Interaction of myeloperoxidase with diclofenac. Inhibition of the chlorinating activity of myeloperoxidase by diclofenac and oxidation of diclofenac to dihydroxyazobenzene by myeloperoxidase

The chlorinating activity of myeloperoxidase, isolated from human polymorphonuclear neutrophils, was inhibited by the non-steroidal anti-inflammatory drug diclofenac (Voltaren). The concentration of diclofenac needed for 50% inhibition was 20 microM, a value comparable with IC50 values found for other drugs. Diclofenac did not react with HOCl nor with H2O2 but was oxidized in the presence of myeloperoxidase and H2O2 to an orange-coloured unstable product. The rate of oxidation was proportional to the enzyme concentration and to the concentration of diclofenac. but independent of the H2O2 concentration. Presumably both Compound I and Compound II, two intermediates formed during the reaction cycle of myeloperoxidase with H2O2 are able to oxidize diclofenac. In these redox reactions, the active short-living Compound I is reduced to Compound II, thereby inhibiting the chlorinating activity of the enzyme. Analysis by Fast Atom Bombardment mass spectrometry showed that in the presence of H2O2 myeloperoxidase oxidizes diclofenac to dihydroxyazobenzene.     

A cost-effectiveness comparison of surgical treatments for mitral valve disease.

This study compares the cost-effectiveness of mitral valve reconstruction and replacement. Published clinical data were used to determine the effectiveness of each procedure. Both direct and indirect costs were calculated. The findings indicate that reconstruction has lower costs per year of life extended than replacement due to better outcomes. Changing outcome probabilities and discount rates did not alter these results. Cost savings in excess of 40% may be achieved by early reconstruction for suitable patients. These results suggest that the prevailing practice of delaying surgery until replacement is needed should be reconsidered, especially for patients who could benefit from reconstruction.     

Experience in hemoconcentration by ultrafiltration in operations using artificial circulation at the All-Union Scientific Center of Surgery of the USSR Academy of Medical Sciences

The article deals with the results of using ultrafiltration hemoconcentration in 649 operations conducted on the open heart with extracorporeal circulation at the All-Union Scientific Center of Surgery, USSR AMS during 1983-1989. The method allows control of hemodilution and colloid-osmotic pressure of plasma during the indicated interventions, lessens the loss of blood, and reduces the expenditure of donor blood.     

Hypoglycaemic activity of dioscoretine from tubers of Dioscorea dumetorum in normal and alloxan diabetic rabbits

Dioscoretine isolated from the aqueous fraction of the methanol extract of Dioscorea dumetorum tubers when administered intra-peritoneally to normal and alloxan diabetic rabbits produces significant hypoglycaemic effects at a dose of 20 mg/kg. The fasting blood sugar in normoglycaemic rabbits was reduced from 112 mg/100 ml to 55 mg/100 ml after 4 hours. In alloxan diabetic rabbits, the blood sugar was lowered from 520 mg/100 ml to 286 mg/100 ml at the same time interval. The aqueous fraction of the methanol extract produced comparable effects at 100 mg/kg. The chloroform fraction of the same extract raised the fasting blood sugar of normal rabbits to 196 mg/100 ml after 6 h. The acute toxicity studies gave LD50 values of 1.4 g/kg for the aqueous fraction and 0.58 g/kg for dioscoretine when tested on mice. The hypoglycaemic effects were compared to those of tolbutamide.     

Increase in brain cerebrospinal fluid volume is greater in older than in younger alcoholic patients: A replication study and CT/MRI comparison

This cross-sectional study used a semi-automated analysis technique to quantify regional brain cerebrospinal fluid (CSF) volumes derived from computed tomography (CT) in 84 healthy men ranging from 21 to 82 years of age and 28 patients meeting Research Diagnostic Criteria for alcohol dependence. The goals were to replicate an earlier CT study of an independent sample of alcoholic and control subjects (Pfefferbaum et al., 1988a; Zipursky et al., 1988) and to compare CT assessments of brain changes with magnetic resonance imaging (MRI) assessments made in the same alcoholic patients (Pfefferbaum et al., 1992). Regional brain changes associated with normal aging were derived by regression analysis, using CT data collected from the healthy control subjects. As in the earlier CT study and in the concurrent MRI study, ventricular and sulcal CSF volumes in alcoholic patients were greater than would be expected for their age. Furthermore, the present CT study replicated the previous CT and MRI findings of a positive relationship between age and CSF volume enlargement in alcoholic patients over and above the normal age-related increase in CSF volume, suggesting greater vulnerability of the aging brain to alcohol. Comparison of CT-and MRI-derived estimates of ventricular and cortical sulcal volume revealed high correlations (>0.80). MRI and CT produced similar absolute ventricular volumes, while MRI produced larger sulcal volume estimates than did CT. The difference in sulcal volume estimate may be due to differences between CT and MRI in slice thickness and sensitivity to partial volume effects.     

Injury to the femoral vessels--the Lebanese War experience

Over a 10-year-period extending from January 1976 to September 1986, 800 peripheral vascular injuries were surgically treated at the American University of Beirut Medical Centre. Of these, 150 were operated on because of injury to the femoral vessels. Bullets were the commonest wounding agents (60% of cases). Thirty-seven patients had a femoral artery injury, 27 a femoral vein injury and 86 combined femoral artery and vein damage. Twenty-three per cent of the patients had an associated fracture of the femur. Patients with fractures had an 11% amputation rate compared with 1% for those without fractures. Our data reveals the importance of venous reconstruction in the presence of an arterial injury instead of its ligation (P less than 0.05), particularly when there is an associated fracture of the femur. Thirty-seven per cent of patients were in shock on admission (systolic BP 90 mmHg). The amputation rate in these patients was 6.8% in contrast to 1% in the haemodynamically stable group (P less than 0.05). The overall amputation rate was 3.3%. Complications occurred in 36.6% of patients and the mortality was 4.0%.     

Energy metabolism and requirements in different ethnic groups

Some studies on energy metabolism of men and women in Third World countries suggested that their basal metabolic rate (BMR) is lower compared to BMRs of people in Northern European and American countries. It is, however, not clear whether this results from ethnic factors, climate or adaptation to, for instance, a low energy intake. A study on energy requirements of people from Third World countries has therefore been performed. People with different ethnic backgrounds participated; they were divided into four ethnic groups: 8 African males, 7 Asian males of Mongolian origin (Asian-M), 8 Asian males of Caucasian origin (Asian-C) and 7 European males, who formed the control group. The participants from outside Europe had spent at least 3 months in the Netherlands. All participants consumed a diet (12 per cent of energy from protein, 22 per cent from fat and 66 per cent from carbohydrate) during 8 d. The dietary energy given to each individual was estimated to maintain energy equilibrium during the experiment. The last 3 nights and 2 days were spent in an indirect whole-body calorimeter. Two 24-h energy expenditure (24hEE) measurements were performed on each subject. The environmental temperature inside the calorimeter was 22.0-24.5 degrees C. Physical activity was light, mainly sedentary, with 75 min bicycling at 15 W. The Asian subjects had a significantly lower body weight and fat-free mass than the Europeans. Energy requirement (ER), 24hEE and EE during the night (8 h sleep) was lower in the Asian and African subjects compared to the Europeans, but the difference only reached significance for the Asian-C and African males. When ER, 24hEE and EE-night were expressed in relation to body weight and fat-free mass the Asian groups showed a higher ER and higher EE than the Europeans. This result is contrary to findings of others and may be caused eg, by a higher body weight and fat-free mass of the European controls. Comparison of EE-night with BMR estimated from FAO/WHO/UNU equations showed that the EE-night was consistently lower by about 9 per cent. This suggests that EE during the night may not be predicted by the BMR estimated by widely used equations. This study does not give conclusive evidence that an ethnic factor is involved in energy metabolism in humans.