Background Postprandial hyperlipidaemia is known to be a high‐risk factor for atherosclerotic disease because of rapid and lasting accumulations of triglyceride‐rich lipoproteins and remnants. The ...Niemann‐Pick C1‐Like 1 (NPC1L1) protein acts as an intestinal cholesterol transporter and ezetimibe, which inhibits NPC1L1, has been used in patients with hypercholesterolaemia. We investigated effects of ezetimibe on fasting lipid and lipoprotein profiles and postprandial hyperlipidaemia in patients with type IIb hyperlipidaemia.
Materials and methods Ezetimibe 10 mg per day was administered in ten patients with type IIb hyperlipidaemia for 2 months, and lipid and lipoprotein profiles were examined during fasting and after an oral fat loading (OFL) test.
Results In the fasting state, ezetimibe significantly decreased not only total cholesterol, low density lipoprotein (LDL)‐cholesterol and apolipoproteinB‐100 (apoB‐100) levels but triglycerides (TG), apoB‐48 and remnant lipoprotein cholesterol (RemL‐C) levels. High performance liquid chromatography analysis showed that ezetimibe decreased cholesterol and TG levels in the very low density lipoprotein (VLDL) and LDL size ranges as well as apoB‐100 levels, suggesting a decrease in numbers of VLDL and LDL particles. After OFL, ezetimibe decreased the area under the curve for TG, apoB‐48 and RemL‐C. Ezetimibe decreased postprandial elevations of cholesterol and TG levels in the chylomicrons (CM) size range, suggesting that the postprandial production of CM particles was suppressed by ezetimibe.
Conclusions These findings suggest that ezetimibe improves fasting lipoprotein profiles and postprandial hyperlipidaemia by suppressing intestinal CM production in patients with type IIb hyperlipidaemia and such treatment may prove to be effective in reducing atherosclerosis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract A 39-year-old man was diagnosed with allopurinol-induced hepatic injury. He did not show any sign of hepatic encephalopathy, but his serum total bilirubin level was >40 mg/dL when he visited ...the local hospital. The therapeutic effects of initial medical treatments were transient, and both renal function and coagulation ability were gradually deteriorated. Four months after the onset of hepatic injury, he was referred to our hospital for the purpose of liver transplantation (LT). Although he was wasting and severely jaundiced, his consciousness level was not disturbed at all, with normal serum ammonia blood concentration before LT. Owing to allopurinol-induced severe cholestatic liver failure, living-donor LT (LDLT) was performed with the use of a right lobe graft from his younger brother. The explanted liver was extremely enlarged, with a weight of 2,480 g, and severely cholestatic. Microscopic findings were also compatible with drug-induced cholestatic liver injury. He was discharged from hospital 55 days after LDLT, whereas his renal dysfunction remained at 6 months after LT. There are 3 types of pathophysiology of drug-induced hepatotoxicity: hepatocellular, cholestatic, and mixed liver injury. Although allopurinol hepatotoxicity is rare, it can be severe and even fatal. This is the 1st case report of successful LDLT for a patient who had developed allopurinol-induced cholestatic liver failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
When considering treatment for chronic hepatitis B (CHB), it is important to discriminate between patients with persistent low HBV DNA and patients with active hepatitis, who may proceed to ...cirrhosis. In this study, we sought to identify mutations in patients expected to have persistent low HBV DNA and ultimately exhibit clearance of hepatitis B surface antigen (HBsAg).
Serum samples were obtained from 33 CHB genotype C patients, divided based on HBV DNA and alanine aminotransferase (ALT) levels following observation for >2 years: Group A (n=10), transient HBV DNA ≥5.0 log copies/mL and ALT ≥120 IU/L; Group B (n=11), persistent HBV DNA <5.0 and ALT <60; and Group C (n=12), persistent HBV DNA <4.0 and ALT <30. Full-length HBV sequences were compared among groups. Subsequently, 82 patients with CHB were evaluated for the I97L mutation and the additional mutation P79Q. We compared cumulative incidences of persistent low HBV DNA and HBsAg clearance in patients with or without I97L and P79Q by the Kaplan–Meier method.
Incidence of Core mutation I97L differed significantly among groups: A, 30% (3/10); B, 36.4% (4/11); C, 83.3% (10/12) (p = 0.021). Cumulative incidences of persistent low HBV DNA and HBsAg clearance were significantly higher in patients with I97L than in those with wild-type I97 (p = 0.003 and p = 0.016, respectively), and even higher in those with P79Q.
In patients with CHB, measurement of I97L and additional mutation P79Q would be useful for predicting persistent low HBV DNA, normal ALT, and HBsAg clearance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage ...in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint.
We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years).
Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63–4.46); liver-related mortality RR, 11.13 (95% CI, 4.15–29.84); liver transplant RR, 5.42 (95% CI, 1.05–27.89); and liver-related events RR, 12.78 (95% CI, 6.85–23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings.
In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.
Abstract Background There are few reports on the short- and long-term follow-up of endoscopic retrograde cholangiography (ERC) in adult patients with hepaticojejunostomy (HJS) stricture after ...living-donor liver transplantation (LDLT). Methods Nine LDLT recipients underwent ERC with the use of double-balloon endoscopy (DBE) for HJS stricture at Nagoya University Hospital. We assessed the rate of reaching biliary anastomosis, procedure success rate, procedure duration, complications, improvement in liver function test results, and biliary anastomosis patency. Results In total, 19 ERC procedures with the use of DBE were performed for 9 adult LDLT recipients with HJS stricture from June 2006 to September 2014. Balloon dilation with the use of DBE was successfully performed in 5 of the 9 patients during the 1st procedure. Of the 4 patients in whom DBE-ERC failed to be completed, 3 patients underwent 2nd procedures successfully. Liver function test results were significantly improved in the successful cases. Four patients underwent 2nd DBE-ERC for stricture recurrence at a mean time of 2.3 years after the 1st successful procedure. Of those, 2 patients required 3rd procedures for stricture recurrence after the 2nd procedure. Conclusions DBE-ERC is promising as a treatment for HJS stricture in adult LDLT recipients in the short term. However, the DBE-ERC procedure may have a considerable risk of restenosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
16.
Chemical treatment of carbon nanotubes Esumi, K.; Ishigami, M.; Nakajima, A. ...
Carbon (New York),
1996, 1996-00-00, Volume:
34, Issue:
2
Journal Article
Peer reviewed
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Some strains of Saccharomyces cerevisiae form a biofilm called a 'flor' on the surface of wine after ethanolic fermentation, but the molecular mechanism of flor formation by the wild-type flor strain ...involved in wine making is not clear. Previously, we found that expression of the C-terminally truncated form of NRG1 (NRG1sup(l-470)) on a multicopy plasmid increases the hydrophobicity of the cell surface, conferring flor formation on the non-flor laboratory strain. Here we show that in Ar5-H12, a wild-type flor haploid strain, flor formation is regulated by NRG1sup(l-470). Moreover, the disruptant of the wild-type flor diploid strain (deltaflo11/deltaflo11) show a weak ability to form the flor. The expression of FLOII is always high in the wild-type flor strain, regardless of carbon source. Thus FLO11 is primary factor for wild-type flor strains. Furthermore, the disruptant (deltaflo11) shows lower hydrophobicity of cell surface than the wild type. However, the hydrophobicity of the wild-type flor strains grown in ethanol medium was much higher than those grown in glucose medium. These results indicate that cell surface hydrophobicity is closely related to flor formation in wild-type flor yeasts.
Hydrogen sulfide (H2S) is recognized as a neuromodulator as well as neuroprotectant in the brain. H2S can be produced from cysteine by enzymes such as cystathionine beta-synthase. However, a ...mechanism for releasing H2S under physiologic conditions has not been identified. Here we show that H2S is released from bound sulfur, an intracellular store of sulfur, in neurons and astrocytes of mice and rats in the presence of physiologic concentrations of endogenous reducing substances glutathione and cysteine. The highest pH to release H2S from another sulfur store, acid-labile sulfur, which is localized mainly in mitochondria, is 5.4. Because mitochondria are not in the acidic condition, acid-labile sulfur may not be a physiologic source of H2S. Free H2S is immediately absorbed and stored as bound sulfur. Our novel method, using silver particles to measure free H2S, shows that free H2S is maintained at a low level in basal conditions. Alkalinization of the cytoplasm is required for effective release of H2S from bound sulfur, and this condition is achieved in astrocytes by the high concentrations of extracellular K+ that are normally present when nearby neurons are excited. These data present a new perspective on the regulation of H2S in the brain.
Mutations in two regions of hepatitis C virus (HCV) have been implicated in influencing response to interferon (IFN) therapy. Substitutions in the NS5A region of HCV have been associated with ...response to IFN therapy, and this region has been known as the IFN sensitivity‐determining region (ISDR). The mutations in the core region of HCV have also been reported to predict IFN response. The aim of this study was to investigate whether amino acid substitutions in the core region and ISDR among patients with HCV genotype 1b affect the response to IFN therapy. A total of 213 patients who completed IFN treatment were randomly selected. All patients received pegylated‐IFN‐alpha 2b once each week, plus oral ribavirin daily for 48 weeks. Of the 213 patients, 117 (54.9%) showed early virologic response (EVR), with HCV‐negativity, at 12 weeks. Factors related to EVR on multivariate analysis were non‐Gln70 and Leu91 in the core region, and ISDR mutant‐type. One hundred and two (47.9%) showed a sustained virologic response (SVR). SVR occurred more frequently in patients without Gln70 (55.4%) than in those with Gln70 (21.3%) (P < 0.0001). SVR was achieved in 43.6% of patients with wild‐type ISDR and 62.5% of patients with mutant‐type (P = 0.0227). Of the 34 patients who simultaneously had non‐Gln70 and mutant‐type ISDR, 26 (76.5%) achieved SVR. Factors related to SVR on multivariate analysis were non‐Gln70 and ISDR mutant‐type. In conclusion, amino acid substitutions in the core region and ISDR were useful for predicting the response to IFN in patients with HCV genotype 1b.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The anti-atherogenic effects of apolipoprotein (apo) E have been attributed to its ability to reduce plasma cholesterol level and to limit foam cell formation. The purpose of this study was to ...ascertain if apoE also may have cytostatic functions that could attenuate vascular occlusive diseases. Purified apoE inhibited smooth muscle cell migration directed to platelet-derived growth factor (PDGF) or oxidized LDL (oxLDL) (p < 0.0001). The purified apoE also suppressed PDGF- and oxLDL-induced smooth muscle cell proliferation (p < 0.001). These apoE inhibitory effects were not because of suppression of PDGF binding to its receptors on the smooth muscle cells, but was correlated with a significant reduction in agonist-stimulated mitogen-activated protein kinase activity (p < 0.01). ApoE also inhibited PDGF-induced cyclin D1 mRNA expression, suggesting that the apoE effect was mediated by growth arrest at the G0 to G1 phase. Taken together, these results suggest that apoE has cytostatic functions in the vessel wall and may protect against vascular diseases through inhibition of cell signaling events associated with growth factor-induced smooth muscle cell migration and proliferation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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