An ultrasensitive bacterial imprinted electrochemical sensor for the determination of Lactobacillus rhamnosus GG.

An ultrasensitive label-free electrochemical sensor based on a homemade imprinted polypyrrole (PPy) polymer film was prepared to achieve quantitative determination of Lactobacillus rhamnosus GG (LGG). The LGG-imprinted polymer (LIP) film was deposited on a portable screen-printed electrode (SPE) via electropolymerization, which constituted an independent integrated system. The main preparation parameters of the LIP sensor were investigated to obtain optimal performance. Under optimized conditions, the peak current response of the LIP sensor showed a linear relationship with the logarithmic value of LGG concentration in the range from 101 to 109 CFU mL-1 and a detection limit of 5 CFU mL-1. The proposed LIP sensor has achieved efficient, ultrasensitive, highly selective, and cost-effective detection of LGG and can be further developed for practical applications in the quality inspection and development of probiotic products.

Five-year outcomes of ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome treated with biodegradable polymer-coated sirolimus-eluting stents: Insights from the CREATE trial.

BACKGROUND: Long-term outcome of drug-eluting stents (DES) for ST-elevation myocardial infarction (STEMI) versus non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unclear. This study sought to compare the long-term outcomes of biodegradable polymer-coated DES in patients with STEMI versus NSTE-ACS. METHODS: We explored a post hoc analysis of the 5-year outcome of the CREATE trial in the subgroup of patients with STEMI (n=318) versus NSTE-ACS (n=1223) who were implanted with biodegradable polymer-coated DES. The primary outcome was the rate of major adverse cardiac events (MACE) at 5 years. Clopidogrel and aspirin for 6 months followed by chronic aspirin therapy were recommended. RESULTS: STEMI patients showed a trend of increase in MACE (8.7% vs. 6.8%, log rank p=0.289) compared to NSTE-ACS patients at 5 years, and a greater risk of cardiac death (5.4% vs. 2.1%, log rank p=0.003), mainly driven by the higher cardiac death rate within the first month after stent placement (log rank p=0.003) and the last year of follow-up (log rank p=0.001). No significant difference in stent thrombosis was found between them (3.1% vs. 2.5%, log rank p=0.653). Prolonged clopidogrel therapy (>6 months) showed no effect on risk of MACE or stent thrombosis between the two groups (both p for interaction >0.1). CONCLUSIONS: STEMI patients have a higher risk of cardiac mortality compared with NSTE-ACS patients after biodegradable polymer-coated DES placement, primarily attribute to more cardiac deaths that happened within the first month after the event and the last year of follow-up.

Phenytoin can accelerate the healing process after experimental myocardial infarction?

BACKGROUND: Over-degradation and/or inadequate accumulation of extracellular matrix after myocardial infarction (MI) may lead to adverse ventricular remodeling, even ventricular aneurysm or rupture. Phenytoin can increase gingival overgrowth by stimulating the proliferation of connective tissue, which implies a novel way to hasten the healing process after MI. METHODS: Experimental MI was induced by permanent coronary ligation. Surviving rats after MI were randomly divided into phenytoin, captopril, phenytoin plus captopril, operation control and sham operation group. Picrosirius red staining plus polarized microscopy was used for collagen analysis. Left ventricular passive pressure-volume relationship was determined ex vivo. The effects of phenytoin concentration gradient (0, 1.25, 2.5, 5.0, 10.0, and 20.0 microg/mL) on transforming growth factor-beta1 (TGF-beta1) mRNA and protein expression by neonatal rat cardiac fibroblast were determined using semi-quantitative RT-PCR and ELISA, respectively. Peritoneal macrophage was incubated with same gradient of phenytoin concentration. Then the supernatant was harvested to stimulate another 6 groups of cardiac fibroblast, to investigate possible role mediated by macrophage. RESULTS: Phenytoin treatment could promote type I collagen cross-linking level and ratio of type I/III collagen in the infarcted region and had no obvious side effect on interstitial collagen volume fraction, subtype ratio and distribution in non-infarcted region. Phenytoin-treated hearts exhibited attenuation of global ventricular dilation. Phenytoin alone had no direct effects on rat cardiac fibroblast proliferation and collagen production in vitro, but phenytoin-stimulated macrophage could exert a positive influence on cardiac fibroblast TGF-beta1 mRNA and protein production, which exhibited a dose-dependent manner. CONCLUSIONS: Phenytoin can accelerate the healing process in the infarcted region and has no obviously detrimental influence on collagen accumulation in non-infarcted region, which implies a potential benefit to patients undergoing early post-infarction ventricular remodeling process.

Modulation of mononuclear phagocyte inflammatory response by liposome-encapsulated voltage gated sodium channel inhibitor ameliorates myocardial ischemia/reperfusion injury in rats.

BACKGROUND: Emerging evidence shows that anti-inflammatory strategies targeting inflammatory monocyte subset could reduce excessive inflammation and improve cardiovascular outcomes. Functional expression of voltage-gated sodium channels (VGSCs) have been demonstrated in monocytes and macrophages. We hypothesized that mononuclear phagocyte VGSCs are a target for monocyte/macrophage phenotypic switch, and liposome mediated inhibition of mononuclear phagocyte VGSC may attenuate myocardial ischemia/reperfusion (I/R) injury and improve post-infarction left ventricular remodeling. METHODOLOGY/PRINCIPAL FINDINGS: Thin film dispersion method was used to prepare phenytoin (PHT, a non-selective VGSC inhibitor) entrapped liposomes. Pharmacokinetic study revealed that the distribution and elimination half-life of PHT entrapped liposomes were shorter than those of free PHT, indicating a rapid uptake by mononuclear phagocytes after intravenous injection. In rat peritoneal macrophages, several VGSC α subunits (NaV1.1, NaV1.3, NaV1.4, NaV1.5, NaV1.6, NaV1.7, NaVX, Scn1b, Scn3b and Scn4b) and ß subunits were expressed at mRNA level, and PHT could suppress lipopolysaccharide induced M1 polarization (decreased TNF-α and CCL5 expression) and facilitate interleukin-4 induced M2 polarization (increased Arg1 and TGF-ß1 expression). In vivo study using rat model of myocardial I/R injury, demonstrated that PHT entrapped liposome could partially suppress I/R injury induced CD43+ inflammatory monocyte expansion, along with decreased infarct size and left ventricular fibrosis. Transthoracic echocardiography and invasive hemodynamic analysis revealed that PHT entrapped liposome treatment could attenuate left ventricular structural and functional remodeling, as shown by increased ejection fraction, reduced end-systolic and end-diastolic volume, as well as an amelioration of left ventricular systolic (+dP/dt max) and diastolic (-dP/dt min) functions. CONCLUSIONS/SIGNIFICANCE: Our work for the first time demonstrates the therapeutic potential of VGSC antagonism via liposome mediated monocyte/macrophage targeting in acute phase after myocardial I/R injury. These results suggest that VGSCs in mononuclear phagocyte system might be a novel target for immunomodulation and treatment of myocardial I/R injury.

A new generation of biodegradable polymer-coated sirolimus-eluting stents for the treatment of coronary artery disease: final 5-year clinical outcomes from the CREATE study.

AIMS: The aim of the present study was to evaluate the five-year safety and efficacy of a biodegradable polymer-coated sirolimus-eluting stent with six months dual antiplatelet therapy in daily practice. METHODS AND RESULTS: Two thousand and seventy-seven daily practice patients, exclusively treated with biodegradable polymer-coated sirolimus-eluting stents (EXCEL; JW Medical Systems, Weihai, China), were prospectively enrolled in the multicentre CREATE study. Clinical follow-up was completed in 1,982 patients (95.4%) at five-year follow-up. The rates of cardiac death, non-fatal myocardial infarction (MI), target lesion revascularisation and overall major adverse cardiac events (MACE) at five-year follow-up were 3.0%, 1.5%, 3.7% and 7.4%, respectively. The rates of definite or probable stent thrombosis (ST) at five years and definite ST from one to five years were 1.1% and 0.3%, respectively. Heart failure (hazard ratio [HR]: 3.324, 95% confidence interval [CI]: 1.729-6.391, p<0.001) and prior MI (HR: 2.664, 95% CI: 1.358-5.227, p=0.004) were independent predictors of ST. Landmark analysis of a propensity score matched patient cohort showed that patients with or without clopidogrel treatment after six months had similar clinical outcomes. CONCLUSIONS: The present study demonstrates satisfactory and sustained five-year clinical safety and efficacy profiles as evidenced by the low rates of MACE and ST for the EXCEL, a biodegradable polymer-based sirolimus-eluting stent, when patients were treated with six months dual antiplatelet therapy in daily practice.