Projected numbers of knee and hip arthroplasties up to the year 2030 in Japan.

BACKGROUND: The aging population is a risk factor for an increase in osteoarthritis, leading to a potential increase in the number of arthroplasties worldwide. This study aimed to calculate the projected numbers of knee and hip arthroplasties in Japan until 2030 using national health insurance claim data. METHODS: Data on the numbers of knee and hip arthroplasties performed in Japan between 2014 and 2018 were obtained from the National Database of Health Insurance Claims and Specific Health Checkups of Open Data Japan. Demographic data were obtained from the National Institute of Population and Social Security Research. Collected data were categorized into three age subgroups (40-64, 65-74, and ≥75 years) for each sex. Projections were based on the Poisson regression model. RESULTS: The number of knee arthroplasties in Japan in 2030 was projected to be 4052 for men aged 40-64 years, 6942 for men aged 65-74 years, 14,986 for men aged ≥75 years, 7092 for women aged 40-64 years, 22,957 for women aged 65-74 years, and 58,340 for women aged ≥75 years. The number of hip arthroplasties in Japan in 2030 was predicted to be 8936 for men aged 40-64 years, 9005 for men aged 65-74 years, 5972 for men aged ≥75 years, 27,327 for women aged 40-64 years, 36,416 for women aged 65-74 years, and 37,011 for women aged ≥75 years. CONCLUSION: The numbers of knee and hip arthroplasties are expected to continue to increase over the next 10 years in Japan in most age groups. These findings are useful for future healthcare resource planning to meet the demand for knee and hip arthroplasties.

Hemodynamically adjusted infrahepatic inferior venous cava clamping can reduce postoperative deterioration in renal function: a retrospective observational study.

PURPOSE: Infrahepatic inferior vena cava (IIVC) clamping is beneficial for reducing the amount of bleeding during hepatic surgery, although the associated systemic circulatory deterioration is noticeable. The relationship between changes in the degree of IIVC clamping and postoperative renal function was retrospectively evaluated. METHODS: A total of 59 patients who underwent elective hepatic surgery with surgical IIVC clamping in the two years were analyzed. In 2016, constant 80% clamping of the IIVC was performed (29 cases), and in 2017, hemodynamically adjusted IIVC clamping was performed (30 cases). Intraoperative parameters, including total blood loss and number of blood transfusions, were examined. The use of each vasoactive agents was analyzed. Renal function in the acute postoperative phase was evaluated using serum creatinine (Cr) and estimated glomerular filtration rate (eGFR) values. RESULTS: Comparison of the two groups showed that bolus doses of both ephedrine and phenylephrine were significantly higher in the 2016 group (P = 0.0221, 0.0017). Continuous doses of dopamine were significantly higher in the 2016 group, while those of noradrenaline were not. Postoperative serum Cr levels relative to baseline (%) were significantly higher in the 2016 group immediately after surgery and on postoperative day (POD) 1 (P = 0.0143, 0.0012). Postoperative eGFR relative to baseline (%) was significantly higher in the 2016 group immediately postoperatively and on PODs 1 and 2 (P = 0.0042, 0.0003, 0.0382). CONCLUSION: Hemodynamically adjustable IIVC clamping might be superior to uniformly fixed clamping in preserving renal function without compromising the desired effect on hemostasis.

Amitriptyline, but Not Pregabalin, Reverses the Attenuation of Noxious Stimulus-Induced Analgesia After Nerve Injury in Rats.

BACKGROUND: Noxious stimulus-induced analgesia (NSIA) is a type of conditioned pain modulation in rats that has been used to assess endogenous pain control systems. The descending noradrenergic system is involved in NSIA, and nerve injury induces plastic changes of descending noradrenergic neurons. Thus, we hypothesized that nerve injury would affect NSIA strength and that amitriptyline and pregabalin, which often are used for treating neuropathic pain, might further modulate NSIA through effects on the descending noradrenergic system. METHODS: We examined the change in NSIA over time after right L5 spinal nerve ligation (SNL) in rats by measuring the contralateral hind paw withdrawal threshold after left forepaw capsaicin injection. In addition, we examined NSIA after 5 daily intraperitoneal injection of amitriptyline or pregabalin. Microdialysis studies were performed to measure noradrenaline levels after left forepaw capsaicin injection in the left spinal dorsal horn in noninjured rats, SNL rats, and SNL rats that had received 5 daily intraperitoneal injections of amitriptyline or pregabalin. RESULTS: NSIA was dramatically attenuated 5 and 6 weeks after SNL (P < 0.001). The noradrenaline level in the lumbar spinal cord was significantly increased in noninjured rats receiving forepaw injection of capsaicin compared with vehicle injection (P < 0.001), but not in rats 6 weeks after SNL surgery. Five daily intraperitoneal injections of amitriptyline (10 mg/kg/d) or pregabalin (10 mg/kg/d) at 5 weeks after SNL gradually increased the ipsilateral hindpaw withdrawal threshold (P < 0.001). At 6 weeks after SNL, amitriptyline, but not pregabalin, reversed the attenuation of NSIA by SNL (P < 0.001) and increased the spinal noradrenaline level after forepaw injection of capsaicin (P = 0.005). CONCLUSIONS: These data suggest that endogenous analgesia in neuropathic pain states is strongly decreased from a certain time after nerve injury and that amitriptyline reverses the attenuation of endogenous analgesia through effects on the descending noradrenergic system.

[Masked hypertension].

Patients with masked hypertension show normal office blood pressure but elevated out-of-office blood pressure. Out-of-office blood pressure is evaluated by ABPM (ambulatory blood pressure monitoring) or HBPM (home blood pressure measurements). HBPM is more popular in Japan because its simplicity. However, ABPM is essential to measure night blood pressure. Patients with masked hypertension have increased cardiovascular morbidity risk as high as seen in those with established hypertension. Many factors, including life style (smoking, excessive alcohol drinking, etc), variability of blood pressure (morning surge, non-dipper, riser) and inappropriate treatment of hypertension, are involved in masked hypertension. Life style modification, strict and sophisticated blood pressure control, and treatment of underlying diseases are necessary to treat masked hypertension.

Variation of 137Cs activity concentration in flood and pore water in paddy fields and its transfer to rice.

Caesium-137 (137Cs) is a major anthropogenic radionuclide released into the environment as a result of the TEPCO Fukushima Daiichi Nuclear Reactor Station accident (occurring on March 11, 2011). Rice, being a staple food in Asian countries, including Japan, and is predominantly cultivated in paddy fields. Consequently, 137Cs present in rice is absorbed from both soil and irrigation water, making it the most important crop for estimating internal radiation doses. In this study, over the 2018-2022 cultivation periods, flood water and pore water samples were collected biweekly from paddy fields. These samples were analyzed to measure the 137Cs activity concentration, as well as the potassium (K+) and ammonium (NH4+) concentrations. Under anaerobic conditions, the 137Cs + activity concentration in pore water increased markedly to reach a value 20-fold higher than that in flood water, correlating with NH4+ concentration. However, despite the release of 137Cs + caused by increased NH4+ concentrations in pore water due to reduction processes, the 137Cs+/K+ ratio did not increase, which was attributed to the simultaneous release of K+. The competition between 137Cs+ and K+ uptake by plants indicates that rice uptake of 137Cs is not necessarily enhanced during the waterlogging period.

Comparison of the antialbuminuric effects of L-/N-type and L-type calcium channel blockers in hypertensive patients with diabetes and microalbuminuria: the study of assessment for kidney function by urinary microalbumin in randomized (SAKURA) trial.

OBJECTIVE: To clarify whether the L-/N-type calcium channel blocker (CCB) cilnidipine is more renoprotective than the L-type CCB amlodipine in patients with early-stage diabetic nephropathy. METHODS: In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of cilnidipine and amlodipine were examined in renin-angiotensin system (RAS) inhibitor-treated patients with hypertension (blood pressure [BP]: 130-180/80-110 mmHg), type 2 diabetes, and microalbuminuria (urinary albumin to creatinine [Cr] ratio [UACR]: 30-300 mg/g). RESULTS: Patients received cilnidipine (n = 179, final dose: 10.27 ± 4.13 mg/day) or amlodipine (n = 186, 4.87 ± 2.08 mg/day) for 12 months. Cilnidipine and amlodipine equally decreased BP. The UACR values for the cilnidipine and amlodipine groups were 111.50 ± 138.97 and 88.29 ± 63.45 mg/g, respectively, before treatment and 107.93 ± 130.23 and 89.07 ± 97.55 mg/g, respectively, after treatment. The groups showed similar changes for the natural logarithm of the UACR, serum Cr, and estimated glomerular filtration rate. CONCLUSIONS: Cilnidipine did not offer greater renoprotection than amlodipine in RAS inhibitor-treated hypertensive patients with type 2 diabetes and microalbuminuria.

Fe and P solubilization under limiting conditions by bacteria isolated from Carex kobomugi roots at the Hasaki coast.

Our objective was simply to report a sedge species, Carex kobomugi Ohwi that has beneficial bacterial associations under low Fe and P conditions of the Hasaki coast, Japan. C. kobomugi is the dominant species in our study area and grows closest to the sea. C. kobomugi showed higher Fe and P content, while these nutrients were less available under alkaline root-zone soil. Within the roots, mycorrhizal fungal colonization was absent, and endophytic fungal colonization was low. On the contrary, endophytic bacteria (e.g. Bacillus sp., Streptomyces luteogriseus, and Pseudomonas fluorescens) were isolated, which exhibited both siderophore production and inorganic phosphate solubilization under Fe or P limited conditions. Our results suggest that colonization of root tissue by these bacteria contribute to the Fe and P uptakes by C. kobomugi by increasing availability in the soil.

Photorefraction with Spot Vision Screener versus Visual Acuity Testing as Community-Based Preschool Vision Screening at the Age of 3.5 Years in Japan.

Nationwide in Japan, a community-based vision-screening program in 3.5-year-old children is conducted in three steps: questionnaires and home visual acuity testing as the primary screening; visual acuity testing by nurses and pediatricians' inspection in community health centers as the secondary screening; and examinations by ophthalmologists as the tertiary screening. In this study, we introduced photorefraction with a Spot vision screener in addition to visual acuity testing to answer the clinical question of whether photorefraction could better detect eye diseases and potentially replace visual acuity testing. Photorefraction was performed on 813 consecutive 3.5-year-old children in a center. The children were sent to tertiary examinations, which were based on the Spot vision screener standard, in addition to the visual acuity testing standard: failure in either eye to pass 0.5 visual acuity in a center. A notice to visit ophthalmologists was issued for 95 children (11%), and documents with the diagnosis were sent back to the Heath Office for 76 children (80%). The rate of children with anisometropic or ametropic amblyopia or accommodative esotropia as treatment-requiring diseases was highest in cases of no pass at both standards (10/15 = 66%), and higher in cases of no pass only at the Spot vision screener standard (13/45 = 28%), compared with cases of no pass only at the visual acuity testing standard (6/33 = 18%, p = 0.0031). Photorefraction, in addition to visual acuity testing and inspection led to additional eye diseases detection at 3.5 years. Visual acuity testing at home would not be omitted in the introduction of photorefraction.

Effects of renal dysfunction on cardiovascular events in diabetic patients with hypertension: challenge-DM Study subgroup analysis.

BACKGROUND: This study investigated the relation between renal dysfunction and cardiovascular events in patients from the Challenge-DM Study (a large-scale investigation of Japanese diabetic patients with hypertension on candesartan therapy). METHODS: The subjects were 4706 patients in whom renal function could be assessed at the time of registration among 16860 patients analyzed in the Challenge-DM Study. The definition of renal dysfunction (low GFR) was an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) calculated by the formula for Japanese. RESULTS: The low GFR group was older, and had a high proportion of females and a high prevalence of cerebrovascular or cardiovascular disease (CVD) compared to the normal GFR group (eGFR ≥ 60 ml/min/1.73 m(2)). Univariate Cox regression analysis of cardiovascular events showed a significant increase in the incidence of primary events and total events in the low GFR group. Among patients <65 years old, the same results were obtained, but no differences were found between the low GFR and normal GFR groups aged over 65 years. Multivariate Cox regression analysis was done with patient characteristics at registration and the presence/absence of achieving the target blood pressure and HbA(1c) before the event as explanatory variables. As a result, low GFR was not the main cause of cardiovascular events, but it had a significant influence on primary events and total events among patients <65 years old. CONCLUSIONS: Low GFR may be an independent risk factor for cerebrovascular and CVD among young and middle-aged Japanese diabetic patients with hypertension on candesartan therapy.

Design and rationale of the study of assessment for kidney function by urinary microalbumin in randomized (SAKURA) trial.

Recently, it has been demonstrated that L-/N-type calcium channel blockers (CCBs), cilnidipine, but not L-type CCB, decreased urinary protein in renin-angiotensin system (RAS), inhibitor-treated hypertensive patients with macroproteinuria. However, the antiproteinuric effect of cilnidipine was weaker in diabetic patients than in nondiabetic patients with macroproteinuria. This may be due to the fact that diabetic neuropathy was also developed in patients with advanced diabetic nephropathy because L-/N-type CCB has been considered to exert its renoprotetive effects through sympatholytic action. If so, the antiproteinuric effect of cilnidipine may be potent in patients with early stages of diabetic nephropathy. To elucidate our hypothesis, we designed a multi-center, open-labeled, randomized trial to compare the antialbuminuric effect between cilnidipine and amlodipine in RAS inhibitor-treated hypertensive (blood pressure [BP]: 130-180/80-110 mmHg) patients with type 2 diabetes and microalbuminuria (urinary albumin/creatinine [Cr] ratio: 30-300 mg/g). The primary study endpoint is the change in the urinary albumin/Cr ratio after a 1-year treatment. Enrollment began in April 2008 and was completed in March 2010. A total of 367 patients were randomly allocated to receive cilnidipine or amlodipine. At baseline, study subjects had 63.3± 8.5 years of age, 145.9 ± 12.2/80.8 ± 10.0 mmHg of BP, 101.0 ± 111.6 mg/g of urinary albumin/Cr. The trial is expected to show whether cilnidipine can exert an antialbuminuric effect in RAS inhibitor-treated hypertensive patients with early stages of diabetic nephropathy.

Combination of angiotensin II receptor antagonist with calcium channel blocker or diuretic as antihypertensive therapy for patients with chronic kidney disease.

We compared treatment with an angiotensin II receptor antagonist (ARB) and a calcium channel blocker (CCB) combination and a fixed-dose ARB and thiazide diuretic in 18 chronic kidney disease (CKD) patients. A randomized crossover study was performed using a fixed-dose combination of losartan-hydrochlorothiazide or losartan combined with controlled-release nifedipine. Both systolic blood pressure (SBP) and diastolic blood pressures (DBPs) were lower during the nifedipine period than during the diuretic period. No significant difference was observed in urinary albumin excretion, but the estimated glomerular filtration rate was higher in the nifedipine than in the diuretic period. Serum uric acid and low-density lipoprotein cholesterol were higher in the diuretic than in the nifedipine period. A significantly low cardio-ankle vascular index, an index of arterial wall stiffness, was observed in the nifedipine period. A combination of ARB and a controlled-release nifedipine at 20-40 mg used showed a superior antihypertensive effect in CKD patients compared to a fixed-dose combination of losartan 50 mg-hydrochlorothiazide 12.5 mg in terms of blood control. The former combination is considered advantageous for maintaining renal function and artery wall elasticity without influencing uric acid or lipid metabolism.

Antiproteinuric effect of cilnidipine in hypertensive Japanese treated with renin-angiotensin-system inhibitors - a multicenter, open, randomized trial using 24-hour urine collection.

Sustained proteinuria is an important risk factor for not only renal but also cardiovascular morbidity and mortality. Although inhibitors of the renin-angiotensin system (RAS) have been shown to reduce proteinuria. Monotherapy with those drugs is often insufficient for optimal blood pressure (BP)-lowering and therefore, combined therapy is needed. Recent reports suggested that cilnidipine, a dual L-/N-type calcium channel blocker, has renoprotective effect by dilating both efferent and afferent arterioles. In this study, a multicenter, open, randomized trial was designed to compare the antiproteinuric effect between cilnidipine and amlodipine when coupled with RAS inhibitors in hypertensive patients with significant proteinuria. Proteinuria was evaluated by 24-h home urine collection for all patients. A total of 35 proteinuric (>0.1 g/day) patients with uncontrolled BP (>135/85 mmHg) were randomized to receive either cilnidipine (n = 18) or amlodipine (n = 17) after a 6-month treatment with RAS inhibitors and were followed for 48 weeks. At baseline, the cilnidipine group was older and had lower body mass index (BMI) compared to the amlodipine group. After 32 weeks of treatment, diastolic blood pressure (DBP) was slightly, but significantly reduced, in the cilnidipine group, although systolic blood pressure (SBP) and mean BP did not differ. The urinary protein did not differ at baseline (cilnidipine group 0.48 g/day, amlodipine group 0.52 g/day); however, it significantly decreased in the cilnidipine group (0.22 g/day) compared to the amlodipine group (0.50 g/day) after 48 weeks of treatment. Our findings suggest that cilnidipine is superior to amlodipine in preventing the progression of proteinuria in hypertensive patients even undergoing treatment with RAS inhibitors.

Year-long antihypertensive therapy with candesartan completely prevents development of cardiovascular organ injuries in spontaneously hypertensive rats.

Most previous studies have examined the effects of antihypertensive drugs in hypertensive animals for only a few months, and little information has been provided as to the protective effects of lifetime antihypertensive medication against cardiovascular organ injury. In this study, spontaneously hypertensive rats (SHR) were treated for 1 year with an angiotensin-II receptor antagonist (ARB) and the development of hypertensive organ injury was evaluated. Male 15-week-old SHR (n = 9) were given 25 mg/L candesartan (CS) in their drinking water for 1 year. Twelve SHR and 9 normotensive Wistar-Kyoto rats (WKY) were given normal tap water. Tail-cuff blood pressure was almost normalized by CS throughout 1 year (at 12-months: WKY 132 ± 3, SHR 229 ± 3, CS 137 ± 4 mmHg). After 1 year, cardiac ventricular weight (SHR +33%, CS -2% versus WKY) and aortic thickness (SHR +34%, CS +4% versus WKY) in the CS-treated SHR rats were not different than those of WKY. Echocardiographic midwall fractional shortening (SHR -18%, CS -1% versus WKY) and left ventricular hydroxyproline content (SHR +47%, CS +11% versus WKY) were also improved by CS to the WKY level. With respect to kidney function, GFR (SHR -24%, CS +9% versus WKY) was preserved, proteinuria (SHR +312%, CS +12% versus WKY) was reduced, and the histological glomerular injury rate (SHR +186%, CS +6% versus WKY) was reduced by CS. These results suggest that long-term antihypertensive therapy with CS can completely prevent hypertensive cardiovascular and renal injuries in SHR.

Stimulatory and Inhibitory regulation of lipolysis by the NPR-A/cGMP/PKG and NPR-C/G(i) pathways in rat cultured adipocytes.

OBJECTIVE: Recent studies have suggested the abundant expression of natriuretic peptide receptor in adipose tissue. This study was designed to investigate the levels of natriuretic receptor-A (NPR-A) and NPR-C gene expression during the process of preadipocyte differentiation and its role in adipogenesis and lipid metabolism. METHODS: We measured mRNA levels of NPR-A and NPR-C during the process of rat preadipocyte differentiation in vitro. We also measured the effects of ANP and C-ANP, a ligand for NPR-C, on preadipocyte differentiation. In addition, we assessed the effects of ANP and C-ANP on lipolysis and the cellular mechanism. RESULTS: The mRNA levels of NPR-A and NPR-C on day 3, 6, 10 are (-26%, +226%), (+6%, +568%), and (+207%, +3232%) respectively as compared with day 1. ANP (10(-)(7) M) and 8-bromo-cGMP (10(-)(4) M) significantly increased Oil Red positive area and cell number of matured-adipocytes. ANP and 8-bromo-cGMP also increased the mRNA levels of adipocyte-related genes such as PPARgamma, leptin, and adiponectin on day 3, whereas C-ANP did not change these parameters. ANP (10(-)(9)-10(-)(6) M) increased intracellular cGMP levels and promoted lipolysis in adipocytes and the effects were abolished by HS-142-1, and KT5823. Conversely C-ANP (10(-)(6) M) decreased intracellular cAMP levels and lipolysis and its effect was inhibited by PTX. CONCLUSION: Results suggest that ANP may promote adipocyte differentiation and lipolysis via the NPR-A/cGMP/PKG pathway. Direct action of ANP via NPR-C in adipogenesis may be either absent or barely present, but ANP may play a counter regulatory role in lipolysis via NPR-C/Gi pathway.

Natriuretic peptide/natriuretic peptide receptor-A (NPR-A) system has inhibitory effects in renal fibrosis in mice.

OBJECT: This study was designed to examine whether natriuretic peptide/natriuretic peptide receptor-A (NPR-A) system attenuates renal fibrosis in a unilateral ureteral obstruction (UUO) model and also examined the mechanism involved. METHODS: Three groups were studied: untreated UUO in wild-type mice; untreated UUO in NPR-A KO mice; and ANP treated (0.05 microg/kg/min) UUO in wild-type mice. We measured histological and immunohistochemical findings (alpha-SMA and F4/80), tissue cGMP levels, various mRNA expression levels by real-time PCR analysis, and transcription factor levels (AP-1 and NF-kappaB) in renal tissue. RESULTS: Compared with wild-type UUO mice, NPRA-KO UUO mice had abnormal morphological findings (fibrous area: +26%, alpha-SMA expression: +30%) with lower tissue cGMP levels and increases in the mRNA expression levels of TGF-beta, collagen I, collagen III, PAI-1, renin and angiotensinogen, whereas there were no differences in F4/80 positive cells or the mRNA expression levels of ICAM-1, osteopontin, or MCP-1 between the two groups. In contrast, ANP pre-treatment significantly improved morphological changes with increase of tissue cGMP levels and reduction in the mRNA expression level of TGF-beta, collagen I, collagen III, PAI-1, ICAM-1, osteopontin, MCP-1, renin, and angiotensinogen. NPRA-KO UUO mice had higher AP-1 levels than wild-type UUO mice and ANP pre-treatment reduced AP-1 and NF-kappaB activity. CONCLUSION: The endogenous natriuretic peptide/NPR-A system may inhibit renal fibrosis partly via inhibition of the angiotensin/AP-1/TGF-beta/collagen pathway and exogenous ANP pre-treatment may inhibit it partly via both the angiotensin/AP-1/TGF-beta/collagen and NF-kappaB/inflammatory pathways.

Is refraction with a hand-held autorefractometer useful in addition to visual acuity testing and questionnaires in preschool vision screening at 3.5 years in Japan?

The vision-screening program for 3.5-year-old children in Japan consists of 3 steps:questionnaires and home visual acuity testing, visual acuity testing by nurses and inspection by medical officers at regional Public Health Centers, and examinations by ophthalmologists. In this study, we tested refraction with a hand-held autorefractometer in addition to visual acuity testing and inspection to reveal whether or not autorefraction leads to better detection of eye problems. Autorefraction was performed in 6 consecutive sessions by a single examiner in 265 children at 3.5 years of age who all visited the same center. The children were sent to the third step of examinations by ophthalmologists based on refractive error criteria:3 diopters myopia or 1 diopter hyperopia, and/or 2 diopters astigmatism in either eye, in addition to the current criteria:1) failure in either eye for 0.5 visual acuity at the center, 2) eye-related symptoms revealed by the questionnaires, or 3) eye problems detected by medical officers. Notices to visit ophthalmologists were issued for 64 children (24%), and 37 of those (58%) made the visits, so that documents containing final diagnoses were sent back to the Public Health Office. Of the 64 children, 12 were sent to ophthalmologists based on the current criteria only, 10 based on both the current criteria and the refractive error criteria, and 42 based on the refractive error criteria only. Twelve of the 13 children visiting ophthalmologists by the current criteria had diagnoses such as amblyopia and strabismus. In contrast, 15 of 24 children visiting ophthalmologists by only the refractive error criteria had mainly diagnoses of refractive errors, with no serious problems. In conclusion, autorefraction in addition to visual acuity testing and inspection led to detection of only one additional case of an eye disease at 3.5 years, while tripling the number of children sending to the third-step examination by an ophthalmologist. Thus, from a cost-effectiveness standpoint, autorefraction is not recommended as an additional test when the current system is conducted as designed.

Implantable cardioverter defibrillator in maintenance hemodialysis patients with ventricular tachyarrhythmias: a single-center experience.

Patients with hemodialysis (HD) are at risk of death due to cardiac arrhythmias, worsening congestive heart failure (CHF), and noncardiac causes. This study reviews our experience with the use of implantable cardioverter defibrillators (ICDs) in patients with ventricular tachycardia who are under maintenance HD. We retrospectively reviewed 71 consecutive patients who underwent an ICD implantation in our hospital. There were 11 patients under maintenance HD and 60 patients without HD. The group of patients with HD (HD group) was compared with the patients without HD (control group). The mean follow-up period was 30+/-9 vs. 39+/-4 months in the HD group vs. the control group, respectively. Among these patients, 6 in the HD group and 26 in the control group received appropriate ICD therapies. There was no difference in appropriate ICD therapy, time to the first therapy, and electrical storm between the 2 groups. In the HD group, 1 patient underwent surgical removal of the ICD system due to infective endocarditis. There were 5 deaths in the HD group (4 from CHF) and 8 deaths in the control group (4 from CHF). There were no sudden cardiac deaths or arrhythmic deaths in both groups of patients during the follow-up period. However, the overall death rate was significantly higher in the HD group (P<0.01). In HD patients, ICD therapy prevented arrhythmic death, but their rate of nonarrhythmic adverse outcomes was high. This risk-benefit association should be considered before implantation of the device.

[Large clinical trials of ARB in Japan and its reflection to new guidelines].

Recently we are seeing reports of large scale clinical trials of ARB conducted in Japan. In CASE-J, candesartan (ARB) and amlodipine (Ca antagonist) show similar preventive effects on cardiovascular events in high risk hypertensive patients, whereas ARB prevents new-onset diabetes more effectively than Ca antagonist. In JIKEI HEART, the valsartan treatment group shows preventive effects on cardiovascular events compared with the non ARB treatment group in patients with hypertension, coronary heart disease and congestive heart failure. In INNOVATION and SMART telmisartan and valsartan indicate renoprotective effects in type 2 diabetic patients. We are now endeavoring to make the best use of the results from these trials in Japan as a source of evidence to support new guidelines (JSH2009).

Globular adiponectin activates nuclear factor-kappaB and activating protein-1 and enhances angiotensin II-induced proliferation in cardiac fibroblasts.

Adiponectin is present in the serum as a trimer, hexamer, or high-molecular weight form. A proteolytic cleavage product of adiponectin, known as globular adiponectin (gAd), also circulates in human plasma. The biological activities of these isoforms are not well characterized. Pressure overload in adiponectin-deficient mice results in enhanced concentric cardiac hypertrophy and increased mortality, suggesting that adiponectin inhibits hypertrophic signaling in the myocardium. Therefore, we examined whether gAd exerts the same effects on myocardium signaling. Nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation were examined using cardiac fibroblasts prepared from the ventricles of 1- to 2-day-old Wistar rats and grown in culture. gAd activated NF-kappaB and enhanced tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB activity. gAd also activated AP-1 and enhanced angiotensin II (Ang II)-induced AP-1 activity. gAd induced mRNA expression of c-fos and c-jun and activated extracellular signal-regulated kinase. Thus, gAd enhanced Ang II-induced DNA and collagen synthesis. Antibodies against adiponectin receptor (AdipoR)1 and AdipoR2 elicit activation of NF-kappaB or AP-1, two redox-sensitive transcription factors. Thus, rather than having an antihypertrophic effect, gAd might contribute to the activation of myocardium signaling, leading to myocardial hypertrophy.