Preoperative planning should incorporate a determination of the specific haemostatic therapies to be used during and after surgery, including dosing regimens and whether continuous selleck screening library or bolus treatment will be used. It is often

helpful for a member of the HTC team to be present in the operating room (OR) to assist in communication between the OR staff and the patient/family and to provide on-site guidance regarding haemostatic management, if needed. The use of high-dose FVIII or FIX concentrates to overcome inhibitors in CHwI undergoing surgery, although ideal and measurable [8, 21], is often restricted to those with low-titre or low-responding inhibitors or those who have successfully achieved tolerance. Both bolus and continuous administration of replacement factor have been Roxadustat effectively used in this setting, although in patients with haemophilia B and inhibitors, the use of high doses of FIX may increase the risk for anaphylaxis [10]. In patients with

haemophilia A receiving FVIII replacement for surgery, an anamnestic increase in inhibitor titre may occur, necessitating a switch to bypassing therapy [22]. Although preoperative attempts to reduce the inhibitor titre using rituximab [9] and ITT [6] have been described, these treatments have limitations, most notably the time required for such regimens to take effect and, with immunosuppressive eliminative agents, the potential for susceptibility to infections. Bypassing agents are the haemostatic products of choice for patients with high-titre or high-responding inhibitors or those with haemophilia B and inhibitors. Each of the commercially available medchemexpress bypassing agents – recombinant activated FVII (rFVIIa; NovoSeven® RT; Novo Nordisk A/S, Bagsvaerd, Denmark) and activated

prothrombin complex concentrate (aPCC; FEIBA®, Factor Eight Inhibitor Bypassing Agent); Baxter Healthcare Corporation (Westlake Village, CA, USA) – have been successfully used for haemostatic coverage for surgery in both children and adults with CHwI, with comparable efficacy and safety. However, there are no evidence-based guidelines for the use of either agent in this setting. Recombinant FVIIa has a relatively short half-life of 2.7 h in adults and 1.3 h in children [23]. Optimal dosing remains uncertain. The choice of product for those with high-titre inhibitors is dependent on the age of the patient, prior exposure to plasma products, type of bleeding episode, volume-of-reconstitution cost, efficacy and safety. At most institutions, for patients who are plasma-naïve or for those with haemophilia B and inhibitors, rFVIIa is used to achieve rapid haemostasis (recombinant porcine FVIII may likewise be used for the same purpose in patients with haemophilia A and inhibitors who are plasma-naïve, when it becomes available). However, for patients with haemophilia A who have been previously exposed to plasma products, either aPCC or rFVIIa may be used [24].

Three primer pair sequences for siRNA–GLP-1R and negative control (Stealth Negative) were purchased from Invitrogen as shown in Table 1. Huh7 cells were transfected using Lipofectamine RNAiMAX reagent (Invitrogen)

following the manufacturer’s reverse transfection protocol. Cells were plated at 50% confluency and transfected with the siRNA sequences at 30 nM and maintained for 48 CH5424802 chemical structure hours. GLP-1R knockdown was confirmed by way of immunoblot analysis. Cell lysates were prepared and subjected to immunoblot analysis for GLP-1R, PDK1, AKT, and PKC-ζ. All data are presented as the mean ± standard error (SE). Statistical analysis was performed using Graphpad Instat 3 software (http://www.graphpad.com). Groups were compared using parametric tests

(paired Student t test or one-way analysis of variance with posttest following statistical standards). P < 0.05 was considered statistically significant. SCH 900776 purchase Western blot analysis revealed the presence of GLP-1R in Huh7 cells and primary human hepatocytes (Fig. 1A). As shown in Fig. 1B, there was a multifold increase of GLP-1R in Huh7 cells compared with preimmune serum-treated controls (P < 0.05). GLP-1R is internalized on stimulation by GLP-1 or exendin-4 (Fig. 2). This was first demonstrated by way of cell surface expression analysis (bioluminescence assay) (Fig. 2A). We then confirmed the microscopic findings by way of subcellular fractionation (Fig. 2B). This demonstrated that following MCE公司 GLP-1R exposure to its agonist, the membrane-bound fraction was reduced. Upon stimulation with either GLP-1 or exendin-4, there was a decrease in the amount of receptor seen on the cell membrane under confocal microcopy (Fig. 2C). These data suggest that there is loss of the receptor from the cell membrane. Both confocal and fluorescent imaging confirmed that GLP-1R is internalized. Fig. 2C (left panel) shows untreated cells in which GLP-1R (in green) is seen lining the cell membrane. On treatment with GLP-1 or exendin-4, the receptor (Fig. 2C, right panel)

was detected primarily in the cytoplasm rather than on the plasma membrane (yellow arrows). These data support the detection of internalization of the receptor by way of bioluminescence assay, which was also confirmed by subcellular fractionation analysis. To determine whether a physiologic endpoint of putative GLP-1 receptor signaling could be achieved, we used several approaches to explore whether there was a significant reduction in the cellular TG content following exendin-4 treatment. As seen on Oil Red O staining (Fig. 3A), following engorgement of Huh7 cells with palmitate and oleate, exendin-4 greatly reduced TG stores; this was further corroborated by TG quantitation (Fig. 3B).

Disruption of the epithelial barrier LY2109761 datasheet is often associated with the increase of cell shedding. This study aims to investigate the mechanisms how mucosal protectants maintain the integrity of intestinal epithelial barrier in

indomethacin-induced enteropathy by observing real-timely the gap density using confocal laser endomicroscopy (CLE). Methods: A method to evaluate real-timely the intestinal epithelial barrier damage after administration of indomethacin in rats were established using a new technique CLE by investigating the gap density in small intestine. Then the mucosal protectant teprenone and proton pump inhibitor rabeprazole were given by gavage before and after the administration of indomethacin. Then, the mechanisms of how these medicines affect the intestinal epithelial barrier were investigated by investigating gap density and TNF- α pathway. Results: Gaps could be clearly observed by CLE, Gap density increased after indomethacin administration. During this process, the expressions of TNF- α, NF-kB and Caspase-3 were up-regulated while the expressions of tight junction were down-regulated. Teprenone and rabeprazole could interfere in the damage process and protect the integrity of the epithelial

barrier. Conclusion: CLE can be more objective, accurate and real-time to INCB024360 ic50 investigate gap density. Teprenone and rabeprazole could prevent indomethacin-induced intestinal demage and improve the integrity of the epithelial barrier mediated by the intervention of TNF-α pathway. Key Word(s): 1. Epithelial barrier; 2. endomicroscopy; 3. Gap density; 4. TNF- α; Presenting Author: YING KIT LEUNG Corresponding Author: YING KIT LEUNG Affiliations: Precious Blood Hospital Objective: We have previously demonstrated that the vasculature in villi are of the reverse fountain pattern, one-uo, one down pattern or the reticular pattern. Whether these pertain to a arteriole-venule pattern

or mainly comprise of capillaries is not yet confirmed 上海皓元医药股份有限公司 scientifically. The aim of this study is to visualize how blood elements flow in the vasculature of the villi in a living human under sedation, hence infer the basic characteristic of such blood vessels. Methods: Ten subjects underwent colonoscopy and probe-based confocal laser endomicroscopy (pCLE) were included into the study. The indications of the procedure being: inflammatory bowel disease, familial adenomatous polyposis, colonic polyps and abdominal pain. Fluorescein was injected after the small intestine was entered, and the villi examined with pCLE which took video images at 12/sec. The velocities of cellular movement in the vessels were determined during playback of the videos, and compared with similar measurement of flow around colonic crypts. Results: Blood elements of diameter around 7–10 microns, move in the vessels in an episodic manner.

[2] Especially, NSAID use is associated with increased risk of developing toxicity not only in the upper but also in the lower GI tract.[3] The long-term uses of NSAID have side-effects such as GI mucosal injury, and serious complications can lead to mortality in some elderly

check details patients.[4] The severity of gastric mucosal injury by NSAIDs is associated with the loss of mucosal integrity, gastric mucosal bleeding, reduction in inherent anti-oxidant defense of gastric mucosa, apoptosis of mucosal cells, inhibition of cell renewal, and migration of cells of gastric pits to the damaged epithelial lining.[5, 6] Therefore, vigorous efforts are being done in discovering safer NSAID molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators to reduce the side-effects associated

with long-term therapies. Because gastric mucosal damages are a common adverse effect of traditional NSAIDs, patients at risk should receive prevention therapies. Current prevention DAPT supplier strategies in patients who need NSAIDs should also take into account the presence of cardiovascular risk factors, as selective COX-2 inhibitors (coxibs) and probably most traditional NSAIDs increase the incidence of serious cardiovascular events. Patients without risk factors should be treated with traditional NSAIDs, whereas patients at risk may receive co-therapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib alone.[7] Patients with risk factors requiring anti-inflammatory drugs may be prescribed a gastroprotectant such as misoprostol, or anti-secretory agents. Selective coxibs, such as celecoxib, became popular because they are as effective as conventional agents in reducing pain and improving physical functioning in people with arthritis, and are associated with fewer gastric adverse events. In addition to selected pharmacological

agents, botanical and medicinal plant extracts are also being investigated. Indomethacin is an indol derivative, NSAID with anti-inflammatory, 上海皓元 analgesic, and antipyretic effects. Indomethacin became the first-choice drug to produce an experimental ulcer model as a result of having a higher ulcerogenic potential than other NSAIDs.[8] There have been several reports about the ulcerogenic mechanism of indomethacin. It has been suggested that indomethacin induces gastric damage via inhibiting the release of protective factors like COX-1, prostaglandin E2 (PGE2), bicarbonate, and mucus, accompanied with increasing aggressive factors like acid and increasing oxidant parameters while decreasing anti-oxidant parameters. Therefore, indomethacin-induced gastric damage model as potent inducer of gastric ulcer is frequently used to study the antiulcer activity of certain drugs. Garlic is one of the oldest medicinal plants and is well recognized for its diverse health benefits. Raw garlic has a relatively low bioactive material content.

[2] Especially, NSAID use is associated with increased risk of developing toxicity not only in the upper but also in the lower GI tract.[3] The long-term uses of NSAID have side-effects such as GI mucosal injury, and serious complications can lead to mortality in some elderly

Poziotinib mw patients.[4] The severity of gastric mucosal injury by NSAIDs is associated with the loss of mucosal integrity, gastric mucosal bleeding, reduction in inherent anti-oxidant defense of gastric mucosa, apoptosis of mucosal cells, inhibition of cell renewal, and migration of cells of gastric pits to the damaged epithelial lining.[5, 6] Therefore, vigorous efforts are being done in discovering safer NSAID molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators to reduce the side-effects associated

with long-term therapies. Because gastric mucosal damages are a common adverse effect of traditional NSAIDs, patients at risk should receive prevention therapies. Current prevention Selleck R788 strategies in patients who need NSAIDs should also take into account the presence of cardiovascular risk factors, as selective COX-2 inhibitors (coxibs) and probably most traditional NSAIDs increase the incidence of serious cardiovascular events. Patients without risk factors should be treated with traditional NSAIDs, whereas patients at risk may receive co-therapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib alone.[7] Patients with risk factors requiring anti-inflammatory drugs may be prescribed a gastroprotectant such as misoprostol, or anti-secretory agents. Selective coxibs, such as celecoxib, became popular because they are as effective as conventional agents in reducing pain and improving physical functioning in people with arthritis, and are associated with fewer gastric adverse events. In addition to selected pharmacological

agents, botanical and medicinal plant extracts are also being investigated. Indomethacin is an indol derivative, NSAID with anti-inflammatory, 上海皓元医药股份有限公司 analgesic, and antipyretic effects. Indomethacin became the first-choice drug to produce an experimental ulcer model as a result of having a higher ulcerogenic potential than other NSAIDs.[8] There have been several reports about the ulcerogenic mechanism of indomethacin. It has been suggested that indomethacin induces gastric damage via inhibiting the release of protective factors like COX-1, prostaglandin E2 (PGE2), bicarbonate, and mucus, accompanied with increasing aggressive factors like acid and increasing oxidant parameters while decreasing anti-oxidant parameters. Therefore, indomethacin-induced gastric damage model as potent inducer of gastric ulcer is frequently used to study the antiulcer activity of certain drugs. Garlic is one of the oldest medicinal plants and is well recognized for its diverse health benefits. Raw garlic has a relatively low bioactive material content.

A recent study dedicated to the analysis of O-linked glycans on VWF Small molecule library molecular weight revealed some interesting details regarding these glycans [21]. First, about one quarter of the T-antigen structures contained di-sialyl structures, indicating that terminal Gal or GalNAc residues are capped with two rather than one sialic acid. Second, a small portion of the O-linked carbohydrates (∼0.8% of all

glycans corresponding to 1 per 10 monomers) is characterized by the presence of ABO blood group structure. Inhibition of the enzyme GlcNAc phosphotransferase, which is responsible for the attachment of the precursor N-glycan structure to the protein backbone, results in a complete inhibition of initial dimerization of VWF protomers and subsequent

targeting to the Golgi [22]. Thus, N-linked glycosylation is indeed an important process to facilitate the production of multimerized VWF molecules. The notion that mutation of the asparagine residue at position 2546 is associated with severe VWD (type 3) supports this view. By contrast, expression of VWF in CHO-cells permitting selective suppression 3-MA concentration of O-linked glycosylation allowed the secretion of fully multimerized VWF molecules [23]. Apparently, O-linked glycosylation is of less relevance for the assembly and secretion of VWF multimers. Whether and how glycan structures affect MCE VWF function is unclear. Opposite results regarding ristocetin-dependent activity of VWF treated with sialidases and other carbohydrate-removing enzymes have been reported (for review see [24]). Of course, these data should be interpreted with care, because not only VWF–platelet interactions but VWF-ristocetin interactions can also be affected upon treatment with these enzymes. This complication was avoided upon testing of sialidase-treated VWF in perfusion assays using different adhesive surfaces [25,26]. Enhanced platelet

adhesion was observed in these studies, indicating that the sialic acid residues negatively modulate VWF-platelet interactions. Interestingly, hypo-sialylation of VWF may occur under some pathological conditions, for instance, in precapillary pulmonary hypertension and upon exposure to sialidase activity in the circulation following micobiological infection [27,28]. Of note, hypo-sialylated VWF molecules are rapidly cleared via ASGPR [28–30], thereby preventing the presence of too high levels of overly-active VWF molecules under such conditions. Sialylation of its carbohydrates also affects the susceptibility of VWF to proteolytic degradation. Whereas the presence of sialic acids protects against degradation by unidentified plasma proteases, it renders the molecule more sensitive to degradation by the VWF cleaving protease ADAMTS13 [31,32].

Overall, 56% of JQ1 manufacturer total costs were HCV-related and this proportion increased with disease severity (46%, 57%, and 71% for patients with NCD, CC, and ESLD, respectively). A breakdown of total medical costs by disease severity showed that the largest cost components were inpatient costs for those with ESLD and ambulatory costs for those with CC and NCD (Table 4). Inpatient costs comprised 62% of all medical costs for patients with ESLD compared to 38% and 33% for patients with NCD and CC, respectively. All medical cost components were significantly higher for those with ESLD when compared to those with NCD, but only ambulatory costs were significantly higher for those with CC when compared to those with NCD (Table

4). Among patients with ESLD the highest total mean healthcare costs were incurred by patients who underwent OLT ($12,087.12 find more versus $4,393.81 PPPM in patients who had not undergone OLT, P < 0.001; Supporting Table S2) and among those with HCC ($9,378.05 versus $4,254.07 PPPM in patients without ESLD, P < 0.001; Supporting Table S2). Both medical and pharmacy costs were significantly higher in patients with OLT and HCC compared with all other patients with ESLD.

Patients with HCC and PHTN also had significantly higher total healthcare costs than those with HCC and without PHTN ($10,790.51 versus $8,233.95 PPPM, respectively, P = 0.004; Supporting Table S2). The significant difference in total medical costs in this subgroup was associated with significantly higher ambulatory

medical costs, with no significant differences in all other cost components included in the analysis. After adjustment for demographic characteristics, comorbidities, baseline healthcare utilization, and treatments, there were statistically significant differences in incremental cost ratios for all-cause healthcare costs between liver disease severity groups (Table 5). Patients with CC and ESLD were estimated to have total healthcare costs that were 1.40-fold higher (cost ratio 1.40; 95% CI 1.31-1.49) and 3.33-fold higher (cost ratio 3.33; 95% CI 3.12-3.56), respectively, than those for patients with NCD. The estimated cost ratios were also significantly higher for both medical costs and pharmacy costs for patients with CC and ESLD when compared with patients with NCD (Table 5). Other factors that MCE公司 were found to be statistically significantly associated with healthcare costs in this model included age 18-34 years (cost ratio 1.40; 95% CI 1.16-1.69) and age >65 years (cost ratio 0.72; 95% CI 0.62-0.83) as compared with the reference category of 35-44 years, male gender (cost ratio 1.164 versus female gender; 95% CI 1.11-1.22), an index year of 2010 relative to 2003 (cost ratio 1.270; 95% CI 1.10-1.47), baseline Charlson comorbidity score (cost ratio 1.08; 95% CI 1.05-1.10), HIV coinfection (cost ratio 1.75; 95% CI 1.49-2.05), a diagnosis of cancer (other than HCC, superficial skin cancer or cancer in situ) (cost ratio 1.13; 95% CI 1.06-1.

0±0.5 to 1.21±0.5. In the 31 cases with no change in fibrosis, WFA-M2BP was also unchanged (0.98±0.50.92±0.4). In the 36 cases in which fibrosis improved, WFA-M2BP was significantly reduced (1.1±0.50.8±0.3; p<0.05). [Conclusion] Assessment of WFA-M2BP in NAFLD was considered useful in predicting progression of fibrosis and histological changes in NASH, as well as therapeutic effects. Specially, WFA-M2BP is useful predicting a Burn out NASH and future of HCC with NASH. Disclosures: The following people have nothing to disclose: Miwa Kawanaka, Ken Nishino, Jun Nakamura, Takahito Oka, Noriyo Urata, Daisuke Goto, Mitsuhiko Suehiro, Hirofumi Kawamoto, Gotaro Yamada Introduction:

X-396 datasheet Non-alcoholic steatohepatitis http://www.selleckchem.com/products/ly2606368.html (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) and an increasingly common cause of end-stage liver disease. While the pathogenesis of NASH is yet to be fully elucidated, recently 25-hydroxyvitamin D [25(OH)D] level has been purported to be independently

associated with the severity of liver histology in NASH. We therefore assessed any association between 25(OH)D level and liver histology in patients with biopsy-proven NASH. Methods: 35 patients with biopsy-proven NASH and recent 25(OH)D level within 4 months of liver biopsy were studied. Liver histology was assessed by a single pathologist using the NAFLD Activity Score (NAS) and Brunt fibrosis stage. Season of 25(OH)D level and use of vitamin D supplementation was noted. Recent anthropometric data, blood tests and liver

stiffness measurement (LSM) via transient elastography were obtained, with FIB-4 and NAFLD Fibrosis Score (NAS) calculated. Univariate and multivariate analysis was performed. Results: Mean age was 52.8 ± 9.6 years, with 18 (51.4%) male and 21 (60%) diabetic patients. Mean 25(OH)D level was 64.0 ± 28.0 nmol/L with 57.1% of 25(OH)D levels measured during Summer/Autumn months and 6 patients (17.1%) using vitamin D supplements. Mean liver biopsy length was 15.2 ± 3.5 mm with a median NAS of 5 and hepatocellular ballooning present in 97.1% (n=34) of patients. MCE Fibrosis stage prevalence was: F1 40.0% (n=14), F2 31.4% (n=11), F3 22.9% (n=8) and F4 5.7% (n=2). Mean 25(OH)D level was not associated with either NAS (OR 1.00, 95% CI 0.98-1.02; P=0.78), fibrosis stage (OR 1.00, 95% CI 0.98-1.02; P=0.89) or advanced (F3/4) fibrosis (OR 1.02, 95% CI 0.99-1.04; P=0.24), irrespective of whether patients on vitamin D supplementation were included in analysis. Predictors of liver histology on multivariate analysis are shown in Table 1. Conclusion: Mean 25(OH)D level appears to not be associated with either NAS or fibrosis stage in NASH. Further study on the impact of vitamin D supplementation on these parameters is warranted. Disclosures: Matthew T. Kitson – Consulting: MSD, Roche; Grant/Research Support: MSD; Speaking and Teaching: Janssen-Cilag Stuart K.

0±0.5 to 1.21±0.5. In the 31 cases with no change in fibrosis, WFA-M2BP was also unchanged (0.98±0.50.92±0.4). In the 36 cases in which fibrosis improved, WFA-M2BP was significantly reduced (1.1±0.50.8±0.3; p<0.05). [Conclusion] Assessment of WFA-M2BP in NAFLD was considered useful in predicting progression of fibrosis and histological changes in NASH, as well as therapeutic effects. Specially, WFA-M2BP is useful predicting a Burn out NASH and future of HCC with NASH. Disclosures: The following people have nothing to disclose: Miwa Kawanaka, Ken Nishino, Jun Nakamura, Takahito Oka, Noriyo Urata, Daisuke Goto, Mitsuhiko Suehiro, Hirofumi Kawamoto, Gotaro Yamada Introduction:

XL765 supplier Non-alcoholic steatohepatitis Selinexor (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) and an increasingly common cause of end-stage liver disease. While the pathogenesis of NASH is yet to be fully elucidated, recently 25-hydroxyvitamin D [25(OH)D] level has been purported to be independently

associated with the severity of liver histology in NASH. We therefore assessed any association between 25(OH)D level and liver histology in patients with biopsy-proven NASH. Methods: 35 patients with biopsy-proven NASH and recent 25(OH)D level within 4 months of liver biopsy were studied. Liver histology was assessed by a single pathologist using the NAFLD Activity Score (NAS) and Brunt fibrosis stage. Season of 25(OH)D level and use of vitamin D supplementation was noted. Recent anthropometric data, blood tests and liver

stiffness measurement (LSM) via transient elastography were obtained, with FIB-4 and NAFLD Fibrosis Score (NAS) calculated. Univariate and multivariate analysis was performed. Results: Mean age was 52.8 ± 9.6 years, with 18 (51.4%) male and 21 (60%) diabetic patients. Mean 25(OH)D level was 64.0 ± 28.0 nmol/L with 57.1% of 25(OH)D levels measured during Summer/Autumn months and 6 patients (17.1%) using vitamin D supplements. Mean liver biopsy length was 15.2 ± 3.5 mm with a median NAS of 5 and hepatocellular ballooning present in 97.1% (n=34) of patients. 上海皓元医药股份有限公司 Fibrosis stage prevalence was: F1 40.0% (n=14), F2 31.4% (n=11), F3 22.9% (n=8) and F4 5.7% (n=2). Mean 25(OH)D level was not associated with either NAS (OR 1.00, 95% CI 0.98-1.02; P=0.78), fibrosis stage (OR 1.00, 95% CI 0.98-1.02; P=0.89) or advanced (F3/4) fibrosis (OR 1.02, 95% CI 0.99-1.04; P=0.24), irrespective of whether patients on vitamin D supplementation were included in analysis. Predictors of liver histology on multivariate analysis are shown in Table 1. Conclusion: Mean 25(OH)D level appears to not be associated with either NAS or fibrosis stage in NASH. Further study on the impact of vitamin D supplementation on these parameters is warranted. Disclosures: Matthew T. Kitson – Consulting: MSD, Roche; Grant/Research Support: MSD; Speaking and Teaching: Janssen-Cilag Stuart K.

It is also possible that there is a temporal dissociation between steatosis and insulin resistance, so that IHTG accumulation is secondary to a primary defect in skeletal muscle insulin action by diverting ingested carbohydrates away from muscle glycogen storage to DNL.36 Calorie restriction and weight loss is an effective therapy for obese patients with NAFLD. A marked decrease in IHTG content and improvement in hepatic insulin sensitivity occurs very rapidly, within 48 hours of calorie restriction (≈1,100 kcal/day diet).88 A comprehensive

review of 14 studies that evaluated the effect of lifestyle weight loss therapy on NAFLD/nonalcoholic

steatohepatitis,89 and data from recent prospective diet intervention studies,88, 90 found that a 5% to 10% weight loss X-396 nmr improved liver biochemistries, liver histology CHIR99021 (steatosis and inflammation), and IHTG content in conjunction with an increase in hepatic and skeletal muscle insulin sensitivity and a decrease in hepatic VLDL-TG secretion rate.91 Bariatric surgery is the most effective available weight loss therapy. There has been concern that the large and rapid weight loss, induced by bariatric surgery, can actually worsen NAFLD by increasing hepatic inflammation and fibrosis.92 However, data from more recent surgical series suggest that weight loss induced by bariatric surgery decreases steatosis, inflammation, and fibrosis.93, 94 In addition, bariatric surgery induced weight loss has considerable

beneficial metabolic effects in the liver manifested by a decrease in (1) hepatic glucose production, (2) hepatic VLDL-triglyceride secretion rate, and (3) hepatic gene expression of factors that regulate hepatic inflammation and fibrogenesis.95 These data suggest that bariatric surgery–induced weight loss is an effective therapy for NAFLD in patients with morbid obesity by normalizing the metabolic abnormalities involved in the pathogenesis and pathophysiology of NAFLD and by preventing the progression of hepatic inflammation 上海皓元医药股份有限公司 and fibrosis. The effect of overfeeding on IHTG content and metabolic function has not been carefully studied in human subjects. Data from a study conducted in rodents suggest that overfeeding first has a metabolic effect on the liver followed by an effect on muscle; insulin resistance in the liver was observed after 3 days and in muscle after 7 days of overfeeding.96 Four weeks of overfeeding in lean men and women, designed to cause a 5% to 15% increase in body weight, resulted in a significant increase in IHTG content (from 1.1% to 2.