The outer root sheath of hair follicles plays an important role in epidermal regeneration in vivo. Keratinocytes isolated by explantation of outer root sheath tissue have extensive proliferative capacity irrespective of donor age, which probably depends on pluripotent epithelial stem cells residing in the outer root sheath. These keratinocytes can be organotypically grown to epidermal equivalents in vitro. We report here that in a multicenter, randomized phase II study, EpiDex trade mark, a tissue-engineered, fully differentiated autologous epidermal equivalent derived from keratinocytes of the outer root sheath of plucked anagen hair follicles, is as effective as split-thickness skin autografting in the promotion of healing and complete closure of recalcitrant vascular leg ulcers.

No abstract

Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression to ward end-stage renal failure. However, some au thors reported disparate renal protective effects of different antihypertensive drugs in diabetic ani mals and humans. In an attempt to resolve the controversy surrounding this possibility, previ ously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca 2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clin ical proteinuria (UProt), treated during >4 weeks with ACE inhibitors, Ca 2+ antagonists, or conven tional therapy (diuretic and/or β-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on av erage -45%) than on conventional therapy (on av erage -23%) or Ca 2+ antagonists other than nifed ipine (on average -35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, Ρ < .05). On the basis of multiple regression anal ysis, ACE inhibitor-induced UProt changes corre lated with BP changes (r = 0.77, Ρ < .00001), aver aged -28% at zero BP change, and varied 1.5% for each percent BP change. On conventional therapy, UProt and BP changes also correlated (r = 0.62, Ρ < .005), but UProt began to decrease only after a BP reduction of >5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors. On Ca 2+ antagonists other than nifedipine, UProt was unchanged at zero BP change, and the regression line for the relationship between changes in UProt (r = 0.55, Ρ < .05) was in an intermediate position between ACE inhibi tors and conventional treatment. Seventy reports also contained data on glomerular filtration rate (GFR). On ACE inhibitors, GFR was on average unchanged, but tended to increase slighty with progressive BP reduction (r = -0.55, Ρ < .0001). On conventional therapy or Ca 2+ .antagonists, vari ations in GFR were unrelated to changes in BP.As ACE inhibitors exert a specific antiproteinuric effect even without a change in systemic BP, they are superior to other agents in treating microalbu minuria or overt proteinuria in initially normoten sive or mildly hypertensive diabetic patients. On the other hand, when systemic BP can be lowered by 20%, as it is desirable in severely hypertensive patients, ACE inhibitors, conventional therapy, and several Ca 2+ antagonists all have a distinct an tiproteinuric action. In contrast, as the example of nifedipine illustrates, drug-specific intrarenal ef fects may antagonize a BP-dependent antiproteinu ric action and even counteract the effect of lower ing systemic pressure. It is of note that ACE inhib itors may, in addition to their antiproteinuric effect, exert a drug-specific beneficial influence on GFR. Am ...

No abstract

Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression to ward end-stage renal failure. However, some au thors reported disparate renal protective effects of different antihypertensive drugs in diabetic ani mals and humans. In an attempt to resolve the controversy surrounding this possibility, previ ously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca 2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clin ical proteinuria (UProt), treated during >4 weeks with ACE inhibitors, Ca 2+ antagonists, or conven tional therapy (diuretic and/or β-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on av erage-45%) than on conventional therapy (on av erage-23%) or Ca 2+ antagonists other than nifed ipine (on average-35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, Ρ < .05). On the basis of multiple regression anal ysis, ACE inhibitor-induced UProt changes corre lated with BP changes (r = 0.77, Ρ < .00001), aver aged-28% at zero BP change, and varied 1.5% for each percent BP change. On conventional therapy, UProt and BP changes also correlated (r = 0.62, Ρ < .005), but UProt began to decrease only after a BP reduction of >5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors. On Ca 2+ antagonists other than nifedipine, UProt was unchanged at zero BP change, and the regression line for the relationship between changes in UProt (r = 0.55, Ρ < .05) was in an intermediate position between ACE inhibi tors and conventional treatment. Seventy reports also contained data on glomerular filtration rate (GFR). On ACE inhibitors, GFR was on average unchanged, but tended to increase slighty with progressive BP reduction (r =-0.55, Ρ < .0001). On conventional therapy or Ca 2+ .antagonists, vari ations in GFR were unrelated to changes in BP. As ACE inhibitors exert a specific antiproteinuric effect even without a change in systemic BP, they are superior to other agents in treating microalbu minuria or overt proteinuria in initially normoten sive or mildly hypertensive diabetic patients. On the other hand, when systemic BP can be lowered by 20%, as it is desirable in severely hypertensive patients, ACE inhibitors, conventional therapy, and several Ca 2+ antagonists all have a distinct an tiproteinuric action. In contrast, as the example of nifedipine illustrates, drug-specific intrarenal ef fects may antagonize a BP-dependent antiproteinu ric action and even counteract the effect of lower ing systemic pressure. It is of note that ACE inhib itors may, in addition to their antiproteinuric effect, exert a drug-specific beneficial influence on GFR.

No abstract

To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg once daily in 14 patients who were hypertensive after 8 weeks on the lower dosage. At entry (before placebo), SI was slightly but not significantly lower in group A than B [2.7 vs. 3.6 x 10(-4) ml.microU-4.min-1]; fasting plasma insulin was 13.6 vs. 12.9 microU.ml-1. After 6 weeks on placebo, S1 averaged 3.7 in group A and 4.4 x 10(-4) microU.ml-1.min-1 in group B; fasting plasma insulin was 14.6 vs. 15.1 microU.ml-1, and glucose 5.5 vs. 5.5 mmol.l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract