Increased Trimethylamine N-Oxide Is Not Associated with Oxidative Stress Markers in Healthy Aged Women.

Increased plasma trimethylamine N-oxide (TMAO) levels have been associated with cardiovascular diseases (CVD). L-carnitine induces TMAO elevation in human blood, and thus, it has been suggested as developing atherosclerosis. The aim of this study was to determine the relation between selected markers of oxidative stress and plasma TMAO concentration induced by L-carnitine supplementation for 24 weeks in healthy aged women. Twenty aged women were supplemented during 24 weeks with either 1500 mg L-carnitine-L-tartrate (n = 11) or isonitrogenous placebo (n = 9) per day. Fasting blood samples were taken from antecubital vein. L-carnitine supplementation induced an increase in TMAO, but not in γ-butyrobetaine (GBB). Moreover, there were no significant changes in serum ox-LDL, myeloperoxidase, protein carbonyls, homocysteine, and uric acid concentrations due to supplementation. Significant reduction in white blood cell counts has been observed following 24-week supplementation, but not attributable to L-carnitine. Our results in healthy aged women indicated no relation between TMAO and any determined marker of oxidative stress over the period of 24 weeks. At the same time, plasma GBB levels were not affected by L-carnitine supplementation. Further clinical studies of plasma GBB level as a prognostic marker are needed.

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women.

BACKGROUND: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. OBJECTIVE: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. METHODS: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. RESULTS: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. CONCLUSION: We demonstrated that -although oral L-carnitine supplementation significantly -increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.

l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function.

Skeletal muscle wasting, associated with aging, may be regulated by the inflammatory cytokines as well as by insulin-like growth factor 1 (IGF-1). l-carnitine possesses anti-inflammatory properties and increases plasma IGF-1 concentration, leading to the regulation of the genes responsible for protein catabolism and anabolism. The purpose of the present study was to evaluate the effect of a 24-week l-carnitine supplementation on serum inflammatory markers, IGF-1, body composition and skeletal muscle strength in healthy human subjects over 65 years of age. Women between 65 and 70 years of age were supplemented for 24 weeks with either 1500 mg l-carnitine-l-tartrate or an isonitrogenous placebo per day in a double-blind fashion. Before and after the supplementation protocol, body mass and composition, as well as knee extensor and flexor muscle strength were determined. In the blood samples, free carnitine, interleukin-6, tumor necrosis factor-α, C-reactive protein and IGF-1 were determined. A marked increase in free plasma carnitine concentration was observed due to l-carnitine supplementation. No substantial changes in other parameters were noted. In the current study, supplementation for 24 weeks affected neither the skeletal muscle strength nor circulating markers in healthy women over 65 years of age. Positive and negative aspects of l-carnitine supplementation need to be clarified.

Medium-chain triglycerides/long-chain triglycerides versus long-chain triglycerides in treatment of cancer patients with major body mass loss. Survival in patients with refractory cachexia.

INTRODUCTION: Currently there are no established guidelines regarding the use of long-chain triglycerides (LCT) vs. medium-chain triglycerides medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) in total parenteral nutrition (TPN). Severe malnutrition of patients with refractory cachexia (RC) often causes their disqualification from invasive methods of treatment thus decreasing their quality of life and survival time. AIM: To compare the changes in nutritional state of patients with RC receiving PN with LCT and LCT/MCT lipid emulsions and to assess the influence of enteral nutrition on their survival time. MATERIAL AND METHODS: The study group comprised of 50 patients (23 female, 27 male) with a median age of 66 years. Refractory cachexia was diagnosed in them due to dysphagia secondary to solid tumours causing obstruction of the gastrointestinal tract (GT). All patients were qualified for surgical gastrostomy due to contraindications to percutaneous endoscopic gastrostomy. The patients were randomly assigned into one of two groups and perioperatively received either LCT or LCT/MCT. Blood samples were collected four times and tested for: total protein, albumin, prealbumin, and C-reactive protein concentration. Patients received Home Enteral Nutrition after discharge from hospital. RESULTS: Changes in nutritional status parameters were similar among patients receiving lipid emulsions LCT vs. MCT/LCT in TPN for 11 days. The mean survival time of all patients operated to gain enteral access to nutrition was 192 ±268 days, and the median survival was 98 days. CONCLUSIONS: Regarding the short-term TPN, the results of the study do not demonstrate any superiority of MCT/LCT lipid emulsions over LCT, or vice versa. The inability to eat significantly accelerates unintended body mass loss among patients with RC. Disqualification from invasive treatment options deprives some patients of the benefits they might have obtained from the surgical access to GT and enteral nutrition.

Obesity and diet awareness among Polish children and adolescents in small towns and villages.

BACKGROUND: In addition to genetic predispositions and environmental factors, healthy lifestyle education is very important for children and adolescents. The purpose of this research was to estimate the number of overweight and obese children and adolescents from small towns and villages and to find out an association between health awareness in children and the risk of becoming overweight or obese. METHODS: The research was conducted in 1,515 healthy children aged 6-18 years from small towns and villages in Poland. Overweight was diagnosed when BMI for age and sex was over the 90th percentile; obesity--when it was over the 95th percentile. The study consisted of a lifestyle interview and anthropometrical measurements. The lifestyle interview was conducted with the use of an anonymous questionnaire form and included questions about food frequency, diet habits and physical activity. The research was analysed using the SAS System for Windows, release 8.02. RESULTS: Overweight status was diagnosed in 9.0% and obesity in 5.1% of respondents. Excess body mass was statistically more frequently diagnosed in girls than in boys aged 14-18 years. Girls of this age group significantly more frequently chose wholemeal bread, smoked sausages, meat and poultry as products that are believed to keep them fit. Older children substantially more often indicated that stress, smoking cigarettes, consuming fatty meat, sweets, being obese, and a lack of physical activity are factors that damage health. Boys spent more time in front of a computer or TV than girls; in the older group of children, the phenomenon even intensified. CONCLUSION: Awareness of healthy lifestyle behaviour is not sufficient to maintain optimal body mass. Knowledge about proper eating habits is better among girls than among boys, especially in the older age groups. However, in older groups, there was less physical activity due to spending more time in front of TV or the computer. High percentage of obese/overweight children and insufficient knowledge of nutrition may consequently result in increased risk of cardio-vascular diseases in adult population.

Evaluation of 12-lipoxygenase (12-LOX) and plasminogen activator inhibitor 1 (PAI-1) as prognostic markers in prostate cancer.

In carcinoma of prostate, a causative role of platelet 12-lipoxygenase (12-LOX) and plasminogen activator inhibitor 1 (PAI-1) for tumor progression has been firmly established in tumor and/or adjacent tissue. Our goal was to investigate if 12-LOX and/or PAI-1 in patient's plasma could be used to predict outcome of the disease. The study comprised 149 patients (age 70±9) divided into two groups: a study group with carcinoma confirmed by positive biopsy of prostate (n=116) and a reference group (n=33) with benign prostatic hyperplasia (BPH). The following parameters were determined by the laboratory test in plasma or platelet-rich plasma: protein level of 12-LOX, PAI-1, thromboglobulin (TGB), prostate specific antigen (PSA), C-reactive protein (CRP), hemoglobin (HGB, and hematocrit (HCT), as well as red (RBC) and white blood cells (WBC), number of platelets (PLT), international normalized ratio of blood clotting (INR), and activated partial thromboplastin time (APTT). The only difference of significance was noticed in the concentration of 12-LOX in platelet rich plasma, which was lower in cancer than in BPH group. Standardization to TGB and platelet count increases the sensitivity of the test that might be used as a biomarker to assess risk for prostate cancer in periodically monitored patients.

The concentration of 12-lipoxygenase in platelet rich plasma as an indication of cancer of the prostate.

AIM OF THE STUDY: The aim of this study was to determine whether measuring concentrations of 12-LOX in platelet-rich plasma patients can:Differentiate between the group of patients with prostate cancer and healthy men.Correlate the degree of severity of the disease and the concentration of the enzyme. MATERIAL AND METHODS: The study group comprised 88 men (40-88 years), including 54 patients diagnosed with prostate cancer. The population was divided into 4 groups:group 1 (22 men, aged 55-84 years) -with a negative biopsy,group 2 (36 men, aged 54-88 years) - with a positive biopsy result,group 3 (18 participants aged 58-83) - patients with cancer metastatic disease,group 4 of healthy men (12 people aged 40-66 years) - biopsy was not performed. Routine PSA, morphology and CRP analysis were performed and platelet rich plasma was used for 12(S)LOX determination using an ELISA kit. RESULTS: There was a weak (r = 0.0487) positive correlation between the number of blood platelets and plasma 12(S)LOX.An inverse relationship between 12(S)LOX and Gleason grade was found.Heterogeneity of 12(S)LOX in the group with prostate cancer metastatic disease may suggest differences in the response to the treatment carried out.There were no statistically significant differences in concentrations of 12(S)LOX in different groups of patients. CONCLUSIONS: Our results suggest that 12(S)LOX is relevant in prostate cancer; however, further study should include a larger, more select group of men with prostate cancer.

Association between intestinal and antioxidant barriers in children with cancer.

OBJECTIVE: Reactive oxygen species (ROS) play a role in cancerogenesis processing and damage tissues. Furthermore, oncological treatment may impair proper function of the gut barrier. The aim of this study was to measure intestinal permeability in children in clinical remission for solid tumours and to search for a possible relationship between free radicals and the intestinal barrier. No such investigation in children has been reported so far. RESEARCH METHODS AND PROCEDURES: The prospective study consisted of 19 paediatric patients with cancer after completion of chemotherapy. 32 healthy children from the outpatients clinics were recruited for measurement of intestinal permeability and antioxidant barrier as a control group. Intestinal permeability was assessed by measurement of urinary lactulose and mannitol after oral challenge. Antioxidant enzymes: superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in erythrocytes were assessed. Ischemia modified albumin (IMA) concentration was measured in serum. RESULTS: Cancer patients excreted less mannitol and more lactulose versus controls. The ratio of lactulose to mannitol was significantly higher in oncological children vs control (mean 0.188 and 0.0453, respectively, p=0.0006,). Significantly higher IMA level in the oncological group vs control was noted (mean 123.8 and 87.3 U/ml, respectively, p=0.0037). No correlation between intestinal permeability and oxidative stress barrier was found. CONCLUSIONS: Our data shows that intestinal barrier is damaged in paediatric cancer patients after chemotherapy. IMA is believed to play a protective role in the defence against tissue damage. No correlation was found between these two barriers.

L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia.

Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial ß-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤ 19 kg/m(2) and BMI >19 kg/m(2). Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤ 19 kg/m(2) had lower plasma FC and TC than those with BMI >19 kg/m(2). Skeletal muscle FC in the BMI ≤ 19 kg/m(2) group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤ 19 kg/m(2)) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

L-carnitine and cancer cachexia. II. Effects of lipid emulsion used in total parenteral nutrition on parameters of hemostasis and inflammatory state in L-carnitine deficiency in myocytes.

Cancer cachexia (CC), a progressive loss of body mass, leads to malnutrition and deficiencies of essential substances including polyunsaturated fatty acids (PUFAs) and L-carnitine (LC). The availability of these 2 compounds determines the rate of eicosanoid synthesis, which modulates inflammatory processes and hemostasis. We compared the effects of administration of emulsions containing long chain triglycerides (LCTs) relative to a 50:50 mix of medium chain triglycerides (MCTs) with LCTs on hemostasis and inflammatory reactions in patients with CC. The study was conducted on 50 patients with CC (23 women, 27 men) aged 66 ± 11 years with a mean loss in body weight of 21 ± 9% in the previous 6 months. Twenty patients received MCTs/LCTs while 30 received LCTs. Total parenteral nutrition (TPN) was administered using the 'all in one' method (25 kcal/kg/day, protein 1.2 g/kg/day). Selected parameters of coagulation and inflammatory state were evaluated on days 1, 5, 7 and 11 of TPN. Initial concentrations of D-dimers, fibrinogen, plasminogen activator inhibitor type 1 (PAI-1), fibronectin, CRP and IL-6 significantly exceeded the upper limit of the reference values. After 10 days of TPN, we detected significant differences in inflammatory state and hemostasis. Immunological state and hemostasis varied depending on the type of fat emulsion administered. The most likely reasons are the 2-fold higher concentrations of PUFAs in LCTs relative to MCTs/LCTs and a deficiency of LC in skeletal muscles. Both of these factors may contribute to the observed increase in the rate of eicosanoid synthesis.

Effect of aliskiren on proteinuria in non-diabetic chronic kidney disease: a double-blind, crossover, randomised, controlled trial.

AIM: To evaluate the proteinuria-lowering effect of a renin inhibitor (aliskiren), compared to placebo and to an angiotensin-converting enzyme inhibitor (perindopril), in patients with non-diabetic chronic kidney disease. METHODS: A randomised, double-blind, crossover trial was performed in 14 patients with nondiabetic chronic kidney disease with 24-h mean proteinuria of 2.01 g (95% CI, 1.36­2.66) and estimated creatinine clearance of 93±6.8 ml/min. The study consisted of five treatment periods. The patients were randomly assigned to receive aliskiren (150 mg), aliskiren (300 mg), perindopril (5 mg), perindopril (10 mg) or placebo. RESULTS: Aliskiren and perindopril reduced proteinuria. These effects were dose-dependent. Furthermore, 24-h proteinuria was reduced by 23% (mean 95% CI; 2­44) by treatment with aliskiren (150 mg), by 36% (95% CI, 17­55; P<0.001) with aliskiren (300 mg), by 7.1% (95% CI, 11­26) with perindopril (5 mg) and by 25% (95% CI, 11­39; P<0.05) with perindopril (10 mg), compared to placebo. No significant difference was found between the effects of aliskiren and perindopril. CONCLUSIONS: Aliskiren significantly reduced proteinuria. The antiproteinuric effect is probably similar to that of perindopril, for equivalent hypotensive dosages. The renin inhibitor provides a promising alternative approach for the treatment of patients with chronic proteinuric non-diabetic kidney disease.

Parameters of antioxidant barrier in different histopathologic types of pediatric cancers.

AIM OF THE STUDY: The goal of this study was to evaluate the activities of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the levels of glutathione (GSH) and ischemia-modified albumin (IMA), as potential markers in different histopathologic types of pediatric neoplasms. No studies on this subject have been reported to date. MATERIAL AND METHODS: SOD, GSH-Px, GSH, and IMA were measured before oncologic treatment in 129 children with neuroblastoma (NB), soft tissue sarcomas (STS), brain tumors, Hodgkin's disease (HD), and acute leukemias, and in 30 healthy controls. RESULTS: The statistical significance of SOD was observed in patients with brain tumors (median 1840.2 U/g Hb, p = 0.0500). The level of GSH was significantly higher in patients with NB (median 6.38 U/g Hb, p = 0.0031) and leukemias (5.16 U/g Hb, p = 0.0200). IMA was statistically significant in cases of STS, NB, and leukemias compared to healthy children (p = 0.0244, p = 0.0069, and p = 0.0000, respectively). The activity of GSH-Px was not statistically significant. CONCLUSIONS: The antioxidant barrier in all types of pediatric cancers is disturbed. None of the measured parameters was specific enough to represent a reliable marker for any particular histopathologic type of children's neoplasm.

Influence of megestrol acetate on nutrition, inflammation and quality of life in dialysis patients.

AIM: Malnutrition is a common clinical problem in dialysis patients. The objective of this study was to evaluate the efficacy and safety of megestrol acetate in malnourished dialysis patients. Thirty-two hypoalbuminemic dialysis patients took 160 mg of megestrol acetate daily for up to 6 months. METHODS: We measured height, dry weight, BMI, modified Subjective Global Assessment (SGA) score, and serum albumin, triglycerides, total cholesterol, hsCRP, IL-1ß and IL-6 concentrations. We used validated questionnaires to evaluate selected dimensions of the quality of life. RESULTS: Only 12 patients completed the study. All patients reported improved appetite, and there were concurrent statistically significant increases in weight, BMI, SGA and albumin concentration (P < 0.05). For the 12 patients who completed 6 months of treatment the increase in these parameters was from 63.26 ± 13.04 to 65.58 ± 12.53 kg, from 23.5 ± 3.8 to 24.66 ± 4.23 kg/m(2), from 5.16 ± 0.94 to 6.16 ± 0.72 points, and from 36.45 ± 1.82 to 40.33 ± 2.71 g/l, respectively. However, there were no significant changes in the levels of inflammatory markers and in quality of life. Side effects included overhydration, excessive weight gain and hyperglycaemia. CONCLUSION: Megestrol acetate may be effective in reversing poor appetite in carefully selected maintenance dialysis patients, but it might not reduce inflammation or improve the quality of life. Because of the potential side effects, close monitoring is essential.

The antioxidant status and response to therapy in children with soft tissue sarcomas and neuroblastoma.

BACKGROUND: Antioxidant systems in cells maintain the proper homeostasis of reactive oxygen species, which at high concentrations can induce carcinogenesis. The aim of this study was to evaluate the serum levels of ischemia-modified albumin (IMA), erythrocyte superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) as markers for prognosis in children with neuroblastoma (NB) and soft tissue sarcomas (STS), two cancer types for which reliable prognostic factors are needed. PROCEDURE: SOD, GSH-Px, and IMA were measured before and during responses to therapy assessment in 99 children with NB and STS and in 30 healthy controls. RESULTS: There were no statistically significant differences in the erythrocyte SOD and GSH-Px activities between the patients with cancer and healthy controls. The levels of IMA in patients with STS and NB were found to be significantly higher than in the controls (P = 0.0013; P = 0.0066, and 0.0164, respectively). Decreased activities of SOD and GSH-Px were found in all patients with poor-responding (PRS) cancers and decreased SOD activity was found in patients with PRS NB. An increase in GSH-Px was observed in patients with good-responding (GR) NB. All patients with GR cancers demonstrated higher SOD and GSH-Px activities than patients with PRS cancers. CONCLUSIONS: While determining the levels of specific antioxidants as antioxidant-barrier parameters in children with cancer may be valuable in predicting therapeutic responses as well as outcomes, additional studies are required.

Diverse inhibition of plasminogen activator inhibitor type 1 by theaflavins of black tea.

Fruits, vegetables, spices and a variety of teas are suggested for the prevention of many diseases. They encompass active, non-nutritional ingredients called nutraceuticals which are defined as food products that provide health benefits. Many nutraceuticals have been tested to identify inhibitors of plasminogen activator inhibitor (PAI-1). PAI-1 is the major and fast acting physiological inhibitor of fibrinolysis. However, preclinical studies of PAI-1 inhibitors have revealed an additional role of PAI-1 in the pathogenesis of vascular remodeling, renal injury, diabetes, obesity, Alzheimer's disease and cancer. Thus PAI-1 is a potential therapeutic target in some of these diseases. Our previous study revealed that a black tea extract (containing mostly theaflavins) inhibits PAI-1. In this study we report results for four pure (>98%) theaflavins. Inactivation of PAI-1 was tested by clot formation and by its lysis using thromboelastometry and measurements of human plasma turbidity. Among four tested theaflavins, theaflavin-3'-gallate was the most potent in PAI-1 inhibition trailed by theaflavin-3,3'-digallate, while the other two i.e., theaflavin and theaflavin-3-gallate did not show inhibitory activity.

Effects of renal-specific oral supplementation in malnourished hemodialysis patients.

BACKGROUND: Protein-energy malnutrition is still a problem in patients with chronic renal failure, especially during replacement renal therapy. The chronic inflammatory status in these patients intensifies the malnutrition, as well as making treatment more complicated. The aim of the present study was to estimate the influence of oral supplementation on the nutritional status of malnourished hemodialysis (HD) patients depending on the existence of an inflammatory state. METHODS: To study the influence of oral supplementation on nutrition status, 30 HD patients with protein-energy malnutrition characteristics and 25 well-nourished HD patients were enrolled in the study. Malnourished HD patients were prescribed Renilon 7.5 at an oral intake dose of 125 mL twice a day for 3 months. The nutritional status was characterized based on body mass index, Subjective Global Assessment score, serum albumin and prealbumin concentrations. The intensity of the inflammatory state was determined by C-reactive protein and interleukin-6. Serum concentrations of leptin and adiponectin were also measured. RESULTS: After 3 months of supplementation, malnourished patients had an increase in prealbumin, albumin, and leptin concentrations. No statistically significant differences were observed between patients lacking inflammation and those with inflammation. CONCLUSIONS: The results indicate an improvement in the nutritional status of HD patients who were prescribed an oral supplementation. Furthermore, patients with inflammatory state characteristics also benefited from Renilon 7.5 treatment.

Atorvastatin improves tubular status in non-diabetic patients with chronic kidney disease - placebo controlled, randomized, cross-over study.

BACKGROUND: There is evidence that dyslipidemia is associated with chronic kidney disease (CKD) and it has been implicated in the progression of renal damage. Optimal management of dyslipidemia should therefore lead to renal benefits. A number of experimental models demonstrate a beneficial effect of statins in ameliorating renal damage. However, the exact mechanism by which statins protect against renal damage remains unclear. METHODS: In a placebo-controlled, randomized, cross-over study we evaluated the influence of atorvastatin (ATO) 40 mg/day added to the renin-angiotensin-aldosterone systeme (RAAS) blockade on proteinuria and surrogate biomarkers of tubular damage or injury in 14 non-diabetic patients with proteinuria (0.4-1.8 g per 24 h) with normal or declined kidney function (eGFR 55-153 ml/min). In the eight-week run-in period, therapy using angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II subtype 1 receptor antagonists (ARB) was adjusted to achieve a blood pressure below 130/80 mm Hg. Next, patients were randomly assigned to one of two treatment sequences: ATO/washout/placebo or placebo/washout/ATO. Clinical evaluation and laboratory tests were performed at the randomization point and after each period of the study. The primary end point of this study was a change in proteinuria measured as 24-h urine protein excretion (DPE). Secondary end points included urine N-acetyl-ß-D-glucosaminidase (NAG) and α1-microglobulin (α1m) excretion. RESULTS: The ATO therapy significantly reduced urine excretion of α1m (p=0.033) and NAG (p=0.038) as compared to placebo. There were no differences in proteinuria, blood pressure, eGFR and serum creatinine between the ATO and placebo groups. CONCLUSION: Atorvastatin treatment is safe and improves biomarkers of tubular damage or injury in non-diabetic patients with CKD.

Adipokines, endothelial dysfunction and nutritional status in peritoneal dialysis patients.

OBJECTIVE: Adipokines such as leptin and adiponectin are adipocyte-specific secretory proteins that play important roles in the metabolic regulation of body weight, insulin resistance and cardiovascular complications. The relationship between the malnutrition-inflammation complex syndrome and high levels of some adipokines in peritoneal dialysis (PD) patients is still unclear. An association between high body mass index (BMI) and improved survival in PD patients has also been proposed. The purpose of this study was to investigate the levels of plasma adipokines and inflammation and oxidative stress markers in overweight and normal weight PD patients. MATERIAL AND METHODS: Thirty PD patients (12 M, 18 F; mean age 57.3 ± 16.6 years) were examined and 23 healthy volunteers were included as a control group. The levels of high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, leptin, the leptin receptor, adiponectin, malondialdehyde/4-hydroxynonenal, oxidized low-density lipoprotein, carbonyl groups and asymmetric dimethylarginine (ADMA) were measured in both groups. The nutritional status of each patient was determined by albumin levels, BMI, percentage of body fat (%F), lean body mass (LBM) and the Subjective Global Assessment (SGA) score. The adequacy of dialysis was estimated by weekly Kt/V measurements. RESULTS: According to the seven-point SGA scores and the albumin levels, the nutrition status of 15 patients was good (6-7 points), while 15 patients were mildly malnourished (3-5 points). The concentrations of hsCRP, leptin and adiponectin were statistically higher in the PD group than in the control group (p < 0.05). Markers of oxidative stress and inflammation were also higher in the PD group. The adiponectin level was inversely correlated with %F and BMI (Spearman's R = -0.3, p ≤ 0.05) and positively correlated with hsCRP level (R = -0.4). The level of leptin was positively correlated with %F, BMI and LBM (R = 0.4, p ≤ 0.05). Patients with normal BMI values had lower leptin concentrations (50.2 vs 242.8 µg/l) and higher adiponectin levels (30.0 vs 20.3 µg/ml) than overweight patients. The statistical analysis indicated that there were no differences in oxidative stress, inflammation and ADMA concentration between the lean and overweight PD patients. CONCLUSION: The nutritional status of lean and overweight patients was comparable. Signs of malnutrition were detected in both groups. The severity of chronic inflammation and oxidative stress were not related to BMI in PD patients.

The effect of N-acetylcysteine on blood pressure and markers of cardiovascular risk in non-diabetic patients with chronic kidney disease: a placebo-controlled, randomized, cross-over study.

BACKGROUND: Cardiovascular complications in patients with chronic kidney disease (CKD) are frequent. They show increased cardiovascular mortality and morbidity attributable to accumulation of several risk factors; e.g., hypertension, oxidative stress and elevated plasma homocysteine concentration. Despite recent progress in their management, there is still no optimal therapy that can stop progression of CKD and decrease cardiovascular outcome in these patients. Antioxidants, e.g., N-acetylcysteine (NAC), have been suggested as a promising medicament in this field. MATERIAL/METHODS: In a placebo-controlled, randomized, two-period cross-over study we evaluated the influence of eight weeks of NAC therapy (1200 mg/day) added to pharmacological renin-angiotensin system blockade on ambulatory blood pressure and surrogate markers of cardiovascular risk and injury in 20 non-diabetic patients with albuminuria [30-915 mg per creatinine mg] and normal or slightly decreased kidney function [eGFR 61-163 ml/min]. After eight weeks run-in period during which the therapy using angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers was settled, patients were randomly assigned to one of two treatment sequences: NAC/washout/placebo or placebo/washout/NAC. RESULTS: No significant changes in blood pressure, albuminuria and homocysteine plasma level were observed. CONCLUSIONS: NAC had no effect on blood pressure and surrogate markers of cardiovascular injury in non-diabetic patients with CKD.