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Biomedical subjects

H C Barnard

Publications and source records attributed to H C Barnard.

34 records · Page 2Linked to original sources

Vitamin B-6 nutrition status and cigarette smoking.

We investigated the vitamin B-6 status in smokers, nonsmokers, and exsmokers by measuring both B-6 aldehyde vitamers, pyridoxal-5'-phosphate (PLP) and pyridoxal (PL), in the plasma as well as in the erythrocyte compartment. Two hundred eighty-six healthy, sedentary male workers from a middle-income group were investigated. There were 159 smokers, 59 exsmokers, and 68 nonsmokers. Plasma PLP and PL concentrations were significantly lower in smokers than in the nonsmokers and exsmokers whereas erythrocyte PLP and PL did not differ significantly between groups. Because PLP mainly functions as an intracellular coenzyme, the clinical significance of a depressed plasma PLP concentration alone is uncertain. It is concluded that circulating plasma PLP is labile and not necessarily indicative of intracellular PLP concentrations. The measurement of erythrocyte PLP and/or PL may be more informative about vitamin B-6 status than is plasma PLP alone.

Adult↗

Purine and oxypurine production in mitochondria of ischemic and reperfused myocardium.

The present study was undertaken to determine whether significant breakdown of adenine nucleotides to purine bases and oxypurines occurred in mitochondria following myocardial ischemia and ischemia followed by reperfusion, and whether allopurinol prevented this effect. The adenine nucleotides adenosine, hypoxanthine, xanthine and uric acid were measured in the mitochondria and the results suggest that breakdown did occur. Malondialdehyde concentration was determined to gauge lipid peroxidation. This substance did not increase during ischemia or reperfusion, but did so in the presence of allopurinol. Xanthine dehydrogenase was converted to xanthine oxidase during reperfusion and the activity of both enzymes were inhibited by allopurinol. The results also suggested the presence of a mitochondrial 5'-nucleotidase. We conclude that significant breakdown of adenine nucleotide took place in myocardial mitochondria during ischemia and ischemia followed by reperfusion and that allopurinol may have a protective effect.

Adenine Nucleotides↗

Towards standardisation of pre- and post-analytical variables in the assessment of lipid risk factors for ischaemic heart disease.

A wide disparity exists between statistical and optimal reference ranges for total cholesterol (TC) levels in South Africa. The haphazard downward adjustments by some laboratories over the years have resulted in highly variable and confusing 'normal cholesterol' values. Using essentially the same enzymatic method and equipment the TC upper limits varied by almost 50% (5.7-8.5 mmol/l) in 24 private laboratories, while it ranged from 5.7 mmol/l to 6.7 mmol/l in 6 academic hospital laboratories. The greatest disparity occurred in the lower limits of 'normal' for high-density lipoprotein cholesterol (HDLC), which ranged from 0.45 mmol/l to 1.43 mmol/l. Although triglycerides may not be an independent risk factor for ischaemic heart disease, the upper limit ranged from 1.69 mmol/l to 2.5 mmol/l despite comparable methods and equipment used. Lipid data obtained on approximately 5,000 healthy adults from the Transvaal, Natal and the Orange Free State revealed remarkable similarities to those obtained in the CORIS study. It therefore confirms the applicability of the CORIS epidemiological findings to other westernized groups in different regions of South Africa. This congruency in blood lipid values and methodologies used in different laboratories should also enable all state and private laboratories to use the same age-specific limits for desirable TC and HDLC levels.

Adult↗

Compartmentalization of pyridoxal-5'-phosphate during the acute phase of myocardial infarction.

Vitamin B6 nutritional status is assessed by measuring the plasma concentration of one of its vitamers, pyridoxal-phosphate (PLP). Several conditions, e.g., myocardial infarction (MI), can disturb the dynamic equilibrium between the different vitamers resulting in transiently low plasma PLP levels. An important question is whether these low plasma PLP levels observed during MI represent a transient state of deficiency and what the possible clinical consequences of such a fall in plasma PLP could be. Since the main metabolic function of PLP is to act as an intracellular coenzyme, it was decided to monitor the changes not only of PLP but also of PL (transport form of vitamin B6) in both the plasma and red blood cells (RBCs) in patients with myocardial infarctions (MI): 16 patients with proven MI were investigated measuring the aforementioned parameters at regular intervals. It was found that the approximately 40% fall in plasma PLP levels was accompanied by an equivalent increase in RBC PLP levels. Subsequently plasma PLP concentrations returned to normal but RBC PLP values were maintained at the newly elevated steady state (without any vitamin supplementation). Since membranes are impermeable to PLP, the only way in which PLP could have been redistributed to the intracellular compartment was through hydrolysis to PL and rephosphorylation once inside the RBCs. This compartmentalization could be an important adaptive response since it has been shown that PLP reduces O2 affinity of deoxygenated hemoglobin, thereby facilitating O2 delivery to the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of normothermic ischemic cardiac arrest and of reperfusion on the free oxygen radical scavenger enzymes and xanthine oxidase (a generator of superoxide anions).

Recent evidence suggests that free oxygen radicals are produced by ischaemic tissues, accounting for at least part of the damage that results. These free oxygen radicals are produced by xanthine oxidase, amongst others, and removed by scavenger enzymes (catalase, superoxide dismutase and glutathione peroxidase) and anti-oxidants. As mitochondria are oxygen-utilising organelles, they are capable of producing free oxygen radicals. Our results indicate that the removal of free oxygen radicals are not diminished during ischaemia, but the activity of the free oxygen radical generator, xanthine oxidase, is increased. This could lead to an increased superoxide anion concentration.

Animals↗

The effect of allopurinol and deferrioxamine on rat heart mitochondrial oxidative phosphorylation after normothermic ischemic cardiac arrest and of reperfusion.

The electron transport chain of the mitochondria is highly sensitive to myocardial ischemia. As free oxygen radicals take part in the damage that occurred during ischemia, this study was undertaken to determine if allopurinol and deferrioxamine had any beneficial effect on mitochondrial function. Our results showed that perfusion with allopurinol did not improve the mitochondrial function, but that reperfusion with allopurinol and deferrioxamine had a beneficial effect. We came to the conclusion that xanthine oxidase, as a generator of superoxide anions, is of minor importance in comparison with the hydroxyl radicals, which are probably formed in the presence of iron in the cell.

Adenosine Diphosphate↗

Vitamin B6 and coronary artery disease. Epidemiological observations and case studies.

The finding of low plasma pyridoxal-5'-phosphate levels in patients suffering from myocardial infarction has been construed as possible evidence for the pathogenetic role that vitamin B6 deficiency may play in causing premature ischaemic heart disease. However, the presence of normal plasma pyridoxal-5'-phosphate levels in patients with angiographic evidence of coronary artery narrowing but with no previous infarctions prompted the investigation of possible short-term alterations in plasma pyridoxal-5'-phosphate levels during the acute phase of myocardial infarction. In the follow-up of 30 patients with acute myocardial infarction, all of them showed a continuous decrease of approximately 45% in plasma pyridoxal-5'-phosphate levels during the acute phase. These levels subsequently returned back to normal before discharge from hospital. A large number of volunteers from an ethnic group known to have a very low incidence of ischaemic heart disease were found to have both significantly lower total cholesterol and plasma pyridoxal-5'-phosphate levels than a Caucasian group in the same geographic area which is known to have a high incidence of ischaemic heart disease. These findings therefore do not support the contention that vitamin B6 deficiency may be a risk index for ischaemic heart disease.

Adult↗

A new perspective in the assessment of vitamin B-6 nutritional status during pregnancy in humans.

Plasma pyridoxal-5'-phosphate (PLP) concentration has been suggested as a valid indicator to assess vitamin B-6 nutritional status. Animal and human studies have shown that plasma PLP concentrations decrease progressively during pregnancy and large doses of vitamin B-6 supplementation are required to maintain plasma PLP at early or prepregnant levels. PLP is known to be hydrolyzed to pyridoxal (PL) by alkaline phosphatase (ALP), resulting in an inverse relationship between PLP and ALP. The object of this study was to compare the PLP-PL equilibrium in a group of healthy pregnant females with that of an age-matched nonpregnant control group from a similar socioeconomic background. The mean plasma PLP level was 37% lower, (P less than 0.0001), whereas the mean PL level was almost 90% higher (P less than 0.001) in the pregnant group than in the nonpregnant control group. The total amount of plasma PLP and PL levels, however, did not differ significantly (P greater than 0.24) between the two groups. Because the PL vitamer is regarded as the ultimate transport form of vitamin B-6, it may serve as a readily available source of vitamin B-6 to meet possible increased metabolic demands. Therefore, the estimation of plasma PLP alone does not permit an accurate assessment or understanding of the nutritional status and the physiology of vitamin B-6 in conditions associated with altered vitamin B-6 homeostases.

Adolescent↗

Plasma pyridoxal-5'-phosphate levels in myocardial infarction.

In 34 patients with acute myocardial infarction (MI) plasma pyridoxal-5'-phosphate (PLP) levels were significantly lower (5.22 +/- 1.88 ng/ml) than those in an age- and sex-matched control group (11.5 +/- 2.03 ng/ml). In another group of patients who had clinical and angiographic evidence of ischaemic heart disease but had not had an MI plasma PLP levels were not significantly different from those in the control group (10.07 +/- 2.98 ng/ml). However, plasma high-density lipoprotein cholesterol levels in this group (0.75 +/- 0.28 mmol/l) as well as in the MI group (0.76 +/- 0.28 mmol/l) were significantly lower than those in the control group (1.26 +/- 0.23 mmol/l). On follow-up, all of 15 patients who had had an acute MI showed a continuous decrease in plasma PLP levels of approximately 50% during the first 48 hours after admission. Sixteen healthy volunteers subjected to a period of prolonged fasting (+/- 30 hours) displayed a decrease of approximately 43% over this period. We conclude that an acute reduction in plasma PLP levels occurred during the acute phase of MI. Other factors, for example prolonged acute starvation, may also produce a rapid decrease in plasma PLP levels.

Cholesterol, HDL↗

Correlation between pyridoxal-5'-phosphate levels and the percentage activation of aspartate aminotransferase enzyme in haemolysate and plasma during in vitro incubation studies with different B6 vitamers.

Conflicting results using erythrocyte aminotransferase (eAST) stimulation to assess vitamin B6 nutritional status in patients with less severe B6 deficiencies are common. It has been claimed that the presence of different B6 vitamers may modify the activation of eAST by pyridoxal-5'-phosphate (PLP) leading to stimulatory or even inhibitory effects. To investigate the possible role of this phenomenon in producing inconsistent AST stimulations, aliquots of whole blood were incubated with equivalent amounts of different B6 vitamers, and the AST stimulation was correlated with the concentrations of PLP, measured by high-performance liquid chromatography. At the end of the incubation period the erythrocytes and plasma were separately analyzed. The conversion of non-PLP B6 vitamers to PLP, by the erythrocytes, was similar (approximately 70%) for all B6 vitamers used in the incubation experiments. The newly formed PLP accumulated in the erythrocytes, but the percentage activation of AST did not change significantly from the basal levels, in spite of the presence of increased levels of PLP and other B6 vitamers used for incubation. When PLP was used in the incubation studies, all of it was retained by the plasma and was associated with a marked suppression of plasma AST stimulation. To determine the degree to which plasma and erythrocyte AST was dose-dependent, plasma and haemolysates were incubated with increasing concentrations of PLP. A very significant inverse relationship was obtained in plasma between AST stimulation and PLP even at modest PLP levels, while haemolysates required incubation with much higher PLP concentrations to demonstrate the same effect. Since plasma PLP is considered to be the most reliable indicator of B6 nutritional status in man, our findings suggest that plasma percentage AST stimulation more closely reflects the B6 nutritional status than erythrocyte AST stimulation test which may reflect B6 status only in severe, longstanding B6 deficiencies. Conflicting results using erythrocyte AST stimulations may be attributed to the insensitivity of red cell AST to changes in PLP content. It is unlikely that the presence of non-PLP B6 vitamers in haemolysate may affect the percentage stimulation of aminotransferase enzymes by PLP.

Aspartate Aminotransferases↗

The effect of acute prolonged starvation on the concentrations of vitamin B6 aldehyde derivatives in whole blood.

Since plasma pyridoxal-x-5'o-phosphate (PLP) levels are used to assess vitamin B6 status low levels are frequently interpreted to indicate B6 deficiency. However plasma PLP is in a dynamic equilibrium with pyridoxal (PL) through the action of non specific alkaline phosphatases (ALP). The object of this study was to monitor possible disturbances of this equilibrium in whole blood during acute prolonged fasting (40 hrs) and the subsequent repletion period in 16 healthy male dogs. Mean plasma PLP decreased by 15 percent (p less than 0.025) and PL increased by 20 percent (p less than 0.05) at the end of the starvation period and returned to baseline values after 48 hrs of refeeding. However total plasma aldehyde (PLP and PL) B6 vitamer concentrations remained unchanged throughout the investigation period. A 35 percent increase in haemolysate PL was the only significant change (p less than 0.0005) in PLP and PL levels observed in erythrocytes during fasting. It is concluded that the use of plasma PLP alone to assess vitamin B6 status may be misleading in conditions with a disturbed plasma PLP/PL equilibrium.

Aldehydes↗

Changes in activation of aspartate aminotransferase by pyridoxal 5'-phosphate after experimental liver damage in rabbits.

The aspartate aminotransferase activity with and without pyridoxal 5'-phosphate supplementation was examined in mitochondrial and cytoplasmic preparations from fresh human heart and liver samples. The apoenzyme was fully saturated in all cases. Liver cell damage was produced by ischaemia and carbon tetrachloride poisoning in two groups of rabbits. The activity of aspartate aminotransferase with and without pyridoxal 5'-phosphate was measured in the plasma and in cytoplasmic and mitochondrial preparations from both groups. After carbon tetrachloride poisoning the enzyme activity in the plasma increased within 2 h but was not enhanced by pyridoxal 5'-phosphate. Following ischaemia, plasma enzyme activity only increased between 4 and 8 h and was progressively stimulated by pyridoxal 5'-phosphate. Up to 15 h after carbon tetrachloride poisoning the liver cytoplasmic and mitochondrial apo-enzyme remained fully saturated with co-enzyme. In contrast, a pronounced loss of co-enzyme occurred in both fractions of the ischaemic group. These result suggest that the type of injury and not necessarily the organ affected could determine the degree of activation of aspartate aminotransferase by pyridoxal 5'-phosphate observed in human myocardial infarction and liver disease.

Animals↗

Processing factors as determinants of tissue valve calcification.

The effect of different processing factors on tissue valve calcification were studied in the subdermal rat model. Factors evaluated, were the influence of tissue ischaemia (4 degrees and 25 degrees C), different blocking reagents (KH2PO4, T6, MgCl2 and AlCl3), fixation pressures (0, 10 and 20 mmHg) and the pH (3.72 and 7.40) of the fixative. Tensile strength tests performed, showed that all blocking reagents tend to weaken valve tissue. Histologically calcification originated mainly in the spongiosa of the valve leaflets. Tissue ischaemia at 4 degrees C significantly (p less than 0.05) decreased the calcification potential of the valve tissue. Ischaemia at 25 degrees C significantly (p less than 0.05) increased this process. Blocking reagents KH2PO4, T6 and MgCl2 significantly (p less than 0.05) reduced calcification of valve tissue. AlCl3 pretreatment virtually prevented it to such an extend that the calcification process was down to 92% of the control group. Different fixation pressures had no influence on the calcification potential of the tissue. AlCl3 was dependent on a low pH (3.72) to act as a blocking reagent on tissue calcification. It is concluded that certain processing factors do influence the calcification potential of valve tissue. These factors should be considered when constructing bioprostheses with glutaraldehyde-treated porcine valves.

Abdominal Muscles↗

Melatonin and steroid-dependent carcinomas.

In this study the concentrations of plasma melatonin in patients with either prostatic or breast carcinoma were compared to the levels of controls. The mean melatonin was statistically lower in patients with breast cancer as compared to controls (p less than 0.005). In prostatic carcinoma patients, the mean melatonin was statistically higher than in the control group (p less than 0.005). From the results it would seem that low melatonin levels could possibly play a role in breast carcinoma, but the same did not necessarily applied to prostatic cancer.

Androgens↗

Melatonin and sperm motility.

Several substances can interfere with microtubular function eg. colchicine. Melatonin, a hormone secreted by the pineal gland has similar effects as colchicine on microtubules. In this study melatonin levels were determined in both plasma and seminal plasma of patients with good or impaired motility and forward progression. There was no statistically significant difference between the mean plasma and seminal plasma values of patients with good or impaired motility and forward progression. There was no correlation between seminal plasma melatonin and impaired motility or any other semen parameter. There was also no correlation between plasma and seminal plasma concentrations of melatonin. High seminal plasma melatonin concentrations were not necessarily associated with impaired sperm motility. From these it is concluded that seminal plasma melatonin plays no important role in sperm motility.

Humans↗