Spectral binding studies of the polymorphically metabolized drugs debrisoquine,sparteine and phenformin by cytochrome P-450 of normal and hydroxylation deficient rat strains

The mechanisms of polymorphic drug hydroxylation of debrisoquine, sparteine and related drugs in vivo have been investigated using Cyt P-450 preparations of inbred rat strains as an in vitro model of the poor and extensive metabolizer phenotypes found in various rat strains and in man. Optical difference spectroscopy with debrisoquine, sparteine, phenformin and three other drugs (selected test compounds with proven or suspected hydroxylation polymorphisms in man) exhibited Type 1 binding in normal Sprague-Dawley, Fischer and Lewis Cyt P-450, whereas no Type I drug binding was found in the hydroxylation deficient DA rat liver Cyt P-450. P-450 content and Type II drug binding of metiamide was the same in normal and hydroxylation deficient rat liver microsomes. The pronounced Type I drug binding in extensive hydroxylation Cyt P-450 and the defective Type I binding in DA Cyt P-450 in vitro, therefore, closely parallels the polymorphic hydroxylation pattern of these test drugs found in the four rat strains studied in vivo. Consequently, missing binding properties of Cyt P-450 or of its micro-environment might represent the enzymatic defect underlying the genetically determined hydroxylation deficiency of polymorphically metabolized drugs in the poor metabolizer phenotype in the DA rat and, by inference, in man.     

Plasma gamma-glutamyl transpeptidase in heroin addicts.

Plasma gamma-glutamyl transpeptidase was measured in 25 heroin addicts. The purpose was to find out if the long term administration of heroin would lead to a stimulation of GGTP due to the detoxication of this drug in the endoplasmatic reticulum of the liver. In 10 patients the elevation of GGTP could be attributed to liver damage, since other liver enzymes were also increased. 15 patients had normal GGTP activities, in 4 of them accompanied by minor elevations of single other hepatic enzymes. In 11 patients the GGTP activity as weel as that of the other enzymes was normal despite heavy chronic herioin abuse. It is therefore improbable that GGTP can be used to diagnose abuse of this drug and to evaluate the progress of drug detoxication treatments and drug abstention as has been proposed in chronic alcoholism.     

Use of the titanium-coated hollow screw and reconstruction plate system in bridging of lower jaw defects

Clinical results obtained with hollow titanium screws and reconstruction plates in the bridging of mandibular bone defects of 17 patients are described. Following implantation the newly forming bone establishes direct contact with the sprayed titanium surface of the screw and the underside of the plate and permeates the screw. The stability of anchorage therefore increases with the duration of implantation. The reconstruction system also allows salvaging of small fragments such as the condyloid process. The adjustable, individually shaped, mandibular condylar prosthesis permits precise restoration of articular guidance on the reconstructed side while preventing incorrect loading of the opposite joint. The clinical results confirm the recently published findings from animal studies.     

Effect of osteoporosis on the clinical and radiological outcomes following one-level posterior lumbar interbody fusion

Background

Cage subsidence or pedicle screw loosening following lumbar fusion surgery is frequently reported in osteoporotic patients. However, few studies have analyzed clinical as well as radiological outcomes after such surgeries as a function of bone mineral density. We aimed to evaluate the impact of osteoporosis on the clinical and radiological outcomes of patients who underwent one-level posterior lumbar interbody fusion (PLIF).

Early Childhood Vegetable,Fruit, and Discretionary Food Intakes Do Not Meet Dietary Guidelines,but Do Show Socioeconomic Differences and Tracking over Time

Background

Dietary intakes of young children are likely to be important determinants of their short- and long-term health, yet there are few longitudinal dietary studies of this age group, and no previous assessments of diets before age 2 years compared with national dietary guidelines.