Advanced fibre optical scanning in thin-layer chromatography for drug identification.

A systematic toxicological analysis procedure using high-performance thin layer chromatography in combination with fibre optical scanning densitometry for identification of drugs in biological samples is presented. Two examples illustrate the practicability of the technique. First, the identification of a multiple intake of analgesics: codeine, propyphenazone, tramadol, flupirtine and lidocaine, and second, the detection of the sedative diphenhydramine.

Acid and base regulation in the proteome of Escherichia coli.

Acid and base conditions have many significant effects on the growth of Escherichia coli. External and internal pH perturbations induce different classes of genes. pH-dependent regulation of genes intersects with other regulatory responses, e.

Acid- and base-induced proteins during aerobic and anaerobic growth of Escherichia coli revealed by two-dimensional gel electrophoresis.

Proteins induced by acid or base, during long-term aerobic or anaerobic growth in complex medium, were identified in Escherichia coli. Two-dimensional gel electrophoresis revealed pH-dependent induction of 18 proteins, nine of which were identified by N-terminal sequencing. At pH 9, tryptophan deaminase (TnaA) was induced to a high level, becoming one of the most abundant proteins observed.

Proteins induced in Escherichia coli by benzoic acid.

Proteins induced by benzoic acid in Escherichia coli were observed on two-dimensional electrophoretic gels (2-D gels). Cultures were grown in glucose-rich medium in the presence or absence of 20 mM benzoate at an external pH of 6.5, where the pH gradient (deltapH) is large and benzoate accumulates, and at an external pH of 8.

A glutamate-dependent acid resistance gene in Escherichia coli.

Stationary-phase cultures of Escherichia coli can survive several hours or exposure to extreme acid (pH 2 to 3), a level well below the pH range for growth (pH 4.5 to 9). To identify the genes needed for survival in extreme acid, a microliter screening procedure was devised.

Progression of coronary artery disease predicts clinical coronary events. Long-term follow-up from the Cholesterol Lowering Atherosclerosis Study.

Background: Progression of coronary artery disease is assumed to be a surrogate end point for clinical coronary events. Because no single method or measure for a coronary angiographic end point is uniformly accepted as optimal, the utility and validity of surrogate end points for predicting clinical coronary events remain unsettled.

Methods And Results: The Cholesterol Lowering Atherosclerosis Study randomized 162 nonsmoking, 40- to 59-year-old men with previous coronary artery bypass graft surgery to colestipol/niacin plus diet or placebo plus diet.

Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS).

To establish whether lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, exhibits a specific effect on apolipoprotein (apo) A- and apoB-containing lipoproteins, 63 subjects, a subset of the 270 Monitored Atherosclerosis Regression Study (MARS) patients with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease, were randomized into either lovastatin 40 mg twice daily or matching placebo tablets twice daily. Both groups consumed a diet containing 27% calories as fat (polyunsaturated fat/saturated fat ratio, 2.85) and a daily cholesterol intake of less than 250 mg.

Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.

Background: The Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions < 50% diameter stenosis (%S) and coronary lesions > or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets.

Methods And Results: Two hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.

Acid and base resistance in Escherichia coli and Shigella flexneri: role of rpoS and growth pH.

Escherichia coli K-12 strains and Shigella flexneri grown to stationary phase can survive several hours at pH 2 to 3, which is considerably lower than the acid limit for growth (about pH 4.5). A 1.

George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis reversal.

This review explores evidence for the reversibility of atherosclerosis and augmentation of angiography with non-invasive arterial wall imaging. Meta-analysis from coronary angiographic trials demonstrates that regression and stabilization are 1.5 to 2 times more common in treated than placebo subjects, and progression is reduced by half in treated subjects.

One-year reduction and longitudinal analysis of carotid intima-media thickness associated with colestipol/niacin therapy.

Background And Purpose: The Cholesterol Lowering Atherosclerosis Study has reported significant reduction of coronary artery disease and of carotid arterial intima-media thickness (IMT) at 2 and 4 years with colestipol/niacin therapy. We now report on treatment effects on carotid IMT at 6 months and 1 year.

Methods: One hundred eighty-eight nonsmoking men, aged 40 to 59 years, with prior coronary artery bypass graft surgery were randomized to colestipol/niacin plus diet therapy or placebo plus diet therapy.

Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).

Objective: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points.

Design: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial.

Setting: Community- and university-based cardiac catheterization laboratories.

Atherosclerosis--reversal with therapy.

Evidence for atherosclerosis reversal comes from studies in animals wherein atherosclerosis is induced and then allowed to regress, autopsy studies of starved humans, and angiographic studies testing antiatherosclerosis treatment. Animal models and autopsy studies have provided detailed histologic and biochemical descriptions of regression. Cellular and subcellular information exists on what can occur, but because the same lesions are not re-examined, what actually does occur is unknown.

Beneficial effects of colestipol-niacin therapy on the common carotid artery. Two- and four-year reduction of intima-media thickness measured by ultrasound.

Background: Controlled clinical trials have reported treatment effects evaluated with serial imaging in coronary and femoral but not cervical arteries. The Cholesterol Lowering Atherosclerosis Study, a coronary, cervical, and femoral angiographic trial of colestipol plus niacin, included a pilot study of standardized carotid ultrasound imaging.

Methods And Results: Seventy-eight subjects had ultrasound studies at baseline, 2, and 4 years.

The lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus.

Lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine were studied in 18 female patients with systemic lupus erythematosus (SLE) with mild or inactive disease. Patients were case matched (200-400 mg hydroxychloroquine daily vs no hydroxychloroquine) on several factors including daily corticosteroid dose in this cross sectional study. All had normal menstrual cycles; none smoked, used alcohol, were taking lipid altering medications or had other concurrent diseases.

Evaluation of colestipol/niacin therapy with computer-derived coronary end point measures. A comparison of different measures of treatment effect.

Background: The Cholesterol Lowering Atherosclerosis Study has demonstrated beneficial effect of colestipol/niacin on coronary atherosclerosis using a panel-determined global coronary change score. We now report treatment group comparisons using quantitative coronary angiographic (QCA) measures from all processable segments in 85 of 162 randomly selected baseline/2-year film pairs.

Methods And Results: Treatment benefit was established for percent stenosis for either continuous or categorical analyses with regression established regardless of the per-patient scoring procedure.

Comparison of computer- and human-derived coronary angiographic end-point measures for controlled therapy trials.

The Cholesterol Lowering Atherosclerosis Study, a randomized angiographic clinical trial, demonstrated the beneficial effect of niacin/colestipol plus diet therapy on coronary atherosclerosis. Outcome was determined by panel-based estimates (viewed in both still and cine modes) of percent stenosis severity and change in native artery and bypass graft lesions. Computer-based quantitative coronary angiography (QCA) was also used to measure lesion and bypass graft stenosis severity and change in individual frames closely matched in orientation, opacification, and cardiac phase.

pH dependence and gene structure of inaA in Escherichia coli.

The weak-acid-inducible locus inaA in Escherichia coli was mapped to 48.6 min by P1 cotransduction of inaA Mud lac fusions and linked Tn10 insertions. The inaA1::lac fusion tested negative for phenotypes characteristic of mutations in the nearby locus ubiG.

Regression of atherosclerosis: which components regress and what influences their reversal.

Two major features of atherosclerosis may be distinguished: (a) atherosis caused by lipid infiltration in cells and extracellularly and (b) sclerosis caused by connective tissue deposition and by functional disturbance of the endothelium, leading to impairment of endothelium-derived relaxing factor (EDRF)-release and reduced arterial compliance. Atherosis generally rarely causes clinical symptoms and, furthermore, is reversible by lowering of LDL-C. However, the clinically significant human lesion is the fibrous atheromatous plaque.

Factors influencing the formation of new human coronary lesions: age, blood pressure, and blood cholesterol.

Background: The Cholesterol Lowering Atherosclerosis Study, a controlled angiographic trial, has reported that new native coronary artery lesions are significantly reduced by aggressive blood lipid lowering therapy with colestipol plus niacin. To study factors relevant to primary atherosclerosis prevention, we have conducted an epidemiologic analysis of new native coronary lesion formation in placebo-treated patients.

Methods: Univariate and multivariate logistic regression procedures were used to examine age at entry into the study, number of years since bypass, body weight, diastolic and systolic blood pressure, plasma total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol, and apolipoproteins A-I,B, and C-III.

Arterial wall oxygenation, oxyradicals, and atherosclerosis.

The oxygen supply of inner media and thickened intima of atherosclerosis prone arteries depends largely on diffusion from the endothelium. Conditions which increase wall thickness and oxygen diffusion or reduce oxygen transmissibility produce hypoxia and steep PO2 gradients within the wall. Cerebral injury and myocardial reperfusion studies indicate that intermittent hypoxia and steep PO2 gradients lead to oxyradical formation and tissue damage.

Fat and cholesterol intake of attendees at two national USA cardiovascular annual meetings.

Using a 1-page bar-coded food frequency questionnaire, the food habits of 996 adults who participated in diet screening at the annual meetings of the American Heart Association (1989) and the American College of Cardiology (1990) were analyzed for sex, age and regional differences. Estimated nutrient intakes were also compared with those from the Department of Agriculture's 1985 and 1986 Continuing Survey of Food Intake of Individuals. The average diet reported in this study satisfied National Cholesterol Education Program guidelines for cholesterol intake, but was higher than that recommended for total and saturated fats.