Terpenes and the lipid-protein-partitioning theory of skin penetration enhancement.

A series of terpenes has been assessed as skin penetration enhancers towards the model polar penetrant 5-fluorouracil (5-FU). Cyclic terpenes were selected from the chemical classes of hydrocarbons (e.g.

Comparison of cefpodoxime proxetil with cefaclor in the treatment of sinusitis.

The efficacy and tolerance of cefpodoxime proxetil were compared with those of cefaclor in a multicentre, international, prospective, double-blind, placebo-controlled study in adult outpatients suffering from acute sinusitis. At the end of treatment, cefpodoxime proxetil was more effective than cefaclor, producing complete clinical cure in 84% of cases (102/122) vs 68% of cases (77/114) in the cefaclor group (P = 0.01).

Tyrosine radicals in photosystem II and related model compounds. Characterization by isotopic labeling and EPR spectroscopy.

Deuteration at selected positions on the phenol ring and at the beta-methylene carbon for the YD.tyrosine radical in Photosystem II in the cyanobacterium Synechocystis 6803 was achieved by growing the organism under conditions in which it is a functional aromatic amino acid auxotroph (Barry, B. A.

Formation and characterization of vesicles from day-10 horse conceptuses.

The objectives of this research were 1) to determine if cellular vesicles could be formed from Day-10 horse conceptuses similar to trophoblastic vesicles reported for other domestic species and 2) to characterize various aspects of their development in vitro and their ability to withstand the freeze-thaw process. Twenty-five conceptuses were recovered from lighthorse mares on Day 10 after ovulation. After two washes in 0.

Effects of active immunization against GnRH on LH, FSH and prolactin storage, secretion and response to their secretagogues in pony geldings.

Six pony geldings were actively immunized against GnRH conjugated to bovine serum albumin (BSA) to study 1) the relative dependency of LH and FSH storage, secretion and response to GnRH analog on GnRH bioavailability and 2) the effects of reduced GnRH bioavailability on GnRH storage in the hypothalamus. Five geldings were immunized against BSA. Geldings were immunized in December and 4, 8, 14, 20, 26 and 32 wk later.

Suppression of lymphocyte proliferation by a greater than 30,000 molecular weight factor in horse conceptus-conditioned medium.

In this experiment we have identified and partially characterized the immunosuppressive activity of preimplantation horse conceptus-conditioned medium (HCCM). Horse conceptuses were nonsurgically flushed from mares at Days 9-10 (n = 6), 15-16 (n = 3), and 25-26 (n = 3). After incubating the conceptuses for 24 h in RPMI-1640 supplemented with 15% fetal calf serum (FCS) and 1% penicillin/streptomycin, HCCM was obtained from cultures and tested for immunosuppressive activity in lymphocyte proliferation assays.

Shed snake skin and hairless mouse skin as model membranes for human skin during permeation studies.

Difficulties in obtaining and using human skin have tempted many workers to employ animal membranes for percutaneous absorption studies. We have investigated the suitability of two species of snake (Elaphe obsoleta, Python molurus) for this purpose and compared our in vitro experimental results for human skin and for hairless mouse, a currently popular model. The effects of long-term hydration on the membranes were investigated over 8 d using tritiated water as a model permeant.

[Mouth and pharyngeal hyperalgesic syndromes in AIDS].

In a series of 12 patients suffering from an HIV infection, including 9 with confirmed AIDS, who complained about pharyngeal pain in a fixed site, having a progressive intensity and not relieved by antalgics and the specific treatments that were prescribed empirically, and for whom etiological investigation yielded negative results, Thalidomide proved to be the only effective means of healing the exulcerated, nail-mark lesions or the ulcerated, budding, neoplastic-like lesions, and of completely suppressing pain.

Olsalazine versus placebo in the treatment of mild to moderate ulcerative colitis: a randomised double blind trial.

The effect of olsalazine, an analogue of sulphasalazine, consisting of two molecules 5-aminosalicylic acid linked by an azobond has been investigated for the treatment of ulcerative colitis. In a randomised double blind trial we compared 2 g olsalazine with placebo for four weeks. Of the 105 patients, with mild to moderate ulcerative colitis, entered in the trial 52 received olsalazine, and 53 placebo.

Effects of sexual stimulation, with and without ejaculation, on serum concentrations of LH, FSH, testosterone, cortisol and prolactin in stallions.

Six lighthorse stallions with previous sexual experience were used to determine the short-term effects of sexual stimulation (SS; 5 min exposure to an estrous mare), SS plus ejaculation (SSE), and no stimulation (control) on serum concentrations of LH, FSH, testosterone, cortisol and prolactin. Stallions received one treatment per day on d 1, 4 and 7. Treatments were assigned such that each stallion 1) received each treatment once and 2) experienced a unique sequence of treatments.

Why are blue visual pigments blue? A resonance Raman microprobe study.

A resonance Raman microscope has been developed to study the structure of the retinal prosthetic group in the visual pigments of individual photoreceptor cells. Raman vibrational spectra are obtained by focusing the probe laser on intact photoreceptors frozen on a 77 K cold stage. To elucidate the mechanism of wavelength regulation in blue visual pigments, we have used this apparatus to study the structure of the chromophore in the 440-nm absorbing pigment found in "green rods" of the toad (Bufo marinus).

Directed mutagenesis indicates that the donor to P+680 in photosystem II is tyrosine-161 of the D1 polypeptide.

Photosystem II contains two redox-active tyrosines. One of these, YZ, reduces the reaction center chlorophyll, P680, and transfers the oxidizing equivalent to the oxygen-evolving complex. The second, YD, has a long-lived free radical state of unknown function.

Action of skin penetration enhancers-the Lipid Protein Partitioning theory.

Synopsis Skin penetration enhancers reversibly decrease the barrier resistance of the stratum corneum and allow drugs to penetrate more readily to the viable tissues and the systemic circulation. This paper presents a general theory for accelerant activity based on possible alterations at the molecular level of the components of the horny layer. Within the intercellular route, enhancers may interact at the polar head groups of the lipids, within aqueous regions between lipid head groups, and between the lipophilic tails of the bilayer.

Isolation and antigenic identification of hamster lung interstitial macrophages.

Lung interstitial macrophages (IMs) are a large, distinctive population of cells with important proliferative capacities. Characterization of their role in health and disease has been hampered by inadequate methods to separate interstitial from residual alveolar macrophages (AMs) in preparations of individual mononuclear cells from lung tissue. In this study, a specific cell-surface antigen (HAM1) present on more than 90% of hamster AMs, but not expressed by hamster IMs, was used to distinguish these populations.

Action of penetration enhancers on human skin as assessed by the permeation of model drugs 5-fluorouracil and estradiol. I. Infinite dose technique.

We have conducted permeation studies to assess the effectiveness of accelerants Azone, oleic acid (OA), decylmethyl sulfoxide (DCMS) and propylene glycol (PG) in promoting the absorption through human skin of model drugs 5-fluorouracil (5FU) and estradiol (ES). Drug permeation from saturated aqueous solutions was monitored before and after accelerant treatment (applied in aqueous and PG vehicles). With ES, the study was repeated with 50% ethanol/water as donor and receptor phases instead of water.

Pulmonary effects of blood replacement with a perfluorochemical emulsion followed by exposure to 85% oxygen or air.

Perfluorochemical emulsions (PCE) have been used as blood substitutes because of their high solubility coefficient for oxygen. However, concerns for their clinical use include both the hyperoxia required by PCE to improve oxygen delivery to tissues and the effects of PCE on lung tissue. We addressed 3 questions: (1) What are the combined effects on the lungs of PCE blood replacement and hyperoxia? (2) Does reduction of circulating white cells by PCE blood replacement modify the injurious effects of hyperoxia? (3) Does PCE alone alter the lungs? Adult rats received either partial or complete PCE blood replacement or no PCE and were then exposed to 85% oxygen for 5 days.

Hairless mouse skin is limited as a model for assessing the effects of penetration enhancers in human skin.

The permeability coefficient of 5-fluorouracil through human abdominal and hairless mouse skins was used as an indicator of the relative effects of 12-h pretreatment of the skins with either penetration-enhancer mixtures [including laurocapram (Azone), decylmethylsulfoxide, oleic acid, and propylene glycol] or saline (control). After treatment with saline, fluxes of 5-fluorouracil through the two skin types were similar, but the mouse skin showed exaggerated responses to all the penetration-enhancer formulations. There was no consistent relationship between enchancer effects on the two skin types, and we conclude that the hairless mouse model should not be used to predict the effects of penetration enhancers in human skin.

Limitations of hairless mouse skin as a model for in vitro permeation studies through human skin: hydration damage.

Hairless mouse skin currently provides a popular model membrane for studies in human percutaneous absorption. Although some similarities between the two skin types have been demonstrated, the effects of prolonged hydration on hairless mouse skin have not previously been rigorously examined. We have measured in vitro the effects of hydration at 31 degrees C on the permeabilities of hairless mouse skin and human abdominal and scalp skin to a model polar compound (water) and a lipid material (hexanol).

Effects of inhalation of 0.25 ppm ozone on the terminal bronchioles of juvenile and adult rats.

Cells of the terminal bronchioles are particularly susceptible to the effects of inhalation of low levels of ozone (O3). One-day-old (juvenile) or 6-week-old (adult) rats were exposed to 0.25 ppm O3 for 12 h/day or to continuous room air for 6 weeks.

Olsalazine in the treatment of mild to moderate ulcerative colitis: a randomized, placebo-controlled, double-blind, clinical trial.

Olsalazine, 2 g/day, was compared with placebo in 126 patients with mild or moderate ulcerative colitis. Evaluation after 4 weeks revealed a significant improvement in endoscopic findings in the rectum and sigmoid colon and in the clinical parameters rectal mucus and blood discharge, whereas no significant difference was found between olsalazine and placebo groups in clinical parameters, such as stool frequency and consistency, urge to defecate, abdominal pain and biopsy findings. It is concluded that olsalazine, 2 g/day, is tolerated as well as placebo except that it caused diarrhoea in some patients.