Procalcitonin, brain natriuretic peptide and albumin as markers to predict prognosis in hospitalized older Japanese patients with a risk of infection.

AIM: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. METHODS: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. RESULTS: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. CONCLUSIONS: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576.

Sarcopenia and decline in appendicular skeletal muscle mass are associated with hypoperfusion in key hubs of central autonomic network on 3DSRT in older adults with progression of normal cognition to Alzheimer's disease.

AIM: Although sarcopenia is common in patients with Alzheimer's disease (AD), the neural substrates involved remain unclear. We investigated the relationship between sarcopenia, as well as its definition components, and regional cerebral blood flow (rCBF) in older adults with progression of normal cognition to AD. METHODS: 99m Tc-ethyl-cysteinate-dimer single-photon emission computed tomography was carried out in 95 older adults with progression of normal cognition to AD (40 men and 55 women, mean ± SD age 80.9 ± 6.8 years). The associations of rCBF determined by 3-D stereotactic region of interest template software, with sarcopenia and its definition components, slower gait speed, weaker grip strength, and decline in appendicular skeletal muscle mass index (ASMI) were analyzed. RESULTS: Logistic regression analysis adjusted by age, sex, mini-mental state examination score and education showed that sarcopenia as well as ASMI less than the cut-off (men 7.0 kg/m2 , women 5.7 kg/m2 ) were associated with significantly reduced rCBF in the key hub of the central autonomic network, including the insula, anterior cingulate cortex, subcallosal area, rectal gyrus, hypothalamus, amygdala and caudate head. Sarcopenia and ASMI decline were associated with hypoperfusion in the aforementioned cortical hubs of the central autonomic network in men, but with hypoperfusion of the hypothalamus in women. Linear regression analysis showed significant correlations of ASMI/cut-off with rCBF in the bilateral medial frontal cortex, as well as rCBF in the aforementioned key hubs. CONCLUSIONS: Hypoperfusion in key hubs of central autonomic network is implicated in the emergence of sarcopenia, probably through ASMI decline in vulnerable older adults. Geriatr Gerontol Int 2023; 23: 16-24.

Examination of Endoscopic Ultrasonographic Diagnosis for the Depth of Early Gastric Cancer.

BACKGROUND: Endoscopic ultrasonography (EUS) is one of the helpful tools to diagnose depth of early gastric cancer (EGC). In this study, we examined efficiencies of EUS for EGC such as overall accuracy, risk factors of over/under-staging, and accuracies of each invasive distance. METHODS: A total of 403 EGC lesions that could be investigated by EUS during pre-operation and histological diagnosis after endoscopic submucosal dissection (ESD) or surgery were enrolled in this study. For the 403 cases, we analyzed the accuracies of depth by conventional endoscopy (CE) and EUS retrospectively. We evaluated the clinical survey items of CE and EUS which will be described later to compare the differences between "accuracy group" and "over-staging group", and between "accuracy group" and "under-staging group", retrospectively. Additionally, 78 EGC lesions which were confined to the submucosa and for which it was possible to measure accurate invasive distance from the muscularis mucosae were examined for the relationship between preoperative diagnosis of depth by CE and EUS and invasive distance retrospectively. RESULTS: The overall accuracies of both CE and EUS in predicting EGC invasion depth were 87.3%. For CE staging, histological classification was the factor which influenced over-staging. Gastric regions and tumor area were the factors which influenced under-staging of CE. For EUS staging, tumor area was the factor which influenced over-staging, and gastric regions were the factors which influenced under-staging. Both CE and EUS were not sufficient for predicting the lesions confined to < 500 µm from the muscularis mucosae because the accuracies of both in predicting depth were less than 50%. However, EUS has a higher accuracy than CE for the lesions confined to 500 - 2,000 µm. CONCLUSIONS: The overall accuracies of both CE and EUS in predicting EGC invasion depth were equal, but the contributing factors for over/under-staging were different. Both CE and EUS are not sufficient at present to predict the lesions confined to < 500 µm from the muscularis mucosae. However, the accuracy of EUS in predicting them may increase if high-performance EUS systems are developed in the future.

A Case of Refractory Esophageal Ulcer Caused by Radiotherapy for Hepatocellular Carcinoma.

A 77-year-old man who underwent radiotherapy for hepatocellular carcinoma 6 months prior consulted for esophageal obstruction. Esophagogastroduodenoscopy revealed an esophageal ulcer caused by radiotherapy for hepatocellular carcinoma. He was treated with dietary counseling and vonoprazan. After 9 months, the ulcer improved but a moderate stenosis remained. Several factors such as high fraction size, history of chemotherapy, and stress associated with food intake might involve in the development of a radiation-associated ulcer. Opportunities to choose radiotherapy for hepatocellular carcinoma may increase, so we hypothesize that esophageal ulcers might be a complication that should be noted associated with this therapy.

Olfactory-cognitive index distinguishes involvement of frontal lobe shrinkage, as in sarcopenia from shrinkage of medial temporal areas, and global brain, as in Kihon Checklist frailty/dependence, in older adults with progression of normal cognition to Alzheimer's disease.

AIM: Olfactory impairment as a prodromal symptom, as well as sarcopenia, frailty and dependence as geriatric syndromes, is often associated with cognitive decline in older adults with progression of Alzheimer's disease. The present study aimed to evaluate the associations of olfactory and cognitive decline with these geriatric syndromes, and with structural changes of the brain in older adults. METHODS: The participants were 135 older adults (47 men and 88 women, mean age 79.5 years), consisting of 64 with normal cognition, 23 with mild cognitive impairment and 48 with Alzheimer's disease. Olfactory function was evaluated by the Open Essence odor identification test. Shrinkage of the regional brain was determined by magnetic resonance imaging. RESULTS: Logistic regression analysis with Open Essence, Mini-Mental State Examination, age and sex as covariates showed higher olfactory-cognitive index (|coefficient for Open Essence (a) / coefficient for Mini-Mental State Examination (b)|) in participants with sarcopenia (Asia Working Group for Sarcopenia), and lower values of (|a/b|) in participants with Barthel Index dependence, Kihon Checklist frailty, Lawton Index dependence and support/care-need certification as objective variables. Logistic regression analysis adjusted by age and sex also showed significant shrinkage of the frontal lobe in participants with AWGS sarcopenia, especially in women, and shrinkage of the medial temporal areas and global brain in participants with Kihon Checklist frailty/dependence. CONCLUSIONS: Olfactory-cognitive index (|a/b|) might be a useful tool to distinguish involvement of frontal lobe shrinkage, as in sarcopenia from shrinkage of the medial temporal areas, and global brain, as in frailty/dependence, in older adults with progression of normal cognition to Alzheimer's disease. Geriatr Gerontol Int 2021; ••: ••-••.

Relationship Between Gastroesophageal Reflux Disease and Endoscopic Finding "Iodine-Unstained Streak".

BACKGROUND: Esophagogastroduodenoscopy (EGD) with iodine stain is a useful and diffused method for diagnosing esophageal cancer. We can perform the procedure easily with endoscopic system which does not comprise image-enhanced endoscopy. Several studies advocated that iodine-unstained streaks are a characteristic finding of gastroesophageal reflux disease (GERD). However, there are only a few reports about the subject. In this study, we investigated the usefulness of iodine chromoendoscopy for GERD consultation. METHODS: The study was conducted with 154 GERD cases in which EGD with iodine stain to the esophagus was performed. For the 154 cases, we analyzed the existence of reflux esophagitis finding and iodine-unstained streaks. In 47 GERD cases (proton pump inhibitor (PPI): 45 cases, histamine H2-receptor antagonist (H2-RA): two cases) where medication was started after EGD, we examined predictive factors of the symptom improvement such as sex, age, weight, reflux esophagitis finding, and iodine-unstained streak. RESULTS: An iodine-unstained streak was observed in 50/154 cases (32.5%). For 50 cases with iodine-unstained streak, there were only 24/50 cases (48.0%) that had both reflux esophagitis findings (≥ Los Angeles classification: grade M) and an iodine-unstained streak. For 47 cases in which medication was started, 34 cases showed improvement in their symptoms, and 13 cases did not show improvement. An iodine-unstained streak was observed more often in "Improved" group rather than in "Not improved" group (P < 0.01). When we supposed an iodine-unstained streak to be the predictive factor of the medication effect for GERD, sensitivity was 61.8% and specificity was 84.6%. CONCLUSIONS: No erosion was often found in the GERD cases without reflux esophagitis, and iodine-unstained streak was observed more often in "Improved" group rather than in "Not improved" group. We think that iodine-unstained streak can be useful for diagnosing of GERD and predictive factor of the medication effect.

Mortality and the Risk Factors in Elderly Female Patients With Femoral Neck and Trochanteric Fractures.

BACKGROUND: The main purpose of this study is to exhaustively explore risk factors, including age, gender, and several clinical indices, for mortality in elderly patients with femoral neck fracture and to evaluate some of them using survival analyses. METHODS: This was a retrospective study tracking 1 year for vital prognosis. Data were collected at post-operation from medical records of the cases. Survival analysis was conducted to investigate the risk factors for death, including albumin, urinary retention, activity of daily living (ADL), and cognitive disorder. RESULTS: We recruited 318 patients with a history of hip surgery carried out at Toyama Municipal Hospital, in which 39 patients died for 1 year after discharge. The results showed a significant decrease in survival rate in low albumin, positive urinary retention, and low ADL (P < 0.01, by log-rank test). The hazard ratios (95% confidence interval) of albumin, urinary retention, ADL, and cognitive disorder were 0.36 (0.19 - 0.69), 0.4 (0.2 - 0.8), 0.29 (0.15 - 0.58) and 0.65 (0.32 - 1.29), respectively. CONCLUSIONS: This study demonstrated that albumin, urinary retention and ADL were the important risk factors for mortality, and suggested that the postoperative management of albumin, urinary retention and ADL is important, especially in elderly female patients receiving surgery of femoral neck and trochanteric fractures.

Risk factors for the development of aspiration pneumonia in elderly patients with femoral neck and trochanteric fractures: A retrospective study of a patient cohort.

Aspiration pneumonia (AP) has been recognized as one of the most common postoperative complications after hip surgery in elderly. The objective of the present study was to evaluate risk for postoperative complications of AP in elderly patients with femoral neck fractures.We recruited 426 patients (age 84.9 ±â€Š7.4 years) with a history of hip surgery carried out at Toyama Municipal Hospital. AP occurred in 18 out of 426 cases (4.23%). Statistical test has found significant differences in age, gender, serum albumin level, and cognitive impairment, between AP and non-AP groups. Subsequently multiple logistic regression analysis was conducted to investigate the risk factors for AP, including age, gender, serum albumin, cognitive impairment, and activities of daily living (ADL). Adjusted odds ratio showed significant differences in age, gender, and serum albumin, whereas no significant differences were found in cognitive impairment and ADL.This study suggested that serum albumin seemed to be a risk factor for AP but were necessary to assess under adjustment of confounding factors, including age and gender. Monitoring serum albumin level seemed to be important for the postoperative management of AP, especially in elderly patients receiving surgery of femoral neck and trochanteric fractures.

Urinary retention as a postoperative complication associated with functional decline in elderly female patients with femoral neck and trochanteric fractures: A retrospective study of a patient cohort.

Urinary retention (UR) has been recognized as one of the most common postoperative complications after hip surgery in elderly. The objective of the present study was to evaluate risk for postoperative complications of UR in elderly female patients with femoral neck fractures.We recruited 221 female patients (age 85.3 ±â€Š7.0 years) with a history of hip surgery carried out at Toyama Municipal Hospital. UR occurred in 34 out of 221 cases (15.4%). Multiple logistic regression analysis was conducted to investigate the risk factors for UR, including age, body mass index (BMI), serum albumin, cognitive impairment, and activities of daily living (ADL).The results showed significant association of UR with cognitive impairment (P = .005, odds ratio [OR] 4.11, 95% confidence interval [CI] 1.53-11.03), and ADL (P = .029, OR 2.61, 95% CI 1.11-6.18), under adjustment with age and BMI.This study demonstrated that cognitive function and ADL were the important risk factors for UR, suggested that the postoperative management of UR is important with taking account of neurofunctional assistance and nursing care in daily living, especially in elderly female patients receiving surgery of femoral neck and trochanteric fractures.

Procalcitonin and albumin as prognostic biomarkers in elderly patients with a risk of bacterial infection.

Aim This study was performed to investigate serum procalcitonin (PCT) and albumin (Alb) as prognostic biomarkers in elderly patients at risk of bacterial infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age, 77.4 years) with suspected bacterial infection. The PCT-negative (<0.5 ng/mL) and PCT-positive (≥0.5 ng/mL) groups comprised 155 and 115 patients, respectively. Logistic regression analysis was performed with various clinical laboratory test values as independent variables and PCT positivity/negativity as the dependent variable. Results C-reactive protein (CRP) was the only independent variable significantly associated with PCT positivity/negativity. In the survival analysis, the 30-day in-hospital death rate was significantly higher in the PCT-positive than -negative group. Within the Alb-positive group (>2.5 g/dL), no significant difference in survival was observed between the PCT-positive and -negative groups. However, within the Alb-negative group (≤2.5 g/dL), the survival rate was significantly lower in the PCT-positive than -negative group. PCT was strongly associated with CRP and Alb, and having both PCT positivity and Alb negativity was a prognostic factor for elderly people at risk of bacterial infection. Conclusions Combined measurement of PCT with Alb is expected to be a valuable tool to assess prognosis in elderly people at risk of bacterial infection.

[Vitamin D in relation to frailty and locomotive syndrome].

Frailty is an extremely common and serious health problem in the elderly. Frailty has been described as "a biologic syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems and causing vulnerability to adverse health outcomes" by Fried and colleagues. Frailty is associated with incident falls, functional limitation, disability, and mortality. There are many reports that vitamin D deficiency may play roles in diabetes mellitus, cancers, multiple sclerosis, and other autoimmune diseases, and was associated with poorer physical performance, falls and fractures, and a greater risk of nursing home admission. Recently, researches suggest that vitamin D may provide treatment and prevention from these diseases lead to frailty. Vitamin D is expected to be a treatment for frailty in an aging society.

[Relationship between participation in a secondary screening test for the frail elderly and new onset of the need for long-term care among the elderly in a rural town].

OBJECTIVES: The present cohort study investigated the relationship between participation in a secondary screening test for the frail elderly and the findings of this screening test, and the relationship between participation and new onset of the need for long-term care in the elderly. METHODS: A primary screening survey was conducted on all 4,050 functionally independent elderly people aged > or = 65 years living in Ishikawa Town, Japan. We included 3,150 subjects for analysis, dividing them into the following 3 groups: 1) non-frail elderly, 2) possible frail elderly who participated in the secondary screening test, and 3) possible frail elderly who did not participate in the secondary screening test. We used Cox's proportional hazards model to calculate the hazard ratios of new onset of the need for long-term care by the participating and non-participating groups as compared to the non-frail group over 2 years. RESULTS: The proportion of non-frail elderly and possible frail elderly was 72.7% (n=2,289) and 27.3% (n=861), respectively. The number of subjects who did not participate in the secondary screening test (n=582) were 2.1-fold greater than that of subjects who did (n=279). The prevalences of withdrawal and impaired instrumental activity of daily living were significantly higher in the non-participating group than in the participating group. During the 2-year follow-up period, 168 subjects developed the need for long-term care. The incidence of new onset of the need for long-term care for each group (/1,000 persons) was 24.0 in the non-frail group, 93.2 in the participating group, and 149.5 in the non-participating group. The hazard ratios of new onset of the need for long-term care were 2.55 (95% confidence interval, 1.59-4.10) for the participating group and 4.46 (3.15-6.32) for the non-participating group after adjustment for confounding factors, including sex, age, and type of household. The hazard ratios were 0.75 (0.41-1.37) for the participating group and 1.09 (0.65-1.82) for the non-participating group after additional adjustment for total points on the Kihon Checklist (a frailty checklist) for assessing the frail elderly. CONCLUSION: Compared to non-frail elderly, the possible frail elderly had an increased risk of developing the need for long-term care. Moreover, compared to the possible frail elderly who participated in the secondary screening test, the possible frail elderly who did not participate in the test had a further increased risk of developing the need for long-term care.

[Frontiers in vitamin D; basic research and clinical application. Activated vitamin D in psoriasis].

Psoriasis is a chronic immune-mediated disease that appears on the skin. It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms. Activated vitamin D3 is the first-line treatment for psoriasis. Psoriasis is often treated with combination therapy of activated vitamin D3 and other treatment. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Thus, the goal for the treatment of psoriasis is to control the signs and symptoms over a long period and to ameliorate the quality of life of psoriasis patients.

[Arterial calcification and risk of cardiovascular events in diabetes mellitus].

The cohort studies reported the subclinical vascular calcification including atheroslerosis starts during prediabetic state characterized by impaired fasting glucose. In the cardiovascular systems of diabetes mellitus there is an original mechanism to induce the medial calcification other than intimal calcification observed in the classical atherosclerosis. This is characterized as the ectipic osteogenesis induced by paracrine signals from inflammatory lesions in the adventitia. On the other hand, many internal systems have been discovered to inhibit vascular calcification.

Mao-to Prolongs the Survival of and Reduces TNF-alpha Expression in Mice with Viral Myocarditis.

Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg(-1) kg(-1) day(-1)) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each, P < 0.05). HW and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-alpha (TNF-alpha) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-alpha. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis.

Silent information regulator, Sirtuin 1, and age-related diseases.

Sirtuin 1 (SIRT1), a member of the silent information regulator 2 in mammals, has recently been found to be involved in age-related diseases, such as cancer, metabolic diseases, cardiovascular disease, neurodegenerative diseases, osteoporosis and chronic obstructive pulmonary disease (COPD), mainly through deacetylation of substrates such as p53, forkhead box class O, peroxisome proliferator activated receptor gamma co-activator 1alpha, and nuclear factor-kappaB. It is widely reported that SIRT1 can promote not only carcinogenesis but also metastasis and insulin resistance, andhave beneficial effects in metabolic diseases, mediate high-density lipoprotein synthesis and regulate endothelial nitric oxide to protect against cardiovascular disease, have a cardioprotective role in heart failure, protect against neurodegenerative pathological changes, promote osteoblast differentiation, and also play a pivotal role as an anti-inflammatory mediator in COPD. However, there are controversial results suggesting that SIRT1 has an effect in protecting against DNA damage and accumulation of mutations, and preventing tumorigenesis. In addition, a high level of SIRT1 can induce cardiomyopathy and even heart failure. This article reviews recent developments relating to these issues.

Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of Hochu-ekki-to (TJ-41).

Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of chronic fatigue syndrome (CFS) and neuron apoptosis. Nevertheless, no study has been performed directly to explore the relationship between CFS, BDNF and neuron apoptosis. We induced a CFS model by six injections of killed Brucella abortus antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running activity, body weight (BW), ratio of cerebral weight to BW (CW/BW) and expression levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily activity and CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA expression levels in the hippocampus were suppressed in the CFS model and TJ-41 treated mice, while no significant difference was found between them. We improved a murine model to investigate the relationship between CFS and brain dysfunction. In this model, reduced daily activity might have been associated with decreased hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41 increased the daily running activity of the model, which was independent of brain recovery.

Candesartan improves myocardial damage in obese mice with viral myocarditis and induces cardiac adiponectin.

PURPOSE: To clarify the mechanism of the effects of angiotensin II receptor type 1 antagonist, candesartan, upon cardiac adiponectin in the combination of myocarditis with obesity, we examined obese KKAy mice with acute viral myocarditis treated by candesartan and investigated cardiac adiponectin regulation. METHODS: Mice were divided into candesartan early treatment group (Can-early) receiving orally candesartan at daily dose of 10 mg/kg 7 days starting before viral inoculation and then 7 days; candesartan late treatment group (Can-late) or vehicle (Vehicle) receiving candesartan starting simultaneously with viral inoculation and then 7 days. Encephalomyocarditis virus was used to induce the acute viral myocarditis. Differences in myocardial damages, serum adiponectin and myocardial expression of adiponectin, tumor necrosis factor-alpha (TNF-alpha), CCAAT/enhancer binding proteinalpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPAR-gamma) and nuclear factor-kappaB (NF-kappaB) mRNA among three groups were determined on days 0, 4 and 7 after viral inoculation. RESULTS: Mice in Can-early and Can-late groups showed reduced myocardial necrosis and cellular infiltration as compared with those in the Vehicle. On day 4 the circulating adiponectin levels were significantly higher in Can-early than those in Vehicle. Mice in Vehicle had significantly reduced in myocardial adiponectin mRNA after viral myocarditis. Cardiac adiponectin mRNA was significantly higher in Can-early and in Can-late than in Vehicle on days 4 and 7. Cardiac C/EBPalpha in Can-early and Can-early groups was significantly increased on day 4. Myocardial NF-kappaB and TNF-alpha mRNA in Can-early and Can-late groups were significantly reduced on day 7. CONCLUSION: Candesartan treatment improved myocardial injury in obese mice with acute viral myocarditis and induced expression of cardiac adiponectin with the induction of C/EBPalpha as well as the reduction of cardiac NF-kappaB and TNF-alpha.

Oral administration of candesartan improves the survival of mice with viral myocarditis through modification of cardiac adiponectin expression.

PURPOSE: We examined the effects of the angiotensin II receptor type 1 blocker candesartan on myocarditis injury in a murine model of acute myocarditis. We hypothesized that candesartan improves cardiac damage by inducing cardiac expression of adiponectin. METHODS AND RESULTS: We examined changes in heart failure caused by myocarditis in mice by candesartan based on induction of cardiac adiponectin expression. We intraperitoneally injected encephalomyocarditis virus in C3H mice, then orally administered candesartan (10 mg/kg/day) or vehicle (control). The 7 day survival rate was 18% in the control group, but 60% in the candesartan group. The heart weight/body weight ratio in the candesartan group was significantly lower than in the control group. Circulating adiponectin concentrations on day 7 were significantly higher in the candesartan group compared with the control group (7.91 +/- 0.61 vs. 6.04 +/- 2.26 microg/ml, P < 0.05). Comparative expression of cardiac adiponectin mRNA in the candesartan group was significantly higher than in the control group on day 7 (55.4 +/- 41.3 vs. 5.3 +/- 7.7, P < 0.05). Immunohistochemical staining and in situ hybridization showed that cardiac expression of adiponectin protein and mRNA was present in the candesartan group on day 7. CONCLUSION: Oral administration of candesartan improves survival and decreases myocardial damage in mice with viral myocarditis and induces expression of cardiac adiponectin. The induction of adiponectin might provide cardioprotective effects against acute heart failure due to viral myocarditis.

Reduced-energy diet improves survival of obese KKAy mice with viral myocarditis: induction of cardiac adiponectin expression.

Obesity is an important risk factor for heart disease. Whether weight loss affects the severity of heart failure induced by viral myocarditis is a matter of debate. We hypothesized that weight loss could improve cardiac dysfunction by inducing cardiac expression of a cardioprotective cytokine, adiponectin. We examined the relationship between weight loss by food restriction and heart failure due to viral myocarditis in obese KKAy mice. We intraperitoneally injected encephalomyocarditis virus (500 plaque-forming units/mouse) into KKAy mice fed ad libitum as a control (CF) or 60% restriction of that eaten by ad libitum (RF). The 14-day survival rate was 0% in FF, whereas it was 23% in RF (P<0.01). Heart weight/body weight ratio in RF was lower than that in FF on day 5 after viral inoculation (P<0.05). Histological scores for myocardial necrosis and inflammation on day 5 were significantly lower in RF than in FF (P<0.05). Circulating adiponectin level on day 0 was significantly elevated in RF compared with that in FF (32+9 vs. 22+2 microg/mL, P<0.05). Comparative expression of cardiac adiponectin mRNA in RF was significantly higher than that in FF (5.1+0.3 vs. 1+0.2, P<0.05). Cardiac tumor necrosis factor-alpha (TNF-alpha) mRNA in RF was significantly decreased compared with that in FF on day 5 (P<0.05). Cardiac expression of nuclear factor kappa B was reduced and that of peroxisome proliferator-activated receptor gamma mRNA was increased in RF in comparison with FF on day 0. Cardiac adiponectin mRNA was negatively correlated with cardiac TNF-alpha mRNA (r=-0.555; P=0.0097). Weight loss improved the survival and myocardial damage in obese mice with viral myocarditis, with cardiac induction of adiponectin. The induction of adiponectin might provide benefit through a cardioprotective effect against acute heart failure due to viral myocarditis in obese subjects.