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Biomedical subjects

R L Engerman

Publications and source records attributed to R L Engerman.

At least 55 records · Page 3Linked to original sources
PubMed1986

Microvascular metabolism in diabetes.

Hyperglycemia has been implicated in the development of retinal vascular disease. Consequently, the effects of excessive hexose concentration on cells of the vascular wall are receiving increasing attention. Techniques for isolating metabolically active microvessels from tissues such as those from the retina and cerebral cortex are providing new opportunities for the study of the uptake and metabolism of hexose by microvessels. Such studies indicate that hexose uptake by microvessels is not insulin dependent and that microvessels are capable of metabolizing hexose by pathways common to many diverse tissues, including anaerobic and aerobic glycolysis, pentose phosphate shunt, and glycogenogenesis. Microvessels isolated from diabetic animals metabolize glucose at a subnormal rate. Hexitol production and accumulation has been implicated in the pathogenesis of diabetic complications in a variety of tissues and might also play a role in the development of diabetic microvascular disease. We have quantitated hexitol-producing metabolic activity of retinal and cerebral microvessels isolated from dogs, a species known to develop a retinopathy similar to that seen in diabetic patients. Erythrocytes were removed by perfusion prior to microvessel isolation because they are known to have hexitol-producing activity. Both retinal and cerebral microvessels produce galactitol from galactose, and this activity is inhibited in the presence of the aldose reductase inhibitor sorbinil. The presence of hexitol-producing activity within microvessels is consistent with a possible role of polyol production in the etiology of diabetic microvascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1985

Corneal endothelial changes in diabetic dogs.

The corneal endothelium of alloxan diabetic dogs was examined by wide-field specular microscopy and compared to that of age-matched non-diabetic dogs. Computer-assisted morphometry of individual cells showed that the diabetic dog endothelium had marked polymegethism and pleomorphism similar to that previously described in diabetic patients. There also appeared to be a positive correlation between the degree of these endothelial changes and the diabetic control as demonstrated by HbA1 concentration.

Alloxan↗
PubMed1985

Hexitol production by canine retinal microvessels.

Hexitol-producing activity has been quantitated in microvessels isolated from retina and cerebral cortex of dogs, a species known to develop a retinopathy similar to that seen in diabetic patients. Both the retinal and cerebral microvessels produce galactitol from galactose, but at a rate several-fold less than that seen in canine lens epithelium. This hexitol-producing activity of the microvessels is not an artifact of erythrocyte contamination and can be inhibited by the aldose reductase inhibitor, Sorbinil.

Animals↗
PubMed1984

Retinal oxygen tension in diabetic dogs following insulin infusion.

We measured preretinal oxygen tensions using a microelectrode in dogs made diabetic with alloxan. The intravenous administration of insulin did not affect preretinal oxygen tension over the two hours it could be continuously accurately measured. Furthermore, the oxygen-hemoglobin equilibrium curves measured before and two hours after insulin administration did not change.

Animals↗
PubMed1984

Experimental galactosemia produces diabetic-like retinopathy.

Six normal dogs were made galactosemic by feeding a 30% D-galactose diet, and were followed up to 5 yr. For comparison, 10 normal dogs and 10 alloxan-diabetic dogs were concurrently fed the diet less the galactose supplement. Retinopathy occurred in each of four dogs glactosemic 3 or more yr, and was absent at lesser durations of galactosemia, and from normal dogs not given the galactose supplement. The retinopathy was marked by saccular capillary aneurysms, hemorrhages, nonperfused or acellular vessels, tortuous hypertrophic capillaries, loss of capillary pericytes, and other lesions typical of diabetic patients and alloxan-diabetic dogs. In galactose-fed dogs, blood galactose varied between 0 (fasted) and 250 mg/dl (postprandial), and glycosylated hemoglobin levels became supranormal. In contrast to diabetic dogs, blood levels of glucose, free fatty acids, and branched-chain amino acids were not elevated in the galactosemic dogs, and their serum insulin seemed normal. The results suggest that the level of blood hexose is itself an important determinant of retinopathy.

Amino Acids, Branched-Chain↗
PubMed1984

Platelet aggregation in experimental diabetes and experimental galactosemia.

Platelet aggregation and related plasma factors have been studied in experimentally diabetic dogs, experimentally galactosemic dogs, and in normal dogs. Platelet aggregation, when induced in vitro by ADP (up to 22 microM) or collagen (up to 4 micrograms/ml), was not significantly different from normal in the diabetic or galactosemic dogs. Plasma (platelet-deficient) from the diabetic or galactosemic dogs did not enhance ADP-induced aggregation of normal canine platelets. Fibrinogen concentration in blood tended to be elevated in hyperglycemic diabetic dogs, and was significantly correlated with the levels of HbA1 and blood glucose, whereas galactosemic animals had normal fibrinogen concentrations. The quantity of 6-keto prostaglandin F1 alpha released from aortas of diabetic dogs was less than that released from aortas of normal dogs. Since alloxan-diabetic dogs and galactosemic dogs develop microaneurysms, occluded capillaries, and other retinal lesions characteristic of diabetic retinopathy in human patients, these studies suggest that retinopathy can develop in the absence of extraordinary in vitro platelet aggregation.

Adenosine Diphosphate↗
PubMed1983

Abnormal amino acid concentrations in plasma and urine of experimentally diabetic dogs.

Free amino acid concentrations have been determined in plasma and urine of nonketotic, severely diabetic dogs and age-matched normal controls. Plasma from fasted (as well as fed) diabetics contained supranormal concentrations of several amino acids, including the branched-chain amino acids. In contrast to other species, however, the concentration of only one plasma amino acid (tryptophan) was subnormal in fasted diabetic dogs. Urine collected at the same time showed that the excretion of most amino acids was not abnormal in diabetes. Urinary concentrations of some amino acids were not abnormal despite supranormal levels in plasma. Nevertheless, eight of the 21 amino acids studied reached concentrations significantly greater than normal in the urine of diabetic dogs. Six of the eight amino acids (arginine, histidine, phenylalanine, tyrosine, tryptophan, glutamic acid) showed elevated concentrations in urine even though their plasma concentrations were not elevated. The observed disturbance in the urine/plasma ratio of certain amino acids suggests a possible defect in the renal handling of amino acids in diabetes.

Amino Acids↗
PubMed1983

Hyperglycemia impairs retinal oxygen autoregulation in normal and diabetic dogs.

Preretinal oxygen tensions were measured continuously using microelectrodes in four normal dogs and four dogs made diabetic with alloxan. The latter were kept under poor control for 8 months. Glucose administered intravenously in 30 to 90 sec to all the dogs when they were normoglycemic caused an immediate increase in preretinal oxygen tension lasting approximately 10 min. When the dogs were given 100% oxygen to breathe, their preretinal oxygen tensions increased. This increase in preretinal oxygen tension was 36.6 +/- 8.5 mmHg (+/-SE) when the animals were normoglycemic and 63.5 +/- 9.2 mmHg when the animals were made hyperglycemic. This suggests that hyperglycemia impairs oxygen autoregulation. Moreover, the diabetic dogs appeared to exhibit a larger preretinal oxygen tension increase than normal dogs when both were given 100% oxygen to breathe. The small number of animals studied, however, makes a comparison between the two groups difficult. These data lead one to speculate that in diabetes there may be an impairment of the normal retinal vascular homeostasis. This could play a role in both the development and in the severity of diabetic retinopathy.

Animals↗
PubMed1982

Epithelial and mesothelial basement membranes in diabetic patients and dogs.

The influence of diabetes on the thickness of basement membrane of the ciliary epithelium, lens epithelium, and corneal mesothelium (endothelium) was investigated post mortem in eyes from 27 human subjects and 30 dogs. Ten of the human subjects were diabetic, 10 were non-diabetic matched for age and sex, and seven were non-diabetic subjects who had been diagnosed as hypertensive 2-8 years before death. The dogs comprised three prospectively identified groups: 10 were alloxan diabetic for 5 years and kept in poor glucose control, 10 were alloxan diabetic for 5 years and kept in good glucose control, and 10 were non-diabetic animals. Basement membranes at the three sites measured appeared to be normal in the seven non-diabetic hypertensive subjects. Basement membrane of the ciliary epithelium was found to be significantly thicker than normal both in diabetic human subjects and in poorly controlled diabetic dogs. The thickness of the anterior lens capsule was significantly greater in poorly controlled diabetic dogs than in non-diabetic dogs, and showed a significant positive correlation with duration of diabetes in human subjects. Better glucose control in diabetic dogs resulted in significant inhibition of the epithelial basement membrane thickening. The basement membrane of the corneal mesothelium failed to thicken with diabetes both in human subjects and in animals.

Adult↗
PubMed1982

Immunohistochemical distribution of aldose reductase.

Aldose reductase (AR) has been purified from canine kidneys, and a monospecific antibody against the enzyme prepared. These antibodies were used in an immunohistochemical test to detect tissue sites of aldose reductase in the dog, a species known to develop diabetic lesions morphologically identical to those seen in diabetic patients. Using this method, the enzyme has been demonstrated in numerous cell types, including lens epithelium, aortic endothelium and smooth muscle, Schwann cells of peripheral nerves, and, in the kidney, interstitial cells and cells of Henle's loop and the collecting tubules. Many other cells and tissues, including capillaries throughout the body, lack immunoreactive aldose reductase. The distribution of the immunoreactive enzyme is compatible with a potential role of the enzyme in the aetiology of some complications of diabetes, namely cataract, neuropathy, macroangiopathy and renal papillary necrosis, but not the microvascular complications.

Aldehyde Reductase↗
PubMed1982

Dogs with induced or spontaneous diabetes as models for the study of human diabetes mellitus.

Diabetes mellitus can be produced readily in dogs by any of several chemical or surgical methods, and in recent years genetically diabetic dogs have also become available for study. These models are suitable for investigating a wide variety of questions relevant to human diabetes mellitus. Especially noteworthy is the occurrence in diabetic dogs of a number of ocular and other complications typical of human diabetes mellitus. Procedures by which canine models of diabetes may be established or maintained have been outlined in this report.

Animals↗
PubMed1980

Fluorophotometry. I. Technique.

A radiometer and photomultiplier assembly was used to measure light intensities under several artificial conditions to assess the efficacy of the fluorophotometer and the technique of ocular fluorophotometer and the technique of ocular fluorophotometry. Using an artificial eye and a cat eye that had undergone vitrectomy, we found that scatter of light from the retinal surface may contribute to the fluorescence recorded.

Animals↗
PubMed1980

Fluorophotometry. II. Streptozocin-treated guinea pigs.

Normal and streptozocin-treated guinea pigs were examined with a fluorophotometer one hour after receiving an intravenous injection of fluorescein sodium. The level of fluorescence in the vitreous was significantly greater in animals showing marked glucosuria than in normal animals or those showing little glucosuria. The excessive fluorescence of the vitreous is similar to that reported by others in diabetic humans and rats but is found in the guinea pig, an animal known normally to have no retinal vasculature.

Animals↗
PubMed1977

Permeability and patency of retinal blood vessels in experimental diabetes.

Increased permeability of retinal blood vessels in human diabetic retinopathy is well known clinically. Its morphologic equivalent is unknown. In dogs with 5 years of poorly controlled alloxan diabetes and nonproliferative diabetic retinopathy comparable to that of man, permeability and patency of retinal blood vessels were tested with the protein tracer horseradish peroxidase and evaluated by electron microscopy. A breakdown of the blood-retinal barrier was found associated with extensive tracer leakage around retinal blood vessels. Tracer had seemingly permeated endothial junctions, and was not transported through the endothelial cytoplasm. Blood vessels which had lost their endothelial cells and were partially occluded by glial cells retained some patency to tracer. These findings suggest the following. (1) Endothelial tight junctions are not a static cell specialization but one that can open due to chronic metabolic or osmotic factors prevailing in diabetes. Opened tight junctions may account for plasma leakage seen clinically in human diabetic retinopathy. (2) In the absence of endothelial cells perfusion does not necessarily end abruptly. The tracer method and electron microscopy may show details of vascular obstruction that are not readily demonstrated clinically.

Animals↗
PubMed1976

Development of the macular circulation.

The development of the primate retinal vasculature has been investigated in fetal monkeys (M. mulatta) during the latter half of gestation. Vascularization is found to be retarded in the region of the macula. The macula is found to become completely encircled by a network of primitive capillaries which then proliferate centripetally towards the presumptive fovea. These encircling vessels normally cease to proliferate before reaching the center of the fovea, and the resulting central avascular zone and centripetal pattern of vessels persist thereafter in the mature macula. The superficial peripapillary network of capillaries, like the outer vascular net, is found to be derived from the inner network of vessels.

Animals↗