Treatment of wrinkles with the nonablative 1,320-nm Nd:YAG laser.

Ablative laser resurfacing with the CO2 and Er:YAG lasers has become a well-accepted and well-reported modality for skin rejuvenation of photoaged and photodamaged skin. However, the side effects associated with these lasers, such as exudation and crusting followed by prolonged erythema, are often socially disturbing for the patient. A nonablative 1,320-nm pulsed Nd:YAG system has been developed that controls dermal collagen damage while preserving the epidermis.

Retinaldehyde alleviates rosacea.

Background: Anecdotal observations suggest that retinoic acid may be effective in mild rosacea.

Aim: Our aim was to investigate, by an exploratory clinical and instrumental study, the effects of a topical formulation with the retinoic acid precursor retinaldehyde, in patients with vascular signs of facial rosacea.

Methods: Female patients were treated with a 0.

Correlation between percutaneous penetration of methyl nicotinate and sensitive skin, using laser Doppler imaging.

Cutaneous penetration of methyl nicotinate has been investigated in 20 women divided into reactors and non-reactors on the basis of response to 10% aqueous solution of lactic acid. The vasodilation induced was measured using a laser Doppler perfusion imager (LDPI) every 5 min for 1 h after application of methyl nicotinate. The intensity and duration of inflammation generated by methyl nicotinate were used to assess penetration of this chemical in persons with sensitive skin compared to those with normal skin.

The effect of crown ethers, tetraalkylammonium salts, and polyoxyethylene amphiphiles on pirarubicin incorporation in K562 resistant cells.

The basic distinguishing feature of all cells expressing functional P-glycoprotein-multidrug resistance (P-gp-MDR) is a decrease in steady-state accumulation drug levels as compared to drug-sensitive controls. In an attempt to identify mechanism(s) by which MDR can be circumvented, we examined the cellular accumulation, in resistant cells, of 4'-O-tetrahydropyranyl-doxorubicin (pirarubicin) alone and in conjunction with various molecules belonging to three different classes: the crown ethers, the tetraalkylammonium salts, and the polyoxethylene amphiphiles. The present study was performed using a spectrofluorometric method which enabled us to follow the uptake and release of fluorescent molecules by living cells while the cells were being incubated with the drug.

P-glycoprotein-mediated efflux of hydroxyrubicin, a neutral anthracycline derivative, in resistant K562 cells.

Hydroxyrubin (OH-Dox), a neutral doxorubicin derivative that is only slightly cross-resistant to doxorubicin (Dox), can be actively pumped out of resistant K562 cells by P-glycoprotein (P-gp). This efflux is saturable and can be inhibited by verapamil. The Michaelis constant is equal to 2 +/- 0.

Mobile ionophores are a novel class of P-glycoprotein inhibitors. The effects of ionophores on 4'-O-tetrahydropyranyl-adriamycin incorporation in K562 drug-resistant cells.

The decrease of the intracellular concentration of drug in resistant cells compared to sensitive cells is, in most cases, correlated with the presence, in the membrane of resistant cells, of a 170-kDa P-glycoprotein responsible for an active efflux of the drug. In an attempt to identify mechanism(s) by which multidrug resistance can be circumvented, we have examined the cellular accumulation of 4'-O-tetrahydropyranyl-adriamycin, alone and in conjunction with various ionophores on the one hand and with cyclosporin A on the other hand. The present study was performed using a spectrofluorometric method with which it is possible to follow continuously the uptake and release of fluorescent molecules by living cells, as the incubation of the cells with the drug proceeds.

Non-competitive inhibition of P-glycoprotein-associated efflux of THP-adriamycin by verapamil in living K562 leukemia cells.

The decrease of the intracellular concentration of drug in resistant cells as compared to sensitive cells is, in most of cases, correlated with the presence, in the membrane of resistant cells, of a 170-kDa P-glycoprotein (P-gp) responsible for an active efflux of the drug. The fluorescence emission spectra from anthracycline-treated cells suspended in buffer have been used to follow the P-gp-associated efflux of these drugs in the absence or presence of verapamil. In the present study, 4'-o-tetrahydro-pyranyladriamycin (THP-adriamycin) was used.

Analysis of Multidrug Transporter in Living Cells. Inhibition of P-glycoprotein-mediated Efflux of Anthracyclines by Ionophores.

One of the major obstacles of chemotherapy is that, after repeated treatments, cellular resistance to the drug appears. The problem is that the tumor cells become resistant not only to the drugs which have been used during the treatment but also to other drugs which are structurally and functionally unrelated. This is termed 'multidrug resistance' (MDR).

Accumulation of degradation products of doxorubicin and pirarubicin formed in cell culture medium within sensitive and resistant cells.

Quantitative study of doxorubicin (Adriamycin), pirarubicin (4'-o-tetrahypyranyladriamycin) and daunorubicin in the nucleus of living cells was performed using microspectrofluorometry. As for the cytotoxic assays, drug-sensitive and drug-resistant K562 cells were incubated for 3 days with concentrations of drug ranging from 4 nM to 1 mM. When drug-sensitive cells were incubated with pirarubicin, the spectrum recorded from inside the nucleus was characteristic of anthracycline intercalated between the base pairs in the nucleus.

Effects of PAF-acether and structural analogues on platelet activation and bronchoconstriction in guinea-pigs.

PAF-acether (platelet-activating factor) (1-O-alkyl-2-acetyl-sn-glycerol-3-phosphorylcholine) induces platelet-dependent bronchoconstriction in the guinea-pig which correlates with its in vivo thrombocytopenic effect. We investigated the influence of modifications of the polar head group in position 3 of the glycerol skeleton of PAF-acether on guinea-pig platelet activation and bronchoconstriction. PAF-acether itself induced concentration-dependent platelet activation (EC50 for aggregation = 0.

Structure-activity relationship in PAF-acether. 2. rac-1-O-Octadecyl-2-O-acetyl-3-O-[gamma-(dimethylamino)propyl]glycerol .

Two products without phosphoryl groups, 1-O-octadecyl-2-O-acetyl-3-O-[gamma-(dimethylamino)propyl]glycerol and its quaternary salt, were synthesized from 1-O-octadecyl-2-O-benzylglycerol. In comparison with PAF-acether, they lost aggregating and bronchoconstrictive activities and did not show any antagonistic effects.

Effect of structural analogues of PAF-acether on platelet desensitization.

The 1-O-alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (PAF-acether) aggregates rabbit platelets and desensitizes them to a second challenge with the same agonist but not to arachidonic acid. The desensitizing activities of 14 analogues of PAF-acether were explored with particular attention to the dose-response dependency of the desensitization process. PAF-acether was 500-fold more active than its 1-O-acyl analogues.

New total synthesis and high resolution 1H NMR spectrum of platelet-activating factor, its enantiomer and racemic mixtures.

A new method of synthesis of octadecyl platelet-activating factor (PAF; 1-O-octadecyl 2-O-acetyl sn-glycero-3-phosphorylcholine) is described. Its advantage is to proceed by way of the 'lyso-PAF' which may be substituted by various groups, while avoiding the inconveniences of the total synthesis already described. Moreover, the intermediates in synthesis are easier to purify, with better yields.