Biomedical subjects

M J Kutryk

Publications and source records attributed to M J Kutryk.

27 records · Page 2Linked to original sources

PubMed1989

Cataract formation is prevented by administration of verapamil to diabetic rats.

The purpose of the present study was to examine the effects on cataractogenesis of daily sc administration of the Ca2+ antagonist drug verapamil to diabetic rats. Streptozotocin-induced diabetic rats were given verapamil half-way through the 8-week experimental period or during the full 8 weeks of diabetes. Verapamil administration had no effect on the high blood glucose values, low circulating insulin levels, or elevated triglyceride and cholesterol concentrations in the diabetic rats. Untreated diabetic rats had a 90% incidence of cataracts. Four weeks of verapamil administration reduced this incidence to 41%, and a full 8 weeks of drug treatment further lowered the incidence to 20%. Diltiazem, another Ca2+ antagonist, lowered the incidence of cataracts in the diabetic rats to a similar extent. Verapamil administration to the diabetic animals also partially protected against the presence of retinal microangiopathy in the diabetic animals. Lenticular hydration and lipid accumulation were only indirectly related to cataractogenesis in the diabetic rats and its protection by verapamil treatment. Lenticular electrolyte imbalance, particularly Ca2+, in the diabetic animals was closely correlated with cataract formation, and verapamil significantly reduced the alterations in these ion concentrations. The present results demonstrate the efficacy of verapamil as a protective agent against cataractogenesis and some retinal damage in diabetic animals. Most importantly, this occurs in the absence of any change in the glycemic status of the diabetic animals. The findings strongly support a role for lenticular Ca2+ imbalance in cataract development in diabetes and provide initial evidence to suggest its clinical use in the diabetic population at risk for blindness.

Animals↗

PubMed1988

Stimulation of sodium-calcium exchange by cholesterol incorporation into isolated cardiac sarcolemmal vesicles.

Modification of the cholesterol content of highly purified cardiac sarcolemma from dog ventricles was accomplished by incubation with phosphatidylcholine liposomes containing various amounts of cholesterol. The degree of cholesterol enrichment could be varied by changing the liposomal cholesterol/phospholipid ratio or varying the liposome-membrane incubation time. Na+-Ca2+ exchange measured in cholesterol-enriched sarcolemmal vesicles was increased up to 48% over control values. The stimulation of Na+-Ca2+ exchange was associated with an increased affinity of the exchanger for Ca2+ (Km = 17 microM compared with Km = 22 microM for control preparations). Na+-Ca2+ exchange measured in cholesterol-depleted membrane preparations was decreased by 15%. This depressed activity was associated with a decreased affinity of the exchanger for Ca2+ (Km = 27 microM). These changes were not due to either a change in membrane permeability to Ca2+ or an increase in the amount of Ca2+ bound to sarcolemmal vesicles. The stimulating effect of cholesterol enrichment was specific to the Na+-Ca2+ exchange process since sarcolemmal Ca2+-Mg2+ ATPase activity was depressed 40% by cholesterol enrichment. Further, K+-p-nitrophenylphosphatase and Na+-K+ ATPase activities were depressed in both cholesterol-depleted and cholesterol-enriched sarcolemmal vesicles. In situ oxidation of membrane cholesterol completely eliminated Na+-Ca2+ exchange. These results suggest that cholesterol is intimately associated with Na+-Ca2+ exchange and may interact with the exchange protein and modulate its activity.

4-Nitrophenylphosphatase↗

PubMed1987

Alterations in cardiac lysosomal hydrolases following induction of the calcium paradox.

Although perfusion of the heart with calcium-free medium for a brief period followed by reperfusion with calcium-containing medium results in marked structural derangements (calcium paradox), the mechanisms for this cell damage are far from clear. Since activation of lysosomal enzymes has been associated with pathological damage, it was the purpose of this study to examine alterations in the activities of several lysosomal enzymes in rat hearts subjected to calcium paradox. No significant changes in the activities of beta-acetylglucosaminidase, beta-galactosidase, alpha-mannosidase, or acid phosphatase were seen in the homogenates of hearts exposed to the calcium paradox. However, there were dramatic alterations in the lysosomal enzyme activities in the sedimentable and nonsedimentable fractions during calcium paradox. The lysosomal enzyme activities were also detected in the perfusate collected during reperfusion with calcium-containing medium. These changes occurred during the reperfusion period since no alterations were apparent after calcium-free perfusion and were dependent upon the time of reperfusion with medium containing Ca2+ as well as the time of perfusion with Ca2+ -free medium before inducing Ca2+ paradox. These data indicate that alterations in lysosomal enzymes owing to reinstitution of calcium in Ca2+-deprived hearts may occur as a part of cardiac damage and general cellular disintegration.

Acid Phosphatase↗

PubMed1985

Changes in lysosomal morphology and enzyme activities during the development of adriamycin-induced cardiomyopathy.

Morphologic and enzymic changes in heart lysosomes were studied following a chronic treatment of animals with a cumulative dose of 15 mg/kg of adriamycin. Myocardial cell damage due to adriamycin included lysosomal changes, sarcotubular swelling, vacuolization and myofibrillar drop-out. These structural changes were more pronounced in the 6-week treated group as opposed to the 3-week treated group. The number of lysosomes per unit area increased from a control value of 3.6 +/- 1.7 to 17.8 +/- 4.0 in the 3-week treated group and 35.9 +/- 9.2 in the 6-week treated groups, respectively. The scatter in the size distribution of lysosomes was much wider in treated animals. Lysosomal hydrolases in the 3-week and 6-week adriamycin-treated group changed as follows: N acetyl beta-glucosaminidase activity fell in the homogenate (H) and nonsedimentable (NS) and rose in the serum (Ser) fractions; a drop in alpha-mannosidase was seen in the sedimentable (S) and Ser fractions; an increase in beta-galactosidase was noted in the H, S and Ser fractions; acid phosphatase was increased in H, S, NS and Ser fractions. Lanthanum staining, used as a cytochemical probe for normal membrane permeability, revealed intracytoplasmic localization of the tracer only in the 6-week group. Malondialdehyde content was increased significantly in the 3-week and 6-weed treated groups. These results show lysosomal changes in adriamycin-treated hearts which precede as well as accompany nonspecific permeability changes in the sarcolemma.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

PubMed1984

Biochemical alterations in heart after exhaustive swimming in rats.

This study investigated alterations in glycogen, catecholamines, and the function of various subcellular membranes of the heart after exhaustive swimming in rats. The rats were exhausted by daily exercise over 1, 3, or 7 consecutive days. Glycogen content of the heart and three selected skeletal muscles was depleted after a single bout of exhaustive exercise. Repeated bouts of exhaustive swimming elicited a depletion of glycogen in only the plantaris and gastrocnemius skeletal muscles. Plasma norepinephrine and epinephrine levels were highly elevated, and cardiac concentrations of these hormones were significantly depleted immediately after all exercise sessions. Cardiac sarcoplasmic reticulum (SR) Ca2+ transport was depressed after a single exhaustive exercise period. After three exercise bouts SR Ca2+ accumulation remained depressed; however, mitochondrial Ca2+ transport was found to be augmented. If the exhaustive exercise protocol was continued up to seven days, only mitochondrial Ca2+ accumulation was depressed. Various parameters of sarcolemmal membrane function were observed to be unaltered after exhaustive exercise. These findings demonstrate that exhaustive swimming exercise in rats is capable of producing significant alterations in the Ca2+ transport capacity of the SR and mitochondrial membrane systems of the heart but is without apparent effect on the sarcolemmal membrane.

Animals↗

PubMed1984

Influence of myosin antiserum on heart sarcolemmal Ca2+ or Mg2+ ATPase activity.

Sarcolemmal Ca2+/Mg2+ ATPase was inhibited only about 30% by myosin antiserum that decreased myofibrillar ATPase activity by about 80%. There was a remarkable difference in the effect of myosin antiserum on sarcolemmal Ca2+/Mg2+ ATPase and myofibrillar ATPase with regard to its pre-incubation time with these organelles. Tryptic digestion of the sarcolemmal membrane did not show any change in its inhibitory effect of the myosin antiserum on Ca2+ ATPase. The data distinguish the Ca2+/Mg2+ ATPase from myosin ATPase and suggest that it is an enzyme of the sarcolemmal origin.

Adenosine Triphosphatases↗

PubMed1983

Alterations in Ca2+ binding by and composition of the cardiac sarcolemmal membrane in chronic diabetes.

Chronic streptozotocin-induced diabetes in rats was associated with a significant loss in the ability of isolated cardiac sarcolemmal membranes to bind Ca2+. Administration of insulin to the diabetic rats normalized the sarcolemmal Ca2+ binding capacity. The content of sialic acid residues, which are considered to represent a superficial Ca2+ pool in sarcolemma, was decreased in preparations from diabetic rats, and this change also was reversible upon insulin treatment of the diabetic rats. Treatment of sarcolemma with neuraminidase decreased Ca2+ binding by 37% in control preparations but had no effect on diabetic preparations. Diphosphatidylglycerol content was decreased but other acidic phospholipids such as phosphatidylinositol and phosphatidylserine, which also bind Ca2+, were not altered during diabetes. An increase in lysophosphatidylcholine and a decrease in phosphatidylethanolamine contents were observed in membranes isolated from diabetic rats. These results suggest that some alterations occur in Ca2+ binding and composition of heart sarcolemma in chronically diabetic rats and may provide further insight into the pathogenesis of diabetic cardiomyopathy.

Animals↗

PubMedDate not supplied

Alterations in heart and serum lysosomal activities in streptozotocin-induced diabetes.

Alterations in the cardiac tissue and serum acid hydrolase activities were studied in chronic streptozotocin-induced diabetes in rats. No changes were observed in total cardiac tissue homogenate lysosomal enzyme activities at 4 weeks of diabetes but there were significant alterations in the distribution of selected enzymes. Significant decreases in nonsedimentable beta-N-acetylglucosaminidase (NAG) and beta-galactosidase (Gal) activities were observed at 4 weeks of diabetes. At 8 weeks of the disease, decreased activities of NAG and Gal were observed in heart homogenates but no changes were apparent in alpha-mannosidase (Man) or acid phosphatase activities. Nonsedimentable activities of NAG and both sedimentable and nonsedimentable activities of Gal were decreased at 8 weeks. At 16 weeks of the diabetic condition, increased activities of NAG, Gal and acid phosphatase were observed. This increase at 16 weeks of the disease was due to an increase in sedimentable enzyme activity. At all times of diabetes, serum enzyme activities were significantly increased. Insulin treatment reversed all of the observed changes in tissue homogenates, but serum levels were not completely reversed. These results suggest that cardiac lysosomal hydrolases are probably only involved in the later stages of the diabetic cardiomyopathy when extensive ultrastructural derangements are evident. The present evidence also suggests that the heart may be a source of serum hydrolase activities.

Acetylglucosaminidase↗

PubMedDate not supplied

Seeding of intravascular stents by the xenotransplantation of genetically modified endothelial cells.

A novel approach of cell seeding of stents using xenotransplanted endothelium is proposed. The advantages of this approach are that these doubly transgenic animals will provide a limitless supply of endothelial cells producing controllable levels of active compound. These foreign cells will act as Trojan horses, graciously accepted at face value by the host organism, but capable of modifying the pathophysiological response to vessel damage, typified by the process of restenosis. Once implanted, the production of the bioactive compound is under exogenous control by means of 'designer' genes coding for modified cell surface receptors, which are introduced with the transgene to provide controllable levels of compound. Interaction of an orally administered compound with the modified cell receptor will switch on the transgene, while in its absence the transgene remains dormant. We have been able to show the feasibility this type of approach has for other animal species, and it shows great potential for application to humans.

Animals↗