Comparison of the effects of intensive insulin treatment modalities on cardiovascular biomarkers in type 1 diabetes mellitus.

AIM: To evaluate effects of intensive insulin treatment modalities on cardiovascular biomarkers in patients with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: A total of 25 patients with T1DM receiving intensive insulin therapy either in the form of continuous insulin pump (IP group; n=13) or as multiple daily injections (MDI group; n=12) and 13 controls (control group, n=13) were included. Data on demographics, anthropometrics, diabetes history, and laboratory findings including glycemic and lipid parameters, and cardiovascular biomarkers [C-reactive protein (mg/dL), homocysteine (µmol/L), fibrinogen (mg/dL), oxidized LDL (ng/dL), PAI-1 (ng/mL), MCP-1 (pg/mL) and VEGF (pg/mL)] were recorded in each group. Correlation of cardiovascular biomarkers to other parameters was also evaluated in T1DM patients. RESULTS: Apart from significantly higher mean (SD) values for HbA1c [6.1 (0.3) vs. 5.6 (0.5)% (43 (3) vs. 38 (5) mmol/mol), p<0.05)] and HDL-cholesterol [71.5 (13.6) vs. 58.2 (10.8), p<0.01) in the IP than in the MDI group, no significance difference was noted between insulin treatment modalities as well as between patient and control groups in terms of demographic, anthropometric and laboratory parameters. Negative correlation of MCP-1 to treatment duration (r=-0.615, p=0.025), and HDL-c to CRP (r=-0.685, p=0.010) and VEGF (r=-0.678, p=0.011) was noted in IP group, whereas positive correlation of PAI-1 to diabetes age (r=0.805, p=0.002) and treatment duration was noted in MDI group. CONCLUSION: Our findings in a cohort of T1DM patients with optimal glycemic control revealed that intensive insulin therapy was not associated with an increase in atherosclerotic markers in T1DM, regardless of whether continuous IP infusion or MDIs was administered.

Different responses of fluvastatin to cholesterol-induced oxidative modifications in rabbits: evidence for preventive effect against DNA damage.

Hypercholesterolemia is a major risk factor for atherosclerosis and related occlusive vascular diseases. We investigated the effect of low-dose fluvastatin (2 mg kg(-1) day(-1)) on antioxidant enzyme activities [superoxide dismutase (SOD), catalase], vascular reactivity changes and oxidatively induced DNA damage in early stage of atherosclerosis in hypercholesterolemic rabbits. The animals were divided into three groups each composed of 10 rabbits. The control group received a regular rabbit chow diet, and the cholesterol group had hypercholesterolemic diet (2%, 4 weeks). The fluvastatin group was given hypercholesterolemic diet plus fluvastatin. Dietary intake of cholesterol significantly increased total cholesterol levels in rabbits (control, 0.85 ± 0.29; cholesterol, 12.04 ± 4.61; fluvastatin, 8.07 ± 2.72 mmol l(-1)). Hypercholesterolemic diet revealed discernible fatty streaks in arcus aortae. Fluvastatin significantly reduced the areas of the lesions. The diet significantly increased SOD activities in both erythrocyte and tissue. Treatment with fluvastatin normalized the increased activity of SOD in both erythrocyte and aortic tissues from the cholesterol group. Cholesterol feeding decreased the sensitivity to acetylcholine, and treatment with fluvastatin significantly restored the diminished sensitivity to acetylcholine in thoracic aortae. Cholesterol feeding caused oxidatively induced DNA damage in liver tissues determined by the increased levels of 8-hydroxyguanine (8-OH-Gua) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua). Fluvastatin decreased only FapyGua level in liver. In conclusion, our results may suggest that fluvastatin seems to play a protective role on high cholesterol-induced oxidative stress and DNA damage.

The effect of 1alpha,25(OH)2D3 vitamin over oxidative stress and biochemical parameters in rats where Type 1 diabetes is formed by streptozotocin.

INTRODUCTION: The 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] plays an essential role in mineral balance but has also been recognized as a powerful modulator of immune response. We aimed to examine the effect of the 1alpha,25(OH)(2)D(3) treatment on insulin/c-peptide, catalase, superoxide dismutase (SOD), and blood glucose in rats that take streptozotocin (STZ). METHODS: Forty pieces of male rats of Albino family whose average weights were 261.00+/-07.62 g were used in the study. Rats were made diabetic by giving STZ of 40 mg/kg during 5 days through intraperitoneal path. Some of the diabetic group and nondiabetic group were received 1alpha,25(OH)(2)D(3). The levels of SOD, insulin, c-peptide, glucose, SOD, and catalase were measured at the zero, second, fourth, and sixth weeks. RESULTS: Erythrocyte SOD levels didn't show a significant difference at the end of the sixth week in all groups when compared to the beginning. While erythrocyte catalase levels didn't show a significant difference in nondiabetic control and nondiabetic with vitamin D, and diabetic with vitamin D groups at the end of sixth week when compared to the beginning, a significant measurement was made in diabetic without vitamin D group. Maximal insulinitis scoring values were observed in diabetic without vitamin D that didn't receive 1alpha,25(OH)(2)D(3) treatment. CONCLUSION: The highness of insulin and c-peptide levels in the group that received treatment when compared to other groups and the lowness of oxidative markers such as SOD, catalase in this study can be explained by the fact that 1alpha,25(OH)(2)D(3) treatment prevents the intervention of apoptosis mechanism.

Comparing the osteogenic capacities of bone substitutes: hydroxyapatite, high-density porous polyethylene, and bone collagen: a biochemical and histological analysis.

Several inorganic materials have been shown previously to hold some osteogenic capacity. The purpose of this study is to compare the bone-forming abilities of hydroxyapatite ceramic, high-density porous polyethylene, and bone collagen within the periosteal island flap of rabbit tibia using histological and biochemical analysis. With this goal, four discrete experimental groups were formed, each comprising 22 New Zealand male rabbits. A sac was created on each rabbit tibial periosteum flap in each of the groups, and each of the previously mentioned materials was placed within this sac separately. One of these groups was thought as a control group without any material being placed inside the periosteal sac. Biopsies were taken at weeks 1, 2, 4, and 8 for biochemical analysis and at weeks 2 and 8 for histological evaluation. Neo-osteogenesis was evaluated quantitatively by determination of alkaline phosphatase and osteocalcin levels biochemically as well as by the percentage of new bone formation inside the periosteal sac histologically. Results show statistically that the osteogenic effect of high-density porous polyethylene is greater than that of the other materials used in this study (P < 0.05).

Alterations of brain tissue in fetal rats exposed to nicotine in utero: possible involvement of nitric oxide and catecholamines.

Histopathological changes in the brains of embryos from female rats treated with nicotine during pregnancy and possible involvement of nitric oxide (NO) and catecholamines in the nicotine-induced abnormalities of developing brain were investigated. Sexually mature female Wistar rats were given 1, 2, and 3 mg/kg nicotine hydrogen tartrate (NHT) subcutaneously for 20 days after mating. Levels of cotinine, a nicotine metabolite, in the maternal plasma increased dose-dependently. Fetus and fetal brain weights were significantly lower in all nicotine-treated groups. Light microscopy of hippocampal CA1 area showed a decrease in the number of cells per unit area. Electron microscopy of the same region revealed a dose-dependent increase in intracytoplasmic edema, mitochondrial swelling, dilation of rough endoplasmic reticulum, nuclear configurative abnormalities, and condensation of the nuclear chromatin. Nitrate + nitrite levels in fetal brain homogenates were significantly lower in the groups treated with 2 and 3 mg/kg NHT. Norepinephrine and normetanephrine (NMN) levels were significantly higher in 2 and 3 mg/kg NHT groups, as well as dopamine, 3-methoxy-4-hydroxyphenylethyleneglycole (MHPG), and dihydroxyphenylacetic acid levels in the 3-mg/kg NHT group. In conclusion, maternal nicotine exposure may lead to structural abnormalities of the fetal brain tissue and may result in decreased levels of NO and increased levels of catecholamines and their metabolites.

Agmatine attenuates neuropathic pain in rats: possible mediation of nitric oxide and noradrenergic activity in the brainstem and cerebellum.

Effect of agmatine (10-400 mg/kg) on neuropathic pain in a rat model produced by loose ligatures around the common sciatic nerve was studied. The involvement of possible alterations in nitric oxide (NO) levels [measured as its stable metabolites nitrate + nitrite] and in noradrenergic activity [measured as norepinephrine and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) levels] in this effect was also investigated biochemically in the brainstem and cerebellum. Agmatine increased the neuropathic pain threshold at 300 and 400 mg/kg. There was almost a twofold increase in nitrate + nitrite levels in the brainstem and cerebellum of the rats with neuropathic pain and agmatine decreased the high nitrate + nitrite levels only in the brainstem at 300 mg/kg and both in the brainstem and cerebellum at 400 mg/kg. Ligation of sciatic nerve resulted in almost twofold increase in norepinephrine and MHPG levels only in the brainstem of the rats. Agmatine decreased MHPG levels at 300 and 400 mg/kg, however it decreased norepinephrine levels only at the higher dose. These findings indicate that agmatine decreases neuropathic pain, an effect which may involve the reduction of NO levels and noradrenergic activity in the brain.