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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiogenesis is a key mechanism that influences several physiological and pathological processes, including wound healing. During the past decades, many groups have shown that controlling angiogenesis might be an answer to overcome pathological situations when this process is out of control. Many altered metabolic states exert considerable influence on the development of angiogenesis. We have chosen diabetes as a model of a progressive metabolic disease with many associated conditions, including an alteration of wound healing dynamics described elsewhere. To evaluate the growth of newly formed blood vessels during diabetes, we induced corneal angiogenesis through silver nitrate cauterization in streptozotocin-induced diabetic rats, always comparing to control non-diabetic or insulin-treated diabetic rats. Computer-aided analysis showed that both the percentage of area taken by vessels on the cornea and their average length were decreased in diabetic animals; furthermore, this diminishment was prevented by insulin treatment in previously diabetic rats. Immunohistochemical staining of neutrophils and macrophages (EDI clone) did not show any differences on number of migrating cells in the cornea. Immunolocalization of vascular endothelial growth factor and basic fibroblast growth factor did not differ considerably among groups either. These results support previous findings that angiogenesis is decreased due to the development of diabetes mellitus but contrasts to descriptions from other investigators in regard to the inflammatory infiltrate and production of growth factors. In our experimental conditions, the cause of the decreased angiogenesis in diabetic rats remains for further elucidation.
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PMID:Inflammatory infiltrate, VEGF and FGF-2 contents during corneal angiogenesis in STZ-diabetic rats. 1254 61

Defective endothelium is a key event in the development of atherosclerosis in diabetes: alteration of the L-arginine-nitric oxide (NO) pathway has been suggested. We propose a modeling approach of the L-arginine-NO pathway in vivo in both control and type 2 diabetic subjects based on the intravenous bolus injection of L-[(15)N]arginine and subsequent noncompartmental and compartmental model analysis of L-[(15)N] arginine in plasma and [(15)N]nitrate in the urine. No differences in arginine kinetics were observed between normal subjects and diabetic patients. [(15)N]nitrates were detectable up to 48 h from the L-(15)[N]arginine administration; no differences were found in the tracer-to-tracee ratio in each urine collection. However, the NO synthesis in plasma from arginine was lower (P = 0.05 for the noncompartmental and 0.1208 for the compartmental analysis, by Mann-Whitney test) in diabetic patients than in control subjects when expressed both in absolute terms (50% decrease) and as percentage of NO turnover (30% decrease). This new modeling approach of L-arginine-NO pathway provides a detailed picture of arginine kinetics and nitrate metabolism. From our data, it appears that noncomplicated type 2 diabetic patients have a decreased conversion of arginine to NO.
Diabetes 2003 Mar
PMID:L-arginine-nitric oxide kinetics in normal and type 2 diabetic subjects: a stable-labelled 15N arginine approach. 1260 22

We analyzed the associations of environmental factors with the regional distribution of Type 1 diabetes mellitus in Austria. All newly diagnosed cases (n=1449) from 1989 to 1999 were allocated to districts using the postal code. Nitrate content of the water was measured by the Austrian Federal Environmental Agency. Data on infant mortality, population density, and percentage of employment by industry were derived from Statistics Austria. An inverse effect was seen between the proportion of children younger than 15 years of age and the risk ratio (P<.01). Infant mortality, population density, and percentage of persons with employment in industry were not of significant influence. The mean nitrate level was positively associated (P=.07). In regions with a higher percentage of children younger than 15 years of age, fewer children developed diabetes, which is in agreement with the observation that early social mixing is a protective factor. Nitrate levels may have a confounding effect.
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PMID:Small area variation in childhood diabetes mellitus in Austria: links to population density, 1989 to 1999. 1272 82

In postmenopausal women (PMW), the effect of a short-term course of estrogen/progestin HT on free radical oxidative stress was evaluated. In addition, HT's effect on plasma nitric oxide (NO) activity was determined as a measure of vascular endothelial function. We investigated the relationship of these markers and HT across race and the cardiovascular risk factors of smoking, diabetes and hypertension.A prospective, observational study comparing preintervention and postintervention. Academic research center.Twenty-seven (14 African American and 13 Caucasian) PMW volunteers. Six weeks of continuous, combined estrogen/progestin HT. Plasma concentrations of free 8-epi-prostaglandin F(2alpha) (8-isoprostane) before and after HT were compared as a measure of oxidative stress. Nitrite, the stable oxidation metabolite of NO, was measured by the Greiss reaction after nitrate reduction to nitrite with cadmium. Plasma levels of free 8-isoprostane decreased significantly after 6 weeks of HT. Although almost all subjects benefited from the reduction in free 8-isoprostane, PMW with at least one cardiovascular risk factor (n = 19) demonstrated higher free 8-isoprostane than did subjects with no risk factors. Plasma levels of nitrite increased after 6 weeks of HT, but the difference was not statistically significant. Caucasian PMW demonstrated a greater increase in plasma levels of nitrite after 6 weeks of HT as compared with African American subjects, who exhibited almost no change.Short-term administration of HT significantly reduces oxidative stress in PMW and is consistent across race. However, there was an observed racial difference in endothelial NO response to HT between African American and Caucasian PMW.
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PMID:Effect of short-term hormone therapy on oxidative stress and endothelial function in African American and Caucasian postmenopausal women. 1273 5

To investigate the antioxidant activity of mustard leaf (Brassica juncea), we prepared four fractions (CH(2)Cl(2), EtOAc, BuOH and H(2)O fractions) and examined their radical scavenging activities in vitro and in vivo. Based on the in vitro results of spin trapping and 1,1-diphenyl-2-picrylhydrazyl radical, we carried out an in vivo study with the BuOH fraction to investigate its effect on oxidative stress in rats with streptozotocin-induced diabetes. We found that in comparison with untreated diabetic control rats, oral administration of the BuOH fraction (100 or 200 mg/kg body weight/day for 10 days) induced a significant decrease in serum glucose and glycosylated protein, which is glycosylated with hemoglobin as an indicator of oxidative stress. Moreover, administration of the BuOH fraction also effectively reduced the serum superoxide and nitrite/nitrate levels. Furthermore, the levels of thiobarbituric acid-reactive substances in serum and liver were also significantly lower than in the control group. These results indicate that the BuOH fraction of mustard leaf controls glucose metabolism and reduces lipid peroxidation as well as the level of oxygen radicals, ameliorating the damage caused by oxidative stress in diabetes.
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PMID:In vitro and in vivo antioxidant effects of mustard leaf (Brassica juncea). 1274 80

L-arginine has been shown to enhance wound strength and collagen deposition in rodents and humans. Diabetes mellitus, which impairs wound healing, is accompanied by a reduction in nitric oxide at the wound site. The amino acid L-arginine is the only substrate for nitric oxide synthesis. We sought to determine whether supplemental L-arginine can restore the impaired wound healing of diabetic rats. Fifty-six male Lewis rats were used in this study, of which twenty-nine rats were rendered diabetic 7 days prior to surgery with intraperitoneal streptozotocin. Twenty-seven untreated rats served as controls. Animals underwent a dorsal skin incision with implantation of polyvinyl-alcohol sponges. Sixteen diabetic and 14 normal rats received 1 g/kg/day of L-arginine by injection, while the remainder received saline injections only. Animals were euthanized 10 days postwounding, and their wounds were analyzed for breaking strength. The wound sponges were assayed for total hydroxyproline and nitrite/nitrate content. Plasma and wound fluid concentrations of L-arginine, ornithine, and citrulline were determined. Wound sponge RNA was extracted and subjected to Northern blot analysis for procollagen I and III. Diabetic wounds had greatly decreased breaking strengths compared with controls. L-arginine significantly enhanced wound breaking strengths in both control (+23%) and diabetic animals (+44%), and also increased wound hydroxyproline levels in both diabetic (+40%) and control animals (+24%) as compared to their saline-treated counterparts. mRNA for procollagen I and III were elevated by L-arginine treatment in both diabetic rats and controls. Treatment with L-arginine significantly increased wound fluid nitrite/nitrate levels in diabetic animals. The data show that the impaired healing of diabetic wounds can be partially corrected by L-arginine supplementation, and that this effect is accompanied by enhanced wound nitric oxide synthesis.
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PMID:Supplemental L-arginine enhances wound healing in diabetic rats. 1275 1

Of four fractions (CH2Cl2, EtOAc, BuOH and H2O) from mustard leaf (Brassica juncea), the EtOAc fraction showed the strongest inhibitory effects, which were concentration-dependent, on the formation of advanced glycation end products and free radical-mediated protein damage in an in vitro system, indicating that this fraction has a potential protective role against diabetes and/or its complications. Based on these results, we carried out an in vivo study to determine whether the EtOAc fraction protected against diabetic oxidative stress induced by streptozotocin. Oral administration of the EtOAc fraction at doses of 50 and 200 mg/kg body weight/d for 10 d reduced the serum levels of glucose and glycosylated protein, implying that the impaired glucose metabolism due to diabetes had been ameliorated. In addition, the EtOAc fraction significantly reduced the thiobarbituric acid-reactive substance levels of serum and hepatic and renal mitochondria. Furthermore, the elevated levels of superoxide and nitrite/nitrate were reduced in a dose-dependent manner by oral administration of the EtOAc fraction. These findings suggest that the EtOAc fraction from mustard leaf might be beneficial in attenuating the damage caused by oxidative stress involved in diabetes and its complications.
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PMID:Protective effects of mustard leaf (Brassica juncea) against diabetic oxidative stress. 1288 53

Reactive oxygen species (ROS) formation plays a major role in diabetes-induced endothelial dysfunction, though the molecular mechanism(s) involved and the contribution of nitric oxide (NO) are still unclear. This study using bovine retinal endothelial cells was aimed at assessing (i) the role of oxygen-dependent vs. NO-dependent oxidative stress in the endothelial cell permeability alterations induced by the diabetic milieu and (ii) whether protein kinase C (PKC) activation ultimately mediates these changes. Superoxide, lipid peroxide, and PKC activity were higher under high glucose (HG) vs. normal glucose throughout the 30 d period. Nitrite/nitrate and endothelial NO synthase levels increased at 1 d and decreased thereafter. Changes in monolayer permeability to 125I-BSA induced by 1 or 30 d incubation in HG or exposure to advanced glycosylation endproduct were reduced by treatment with antioxidants or PKC inhibitors, whereas NO blockade prevented only the effect of 1 d HG. HG-induced changes were mimicked by a PKC activator, a superoxide generating system, an NO and superoxide donor, or peroxynitrite (attenuated by PKC inhibition), but not a NO donor. The short-term effect of HG depends on a combined oxidative and nitrosative stress with peroxynitrite formation, whereas the long-term effect is related to ROS generation; in both cases, PKC ultimately mediates permeability changes.
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PMID:Oxidative stress in diabetes-induced endothelial dysfunction involvement of nitric oxide and protein kinase C. 1295 60

The experimental data of endothelium-dependent and endothelium-independent responses of vascular smooth muscles of isolated preparations of the thoracic aorta of rats with experimental diabetes mellitus (streptozotocin-induced diabetes) and a control group of animals are presented in the article. It has been shown that at diabetes mellitus endothelium-dependent vasodilation was deteriorated to the most extent. It resulted from dysfunction of the endothelium due to a reduce in the synthesis of NO. This conclusion was based on the data of the parameters of the contents of steady metabolites of nitric oxide (NO2- and NO3-), as well as activities of inducible and constitutive NO-synthases (iNOS and cNOS) in heart, aorta, erythrocytes and blood plasma in diabetic and control animals.
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PMID:[Changes in vasodilator responses of vascular smooth muscles and nitric oxide system in experimental diabetes mellitus]. 1450 24

Sildenafil citrate, the first internationally approved and widely used oral agent for the treatment of erectile dysfunction (ED), has revolutionized the treatment of ED throughout the past 5 years. This phosphodiesterase type-5 (PDE-5) inhibitor is selective for corpus cavernosum smooth muscle tissue and produces excellent erectile function. Its efficacy and safety over a wide variety of etiologies of ED and severities of ED demonstrates its usefulness in the clinical treatment of these patients. More than 20 million men have been treated worldwide with sildenafil with excellent results. ED caused by difficult-to-treat etiologies such as radical prostatectomy, severe diabetes, and spinal cord injury have demonstrated efficacy. Although sildenafil citrate, like all PDE-5 inhibitors, is contraindicated in patients taking nitrate medications for cardiac disease, it is effective and safe for those cardiovascular patients who are not taking nitrate medications. The incidence of adverse cardiovascular events in patients taking sildenafil does not differ from those of the general population. Investigations into the pharmacologic effect of sildenafil on coronary myocardial tissue further supports the safety of this medication. Sildenafil has been safe and effective in patients taking various medications including multiple antihypertensive drugs, selective serotonin reuptake inhibitors, cardiac, and diabetic medications.
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PMID:Sildenafil: a 4-year update in the treatment of 20 million erectile dysfunction patients. 1462 3


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