder hypokinesia to have significantly larger sizes of liver lobes compared to group 4 (children without steatosis with gallbladder normofunction. Also, the stiffness of the liver parenchyma was highest in patients with hepatic steatosis and gallbladder hypokinesia. Discussion. The combination of hepatic steatosis and hypokinesia of the gallbladder in children is accompanied by a significant increase in liver size, increased stiffness of the liver parenchyma and increasing degree of steatosis. The data indicate the relationship of the gallbladder function and the liver structural changes.
Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: firstname.lastname@example.org [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)
Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids
Moon, Seong-Su; Lee, Young-Sil; Kim, Sung Woo
Osteoporosis is a disease associated with insulin resistant states such as central obesity, diabetes, and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is also increased in such conditions. However, little is known about whether osteoporosis and nonalcoholic fatty liver disease are etiologically related to each other or not. We examined whether bone mineral density (BMD) is associated with NAFLD in pre- and postmenopausal women. Four hundred eighty-one female subjects (216 premenopausal and 265 postmenopausal) were enrolled. Lumbar BMD was measured using dual-energy X-ray absorptiometry. Liver ultrasonography was done to check the severity of fatty liver. We excluded subjects with a secondary cause of liver disease. Blood pressure, lipid profile, fasting plasma glucose, alanine aminotransferase (ALT), aspartate aminotransferase, and body mass index were measured in every subject. Mean lumbar BMD was lower in subjects with NAFLD than those without NAFLD in postmenopausal women (0.98 ± 0.01 vs. 1.01 ± 0.02 g/cm², P = 0.046). Multiple correlation analysis revealed a significant association between mean lumbar BMD and NAFLD in postmenopausal subjects after adjusting for age, body mass index, ALT, smoking status, and alcohol consumption (β coefficient -0.066, 95% CI -0.105 to -0.027, P = 0.001). Even after adjusting the presence of metabolic syndrome, the significance was maintained (β coefficient -0.043, 95% CI -0.082 to -0.004, P = 0.031). Lumbar BMD is related with NAFLD in postmenopausal females. We suggest that postmenopausal women with NAFLD may have a higher risk of osteoporosis than those without.
Xanthakos, Stavra A; Jenkins, Todd M; Kleiner, David E; Boyce, Tawny W; Mourya, Reena; Karns, Rebekah; Brandt, Mary L; Harmon, Carroll M; Helmrath, Michael A; Michalsky, Marc P; Courcoulas, Anita P; Zeller, Meg H; Inge, Thomas H
Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m(2)). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Full Text Available Evidence suggests that nonalcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH are associated with an increased risk of chronic kidney disease (CKD. In this study we aimed to evaluate whether the severity of liver fibrosis estimated by NAFLD fibrosis score is associated with higher prevalence of CKD in individuals with NAFLD. To this end NAFLD fibrosis score and estimated glomerular filtration rate (eGFR were assessed in 570 White individuals with ultrasonography-diagnosed NAFLD. As compared with subjects at low probability of liver fibrosis, individuals at high and intermediate probability showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein, fibrinogen, uric acid and lower insulin-like growth factor-1 levels. Individuals at high and intermediate probability of liver fibrosis have lower eGFR after adjustment for gender, smoking, glucose tolerance status, homeostasis model assessment index of insulin resistance (HOMA-IR index, diagnosis of metabolic syndrome, statin therapy, anti-diabetes and anti-hypertensive treatments (P = 0.001. Individuals at high probability of liver fibrosis had a 5.1-fold increased risk of having CKD (OR 5.13, 95%CI 1.13-23.28; P = 0.03 as compared with individuals at low probability after adjustment for age, gender, and BMI. After adjustment for glucose tolerance status, statin therapy, and anti-hypertensive treatment in addition to gender, individuals at high probability of liver fibrosis had a 3.9-fold increased risk of CKD (OR 3.94, 95%CI 1.11-14.05; P = 0.03 as compared with individuals at low probability. In conclusion, advanced liver fibrosis, determined by noninvasive fibrosis markers, is associated with CKD independently from other known factors.
Uma Shankar Mishra
Full Text Available BACKGROUND Nonalcoholic steatohepatitis (NASH represents only a part of a wide spectrum of non-alcoholic fatty liver disease (NAFLD and its prevalence is only 2-3% in the general population. Diabetes mellitus increases the risk for severe necroinflammation. The diagnosis rests on the hallmark histological features. Liver biopsy is essential for positive diagnosis and prognostication of NASH. The aim of this study was to evaluate the correlation between NASH and risk factor like diabetes, BMI and other risk factors. MATERIALS AND METHODS 36 patients with histologically confirmed NASH with elevated liver aminotransferase and negative markers for other diseases admitted to our institution from Sept-2012 to August-2014, were included in the study, meeting our inclusion & exclusion criteria. Investigations were done & data was collected. Data were pooled & interpreted using standard statistical methods. RESULTS Twenty out of thirty-six patients had diabetes in our study i.e. 55.6% were diabetes. 22 out of 36 patients i.e. 61.1% had BMI >28 kg/m2 . the mean waist circumference in our study was 93.13 Cm. 15 out of 24 female patients i.e. 62.5% females had WC>88 cm and 8 out of 12 male patients i.e. 66.7% males had WC >102 cm., 20 out of 36 patients i.e. 55.6% patients fulfilled at least 3 out of 5 criteria and therefore had insulin resistance syndrome or metabolic syndrome. CONCLUSION Patients with NASH are typically asymptomatic unless cirrhosis develops. 97.22% patients were dyslipidaemics. NASH may be considered an additional features of insulin resistance & metabolic syndrome. Age, gender, waist circumference, BMI, ALT, AST: ALT ratio, serum triglyceride levels, HTN & BAAT score are independent predictors of NASH.
Pacifico, Lucia; Bonci, Enea; Marandola, Lidia; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio
To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue. Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P zonulin concentrations increased significantly with the severity of steatosis and the Spearman's coefficient revealed a positive correlation between zonulin values and steatosis (r = 0.372, P zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical significance. Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of
Full Text Available Border effects are very common in many finite signals analysis and processing approaches using convolution operation. Alleviating the border effects that can occur in the processing of finite-length signals using wavelet transform is considered in this paper. Traditional methods for alleviating the border effects are suitable to compression or coding applications. We propose an algorithm based on Fourier series which is proved to be appropriate to the application of time-frequency analysis of nonlinear signals. Fourier series extension method preserves the time-varying characteristics of the signals. A modified signal duration expression for measuring the extent of border effects region is presented. The proposed algorithm is confirmed to be efficient to alleviate the border effects in comparison to the current methods through the numerical examples.
Klein, Christopher; Olsson, Lisbeth; Rønnow, B.
The MIG1 gene was disrupted in a haploid laboratory strain (B224) and in an industrial polyploid strain (DGI 342) of Saccharomyces cerevisiae. The alleviation of glucose repression of the expression of MAL genes and alleviation of glucose control of maltose metabolism were investigated in batch...... cultivations on glucose-maltose mixtures. In the MIG1-disrupted haploid strain, glucose repression was partly alleviated; i.e., maltose metabolism was initiated at higher glucose concentrations than in the corresponding wild-type strain. In contrast, the polyploid Delta mig1 strain exhibited an even more...... stringent glucose control of maltose metabolism than the corresponding wild-type strain, which could be explained by a more rigid catabolite inactivation of maltose permease, affecting the uptake of maltose. Growth on the glucose-sucrose mixture showed that the polyploid Delta mig1 strain was relieved...
Forestry development in China has gained great achievements and made great progress in realizing sustainable forest management and alleviating global climate change. The main measures to mitigate greenhouse effects through the means of forestry development include afforestation to increase the forested area, fuel wood forest development, management improvement, wise utilization, international cooperation, investment increase, forest related scientific research, strengthening the forest law enforcement system. Climate change as well as how to alleviate the greenhouse effects is a hot topic at present. This paper describes the achievements of China`s forestry development and its role to alleviate the greenhouse effects, and puts forward the measures to mitigate greenhouse effects through the means of forestry development.
Karakalas, A.; Machairas, T.; Solomou, A.; Riziotis, V.; Saravanos, D.
Wind turbine rotor upscaling has entered a range of rotor diameters where the blade structure cannot sustain the increased aerodynamic loads without novel load alleviation concepts. Research on load alleviation using morphing blade sections is presented. Antagonistic shape memory alloy (SMA) actuators are implemented to deflect the section trailing edge (TE) to target shapes and target time-series relating TE movement with changes in lift coefficient. Challenges encountered by the complex thermomechanical response of morphing section and the enhancement of SMA transient response to achieve frequencies meaningful for aerodynamic load alleviation are addressed. Using a recently developed finite element for SMA actuators , actuator configurations are considered for fast cooling and heating cycles. Numerical results quantify the attained ranges of TE angle movement, the moving time period and the developed stresses. Estimations of the attained variations of lift coefficient vs. time are also presented to assess the performance of the morphing section.
Full Text Available Freezing of gait (FOG is a disabling gait disorder in parkinsonian patients characterized by the inability to initiate or continue locomotion. I herein present a 65-year-old man with Parkinson's disease who invented a unique method (foot loop band to alleviate FOG, which has not been previously described in the literature. The mechanisms to alleviate FOG include not only facilitating mechanical weight shift, but also restoring internal cueing and driving motor commands for gait initiation. This patient-invented maneuver may be recommended for patients having intractable FOG, because it is portable, cheap and safe.
Major economic crises tend to be followed by crises in subjective well-being. Following the financial and debt crises, politicians and social scientists have engaged in heated discussions of ways to alleviate such losses. In particular, should governments intervene more or less? This paper explores...... whether liberalizing economic institutions, a type of reform favoured by some economists, is likely to alleviate such loses. Estimating the effects of crises across European states 1975–2011 suggest that countries with relatively easy market regulations suffered smaller well-being losses....
Mishra, Pramod Kumar
Access to electricity is important for alleviation energy poverty in rural areas of developing countries. In spite of rural electrification schemes people in numerous villages do not have access to electricity because of inadequate and erratic power supply. The Jyotigram Yojana (Rural Lighting Scheme) of Gujarat in India transformed the rural electricity distribution scenario creating immense opportunities for socio-economic development. It shows how vision and political will can transcend the boundaries of technical and financial expertise and systemic rigidities, and facilitate successful adoption of simple but innovative approaches for alleviation of energy poverty and bringing about socio-economic development.
Yilmaz, Yusuf; Eren, Fatih; Yonal, Oya; Polat, Zulfikar; Bacha, Mohammad; Kurt, Ramazan; Ozturk, Oguzhan; Avsar, Erol
Background: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. Subjects and methods: We measured serum progranulin levels in 95 pa...
Sunny, Nishanth E.; Kalavalapalli, Srilaxmi; Bril, Fernando; Garrett, Timothy J.; Nautiyal, Manisha; Mathew, Justin T.; Williams, Caroline M.; Cusi, Kenneth
Elevated plasma branched-chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tricarboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperin...
Plutecki, Michal M.; Wierzbicka, Aldona; Socha, Piotr; Mulawka, Jan J.
The paper describes an innovative approach to discover new knowledge in non-alcoholic fatty liver disease (NAFLD). In order to determine the factors that may cause the disease a number of classification and attribute selection algorithms have been applied. Only those with the best classification results were chosen. Several interesting facts associated with this unclear disease have been discovered. All data mining computations were made in Weka environment.
Full Text Available Fluid and electrolyte status have a significant impact on physical performance and health. Pre-exercise recommendations cite the possibility of consuming beverages with high amounts of sodium. In this sense, non-alcoholic beer can be considered an effective pre-exercise hydration beverage. This double-blind, randomized study aimed to compare the effect of beer, non-alcoholic beer and water consumption before exercise on fluid and electrolyte homeostasis. Seven male soccer players performed 45 min of treadmill running at 65% of the maximal heart rate, 45 min after ingesting 0.7 L of water (W, beer (AB or non-alcoholic beer (NAB. Body mass, plasma Na+ and K+ concentrations and urine specific gravity (USG were assessed before fluid consumption and after exercise. After exercise, body mass decreased (p < 0.05 in W (−1.1%, AB (−1.0% and NAB (−1.0%. In the last minutes of exercise, plasma Na+ was reduced (p < 0.05 in W (−3.9% and AB (−3.7%, plasma K+ was increased (p < 0.05 in AB (8.5%, and USG was reduced in W (−0.9% and NAB (−1.0%. Collectively, these results suggest that non-alcoholic beer before exercise could help maintain electrolyte homeostasis during exercise. Alcoholic beer intake reduced plasma Na+ and increased plasma K+ during exercise, which may negatively affect health and physical performance, and finally, the consumption of water before exercise could induce decreases of Na+ in plasma during exercise.
Graffigna, Mabel Nora; Belli, Susana H; de Larrañaga, Gabriela; Fainboim, Hugo; Estepo, Claudio; Peres, Silvia; García, Natalia; Levalle, Oscar
to assess the presence of nonalcoholic fatty liver disease in patients with risk factors for this pathology (obesity, dyslipidemia, metabolic syndrome and diabetes type 2) and to determine the role of insulin, HOMA index, insulin-like growth factor-binding protein-1, sex hormone-binding globulin and plasminogen activator inhibitor type 1, as biochemical markers. Ninety-one patients with risk factors for nonalcoholic fatty liver disease were evaluated. Serum transaminases, insulin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 and plasminogen activator inhibitor type 1 were measured. The diagnosis of fatty liver was performed by ultrasonography and liver biopsies were performed to 31 subjects who had steatosis by ultrasonography and high alanine aminotransferase. Nonalcoholic fatty liver disease was present in 65 out of 91 patients (71,4%). Liver biopsy performed to 31 subjects confirmed nonalcoholic steatohepatitis. Twenty-five patients had different degrees of fibrosis. Those individuals with fatty liver had higher waist circumference, serum levels of triglycerides, insulin and HOMA index, and lower serum insulin-like growth factor-binding protein-1 concentration. The degree ofhepatic steatosis by ultrasonography was positively correlated to waist circumference, triglycerides, insulin and HOMA index (p<0,003; p<0,003; p<0,002 and p<0,001, respectively), and was negatively correlated to HDL-cholesterol and insulin-like growth factor-binding protein-1 (p<0,025 and p<0,018, respectively). We found a high prevalence of NAFLD in patients with risk factors, most of them overweight or obese. Although SHBG and PAI-1 have a closely relationship to insulin resistance, they did not show to be markers of NAFLD. Regardless of low IGFBP-1 levels associated with NAFLD, serum IGFBP-1 measure is less accessible than insulin and triglycerides levels, HOMA index and waist circumference. Moreover, it is not a better marker for NAFLD than the above
Castro-Sepulveda, Mauricio; Johannsen, Neil; Astudillo, Sebastián; Jorquera, Carlos; Álvarez, Cristian; Zbinden-Foncea, Hermann; Ramírez-Campillo, Rodrigo
Fluid and electrolyte status have a significant impact on physical performance and health. Pre-exercise recommendations cite the possibility of consuming beverages with high amounts of sodium. In this sense, non-alcoholic beer can be considered an effective pre-exercise hydration beverage. This double-blind, randomized study aimed to compare the effect of beer, non-alcoholic beer and water consumption before exercise on fluid and electrolyte homeostasis. Seven male soccer players performed 45 min of treadmill running at 65% of the maximal heart rate, 45 min after ingesting 0.7 L of water (W), beer (AB) or non-alcoholic beer (NAB). Body mass, plasma Na⁺ and K⁺ concentrations and urine specific gravity (USG) were assessed before fluid consumption and after exercise. After exercise, body mass decreased (p beer before exercise could help maintain electrolyte homeostasis during exercise. Alcoholic beer intake reduced plasma Na⁺ and increased plasma K⁺ during exercise, which may negatively affect health and physical performance, and finally, the consumption of water before exercise could induce decreases of Na⁺ in plasma during exercise.
Welcome, Mo; Pereverzev, Va
Glycemic allostasis is the process by which blood glucose stabilization is achieved through the balancing of glucose consumption rate and release into the blood stream under a variety of stressors. This paper reviews findings on the dynamics of glycemic levels during mental activities on fasting in non-alcohol users and alcohol users with different periods of abstinence. Referred articles for this review were searched in the databases of PubMed, Scopus, DOAJ and AJOL. The search was conducted in 2013 between January 20 and July 31. The following keywords were used in the search: alcohol action on glycemia OR brain glucose OR cognitive functions; dynamics of glycemia, dynamics of glycemia during mental activities; dynamics of glycemia on fasting; dynamics of glycemia in non-alcohol users OR alcohol users; glycemic regulation during sobriety. Analysis of the selected articles showed that glycemic allostasis during mental activities on fasting is poorly regulated in alcohol users even after a long duration of sobriety (1-4 weeks after alcohol consumption), compared to non-alcohol users. The major contributor to the maintenance of euglycemia during mental activities after the night's rest (during continuing fast) is gluconeogenesis.
Chu, Yu-Hua; Wang, Lee; Ko, Pei-Chieh; Lan, Shou-Jen; Liaw, Yung-Po
The association of betel nut with liver cirrhosis among alcohol drinkers has been clearly shown. However, very few studies have shown such an association among non-alcohol drinkers. The aim of this study was to assess the relationship between betel nut chewing and cirrhosis among non-alcohol drinkers. This study retrospectively analyzed data retrieved from the 2012 Adult Preventive Medical Services and the National Health Insurance Research Datasets in Taiwan. Participants' information included physical examination and lifestyle, alongside laboratory tests. Betel nut chewers were grouped into three categories: never, occasional and frequent. Diseases were diagnosed using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Initially, 1573024 adults aged 40 years and above who engaged in the free adult preventive medical services in 2012 were recruited. However, only 1065246 of them were included in the analysis. Chi-square test and logistic regression were used for the analyses. After multivariable adjustments, there were significant relationships between cirrhosis and betel nut chewing in both sexes (P-trend betel nut chewing and cirrhosis in both male and female non-alcohol drinkers. The risk of cirrhosis was greater in female than male chewers.
... unemployment or underemployment. 310.2 Section 310.2 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE SPECIAL IMPACT AREAS § 310.2 Pressing need; alleviation of unemployment or... Special Need. (b) For purposes of this part, excessive unemployment exists if the twenty-four (24) month...
Fanourakis, D.; Gebraegziabher, Habtamu; Li, Tao; Kambourakis, Emmanouil; Ligoxigakis, Eleftherios K.; Padadimitriou, Michael; Strataridaki, Argiro; Bouranis, Dimitrios; Fiorani, F.; Heuvelink, E.; Ottosen, Carl-Otto
The vase life sensitivity to mild desiccation (12% weight loss) was addressed in rose, together with alleviation possibilities. The postharvest longevity upon arrival or following mild desiccation was determined on eight cultivars, combined with several morpho-physiological traits. Mild desiccation
The entrepreneurial performance of women in developing countries is influenced by microfinance factors such as social capital. However, there are mixed findings on the effect of social capital on poverty alleviation. Thus, this study assessed the effect of social capital on self-employment, education, training and skills ...
In recent years, entrepreneurship has been gaining more prominence as a potential tool for solving poverty in developing countries. This paper mainly examines the relationship between farmer entrepreneurship and rural poverty alleviation in China by assessing the contribution of farm entrepreneurs towards overcoming poverty. Data were collected from 309 employees of farmer entrepreneurships in Guangxi Province through survey questionnaires. Structural equation modeling was used to conduct an analysis of the effects of three identified capabilities of farm entrepreneurs—economic, educational and knowledge, and socio-cultural capabilities—on attitude towards farmer entrepreneurship growth and the qualitative growth of farmer entrepreneurship and how these in turn affect rural poverty, using AMOS 21. The findings show that socio-cultural capability has the greatest influence on farmer entrepreneurship growth (β = 0.50, pentrepreneurship also more significantly impacts rural poverty (β = 0.69, pentrepreneurship growth. This study suggests that policy makers in China should involve more rural farmers in the targeted poverty alleviation strategies of the government by equipping rural farmers with entrepreneurial skills. This can serve as a sustainable, bottom-up approach to alleviating rural poverty in remote areas of the country. The study also extends the literature on the farmer entrepreneurship-rural poverty alleviation nexus in China, and this can serve as a lesson for other developing countries in the fight against rural poverty. PMID:29596517
W. Xian; Y. Chen; J. Chen; X. Luo; H. Shao
According to the overall requirements of ecological construction and environmental protection, rely on the national key ecological engineering, strengthen ecological environmental restoration and protection, improve forest cover, control soil erosion, construct important ecological security barrier in poor areas, inhibit poverty alleviation through ecological security in this area from environmental damage to the vicious cycle of poverty. Obviously, the dynamic monitoring of ecological securi...
Natural products are widespread for the alleviation and prevention of the risk factors of the metabolic syndrome and diabetes. We have shown that glucose, insulin, cholesterol, and hemoglobin A1c levels are all improved in people with type 2 diabetes following chromium supplementation in a double-b...
Full Text Available The effect of exogenous CaCl2 on photosystem I and II (PSI and PSII activities, cyclic electron flow (CEF, and proton motive force of tomato leaves under low night temperature (LNT was investigated. LNT stress decreased the net photosynthetic rate (Pn, effective quantum yield of PSII [Y(II], and photochemical quenching (qP, whereas CaCl2 pretreatment improved Pn, Y(II, and qP under LNT stress. LNT stress significantly increased the non-regulatory quantum yield of energy dissipation [Y(NO], whereas CaCl2 alleviated this increase. Exogenous Ca2+ enhanced stimulation of CEF by LNT stress. Inhibition of oxidized PQ pools caused by LNT stress was alleviated by CaCl2 pretreatment. LNT stress reduced zeaxanthin formation and ATPase activity, but CaCl2 pretreatment reversed both of these effects. LNT stress caused excess formation of a proton gradient across the thylakoid membrane, whereas CaCl2 pretreatment decreased the said factor under LNT. Thus, our results showed that photoinhibition of LNT-stressed plants could be alleviated by CaCl2 pretreatment. Our findings further revealed that this alleviation was mediated in part by improvements in carbon fixation capacity, PQ pools, linear and cyclic electron transports, xanthophyll cycles, and ATPase activity.
Qian, Linbo; Chen, Baoliang; Chen, Mengfang
Replacing biosilicon and biocarbon in soil via biochar amendment is a novel approach for soil amelioration and pollution remediation. The unique roles of silicon (Si)-rich biochar in aluminum (Al) phytotoxicity alleviation have not been discovered. In this study, the alleviation of Al phytotoxicity to wheat plants (root tips cell death) by biochars fabricated from rice straw pyrolyzed at 400 and 700 °C (RS400 and RS700) and the feedstock (RS100) were studied using a slurry system containing typical acidic soils for a 15-day exposure experiment. The distributions of Al and Si in the slurry solution, soil and plant root tissue were monitored by staining methods, chemical extractions and SEM-EDS observations. We found that the biological sourced silicon in biochars served dual roles in Al phytotoxicity alleviation in acidic soil slurry. On one hand, the Si particles reduced the amount of soil exchangeable Al and prevented the migration of Al to the plant. More importantly, the Si released from biochars synchronously absorbed by the plants and coordinated with Al to form Al-Si compounds in the epidermis of wheat roots, which is a new mechanism for Al phytotoxicity alleviation in acidic soil slurry by biochar amendment. In addition, the steady release of Si from the rice straw-derived biochars was a sustainable Si source for aluminosilicate reconstruction in acidic soil.
Bigman, D.; Srinivasan, P.V.
The paper presents a methodology for mapping poverty within national borders at the level of relatively small geographical areas and illustrates this methodology for India. Poverty alleviation programs in India are presently targeted only at the level of the state. All states includes, however, many