PubMed Health⌕ Search

Biomedical subjects

C Kilo

Publications and source records attributed to C Kilo.

At least 37 records · Page 2Linked to original sources
PubMed1990

The dyschromatopsia of optic neuritis is determined in part by the foveal/perifoveal distribution of visual field damage.

Most hypotheses of acquired dyschromatopsia invoke the mechanism of selective damage to specific components of the afferent visual system to explain the predominance of red-green and blue-yellow hue-discrimination defects found in neural and retinal disorders, respectively. However, this pattern of hue-discrimination disturbance in ocular disease may vary. There are frequent exceptions which are inadequately explained by existing hypotheses. In an effort to explain the pattern and pathogenesis of acquired dyschromatopsias better, the authors examined patients with nonproliferative diabetic retinopathy (DR) and late-stage retrobulbar neuritis (RBN) using age-corrected Farnsworth-Munsell 100-hue testing and threshold static perimetry. As expected, most DR eyes showed some degree of relative blue-yellow dyschromatopsia (89%) with few showing a greater weighting towards red-green dyschromatopsia (11%). However, an approximately equal number of RBN eyes had a relative blue-yellow (48%) versus red-green dyschromatopsia (52%). For RBN, the authors found a strong association between the spatial distribution of field defect and the type of relative hue-discrimination disturbance. Eyes with greater field depression at the fovea relative to the perifovea showed a relative preponderance of red-green dyschromatopsia (68%) as opposed to blue-yellow dyschromatopsia (32%), whereas eyes with greater relative perifoveal impairment showed a relative preponderance of blue-yellow dyschromatopsia (100%). This relationship between the relative spatial distribution of visual field damage and the relative hue-discrimination deficit in RBN was statistically significant (P = 0.002). Such an association was not found for DR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Effects of hypothyroidism on vascular 125I-albumin permeation and blood flow in rats.

Effects of hypothyroidism on vascular 125I-albumin permeation and on blood flow were assessed in multiple tissues of male Sprague-Dawley rats rendered hypothyroid by dietary supplementation with 0.5% (wt/wt) 2-thiouracil or by thyroidectomy. In both thiouracil-treated and thyroidectomized rats, body weights, kidney weight, arterial blood pressure, and pulse rate were decreased significantly v age-matched controls. After 10 to 12 weeks of thiouracil treatment, 125I-albumin permeation was increased significantly in the kidney, aorta, eye (anterior uvea, choroid, retina), skin, and new granulation tissue, remained unchanged in brain, sciatic nerve, and heart, and was decreased in forelimb skeletal muscle. A similar pattern was observed in thyroidectomized rats, except that increases in 125I-albumin permeation for all tissues were smaller than those observed in thiouracil-treated rats, and 125I-albumin permeation in retina did not differ from controls. In both thiouracil-treated and thyroidectomized rats, changes in blood flow (assessed with 15-microns, 85Sr-labeled microspheres) relative to the decrease in arterial blood pressure were indicative of a decrease in regional vascular resistance except in the choroid and in the kidney, in which vascular resistance was increased significantly. Glomerular filtration rate was decreased, but filtration fraction and urinary excretion of albumin remained unchanged by thiouracil treatment and thyroidectomy. These results indicate that vascular hemodynamics and endothelial cell barrier functional integrity are modulated in many different tissues by the thyroid. In view of the correspondence of hypothyroid- and diabetes-induced vascular permeability changes, these results raise the possibility that altered thyroid function in diabetes may play a role in the pathogenesis of diabetic vascular disease.

Animals↗
PubMed1989

Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors.

This study investigated hemodynamic changes in diabetic rats and their relationship to changes in vascular albumin permeation and increased metabolism of glucose to sorbitol. The effects of 6 wk of streptozocin-induced diabetes and three structurally different inhibitors of aldose reductase were examined on 1) regional blood flow (assessed with 15-microns 85Sr-labeled microspheres) and vascular permeation by 125I-labeled bovine serum albumin (BSA) and 2) glomerular filtration rate (assessed by plasma clearance of 57Co-labeled EDTA) and urinary albumin excretion (determined by radial immunodiffusion assay). In diabetic rats, blood flow was significantly increased in ocular tissues (anterior uvea, posterior uvea, retina, and optic nerve), sciatic nerve, kidney, new granulation tissue, cecum, and brain. 125I-BSA permeation was increased in all of these tissues except brain. Glomerular filtration rate and 24-h urinary albumin excretion were increased 2- and 29-fold, respectively, in diabetic rats. All three aldose reductase inhibitors completely prevented or markedly reduced these hemodynamic and vascular filtration changes and increases in tissue sorbitol levels in the anterior uvea, posterior uvea, retina, sciatic nerve, and granulation tissue. These observations indicate that early diabetes-induced hemodynamic changes and increased vascular albumin permeation and urinary albumin excretion are aldose reductase-linked phenomena. Discordant effects of aldose reductase inhibitors on blood flow and vascular albumin permeation in some tissues suggest that increased vascular albumin permeation is not entirely attributable to hemodynamic changes. We hypothesize that 1) increases in blood flow may reflect impaired contractile function of smooth muscle cells in resistance arterioles and 2) increases in vascular 125I-BSA permeation and urinary albumin excretion reflect impaired vascular barrier functional integrity in addition to increased hydraulic conductance secondary to microvascular hypertension associated with decreased vascular resistance.

Albuminuria↗
PubMed1989

Myocyte contracture, vascular resistance, and vascular permeability after global ischemia in isolated hearts from alloxan-induced diabetic rabbits.

Coronary vascular hemodynamics, albumin permeation, and myocyte contractility were assessed in isolated hearts from 6-mo alloxan-induced diabetic (ALX-D) rabbits during 3 h of reperfusion after 40 min of global no-flow ischemia. Residue-detection data, generated during the single passage of a bolus of 125I-labeled bovine serum albumin (125I-BSA) through the coronary vasculature, were used to estimate indices of vascular function, including the mean transit time of 125I-BSA, the fractional rate of intravascular clearance of 125I-BSA, and 125I-BSA permeation of coronary vessels. During reflow after ischemia in hearts from control rabbits, vascular resistance increased approximately three times that at baseline, left ventricular end-diastolic pressure (LVEDP) increased 8-10 times, and maximum +dP/dt recovered 0.4 times baseline, whereas the fractional rate of washout of intravascular 125I-BSA decreased to less than one-half of baseline values (was prolonged 2-fold), and albumin permeation and mean-transit time were increased 3 and 5 times baseline, respectively. In hearts from diabetic rabbits, vascular resistance was similar to the control group before ischemia but increased only one-third as much during reflow after ischemia. Increases in LVEDP during reflow were approximately 50% lower than controls, and +dP/dt recovered approximately 2.5 times more than in control hearts. 125I-BSA permeation in diabetics was similar to controls before ischemia, but during reflow increased 6 times (approximately 2 times controls). Washout of intravascular 125I-BSA was prolonged approximately 20% versus baseline during 3 h of reflow in hearts from diabetic rabbits. Thus, ALX-D in the rabbit delayed ischemia-reperfusion injury to myocytes and vascular smooth muscle cells while increasing vascular albumin permeation.

Animals↗
PubMed1988

Retinocortical conduction time in diabetics with abnormal pattern reversal electroretinograms and visual evoked potentials.

Clinically evident retinal vascular disease in patients with diabetes mellitus may be preceded by an increase in visual evoked potential latency in electrophysiologic testing. This increase may indicate either retinal or optic nerve dysfunction. To determine the origin of the latency increase we initiated a cross-sectional study of simultaneous pattern-reversal electroretinograms and visual evoked potentials. We recorded transient (3.8 reversals/second) pattern electroretinograms and visual evoked potentials using both 15' and 60' high-contrast black-white checks. Fifty-five diabetic patients (34 with no retinopathy and 21 with background retinopathy) and 34 age-matched visual normals (controls) were tested. Group data in diabetics showed significant latency increases in both tests, but not significant differences in retinocortical conduction time were noted. These results suggest that the increases in visual evoked potential latency exhibited by diabetic patients with little or no retinopathy usually reflect altered retinal function rather than optic neuropathy. Two patients with background retinopathy exhibited retinocortical conduction times that exceeded the normal mean by more than two standard deviations, suggesting that optic neuropathy may occasionally occur in diabetic patients with background retinopathy.

Adult↗
PubMed1988

The relationship between hue discrimination and contrast sensitivity deficits in patients with diabetes mellitus.

In an attempt to elucidate more fully the pathophysiologic basis of early visual dysfunction in patients with diabetes mellitus, color vision (hue discrimination) and spatial resolution (contrast sensitivity) were tested in diabetic patients with little or no retinopathy (n = 57) and age-matched visual normals (n = 35). Some evidence of visual dysfunction was observed in 37.8% of the diabetics with no retinopathy and 60.0% of the diabetics with background retinopathy. Although significant hue discrimination and contrast sensitivity deficits were observed in both groups of diabetic patients, contrast sensitivity was abnormal more frequently than hue discrimination. However, only 5.4% of the diabetics with no retinopathy and 10.0% of the diabetics with background retinopathy exhibited both abnormal hue discrimination and abnormal contrast sensitivity. Contrary to previous reports, blue-yellow (B-Y) and red-green (R-G) hue discrimination deficits were observed with approximately equal frequency. In the diabetic group, contrast sensitivity was reduced at all spatial frequencies tested, but for individual diabetic patients, significant deficits were only evident for the mid-range spatial frequencies. Among diabetic patients, the hue discrimination deficits, but not the contrast sensitivity abnormalities, were correlated with the patients' hemoglobin A1 level. A negative correlation between contrast sensitivity at 6.0 cpd and the duration of diabetes also was observed.

Adult↗
PubMed1988

Effect of rapid normalization of plasma glucose levels on microvascular dysfunction and polyol metabolism in diabetic rats.

Effects of rapid normalization of plasma glucose levels (by insulin infused via Alzet pumps implanted intraperitoneally) on plasma insulin-like growth factor I (IGF-I) levels, granulation tissue polyol levels, and vascular permeation by 125I-labeled albumin were examined in male Sprague-Dawley rats with streptozocin-induced (60-65 mg/kg) diabetes. Two days after implantation of pumps, plasma insulin levels were twice normal levels and remained elevated (1.4-2.5 times normal) throughout the remainder of the study. Plasma glucose levels and granulation tissue polyol levels were normalized within 2 days after initiation of insulin treatment. Plasma IGF-I levels were significantly increased (2 times) by 2 days, but were not normalized until 7 days. In contrast, 125I-albumin permeation normalized at a much slower relatively linear rate and was still not completely normal after 14 days of insulin treatment. In view of 1) previous studies demonstrating that diabetes-induced increases in 125I-albumin permeation in this tissue are linked to increased metabolism of glucose to sorbitol and 2) the rapid normalization of tissue polyol levels in this study, the relatively linear rate of normalization of vascular permeability over 14 days in these studies suggests that impaired vascular barrier functional integrity in this model is mediated by structural and/or functional vascular alterations associated with sustained increased polyol metabolism rather than by increased polyol levels per se and/or by readily reversible functional and metabolic alterations associated with acute increases in polyol metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Multicenter comparison of glyburide and glipizide in the treatment of non-insulin-dependent diabetes mellitus.

A multicenter, randomized, open-label comparison of glyburide and glipizide was made in 109 patients with non-insulin-dependent diabetes mellitus whose fasting plasma glucose levels had been maintained at less than or equal to 140 mg/dl by tolbutamide, chlorpropamide, or glyburide. After an initial evaluation, patients entered a dose-adjustment phase to establish the optimal daily dose of the assigned drug--glyburide or glipizide--needed to maintain metabolic control. A second evaluation was made at the end of this phase. Patients then proceeded into the maintenance phase, which lasted approximately three months. A final evaluation was made upon completion of or withdrawal from the maintenance phase. Metabolic control was monitored by means of determinations of fasting plasma glucose and hemoglobin A1c. Comparative efficacy was assessed in relation to the doses of the respective drugs needed to maintain acceptable metabolic control. Safety was evaluated through reports of adverse effects as well as through laboratory tests and measurements of vital signs at each patient visit.

Blood Glucose↗
PubMed1988

Increased ocular blood flow and 125I-albumin permeation in galactose-fed rats: inhibition by sorbinil.

125I-Albumin permeation and blood flow (assessed with 15 micron, 85Sr-labelled microspheres) were determined in the retina, choroid, anterior uvea, and brain of male Sprague-Dawley rats fed diets containing 50% dextrin (control) or 50% galactose. Blood flow was increased in the retina, choroid, and anterior uvea but not in the brain of rats fed galactose for 3 weeks and 3 months versus controls, and was normalized by sorbinil (an inhibitor of aldose reductase) in the 3-week group. After 8 months of galactose feeding, blood flow was reduced to normal levels in the retina and was slightly below normal in the choroid; blood flow remained elevated in the anterior uvea but was significantly lower than that observed at 3 weeks and at 3 months. In rats fed galactose for 8 months, sorbinil completely normalized blood flow in the choroid, and decreased, but did not normalize, blood flow in the anterior uvea. 125I-Albumin permeation was increased in the retina, choroid, and anterior uvea of rats fed 50% galactose for 3 weeks, 3 months, and 8 months versus controls, but was unchanged in the brain. Sorbinil normalized 125I-albumin permeation in all three ocular tissues in 8-month galactose-fed rats. Polyol levels were increased significantly in all three ocular tissues of 3-week galactose-fed rats; sorbinil markedly decreased, but did not normalize, polyol levels in all three tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Increased ischemia-reperfusion injury to the heart associated with short-term, diet-induced hypercholesterolemia in rabbits.

The effects of increased dietary cholesterol content on coronary vascular hemodynamics and endothelial cell transport function were assessed in isolated rabbit hearts during 3.5 hours of reperfusion after 30 minutes of global, no-flow ischemia. In control hearts from rabbits fed normal chow, perfusion pressure, left ventricular end-diastolic pressure, maximum +dP/dt, and the rate of intravascular clearance of radiolabelled albumin remained constant during 5 hours of continuous perfusion, while the mean transit time of radiolabelled albumin increased 1.6 X baseline. In ischemic hearts from rabbits fed normal chow, perfusion pressure increased 59% during reperfusion while left ventricular end-diastolic pressure and maximum +dP/dt returned toward control levels. The rate of intravascular clearance of radiolabelled albumin decreased 36%, and the mean transit time of albumin increased approximately 3 X baseline. Ischemia-reperfusion injury to the cardiac vasculature and musculature was markedly increased in hearts of rabbits fed chow supplemented with 2% cholesterol for 2-3 weeks compared to rabbits fed the same diet for a longer duration (5-16 weeks) or rabbits fed normal chow. Prior to ischemia, permeation of the coronary vasculature by albumin was increased twofold in rabbits fed cholesterol for 2-3 weeks while myocyte contractile function was normal relative to chow-fed controls or the group fed cholesterol for 5-16 weeks. These effects of acute cholesterol feeding precede occlusive atherosclerotic coronary artery disease and occur at plasma cholesterol concentrations one third of those in rabbits fed cholesterol for the longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Galactose ingestion increases vascular permeability and collagen solubility in normal male rats.

In view of the similarity of cataracts and neuropathy in galactose-fed and diabetic rats, the present experiments were undertaken to determine whether consumption of galactose-enriched diets (10, 25, or 50% by weight) also increases collagen crosslinking and permeation of vessels by 125I-albumin analogous to that observed in diabetic rats. The observations in these experiments: demonstrate that consumption of galactose-enriched diets for 3 wk selectively increases 125I-albumin permeation of the same vascular beds affected in diabetic rats and by diabetic vascular disease in humans (i.e., the aorta and vessels in the eye, kidney, sciatic nerve, and new tissue formed in the diabetic milieu); demonstrate that the susceptibility of the vasculature to aldose reductase-linked injury (increased permeability) varies greatly in different tissues; indicate that collagen solubility (crosslinking) changes in galactose-fed rats differ sharply from those in diabetic rats; and provide new evidence that consumption of galactose-enriched diets induces a hypogonadal state in male rats.

Aldehyde Reductase↗
PubMed1987

Increased vascular permeability in spontaneously diabetic BB/W rats and in rats with mild versus severe streptozocin-induced diabetes. Prevention by aldose reductase inhibitors and castration.

125I-labeled albumin permeation (IAP) has been assessed in various tissues in spontaneously diabetic insulin-dependent female BB/W rats and in male Sprague-Dawley rats with severe or mild forms of streptozocin-induced diabetes (SS-D and MS-D, respectively). In BB/W diabetic rats and in rats with SS-D, indices of IAP were significantly increased in tissues and vessels predisposed to diabetic vascular disease in humans, including the eyes (anterior uvea, posterior uvea, and retina), sciatic nerve, aorta, kidney, and new vessels formed after induction of diabetes. No evidence of increased IAP was observed in heart, brain, testes, or skeletal muscle in BB/W or SS-D rats. In MS-D rats, indices of IAP were increased only in the kidney and in new vessels formed after the onset of diabetes. Marked tissue differences were observed in the effects of two structurally different aldose reductase inhibitors (sorbinil and tolrestat) and of castration on diabetes-induced increases in IAP and in tissue levels of polyols in SS-D rats. Both aldose reductase inhibitors and castration completely prevented diabetes-induced increases in IAP in new vessels and in sciatic nerve in BB/W and SS-D rats. Both aldose reductase inhibitors also markedly decreased IAP in the anterior uvea (approximately 85%), posterior uvea (approximately 65-75%), retina (approximately 65-70%), and kidney (approximately 70-100%); castration reduced IAP in the anterior uvea (approximately 55%), kidney (approximately 50%), and retina (approximately 30%) but had no effect on the posterior uvea. The diabetes-induced increases in IAP in the aorta were reduced only slightly (approximately 20%) by aldose reductase inhibitors and castration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1986

Islet transplants in diabetic Lewis rats prevent and reverse diabetes-induced increases in vascular permeability and prevent but do not reverse collagen solubility changes.

The effects of islet transplantation on diabetes-induced increases in vascular permeability and collagen solubility were examined in new granulation tissue vessels and collagen formed after induction of streptozotocin diabetes in male Lewis rats. Albumin permeation was increased by 50% (p less than 0.001) and collagen solubility was decreased by 50% (p less than 0.001) in granulation tissue from untreated diabetic animals as compared with controls. The islet transplants reversed diabetes-induced vascular permeability increases in tissues formed prior to islet transplantation (tissue to blood isotope ratio = 2.1 +/- 0.1 - SD for controls, 3.2 +/- 0.2 for diabetic rats and 2.0 +/- 0.2 for diabetic rats given islets) and prevented permeability increases in new tissues formed following transplantation (tissue to blood isotope ratio = 2.1 +/- 0.1 for controls, 3.3 +/- 0.8 for diabetic rats and 1.9 +/- 0.2 for diabetic rats given islets). In contrast, while islet transplants prevented diabetes-induced decreased collagen solubility in tissues formed after transplantation (controls = 24%, diabetic rats = 12%, and diabetic rats given islets = 24%), collagen solubility in tissues formed prior to islet transplantation was virtually unaffected. These findings indicate that collagen changes induced by the diabetic milieu are not nearly as readily reversed by normalization of the diabetic milieu as (diabetes-induced) alterations in vascular functional integrity.

Animals↗
PubMed1986

Diabetes-induced increases in vascular permeability and changes in granulation tissue levels of sorbitol, myo-inositol, chiro-inositol, and scyllo-inositol are prevented by sorbinil.

In a recently developed animal model, we investigated the pathogenesis of diabetic vascular disease and demonstrated that 125I-albumin permeation is markedly increased in new "granulation tissue" vessels formed in subcutaneous tissue after the onset of diabetes. The studies described in this report were undertaken to examine the effects of an aldose reductase inhibitor on diabetes-induced increases in vascular permeability in this animal model. 125I-albumin permeation was assessed 3 weeks after the subcutaneous implantation of sterile preweighed polyester fabric (to stimulate angiogenesis) in diabetic male Sprague-Dawley rats, in controls, and in diabetic rats given sorbinil approximately 12 or approximately 25 mg/kg/d mixed in ground rat chow. Sorbinil administration prevented the diabetes-induced increase in vascular permeability by approximately 60% at the lower dose and by approximately 80% at the higher dose without affecting body weight or plasma glucose levels. Diabetes-induced changes in tissue levels of sorbitol, myo-inositol, scyllo-inositol, and chiro-inositol were also prevented by the high dose of sorbinil (data were not obtained for the lower dose). These observations are consistent with evidence linking diabetic cataracts and neuropathy to imbalances in sorbitol/inositol metabolism and support the hypothesis that diabetic vascular disease as well as neuropathy and cataracts are mediated by excess metabolism of glucose through the polyol pathway. Furthermore, these observations suggest that increased vascular permeability associated with diabetic microangiopathy in humans may be prevented by inhibitors of aldose reductase without the need to normalize blood glucose levels.

Adolescent↗
PubMed1986

Sex steroid dependency of diabetes-induced changes in polyol metabolism, vascular permeability, and collagen cross-linking.

The effects of castration on diabetes-induced increases in collagen cross-linking and vascular permeability and on polyol levels in new granulation tissue formed after induction of streptozocin (STZ) diabetes were examined in male Sprague-Dawley rats. New granulation tissue formation was induced by implanting sterile polyester fabric subcutaneously (s.c.) at the time of STZ injection 3 wk before assessment of vascular permeability and collagen cross-linking. Castration was performed 10 days before implanting the fabric. The characteristic increases in collagen cross-linking (manifested by decreased solubility in 0.5 M acetic acid) and in albumin permeation of the vasculature seen in intact diabetic rats were completely prevented by castration. Net collagen accumulation was not affected by diabetes or castration. Castration also markedly diminished diabetes-induced increases in tissue levels of sorbitol and completely prevented the decreases in tissue levels of myo-inositol and scyllo-inositol observed in intact diabetic rats, but had no effect on serum glucose levels, nonenzymatic glycosylation of plasma and granulation tissue proteins, or plasma somatomedin-C levels. The demonstration that castration prevents diabetes-induced increases in vascular permeability and collagen cross-linking as well as imbalances in tissue levels of sorbitol, myo-inositol, and scyllo-inositol in this model indicates that all of these changes are sex steroid-dependent phenomena. While the pathogenesis of these vascular permeability and collagen cross-linking changes is clearly multifactorial, these new findings: indicate that the role of sex steroids in the development of late complications of diabetes may be far more important than hitherto suspected, and suggest an explanation for the clinical observation that diabetic complications are uncommon in prepubertal diabetic subjects regardless of duration of diabetes.

Animals↗
PubMed1986

Absence of degenerative changes in retinal and uveal capillary pericytes in diabetic rats.

Ultrastructural morphometric techniques were used to quantify pericyte degeneration in retinal and uveal capillaries of streptozotocin-diabetic rats in order to assess the suitability of this small rodent model of diabetes for studies of the pathogenesis of microvascular eye disease in diabetic humans. Male, Sprague-Dawley rats were killed by intraaortic perfusion of fixative 6 and 9 mos after induction of diabetes with 50 mg/kg streptozotocin. No differences were evident between diabetics and age-matched controls in capillary circumference, numbers of endothelial cells per capillary, and capillary cytoplasmic area of retinal, choroidal, and iridial vessels. Capillary basement membrane width and the percentage of the capillary circumference covered by pericytes were increased in retinas of diabetic vs age-matched control rats after 9 mos of diabetes (P less than 0.05), but no differences were evident in the number of pericyte processes per capillary and the percentage of vessels with pericyte nuclei. No differences in pericyte distributions were observed between control and diabetic rats in the choriocapillaris and iris after 9 mos of diabetes. These findings indicate that retinal capillary basement membrane thickening precedes any evidence of pericyte degenerative changes and suggest that pericyte degeneration analogous to that associated with human diabetic microangiopathy does not occur in this experimental animal model.

Animals↗