Clinical efficacy assessment in photodamaged skin of 0.5% and 1.0% idebenone.

Idebenone is an antioxidant lower molecular weight analogue of coenzyme Q10. Previously, idebenone was shown to be a very effective antioxidant in its ability to protect against cell damage from oxidative stress in a variety of biochemical, cell biological, and in vivo methods, including its ability to suppress sunburn cell (SBC) formation in living skin. However, no clinical studies have been previously conducted to establish the efficacy of idebenone in a topical skincare formulation for the treatment of photodamaged skin. In this nonvehicle control study, 0.5% and 1.0% idebenone commercial formulations were evaluated in a clinical trial for topical safety and efficacy in photodamaged skin. Forty-one female subjects, aged 30-65, with moderate photodamaged skin were randomized to use a blind labelled (either 0.5% or 1.0% idebenone in otherwise identical lotion bases) skincare preparation twice daily for six weeks. Blinded expert grader assessments for skin roughness/dryness, fine lines/wrinkles, and global improvement in photodamage were performed at baseline, three weeks and six weeks. Electrical conductance readings for skin surface hydration and 35 mm digital photography were made at baseline after six weeks. Punch biopsies were taken from randomly selected subjects, baseline and after six weeks, and stained for certain antibodies (interleukin IL-6, interleukin IL-1b, matrixmetalloproteinase MMP-1, collagen I) using immunofluorescence microscopy. After six weeks' use of the 1.0% idebenone formula, a 26% reduction in skin roughness/dryness was observed, a 37% increase in skin hydration, a 29% reduction in fine lines/wrinkles, and a 33% improvement in overall global assessment of photodamaged skin. For the 0.5% idebenone formulation, a 23% reduction in skin roughness/dryness was observed, a 37% increase in skin hydration, a 27% reduction in fine lines/wrinkles, and a 30% improvement in overall global assessment of photodamaged skin. The immunofluorescence staining revealed a decrease in IL-1b, IL-6, and MMP-1 and an increase in collagen I for both concentrations.

Idebenone: a new antioxidant - Part I. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants.

Topical applications of skin care products containing antioxidants have become increasingly popular. Numerous studies have elucidated the biological effects of these substances. General antiaging effects, anti-inflammatory properties, photoprotective properties, and prevention of ultraviolet (UV) immunosuppression have been documented. However, a standardized method to characterize and compare the properties and oxidative stress protection capacity of antioxidants was lacking. A multistep in vitro process utilizing a variety of biochemical and cell biological methods combined with in vivo studies was designed to compare the oxidative stress protective capacity of commonly used antioxidants. Data were presented for L-ascorbic acid, dl-alpha-tocopherol, kinetin, dl-alpha lipoic acid, ubiquinone, and idebenone. Methods included using UV-induced radical trapping/scavenging capacity measured by photochemiluminescence, pro-oxidative systems (LDL-CuSO(4), microsome-NADPH/ADP/Fe(3+)) with measurement of primary and secondary oxidation products, UVB irradiation of human keratinocytes, and in vivo evaluation, using the human sunburn cell (SBC) assay. Correlation and trends between in vitro and in vivo results were established, and the standardized test protocol was used to quantify oxidative stress protection capacity of antioxidants. Summarizing and totaling the data equally weighted for each oxidative stress study, the overall oxidative protection capacity scores of 95, 80, 68, 55, 52, and 41 were obtained for idebenone, dl-alpha tocopherol, kinetin, ubiquinone, L-ascorbic acid, and dl-alpha lipoic acid, respectively. The higher the score, the more effective the overall oxidative stress protection capacity of the antioxidant became. This multistep protocol may serve as a standard in investigating and comparing new putative antioxidants for topical use as well as a valuable tool to assess the anti-inflammatory properties, photoprotective properties, and prevention of UV immunosuppression of topical antioxidants.

Use of transesophageal echocardiography for delivery of a parturient with severe pulmonary hypertension.

The anesthetic management of a parturient with severe pulmonary hypertension during labor and subsequent cesarean delivery is presented. Transesophageal echocardiography was used intraoperatively to manage the patient's hemodynamics, while pulmonary artery pressure monitoring was of little use. The benefits of transesophageal echocardiography for management of these patients are discussed.

Alcohol, marijuana, and American youth: the unintended consequences of government regulation.

This paper analyzes the impact of increases in the minimum drinking age on the prevalence of alcohol and marijuana use among high school seniors. The empirical analysis is based on a large sample of students from 43 states over the years 1980-1989. We find that increases in the legal minimum drinking age did slightly reduce the prevalence of alcohol consumption. We also find, however, that increased legal minimum drinking ages had the unintended consequence of slightly increasing the prevalence of marijuana consumption. Estimates from a structural model suggest that this unintended consequence is attributable to standard substitution effects.

Blood loss and transfusion requirements in patients implanted with a mechanical circulatory support device undergoing cardiac transplantation.

Patients implanted with mechanical circulatory support devices (MCSD's) are at high risk for post-operative bleeding at cardiac transplantation. However, the magnitude of the risk and transfusion requirements for MCSD patients at the time of transplantation have not been previously reported. The purpose of this study was to characterize and compare the bleeding characteristics and transfusion requirements of 3 sub-groups of cardiac transplant patients: primary (n = 45), redo (n = 26), and MCSD (n = 23) patients.

You are what you eat: healthy food choices, nutrition, and the child with juvenile rheumatoid arthritis.

Children with juvenile rheumatoid arthritis (JRA) often experience nutrition related concerns. Growth abnormalities are common. Protein-calorie malnutrition and inadequate intake of other nutrients result from aspects of the disease process, treatment (including drug treatment), and dietary choices. Mechanical feeding difficulties can also compromise adequate intake. Because nursing assessments usually explore eating habits and family issues, the registered nurse is in a good position to identify nutrition concerns, to provide intervention recommendations, or to act as a referral source.

Clinical and histological effects of glycolic acid at different concentrations and pH levels.

BACKGROUND: Much has been said about the effects of glycolic acid with little scientific evidence to substantiate the findings. OBJECTIVE. This study reports on the clinical and histological effects of glycolic acid at pH levels 3.25, 3.80, and 4.40, and at 3.25%, 6.50%, 9.75%, and 13.00% on ichthyotic/xerotic skin. METHODS: Product treatment consisted of a 2-week washout period followed by 3 weeks of product application (BID) with A 1-week regression period. Shave biopsies and clinical evaluations for dryness, moisturization, and transepidermal water loss were made at baseline, 1, 2, and 3 weeks of use, and at the regression period. RESULTS: Clinically, ichthyotic/xerotic skin was normalized with histologic evidence of stratum corneum thinning, viable epidermal thickening, and marked increases in glycosaminoglycan and collagen content. CONCLUSION: All pH levels and concentrations demonstrated significant improvement in the condition of the skin with trends implying that increasing the pH increases efficacy.

Photoprotective and antiinflammatory effects of topical glycolic acid.

BACKGROUND: Concerns about photosensitizing potential of alpha hydroxy acids have been expressed. A previous study, however, reported topical glycolic acid showing the opposite potential, that is, photoprotective. This study was designed to test the antiinflammatory and photoprotective capabilities of glycolic acid. OBJECTIVE: The effects of short-wave ultraviolet light (UVB) on skin treated with glycolic acid were evaluated in two different studies at two different locations. METHODS: In the first study the antiinflammatory potential of topical glycolic acid was tested on erythematous templates on the backs of human volunteers. Erythema was induced by exposure to three times the minimum erythema dose (MED) of UVB. Glycolic acid cream in an oil-in-water vehicle at 12% partially neutralized with ammonium hydroxide to a pH of 4.2 was applied to the template beginning 4 hours postirradiation four times a day. A second template on the same subject was used as a vehicle control. After 48 hours a marked reduction of erythema was noted when compared with the vehicle control site. In the second study, four test sites were exposed to UVB light in the following manner. Site 1 was a nontreated control site and was used to establish the MED for the subjects being tested; site 2 was also exposed to a MED series but was treated 24 hours postirradiation for 7 days with two glycolic acid-based products (cleanser and oil-free moisture lotion, both containing 8.0% glycolic acid at a pH of 3.25); site 3 was treated first with the two glycolic acid-based formulas for 3 weeks prior to being exposed to UVB light; and site 4 was treated as outlined in site 3, with the inclusion that the site was chemically peeled for 6 minutes (with a 50% glycolic solution at a pH of 2.75) 15 minutes prior to UVB exposure. RESULTS: When UVB-burned skin was treated with glycolic acid daily for 7 days (site 2), a 16% reduction in irritation was observed compared to nontreated skin (site 1), implying that skin healed sooner when treated with glycolic acid. When a comparison of nontreated skin was made to skin treated with glycolic acid for 3 weeks prior to UVB exposure (site 1 vs site 3), a sun protection factor (SPF) of 2.4 was achieved. When a comparison of skin treated for 3 weeks was made to skin treated for 3 weeks and chemically peeled (site 3 vs site 4) the data implied that the chemical peel reduced the SPF value of skin treated with glycolic by approximately 50%, however, an SPF trend of 1.7 was still obtained when compared with untreated skin. CONCLUSIONS. The studies demonstrated that topical glycolic acid provides a photoprotective effect to pretreated skin yielding an SPF of approximately 2.4. In addition, when glycolic acid is applied to irradiated skin, it accelerates resolution of erythema. The data obtained from both studies support the hypothesis that glycolic acids acts as an antioxidant.

Cardiovascular effects of sevoflurane compared with those of isoflurane in volunteers.

BACKGROUND: Sevoflurane is a new inhalational anesthetic with desirable clinical properties. In some clinical situations, an understanding of the detailed cardiovascular properties of an anesthetic is important, so the authors evaluated the hemodynamic effects of sevoflurane in healthy volunteers not undergoing surgery. METHODS: Twenty-one subjects were randomized to receive sevoflurane, isoflurane, or sevoflurane: 60% N2O. Anesthesia was induced and maintained by inhalation of the designated anesthetic. Hemodynamic measurements were performed before anesthesia, during controlled ventilation, during spontaneous ventilation, and again during controlled ventilation after 5.5 h of anesthesia. RESULTS: A few subjects became excessively hypotensive at high anesthetic concentrations (2.0 minimum alveolar concentration [MAC] sevoflurane, 1.5 and 2.0 MAC isoflurane), preventing data collection. Sevoflurane did not alter heart rate, but decreased mean arterial pressure and mean pulmonary artery pressure. Cardiac index decreased at 1.0 and 1.5 MAC, but in subjects with mean arterial pressure > or = 50 mmHg returned to baseline values at 2.0 MAC when systemic vascular resistance decreased. Sevoflurane did not alter echocardiographic indices of ventricular function, but did decrease an index of afterload. Sevoflurane caused a greater decrease in mean pulmonary artery pressure than did isoflurane, but the cardiovascular effects were otherwise similar. Administration of sevoflurane with 60% N2O, prolonged administration or spontaneous ventilation resulted in diminished cardiovascular depression. CONCLUSIONS: At 1.0 and 1.5 MAC, sevoflurane was well tolerated by healthy volunteers. At 2.0 MAC, in subjects with mean arterial pressure > or = 50 mmHg, no adverse cardiovascular properties were noted. Similar to other contemporary anesthetics, sevoflurane caused evidence of myocardial depression. Hemodynamic instability was noted in some subjects at high anesthetic concentrations in the absence of surgical stimulation. The incidence was similar to that with isoflurane. The cardiovascular effects of sevoflurane were similar to those of isoflurane, an anesthetic commonly used in clinical practice since 1981.

The effect of esmolol given during cardiopulmonary bypass.

beta-Adrenergic antagonism decreases the size of myocardial infarction and provides myocardial protection during hypothermic arrest for cardiac surgery. However, concern regarding the negative inotropic and chronotropic effects of beta-adrenergic antagonism persisting after cardiopulmonary bypass (CPB) has impeded the use of esmolol for this purpose during cardiac surgery. This is a randomized, double-blind prospective study of the effects of esmolol infused during CPB and the effects of hypothermic CPB on esmolol. Patients scheduled for CPB were randomized to receive intravenous esmolol (300.micrograms.kg-1.min-1 during CPB after a bolus of 2 mg/kg prior to CPB) or placebo. Infusion was stopped at 10 min after release of aortic cross-clamp. Hemodynamics were measured, as well as serum esmolol, catecholamines, lactate, and potassium. Postoperative variables measured included electrocardiographic changes, creatine kinase (CK)-MB fractions, post-CPB dysrhythmias and drugs, hospitalization time and cost, and mortality. Esmolol was administered to 16 patients and placebo to 14. Esmolol levels reached a high of 10.5 +/- 0.9 micrograms/mL during CPB, but decreased to 0.1 +/- 0.02 microgram/mL within 30 min after stopping infusion. Cardiac indices (cardiac index, stroke volume index, left cardiac work index, left ventricular stroke work index, right cardiac work index, and right ventricular stroke work index) were higher in the esmolol group for the first hour post-CPB (P < 0.05). Systemic arterial lactate and coronary sinus lactate were lower in the esmolol group after CPB (P < 0.05), but myocardial lactate extraction was not significantly different between groups. After CPB, hemoglobin was lower in the esmolol group (P < 0.05) due to longer CPB and aortic cross-clamp time (P < 0.05), but oxygen consumption was less than in the control group (P < 0.05). Post-CPB serum potassium was higher in the esmolol group (P < 0.05). Results are confounded by more chronically beta-adrenergically blocked patients randomized to the esmolol group (P < 0.05). Esmolol infused during CPB in this series of patients was associated with high concentrations during CPB but did not result in any adverse clinical effects after CPB.

Clinical comparison of sevoflurane and isoflurane in healthy patients.

We compared blood pressure and heart rate changes in healthy patients during anesthesia with sevoflurane (n = 50) versus isoflurane (n = 25) and the rate of recovery after such anesthesia. After premedication with intravenous administration of midazolam, induction of anesthesia with thiopental, and intubation of the trachea facilitated with succinylcholine or vecuronium, anesthesia was maintained with approximately 1 MAC (sevoflurane, 2.05%; isoflurane, 1.15%) of the volatile anesthetic in oxygen for the duration of the operation. Anesthetic concentration was varied as indicated to maintain arterial blood pressure at +/- 20% of baseline values. Sevoflurane and isoflurane produced similar systolic and diastolic arterial blood pressures, but heart rate after incision was faster in patients given isoflurane. Recovery of response to command was shorter in patients given sevoflurane than that in patients given isoflurane (7.5 +/- 0.5 min versus 18.6 +/- 2.0 min). Consistent with this finding, venous blood drawn after anesthesia showed a more rapid initial decay with sevoflurane. Nausea and vomiting were comparable in both groups. We conclude that sevoflurane anesthesia, as compared with isoflurane, is associated with possible advantageous effects on heart rate and recovery.

Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man.

Vasoactive agents are commonly used in the postcardiopulmonary bypass period to elevate the mean arterial pressure of myocardial revascularization patients. Concern exists that administration of vasoactive agents in this setting may affect flow through saphenous vein and internal mammary artery grafts. Twenty-eight patients were randomly assigned to receive one of the six two-drug combinations of phenylephrine, norepinephrine, and epinephrine. After termination of cardiopulmonary bypass baseline, hemodynamic measurements and electromagnetic flow probe measurements of saphenous vein and internal mammary artery graft flow were made. The first agent was then infused to elevate mean arterial pressure 20 mm Hg. After 5 minutes of stability, hemodynamic and graft flow measurements were repeated. The infusion was terminated, 5 minutes of stability were obtained, and baseline measurements were repeated. The second agent was then infused, and measurements were repeated after a 5-minute stabilization period. Phenylephrine induced a nonsignificant increase in saphenous vein graft flow (68 +/- 31 versus 81 +/- 49 ml/min) and a significant decrease in internal mammary artery graft flow (40 +/- 16 versus 32 +/- 12 ml/min). Norepinephrine induced a significant increase in saphenous vein graft flow (80 +/- 39 versus 97 +/- 39 ml/min) and no significant change in internal mammary artery graft flow (44 +/- 20 versus 45 +/- 20 ml/min). Epinephrine induced a significant increase in both saphenous vein (82 +/- 38 versus 96 +/- 40 ml/min) and internal mammary artery (38 +/- 12 versus 55 +/- 24 ml/min) graft flows. We conclude that administration of vasoactive agents in the postcardiopulmonary bypass period may significantly affect saphenous vein and internal mammary artery graft flows.