AimsLoop diuretics are first‐line medications for congestive heart failure (CHF); however, they are associated with serious adverse effects, including decreased renal function, and sympathetic nervous and renin–angiotensin system activation. We tested whether tolvaptan, a vasopressin V2‐receptor antagonist, could reduce unfavourable furosemide‐induced effects during CHF treatment.Methods and resultsSixty patients emergently hospitalized owing to CHF‐induced dyspnea were randomly assigned to receive either 40 mg intravenous furosemide daily or 7.5 mg oral tolvaptan for 5 days after admission. Both groups also received intravenous carperitide and canrenoate potassium. As results, baseline patient characteristics were similar between the furosemide (n = 30) and the tolvaptan (n = 30) groups, with no significant difference in 5 day urine volume or fluid balance. Brain natriuretic peptide and body weight improvements were similar between groups. However, serum creatinine (Cr) level did not increase, and the incidence of worsening renal function was significantly lower in the tolvaptan group. Consequently, the Cr increase to gain 1000 mL urine was 2.5‐fold lower in the tolvaptan group. Furthermore, the blood urea nitrogen (BUN)/Cr ratio significantly decreased in the tolvaptan group, suggesting that renal perfusion was preserved, and urea reuptake and passive water reabsorption were suppressed following tolvaptan treatment. Although catecholamine improvements after treatment were not significantly different, plasma renin activity was enhanced in the furosemide group.ConclusionsAs compared with furosemide, tolvaptan in patients with acute heart failure is associated with comparable decongestion, better preservation of renal function and less activation of renin–angiotensin system. (UMIN 000014134).
AimsTo elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L).Methods and resultsThe HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70 mg/dL [1.8 mmol/L]; pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3–2.6 mmol/L]; pitavastatin monotherapy). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischaemia-driven revascularization. Between January 2010 and April 2013, 1734 patients were enroled at 19 hospitals in Japan. Patients were followed for at least 36 months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1 mg/dL (1.68 mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19 mmol/L) for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not reduce primary endpoint occurrence in comparison with standard statin monotherapy (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76–1.04, P = 0.152). In, ACS patients with higher cholesterol absorption, represented by elevated pre-treatment sitosterol, was associated with significantly lower incidence of the primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56–0.91).ConclusionAlthough intensive lowering with standard pitavastatin plus ezetimibe showed no more cardiovascular benefit than standard pitavastatin monotherapy in ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than statin monotherapy in patients with higher cholesterol absorption; further confirmation is needed.Trial NoUMIN000002742, registered as an International Standard Randomized Controlled Trial.
Two mutations, one at the nalB and the other at the mexR locus, in the Pseudomonas aeruginosa chromosome are known to cause overexpression of the MexAB-OprM efflux pump. Based on the following results, we concluded that nalB is the mutation that has occurred within the mexR gene of the P. aeruginosa chromosome. (i) Nucleotide sequencing of the mex operon upstream region of 21 independent nalB-type mutants including the original nalB9 revealed that all the mutations were located within the mexR gene. The mutations were classified into three different groups and nine types including single base substitutions, single base deletions and base insertions. (ii) Substitution of the mutant mexR with the wild-type mexR and replacement of the wild-type mexR with a defined mexR mutation resulted in the expression of wild-type and nalB-type MexAB-OprM respectively, which was confirmed by testing the antibiotic susceptibility and L-galactosidase activity of the mexA-lacZ translational fusion. ß
The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.
Free radicals are not only destructive to the living cells but also reduce the quality of animal products through oxidation. As a result the superoxide anion radical (O2・-), one of the most destructive reactive oxygen species, is a matter of concern for the animal scientists as well as feed manufacturers to ensure the quality of product to reach consumers demand. The superoxide anion radical scavenging activities (SOSA) of water and MeOH extracts of 2 herbs and 9 pasture samples collected from lowland and highland swards were determined against a 5,5-dimethyl-1-pyroline-N-oxide-O2・-spin adduct based on a hypoxanthine-xanthine oxidase reaction using electron spin resonance spectrometry. Both the water and MeOH extracted SOSA differed among the herbs and pastures. Species and altitudinal variations were observed between extraction methods. The herbs were higher in both water and MeOH extracted SOSA than the pastures except for water extracts of one pasture, white clover (Trifolium repens L.). Among the pastures, quackgrass (Agrophyron repens L.) showed higher SOSA in both the MeOH and water extracts, and timothy (Phleum pretense L.) showed higher MeOH extracted SOSA. It is apparent that the kind and amount of antioxidants differ among herbs and pastures. Animal health and quality of animal products could be improved by adequate selection and combining of herbs and pastures having higher SOSA.
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