Biomedical subjects
P Heron
Publications and source records attributed to P Heron.
Paradoxical effects of copper and manganese on brain mitochondrial function.
Defects in the mitochondrial genome have been associated with Parkinson's and Alzheimer's disease, and apoptosis can be triggered by the presence of energetically compromised mitochondria. Thus, in this study we have examined whether the divalent cations Cu2+ and Mn2+ could influence mitochondrial function in vitro. Mitochondrial electron transport was dose and time dependently reduced by Cu2+ to a greater extent with succinate as a substrate. Following a 60 min preincubation period, Mn2+ dose dependently inhibited electron transport to a greater extent with lactate and malate. In contrast, paradoxical effects were seen following a 5 min preincubation period with Mn2+. Cu2+ dose-dependently reduced NADH-dependent lactate dehydrogenase (LDH) activity, with almost complete inhibition apparent at 10 microM. An initial induction of LDH by 10 microM Mn2+ was partially reversed by higher concentrations of the metal. Cu2+ dose-dependently reduced flavin adenine dinucleotide (FAD)-dependent monoamine oxidase A (MAO-A) activity in a time-independent manner, with an IC50 value approximately 20 microM, whereas Mn2+ had no effect. In conclusion, it is proposed that Cu2+ and Mn2+ have differential effects on nicotinamide adenine dinucleotide (NAD) and FAD-dependent mitochondrial enzymes at the level of the essential cofactors. Cu2+ appears to exert an inhibitory effect on both NAD and FAD-dependent enzymes, but predominantly against the latter, including MAO-A and succinate dehydrogenase. The complex responses to Mn2+ may be due to dose-related effects on the interconversion of NAD and NADH and reversible enzymatic reactions employing this nucleotide cofactor.
17Beta-estradiol attenuates quinolinic acid insult in the rat hippocampus.
A number of studies have shown that 17beta-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17beta-estradiol against quinolinic-acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17beta-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 micromol quinolinic acid in 2 microL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM-5 microM 17beta-estradiol or quinolinic acid. The results show that 17beta-estradiol protects hippocampal neurons from quinolinic-acid-induced neurodegeneration by competing with quinolinic acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.
17Beta-estradiol protects against quinolinic acid-induced lipid peroxidation in the rat brain.
The neurotoxin quinolinic acid has been identified as a causative agent in Huntington's disease and is a metabolite of the tryptophan pathway in the brain. In the present study, the in vivo and in vitro effect of 17beta-estradiol on lipid peroxidation induced by quinolinic acid was investigated. For the in vivo experiments ovariectomized female rats were administered with 100 microg 17beta-estradiol daily for seven days prior to and seven days following the intrahippocampal injection of 1 micromol quinolinic acid. The level of lipid peroxidation in brain homogenate was investigated using the thiobarbituric acid test. The in vitro experiments were performed in brain homogenates of ovariectomized female rats. The homogenate was treated with quinolinic acid alone or in combination with 17beta-estradiol. Quinolinic acid increased lipid peroxidation in a dose dependent manner in vitro, while homogenate co-treated with 17beta-estradiol showed a significant reduction in lipid peroxidation. 17Beta-estradiol was also shown to be protective against quinolinic acid in vivo. These results could explain the neuroprotective effect of 17beta-estradiol.
Effect of increasing the tidal volume of smoke breaths on smoke-induced lung dysfunction.
We determined the effect of a graded increase in lung exposure to a toxic smoke by increasing smoke tidal volume (VT) or the number of smoke breaths. Sheep were anesthetized and then insufflated with cooled cotton toweling smoke; VT was 5, 10, or 20 ml/kg, and smoke breaths were varied from 12 to 48. The smoke had a uniform particle size (3 +/- 0.4 microns diam). Peak carboxyhemoglobin levels varied from 8 +/- 2 to 45 +/- 4% in the lowest to highest exposure groups, respectively. Animals were monitored unanesthetized for 24 h, and then they were killed. Oxygenation (ratio of arterial PO2 to fraction of inspire O2) decreased from 480 +/- 21 to 200 Torr, and compliance decreased by approximately 50% in the highest smoke exposure groups, whereas only a modest decrease in oxygenation and no compliance changes were seen with lesser exposures. A moderate tracheobronchitis, some atelectasis, and no alveolar edema were noted in the lower smoke exposure groups, whereas severe tracheobronchitis, airway edema, and alveolar atelectasis were observed in the highest exposure group. Only modest alveolar flooding was noted. Impaired oxygenation and anatomic injury correlated best with the total smoke delivered (r = 0.59). Increasing VT from 5 to 20 ml/kg did not increase airway or alveolar injury if the total smoke mass delivered was maintained constant. The degree of impaired oxygenation did not correlate with measured lung water (r = 0.27) or lung lymph flow (r = 0.31).
Initial effect of smoke inhalation injury on oxygen consumption (response to positive pressure ventilation).
BACKGROUND: Our purpose was to determine the effect of a smoke inhalation injury on initial oxygen demands measured as oxygen consumption. In addition, we wanted to determine the effect of positive pressure ventilation (PPV) on this process. METHODS: Adult sheep were insuffated with cotton toweling smoke to a carboxyhemoglobin level of 45% +/- 3% and then monitored unanesthetized for 24 hours. Oxygen delivery was maintained at a constant state. RESULTS: A significant increase in oxygen consumption (VO2), indicating increased metabolic demands, occurred during the first 2 hours after smoke with peak increase of 75% +/- 10% above baseline. A second increase occurred peaking at 18 hours with a 40% +/- 11% increase. Both increases were due to increased O2 extraction from hemoglobin rather than increased cardiac output. Use of PPV during the first 2 hours had no effect on VO2 but did correct impaired lung function manifested by an increased shunt fraction. Use of PPV during the later increased VO2 totally reversed the process but had less effect on improving lung function. CONCLUSIONS: We concluded that the initial increase in oxygen demands is likely due to an acute release of inflammatory mediators from the airway injury. The PPV response is to reexpand airways and alveoli, but it has no effect on the metabolic response. The late increase is likely due to increased work of breathing, which is removed by PPV. However, lung dysfunction from established airway edema at this stage is less reversible with PPV.
Hypostop for neonatal hypoglycaemia.
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Avoidable hazard to New Zealand children: case reports of haemorrhagic disease of the newborn.
Haemorrhagic disease of the newborn is preventable by the routine administration of vitamin K to newborn babies. Despite this, prophylactic administration of Vitamin K1 remains controversial and haemorrhagic disease of the newborn continues to cause significant morbidity and mortality. We present two cases of this disease occurring recently in this region of New Zealand; one resulting in an infant's death, the other baby suffering from an intraventricular haemorrhage and secondary hydrocephalus. These cases prompted us to survey major New Zealand hospitals to assess their policy as regards routine vitamin K administration to newborn infants. The results of this survey suggest that there is now a uniform policy in New Zealand hospitals of giving intramuscular vitamin K. However, intramuscular vitamin K administration may still be objected to by some parents and lead to further cases of this preventable disease. Evidence now available shows that vitamin K1 given orally in a dose of 1 mg is effective in preventing haemorrhagic disease of the newborn.
Insulin infusions in infants of birthweight less than 1250 g and with glucose intolerance.
Fifteen preterm babies (mean gestation: 26.7 weeks; mean birthweight 860 g) with significant glucose intolerance were treated with insulin infusions. During the insulin infusions there was a significant increase in both the mean energy intake (60.8 +/- 25.1 cal/kg per day to 79.9 +/- 24.5 cal/kg per day; P less than 0.001) and the mean amount of intravenous dextrose tolerated (7.0 +/- 2.7 mg/kg per min to 9.2 +/- 2.6 mg/kg per min; P less than 0.01). The infusions were initiated at a mean postnatal age of 5.3 days (range: 2-12 days) and were continued for 1.5-17.5 days. Of the 998 blood glucose estimations performed during the insulin infusions, 28 (2.8%) were less than 2 mmol/l and 216 (21.6%) greater than 8 mmol/l. We conclude that continuous insulin infusion is a safe and effective way of managing glucose intolerance in very low birthweight infants, provided adequate means for continuous monitoring of blood glucose are available.
Disturbance of the oculomotor system due to lateral fixation.
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