Biotransformation of finasteride (MK-0906) by Selenastrum capricornutum (green algae).

Finasteride (MK-0906), a drug used for the treatment of benign prostatic hyperplasia, is a highly specific inhibitor of steroid 5 alpha-reductase, an enzyme that converts testosterone (T) to dihydrotestosterone (DHT) in animals and humans. In a study to evaluate the effect of finasteride on the growth of green alga, Selenastrum capricornutum, the parent drug was not detected by HPLC in the posttreatment (14 day) samples, suggesting complete biotransformation. Thermospray LC/MS, followed by NMR analysis, indicated that the major algal metabolite was 11 alpha-hydroxy-finasteride. This metabolite has negligible in vitro bioactivity against human prostatic 5 alpha-reductase; its potency is only 2% that of finasteride. The primary metabolite of finasteride produced by the green alga involved a biotransformation not previously observed in mammalian and human studies. The green alga effectively deactivates the drug, thereby mitigating any potential environmental impact.

Studies on heparin immobilization to collagen.

After activation of carboxyl groups with carbodiimide, heparin binds to collagen by a stable covalent linkage. Covalent binding of heparin to collagen results in enhanced stability of the preparation. Also, heparin bound collagen retains its anticoagulative activity.

Nonthrombogenic small-caliber human umbilical vein vascular prosthesis.

The present investigation demonstrates covalent binding of heparin with carbodiimide to ammonium hydroxide-treated collagenous surfaces. Human umbilical vein grafts (HUVG) outperform carotid arteries of goat, porcine, and canine origin in both heparin loading and stability of the immobilized heparin preparation. The average heparin loading on the untreated carotid arteries and HUVGs and ammonium hydroxide-treated HUVGs were 18, 27, and 31.5 micrograms/cm2, respectively. There was negligible loss of heparin activity under in vitro and in vivo conditions. In vitro studies demonstrate that heparin-bound HUVGs discourage platelet adhesion and subsequent fibrin clot formation. In vivo studies with heparin-bound HUVGs show a significant increase in thrombus-free surface compared with control grafts. Heparin-bound HUVGs also show an enhanced patency rate in the two sets of protocols tested--one lasting for 3 in vivo days (seven grafts) and the other lasting for 7 (15 grafts) in vivo days. The studies conducted so far demonstrate the promise of developing a nonthrombogenic small-caliber HUVG prosthesis.

Role of cometabolism in biological oxidation of synthetic compounds.

A significant portion of the total biodegradative activity toward synthetic compounds may involve cometabolism; thus, the latter represents an important type of microbial process. A mixed microbial population acclimated to highstrength industrial wastewater degraded about 90% of the organic carbon present in the wastewater. A reasonable agreement in the carbon balance provided clear evidence for the biodegradability of residual organic species. Based on the growth expression of Haldane to account for substrate inhibition, a substrate utilization model to quantify the role of cometabolism coupled with cellular maintenance is proposed. The kinetic parameters of the model have been estimated from experimental data. If the maintenance values are assumed negligible, as has been observed for wastewater systems, it is possible to quantify the magnitude of co-metabolism encountered in the biological oxidation of synthetic organic compounds.

Nonthrombogenic arterial reconstruction.

Carboxyl groups of heparin were activated by carbodiimide (EDC) to allow stable covalent binding of heparin to various arterial reconstructions. Ammonium hydroxide treated Human Umbilical Veins Grafts (HUVG) outperform carotid arteries of goat, porcine and canine origin in both heparin loading and stability. In-vitro studies reveal that heparin bound HUVG retains its anticoagulative activity, showing promise towards the development of a nonthrombogenic small-caliber vascular prosthesis.