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Biomedical subjects

R S Clements

Publications and source records attributed to R S Clements.

At least 73 records · Page 4Linked to original sources
PubMed1971

Metabolic alterations in the human erythrocyte produced by increases in glucose concentration. The role of the polyol pathway.

Human erythrocytes incubated in medium containing 50 mM glucose have increased intracellular sorbitol and fructose concentrations as compared with samples incubated with 5 mM glucose. Increased medium glucose concentration did not significantly alter total glucose consumption or lactate production. However, the intracellular lactate:pyruvate ratio rose, the concentrations of fructose diphosphate, and triose phosphates increased, and the 2,3-diphosphoglycerate concentration fell. [(14)C]O(2) production from glucose-1-(14)C also increased with increased medium glucose concentration. These changes are believed to reflect changes in the redox states of the diphosphopyridine nucleotide/reduced form of diphosphopyridine nucleotide (NAD/NADH) and nicotinamide-adenine dinucleotide phosphate/reduced form of nicotinamide-adenine dinucleotide phosphate (NADP/NADPH) couples resulting from increased activity of the polyol pathway. Addition of pyruvate to the incubation media prevented these changes. These studies illustrate that an increase in the red cell's normal substrate, glucose, can produce changes in red cell metabolism.

Adenosine Triphosphate↗
PubMed1969

Polyol pathway in aorta: regulation by hormones.

Aldose reductase is present in human and rabbit aortas and provides a mechanism whereby hyper-glycemia can alter the metabolism of the arterial wall. Aortic sorbitol concentration is regulated by ambient glucose concentration and is increased by epinephrine, isoproterenol, dibutyryl-3',5'-adenosine monophosphate, ouabain, and angiotensin II.

Alcohol Oxidoreductases↗
PubMedDate not supplied

Coping with autonomic neuropathy.

Diabetic autonomic neuropathy, the most common of all the complications associated with diabetes mellitus, is manifested as cardiovascular or gastrointestinal denervation, counterregulatory hormone dysfunction, and genitourinary tract denervation. Its treatment at this time is largely palliative, although there is some indication that control of hyperglycemia, hypertension, and obesity may prevent or delay its development. Both counseling and pharmaceutical approaches are essential to permit the afflicted diabetic patient a reasonably good quality of life.

Autonomic Nervous System↗
PubMedDate not supplied

Anti-glycated albumin therapy ameliorates early retinal microvascular pathology in db/db mice.

Hyperglycemia plays a primary causal role in the early vascular damage leading to diabetic retinopathy, but the intermediate biochemical mechanisms involved are not known. Because albumin modified by Amadori glucose adducts has been implicated in the pathogenesis of diabetic nephropathy, we investigated whether or not glycated albumin plays a similar role in diabetic retinopathy. We observed basement membrane thickening and an accumulation of basement membrane material in the capillaries of the outer plexiform layer of retinae from diabetic db/db mice compared with their nondiabetic db/m littermates. Both of these abnormalities were ameliorated by chronic (8 week) treatment with monoclonal antibodies that specifically recognize Amadori-modified glycated albumin (and not other glucose-modified or advanced glycation endproducts-modified proteins), despite the fact that the administration of these antibodies did not alter the glycemic status of the diabetic animals. Thus, albumin containing Amadori glucose adducts contributes to the pathogenesis of diabetic retinal vascular disease, and agents that neutralize or prevent the formation of excess glycated albumin in diabetes may offer prophylaxis against the early changes of diabetic retinopathy.

Animals↗
PubMedDate not supplied

Inhibiting albumin glycation ameliorates diabetic nephropathy in the db/db mouse.

Albumin modified by Amadori glucose adducts stimulates the expression of extracellular matrix proteins by glomerular mesangial and endothelial cells, and has been mechanistically linked to the pathogenesis of diabetic nephropathy. To test the hypothesis that inhibiting the formation of glycated albumin might beneficially influence the development of kidney disease in diabetes, we treated diabetic db/db mice for 12 weeks with a low-molecular-weight compound (EXO-226) that impedes the condensation of free glucose with lysine epsilon-amino groups in albumin. Administration of EXO-226 (3 mg/kg) twice daily by gavage normalized the plasma concentration of glycated albumin within days after initiation of treatment and maintained glycated albumin within the normal range throughout the study, despite persistent and severe hyperglycemia. Urine albumin excretion, which was markedly increased at the start of the study (age 12 weeks), was significantly reduced in treated diabetic animals compared with their untreated diabetic littermates. The fall in creatinine clearance that was observed in untreated diabetic animals was prevented in diabetic littermates that received treatment. Compared with the nondiabetic controls, the amount of glomerular mesangial matrix was threefold greater in untreated diabetic mice; in contrast, the mesangial matrix fraction was only 1. 5 times that of nondiabetic controls in the treated diabetic animals, representing a reduction in mesangial matrix accumulation of more than 50%. EXO-226 also reduced the overexpression of mRNA encoding for alpha1 (IV) collagen in renal cortex of db/db mice. We conclude that normalization of plasma glycated albumin concentrations with the glycation inhibitor EXO-226 ameliorates the glomerular structural and functional abnormalities associated with diabetic nephropathy in the db/db mouse.

Albuminuria↗
PubMedDate not supplied

Comparison of various methods for rapid glucose estimation.

We studied the accuracy of three techniques for the rapid estimation of the blood glucose concentration with reagent strips in samples of blood from inpatients with diabetes mellitus. We observed that the visual inspection of Dextrostix gave results that were too inaccurate for this technique to be of practical clinical benefit. In contrast, when performed by registered nurses, both the Dextrostix-Eyetone method and the visual inspection of Chemstrips yielded results that were closely correlated with the measured serum glucose concentrations. With both of the latter techniques, less than 11% of the determinations varied from the actual serum glucose concentration by more than 20%. We conclude that both these techniques are sufficiently accurate to be of potential use in the home monitoring of blood glucose concentrations.

Blood Glucose↗
PubMedDate not supplied

An evaluation of patient performance of and their satisfaction with various rapid blood glucose measurement systems.

We evaluated the performance of 50 insulin-dependent diabetic patients in the measurement of their own capillary blood glucose concentrations using Chemstrip bG, Dextrostix-Dextrometer, and Stat Tek systems. With all systems, patient performance was suboptimal when compared with the accuracy of paramedical personnel. The percentage of patient determinations that differed from the laboratory value by more than 20% was 37%, 30%, and 14% for the Chemstrip bG, Dextrostix-Dextrometer, and Stat Tek systems, respectively. Only 39 of the patients (78%) could perform accurately with any system. Youth, lack of a higher education, and lower income status contributed significantly to the patients' inaccuracy with the Chemstrip bG technique, whereas these factors had no effect on patient performance with the reflectance meter techniques. Nearly all of the patients were enthusiastic about the value of home glucose monitoring as a means to assess their glycemic control. However, only 30% of the patients selected for home use a technique at which they were suitably adept. In part, this selection error appeared to be due to the greater cost and inconvenience of the reflectance meter techniques compared with the Chemstrip bG technique. These data indicate that unless proper instruction is provided, home glucose monitoring should only be used by a fraction of insulin-requiring diabetic patients and the choice of a particular system for use by an individual patient should be predicated upon his or her demonstrated proficiency with that system.

Adolescent↗