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1.  Automated measurement method for the determination of vitamin E in plasma lipoprotein classes 
Scientific Reports  2014;4:4086.
In a subendothelial space of atherosclerotic arteries, apolipoprotein B-containing lipoproteins are accumulated and oxidized, and the oxidized lipoproteins promote macrophage foam cell formation. Therefore, the analysis of vitamin E, a major antioxidant in lipoproteins, is important for understanding atherosclerotic pathogenesis. A new method for the automated measurement of vitamin-E (γ- and α-tocopherols) in plasma HDL, LDL, and VLDL was established by using anion-exchange-chromatography for separation of lipoproteins, reverse-phase-chromatography for separation of γ- and α-tocopherols in each of lipoproteins, and fluorescent detection. The within-day assay and between-day assay coefficients of variation for lipoprotein tocopherol levels were 4.73–12.84% and 7.00–14.73%, respectively. The γ- and α-tocopherol/cholesterol ratios of VLDL were higher in healthy plasma than in plasma of untreated patients with dyslipidemia, but the ratios of LDL and HDL were not different. This new estimated method can provide the reliable data of lipoprotein vitamin-E and would be useful for the clinical settings.
doi:10.1038/srep04086
PMCID: PMC3923214  PMID: 24522390
2.  Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C 
AIM: To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon α plus ribavirin for chronic hepatitis C.
METHODS: Five hundred and sixty-one Japanese patients with hepatitis C virus genotype 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction. Factors influencing significant anemia (hemoglobin concentration < 10.0 g/dL at week 4 of treatment) and significant hemoglobin decline (declining concentrations > 3.0 g/dL at week 4) were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors.
RESULTS: Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline: hemoglobin decline at week 2 [P = 3.29 × 10-17, odds ratio (OR) = 7.54 (g/dL)], estimated glomerular filtration rate [P = 2.16 × 10-4, OR = 0.962 (mL/min/1.73 m2)], rs1127354 (P = 5.75 × 10-4, OR = 10.94) and baseline hemoglobin [P = 7.86 × 10-4, OR = 1.50 (g/dL)]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia.
CONCLUSION: Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.
doi:10.3748/wjg.v18.i41.5879
PMCID: PMC3491594  PMID: 23139603
Chronic hepatitis C virus infection; Ribavirin; Pegylated interferon α; Prediction model; Hemolytic anemia; Single nucleotide polymorphism
3.  Aseptic spondylodiscitis in a patient with polymyalgia rheumatica 
BMJ Case Reports  2009;2009:bcr02.2009.1555.
doi:10.1136/bcr.02.2009.1555
PMCID: PMC3029872  PMID: 21709837
5.  A mutation of the start codon in the X region of hepatitis B virus DNA in a patient with non-B, non-C chronic hepatitis 
World Journal of Hepatology  2011;3(2):56-60.
There are cases of hepatitis involving occult hepatitis B virus (HBV) infection in which, even though the HB surface antigen (HBsAg) is negative, HBV-DNA is detected by a polymerase chain reaction (PCR). We conducted a sequence analysis of the entire HBV region in a case of non-B non-C chronic hepatitis in a 46-year-old female. A diagnosis of non-B non-C chronic hepatitis was made. Although HBV markers, such as HBs antibody (anti-HBs), anti-HBc, HBeAg and anti-HBe, were negative, HBV-DNA was positive. Nested PCR was performed to amplify the precore region of HBV-DNA and all remaining regions by long nested PCR. Sequence analysis of the two obtained bands was conducted by direct sequencing. Compared with the control strains, the ATG (Methionine) start codon in the X region had mutated to GTG (Valine). It is assumed that a mutation at the start codon in the X region may be the reason why HBV markers are negative in some cases of hepatitis that involve occult HBV infection.
doi:10.4254/wjh.v3.i2.56
PMCID: PMC3060996  PMID: 21423595
Hepatitis B virus; X region; Mutation; Non-B non-C chronic hepatitis; Occult infection
6.  Peginterferon and ribavirin treatment for hepatitis C virus infection 
Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.
doi:10.3748/wjg.v17.i4.419
PMCID: PMC3027008  PMID: 21274371
Pegylated interferon α; Ribavirin; Chronic hepatitis C virus infection; Difficult-to-treat patient; Individualized treatment; Response-guided therapy; Specifically targeted antiviral therapy for hepatitis C virus
7.  A molecular mechanism for diacylglycerol-mediated promotion of negative caloric balance 
Aims
A substitution of diacylglycerol (DAG) oil for triacylglycerol (TAG) oil in diet has been reported to reduce body fat and body weight, possibly by increasing postprandial energy expenditure (EE). We have previously studied plasma serotonin, which increases EE and exists in the small intestine, in individuals who ingested TAG and DAG oil, and found that DAG ingestion elevates plasma serotonin levels by about 50% compared with TAG ingestion. We studied the molecular mechanisms for DAG-mediated increase in serotonin and EE.
Methods
We studied effects of 1-monoacylglycerol and 2-monoacylglycerol, distinct digestive products of DAG and TAG, respectively, on serotonin release from the Caco-2 cells (the human intestinal cell line, n = 8). Further, we studied effects of 1- and 2-monoacylglycerol, and serotonin on expression of mRNA associated with β-oxidation, FA metabolism, and thermogenesis, in the Caco-2 cells (n = 5).
Results
1-monoacylglycerol (100 μM 1-monooleyl glycerol [1-MOG]) significantly increased serotonin release from the Caco-2 cells compared with 2-monoacylglycerol (100 μM 2-MOG) by 36.6%. Expression of mRNA of acyl-CoA oxidase (ACO), fatty acid translocase (FAT), and uncoupling protein-2 (UCP-2) were significantly higher in 100 μM 1-MOG-treated Caco-2 cells than 100 μM 2-MOG-treated cells by 12.8%, 23.7%, and 35.1%, respectively. Further, expression of mRNA of ACO, medium-chain acyl-CoA dehydrogenase, FAT, and UCP-2 were significantly elevated in serotonin (400 nM)-treated Caco-2 cells compared with cells incubated without serotonin by 28.7%, 30.1%, and 39.2%, respectively.
Conclusions
Our study demonstrated that 1-monoacylglycerol, a digestive product of DAG, increases serotonin release from the Caco-2 cells, and enhances expression of genes associated with β-oxidation, FA metabolism, and thermogenesis, and that serotonin increases expression of these genes, proposing a novel molecular mechanism for DAG-mediated promotion of negative caloric balance.
PMCID: PMC3047988  PMID: 21437070
diacylglycerol; energy expenditure; intestine; serotonin; triacylglycerol
8.  Clinical, radiological, and biochemical characteristics in patients with diseases mimicking polymyalgia rheumatica 
To find out clues to differentiate between polymyalgia rheumatica (PMR) and other diseases that mimic PMR. We studied Japanese patients with PMR (n = 7), pseudogout (n = 1), remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome (n = 1), and post-infectious polyarthritis (n = 1). The distribution of inflammation in patients was evaluated using a gallium-67 scintigraphy. We measured serum C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), and vascular endothelial growth factor (VEGF) in patients before and after treatment. Further, we compared the clinical course of PMR with that of other diseases that mimic PMR. Patients with pseudogout, RS3PE syndrome, post-infectious polyarthritis manifested similar changes in scintigraphic findings and serum CRP, MMP-3, and VEGF levels to PMR before the treatment. A significant reduction in serum CRP levels at one week after use of nonsteroidal anti-inflammatory drugs (NSAIDs) is a good clue to differentiate pseudogout and post-infectious polyarthritis from PMR. Chondrocalcinosis in the radiographs of joints is also effective to differentiate pseudogout from PMR. A small reduction of CRP levels after NSAIDs use and promptly ameliorated CRP and symptoms by a low-dose steroid therapy, which was commonly observed in patients with PMR, were also found in a patient with RS3PE syndrome. Pitting edema of the back of hands and gallium uptake in metacarpophalangeal (MCP) joints were useful to differentiate RS3PE syndrome from PMR. In conclusion, pseudogout, RS3PE syndrome, post-infectious polyarthritis should be included in the spectrum of diseases mimicking PMR. A promptly decreased serum CRP level by NSAIDs is a good clue to differentiate pseudogout and post-infectious polyarthritis from PMR. Pitting edema of the back of hands and symmetric gallium uptake in MCP joints are characteristic for RS3PE syndrome.
PMCID: PMC2762363  PMID: 19851514
gallium-67 scintigraphy; polymyalgia rheumatica; pseudogout; post-infectious polyarthritis; RS3PE syndrome
9.  Myositis, Vasculitis, Hepatic Dysfunction in Adult-Onset Still's Disease 
Case Reports in Medicine  2009;2009:504897.
Although hepatic dysfunction is common in adult-onset Still's disease (AOSD), sometimes it is difficult to differentiate hepatic dysfunction due to AOSD itself from drug-induced hepatic dysfunction. Further, myalgia often occurs in patients with AOSD; however, AOSD patients complicated with myositis are rare. We report a 43-year-old Japanese man with AOSD who developed myositis and hepatic dysfunction which were deteriorated by multiple nonsteroidal antiinflammatory drugs (NSAIDs) and were dramatically ameliorated by a low-dose steroid therapy. A skin biopsy of salmon pink rash which is characteristic for AOSD showed leukocytoclastic vasculitis, and the markers for vasculitis, plasma von Willebrand factor, and vascular endothelial growth factor levels were elevated in this patient, suggesting an association between AOSD and systemic vasculitis.
doi:10.1155/2009/504897
PMCID: PMC2729264  PMID: 19718245
10.  Antihypertensive effects of astaxanthin 
Astaxanthin is a biological antioxidant naturally found in a wide variety of aquatic living organisms, and has shown various pharmacological activities, such as anti-inflammatory and antidiabetic activities. A recent study reported that the administration of astaxanthin induced a significant reduction in blood pressure and delayed the incidence of stroke in stroke-prone spontaneously hypertensive rats, suggesting that astaxanthin also has antihypertensive effect. In a study using aortic rings of spontaneously hypertensive rats, astaxanthin induced a significant reduction of the contractile responses of the aorta to α-adrenergic receptor agonist and angiotensin II, which may contribute to the antihypertensive effect of astaxanthin. In a histopathological study, astaxanthin decreased coronary artery wall thickness compared with the control, indicating the possibility that astaxanthin ameliorates hypertension-induced vascular remodeling. Astaxanthin has anti-inflammatory, antidiabetic, antihypertensive, and antioxidative activities; therefore, we should perform further studies to elucidate an antiatherogenic effect of astaxanthin.
PMCID: PMC3172056  PMID: 21949609
astaxanthin; antioxidant; antihypertensive effect; atherosclerosis
11.  A simple hepatic cyst with elevated serum and cyst fluid CA19-9 levels: a case report 
Introduction
Simple hepatic cysts rarely cause symptoms, however, occasionally they become symptomatic due to mass effect, rupture, hemorrhage, and infection. We report a patient with a large hepatic cyst with elevated serum and cyst fluid CA19-9 levels. We studied serum and cyst fluid CA19-9 levels in this patient, before and after the intracystic instillation of minocycline hydrochloride.
Case presentation
A 76-year-old Japanese woman was diagnosed as having an infected hepatic cyst, by physical examination and enhanced abdominal computed tomography. Serum (170 U/ml; reference: < 37 U/ml) and hepatic cyst fluid (371 U/ml) CA19-9 levels were elevated. After the intracystic instillation of minocycline hydrochloride, necrotic cells in the cyst were drained, and it totally collapsed after 1 week. Cyst fluid CA19-9 levels increased remarkably after the intracystic instillation of minocycline hydrochloride, while serum CA19-9 levels decreased significantly.
Conclusion
Our study is the first report to reveal the influence of intracystic instillation of minocycline hydrochloride on serum and cyst fluid CA19-9 levels in a patient with a simple hepatic cyst.
doi:10.1186/1752-1947-2-329
PMCID: PMC2572621  PMID: 18851758
12.  Characteristic comparison of triglyceride-rich remnant lipoprotein measurement between a new homogenous assay (RemL-C) and a conventional immunoseparation method (RLP-C) 
Background
Increased serum remnant lipoproteins are supposed to predict cardiovascular disease in addition to increased LDL. A new homogenous assay for remnant lipoprotein-cholesterol (RemL-C) has been developed as an alternative to remnant-like particle-cholesterol (RLP-C), an immunoseparation assay, widely used for the measurement of remnant lipoprotein cholesterol.
Methods
We evaluated the correlations and data validation between the 2 assays in 83 subjects (49 men and 34 women) without diabetes, hypertension and medications for hyperlipidemia, diabetes, and hypertension, and investigated the characteristics of remnant lipoproteins obtained by the two methods (RLP-C and RemL-C) and their relationships with IDL-cholesterol determined by our developed HPLC method.
Results
A positive correlation was significantly found between the two methods (r = 0.853, 95%CI 0.781–0.903, p < 0.0001). Bland & Altman analysis revealed that RemL-C values were likely to be significantly higher than RLP-C values, particularly in samples with high levels of remnant lipoproteins. Several data dissociations between the RemL-C and RLP-C were also observed. The HPLC chromatograms show high concentrations of chylomicron cholesterol in serum samples with RemL-C level < RLP-C level, but high concentrations of IDL-cholesterol in samples with RemL-C level > RLP-C level. RemL-C (r = 0.339, 95%CI 0.152–0.903; p = 0.0005) significantly correlated with IDL-cholesterol, but not RLP-C (r = 0.17, 95%CI -0.047–0.372; p = 0.1237) in all the samples (n = 83).
Conclusion
These results suggest that there is generally a significant correlation between RemL-C and RLP-C. However, RemL-C assay is likely to reflect IDL more closely than RLP-C.
doi:10.1186/1476-511X-7-18
PMCID: PMC2396627  PMID: 18485227
13.  The underlying mechanisms for development of hypertension in the metabolic syndrome 
Nutrition Journal  2008;7:10.
High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome.
doi:10.1186/1475-2891-7-10
PMCID: PMC2335113  PMID: 18416854
14.  Diacylglycerol oil for the metabolic syndrome 
Nutrition Journal  2007;6:43.
Excess adiposity has been shown to play a crucial role in the development of the metabolic syndrome. The elevated fasting and postprandial triglyceride-rich lipoprotein levels is the central lipid abnormality observed in the metabolic syndrome. Recent studies have indicated that diacylglycerol (DAG) is effective for fasting and postprandial hyperlipidemia and preventing excess adiposity by increasing postprandial energy expenditure. We will here discuss the mechanisms of DAG-mediated improvements in hyperlipidemia and in postprandial energy expenditure, and effects of DAG oil on lipid/glucose metabolism and on body fat. Further, the therapeutic application of DAG for the metabolic syndrome will be considered.
doi:10.1186/1475-2891-6-43
PMCID: PMC2235882  PMID: 18072966
16.  Effects of simvastatin 20 mg/d on serum lipid profiles in Japanese hyperlipidemic patients: A prospective, open-label pilot study 
Background:
Hyperlipidemia is a major risk factor for ischemic heart disease. Hydroxymethylglutaryl coenzyme A reductase inhibitors (“statins”) (eg, simvastatin) are considered first-line cholesterol-lowering therapy because they are effective and well tolerated, even at high doses. Based on a literature search, no studies have been published concerning the effects of simvastatin 20 mg/d in Japanese patients who had not previously received lipid-lowering treatment.
Objective:
The aim of this study was to assess the clinical tolerability and effectiveness of simvastatin 20 mg/d in achieving the target lipid concentrations recommended in the 2002 Japan Atherosclerosis Society (JAS) guidelines in Japanese patients with hyperlipidemia.
Methods:
This prospective, open-label pilot study was conducted at Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan. Male and postmenopausal female patients aged ≥18 to 70 years with hyperlipidemia (total cholesterol [TC], ≥220 mg/dL; triglycerides [TG], 150–400 mg/dL) who had not received lipid-lowering medications for at least 6 months before the study were enrolled. Patients received simvastatin 20 mg PO QD for 4 weeks. Effectiveness was assessed using serum concentrations of TC, low-density lipoprotein cholesterol (LDL-C), TG, and lipid peroxide, measured at 0 (baseline) and 4 weeks. Target serum TC and LDL-C concentrations as outlined by the JAS were as follows: category A, TC <240 mg/dL and LDL-C <160 mg/dL; category B1 and B2, TC <220 mg/dL and LDL-C <140 mg/dL; and category C, TC <200 mg/dL and LDL-C <120 mg/dL. A subanalysis of the correlation between baseline high-density lipoprotein cholesterol (HDL-C) and target achievement rates was conducted by baseline HDL-C concentration (<50 or ≥50 mg/dL). Tolerability was assessed using spontaneous reporting of adverse events and laboratory analysis, including liver function tests.
Results:
Twenty-two patients participated in the study (16 women, 6 men; mean [SD] age, 56.0 [8.0] years; mean [SD] body mass index, 23.6 [3.4] kg/m2). Mean serum TC, LDL-C, TG, and lipid peroxide concentrations significantly decreased from baseline (changes, −28.6%, −40.4%, −24.0%, and −14.5%, respectively; P < 0.001, <0.001, <0.001, and <0.01, respectively). The mean HDL-C concentration significantly increased from baseline (change, 7.2%; P < 0.001); the mean increase was significantly greater in patients with baseline HDL-C <50 mg/dL compared with those with baseline HDL-C ≥50 mg/dL (changes, 11.3% vs 4.4%; P < 0.05). Target TC and LDL-C concentrations were achieved in 90.9% of patients. No serious adverse events were observed, and liver enzyme and creatine kinase concentrations did not increase to above-normal values.
Conclusions:
The results of this study suggest that simvastatin 20 mg/d might be useful in the clinical treatment of hyperlipidemia in Japanese patients. The study drug was well tolerated.
doi:10.1016/j.curtheres.2005.12.008
PMCID: PMC3997116  PMID: 24764596
simvastatin 20 mg; low high-density lipoprotein cholesterol; 2002 Japanese Atherosclerosis Society guideline; lipid goal; Japanese hyperlipidemic patients

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