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Biomedical subjects

M L Reynolds

Publications and source records attributed to M L Reynolds.

50 records · Page 3Linked to original sources

The effect of hypercapnia on a blood-brain barrier mechanism in foetal and new-born sheep.

1. The effect of marked hypercapnia (arterial PCO2 100 mmHg), nonrespiratory acidosis (pH 6-95-7-15) or hypoxia (arterial PO2 10-15 mmHg) upon penetration of labelled sucrose from blood into brain and c.s.f. has been investigated in exteriorized foetal sheep and new-born lambs. 2. In hypercapnia there was a consistent increase in c.s.f./plasma sucrose ratio after 90 min I.V. sucrose to four to five times control. Brain/plasma sucrose ratios were more variable. Usually there was an increase (up to three-and-a-half-times control); sometimes there was no change or even a decrease. The effect of hypercapnia on sucrose penetration was reversible. 3. Hypercapnia reduced c.s.f. secretion rate to approximately half the control value. Hypercapnia also caused a decrease in brain extracellular space. 4. Non-respiratory acidosis did not affect sucrose penetration. Hypoxia caused a decrease in brain/plasma sucrose ratio. 5. It is concluded that hypercapnia can cuase an increase in cerebral vascular permeability to sucrose in foetal and new-born sheep. Some possible mechanisms are discussed.

Acid-Base Equilibrium↗

The development of a blood-brain barrier mechanism in foetal sheep.

1. The penetration of a metabolically inert, small molecular radius lipid insoluble substance ([(13)C] and [(4)H]sucrose), from blood into brain and c.s.f., has been studied in developing sheep from 50 days gestation (term, 150 days) through to the new-born stage. Around 50 days gestation sucrose accumulated rapidly into brain and c.s.f., and reached a steady-state level in brain of about 12% of the plasma level by 3 hr. By 60 days sucrose penetrated less freely into brain and c.s.f.; the brain steady-state level was 10% by 4(1/2) hr. A large decrease in sucrose penetration occurred by 70 days gestation, and by 123 days (just before the time when a foetal lamb becomes viable) both the rate of penetration and the brain steady-state level of sucrose were similar to those of the adult of other species.2. The rate of c.s.f. secretion at different ages has been estimated by dye dilution during ventriculo-cisternal perfusion. The turnover of c.s.f. in 60 day foetuses was high (1.36%/min.g wet weight brain). From 123 days gestation to the adult stage the turnover was much lower, 0.02%/min.g at 123 and 137 days gestation and 0.01%/min.g in the adult ewe.3. A simple new method for measuring c.s.f. volume is described. The volume at 51 days was estimated to be 0.14 ml., S.E. +/- 0.03, n = 4 (brain weight = 0.87 g +/- 0.11), at 59 days it was 0.45 ml., S.E. +/- 0.04, n = 6 (brain weight = 2.0 g +/- 0.1) and near term it was 7.28 ml S.E. +/- 1.29, n = 4 (brain weight 42.0 g +/- 0.5).4. The results are discussed in relation to possible changes in permeability of the cerebral capillary endothelium, the sink effect of c.s.f., and changes in extracellular space of the brain during its development. It is concluded that the high rate of penetration and raised brain steady-state level of sucrose in immature sheep foetuses is probably due to immaturity of a permeability barrier at the level of the cerebral capillary endothelium or its associated glial processes. Some clinical implications of these findings are considered briefly.

Animals↗

The transfer of free alpha-amino nitrogen across the placental membrane in the guinea-pig.

1. Transfer of endogenous alpha-amino nitrogen from the maternal to foetal side of the placental membrane was studied in the foetal guinea-pig placenta perfused, in situ via the umbilical vessels, with an artificial fluid. Changes in maternal placental blood flow were followed by measuring the transfer of antipyrine into the perfusate.2. Active transport by the membrane was demonstrated under these conditions by observing the increased ratio of L/D leucine appearing in the perfusate in comparison with the maternal plasma ratio.3. Reduction in maternal placental flow following haemorrhage was associated with a fall in transfer of amino nitrogen to about half of the control values.4. The concentration of alpha-amino nitrogen in the perfusate was inversely proportional to the foetal placental flow which had a smaller influence on amino nitrogen transfer per min than did the maternal blood flow.5. Hypoxia and some inhibitors of oxidative metabolism were without influence on the transfer of alpha-amino nitrogen in this preparation.

Amino Acids↗

Stability of sulbactam/ampicillin in diluents for parenteral administration.

Compatibility studies were conducted of sulbactam/ampicillin in infusion diluents that are reported to be compatible with ampicillin sodium. A high-performance liquid chromatographic system that simultaneously detects sulbactam and ampicillin was used to determine whether the infusion diluents and the conditions of use recommended for ampicillin sodium are applicable to sulbactam/ampicillin. The results show that the sulbactam/ampicillin preparation for parenteral administration is compatible with all diluents recommended for ampicillin sodium. In all diluents sulbactam was more stable than ampicillin. At the end of the reported use periods, the average retention value for sulbactam in the combination solutions was 96% (range, 91%-101%), whereas the average retention value for ampicillin in the same solutions was 90% (range, 84%-95%). The presence of sulbactam had no adverse effect on the stability of ampicillin. The average retention value for ampicillin alone in the same diluents was 92% (range, 82%-99%). The conditions of use for sulbactam/ampicillin in diluents for parenteral administration are unrestricted by the presence of sulbactam and are, in fact, governed by those of ampicillin sodium.

Ampicillin↗