Skin penetration of epigallocatechin-3-gallate and quercetin from green tea and Ginkgo biloba extracts vehiculated in cosmetic formulations.

Green tea (Camellia sinensis) and Ginkgo biloba extracts in cosmetic formulations have been suggested to protect the skin against UV-induced damage and skin ageing. Thus, it is very important to assess the human skin penetration of their major flavonoids to verify if they penetrate and remain in the skin to exert their proposed effects. The aim of this study was to evaluate the human skin penetration of epigallocatechin-3-gallate (EGCG) and quercetin from green tea and G. biloba extracts vehiculated in cosmetic formulations. This study was conducted with fresh dermatomed human Caucasian skin from abdominal surgery mounted on static Franz diffusion cells. Skin samples were mounted between two diffusion half-cells and 10 mg/cm(2) of formulations supplemented with 6% of green tea or G. biloba extract were applied on the skin surface. The receptor fluid was removed after 6 and 24 h and analyzed by high-performance liquid chromatography for the quantification of the flavonoids. The stratum corneum was removed by tape stripping and immersed in methanol and the epidermis was mechanically separated from the dermis and triturated in methanol to extract EGCG and quercetin. The results showed that the flavonoids under study penetrated into the skin, without reaching the receptor fluid. The majority of EGCG was quantified in the stratum corneum (0.87 microg/cm(2)), which was statistically higher than the EGCG concentrations found in viable epidermis (0.54 microg/cm(2)) and in the dermis (0.38 microg/cm(2)). The majority of quercetin was quantified in the viable epidermis (0.23 microg/cm(2)), which was statistically higher than the EGCG concentration found in the stratum corneum layer (0.17 microg/cm(2)). Finally, it can be concluded that EGCG and quercetin from green tea and G. biloba extracts vehiculated in cosmetic formulations presented good skin penetration and retention, which can favor their skin effects.

Sevoflurane with remifentanil allows rapid tracheal intubation without neuromuscular blocking agents.

PURPOSE: After inhalational induction with sevoflurane, we compared the effects of adding remifentanil 1 microg x kg(-1) or remifentanil 2 microg x kg(-1) on conditions for tracheal intubation without neuromuscular blocking agents. METHODS: Before anesthetic induction, all patients were given 0.2 mg of glycopyrrolate iv to counteract the bradycardic effects of remifentanil. Two minutes after inhalational induction with 8% sevoflurane and 50% nitrous oxide, 56 female patients with normal airways scheduled for gynecologic surgery were randomized to receive remifentanil 1 or 2 microg x kg(-1) in a double-blind fashion. One minute later, laryngoscopy was initiated for tracheal intubation. Conditions for tracheal intubation and hemodynamic response to tracheal intubation were assessed. RESULTS: Tracheal intubation was successful in all patients. The incidence of post-intubation coughing was lower in the remifentanil 2 microg x kg(-1) group compared to remifentanil 1 microg x kg(-1) group (11% vs 39%, P <0.02). Optimal intubation conditions were also higher in the remifentanil 2 microg x kg(-1) group at 89% vs 54% (P <0.01). However, the higher dose of remifentanil also resulted in a greater decrease in mean arterial pressure (P <0.05). CONCLUSIONS: The addition of remifentanil after sevoflurane induction allows for rapid tracheal intubation without neuromuscular blocking agents. The higher dose of remifentanil results in improved conditions for tracheal intubation but also caused a greater decrease in mean arterial pressure. Tracheal intubation using sevoflurane and remifentanil may be an alternative to traditional tracheal intubation with neuromuscular blocking agents.

Additive anti-emetic efficacy of prophylactic ondansetron with droperidol in out-patient gynecological laparoscopy.

PURPOSE: To determine the efficacy of ondansetron and droperidol, alone and in combination, administered for prophylaxis of postoperative nausea and vomiting (PONV) in women undergoing general anesthesia for outpatient gynecological laparoscopy. METHODS: Following Institutional Ethics Board approval and patient consent, 160 female out- patients scheduled for laparoscopy were randomly allotted in a double-blind fashion to receive: i) saline (placebo), ii) 4 mg ondansetron, iii) 1.25 mg droperidol, or iv) 4 mg ondansetron and 1.25 mg droperidol combination intravenously on induction. Following a standardized general anesthesia, patients were interviewed and assessed for PONV at various times. RESULTS: During the first 24 hr after surgery, the incidence of PONV in the placebo group was 71%. This was reduced to 61% with droperidol alone (P = 0.334), to 46% with ondansetron alone (P = 0.027), and to 23% with the combination group (P<0.001). A statistically significant difference was observed between combination and droperidol (P<0.001) and between combination and ondansetron (P = 0.036). There were fewer requests for rescue medication from the combination group (7.7%) than from the ondansetron and placebo groups. CONCLUSION: The results of this study suggest that the combination of 4 mg ondansetron and 1.25 mg droperidol is more efficacious as a prophylactic anti-emetic than either agent alone during the 24 hr post-surgery. This additive effect may be due to the different mechanisms of action of ondansetron and droperidol.

Treating "rebound" emesis following outpatient gynecologic laparoscopy: the efficacy of a two-dose regimen of droperidol and ondansetron.

STUDY OBJECTIVE: To evaluate the efficacy of a two-dose combination of droperidol and ondansetron as compared with single-dose droperidol alone, single-dose combined droperidol and ondansetron, and two-dose droperidol alone, for management of postoperative nausea and vomiting (PONV) among gynecologic laparoscopy outpatients. DESIGN: Randomized, double-blind comparison trial. SETTING: Tertiary outpatient gynecologic unit. PATIENTS: A total of 120 female patients scheduled for gynecologic laparoscopy were enrolled. Patients who had experienced nausea or vomiting, or who had taken drugs with antiemetic action in the 24-hour period prior to the study, as well as breast-feeding mothers, were excluded from participation. INTERVENTIONS: Patients were assigned to four treatment groups: i) single dose of droperidol 1.25 mg, ii) two doses of droperidol 1.25 mg, iii) single dose of droperidol 1.25 mg and ondansetron 4 mg in combination, and iv) two doses of droperidol 1.25 mg and ondansetron 4 mg in combination. The first dose of antiemetic was administered prior to induction and the second dose was given by infusion 4 hours later, prior to discharge. MEASUREMENTS AND MAIN RESULTS: A visual analogue scale (VAS, 10 cm) was used to obtain patients' experience of nausea, vomiting, and pain at 0.5, 1.5, 2.5, and 3.5 hours after arrival at the postanesthetic care unit (PACU). Following discharge, approximately 24 hours after arrival at the PACU, the same measures were obtained by a follow-up interview using a verbal 10-point scale. No significant differences in incidence of PONV were noted among the four treatment groups (p = 0.419). However, both single- and two-dose droperidol and ondansetron combination therapy demonstrated attenuation of PONV severity in the 3.5- to 24-hour postinduction period (p < 0.05). CONCLUSIONS: The findings of this study suggest that prophylactic two-dose combined ondansetron and droperidol offers no added benefit over single-dose therapy for routine use in the gynecologic outpatient population.

Intracoronary propofol does not decrease myocardial contractile function in the dog.

The intravenous administration of propofol is associated with a considerable decrease in arterial blood pressure. The present study was undertaken to test the hypothesis that myocardial function is not affected by propofol and therefore does not contribute to the hypotensive effect of this anaesthetic agent. Propofol was administered in anaesthetized, open-chest dogs by direct arterial infusion into the left anterior descending coronary artery (LAD). Mean arterial blood pressure, heart rate, left ventricular pressure, dP/dt, regional lactate and oxygen extraction, as well as coronary blood flow were measured. Diastolic function was determined by calculation of the time constant of isovolumetric relaxation from the left ventricular pressure measurement and dP/dt. Contractility was evaluated by measuring regional systolic shortening in an area of the myocardium supplied by the LAD. This was compared with systolic shortening in the distribution of the circumflex (CIRC) artery and with the effects obtained with the intracoronary administration of thiopentone. Intracoronary infusions of propofol and thiopentone did not produce any change in systemic arterial blood pressure, heart rate, or left ventricular end diastolic pressure. Propofol, at a concentration of 5 or 10 micrograms.ml-1 did not decrease systolic shortening in the area perfused by the LAD while thiopentone (40 micrograms.ml-1) reduced systolic shortening by 33% (P < or = 0.05). Neither drug had an effect on systolic shortening in the CIRC area, LAD blood flow or diastolic function. The results of this study suggest that propofol does not have an effect on myocardial contractility. The hypotension associated with the intravascular administration of propofol is more likely due to either a direct vascular or a central effect.

Effect of halothane and isoflurane on postischemic "stunned" myocardium in the dog.

Short periods of coronary artery occlusion are known to produce prolonged periods of ventricular dysfunction. The effects of halothane or isoflurane on contractility and metabolism in postischemic "stunned" myocardium were studied in an open-chest canine model in which the left anterior descending artery (LAD) was occluded for 15 min and then reperfused. Regional function in the LAD and circumflex artery (CIRC) areas were measured with sonomicrometry, and metabolic data were determined from simultaneous arterial and venous measurements of oxygen and lactate. Halothane and isoflurane produced equivalent decreases in systolic shortening in both normal (CIRC) and stunned (LAD) areas of the heart. Furthermore, the amount of depression was similar with either halothane or isoflurane. Halothane 0.75 MAC significantly decreased systolic shortening in both the LAD region (from 38.8 +/- 25.9% to 11.0 +/- 21.8%) and in the CIRC region (from 116.7 +/- 24.7% to 87.5 +/- 23.3%). At equivalent MAC concentrations of isoflurane, the values were 42.5 +/- 45.7 to -7.0 +/- 49.9% in the LAD region and 91.5 +/- 11.9% to 66.9 +/- 23.9% in the CIRC area. At 1.5-MAC halothane, systolic shortening in the LAD region decreased from 47.9 +/- 47.2% to -0.6 +/- 20.3% and in the CIRC area from 114.6 +/- 16.8% to 76.0 +/- 18.7%. Isoflurane at 1.5 MAC produced significant decreases, from 23.4 +/- 54.5% to -15.6 +/- 27.1% in the LAD region and from 94.4 +/- 33.2% to 61.3 +/- 28.2 in the CIRC area.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasoconstrictor and vasodilator actions of arachidonic acid in the isolated perfused heart of the rat.

The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator. The non-steroidal anti-inflammatory agents (NSAA) indomethacin (1-5 mg/l) and naproxen (12.5-25 mg/1) reversibly inhibited both phases of the response induced by AA. Pretreatment of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg) daily, resulted in unaltered coronary response to AA. Subsequent addition of NSAA to the perfusate produced inhibition of the AA effect. Short infusions of acetylsalicylic acid at low concentrations (2.9 micrograms/ml), dipyridamole (0.6 micrograms/ml) and sulphinpyrazone (28.7 micrograms/ml) selectively inhibited the vasoconstrictor phase of the response to AA. It was confirmed that metabolic coronary dilatation induced by cardiostimulation was inhibited by prolonged AA administration; this effect was prevented by NSAA pretreatment. Reactive hyperaemic responses to short lasting occlusions of coronary inflow were unaffected by NSAA. Linolenic, linoleic, dihomo-gamma-linolenic and oleic acid usually produced decreases in coronary flow which were unaffected by NSAA, dipyridamole or sulphinpyrazone. Intra-aortic injections of AA, prostacyclin (PGI2) and prostaglandin E2 (PGE2) in the intact rat produced a dose-dependent decrease in blood pressure with the AA response inhibited by indomethacin. PGI2 and PGE2 produced long lasting coronary vasodilatation in the isolated heart. The coronary actions of AA appear to be due to its transformation, within the easily accessible vascular wall, into prostaglandin and thromboxane-like substances. We suggest that a vasoconstrictor thromboxane A2-like substance may be responsible for coronary vasospasm. Coronary insufficiency may also result from an inhibition of compensatory metabolic coronary dilatation by increased synthesis of PGE2 within the myocardial cell.