Safety evaluation of Lactobacillus pentosus strain b240.

Lactobacillus pentosus has a long history of use in cooked and uncooked fermented foods. Viable and heat-killed nonviable preparations of L. pentosus strain b240 were evaluated for short term and subchronic toxicity and genotoxic potential. Dose levels were determined through acute oral toxicity tests with viable (LD(50)>2500 mg/kg) and nonviable (LD(50)>2000 mg/kg) b240. In the short term study, rats received 2500 mg/kg/day (∼1.7×10(11)cfu/kg/day) viable b240 for 28 days. In the subchronic study, rats received 500, 1000 or 2000 mg/kg/day (up to ∼3.0×10(12) cfu equivalents/kg/day) nonviable b240 for 91 days followed by a 28-day recovery. No mortalities occurred. No treatment-related effects were identified for general condition, body weight, food-water consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights, histopathology and gross pathology. Although statistically significant effects were noted for several endpoints in the short term and subchronic studies, none were related to the test materials. The NOAEL for nonviable b240 was 2000 mg/kg/day, the highest dose tested. Additionally, nonviable b240 (≤ 5000 µg/plate) was not mutagenic in Salmonella typhimurium or Escherichia coli tester strains nor did nonviable b240 orally administered to rats at levels ≤ 2000 mg/kg/day for two days, induce a clastogenic response.

Pump failure death and sudden cardiac death in patients with cardiac dysfunction: a search for prognostic predictive factors--a long-term follow-up study.

BACKGROUND: There have been few reports that have analyzed the predictive factors for heart failure death, which is sub-divided into pump failure death and sudden cardiac death, in the long term. METHODS AND RESULTS: We followed 186 consecutive patients with myocardial infarction (MI) and 115 consecutive patients with non-ischemic heart failure (NIHF) during 73+/-3 months. In the MI group, 26 died from pump failure and 12 died from sudden cardiac death. In the NIHF group, 21 died from pump failure and 9 died from sudden cardiac death. Multivariate analysis revealed that the log B-type natriuretic peptide (BNP) was an independent predictor for pump failure death in both groups. In the MI group, the estimated glomerular filtration rate (eGFR) was an independent predictor for sudden cardiac death. Kaplan-Meier analysis revealed that a high BNP level was a risk factor for pump failure death in either MI or NIHF patients. On the other hand, the sudden cardiac death rate was significantly higher in the MI patients with low eGFR than in those with high eGFR. CONCLUSIONS: The plasma BNP level is an independent predictor for pump failure death in both MI and NIHF patients. The eGFR is an independent predictor for sudden cardiac death in MI patients.

Clinical factors affecting serum potassium concentration in cardio-renal decompensation syndrome.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors are currently indispensable for the treatment of heart failure. It is well known that hyperkalemia is likely to occur in renal failure; however, it has not yet been clarified how the serum potassium concentration changes as heart failure progresses. Currently, the cardio-renal decompensation syndrome holds that the serum potassium concentration is altered similarly by both heart failure and renal failure; however, there are no definitive reports on this. In order to use RAAS inhibitors more safely and effectively in heart failure, it is necessary to understand the factors affecting serum potassium concentration in the clinical setting. METHODS AND RESULTS: We examined the clinical factors affecting serum potassium concentration in 1035 consecutive patients with cardiovascular disease who were hospitalized in our institution. Multiple regression analysis showed that the independent factors associated with an elevated serum potassium concentration were renal insufficiency evaluated by estimated glomerular filtration rate (eGFR) (P<0.0001), diabetes mellitus evaluated by HbA(1c) (P=0.0005) and the use of RAAS inhibitors (P=0.0010). The independent factors associated with a decreased serum potassium concentration were mean blood pressure (P<0.0001), heart failure evaluated by log BNP (P=0.0164) and the use of diuretics (P=0.0232). CONCLUSIONS: The serum potassium concentration decreases with the severity of heart failure if renal function is preserved. From the perspective of potassium homeostasis, we could use the RAAS inhibitors more aggressively in patients with heart failure who do not have renal failure.

Increased density of the liver and amiodarone-associated phospholipidosis.

This is a case report in which a 60-year-old man who suffered from ventricular tachycardia with dilated cardiomyopathy was prescribed amiodarone. After taking amiodarone, liver enzymes were increased and computed tomographic (CT) scanning of the abdomen showed a significant increase in the density of the liver without contrast medium. He was suspected as hemochromatosis and liver biopsy was performed. An abnormal high density of liver tissue may be observed in an unenhanced CT in patients treated with amiodarone and we suggest that periodic monitoring of liver function and/or liver biopsy is warranted before an irreversible stage is reached.

The synergistic combined effect of anemia with high plasma levels of B-type natriuretic peptide significantly predicts an enhanced risk for major adverse cardiac events.

The prevalence of anemia in patients with heart failure (HF) increases according to disease severity as a consequence of renal insufficiency, cytokine production, plasma volume expansion, and/or malnutrition. B-type natriuretic peptide (BNP) has been recognized as a biochemical marker of ventricular dysfunction. The aim of this study was to evaluate the clinical significance of anemia in HF patients and furthermore, to investigate whether a significant correlation exists between anemia, BNP, and poor clinical outcomes in HF patients. We studied 185 consecutive HF patients. We assessed the occurrence of major adverse cardiac events (MACE) post hospital discharge. Anemia was defined as Hb concentrations <12.9 g/dl in men and <11.3 g/dl in women, respectively. Kaplan-Meier analysis revealed that anemia and high BNP levels (>259 pg/ml) were significantly associated with the occurrence of MACE. Multiple logistic analysis revealed that the most predictive independent risk factor for the occurrence of MACE was high BNP levels, followed by anemia (relative risk [RR] = 2.803 and 2.241, respectively). We divided the patients with or without anemia and high or low BNP levels into four groups according to their respective Hb and BNP levels. The hazard ratio for MACE in the group with anemia and high BNP levels was 10.3 in comparison to the group without anemia and with low BNP levels (P = 0.0002). Both anemia and high plasma levels of BNP are significantly and independently associated with the occurrence of MACE in HF patients; furthermore, the synergistic effect of anemia combined with high BNP levels significantly predicts an enhanced risk for MACE.

Relationship between plasma glutathione levels and cardiovascular disease in a defined population: the Hisayama study.

BACKGROUND AND PURPOSE: Glutathione (GSH) appears to have marked antioxidant activities and therefore may prevent cardiovascular disease (CVD). However, there are very few reports on this subject. In a community-based case-control study, we tested the hypothesis that low levels of plasma GSH are closely associated with CVD and its clinical types. METHODS: The association between fasting plasma total GSH (tGSH) levels and CVD were assessed using conditional logistic regression analysis among 134 CVD cases and 435 age- and sex-matched healthy control subjects. RESULTS: Mean tGSH concentrations were lower in all CVD cases than in the control subjects (3.06 versus 3.71 micromol/L; P=0.0001). Among the CVD types, both the cerebral infarction cases (2.98 versus 3.59 micromol/L; P=0.001) and cerebral hemorrhage cases (2.51 versus 3.43 micromol/L; P=0.0027) had significantly lower tGSH levels than the corresponding control groups had. The same tendency was observed for cases of subarachnoid hemorrhage (3.45 versus 3.83 micromol/L; P=0.36) and myocardial infarction (3.65 versus 3.77 micromol/L; P=0.69), but these differences were not statistically significant. After adjustment for other confounding factors, the risk of CVD was significantly lower in the third (adjusted odds ratio, 041; 95% CI, 0.21 to 0.77) and the fourth quartiles (adjusted odds ratio, 0.25; 95% CI, 0.12 to 0.51) than in the first. This association was most prominent in patients with lacunar infarction or cerebral hemorrhage. CONCLUSIONS: These findings suggest that reduced plasma tGSH levels are a risk factor for CVD, especially for cerebral small vessel disease.

Plasma homocyst(e)ine concentrations and the risk of subtypes of cerebral infarction. The Hisayama study.

Moderately elevated plasma total homocyst(e)ine (tHcy) levels have been linked with cardiovascular disease. However, the findings of previous studies regarding the relationship between tHcy levels and subtypes of cerebral infarction (CI) have been conflicting. The aim of the present study was to examine this issue in a community-based case-control study performed in Hisayama Town in Japan. Fasting tHcy levels were compared among 75 CI cases, of which 43 were lacunar (LI), 24 atherothrombotic (ATI) and 8 cardioembolic infarctions (CEI), and 248 age- and sex-matched healthy controls. The mean tHcy concentrations were higher in CI than in controls (13.0 vs. 11.8 micromol/l; p = 0.018). LI and CEI also had significantly higher tHcy levels than did the corresponding controls (12.3 vs. 11.3 micromol/l for LI; p = 0.037 and 16.3 vs. 12.7 micromol/l for CEI; p = 0.036). The same tendency was also observed for ATI, but the difference was only marginally significant probably due to the small number of the cases (13.4 vs. 11.9 micromol/l; p = 0.087). After adjustment for age, sex, hypertension, serum creatinine, total protein, folate and vitamin B(12) levels, the risk of LI was not significant in the second tertile of the tHcy distribution, but significantly increased in the third compared with the first tertile (adjusted odds ratio, AOR, 3.4; 95% confidence limits, CL, 1.3-8.9; p = 0.015), while the risk of ATI was significant even in the second tertile (AOR, 5.0; 95% CL, 1.0-23.7; p = 0.042) and higher in the third tertile (AOR, 7.5; 95% CL, 1.5-38.3; p = 0.015). However, the odds ratios for CEI could not be estimated, as there was no case of CEI in the first tertile. These findings suggest that elevated tHcy is an independent risk factor for all subtypes of CI, but that its impact is higher in ATI and probably in CEI than in LI.