Glucosamine

We have taken a stepwise approach to improving the dosing of continuous intravenous heparin in patients with acute coronary syndromes. Our primary objective was to use computer modeling to develop a nomogram for managing heparin therapy and to put in place a continuous quality monitoring system to evaluate the nomogram's effectiveness. We prospectively collected data on 41 patients with unstable angina or myocardial infarction who were treated with heparin. Their response to heparin was computer modeled and the dose to achieve an activated partial thromboplastin time (aPTT) ratio of 2.0 was established. This dose was regressed against all demographic characteristics to establish predictors of heparin dose (phase I). The regression formula was used prospectively in 110 patients to initiate the infusion rate of heparin and a bolus dose to achieve an aPTT ratio of 2.5. Subsequent dosage adjustments were achieved by computer modeling the patient's aPTT response (phase II). A nomogram was developed that simulated the decisions achieved using computer-assisted methods. This was retrospectively tested and then prospectively tested in 50 patients using nursing staff (phase IV). The nomogram was then made generally available (phase IV) and has been tested in an additional 310 patients. Phase I: Of the original 41 patients, 32% of the aPTT ratios were in the therapeutic range, 36% were supratherapeutic, and 32% were subtherapeutic after the first 24 hours. Phases II and III resulted in 85% of the aPTT ratios between 1.5 and 2.5 at 24 hours. Phase 4 had similar results in 310 patients. The use of computer-assisted or a computer-generated nomogram to adjust heparin therapy results in better control of heparin therapy than using standard methods.     

Amino-acid release from human cerebral cortex during simulated ischaemia in vitro

The aim of the present study was to investigate the release of amino-acids in human cerebral cortex during membrane depolarization and simulated ischaemia (energy deprivation). Superfluous tissue from temporal Iobe resections for epilepsy was cut into 500 microns thick slices and incubated in vitro. Membrane depolarization with 50 mM K+ caused a release of glutamate, aspartate, GABA and glycine, but not glutamine or leucine. The release of glutamate and GABA was Ca(++)-dependent. Slices were exposed to simulated ischaemia (energy deprivation; ED) by combined glucose/oxygen deprivation. This caused a Ca(++)-independent release of glutamate, aspartate, GABA, glycine, and taurine which started after 8 min, peaked at the end or shortly after the 27 min period of ED, and returned to control levels within 11 min following termination of ED. Preloaded D-[3H]aspartate was released both during K(+)-stimulation and ED. Release of D-[3H]aspartate during ED was delayed compared to glutamate supporting an initial phase of synaptic glutamate release. Uptake of L-[3H]glutamate was increased during the period of glutamate release, suggesting passive diffusion across the cell membrane or enhanced transport efficacy in cellular elements with functioning uptake mechanisms.     

Quality of life in relation to overweight and body fat distribution

OBJECTIVES: This study quantified the impairment of quality of life attributable to body fatness by using the standardized SF-36 Health Survey. METHODS: Tertiles of waist circumference and body mass index (BMI) in 1885 men and 2156 women aged 20 to 59 years in the Netherlands in 1995 were compared. RESULTS: The odds ratios and 95% confidence intervals of subjects with the largest waist circumferences, compared with those in the lowest tertile, were 1.8 (1.3, 2.4) in men and 2.2 (1.7, 2.9) in women with difficulties in bending, kneeling, or stooping; 2.2 (1.4, 3.7) in men and 1.7 (1.2, 2.6) in women with difficulties in walking 500 m; and 1.3 (1.0, 1.9) in men and 1.5 (1.1, 1.9) in women with difficulties in lifting or carrying groceries. Anthropometric measures were less strongly associated with social functioning, role limitations due to physical or emotional problems, mental health, vitality, pain, or health change in 1 year. The relationship between quality of life measures and BMI were similar to those between quality of life measures and waist circumference. CONCLUSIONS: Large waist circumferences and high BMIs are more likely to be associated with impaired quality of life and disability affecting basic activities of daily living.     

Treatment of extrahepatic occlusive jaundice with activated charcoal hemoperfusion in dogs

To find the feasibility of treatment for congenital bile duct atresia, we studied the usefullness of extracorporeal hemoperfusion over activated charcoal in canine obstructive jaundice. One, three and five weeks after ligation and disection of common bile duct in 5 dogs we performed the hemoperfusion over activated charcoal extracorporeally (group 3). In this animals we examined hematological and blood coagulation studies, serum electrolyte levels, kidney function tests and liver chemistries. As control in 5 animals we carried out after sham operation the perfusion without common bile duct ligation (group 2) and in 5 animals only common bile duct ligation without perfusion (group 1). In the liver chemistries we found 2 weeks after 2nd and 3rd perfusion (5 and 7 weeks after bile duct ligation) lower levels of serum bilirubin, GOT, GPT and SDH in treated group than in non-treated jaundiced animals. It suggest the effectiveness of hemoperfusion with activated charcoal in the treatment of occlusive jaundice. There were no alteration in the hematological studies, serum electrolyte levels and kidney function tests. PT and PTT was prolonged in the jaundiced animals there were no significant differences with and without hemoperfusion.     

Succinylation of proteins associated with the ribosomal attachment site on microsomal membranes

Ribosome-free membranes, prepared from rat liver endoplasmic reticulum by means of 2M LiCl, lost 90% of their ability to accept ribosomes for reattachment after exposure to succinic anhydride. However, treatment of rough-surfaced endoplasmic reticulum with succinic anhydride, prior to the removal of bound ribosomes by 2M LiCl, gave rise to membranes that were still able to accept ribosomes for reattachment. Succinylation of rough-surfaced endoplasmic reticulum resulted in the removal of some loosely-bound ribosomes and also a slight loss in glucose-6-phosphatase activity. Rough-surfaced endoplasmic reticulum, preincubated with succinic anhydride prior to treatment with lithium chloride, was exposed to [3H]succinic anhydride and subsequently analysed by dodecylsulfate polyacrylamide gel electrophoresis. By this means it was found that there were at least three proteins of different molecular weights that were associated with the membrane ribosomal attachment site.