Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994).

BACKGROUND: The prevalence and incidence of end-stage renal disease in the United States are increasing, but milder renal disease is much more common and may often go undiagnosed and undertreated. METHODS: A cross-sectional study of a representative sample of the US population was conducted using 16 589 adult participants aged 17 years and older in the Third National Health and Nutrition Examination Survey (NHANES III) conducted from 1988 to 1994. An elevated serum creatinine level was defined as 141 micromol/L or higher (>/=1.6 mg/dL) for men and 124 micromol/L or higher (>/=1.4 mg/dL) for women (>99th percentile for healthy young adults) and was the main outcome measure. RESULTS: Higher systolic and diastolic blood pressures, presence of hypertension, antihypertensive medication use, older age, and diabetes mellitus were all associated with higher serum creatinine levels. An estimated 3.0% (5.6 million) of the civilian, noninstitutionalized US population had elevated serum creatinine levels, 70% of whom were hypertensive. Among hypertensive individuals with an elevated serum creatinine level, 75% received treatment. However, only 11% of all individuals with hypertension had their blood pressure reduced to lower than 130/85 mm Hg (the Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommendation for hypertensive individuals with renal disease); 27% had a blood pressure lower than 140/90 mm Hg. Treated hypertensive individuals with an elevated creatinine level had a mean blood pressure of 147/77 mm Hg, 48% of whom were prescribed one antihypertensive medication. CONCLUSION: Elevated serum creatinine level, an indicator of chronic renal disease, is common and strongly related to inadequate treatment of high blood pressure.

[Novel affinity membrane used for bilirubin removal].

Bilirubin is a toxic substance. In order to effectively remove it from the hepatic patients' blood, two novel affinity membranes were prepared. These were prepared by chemically grafting on cellulose and immobilized with different ligands. One kind of ligand was poly-D-lysine, the other one was quaternary ammonium salt. Both affinity membranes were used for removal bilirubin from phosphate buffer and HSA solutions, and the effects of temperature, HSA concentration, adsorption time in static state experiment and flow rate in dynamic state experiment have been investigated. The results indicated that the membranes could remove over 70% bilirubin from phosphate buffer and at least 50% from low concentration HSA solutions. The results also indicated that the removal efficiency was better at higher temperature. In the static state experiment, four hours can be selected as adsorption time. In the dynamic state experiment, the flow rate can be properly increased.

[Pharmacokinetics of epristeride in rats and beagle dogs].

AIM: To study the pharmacokinetics of epristeride (EPR) in rats and Beagle dogs. METHODS: The concentrations of EPR in biological samples were determined by an HPLC method with UV detection. RESULTS: The concentration-time curves in rat serum showed two peak concentrations after i.g. doses of 10, 20 and 40 mg.kg-1. The Tpeak1 and Tpeak2 were attained within 0.5-1 h and 3-4 h, respectively. The elimination half-life(T1/2 beta) was 2.43-3.14 h. The Tpeak and T1/2 beta in Beagle dogs were 1 h and 5 h, respectively. EPR was shown to be widely distributed to various tissues after i.g. dose of 20 mg.kg-1. The concentrations in most tissues at 3 h were higher than those of 6 h. The excretion of parent drug in urine amounted to only 0.09% of the dosage and in feces to 42.9% within 24 h after dosing. The biliary excretion were mainly metabolites and only 0.14% of parent drug of the dosage within 12 h. Plasma protein binding ratio of EPR was 92.3% at the concentration range of 50-3,000 ng.mL-1. CONCLUSION: The absorption of EPR was shown to be of first order processes at doses of 10-40 mg.kg-1, both the Cmax and AUC increased proportionally with the dosages. EPR was shown to be widely distributed to the various tissues and mainly eliminated via the feces and bile.

[Pharmacokinetics of sodium bimetrondazole glycinate in mice and rats].

AIM: To study the pharmacokinetic properties of sodium bimetrondazole glycinate (CMNa) in animals. METHODS: The concentrations of CMNa and its metabolite metronidazole in biological samples were determined by an HPLC method with UV detection. RESULTS: The transformation studies in vitro indicated that the CMNa transformation rate and metronidazole generation rate in whole blood at 90 min were 91.8% and 67.3%, respectively. After single i.v. doses of 57.3, 171.9 and 515.7 mg.kg-1 CMNa in mice, the T1/2 beta of the parent drug was 0.5, 0.8 and 1.0 min, the T1/2 beta of metronidazole was 63.2, 68.2 and 64.3 min. After a single i.v. dose of 171.9 mg.kg-1 CMNa in rats, the levels of CMNa and metronidazole in various tissues were higher at 2 and 5 min. The urinary excretion of the parent drug and metronidazole were 8.4% and 16.7% of the dose, the biliary excretion were 11.5% and 5.1% and the fecal excretion were 0.14% and 0.03%, respectively. The average plasma protein binding ratio (PPBR) of CMNa was 14.2%. CONCLUSION: CMNa was rapidly metabolized into metronidazole in vivo. The levels of Cmax and AUC of the parent drug and metronidazole increased proportionally with increasing doses. CMNa and metronidazole were predominantly excreted with the urine and bile.

Temporally and spatially coordinated expression of cell cycle regulatory factors after angioplasty.

Intimal hyperplasia following angioplasty results in part from the migration and proliferation of vascular smooth muscle cells (VSMCs). However, the cell cycle regulatory networks underlying injury-induced VSMC proliferation are largely unknown. In the present study, we examined the kinetics of expression and activity of cell cycle regulatory factors after angioplasty in rat and human arteries. Cell lysates were prepared from uninjured rat carotid arteries and at different time points after balloon denudation. Marked induction of the proliferating cell nuclear antigen (PCNA), the G1/S cyclin-dependent kinase (cdk2), and its regulatory subunits (cyclin E and cyclin A) occurred between 1 and 2 days after angioplasty, was sustained up to 10 days after injury, and then declined. Induction of these factors correlated with increased cdk2-, cyclin E-, and cyclin A-dependent kinase activity, indicating the assembly of functional cdk2/cyclin E and cdk2/cyclin A holoenzymes in the injured arterial wall. Immunohistochemical analysis revealed early expression of cdk2, cyclin E, and PCNA within the media of injured carotid arteries. At later time points, expression of these markers declined to basal levels in the media but was detected within the intimal lesion. Thus, VSMC proliferation after angioplasty in the rat carotid artery is associated with a temporally and spatially coordinated expression of cdk2, cyclins E and A, and PCNA. Analysis of human arteries also revealed expression of these factors in VSMCs within restenotic lesions. Thus, cdk2 and its regulatory cyclins may be suitable targets to limit human restenosis.

Pharmacokinetic-pharmacodynamic analysis of changrolin in dogs with arrhythmia.

The pharmacokinetics and pharmacodynamics of changrolin (CRL) were studied in 7 dogs with arrhythmia induced by coronary artery ligature. The ECG and the percentage of reduction ratio of ventricular premature were used to evaluate the effect of CRL, and an HPLC method was used to determine the serum drug concentration. A pharmacokinetic program was used to fit concentration-time (C-T) data and a combined pharmacokinetic-pharmacodynamic model was used to analyze effect-time (E-T) data in individual dogs. After infusion with CRL 83.33 micrograms.kg-1.min-1 for 60 min, it was found that K10, T1/2, Vd, Cl and Ce were 0.0087 min-1, 78.03 min, 40.55 ml.kg-1, 0.42 ml.kg-1.min-1, and 2.01 micrograms.ml-1, respectively.