Gene therapy for the treatment of malignant brain tumors with in vivo tumor transduction with the herpes simplex thymidine kinase gene/ganciclovir system.

Murine retroviral vectors can infect a wide variety of proliferating mammalian cell types (e.g. lymphocytes). Non-proliferating tissues (e.g. neurons) are not transduced by murine retroviral vectors. These findings suggest that this type of vector may be useful for the selective introduction of genes into growing tumors in the brain, since the tumor is essentially the only tissue that will integrate and express the vector genes.

Utilization of dietary precursors for carnitine synthesis in human adults.

Endogenous synthetic pathways are presumed to be sufficient to provide adequate amounts of carnitine to meet the needs of the body. However, circulating carnitine levels of strict vegetarian adults and children, and particularly of infants fed carnitine-free formulas, are significantly lower than normal. Therefore, we investigated loci at which rates of carnitine synthesis may be restricted in human adults. Excess amounts of the carnitine precursors lysine plus methionine, epsilon-N-trimethyllysine or gamma-butyrobetaine were fed as supplements to a low carnitine diet for 10 d. Rate of carnitine synthesis was estimated by changes in carnitine excretion and changes in serum and muscle carnitine levels. Dietary gamma-butyrobetaine dramatically increased carnitine production, epsilon-N-trimethyllysine had a somewhat smaller effect, and lysine plus methionine had even less effect on carnitine synthesis. We conclude that carnitine synthesis is not limited by the activity of gamma-butyrobetaine hydroxylase. Carnitine synthesis from exogenous epsilon-N-trimethyllysine is limited either by enzymatic processes that lead to the final intermediate, gamma-butyrobetaine, or by the ability of this substrate to enter tissues capable of carrying out these transformations.

Once-daily propranolol for hypertension: a comparison of regular-release, long-acting, and generic formulations.

This randomized, single-blind, crossover study compared three formulations of propranolol, each given once daily for hypertension. After an initial titration phase, subjects randomly received regular-release, long-acting, or a generic propranolol formulation. Each drug was given for 4 weeks and each active treatment was separated by a washout phase to allow blood pressure to return to baseline. Twelve subjects received all three active treatments. Systolic and diastolic blood pressures and pulses were significantly reduced from baseline by all formulations. There was no significant difference among drugs. Examination of diastolic blood pressures suggested some loss of antihypertensive control at the end of the dosing interval. These results indicate that it may be possible to administer propranolol once daily for hypertension and that there is no advantage for using the long-acting form.