Cardiovascular risk assessment and homocysteine and leptin levels in peritoneal dialysis and hemodialysis patients.

In the present study, we used high sensitivity C-reactive protein (hs-CRP) analysis in combination with lipid screening [which has been reported to be a more valuable risk marker than other novel markers such as homocysteine (Hcy) and lipoprotein a] to perform cardiovascular risk assessment in peritoneal dialysis (PD) and hemodialysis (HD) patients. We selected 9 PD patients, 10 HD patients, and 9 control subjects for the study. In those patients, we determined levels of serum lipids, hs-CRP, Hcy, vitamin B12, folic acid, and leptin. Patients on PD had a significantly elevated hs-CRP concentration (3.14 +/- 0.79 mg/L) and ratio of total cholesterol (TC) to high density lipoprotein (HDL) cholesterol (4.71 +/- 0.40), and their cardiovascular risk was found to be three times that of control subjects. In HD patients, the elevation of hs-CRP was more profound (5.66 +/- 1.30), but their TC:HDL ratio fell within the normal range (3.18 +/- 0.13). However, a cardiovascular risk assessment of the HD group showed the same risk as in the PD group. Serum Hcy was also elevated in patients on PD (54.95 +/- 18.08 microl/L) and on HD (25.33 +/- 3.70 micromol/L) as compared with healthy subjects (13.76 +/- 0.94 micromol/L). Folic acid and vitamin B12 levels (needed to remethylate Hcy to methionine) were not compromised in the dialysis population. On the other hand, leptin secreted by adipose tissue was found to be mildly higher in PD patients (37.08 +/- 12.59 ng/mL). The mean leptin level in control subjects was 14.14 +/- 3.60 ng/mL. The proinflammatory and proangiogenic action of excess leptin may aggravate cardiovascular risk in PD patients. Increased values of known risk factors were found in dialysis patients on PD and on HD. However, lower levels of HDL cholesterol, higher cardiovascular risk assessment and Hcy levels, and mildly increased leptin levels seem to increase the potential threat of vascular disease in PD patients more than in HD patients.

The evaluation of oxidative stress in patients with chronic renal failure.

BACKGROUND: Free radical-mediated changes are thought to be involved with atherosclerosis in patients with chronic renal failure. METHODS: The protein carbonyl and malondialdehyde (MDA) levels in serum as the markers of radical-induced protein and lipid oxidations were measured in chronic renal failure patients. RESULTS: Serum carbonyl and MDA levels in both hemodialysis and peritoneal dialysis patients were not found to be different as compared with healthy subjects. In both patient groups, the approximately twofold increment in total antioxidant activity (ferric reducing/antioxidant power; FRAP) and uric acid values in serum were found. The high uric acid levels in both patient groups might be partly responsible for the increment in FRAP values. In addition, all patients received multivitamin preparations including ascorbate, which was also a major antioxidant in serum. CONCLUSIONS: Our data suggest that oxidative stress does not become the major threat for patients with chronic renal failure. The increment in endogenous and exogenous antioxidant capacities in serum might be thought to prevent any possible radical-induced damage in patients with chronic renal failure. In addition, the increased nitric oxide (NO) levels especially in hemodialysis patients might likely favor an antioxidant effect.

[The role of supplementation or inhibition of nitric oxide production in burn injury to reduce ischemic damage]. / Yanikta nitrik oksit üremtiminin desteklenmesi veya azaltilmasinin iskemik hasari azaltmadaki rolü.

BACKGROUND: To determine the role of nitric oxide (NO) which is vasodilator agent and inflammatory cytokine, in burn injury. METHODS: Rats were divided into 5 groups, and a 30 % burn was inflicted. In addition to sham control and burn control groups, other 3 groups were given L-Arginine, and L-nitro-L-Arginine methylester (L-NAME), and both. Neutrophil and hematocrit percentage in blood, NO, TNF-alpha and malondialdehyde (MDA) levels in plasma and neutrophil infiltration in the lung were evaluated at 24 hours after thermal injury. RESULTS: The inhibition of NO production with L-NAME treatment significantly decreased these parameters when compared to burned control group. MDA was decreased significantly in all groups which were given drugs. CONCLUSION: The induction and inhibition of NO production both reduced lipid peroxidation but induction increased the mortality, plasma TNF-alpha and neutrophil in the blood. Inhibition of NO production is found more useful after thermal injury in rats.

Adiponectin is a link among inflammation, insulin resistance, and high-density lipoprotein cholesterol but is not associated with paraoxonase activity in premenopausal women.

The aim of this study was to evaluate whether insulin sensitivity, inflammatory response, and plasma lipid profile are associated with circulating adiponectin levels in nondiabetic healthy women. The authors also assessed whether adiponectin has any effect on high-density lipoprotein cholesterol-linked paraoxonase 1 (PON-1) activity and on the susceptibility of low-density lipoproteins to oxidation. Plasma adiponectin was measured in 91 nondiabetic premenopausal women, and the patients were then divided into quartiles. Circulating adiponectin was found to be associated with body mass index (r=.55, P<.001). After adjustment for body mass index, adiponectin showed an inverse correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r=-.41, P<.001) and a positive correlation with high-density lipoprotein cholesterol (r=.43, P<.001). In linear regression analysis, HOMA-IR, tumor necrosis factor alpha, and high-density lipoprotein cholesterol levels were found to be independently associated with adiponectin. However, high-density lipoprotein cholesterol-linked PON-1 activity and the susceptibility of low-density lipoproteins to in vitro oxidation did not seem to be related to plasma adiponectin concentrations.

Unchanged asymmetric dimethylarginine levels in non-diabetic, premenopausal obese women who have common risk factors for cardiovascular disease.

This study was performed to test whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to obesity and obesity complications including decrement in insulin sensitivity and adiponectin levels, dyslipidemia and low-grade inflammation. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations were analyzed by HPLC in 17 overweight (BMI > or = 25 kg/m2) and 40 obese (BMI > or = 30 kg/m2) premenopausal women. Age-matched healthy women were studied as controls. Obesity did not give rise to a significant change in circulating ADMA levels but reduced in SDMA levels. As compared with control subjects (0.441 +/- 0.102 microM), ADMA values in overweight and obese subjects were found to be as 0.412 +/- 0.102 and 0.436 +/- 0.093, respectively. No Pearson's association of ADMA with relevant risk variables for cardiovascular disease, including blood pressure, insulin sensitivity, inflammatory markers, lipid and adiponectin levels. However, in linear regression analysis, BMI, diastolic blood pressure, glucose, insulin, and IL-8 emerged as significant predictors of ADMA. In spite of obese women have elevated hs-CRP, triglyceride levels and decreased insulin sensitivity, adiponectin and HDL-cholesterol levels, all of which is closely linked risk factors for cardiovascular disease, circulating ADMA levels remained unchanged in obese individuals as compared with controls.

A study on the relationship between homocysteine and diabetic nephropathy in rats.

Hyperhomocysteinemia is known to be associated with many of the occlusive vascular diseases including ischemic heart disease. Elevated plasma total homocysteine (t-Hcy) is also remarkably common among patients with moderate to severe renal failure. The purpose of this study was to investigate the role of homocysteine (Hcy) in the pathogenesis of diabetic nephropathy in the rat. Additionally, any effect of aminoguanidine (AG), an inhibitor of advanced glycation end product (AGE) formation, on the onset of nephropathic symptoms and on the concentrations of Hcy was searched for. Diabetes was induced in male Wistar albino rats (6 months old) by a single injection of 50 mg x kg (-1)streptozotocin (STZ) into the penile vein. Animals with blood glucose levels higher than 350 mg x dl (-1)72 h after STZ injection were included in the study. Age-matched rats receiving a single dose of citrate buffer served as controls. One half of the control and diabetic groups received AG via drinking water (1 g l (-1)). The experimental period lasted for ten weeks. Animals were killed by cardiac venipuncture after 24 hour urine samples were collected. Serum t-Hcy was quantified using HPLC, and urinary GAGs using the spectrophotometric 1,9-dimethyl methylene blue dye method. Serum glucose, protein, creatinine and total sulfydryl (t-SH) measurements, and urinary protein determinations were carried out spectrophotometrically. In diabetic rats, serum t-Hcy levels were significantly decreased (P< 0.001), and were negatively correlated with the urinary protein concentration (r= -0.67, P< 0.05). Urinary GAG levels were also increased in diabetic rats (P< 0.001). AG neither affected the t-Hcy levels, nor ameliorated the nephropathic symptoms. These results indicate that diabetic nephropathy is not linked to homocysteinemia in the rat.