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Background: Two important regulators for circulating lipid metabolisms are lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). In relation to this, glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1 (GPIHBP1) has been shown to have a vital role in LPL lipolytic processing. However, the relationships between skeletal muscle mass and lipid metabolism, including LPL, GPIHBP1, and HTGL, remain to be elucidated. Demonstration of these relationships may lead to clarification of the metabolic dysfunctions caused by sarcopenia. In this study, these relationships were investigated in young Japanese men who had no age-related factors; participants included wrestling athletes with abundant skeletal muscle., Methods: A total of 111 young Japanese men who were not taking medications were enrolled; 70 wrestling athletes and 41 control students were included. The participants' body compositions, serum concentrations of lipoprotein, LPL, GPIHBP1 and HTGL and thyroid function test results were determined under conditions of no extreme dietary restrictions and exercises., Results: Compared with the control participants, wrestling athletes had significantly higher skeletal muscle index (SMI) (p < 0.001), higher serum concentrations of LPL (p < 0.001) and GPIHBP1 (p < 0.001), and lower fat mass index (p = 0.024). Kruskal-Wallis tests with Bonferroni multiple comparison tests showed that serum LPL and GPIHBP1 concentrations were significantly higher in the participants with higher SMI. Spearman's correlation analyses showed that SMI was positively correlated with LPL (ρ = 0.341, p < 0.001) and GPIHBP1 (ρ = 0.309, p = 0.001) concentration. The serum concentrations of LPL and GPIHBP1 were also inversely correlated with serum concentrations of triglyceride (LPL, ρ = - 0.198, p = 0.037; GPIHBP1, ρ = - 0.249, p = 0.008). Serum HTGL concentration was positively correlated with serum concentrations of total cholesterol (ρ = 0.308, p = 0.001), low-density lipoprotein-cholesterol (ρ = 0.336, p < 0.001), and free 3,5,3'-triiodothyronine (ρ = 0.260, p = 0.006), but not with SMI., Conclusions: The results suggest that increased skeletal muscle mass leads to improvements in energy metabolism by promoting triglyceride-rich lipoprotein hydrolysis through the increase in circulating LPL and GPIHBP1.

Aims: In order to clarify hepato-protective actions of estrogen, we examined the progress of carbon tetrachloride (CCl 4 )-induced acute liver injury (ALI) in sham and ovariectomized (ovx) mice and the effects of dimethylthiourea (DMTU), a hydroxyl radical scavenger, and meloxicam (Melo), a selective cox-2 inhibitor, on the development of CCl 4 -induced ALI., Main Methods: Female C57BL/6 J mice weighing 15-20 g were performed sham or ovx operation at 8 weeks of age. Blood and liver samples were collected 15 and 24 h after CCl 4 administration. Sham and ovx mice were given DMTU, Melo or saline intraperitoneally 30 min before CCl 4 or corn oil administration., Key Findings: ALT levels in ovx mice were significantly increased compared to those in sham mice. DMTU reduced ALT levels in ovx mice to the same levels as those in sham mice after CCl 4 injection. CCl 4 upregulated TNF-α, IL-6, cox-2 and iNOS expression in ovx mice compared to the levels in sham mice. DMTU significantly reduced cox-2 and iNOS expression levels upregulated by CCl 4 in ovx mice. However, pretreatment with Melo had no effects on ALT levels and the gene expression levels of TNF-α, IL-6 and HO-1 in either sham or ovx mice, indicating that cox-2 may not participate in increase of CCl 4 -induced ALI caused by estrogen deficiency., Significance: Ovariectomy accelerated the development of CCl 4 -induced acute liver injury, and DMTU reduced liver injury. These results suggest that estrogen may act as an antioxidant in the development CCl 4 -induced acute liver injury., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

In Japanese pediatric patients with thyrotropin (TSH) resistance, the R450H mutation in TSH receptor gene (TSHR) is occasionally observed. We studied the frequency and clinical implication of the R450H mutation in TSHR in the general population of Japanese adults using smart amplification process 2 (SmartAmp2). We designed SmartAmp2 primer sets to detect this mutation using a drop of whole blood. We analyzed thyroid function, antithyroid antibodies, and this mutation in 429 Japanese participants who had not been found to have thyroid disease. Two cases without antithyroid antibodies were heterozygous for the R450H mutation in TSHR. Thus, the prevalence of this mutation was 0.47% in the general population and 0.63% among those without antithyroid antibodies. Their serum TSH concentrations were higher than the average TSH concentration not only in subjects without antithyroid antibodies but also in those with antithyroid antibodies. The R450H mutation in TSHR is relatively common in the Japanese population and potentially affects thyroid function. The present study demonstrates that the SmartAmp2 method is useful to detect the R450H mutation in TSHR, which is one of the common causes of TSH resistance in the Japanese population.

The effect of stress associated with acute weight reduction on adipocytokine production is incompletely understood. In the present study, we have investigated the changes in circulating adipocytokine concentrations and urinary concentrations of stress markers in male collegiate wrestlers during acute weight reduction for a competition. Twenty healthy Japanese male wrestlers (18-22 years of age) who participated in the national collegiate wrestling tournament were studied. Body weight, body fat amount, serum testosterone, serum leptin, serum adiponectin, urinary 8-hydroxy-2'- deoxyguanosine (8-OHdG) and urinary biopyrrins were analyzed during acute weight reduction for the competition. Body weight, body fat amount and the serum concentrations of testosterone, leptin and adiponectin significantly decreased on the day of weigh-in compared with the levels 12 days before weigh-in. In contrast, urinary concentrations of 8-OHdG and biopyrrins significantly increased on the day of weigh-in compared with the concentrations 12 days before weigh-in. A positive correlation was observed between the serum concentrations of adiponectin and testosterone, and a negative correlation was observed between the concentrations of serum adiponectin and urinary biopyrrins. The present results suggest that rapid weight reduction increases the urinary concentrations of stress markers, which is associated with a decrease in serum concentrations of adiponectin.

Purpose: To investigate age-related changes in hyaluronan levels in human eyes before and after vitrectomy surgery, we measured the hyaluronan levels in the vitreous samples obtained during vitrectomy and postoperative fluid-air exchange., Methods: We obtained the vitreous during vitrectomy from 26 eyes of 26 patients with macular hole (MH) and 52 eyes of 52 patients with diabetic retinopathy (DR). After vitrectomy, we collected fluid samples during fluid-air exchange from 6 eyes with MH and 9 eyes with DR. The hyaluronan level was measured by the sandwich binding protein assay., Results: In the vitreous of the 54 eyes (26 eyes with MH and 28 eyes with DR and no vitreous hemorrhage), hyaluronan levels significantly decreased with patient age (r = -0.66, p < 0.00000005). Hyaluronan levels in postoperative vitreous fluid were significantly lower in 6 eyes with MH (p < 0.05) and 9 eyes with DR (p < 0.01) than those obtained during vitrectomy., Conclusions: There was a significant decrease in vitreous hyaluronan with aging. High-molecular-weight hyaluronan appears not to be formed in vitreous fluid after vitrectomy., (Copyright 2008 S. Karger AG, Basel.)

Purpose: To assess vitreous metabolism by measuring C-propeptide levels of type II procollagen (pCOL-II-C) and hyaluronan levels in the vitreous and in the vitreous fluid after vitrectomy for macular hole., Methods: We obtained 1-ml vitreous samples during vitrectomy from 34 patients (34 eyes) with a macular hole (age range 50-77 years, mean 64 years). After vitrectomy, we performed fluid-air exchange in six eyes because of unresolved macular holes and collected 4-ml fluid samples. Gel-filtration high-performance liquid chromatography (HPLC) was used to determine the molecular weight of pCOL-II-C in the samples. The pCOL-II-C level was measured by sandwich enzyme immunoassay and hyaluronan by sandwich binding protein assay., Results: HPLC showed that pCOL-II-C in the vitreous samples corresponded to purified pCOL-II-C from cartilage. The vitreous pCOL-II-C level (4.7+/-0.3 ng/ml) was similar to reported synovial fluid levels. In six eyes that underwent fluid-air exchange, pCOL-II-C in the fluid samples remained at a level similar to that in the vitreous samples, while hyaluronan levels in the fluid samples were significantly lower than in the vitreous samples., Conclusions: The molecular weight and concentrations of pCOL-II-C in the vitreous are similar to those in joint fluid. In patients with a macular hole, type II procollagen may be secreted persistently into the vitreous cavity before and after vitrectomy.

Purpose: Neovascular glaucoma is a frequent complication of vitrectomy performed to treat proliferative diabetic retinopathy (PDR). We assessed the level of vascular endothelial growth factor (VEGF) in the vitreous fluid obtained during vitrectomy and at postoperative fluid-air exchange., Methods: We measured VEGF levels in vitreous samples from 17 eyes of 15 patients with PDR during vitrectomy and fluid samples obtained during fluid-air exchange 5 to 36 days postoperatively. Six of the 17 eyes had iris neovascularization after vitrectomy. Vascular endothelial growth factor levels also were measured in the vitreous fluid obtained from 8 eyes with a macular hole during vitrectomy and postoperative fluid-air exchange. We measured the plasma VEGF levels in all patients., Results: The mean VEGF levels in 17 eyes with PDR were 1162.3+/-173.2 pg/ml in the vitreous samples and 1180.4+/-182.8 pg/ml in the postoperative fluid samples. The mean plasma VEGF level was 116.1+/-10.2 pg/ml in eyes with PDR, and the mean plasma VEGF level was 118.5+/-15.2 pg/ml in patients with a macular hole. The mean VEGF levels were 96.9+/-11.5 pg/ml in the vitreous samples and 73.9+/-12.3 pg/ml in the fluid samples in eyes with a macular hole., Conclusions: A high VEGF level was maintained in the vitreous cavity after vitrectomy for PDR. The VEGF level in eyes with PDR was 10 times higher than that in the plasma. The results suggest that there is persistent secretion of VEGF into the vitreous cavity even after vitrectomy for PDR.

Ferritin is an indispensable parameter in the diagnosis of latent iron deficiency anemia or siderosis. In this study, we evaluated the utility of a reagent for ferritin measurement in a latex agglutination (LA) test, using general chemistry analyzers. The intraassay coefficient of variation (CV) was 0.8-3.4% and the interassay CV was 0.0-0.7%. Linearity was observed up to 1100 ng/mL. The effective sensitivity value was 4.0 ng/mL. In addition, good results were obtained with the prozone test, the effects of interferences, correlation with the enzyme immunoassay (EIA) method, and functional assay sensitivity. A significant positive correlation with C-reactive protein (r=0.586, P<0.001) was found. When compared with liver-related biochemical parameters (asparate aminotransferase (AST) and alanine aminotransferase (ALT)) in patients with impaired liver function, ferritin varied in parallel with the liver-related parameters. This assay system was able to measure ferritin accurately over a wide range, and thus could be used to diagnose cancer, siderosis, and iron deficiency anemia. The LA assay system can be employed for measurement with general chemistry analyzers, with rapid and convenient execution. In addition, the LA test allows the simultaneous measurement of other markers of iron deficiency anemia, so clinicians can rapidly obtain examination results., (Copyright 2003 Wiley-Liss, Inc.)

In patients with acute myocardial infarction (AMI), euthyroid sick syndrome (ESS) has been reported to be linked to increase in interleukin (IL)-6 and activation of its receptors. Recent reports have shown that IL-10, an anti-inflammatory cytokine, also plays a key role in the pathogenesis of AMI. Therefore we investigated the relationship between thyroid state and IL-10 in patients with AMI. We measured thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), IL-10, and IL-6 in plasma from 20 patients with AMI and 20 healthy controls. All 20 AMI patients showed significantly lower concentrations of FT3 than in controls accompanied by normal or subnormal levels of TSH, characterized ESS. Concentrations of IL- 10 and IL-6 were higher in patients than in controls. Both IL-10 and IL-6 significantly (p<0.05, respectively) correlated with thyroid hormone in patients with AMI. Time course of IL-10, IL-6, and FT3 seemed to be tightly linking. In conclusion, IL-10 and IL-6 appears to affect thyroid hormone homeostasis in patients with AMI.

Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disorder of unknown etiology that is characterized pathologically by fibrofatty replacement of the right ventricular myocardium. We investigated the relationship between the electrocardiogram (ECG) appearances and signal-averaged ECG (SAECG) in 7 cases with ARVD, and evaluated the usefulness of SAECG as a screening test to detect patients with ARVD. Compared with the conventional 12-lead ECG, the SAECG detects abnormalities at a higher rate in ARVD patients (57% versus 86%). SAECG was more sensitive as a screening test to detect patients with ARVD than 12-lead ECG.

Long QT syndrome (LQTS) is a prime example of interplay between molecular biology, cellular physiology, and organ physiology. Both the congenital and acquired forms of LQTS are due to intrinsic and/or acquired abnormalities of the ionic currents responsible for cardiac repolarization. We analyzed the QTc interval, QRS axes and interventricular septal thickness (IVST) in 41 patients who had a prolonged QT interval on routine electrocardiography (ECG) (5 females and 36 males, mean age 65+/-13 years). The QRS axis of patients in the LQTS group (27+/-49 degrees) was significantly lower (p < 0.05) than in the control group (46+/-26 degrees). However, the IVST in the LQTS group (10+/-2 mm) was significantly thicker than in the control group (9+/-1 mm) (p < 0.05), while the WTd was not significantly different. The QTc interval in patients with ventricular septal hypertrophy (IVST > or = 12 min, 478.8+/-7.9 msec) was significantly longer (p < 0.05) than in the normal group (IVST < 12 mm, 472.1+/-17.5 msec). In conclusion, the results of this preliminary study suggest that prolongation of the QT interval on ECG should prompt screening for electrocardiographic evidence of ventricular hypertrophy in patients with this disease.

The euthyroid sick syndrome is reported to exist in acute myocardial infarction(AMI). Previous reports showed serum levels of triiodothyronine(T3) are low and thyroid stimulating hormone(TSH) is normal or subnormal levels in patients with AMI. However, the mechanism of altered thyroid hormone metabolism is unknown. Interleukin-6(IL-6) is reported to be a key role in the pathogenesis of AMI and euthyroid sick syndrome. We measured circulating TSH, free T3(FT3), free thyroxine (FT4), IL-6, soluble IL-6 receptor, soluble transducing 130-kD glycoprotein, atrial natriuretic peptide(ANP) and brain natriuretic peptide in 25 patients and 32 healthy subjects. Circulating FT3 levels in patients with AMI became lower than in control group(p < 0.05). IL-6 levels were significantly(p < 0.05) higher than those of healthy subjects. The peak levels of IL-6 was 30.5 +/- 46.9 pg/ml at 25-27 hours(the first peak) and 64.4 +/- 24.6 pg/ml at 70-72 hours(the second peak). FT3 was negatively related to IL-6(p < 0.05) and hANP(p < 0.05) in patients with AMI. These results indicate that the lower levels of FT3 show the greater severity of AMI. We conclude that euthyroid sick syndrome occurs in patients with AMI and euthyroid sick syndrome may regulated by IL-6 through suppressed of thyroid function.

Interleukin-6 (IL-6), a proinflammatory cytokine, plays a key role in the pathogenesis of coronary artery disease (CAD). We investigated circulating IL-6 and its receptors in patients with CAD. We evaluated 39 Japanese patients with CAD (30 males and 9 females aged 36-79 years), measuring their plasma levels of IL-6 and IL-6 receptors alpha and beta (IL-6R alpha, IL-6R beta). Circulating levels of IL-6, IL-6R alpha and IL-6R beta were measured by an enzyme-linked immunosorbent assay. Blood was sampled immediately after admission and again after 1, 2, 3, 6 and 9 h, then every 12 h for 5 days. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were measured on day 3 after symptom onset. Plasma levels of IL-6 and IL-6Rs were significantly increased in 28 patients with acute myocardial infarction (AMI) compared with 15 normal controls. However, neither IL-6 nor IL-6Rs showed an increase in 6 patients with angina pectoris. We observed two peaks for circulating IL-6 in AMI, the first of which showed a significant correlation with ANP as well as BNP. These results may help to explain why the amount of IL-6 produced is closely related to the severity of myocardial dysfunction in patients with CAD., (Copyright 2000 S. Karger AG, Basel)

Disseminated intra-vascular coagulation (DIC) is associated with severe bleeding tendency and organ failure, the extent of which is thought to be related to the prognosis of DIC patients. Thrombomodulin (TM) is a high-affinity thrombin receptor on vascular endothelial cells. Clinical importance of soluble TM is still controversy as a diagnostic and prognostic indicator in patients with disseminated intravascular coagulation (DIC). We compared plasma levels of TM with fibrin degradation product (FDP) in patients with DIC through the clinical course. The significant elevation of circulating TM in nonsurvivors with DIC compared with survived patients with DIC(TM 3.1+/-1.52 vs 8.1+/-3.89 FU/ml), as well as FDP (12.9+/-12.12 vs 49.8+/-55.42 microg/ml) but the levels of FDP were not different between the two groups. The measurement of circulating TM was a relatively good prognostic marker of patients with DIC.

The combination of atrial fibrillation (Af) and tricuspid regurgitation (TR) may induce the congestive heart failure (HF) due to insufficient output. However, these associations have not been elucidated. We examined the clinical course with echocardiographic data in 119 patients with Af and/or TR and/or HF. Their mean age was 65 +/- 14 years. The patients were classified into 6 groups as follows: Group I contained patients with Af, TR and HF(n = 13); Group II contained patients with Af and TR, without HF(n = 59); Group III contained patients with TR and HF, without Af(n = 15); Group IV contained patients with TR and without AF and HF(n = 15); Group V contained patients with Af and HF, without TR(n = 24); Group VI contained patients with Af and without TR and HF(n = 13). The fractional shortening and ejection fraction in Group I and II were significantly (p < 0.05) decreased compared to Group IV. Moreover, the fractional shortening in Group V was significantly (p < 0.05) lower than in Group IV. Among 72 cases in Group I and II, 24 cases were followed by echocardiography for 2 to 5 years. Eight cases of HF exhibited a no HF state and 1 demonstrated had the HF state. All 9 cases (38%) showed a decreased heart rate and no alternation of TR. Four of the 24 patients (17%) had developed worsened TR and a lowered ejection fraction but none developed them became HF. Therefore, tachycardia may be an accelerative factor for HF due to the combination of Af and TR, not due to the grade of TR.

Recently, we have developed a highly sensitive assay system for quantitative measurement of urinary type IV collagen. To obtain a basic evaluation of the assay system we used urine specimens, collected randomly and studied the relation to diabetic nephropathy in patients with non-insulin dependent diabetes mellitus (NIDDM). It was shown that this assay system could measure the samples without concentrating the urine. Urinary sediments which were reported to interfere with the assay could be removed by adding Tris-buffer. In the clinical studies, urinary type IV collagen concentrations were significantly higher in patients with NIDDM regardless of the presence or the absence of albumin. Cases with abnormal values of urinary type IV collagen in the normal albuminuria group were 41.6%, while those with abnormal values of urinary transferrin excretion were 31.0%. Furthermore, among the normal albuminuria group, glycosylated hemoglobin (HbA1c) levels were higher in the groups of abnormal values of urinary type IV collagen than those within the reference values. These results obtained herein suggest that urinary type IV collagen could be a useful marker for the early stage of diabetic nephropathy.