Plasma lipids and apolipoproteins in a population of Orang Asli ('aborigines') from West Malaysia.

Plasma total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDLC) and apolipoproteins Al (apo Al) and B (apo B) were measured in a sample of subjects from the Semai tribe of Orang Asli in peninsular Malaysia. They appeared to exhibit the lowest TC ever recorded (1.6 for males and 1.9 mmol/l for females) and relatively high TG (1.4 mmol/l for males and 1.5 mmol/l for females)(means for the whole sample). There was little apparent aging gradient in any of the plasma analytes. but the group of men aged 21-40 had lower HDLC than the corresponding female group. Both low density lipoprotein cholesterol (LDLC) (calculated) and HDLC as well as their corresponding apolipoproteins were correspondingly very low. There was a significant correlation between apo AI and HDLC in both sexes.

Inhibition of the neutrophil respiratory burst by neoglycoalbumin.

Both human serum fraction V albumin subjected to enhanced glycation by incubation with glucose, and a highly glycated albumin fraction prepared by m-phenyl boronic acid agarose affinity chromatography, when compared with albumin preparations of lesser glycation but equal concentration, inhibited the respiratory burst of the human neutrophil. Native albumin also inhibited the respiratory burst in proportion to its concentration. It is suggested that the neoglycoalbumin impairs glucose utilization by the neutrophil.

Correlates of diabetes markers with erythrocytic enzymes decomposing reactive oxygen species.

Superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase were assayed in the erythrocytes of a diabetic population on various treatment regimens (diet, oral therapy, and insulin), to investigate any relationships between their activities and diabetes markers (serum glucose, lipids, and fructosamine, as well as glycated haemoglobin). In the group of patients as a whole, there was significant negative correlation of SOD, but not of the other two enzymes with glycated haemoglobin and fructosamine. Specifically, there was a lower activity of the enzyme in the poorly-controlled patients. It is concluded that SOD in particular is potentially an additional marker for long-term diabetic pathophysiology.

Erythrocyte enzymes decomposing reactive oxygen species and gestational age.

Superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6) and glutathione peroxidase (GSH-Px; EC 1.19.1.1) were assayed in erythrocytes from neonates over a range of gestational ages. Both SOD and CAT activities were found to increase, but GSH-Px to decline, with gestational age. Enzyme activities in the erythrocytes of 13 babies who had respiratory distress syndrome (RDS) were not significantly different from controls matched for gestational age, but four with bronchopulmonary dysplasia (BPD) were found to have lower SOD activity. The importance of SOD in the preparation for extrauterine life is substantiated.

Antioxidants in food and chronic degenerative diseases.

Both preventive and chain breaking antioxidants have a role in the limitation of free radical damage. Some of these may be regarded as "classical", like vitamins E and C but others are more recently discovered, such as the flavonoids, widespread in plant tissues, and the muscle constituents anserine and carnosine. The major conditions in which the role of antioxidants is under intense investigation include coronary artery disease, cancer and diabetes. There are theoretical underpinnings for the efficacy of antioxidants in each of these, with the protection of low density lipoprotein (in respect of the first) being exceptionally persuasive. Much attention is now being focussed on the flavonoids, which are surprisingly pleiotropic in their effects. For one of them, quercetin, over a dozen seemingly independent biological effects can be listed, including the inhibition of low density lipoprotein oxidation. Flavonoids also inhibit peroxidation in foodstuffs, as opposed to tissues. There is much controversy over antioxidant supplementation policies, some authorities recommending a massive programme of supplementation for all ages and classes, others stressing the value of the traditional mixed diet. This matter is unlikely to be resolved soon, but in the meantime sensible supplementation policies should be continued for those most vulnerable, that is, babies and the aged.

Creatine phosphokinase and schizophrenia in Singapore.

This is a study to find out whether serum creatine phosphokinase activity (CPK) is raised in Oriental schizophrenic patients. CPK was found to be elevated in Caucasian schizophrenic patients more commonly during the acute period of the illness. The CPK involved is the skeletal isoenzyme CPK (MM) and not the brain isoenzyme CPK(BB). CPK elevation is associated with motor nerve and myoneural abnormalities. In this study of 150 patients the CPK activity varied from 12 to 902 mu/l with 78 patients having CPK activity above the normal range of 15-55 mu/l. This shows that Oriental schizophrenic patients may have similar pathophysiology. There is no relation between the CPK activities and the patients' age, duration of illness, presence of delusions or hallucinations, or abnormal behaviour. Such results support a genetic basis for the abnormality.

Superoxide dismutase and glutathione peroxidase activities in erythrocytes as indices of oxygen loading in disease: a survey of one hundred cases.

It has been established that the pyrogallol autoxidation method for the estimation of the activity of superoxide dismutase (SOD) (EC 1.15.1.1) is superior in precision and sensitivity to a superoxide-generating method (NADH/phenazine methosulfate linked to nitroblue tetrazolium reduction). Reference intervals were established in an urban population in the Far East for SOD activity in erythrocytes using the pyrogallol method, and for glutathione peroxidase (GSH-Px) (EC 1.11.1.9) activity in erythrocytes using a standard glutathione reductase-linked method. On this basis, erythrocyte SOD activities were significantly (P less than 0.05) depressed in cases of visceral cancer, acute myocardial infarct, congestive heart failure, respiratory failure, chronic renal failure, and diabetes mellitus, but within the reference interval in cases of lung cancer and asthma. Erythrocyte GSH-Px activity was significantly (P less than 0.05) depressed in cases of diabetes mellitus and chronic renal failure but elevated in respiratory failure and asthma. GSH-Px and SOD activities were well correlated in patients but not in the reference population.

Effects of shiitake (Lentinus edodes) extract on human neutrophils and the U937 monocytic cell line.

The aqueous extract of the shiitake mushroom was found to decrease IL-1 production and apoptosis in human neutrophils, as measured by ELISA and flow cytometry respectively. It was found to increase IL-1 production and apoptosis in the U937 monocytic cell line. The extract showed no significant effects on the superoxide production of both neutrophils and U937 cells, as measured by chemiluminescence. The extract was further separated into high and low molecular weight components, and it was found that the low molecular weight component retained the activity of the whole extract. This further suggests that the active substance is a novel compound distinct from lentinan, a well-studied high molecular weight anti-tumour agent found in shiitake.

Carnosine and anserine as modulators of neutrophil function.

Carnosine and anserine, the bioactive peptides found in most meats and fish, were tested for their ability to modulate neutrophil and U937 cell function, specifically with respect to respiratory burst, interleukin-1 beta production and apoptosis. Both peptides increased the respiratory burst and interleukin-1 beta production of human neutrophils but not of U937 cells. They suppressed apoptosis of human neutrophils but enhanced apoptosis of U937 cells as assessed by DNA strand breaks. These results suggest that carnosine and anserine have the capacity to modulate the immune response at least in human neutrophils.

Factors in serum and cerebrospinal fluid from children with viral encephalopathies impair glucose transport.

Since glucose transport appears to be inhibited in viral infections, we looked for inhibitors in cerebrospinal fluid (CSF) and serum of children with febrile convulsions (FC) and Singapore syndrome (SS). When incubated with rat and human adipocytes both fluids from FCs inhibited the utilization of glucose supplied in the medium as exhibited by decreased synthesis of triglycerides. Sera in the acute stage of the illness were more inhibitory than those from convalescents. There was competition between 3-0 methyl glucose and the CSF factors suggesting competitive inhibition at the plasma membrane. This may be due to anti-idiotypic antibodies. The likelihood of a second inhibitor is suggested by (1) the inhibitory activity of the larger of two fractions (about 80,000 molecular weight, corresponding to albumin) obtained in gel filtration chromatography of pooled CSF and (2) failure to observe a decrease in inhibitory activity with recovery from SS following management with hyperglycaemia-producing infusions. These observations are consistent with glycated albumin as a possible factor. Further characterization is called for to ascertain the genesis of viral encephalopathies.

Superoxide production by neutrophils from diabetics and normal subjects in response to glucose and galactose.

Glucose added to the medium was found to enhance superoxide production by isolated circulating neutrophils from both diabetic and normal subjects, but quantitatively the enhancement decreased from 4 to 50 mmole/liter. Galactose up to 50 mmole/liter had no effect on superoxide production in cells from the control subjects, but appeared to depress it in those from diabetics. No correlations were found between indices of the degree of hyperglycemia (plasma glucose and hemoglobin A1c) and the magnitude of the respiratory burst in cells from diabetics. When the isolated cells from normal and diabetic subjects were restored to a medium containing glucose at the original concentration in plasma at phlebotomy, the rate of superoxide production was approximately doubled in every case and there was no significant difference between diabetic and normal cells. Preincubation of cells for 1 hr in the presence of 0-50 mmole/liter glucose or galactose prior to activation had no significantly depressant effect on the respiratory burst except at 50 mmole/liter glucose in diabetic cells. It is concluded that circulating neutrophils from the diabetic population under the conditions studied are just as competent as control cells in their ability to sustain superoxide production over a wide range of energy availability.

Effect of glucose on the respiratory burst of circulating neutrophils from asthmatics.

The respiratory burst is dependent on a source of glucose. We wished to investigate the effect of glucose on the superoxide production of circulating neutrophils. Superoxide production of neutrophils was significantly enhanced by glucose concentration of from 1 to 50 mmole/liter in the medium. The neutrophils from asthmatics in both the acute and remission phases showed greater production of superoxide than those of controls. When the neutrophils were made to undergo the respiratory burst, initially in the absence of glucose, and thereafter in the presence of 5 and 20 mmole/liter glucose, the rate of superoxide formation with higher glucose medium was decreased in the control cells but significantly increased in the cells of the acute asthmatics in remission. It is concluded that glucose as an energy source is potentially critical in determining the rate of the respiratory burst and that the neutrophils from asthmatic subjects in some way have an enhanced uptake or metabolism of this substrate. Glycemic status may then have some role in determining the amount of superoxide production, and therefore airway inflammation, in asthma.

Effect of apolipoprotein E variants on plasma lipids and apolipoproteins in the Orang Asli ('aborigines') of Malaysia.

Members of the Semai group of Orang Asli ('aborigines') in peninsular Malaysia were examined for apolipoprotein E (apo E) variants in relation to plasma total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDLC), triglycerides (TG), apolipoprotein AI and apolipoprotein B (apo B). The e2 and e4 alleles were found to be higher than in most other groups as reported. The sample as a whole was normotriglyceridaemic (mean plasma TG, 1.5 mmol/l) and very markedly hypocholesterolaemic (mean plasma TC 1.7 mmol/l). The distribution of apo E variants was not related to any of the plasma lipids or apolipoprotein fractions using results from all subjects, but if a distinctly hypertriglyceridaemic sub-section was omitted (TG > 1.7 mmol/l) then apo E variants were determinants of plasma TC, LDLC, and apo B concentrations, the lower values of these being associated with the 2-2 and 2-3 genotypes, and the higher with 3-4, and 4-4.