beta-Carbolines occur in man and rat. The concentration in various tissues is about 100 to 1000 times lower than that of classical neurotransmitters. Administration of beta-carbolines in animals induces overlapping but not identical activity profiles. The molecular modes of action differ. For example, harman (1-methyl-beta-carboline) acts as an endogenous inhibitor of monoamine oxidase [E.C. 1.4.3.4.], subtype A, whereas norharman (beta-carboline) probably acts by stimulation of a specific beta-carboline receptor which is different from the benzodiazepine-GABA receptor complex. There is substantial evidence that tetrahydroisoquinolines occur under physiological conditions as well. Whether tetrahydropapaveroline serves as a precursor of morphinanes in mammals, as has been found in opium poppies, remains to be elucidated.

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BACKGROUND: The wound healing process includes inflammation, proliferation, and remodelling phases, the main features of which are inflammation, neoangiogenesis, and epithelialization. Hyperbaric oxygen therapy (HBOT) is one modality postulated to improve wound healing. The objective of this study was to determine whether HBOT could improve selected features of burn wound healing in an experimental rabbit model. METHODS: Researchers conducted an experimental study with 36 rabbits given second-degree burns. Subjects were separated into two groups: a control group (n = 18) and an intervention group that was given HBOT at 2.4 atmospheres absolute for 6 days (n = 18). The main outcome measure was wound healing. RESULTS: Compared with the control group, the HBOT group showed more robust inflammatory cells ( P = .025) and epithelialization ( P = .024), but no significant difference in angiogenesis ( P = .442). CONCLUSIONS: The authors conclude that HBOT may improve second-degree burn healing by increasing inflammatory cell migration and re-epithelialization.

Tritium labelled 1-carboxy-tetrahydroharman was identified in rat brain following i.c.v.-injection of [3H]tryptamine and pyruvic acid. The animals had been treated with the MAO inhibitor pargyline (40 mg/kg) 30 min before i.c.v. injection. Under these conditions, only trace amounts of [3H]indole acetic acid could be detected in the brain. The formation of 1-CTHH was time-dependent. Five minutes following the i.c.v. injection, approximately 0.45% of the administered tryptamine was converted into 1-CTHH and 23% were still unchanged. The amount of the radioactive 1-CTHH increased slightly within 1 h (0.8%; [3H] tryptamine: 6%). Pretreatment of the rats with high doses of pargyline (75 mg/kg; 90 min before i.c.v. injection) prevented the formation of both [3H]1-CTHH and [3H]indole acetic acid (IAA) suggesting that high doses of pargyline inhibit the formation of 1-CTHH. As control for a possible non-enzymatic formation of 1-CTHH, [3H]tryptamine and various concentrations of pyruvic acid were incubated in phosphate buffer at pH 7.4. 1-CTHH was not detected under these conditions. However, the formation of 1-CTHH was observed at high pyruvic acid concentrations (final concentration = 100 mM) and low pH values (less than pH4). To support the assumption that the observed condensation of both precursors to 1-CTHH occurred intracellularly, the metabolism of tryptamine was studied. Two minutes after i.c.v. injection of [3H]tryptamine approximately 4% of the injected dose remained unchanged and 10% were metabolized to [3H]IAA. These findings suggest a rapid disappearance of [3H]tryptamine from the cerebrospinal fluid as well as a rapid penetration into the cerebral tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this open study was to evaluate the rate and extent of the penetration of sertaconazole nitrate (CAS 99592-32-2, Zalaïn) penetration into the stratum corneum/lucidum of the human skin. Selected areas of 9 cm2 each of the back skin of 12 healthy volunteers were exposed over 8 different time intervals (between 0 and 48 h) to 100 mg of a 2% cream preparation of the compound or to placebo. Using a HPLC-assay the relative amounts of the applied dose of sertaconazole nitrate were determined in the residual cream of the skin surface as well as in 3 layers of the epidermis obtained by the stripping technique. Sertaconazole nitrate was shown to penetrate into the stratum corneum shortly after application, disappearing from the application areas with a mean apparent half-life of approximately 60 h. Immediately after topical application the residual amount of the applied mean dose of 2103 +/- 146.3 microg on the skin's surface was 88.9 +/- 2.3%, decreasing steadily to 52.4 +/- 8.5% after 48 h. A relevant amount of the applied dose (5.3 +/- 3.0%) was recovered from the stratum corneum already 30 min after application, and 3 h after administration a plateau was reached (6.9 +/- 3.2) which could be maintained until 48 h. A gradient from the site of application to the epidermis was apparent since the amounts recovered in The estimated average level of sertaconazole nitrate for a volume of 1 mL of stratum corneum after application of 100 mg cream was 1409 microg immediately after application and reached a plateau at 3 h with 9029 microg. Although not directly measured, the results also gave information about the mean amount of sertaconazole nitrate that penetrated through the stratum corneum and deeper layers allowing an estimate of the total mean amount of compound penetrating into the skin. The relative portion of this amount steadily increased from 1.1% of the applied dose at 0 h to 24.1% at 12 h, 34.2% at 24 h and finally to 37.6% of dose after 48 h of exposure. In view of the high target organ levels of the compound maintained over days, its rapid appearance in the stratum corneum after application and the earlier finding that Sertaconazole nitrate is not distributed into blood in substantial quantities the pharmacokinetic properties of this antifungal preparation therapy can be regarded as favourable.

Tryptamine was degraded by incubation with rat brain homogenate to an unknown product. The reaction was stimulated by the nonionic detergents Triton X-100 and Lubrol PX and less by the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]1-propanesulfonate (CHAPS). The same results were obtained with pig brain and bovine brain. The monoamine oxidase inhibitor pargyline inhibited the reaction strongly, indicating the participation of the enzyme on the reaction. Addition of 17,000 g supernatant from rat brain homogenate increased the formation effectively whereas phospholipids or chloroform/methanol (7:3) extract from the 17,000 g supernatant showed only little or no effect. Chromatographic and electrophoretic properties as well as the chemical reaction of the product with specific reagents suggest that the compound consists of an indole part and an amino acid part. The product could be identified by fast atom bombardment mass spectrometry and by comparison with the synthetic substance (4R)-2-(3-indolylmethyl)-1,3-thiazolidine-4-carboxylic acid. It is formed by the enzymatic oxidation of tryptamine producing indole-3-acetaldehyde which spontaneously cyclizes with free L-cysteine from the tissue. The results suggest that the reaction of biogenic aldehydes with brain macromolecules may proceed via an analogous reaction.