The desquamative and proliferation-stimulating effects of lactic acid are very pH and concentration dependent, suggesting the "free acid" concentration is the active moiety.

The possible role of glutathione S-transferases (GTSs) in vascular glyceryl trinitrate (GTN) metabolism was investigated. GTN degradation to form its dinitrate metabolites (GDNs) in the 9000g (9k) supernatant fraction of bovine coronary arteries (BCA) was examined. BCAs were homogenized with a 3x volume of phosphate buffer, and the 9k fraction was obtained by centrifugation. GTN (40 ng/ml; 1.76 x 10(-7) M) was incubated for 2 hr in the 9k fraction of BCA in the presence of reduced glutathione (2 x 10(-3) M). Samples were taken at 10, 20, 40, 60, and 120 min. GTN was observed to degrade readily, exhibiting a half-life of 26 min in the incubate. While both 1,2- and 1,3-GDNs were generated from GTN, formation of 1,3-GDN was predominant (GDN ratio, as 1,2/1,3-GDN, = 0.7-0.8). Coincubation with 2 x 10(-5) M concentrations of two GST inhibitors, sulfobromophthalein (SBP) and ethacrynic acid (ECA), decreased the rate of GTN loss. The GTN half-lives in SBP- and ECA-treated incubations were 66 and 84 min, respectively. In addition, the pattern of GDN formation was also altered. The resultant GDN ratios exceeded unity in the presence of these inhibitors, indicating that 1,3-GDN formation was attenuated to a greater extent than that of 1,2-GDN. These data suggest that vascular GTN metabolism in BCA is carried out by cytosolic GST isozymes which possess a preference for C-2 denitration of GTN.

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In summary, within a controlled study situation, psyllium seems to be effective in lowering total and LDL cholesterol by 4-8% and 6-13%, respectively. Compared with conventional antilipidemic agents such as lovastatin, which lowers total cholesterol 30%, LDL cholesterol 40%, and triglycerides 20%, the effect of psyllium on lipids is minimal, and its use as a form of drug therapy in patients with moderate-to-severe hypercholesterolemia is not recommended. As an adjunct to AHA step 1 diet therapy, however, psyllium can be useful. The NCEP recently has stressed diet therapy as a first-line primary intervention in patients not a high risk from multiple risk factors or very high LDL cholesterol concentrations. Men ( < or = 45 y) and premenopausal women with no other risk factors and moderately high LDL cholesterol concentrations (4.1-5.7 mmol/l) are at relatively low risk for coronary events in the near future, and would therefore be suitable for diet therapy combined with adjunctive psyllium therapy. Psyllium is well tolerated with minor transient adverse effects (abdominal distention, excessive gas, flatulence) and has a good compliance record ( > or = 90%). It would be a useful adjunct to dietary intervention in low-risk patients with mild-to-moderate hypercholesterolemia. Further research is needed to evaluate psyllium's effect in women and its efficacy in long-term use.