Changes of imidazoline receptors in spontaneously hypertensive rats.

The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar-Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I(2) -receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I(1) -receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (K(ATP) ) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I(2) -receptor, which is expressed more highly in SHRs.

Using a nutritional screening tool to evaluate the nutritional status of patients with colorectal cancer.

We assessed which nutrition evaluation method [subjective global assessment (SGA); malnutrition universal screening tool (MUST); nutritional risk index (NRI)] provided the most efficacious combination of high validity, low cost, and ease of use to examine and improve the status of malnutrition for colorectal cancer (CRC) patients. The SGA, MUST, and NRI scales were used to analyze the preoperative status of malnutrition for 45 CRC patients in a medical center in Taiwan. Differences in the reliability of the 3 methods were compared using the kappa (κ) coefficient of agreement. Lengths of hospital stays were compared using the Mann-Whitney U test to examine the effect of malnutrition in CRC patients. The SGA κ coefficient was higher with the MUST than with the NRI. Preoperative and postoperative weight losses were significantly different on the NRI, and the longer the length of the hospital stay, the greater was the weight loss. Although the SGA had a higher validity and lower cost than the NRI, we recommend using the MUST method for a routine nutrition evaluation because it is easier to use and is less expensive than the SGA and the NRI.

Intraclass reliability for assessing how well Taiwan constrained hospital-provided medical services using statistical process control chart techniques.

BACKGROUND: Few studies discuss the indicators used to assess the effect on cost containment in healthcare across hospitals in a single-payer national healthcare system with constrained medical resources. We present the intraclass correlation coefficient (ICC) to assess how well Taiwan constrained hospital-provided medical services in such a system. METHODS: A custom Excel-VBA routine to record the distances of standard deviations (SDs) from the central line (the mean over the previous 12 months) of a control chart was used to construct and scale annual medical expenditures sequentially from 2000 to 2009 for 421 hospitals in Taiwan to generate the ICC. The ICC was then used to evaluate Taiwan's year-based convergent power to remain unchanged in hospital-provided constrained medical services. A bubble chart of SDs for a specific month was generated to present the effects of using control charts in a national healthcare system. RESULTS: ICCs were generated for Taiwan's year-based convergent power to constrain its medical services from 2000 to 2009. All hospital groups showed a gradually well-controlled supply of services that decreased from 0.772 to 0.415. The bubble chart identified outlier hospitals that required investigation of possible excessive reimbursements in a specific time period. CONCLUSION: We recommend using the ICC to annually assess a nation's year-based convergent power to constrain medical services across hospitals. Using sequential control charts to regularly monitor hospital reimbursements is required to achieve financial control in a single-payer nationwide healthcare system.

Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats.

AIM: To assess the therapeutic effect of melatonin on heat-induced acute lung inflammation and injury in rats. METHODS: Heatstroke was induced by exposing anesthetized rats to heat stress (36 °C, 100 min). Rats were treated with vehicle or melatonin (0.2, 1, 5 mg/kg) by intravenous administration 100 min after the initiatioin of heatstroke and were allowed to recover at room temperature (26 °C). The acute lung injury was quantified by morphological examination and by determination of the volume of pleural exudates, the number of polymorphonuclear (PMN) cells, and the myeloperoxidase (MPO) activity. The concentrations of tumor necrosis factor, interleukin (IL)-1ß, IL-6, and IL-10 in bronchoalveolar fluid (BALF) were measured by ELISA. Nitric oxide (NO) level was determined by Griess method. The levels of glutamate and lactate-to-pyruvate ratio were analyzed by CMA600 microdialysis analyzer. The concentrations of hydroxyl radicals were measured by a procedure based on the hydroxylation of sodium salicylates leading to the production of 2,3-dihydroxybenzoic acid (DHBA). RESULTS: Melatonin (1 and 5 mg/kg) significantly (i) prolonged the survival time of heartstroke rats (117 and 186 min vs 59 min); (ii) attenuated heatstroke-induced hyperthermia and hypotension; (iii) attenuated acute lung injury, including edema, neutrophil infiltration, and hemorrhage scores; (iv) down-regulated exudate volume, BALF PMN cell number, and MPO activity; (v) decreased the BALF levels of lung inflammation response cytokines like TNF-alpha, interleukin (IL)-1ß, and IL-6 but further increased the level of an anti-inflammatory cytokine IL-10; (vi) reduced BALF levels of glutamate, lactate-to-pyruvate ratio, NO, 2,3-DHBA, and lactate dehydrogenase. CONCLUSION: Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung inflammation and injury.

Activation of ß-adrenoceptors by dobutamine may induce a higher expression of peroxisome proliferator-activated receptors δ (PPARδ) in neonatal rat cardiomyocytes.

Recent evidence showed the role of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Cardiac contraction induced by various agents is critical in restoring the activity of peroxisome proliferator-activated receptors δ (PPARδ) in cardiac myopathy. Because dobutamine is an agent widely used to treat heart failure in emergency setting, this study is aimed to investigate the change of PPARδ in response to dobutamine. Neonatal rat cardiomyocytes were used to examine the effects of dobutamine on PPARδ expression levels and cardiac troponin I (cTnI) phosphorylation via Western blotting analysis. We show that treatment with dobutamine increased PPARδ expression and cTnI phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. These increases were blocked by the antagonist of ß1-adrenoceptors. Also, the action of dobutamine was related to the increase of calcium ions and diminished by chelating intracellular calcium. Additionally, dobutamine-induced action was reduced by the inhibition of downstream messengers involved in this calcium-related pathway. Moreover, deletion of PPARδ using siRNA generated the reduction of cTnI phosphorylation in cardiomyocytes treated with dobutamine. Thus, we concluded that PPARδ is increased by dobutamine in cardiac cells.

Effect of 1PC111, a Fixed-dose Combination of Pitavastatin and Ezetimibe, Versus Pitavastatin or Ezetimibe Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia or Mixed Dyslipidemia: A Randomized, Double-blind, Multicenter, Phase III Study.

PURPOSE: This study aimed to show that the efficacy of 1PC111 is superior to that of either ezetimibe or pitavastatin alone (monotherapy) for the treatment of hypercholesterolemia. METHODS: This was a multicenter, randomized, double-blind, Phase III study. Patients with hypercholesterolemia or mixed dyslipidemia were randomized to receive 1PC111 (which was a fixed-dose combination of pitavastatin 2 mg and ezetimibe 10 mg), pitavastatin 2 mg, or ezetimibe 10 mg daily for 12 weeks. The primary end point was the difference in the percent change in LDL-C from baseline to week 12 between the 1PC111 and each monotherapy group. The secondary end points were the percent change in other lipid profiles from baseline to each visit. All patients were assessed for adverse events until end of study. FINDINGS: A total of 388 patients were randomly assigned to the 1PC111 (n = 128), pitavastatin (n = 132), or ezetimibe (n = 128) group. Generally, baseline characteristics were similar among the 3 groups. A statistically significant decrease in the LDL-C level at week 12 was observed in the 1PC111 group (-50.50% [14.9%]) compared with either the pitavastatin (-36.11% [11.4%]; P < 0.001) or ezetimibe (-19.85% [12.4%]; P < 0.001) group. Also, there was a statistically significant difference between 1PC111 and each monotherapy group in the reduction in total cholesterol, non-HDL-C, and apolipoprotein B levels. Moreover, there was a trend toward more efficient lowering of LDL-C levels in elderly patients (age ≥65 years) than in younger patients (age <65 years) by 1PC111 treatment. In patients given a class I recommendation for atherosclerotic cardiovascular disease prevention, the percentage of patients achieving the LDL-C target of <100 mg/dL at week 12 was significantly higher in the 1PC111 group than in both monotherapy groups (P < 0.001). Overall, the incidence of adverse events was similar among 3 groups. IMPLICATIONS: 1PC111 was more effective in improving lipid profiles and achieving the LDL-C goal than pitavastatin or ezetimibe alone for hypercholesterolemia treatment. Furthermore, 1PC111 may provide more benefit in treating elderly patients. CLINICALTRIALS: gov identifier: NCT04643093.

Radial artery occlusion with a kaolin-filled pad after transradial cardiac catheterization.

Radial artery occlusion (RAO) occurs in 2% to 18% of patients after transradial access (TRA) cardiac catheterization. Using a kaolin-filled pad (QuikClot) reduces compression time during TRA and might reduce RAO. We examined the RAO risk with the kaolin-filled pad after TRA cardiac catheterization.This was a prospective cross-sectional study of 260 patients who underwent TRA cardiac catheterization in a cardiac ward of a Medical Center from 2012 to 2016. Patients were randomly assigned to 1 of 2 groups: the case group (n = 130) was postoperatively treated with a kaolin-filled pad, and the control group (n = 130) was treated with conventional hemostasis. Color duplex ultrasound was used to evaluate the 24-hour and 1-month postoperative radial artery flow velocity, diameter, patency, and RAO risk.RAO risk was not significantly different between the case and control groups after 24 hours (4.6% vs 5.4%, P = .776) or after 1 month (5.4% vs 6.1%, P = .789), regardless of whether it was a first TRA cardiac catheterization (after 24 hours [P = .153] or after 1month [P = .617], respectively) or a repeated TRA cardiac catheterization (after 24 hours [P = .754] or after 1month [P = .753], respectively).Using a kaolin-filled pad after TRA cardiac catheterization did not significantly reduce RAO risk compared with conventional hemostasis.

Epidemiologic features and long-term outcome of dialysis patients with infective endocarditis in Taiwan.

BACKGROUND: The incidence of infective endocarditis (IE) is high in dialysis patients. Limited data are available on the risk factors for IE and long-term outcome after IE in dialysis patients, especially in Asian populations. METHODS: We used Taiwan National Health Insurance Research Database to design a longitudinal cohort study. 68,426 ESRD patients who began dialysis between 1999 and 2007 were included. The follow-up period was from the start of dialysis to death, end of dialysis, or end of 2008. Cox proportional hazards models were used to identify the risk factors for IE. RESULTS: IE was diagnosed in 502 patients during follow-up (201.4 per 100,000 person-years). Diabetes mellitus (DM), congestive heart failure (CHF), cerebro-vascular accident (CVA), and rheumatic heart disease (RHD) (HR: 3.07, 95% CI: 1.99-4.75) were associated with an increasing risk of development of IE. The cumulative incidence rate of IE in patients with RHD was 1.4, 2.2, and 3.9% at 1, 3, and 5 years. In-hospital mortality was 23.5%. Cumulative survival rates post-IE were 54.3% at 1 year and only 35.3% at 5 years. CONCLUSION: Dialysis patients had a higher risk of IE. Those who were older and had DM, CHF, CVA, or especially RHD were at a greater risk. Dialysis patients with IE also had high mortality.

Epidemiology and mortality among dialysis patients with acute coronary syndrome: Taiwan National Cohort Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) on dialysis have poor outcomes after acute coronary syndrome (ACS). Epidemiological data for Asian patients are scarce. METHODS: This longitudinal cohort study investigated the incidence, risk factors, and outcomes of ACS in 19,974 ESRD incident dialysis patients in the Taiwan National Health Insurance research Database between January 1999 and December 2001. The follow-up period was from the start of dialysis to the date of death, end of dialysis, or December 31, 2008. RESULTS: ACS was diagnosed in 1785 patients during follow-up (1.78/100 person-years): 832 (46.6%) had acute myocardial infarction (AMI), 681 (38.2%) underwent cardiac catheterization, 398 (22.3%) underwent percutaneous transluminal coronary angioplasty (PTCA), and 50 (2.8%) underwent coronary artery bypass grafting. Male (HR 1.35, 95% CI: 1.23-1.49) and elderly (HR 3.289, 95% CI: 2.71-4.00) patients had a high rate of ACS. Patients with baseline comorbidities (diabetes mellitus, hypertension, congestive heart failure, coronary artery disease, dysrhythmia, and other cardiac and chronic obstructive lung diseases) had a higher incidence of ACS than did those without. Overall in-hospital mortality was 9.7%. The cumulative 6-month post-hospitalization survival rate was 79.3%; the 1-year rate was 72.3%. Being elderly (≥ 65 years old), and having DM or AMI were associated with an increased risk for mortality; PTCA was associated with a decreased risk (HR 0.77, 95% CI: 0.66-0.91). CONCLUSION: ESRD dialysis patients had a high incidence of ACS and mortality. Being male, elderly and having baseline comorbidities were independent risk factors for ACS. Coronary intervention is the possible benefits for dialysis patients.

Reverse epidemiology of hypertension-mortality associations in hemodialysis patients: a long-term population-based study.

BACKGROUND: Although hypertension (HTN) is a predictor of mortality, recent data have questioned the link between baseline HTN and mortality in incident hemodialysis (HD) patients. We used Taiwan's National Health Insurance claim data (NHRI-NHIRD-99182) to investigate the association. METHODS: In 1999, this longitudinal cohort study enrolled 5752 new HD patients. Follow-up began from the initiation of HD until death, the end of HD, or the end of 2008. A Kaplan-Meier survival analysis was done. Cox proportional hazard analysis was used to identify the risk factors for mortality. RESULTS: The prevalence of baseline HTN was 75.47%. Patients with HTN had a higher prevalence of diabetic mellitus (DM) and cardiovascular diseases. The 1-, 5-, and 9-year cumulative survival rates were 95.5, 63.7 and 41.8% in patients with HTN, and 95.5, 71.0, and 52.0% in those without HTN (log-rank test: P <0.001). Multivariate analysis showed that patients with baseline HTN may have a higher survival rate (hazard ratio (HR) 0.901, 95% confidence interval (CI): 0.819-0.992). After stratification by age and DM, only elderly (≥65) patients without DM had a significantly higher survival rate (HR 0.769, 95% CI: 0.637-0.927). HTN predicts lower mortality with increasing age in patients with congestive heart failure (CHF) or coronary artery disease (CAD). CONCLUSIONS: There is a reverse (counterintuitive) association between baseline HTN and mortality in elderly HD patients without DM and a clear tendency for a reverse association with increasing age in patients with CHF or CAD. Further study of the association between HTN and mortality in older HD patients may be warranted.