Evaluation of NR-LU-10 with the Neoprobe gamma detector in a mouse model

1. The effects of diethyl maleate (DEM) on the cytotoxicity of phenyl-hydroquinone (PHQ) and other hydroquinones were studied in freshly isolated rat hepatocytes. 2. Addition of PHQ (0.5 or 0.75 mM) to hepatocytes resulted in dose-dependent cell death accompanied by the abrupt depletion of both GSH and protein thiols and the accumulation of phenyl-benzoquinone (PBQ). 3. Pretreatment with DEM (1.25 mM), which causes an abrupt depletion of cellular GSH in hepatocytes, delayed the onset of PHQ-induced cytotoxicity. The delay correlated with inhibition of PBQ formation. 4. Although the pH of the cell suspension was increased slightly (mean pH 0.18) by incubation under carbogen flow, the addition of DEM to the cell suspension inhibited both the increase in pH and the formation of PBQ from PHQ. 5. In hepatocyte suspensions without DEM, PHQ cytotoxicity was dependent on pH, and toxicity was associated with oxidation of PHQ and accumulation of PBQ. 6. Among other hydroquinones (0.5 mM), tert-butyl-hydroquinone-induced cytotoxicity was decreased by DEM (1.25 mM), but DEM did not affect the cytotoxicity of 2,5-di(tert-butyl)-1,4-benzohydroquinone. 7. PHQ-induced cytotoxicity correlated with the accumulation of PBQ in the cell, and the inhibition of PHQ-induced cytotoxicity by DEM correlated with pH-dependent changes in PBQ formation.     

Electrolyte minerals intake and cardiovascular health

ABSTRACT

Appropriate intake of micronutrient, such as electrolyte minerals is critical for the well-being of the cardiovascular health system. However, there are some debates regarding the impacts of dietary and/or supplemental intake of these minerals, on the risk of cardiovascular events and associated risk factors. High sodium intake is adversely associated with the risk of hypertension. Although many reports refered to the positive association of Na intake and cardiovascular events and all-cause mortality, however, other studies indicated that low Na intake is related to higher risk of all-cause mortality and HF-related events. By contrast, dietary potassium, magnesium and calcium have an inverse correlation with cardiovascular events and risk factors, especially with blood pressure. There are some controversies about cardiovascular effects and all-cause mortality of high Ca intake, including no effect, preventive or adverse effect with or without vitamin D. Calcium supplementation might be beneficial for prevention of cardiovascular events and all-cause mortality only in individuals with low intake. Moreover, calcium intake showed a J- or U-shaped association with the risk of cardiovascular diseases. Due to the controversies of the effect of electrolyte minerals especially sodium and calcium intake on cardiovascular events, large scale, well-designed long-term randomized clinical trials are required to evaluate the effect of minerals intake on cardiovascular events and all-cause mortality. In this review, we discuss the role of dietary and or supplemental sodium, potassium, magnesium, calcium, in cardiovascular health, as well as their clinical applications, benefits, and risks for the primary prevention of cardiovascular disease, in general population.     

Changing practice patterns in the management of acute myocardial infarction complicated by cardiogenic shock: elderly compared with younger patients

BACKGROUND: Cardiogenic shock continues to be an ominous complication of acute myocardial infarction (AMI). Evidence from retrospective analyses, registries and observational studies suggests that aggressive management using emergent revascularization strategies can bring about significant improvement in survival in this setting. Several studies have identified age as an independent predictor of survival. OBJECTIVE: To study retrospectively the possible changes in practice patterns in the management of patients with AMI complicated by cardiogenic shock in a tertiary care referral centre, and to determine what effect these changes may have had on survival of the patients, stratified by age. METHODS: From 1989 to 1995, 115 patients fulfilled the study criteria of cardiogenic shock based on pump failure and of presenting within 48 h of onset of shock. Prespecified data were extracted from medical records. All available coronary angiograms (n = 72) were analyzed by two experienced angiographers and consensus of findings was obtained. RESULTS: The study revealed a significant increase in the use of cardiac catheterization, interventional procedures and intra-aortic balloon pump (IABP) support in patients in the age groups 65 years or less, 66 to 75 years, and older than 75 years in 1989 to 1990, through 1991 to 1992, to 1993 to 1995. Significantly fewer patients aged older than 75 years received cardiac catheterization, coronary intervention and IABP support throughout the study period and even in the final period analyzed. In-hospital survival improved from 4% in 1989-90 to 33% in 1991-92, and 44% in 1993-95 (P = 0.001). Patients aged 65 years or less improved from 10% in 1989-90 to 59% in 1993-95 (P = 0.032). Only 20% of patients aged older than 75 years survived in the 1993-95 period. By univariate analysis, use of coronary angiography (catheterization 46% versus no catheterization 5%; P < 0.0001), coronary intervention procedures (percutaneous transluminal coronary angioplasty or coronary artery bypass grafting) (intervention 48% versus no intervention 9%; P < 0.0001) and IABP support (IABP 41% versus no IABP 18%; P = 0.0096) were all associated with improved in-hospital survival. Use of thrombolytic therapy showed possible survival benefit only in patients aged older than 75 years (thrombolysis 33% versus no thrombolysis 5%; P = 0.10). Patients who underwent coronary intervention were younger (P = 0.002), had a lower incidence of previous myocardial infarction (P = 0.0002), lower heart rate (P = 0.04), higher peak creatine phosphokinase (P = 0.04) and fewer vessels with at least 70% stenosis (P < 0.0001). On multivariate analysis only lower age, lower heart rate and presence of coronary intervention procedures were found to have an independent effect on survival. CONCLUSIONS: Use of invasive treatment strategies has increased significantly since 1989-90 in the management of patients with AMI complicated by cardiogenic shock. This increase has been associated with improved in-hospital survival in all age groups except possibly the very elderly. Patients undergoing coronary interventional procedures are significantly different in baseline clinical characteristics from patients not undergoing these procedures. These observations underscore the need for randomized trials to define the optimal treatment strategies in these patients. Efficacy of invasive treatment strategies in elderly patients aged older than 75 years-deserves special attention.     

Parallel synthesis and fast screening of heterogeneous catalysts

We are presenting an effective method to prepare and test heterogeneous catalysts much faster than by the conventional way. A catalyst array was prepared via an incipient wetness method by combination of different amounts of Pt, Zr, and V on Al₂O₃ by means of an automatic liquid handler. For catalytic testing for methane oxidation a ceramic monolith reactor module, the channels of which contain the different catalyst compositions, was developed in which up to 250 catalyst compositions can be prepared and tested in parallel. Gas samples from each channel of the monolith were analysed sequentially by a mass spectrometer by moving the QMS inlet capillary into the channels using a three-dimensional positioning system which works at high temperatures. By comparison of the testing results with experiments carried out in flow reactors it is shown that the monolithic reactor is an efficient tool for fast screening of heterogeneous catalysts. This revised version was published online in June 2006 with corrections to the Cover Date.