Subclinical hypothyroidism revisited. When is not enough really not enough?
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Biomedical subjects
Publications and source records attributed to D R Goldmann.
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Patients with diabetes mellitus, thyroid dysfunction, and adrenal suppression from exogenous steroid therapy frequently undergo surgery. An understanding of the pathophysiology of these disorders enables the medical consultant to have valuable input into the preoperative evaluation and perioperative management of these patients. This article serves as a practical guide in following such patients through surgery, thereby decreasing overall morbidity and mortality.
Proline uptake by rat renal brush border membrane vesicles from animals 7 days of age and older has been examined to delineate developmental changes in membrane function that may underlie the physiological hyperprolinuria of young animals. Although the two proline transport systems normally present in adult membranes were found in membranes from young animals, the proline "overshoot" resulting from a sodium ion gradient is minimal and increases with age of the animal from which the membranes were isolated. This is associated with a severalfold faster entry of 22Na into vesicles of the 7-day-old animal compared to entry into membranes prepared from adult kidneys. The very rapid dissipation of the sodium gradient thus diminishing the driving force for transmembrane proline movement may explain the changes in proline overshoot observed in membranes from young animals. The altered sodium permeability is consistent with the fact that young animals have a generalized inability to reabsorb other amino acids whose transport is known to be sodium gradient stimulated.
The transport of L-proline was studied in brush-border membrane vesicles isolated from the kidneys of newborn rats. In contrast with the rapid initial uptake with an 'overshoot' observed in adult vesicles, uptake by the newborn vesicle was slow, showed no 'overshoot', and proline continued to accumulate at a time when the adult vesicle had already equilibrated. L-Proline transport in the newborn rat occurs by Na+-dependent and independent mechanisms. There appeared to be essentially no uptake by anti-luminal vesicles isolated from newborn rat kidney. These observations may help to explain the prolinuria that occurs in the newborn animal.
The transport of alpha-aminoisobutyric acid and alpha-methyl-d-glucoside by isolated tubules from Sprague-Dawley rats at different stages of development follows a separate age-dependent pattern for each substrate. The effects of 6 M maleic acid on transport processes differ for amino acids and sugars and become manifest at distinct points during development. Maximum inhibition by maleic acid occurs at a time subsequent to maturity of these transport systems. In an effort to explain these transport phenomena, the uptake and metabolism of 14C-labeled maleic acid by the newborn or adult renal tubule was studied, showing significant binding by the tubule membrane, penetration of the cell by diffusion, and no conversion to 14CO2. Maleic acid has no demonstrable effect on the membrane-associated enzymes which are thought to play a role in the transport of small molecules.
gamma-Glutamyltranspeptidase, known to be localized in the proximal tubule cell brush border in the rat, is a membrane-bound enzyme which transfers the gamma-glutamyl moiety of glutathione or its analogue gamma-glutamyl-p-nitroanilide to an amino acid or dipeptide acceptor. Brush borders were isolated from the kidneys of newborn and adult Sprague-Dawley rats and assayed for gamma-glutamyltranspeptidase activity. There is an increase in specific activity in the brush border with maturation. Newborn and adult brush border preparations exhibit similar pH optima, substrate affinities, apparent Km values, patterns of heat inactivation, inhibition by glutathione, and migration on polyacrylamide gels. Polyacrylamide gel electrophoresis of a deoxycholate extract of brush border proteins and subsequent reaction with substrate within the gel reveal the presence of two bands, suggesting the presence of two forms of gamma-glutamyltranspeptidase in the rat kidney brush border.
A renal brush border fraction was isolated from newborn Sprague-Dawley rats, and its morphological and enzymatic characteristics were studied in comparison to that from the adult. Definite microvillar structures are seen by electron microscopy, and border preparations from the newborn are enriched in known marker enzymes. Though morphological development is more advanced and enzyme specific activities are greater in the adult, polyacrylamide gel electrophoresis of membrane proteins reveals no significant change in pattern with increasing age. These studies suggest that the brush border of the proximal tubule cell is present at birth as a significantly developed structure.
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