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Biomedical subjects

C Bowe

Publications and source records attributed to C Bowe.

5 recordsLinked to original sources

D-2-hydroxyglutaric aciduria.

Hydroxyglutaric aciduria is detected by gas chromatographic-mass spectrometric analysis, and the D and L forms are quantified by chemical ionization with deuterated internal standards. Patients have recently been described who accumulate the D form, and they appear to be quite different from those with the more common L form. Experience is reported with three patients and an animal model with D-2-hydroxyglutaric aciduria. The phenotype appears to include mental retardation, macrocephaly, hypotonia, seizures, and involuntary movements, although neurologic and systemic manifestations of the disorder varied considerably between individual patients, even within the same family.

Animals

Nodal spacing along regenerated axons following a crush lesion of the developing rat sciatic nerve.

The relation between internodal length (L) and fibre diameter (D) was examined light microscopically in teased specimens from normal developing rat sciatic nerves, and from rat sciatic nerves which had regenerated following crush lesions at various postnatal ages. In newborn rat pups virtually all sciatic nerve axons are unmyelinated and myelination is an essentially postnatal event. Between 2 weeks and 6 months maximal L increases from 500 microns to 1400 microns and maximal D increases from 6-8 microns to 16 microns. The increase in L matches the length growth of the hindlimb. Signs of myelin sheath remodelling are absent during normal development. Examination of regenerated nerves showed that the lengths of the internodes along large-medium-sized axons, are strongly dependent on crush age. In neonatally crushed nerves, the slope is close to normal. With increasing crush age the inclination of the regression line gradually decreases. Signs of myelin sheath remodelling are not seen in regenerated nerves crushed at birth or 1-2 weeks after birth. However, such signs are present in regenerated nerves crushed 3 weeks or more after birth. These observations support the view that myelin sheath remodelling in regenerated rat sciatic nerves is directly related to a deficient length growth following myelination.

Age Factors

Calcium blocking properties of piprofurol.

Piprofurol is a benzofuran chalcon derivative. It was studied under various experimental conditions which allow the recognition of calcium antagonistic activity. Piprofurol inhibited in a concentration-dependent manner the calcium-induced contractions in isolated potassium depolarized preparations of rat aorta (pA2: 9.29) and relaxed the K+-induced contraction of the dog coronary artery and the rabbit basilar artery (IC's 50: 2 10(-8) M; 3 10(-9) M). Piprofurol also inhibited noradrenaline-induced vascular smooth muscle contractions but the antagonism was clearly noncompetitive and the contractions induced were altered by concentrations two orders of magnitude higher than the concentration inhibiting calcium-induced contractions. Calcium antagonism was demonstrated in cardiac muscle: calcium mediated slowly rising action potentials were evoked in partially depolarized guinea-pig papillary muscle by electrical stimulation in the presence of isoprenaline. Piprofurol decreased the rate of rise of these slow action potentials. The inhibitory effect was reversed by an elevation of the calcium concentration in the bath fluid. Piprofurol exerts a negative inotropic effect (IC50: 5 10(-6) M) on guinea-pig papillary muscle. The ratio IC50 inotropic action/IC50 relaxant activity was 230, i.e. higher than that obtained with verapamil or diltiazem, and near that observed for cinnarizine. The pharmacological profile from in vivo dog experiments is in agreement with its in vitro properties: coronary sinus blood flow was increased and heart rate decreased. These effects suggested a potentially anti-ischaemic activity. This is confirmed in anaesthetized dogs, where piprofurol reduced the epicardial ST-segment elevation following coronary artery occlusion, and in isolated heart preparations, where it decreased the leakage of LDH during periods of anoxia and reoxygenation.

Action Potentials

Lipid intermediates in chronically volume-overloaded rat hearts. Effect of diffuse ischemia.

Tissue contents of intermediates of fatty acid metabolism were determined in isolated volume-overloaded rat hearts, 3 months after creation of an aorto-caval fistula. In the absence of any modification of blood carnitine, tissue levels of total carnitine were reduced by 33% in overloaded hearts compared to normal hearts. Total tissue CoA was unchanged. Fifteen minutes of whole-heart ischemia (i.e. a 50% reduction in coronary flow) did not increase levels of long-chain acyl esters of CoA and carnitine of the overloaded myocardium, in the presence of glucose as the only exogenous substrate. This was associated with lower than normal levels of long-chain acyl carnitine under normoxic conditions. The addition of exogenous palmitate (1.5 mM) resulted in an ischemia-induced accumulation of long-chain acyl-CoA and acyl carnitine in the overloaded heart although to a smaller extent than in the normal heart under similar perfusion conditions.

Acyl Coenzyme A