Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension.

BACKGROUND: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. METHODS: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). RESULTS: A total of 532 patients were randomized: Per/Ind/Aml ( n  = 262) and Per/Ind + Aml ( n  = 269). Overall, the mean (±SD) age was 55.7 ±â€Š8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ±â€Š14.46 mmHg Per/Ind/Aml versus -14.49 ±â€Š12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P  < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated. CONCLUSIONS: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.

Drug sensitivity and genome-wide analysis of two strains of Mycoplasma gallisepticum with different biofilm intensity.

Mycoplasma gallisepticum (MG) is one of the major causative agents of chronic respiratory diseases in poultry. The biofilms of MG are highly correlated to its chronic infection. However data on genes involved in biofilm formation ability are still scarse. MG strains with distinct biofilm intensity were screened by crystal violet staining morphotyped and characterized for the drug sensitivity. Two MG strains NX-01 and NX-02 showed contrasted ability to biofilm formation. The biofilm formation ability of NX-01 strain was significantly higher than that of NX-02 strain (p < 0.01). The drug sensitivity test showed that the stronger the ability of MG stain to form biofilms, the weaker its sensitivity to 17 antibiotic drugs. Moreover, putative key genes related to biofilm formation were screened by genome-wide analysis. A total of 13 genes and proteins related to biofilm formation, including ManB, oppA, oppD, PDH, eno, RelA, msbA, deoA, gapA, rpoS, Adhesin P1 precursor, S-adenosine methionine synthetase, and methionyl tRNA synthetase were identified. There were five major discrepancies between the two isolated MG strains and the five NCBI-published MG strains. These findings provide potential targets for inhibiting the formation of biofilm of MG, and lay a foundation for treating chronic infection.

Cryptococcal endocarditis of native valves without immunodeficiency or drug abuse: a case report.

Cryptococcal endocarditis has rarely been reported. Most patients with this condition are associated with risk factors, such as structural heart disease/valve replacement, immunodeficiency/immunosuppression or drug abuse. We report a case of cryptococcal endocarditis of the native valves without any risk factors. A 50-year-old Chinese man was admitted to hospital with fever for 1 month without any underlying heart disease, immunodeficiency, or drug use. He was diagnosed as having Cryptococcus neoformans infective endocarditis and was discharged after valve replacement surgery and long-term antifungal therapy.

APELA/ELA32 Reduces Iodixanol-induced Apoptosis, Inflammatory Response and Mitochondrial and DNA Damage in Renal Tubular Epithelial Cells.

BACKGROUND/AIM: Contrast-induced AKI (CI-AKI) is an important clinical complication of intravascular use of iodinated contrast agents. The aim of the present study was to investigate the renoprotective effect of Apela on contrast-induced acute kidney injury. MATERIALS AND METHODS: Blood samples from patients exposed to iodinated contrast agent were collected to assay for Apela and creatinine levels. The effects of ELA32 (Apela 32) on iodixanol-induced apoptosis, inflammation response, mitochondrial ROS production and DNA damage were examined in NRK-52E renal tubular epithelial cells. RESULTS: Plasma Apela levels were decreased in patients exposed to the contrast agent. Iodixanol-induced apoptosis was reduced in ELA32 treated NRK-52E cells (p<0.05). ELA32 treatment inhibited iodixanol-induced mitochondrial ROS generation (p<0.01). Iodixanol-induced inflammatory cytokines TNFa and IL-6 and inflammatory genes Nrf2 and ICAM-1 were reduced by ELA32 treatment (p<0.01). Reduced Apela expression in iodixanol-treated cells was partially restored by ELA32 treatment (p<0.05). ELA32 treatment suppressed iodixanol-induced up-regulation of DNA damage-associated gene P-ATR and p-CHK1 as well as apoptosis-associated gene C-caspase 3 (p<0.05). CONCLUSION: Administration of iodinated contrast agent reduces Apela expression. ELA32 treatment reduces iodixanol-induced apoptosis, inflammatory response and mitochondrial and DNA damage in renal tubular epithelial cells.

Rat IgG mediated circulatory cell depletion in mice requires mononuclear phagocyte system and is facilitated by complement.

Application of exogenous Abs targeting cell surface Ags has been widely used as an experimental approach to induce cell depletion or to inhibit receptor functionality. Moreover, Ab therapy is emerging as one of the mainstream strategies for cancer treatment. Previous studies on the mechanisms of Ab-mediated cell depletion mainly employed Abs from the same species as the research subject. However, there has been a recent trend toward using xenogeneic (cross-species) Abs to achieve cell depletion or block receptor-ligand interactions; with rat Abs used in mice being the most common approach. Considering the molecular differences in Abs from different species, the mechanism(s) of xenogeneic Ab-mediated cell depletion is likely to be different than species-matched Ab supplementation. The current work describes our efforts to identify the mechanism of rat anti-mouse Ly6G (clone: 1A8) mAb mediated depletion of mouse neutrophils. The results showed that neutrophils circulating in the blood but not those in the bone marrow are depleted, and depletion depends on mononuclear phagocyte system, especially liver Kupffer cells that efficiently capture and phagocytize targeted cells. Interestingly, whereas species-matched Ab depletion does not require complement functionality, we found that complement activation significantly facilitates cross-species neutrophil depletion. Finally, we found that some rat mAbs (anti-C5aR, anti-CD11a, anti-CD11b, and anti-VLA4) used to block cell surface receptors also induce cell depletion. Thus, our work strongly recommends controlling for cell depletion effect when using these Abs for receptor blockade purposes.

A meta-analysis of the association between poultry and egg consumption and the risk of brain cancer.

Poultry consumption, as well as egg consumption for brain cancer risk remains an important topic. The objective of this meta-analysis is to investigate the role of poultry and egg consumption for brain cancer risk. All articles about poultry and egg consumption for brain cancer were retrieved from PubMed, Web of knowledge and Wan Fang Med Online. The data was analyzed using Stata 12.0 software. Ten articles (6 articles for poultry and 5 articles for egg) were included. For poultry consumption, the summarized relative risk (RR) was 0.901 (95%CI= 0.703-1.154) for brain cancer risk, with high between-study heterogeneity (I2= 60.7%, P=0.018). Four studies reported the association between poultry consumption and glioma risk, yielding a RR of 0.873 (95%CI= 0.737-1.034, I2= 0.0%, P=0.838). The association between egg consumption and brain cancer risk was not significant (RR= 0.998, 95%CI= 0.552-1.805), with significant heterogeneity (I2= 82.6%, P< 0.001). The pooled RR for glioma risk was 1.472 (95%CI= 0.935-2.316). In summary, our results concluded that poultry and egg consumption may be not associated with the risk of brain cancer. Due to the limited quality of evidence currently available, more studies related to poultry and egg consumption for brain cancer is necessary.

Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium.

BACKGROUND/OBJECTIVES: Induced pluripotent stem cells (iPS) exhibit enhanced survival and proliferation in ischemic tissues. However, the therapeutic application of iPS cells is limited by their tumorigenic potential. We hypothesized that iPS cells can transmit cytoprotective signals to cardiomyocytes via exosomes/microvesicles. METHODS: Exosomes/microvesicles secreted from mouse cardiac fibroblast (CF)-derived iPS cells (iPS-exo) were purified from conditioned medium and confirmed by electron micrograph, size distribution and zeta potential by particle tracking analyzer and protein expression of the exosome markers CD63 and Tsg101. RESULTS: We observed that exosomes are at low zeta potential, and easily aggregate. Temperature affects zeta potential (-14 to -15 mV at 23 °C vs -24 mV at 37 °C). The uptake of iPS-exo protects H9C2 cells against H2O2-induced oxidative stress by inhibiting caspase 3/7 activation (P < 0.05, n = 6). Importantly, iPS-exo treatment can protect against myocardial ischemia/reperfusion (MIR) injury via intramyocardial injection into mouse ischemic myocardium before reperfusion. Furthermore, iPS-exo deliver cardioprotective miRNAs, including nanog-regulated miR-21 and HIF-1α-regulated miR-210, to H9C2 cardiomyocytes in vitro. CONCLUSIONS: Exosomes/microvesicles secreted by iPS cells are very effective at transmitting cytoprotective signals to cardiomyocytes in the setting of MIR. iPS-exo thus represents novel biological nanoparticles that offer the benefits of iPS cell therapy without the risk of tumorigenicity and can potentially serve as an "off-the-shelf" therapy to rescue ischemic cardiomyocytes in conditions such as MIR.

Combined electrocardiography, coronary angiography and magnetic resonance imaging for the diagnosis of viral myocarditis: A case report.

Endomyocardial biopsy is the gold standard for diagnosing viral myocarditis. However, this method is rarely used as it is more invasive, less sensitive and has a higher incidence of complications than other methods. With recent developments in myocarditis research, cardiovascular nuclear magnetic resonance imaging has been demonstrated to have a marked advantage over endomyocardial biopsy, specifically regarding the differential diagnosis of acute coronary syndrome, as it is noninvasive, repeatable, highly sensitive and highly specific for diagnosing myocarditis. Myocardial edema is characteristic of myocardial inflammation, myocardial necrosis and myocardial fibrosis. T2-weighted nuclear magnetic resonance imaging sensitively detects myocardial tissue edema and additional imaging parameters contribute to the diagnosis of myocarditis. Therefore, combining these methods with the current sophisticated electrocardiogram and coronary angiography examination methods may facilitate the rapid and accurate assessment of viral myocarditis. A 44-year-old male patient with symptoms of dyspnea and shortness of breath accompanied by dizziness, through electrocardiography, coronary angiography and magnetic resonance imaging, was diagnosed viral myocarditis.

Repeated intracoronary infusion of peripheral blood stem cells with G-CSF in patients with refractory ischemic heart failure--a pilot study.

BACKGROUND: Recent investigations have suggested the clinical efficacy of granulocyte colony-stimulating factor (G-CSF) infusion alone or in combination with a single dose delivery of peripheral blood stem cells (PBSC) infusion in patients with myocardial infarction (MI) and congestive heart failure (HF). The current study tested the feasibility and effect of repeated intracoronary infusions PBSC and the mobilization of G-CSF in patients with refractory HF after MI. METHODS AND RESULTS: Patients with recent large MI and a lower left ventricular ejection fraction (LVEF) were enrolled into one of the following 3 groups: Group R (n=15) received repeated intracoronary infusion of PBSC and one-dose of G-CSF; Group S (n=15) received a single infusion of PBSC and a G-CSF dose; and Group C (n=15) received neither PBSC nor a G-CSF dose. Cardiac performance was evaluated by echocardiography and single photon-emission computed tomography (SPECT). All the patients underwent 12-month follow-up. LVEF in Group R (47.00±4.90%) was significantly higher than that in Group S (44.40±3.87%, P<0.01) and Group C (40.80±3.41%, P<0.01). Similarly, the improvement of myocardial perfusion assessed by SPECT in Group R was more than that in Group S (P=0.012) and Group C (P<0.01). Neither death nor new MI occurred. CONCLUSIONS: Repeated intracoronary infusions of PBSC plus mobilization of G-CSF might be an optional effective strategy for treating patients with refractory HF after recent large MI.