Screening tests of free radical scavengers for preventing sun-accelerated cutaneous ageing.

Synopsis Free radical formation has been shown to occur in UV-irradiated skin and a large body of evidence suggests that these reactive agents are responsible for sun-accelerated cutaneous ageing. The paper describes two tests for screening free radical scavengers potentially capable of inhibiting photo-induced skin alterations. They are based on analysis of thiobarbituric acid-reactive materials either in an acellular model in vitro or in the epidermis of rose bengal-sensitized mice after white light irradiation.

Inhibition of platelet thromboxane synthetase by 1-(3-benzyloxy-1[E]octenyl)imidazole.

1-(3-Benzyloxy-1[E]octenyl)imidazole (CBS-645) is a specific inhibitor of thromboxane synthetase. It inhibits the platelet enzyme in human and rabbit at micromolar concentrations. At a dose of 12.

Corneal penetration and metabolism of the antiherpetic 5-iodo-2'-deoxycytidine.

The study of the permeability of the cornea to 5-iodo-2'-deoxycytidine (IDC), an antiherpetic agent was performed in the rabbit. In a first experiment, using 125I-IDC eye-drops and a sustained contact between the drug and the cornea, we showed that the penetration of IDC in the aqueous humor was important. In a second experiment, using a HPLC method, we studied comparative ocular penetration and metabolism of IDC and 5-iodo-2'-deoxyuridine (IDU).

Anti-inflammatory activity of a dual inhibitor of cyclooxygenase and lipoxygenase pathways, CBS-1108 (2-acetylthiophene-2-thiazolylhydrazone).

Anti-inflammatory therapy is actually devolved to glucocorticoids which prevent the release of arachidonic acid from phospholipids and consequently its subsequent transformation into prostaglandins and leukotrienes. This activity explains in part why steroids are better anti-inflammatory agents than acetylsalicylic acid (ASA)-like drugs which only reduce prostaglandin production. Despite their superior therapeutic actions, there are many side effects associated with corticosteroids.

Pilocarpine hydrochloride liposomes: characterization in vitro and preliminary evaluation in vivo in rabbit eye.

Liposomes containing either pilocarpine hydrochloride or pilocarpine free base were prepared by the sonication method. This manufacturing process yielded after removal of non-encapsulated solute, small multilamellar vesicles (MLV) as was confirmed by electron microscopy examinations. For an identical liposomal composition, the encapsulation capacity and the drug content of the liposomes were drastically higher for pilocarpine hydrochloride than for pilocarpine free base.

Dual inhibition of cyclooxygenase and lipoxygenase by 2-acetylthiophene 2-thiazolylhydrazone (CBS-1108) and effect on leukocyte migration in vivo.

CBS-1108, 2- acetylthiophene 2- thiazolyhydrazone , inhibits 5-lipoxygenase activity in polymorphonuclear leukocytes (PMNs) (IC50 = 2 X 10(-6) M), 12-lipoxygenase (IC50 = 9 X 10(-6) M) and cyclooxygenase (IC50 = 2 X 10(-6) M) in platelets. Inhibition of the two pathways of arachidonic acid cascade could lead to additional beneficial anti-inflammatory activity by comparison with classical aspirin-like drugs. In fact, only inhibitors of both cyclooxygenase and lipoxygenase such as NDGA and CBS-1108 inhibit leukocyte migration in an animal model of acute inflammatory response.

Percutaneous absorption of 5-iodo-2' deoxycytidine in the hairless rat and in man.

A study of percutaneous absorption of the anti-herpetic agent 5-iodo-2' deoxycytidine (IDC) was performed in vitro on the rat and on man and in vivo on the rat, using samples of normal skin and skin stripped of its stratum corneum. With normal skin, absorption was 1.84 cm.

In vitro study of gamma-glutamyl transpeptidase in rat lens.

gamma-Glutamyl transpeptidase catalyzes the initial step in the utilization of glutathione. In the lens, this enzyme is accessible to externally supplied substrates. An efflux of glutathione from the lens occurs when it was incubated in saline.

Evidence of leukotriene B4 biosynthesis in epithelial lens cells.

Metabolism of sodium (14C)-arachidonate by bovine epithelial lens cells was studied in culture. The cells converted arachidonic acid into a major product whose formation was not inhibited by aspirin, a cyclo-oxygenase inhibitor, but was suppressed by nordihydroguaiaretic acid, a lipoxygenase inhibitor and by dexamethasone. This metabolite co-migrated with leukotriene B4 in thin layer chromatography and high pressure liquid chromatography.