Morphine-mediated alteration of hypertension-related gene expression in human white blood cells and multilineage progenitor cells.

It has been shown that vascular endothelial cells functionally express a local circuit autocrine-paracrine regulatory pathway driven by endogenously expressed chemically authentic morphine, its cognate opiate alkaloid-selective mu3 and mu4 receptors, and constitutive nitric oxide (NO). Accordingly, the aim of the study was to examine morphine-mediated changes in hypertension-associated gene expression in two independent cell models: primary cultures of human white blood cells (WBCs) and human multilineage progenitor cells (MLPCs). In separate incubations, primary cultures of human WBC and MLPC were treated with morphine at a final concentration of 1 µM morphine for 2-4 h. After RNA extraction and reverse transcription, Human Genome Survey Arrays were used to construct and differentially analyze by strict statistical criteria transcriptional/gene expression profiles of WBC and undifferentiated human MLPC in three independent experiments. The Applied Biosystems Human Genome Survey Array contains 31,700 60-mer oligonucleotide probes representing a set of 27,868 individual human genes and >1000 control probes. After DNA microarray analyses, a variety of hypertension-associated genes from both cell types were observed to be significantly downregulated. The only genes expressed in both cell types were ß-adrenergic receptor kinase 2 (ADRBK2) and coding protein kinase WNK1 (PRKWNK1); however, only PRKWNK1 showed downregulation of its expression after morphine exposure. Only two genes were observed to be significantly upregulated after morphine treatment: ADRBK2 in stem cells and ß3-adrenergic receptor in WBC. Morphine administration to primary cultures of human WBC and MLPC altered the expression profile of 16 candidate hypertension-associated genes. The majority of relevant genes was observed to be downregulated, suggesting ongoing homeostatic regulation by endogenous morphine coupled to NO production and release. In sum, these data suggest a predominantly antihypertensive role for endogenous morphine/NO signaling events.

Two polymorphisms of the FVII gene and their impact on the risk of myocardial infarction in poles under 45 years of age.

High levels of coagulation factor VII (FVII) in plasma have been associated with the increased risk of myocardial infarction (MI) in some studies. Both environmental and genetic factors are responsible for different levels of FVII in plasma. In the FVII gene there are two common polymorphisms (-323A1/A2 and IVS7)which are related to the level of FVII. The purpose of this study was to evaluate the influence of these polymorphisms on the risk of acute myocardial infarction in Poles under 45 years of age. We performed a case-control study of 266 patients with the history of MI. All patients had the first incidence of MI before 45 years of age. The control group consisted of 137 healthy individuals older than 45 years. Carriers of the A2 allele (-32341/A2 polymorphism) have a lower risk of MI than noncarriers (OR = 0.40, 95% CI = 0.20 to 0.80). The IVS7 polymorphism was shown not to be related to MI in this study. Our findings suggest that the -323A1/A2 polymorphism of the FVII gene is related to the risk of MI in Polish individuals. We pointed that plasma cholesterol (OR = 1.11, 95% CI = 1.03 to 1.18), arterial hypertension (OR = 3.84, 95% CI = 1.99 to 7.43) and family history (OR = 2.72, 95% CI = 1.57 to 4.73) are significant predictors of acute myocardial infarction.

Continuous quality improvement: implementation made easier for materiel management.

The author describes the step-by-step implementation of continuous quality improvement, based on the Hospital Corporation of America's model for CQI, to correct a persistent problem in CS.