allopurinol and Hyperglycemia

Topics: Acidosis, Lactic; Acute Disease; Ammonia; Galactosemias; Humans; Hyperglycemia; Infant; Infant, Newborn; Metabolism, Inborn Errors; Microbodies; Xanthine Oxidase

Allopurinol (ALP) attenuates oxidative stress and diabetic cardiomyopathy (DCM), but the mechanism is unclear. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) following the disassociation with its repressor Keap1 under oxidative stress can maintain inner redox homeostasis and attenuate DCM with concomitant attenuation of autophagy. We postulated that ALP treatment may activate Nrf2 to mitigate autophagy over-activation and consequently attenuate DCM. Streptozotocin-induced type 1 diabetic rats were untreated or treated with ALP (100 mg/kg/d) for 4 weeks and terminated after heart function measurements by echocardiography and pressure-volume conductance system. Cardiomyocyte H9C2 cells infected with Nrf2 siRNA or not were incubated with high glucose (HG, 25 mmol/L) concomitantly with ALP treatment. Cell viability, lactate dehydrogenase, 15-F2t-Isoprostane and superoxide dismutase (SOD) were measured with colorimetric enzyme-linked immunosorbent assays. ROS, apoptosis, was assessed by dihydroethidium staining and TUNEL, respectively. The Western blot and qRT-PCR were used to assess protein and mRNA variations. Diabetic rats showed significant reductions in heart rate (HR), left ventricular eject fraction (LVEF), stroke work (SW) and cardiac output (CO), left ventricular end-systolic volume (LVVs) as compared to non-diabetic control and ALP improved or normalized HR, LVEF, SW, CO and LVVs in diabetic rats (all P < .05). Hearts of diabetic rats displayed excessive oxidative stress manifested as increased levels of 15-F2t-Isoprostane and superoxide anion production, increased apoptotic cell death and cardiomyocytes autophagy that were concomitant with reduced expressions of Nrf2, heme oxygenase-1 (HO-1) and Keap1. ALP reverted all the above-mentioned diabetes-induced biochemical changes except that it did not affect the levels of Keap1. In vitro, ALP increased Nrf2 and reduced the hyperglycaemia-induced increases of H9C2 cardiomyocyte hypertrophy, oxidative stress, apoptosis and autophagy, and enhanced cellular viability. Nrf2 gene silence cancelled these protective effects of ALP in H9C2 cells. Activation of Nrf2 subsequent to the suppression of Keap1 and the mitigation of autophagy over-activation may represent major mechanisms whereby ALP attenuates DCM.

Topics: Allopurinol; Animals; Apoptosis; Cell Line; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Diastole; Glucose; Heart Ventricles; Hemodynamics; Hyperglycemia; Kelch-Like ECH-Associated Protein 1; Male; Models, Biological; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Rats, Sprague-Dawley; Sequestosome-1 Protein; Signal Transduction; Systole

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial.. A retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG).. The causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection.. The mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Blood Glucose; Body Surface Area; Chemical and Drug Induced Liver Injury; China; Cohort Studies; Drugs, Chinese Herbal; Female; Gastrointestinal Hemorrhage; Glucocorticoids; Gout Suppressants; Humans; Hyperglycemia; Hypertension; Immunoglobulins, Intravenous; Immunologic Factors; Klebsiella Infections; Male; Middle Aged; Pneumonia; Pulmonary Aspergillosis; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Stevens-Johnson Syndrome; Survival Rate; Water-Electrolyte Imbalance; Wound Infection

Hyperuricemia has been recognized as a risk factor for insulin resistance as well as one of the factors leading to diabetic kidney disease (DKD). Since DKD is the most common cause of end-stage renal disease, we investigated whether febuxostat, a xanthine oxidase (XO) inhibitor, exerts a protective effect against the development of DKD. We used KK-Ay mice, an established obese diabetic rodent model. Eight-week-old KK-Ay mice were provided drinking water with or without febuxostat (15 μg/mL) for 12 weeks and then subjected to experimentation. Urine albumin secretion and degrees of glomerular injury judged by microscopic observations were markedly higher in KK-Ay than in control lean mice. These elevations were significantly normalized by febuxostat treatment. On the other hand, body weights and high serum glucose concentrations and glycated albumin levels of KK-Ay mice were not affected by febuxostat treatment, despite glucose tolerance and insulin tolerance tests having revealed febuxostat significantly improved insulin sensitivity and glucose tolerance. Interestingly, the IL-1β, IL-6, MCP-1, and ICAM-1 mRNA levels, which were increased in KK-Ay mouse kidneys as compared with normal controls, were suppressed by febuxostat administration. These data indicate a protective effect of XO inhibitors against the development of DKD, and the underlying mechanism likely involves inflammation suppression which is independent of hyperglycemia amelioration.

Topics: Animals; Anti-Inflammatory Agents; Body Weight; Chemokine CCL2; Collagen; Diabetic Nephropathies; Febuxostat; Glucose Intolerance; Hyperglycemia; Hyperuricemia; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-6; Kidney Glomerulus; Mice; Mice, Inbred C57BL; Mice, Obese; Oxidative Stress; Peptide Fragments; Uric Acid; Xanthine Oxidase

Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms.. Cells were treated with normal glucose (5.5 mmol/L), constant high glucose (CHG) (25 mmol/L), and IHG (rotation per 24 h in 11.1 or 25 mmol/L) for 7 days. Reactive oxygen species (ROS), xanthine oxidase (XOD) level, apoptosis, cell viability, cell cycle, and expression of cyclinD1, p21, p27, and Skp2 were determined.. We found that IHG induced more significant apoptosis than CHG and normal glucose; intracellular ROS and XOD levels were more markedly increased in cells exposed to IHG. Cells treated with IHG showed significant decreased cell viability and increased cell proportion in G0/G1 phase. Cell cycle related proteins such as cyclinD1 and Skp2 were decreased significantly, but expressions of p27 and p21 were increased markedly.. This study suggested that IHG plays a more toxic effect including both apoptosis-inducing and antiproliferative effects on INS-1 cells. Excessive activation of cellular stress and regulation of cyclins might be potential mechanism of impairment in INS-1 cells induced by IHG.

Topics: Animals; Apoptosis; Cell Line; Cell Proliferation; Cell Survival; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Down-Regulation; Glucose; Hyperglycemia; Insulin-Secreting Cells; Oxidative Stress; Rats; Reactive Oxygen Species; Resting Phase, Cell Cycle; S-Phase Kinase-Associated Proteins; Time Factors; Up-Regulation; Xanthine Oxidase

Nigella sativa fixed (NSFO) and essential (NSEO) oils have been used to treat diabetes mellitus and its complications. Present study was undertaken to explore and validate these folkloric uses.. Sprague dawley rats having streptozotocin (STZ) induced diabetes mellitus were used to assess the role of NSFO and NSEO in the management of diabetes complications. Parameters investigated were antioxidant potential, oxidative stress, and the immunity by in vivo experiments.. The results indicated that STZ decreased the glutathione contents (25.72%), while NSFO and NSEO increased the trait significantly (P < 0.05). Experimental diets increased the tocopherol contents (P < 0.01) and enhanced the expression of hepatic enzymes (P < 0.01). Correlation matrix further indicated that antioxidant potential is positively associated (P < 0.05) responsible for the modulation of hepatic enzymes and the decrease of the nitric oxide production thus controlling the diabetes complications.. Overall, results of present study supported the traditional use of N. sativa and its derived products as a treatment for hyperglycemia and allied abnormalities. Moreover, N. sativa fixed and essential oils significantly ameliorate free radicals and improve antioxidant capacity thus reducing the risk of diabetic complications.

Topics: Adjuvants, Immunologic; Animals; Antioxidants; Diabetes Mellitus, Experimental; Glutathione; Hyperglycemia; Liver; Nigella sativa; Nitric Oxide; Oils, Volatile; Oxidative Stress; Peroxidase; Plant Oils; Rats; Rats, Sprague-Dawley; Tocopherols; Xanthine Oxidase

Oxidative stress plays a crucial role in the progression of diabetic nephropathy in hyperglycemic conditions. It has already been reported that mangiferin, a natural C-glucosyl xanthone and polyhydroxy polyphenol compound protects kidneys from diabetic nephropathy. However, little is known about the mechanism of its beneficial action in this pathophysiology. The present study, therefore, examines the detailed mechanism of the beneficial action of mangiferin on STZ-induced diabetic nephropathy in Wister rats as the working model. A significant increase in plasma glucose level, kidney to body weight ratio, glomerular hypertrophy and hydropic changes as well as enhanced nephrotoxicity related markers (BUN, plasma creatinine, uric acid and urinary albumin) were observed in the experimental animals. Furthermore, increased oxidative stress related parameters, increased ROS production and decreased the intracellular antioxidant defenses were detected in the kidney. Studies on the oxidative stress mediated signaling cascades in diabetic nephropathy demonstrated that PKC isoforms (PKCα, PKCβ and PKCε), MAPKs (p38, JNK and ERK1/2), transcription factor (NF-κB) and TGF-β1 pathways were involved in this pathophysiology. Besides, TNFα was released in this hyperglycemic condition, which in turn activated caspase 8, cleaved Bid to tBid and finally the mitochorndia-dependent apoptotic pathway. In addition, oxidative stress also disturbed the proapoptotic-antiapoptotic (Bax and Bcl-2) balance and activated mitochorndia-dependent apoptosis via caspase 9, caspase 3 and PARP cleavage. Mangiferin treatment, post to hyperglycemia, successfully inhibited all of these changes and protected the cells from apoptotic death.

Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Glycation End Products, Advanced; Hydroxyproline; Hyperglycemia; Kidney Glomerulus; Male; Mitochondria; Mitogen-Activated Protein Kinases; NF-kappa B; Oxidative Stress; Protein Kinase C; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction; Streptozocin; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Xanthine Oxidase; Xanthones

Recently, sodium tungstate was suggested to improve cardiac performance of diabetic rats in perfused hearts based on its insulinomimetic activity. In this study, we aimed to investigate the cellular and molecular mechanisms underlying this beneficial effect of sodium tungstate. Tungstate was administered (100 mg/kg/day) to diabetic and control rats intragastrically for 6 weeks. Blood glucose levels increased, whereas body weight, heart weight and plasma insulin levels decreased significantly in diabetic animals. Interestingly, none of these parameters was changed by tungstate treatment. On the other hand, fractional shortening and accompanying intracellular Ca(2+) [Ca(2+)](i) transients of isolated ventricular myocytes were measured, and sodium tungstate was found to improve the peak shortening and the amplitude of [Ca(2+)](i) transients in diabetic cardiomyocytes. Potassium and L-type Ca(2+) currents were also recorded in isolated ventricular cells. Significant restoration of suppressed I (to) and I (ss) was achieved by tungstate administration. Nevertheless, L-type calcium currents did not change either in untreated or treated diabetic rats. Tissue biochemical parameters including TBARS, protein carbonyl content, xanthine oxidase (XO) and xanthine dehydogenase (XDH) were also determined, and diabetes revealed a marked increase in TBARS and carbonyl content which were decreased significantly by tungstate treatment. Conversely, although XO and XDH activities didn't change in untreated diabetic rats, a remarkable but insignificant decrease was detected in treated animals. In conclusion, tungstate treatment improved diabetes-induced contractile abnormalities via restoration of dysregulated [Ca(2+)](i) and altered ionic currents. This beneficial effect is due to antioxidant property of sodium tungstate rather than normalization of hyperglycemia.

Topics: Animals; Blood Glucose; Body Weight; Calcium; Calcium Channels, L-Type; Cardiotonic Agents; Diabetes Complications; Diabetes Mellitus, Experimental; Electrophysiological Phenomena; Heart; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Myocardial Contraction; Myocytes, Cardiac; Organ Size; Oxidative Stress; Patch-Clamp Techniques; Protein Carbonylation; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Tungsten Compounds; Xanthine Dehydrogenase; Xanthine Oxidase

Reactive oxygen species (ROS) have been widely implicated in the pathogenesis of diabetes and more recently in mitochondrial alterations in skeletal muscle of diabetic mice. However, so far the exact sources of ROS in skeletal muscle have remained elusive. Aiming at better understanding the causes of mitochondrial alterations in diabetic muscle, we designed this study to characterize the sites of ROS production in skeletal muscle of streptozotocin (STZ)-induced diabetic mice. Hyperglycemic STZ mice showed increased markers of systemic and muscular oxidative stress, as evidenced by increased circulating H(2)O(2) and muscle carbonylated protein levels. Interestingly, insulin treatment reduced hyperglycemia and improved systemic and muscular oxidative stress in STZ mice. We demonstrated that increased oxidative stress in muscle of STZ mice is associated with an increase of xanthine oxidase (XO) expression and activity and is mediated by an induction of H(2)O(2) production by both mitochondria and XO. Finally, treatment of STZ mice, as well as high-fat and high-sucrose diet-fed mice, with oxypurinol reduced markers of systemic and muscular oxidative stress and prevented structural and functional mitochondrial alterations, confirming the in vivo relevance of XO in ROS production in diabetic mice. These data indicate that mitochondria and XO are the major sources of hyperglycemia-induced ROS production in skeletal muscle and that the inhibition of XO reduces oxidative stress and improves mitochondrial alterations in diabetic muscle.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet; Enzyme Inhibitors; Hydrogen Peroxide; Hyperglycemia; Insulin; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Mitochondria, Muscle; Muscle, Skeletal; Oxidative Stress; Oxypurinol; Protein Carbonylation; Reverse Transcriptase Polymerase Chain Reaction; RNA; Xanthine Oxidase

Elevated glutamate levels have been reported in humans with diabetic retinopathy. Retinal Müller glial cells regulate glutamate levels via the GLAST transporter and system x(c)(-) (cystine-glutamate exchanger). We have investigated whether transporter function and gene and/or protein expression are altered in mouse Müller cells cultured under conditions of hyperglycemia or oxidative stress (two factors implicated in diabetic retinopathy). Cells were subjected to hyperglycemic conditions (35 mM glucose) over an 8-day period or to oxidative stress conditions (induced by exposure to various concentrations of xanthine:xanthine oxidase) for 6 h. The Na(+)-dependent and -independent uptake of [(3)H] glutamate was assessed as a measure of GLAST and system x(c)(-) function, respectively. Hyperglycemia did not alter the uptake of [(3)H] glutamate by GLAST or system x(c)(-); neither gene nor protein expression decreased. Oxidative stress (70:14 or 100:20 microM xanthine:mU/ml xanthine oxidase) decreased GLAST activity by approximately 10% but increased system x(c)(-) activity by 43% and 89%, respectively. Kinetic analysis showed an oxidative-stress-induced change in V(max), but not K(m). Oxidative stress caused a 2.4-fold increase in mRNA encoding xCT, the unique component of system x(c)(-). Of the two isoforms of xCT (40 and 50 kDa), oxidative stress induced a 3.6-fold increase in the 40-kDa form localized to the plasma membrane. This is the first report of the differential expression and localization of xCT isoforms as caused by cellular stress. Increased system x(c)(-) activity in Müller cells subjected to conditions associated with diabetic retinopathy may be beneficial, as this exchanger is important for the synthesis of the antioxidant glutathione.

Topics: Amino Acid Transport System y+; Animals; Blood Glucose; Cells, Cultured; Excitatory Amino Acid Transporter 1; Female; Gene Expression; Glutamic Acid; Humans; Hyperglycemia; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Neuroglia; Oxidative Stress; Retina; Vimentin; Xanthine; Xanthine Oxidase

Diabetes mellitus is characterized by a chronic hyperglycemia and might cause skin pathologies resulting from an ischemic insult. A variety of mechanisms have been suggested for the damage provided by ischemia-reperfusion injury (IRI) or for hyperglycemic conditions. Yet, the association between IRI and hyperglycemia together in skin has been poorly investigated even thought they are both present in diabetic patients.. To examine the effect of a dual stress combining IRI and hyperglycemia on human keratinocytes-its ability to cause oxidative damage and inflammatory response via the enzymes xanthine oxidase (XO) and inducible nitric oxide synthase (iNOS).. HaCaT cells were used as a model to induce IRI and hyperglycemia. In order to assess the oxidative damage, total antioxidant scavenging capacity (TSC) and GSH/GSSG ratio were evaluated. iNOS expression was evaluated and its metabolite nitric oxide was estimated by measuring nitrite levels. XO activity was assessed by uric acid quantification and by superoxide radical formation. Inflammatory response was determined through interleukin-6 secretion.. Our observations demonstrate different responses of the cells exposed to single stress (IRI) compared to dual stress combining also hyperglycemia. However, cells response exhibited similarity during reperfusion, by enhancing iNOS expression as well as superoxide levels. While ischemia led to changes in TSC and redox state, reperfusion restored them to basal levels. IRI also caused the enhancement of secreted IL-6 and uric acid levels.. iNOS and XO play a major role in IRI and hyperglycemia. Inhibition of one of these enzymes may be beneficial to skin cells under these conditions.

Topics: Biomarkers; Cell Hypoxia; Cell Line; Cell Survival; Glucose; Glutathione; Glutathione Disulfide; Humans; Hyperglycemia; Inflammation Mediators; Interleukin-6; Ischemia; Keratinocytes; Nitric Oxide; Nitric Oxide Synthase Type II; Nitrites; Oxidative Stress; Reperfusion Injury; Superoxides; Uric Acid; Xanthine Oxidase

The objective of the present study was to investigate the possible neuroprotective effect of resveratrol against streptozotocin-induced hyperglycaemia in the rat brain and medulla spinalis. Thirty adult male Wistar rats were divided into three groups as follows: control group, streptozotocin-induced diabetic-untreated group, and streptozotocin-induced diabetic resveratrol-treated group. Diabetes was induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). Three days after streptozotocin injection, resveratrol (10 mg/kg) was injected intraperiteonally daily over 6 weeks to the rats in the treatment group. Six weeks later, seven rats from each group were killed and the brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical studies (lipid peroxidation measuring malondialdehyde [MDA], xanthine oxidase [XO], nitric oxide [NO] and glutathione). MDA, XO and NO levels in hippocampus, cortex, cerebellum, brain stem and spinal cord in the streptozotocin-induced diabetic-untreated group increased significantly. Treatment with resveratrol significantly reduced MDA, XO and NO production and increased glutathione levels when compared to the streptozotocin-induced diabetic-untreated group. This study demonstrates that resveratrol is a potent neuroprotective agent against diabetic oxidative damage.

Topics: Animals; Central Nervous System Diseases; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Free Radical Scavengers; Glutathione; Hyperglycemia; Lipid Peroxidation; Male; Malondialdehyde; Medulla Oblongata; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Resveratrol; Spinal Cord; Stilbenes; Vasodilator Agents; Xanthine Oxidase

Fructose is a commonly used sweetener associated with diets that increase the prevalence of metabolic syndrome. Thiazide diuretics are frequently used in these patients for treatment of hypertension, but they also exacerbate metabolic syndrome. Rats on high-fructose diets that are given thiazides exhibit potassium depletion and hyperuricemia. Potassium supplementation improves their insulin resistance and hypertension, whereas allopurinol reduces serum levels of uric acid and ameliorates hypertension, hypertriglyceridemia, hyperglycemia, and insulin resistance. Both potassium supplementation and treatment with allopurinol also increase urinary nitric oxide excretion. We suggest that potassium depletion and hyperuricemia in rats exacerbates endothelial dysfunction and lowers the bioavailability of nitric oxide, which blocks insulin activity and causes insulin resistance during thiazide usage. Addition of potassium supplements and allopurinol with thiazides might be helpful in the management of metabolic syndrome.

Topics: Allopurinol; Animals; Blood Pressure; Body Weight; Diuretics; Fructose; Gout Suppressants; Hydrochlorothiazide; Hyperglycemia; Hypertension; Hypertriglyceridemia; Hyperuricemia; Hypokalemia; Insulin; Insulin Resistance; Kidney; Male; Metabolic Syndrome; Nitric Oxide; Potassium; Rats; Rats, Sprague-Dawley; Sodium; Uric Acid

In diabetes mellitus, the risk for cardiovascular complications and development of atherosclerosis is increased compared with healthy individuals. Recently evidence was provided that increased production of superoxide anions occurs in endothelial cells during hyperglycemia. In order to evaluate the potential impact of the enhanced formation of this oxygen radical for vascular cell dysfunction and its role in tissue adaptation, it is essential to assess the effect of superoxide anions on endothelial cell function. Here, we present new data and review our previous work on the effects of superoxide anions on endothelial vascular function, such as intracellular Ca2+ signal cascade, formation and bioactivity of nitric oxide. Based on the presented data we discuss superoxide anion production as a two faced phenomenon. In lower concentrations, superoxide anions are mediators of an endothelium adaptation to ensure endothelial vasomotion control. However, in higher concentrations superoxide anions disrupt endothelial-smooth muscle crosstalk resulting in vessel wall dysfunction and vascular wall dysfunction.

Topics: Adaptation, Physiological; Animals; Aorta; Arteries; Calcium; Cells, Cultured; Diabetic Angiopathies; Endothelium, Vascular; Female; Glucose; Hyperglycemia; Models, Cardiovascular; Muscle, Smooth, Vascular; Nitric Oxide; Signal Transduction; Superoxides; Swine; Uterus; Xanthine; Xanthine Oxidase

Topics: Adenosine; Allopurinol; Animals; Blood Glucose; Dogs; Female; Fluorocarbons; Glutathione; Hyperglycemia; Insulin; Ischemia; Male; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Raffinose; Solutions; Temperature; Transplantation, Autologous

Topics: Adolescent; Adult; Aged; Allopurinol; Anaphylaxis; Asparaginase; Blood Coagulation Disorders; Cytarabine; Daunorubicin; Drug Hypersensitivity; Female; Fever; Gastrointestinal Hemorrhage; Hallucinations; Humans; Hyperglycemia; Injections, Intravenous; Jaundice; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Liver; Male; Mercaptopurine; Methotrexate; Middle Aged; Oral Hemorrhage; Prednisone; Thioguanine; Uremia; Vincristine; Vomiting