Evaluation of the pharmacokinetic and pharmacodynamic interaction between quinidine and nifedipine

Quinidine and nifedipine appear to be subject to metabolism by the same isozyme of cytochrome P-450. In addition, both drugs have been reported to alter the pharmacokinetics of other compounds. To investigate a potential interaction, 10 healthy subjects (five male, five female) received quinidine sulfate (200 mg orally), nifedipine (20 mg orally), or the combination of both drugs every 8 hours for 4 doses using a randomized, cross-over study design with a 2-week washout period between treatments. Drug concentration, heart rate, and mean arterial pressure were measured at frequent intervals after the final dose. Quinidine concentrations were unchanged by the co-administration of nifedipine. Nifedipine area under the curve (AUC0-8) increased 36.6% from 333 to 455 micrograms.hr/L (P < .05) after quinidine administration. Heart rate was significantly higher in the nifedipine-quinidine treatment at 0.5, 1.0, 1.5, and 2.0 hours when compared with either drug alone. The maximum increase in heart rate (17.9 beats/minute) occurred at 0.5 hours after nifedipine administration and was significantly correlated with serum concentrations at that time (r = .78). These results suggest that quinidine inhibits nifedipine metabolism, and this pharmacokinetic interaction results in enhanced pharmacologic response.     

Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group

BACKGROUND: Improvement of angina pectoris symptoms after cholesterol lowering has raised questions as to the underlying mechanisms. METHODS: Rabbit experiment: We compared arterial blood samples from New Zealand White cholesterol-supplemented rabbits (n = 6) with nonsupplemented rabbit samples (n = 4) in a closed-loop circulation diffusion system. The pH and partial pressures of oxygen (pO2) and carbon dioxide (pCO2) were measured continuously. The samples were first oxygen (O2) saturated (pO2, 160 mm Hg; pCO2, 4 mm Hg) and then desaturated in 100% nitrogen. Cholesterol levels were determined in whole blood, plasma (P Chol), red blood cells (RBCs), and RBC membranes. Human experiment: We exposed quadruple desaturated venous blood samples (n = 4) with P Chol levels of 87 to 400 mg/dL in a gas exchanger to capillary gas conditions (pO2, 23 mm Hg; pCO2, 46 mm Hg). After 15 minutes we performed blood gas analyses and compared our results to baseline values. RESULTS: In the rabbit experiment the cholesterol-supplemented group as compared to the control group showed higher plasma pO2 levels during the saturation phase and lower plasma pO2 levels during the desaturation phase. It also had a markedly increased RBC membrane cholesterol content: 121 +/- 3 (standard error of the mean [SEM]) mg/dL versus 22 +/- 1.7 mg/dL in the control group (P < .05). This barrier to RBC membrane O2 diffusion caused delayed O2 entry into the RBCs during saturation, with a higher plasma pO2, and delayed O2 release from the RBCs during desaturation, with a lower plasma pO2. In the human experiment the P Chol level was inversely correlated with the percentage change of O2 content in milliliters of O2 per deciliter of blood (P < .05). CONCLUSIONS: Increased RBC membrane cholesterol in hypercholesterolemia appears to decrease the transmembrane O2 diffusion rate.     

Embolization with temporary balloon occlusion of the internal carotid artery and in vivo proton spectroscopy improves radical removal of petrous-tentorial meningioma

A highly vascular petroclival meningioma supplied by tentorial branches of the internal carotid artery was embolized by temporary balloon occlusion of the parent vessel distal to the tumor, followed by obliteration of the tumor vascularity with polyvinyl alcohol particles. Subsequently, in vivo proton spectroscopy showed necrosis of a large portion of the tumor and helped determine the timing of surgery. Both innovative techniques considerably facilitated the subsequent radical excision of the tumor with no neurological morbidity.     

The effect of petrochemical and oil-refining enterprises on the sanitary state of the soil cover]

Pollution of soil and agricultural plants was studied in the areas of petrochemical and oil-processing enterprises. Massive soil pollution was found in the adjacent 1-3-km areas. Hydrocarbons and metals from wastes accumulate in onions, radish, potatoes, and apples.     

T cell responses to synthetic peptides of herpes simplex virus type 1 glycoprotein D in naturally infected individuals

To locate T cell determinants of glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1), proliferation assays of lymphocytes obtained from 10 healthy HSV-seropositive individuals were performed using 34 overlapping gD peptides as antigens. Despite large differences between individual responses to the peptides both in number of stimulating peptides and gD regions, three regions (1-54, 110-214, and 290-314) induced a response in 50% or more of the HSV-seropositives. T cells were less frequently stimulated by peptides of region 210-294. No correlation was found between serological data and proliferative responses to the peptides. The diversity in T cell response to the peptides suggests a lack of immunodominance, implying that a single peptide/region of gD, or a combination of peptides, will not be sufficient to serve as a basis for a future HSV-1 vaccine.     

Evaluation of the renal protective effect of misoprostol in elderly, osteoarthritic patients at risk for nonsteroidal anti-inflammatory drug-induced renal dysfunction

An age greater than 60 and diuretic use have been implicated as risk factors for nonsteroidal anti-inflammatory drug (NSAID)-induced decreases in renal function. Misoprostol, a prostaglandin E1 analog, was studied in nine elderly osteoarthritic patients at risk for NSAID-induced renal dysfunction to determine whether it could prevent NSAID-induced renal dysfunction. Subjects received ibuprofen 2400 mg/day and either misoprostol 800 mcg/day or placebo for 14 days in a randomized, double-blinded, crossover trial. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) studies using inulin and PAH plasma clearance, urinary prostaglandin E2 (PGE2) and protein excretion, and serum electrolytes were obtained at baseline, after the first dose, and on day 7 and 14 of each treatment period. Prostaglandin E2 excretion was significantly reduced after the first dose of ibuprofen and throughout the 14 days in both the misoprostol and placebo treatment groups. No statistically significant differences in GFR, ERPF, protein excretion, serum potassium, or serum sodium were detected between misoprostol and placebo treatment during the 14 days of ibuprofen treatment. However, a subset of two patients who exhibited a decrease of greater than 20% in GFR during placebo treatment, appeared to demonstrate an attenuation of this decline when treated with misoprostol. Effect of time, independent of treatment group, indicated that ERPF was significantly decreased from baseline after the first dose of ibuprofen (P < or = 0.05), whereas GFR was notably diminished from baseline on day 14 only (P < or = 0.05). Misoprostol does not influence GFR and ERPF in unselected subjects purportedly at risk for NSAID-induced renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)