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Electrophoresis. 2001 Jan;22(1):59-65.
pH-mediated field-amplified sample stacking of pharmaceutical cations in high-ionic strength samples.

Weiss DJ, Saunders K, Lunte CE.

Department of Chemistry, University of Kansas, Lawrence, KS, USA.

Capillary electrophoretic separation of samples of physiological origin typically have both poor resolution and efficiency due to destacking. We have previously reported a stacking method for concentration of catecholamines in artificial dialysate, or Ringer's solution. However, pH-mediated sample stacking of other cations has not been investigated. In this report, pH-mediated stacking has been extended to eletripan, dofetilide, doxazosin, sildenafil, UK-103,320, UK-202,581, and CP-122,288. These compounds were chosen without prior structural screening except that they were cationic at the pH of our background electrolyte (BGE). Capillary electrophoretic behavior of samples in BGE is compared with those of samples in Ringer's solution with and without pH-mediated acid stacking. Results indicate that the peak heights and efficiencies for acid-stacked samples are increased compared to the unstacked samples in Ringer's solution or BGE. For example, the peak efficiencies for 5 s injections of eletriptan in BGE and Ringer's solution are 138,000 and 72,000 plates, respectively. In contrast, a 10 s injection of eletriptan followed by acid injection for 16 s produces a peak with 246,000 plates. Evaluation of the stacking effect was performed by comparison of the peak height at similar peak efficiencies for samples in Ringer's solution with and without stacking. Using this method, pH-mediated acid stacking provides a 10- to 27-fold sensitivity enhancement for the seven cations.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11197180&dopt=Abstract




Hypertension. 2001 Jan;37(1):19-27.
Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Grimm RH Jr, Margolis KL, Papademetriou V V, Cushman WC, Ford CE, Bettencourt J, Alderman MH, Basile JN, Black HR, DeQuattro V V, Eckfeldt J, Hawkins CM, Perry HM Jr, Proschan M.

Berman Center for Outcomes and Clinical Research and Hennepin County Medical Center (R.H.G., K.L.M.), Minneapolis, Minn.

-Diuretics and ss-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and alpha-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged >/=55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged >/=70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics?

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11208751&dopt=Abstract [PubMed - as supplied by publisher]




Hypertension. 2001 Jan;37(1):40-45.
Vascular Effects of ACE Inhibition Independent of the Renin-Angiotensin System in Hypertensive Renovascular Disease : A Randomized, Double-Blind, Crossover Trial.

van Ampting JM, Hijmering ML, Beutler JJ, van Etten RE, Koomans HA, Rabelink TJ, Stroes ES.

Department of Nephrology and Hypertension (J.M.A. van A., J.J.B., H.A.K.), University Medical Center Utrecht, Utrecht, the Netherlands.

-To evaluate whether ACE inhibition and angiotensin II type 1 blockade exert beneficial effects on NO availability independent of their blood pressure-lowering effect, we used a double-blind crossover design to study vascular function in 18 patients with hypertensive renovascular disease during 6 weeks of therapy with enalapril (Ena) and valsartan (Val) compared with non-renin-angiotensin system-mediated treatment with the alpha(1)-blocker doxazosin (Dox). Control measurements were performed in 13 age-matched volunteers. Forearm blood flow was assessed with venous occlusion plethysmography, and serotonin and nitroprusside were used as endothelium-dependent and -independent vasodilators, respectively. Blood pressure was similar during all treatment periods. Serotonin-induced vasodilation was decreased in patients during Dox treatment (n=12) compared with control subjects (n=13) (increase 42+/-20% versus 107+/-65%, P:<0.05). Crossover from Dox to Val (n=6) had no effect on serotonin response (increase 50+/-14%), but crossover to Ena (n=6) caused a significant improvement (increase 79+/-39%, P:<0.05 versus Dox). In an assessment of all patients, serotonin-induced vasodilation during Ena (n=12, increase 75+/-31%) was increased compared with both Val and Dox (43+/-14% and 42+/-20%, respectively; both P:<0.05 versus Ena). The nitroprusside response remained unaltered during all treatment periods. In conclusion, ACE inhibition improves the impaired endothelium-dependent vascular function in patients with hypertensive renovascular disease. This effect is unrelated to blood pressure-lowering or angiotensin II-mediated effects.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11208754&dopt=Abstract [PubMed - as supplied by publisher]





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