Arginine/asymmetric dimethylarginine ratio and cardiovascular risk factors in patients with predialytic chronic kidney disease

ObjectivesAsymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) that accumulates in patients with chronic kidney disease (CKD) and predicts cardiovascular outcome. Arginine is the substrate for NOS and a low arginine/ADMA ratio may lead to a reduced NO production and a worse prognosis. We have studied how other important CKD variables predict the arginine/ADMA ratio.Design and methodsThe population is 160 predialytic CKD patients (median age 61 years). We used backward stepwise regression to indentify the best predictors of p-arginine, p-ADMA and arginine/ADMA ratio.ResultsP-ADMA was predicted by estimated GFR (eGFR) (adjusted R² = 0.17, p > 0.00). Arginine/ADMA ratio was predicted by gender, eGFR, use of renin angiotensin aldosteron (RAAS) inhibitors, current smoking and use of platelet inhibitors (adjusted R² = 0.18, p < 0.00).ConclusionsReduced eGFR is associated with reduced arginine/ADMA ratio. The use of RAAS inhibitors and male gender may be protective against a low arginine/ADMA ratio.     

Serum vascular adhesion protein-1 is higher in subjects with early stages of chronic kidney disease

ObjectivesAn increased level of serum vascular adhesion protein-1 (VAP-1) has been found in patients with diabetes mellitus and vascular disorders. This study examined whether serum VAP-1 levels are associated with chronic kidney disease (CKD).Design and methodsWe included 262 subjects aged 30 and above with fasting plasma glucose level < 7 mmol/L checked within 1 year. First morning urine specimens were collected. Microalbuminuria was defined if urinary albumin-to-creatinine ratio ≥ 30 μg/mg creatinine. The glomerular filtration rate (GFR) was estimated. CKD stages were defined according to the suggestions of the National Kidney Foundation. Serum VAP-1 levels were analyzed by immunofluorometric assay.ResultsSerum VAP-1 levels were positively associated with the urinary albumin-to-creatinine ratio ( r = 0.29, p < 0.0001) and negatively associated with estimated GFR (r = ?0.24, p =  0.0001). Subjects with CKD stage 2 (N =  51) and stage 3 (N =  91) had significantly higher levels of serum VAP-1 than those without CKD (p =  0.0003 and p =  0.035, adjusted for age and gender, respectively). A high serum VAP-1 level was associated with the presence of CKD (OR 1.63 for 1 SD increase of VAP-1, p =  0.018), adjusting for age, sex, and smoking. Ordered logit models revealed that high serum VAP-1 levels correlated with advanced stages of CKD.ConclusionsSerum levels of VAP-1 are associated with the severity of kidney damage or stages of kidney disease. The true mechanism which links the serum VAP-1 and CKD remains to be elucidated in further studies.     

Diabetes in pregnancy: Effect on glycation and acetylation of the different chains of fetal and maternal hemoglobin

BackgroundMeasurement of glycated fetal hemoglobin to assess maternal glycemic control is unreliable. Electrospray ionization–mass spectrometry (ESI-MS) has been suggested as a definitive procedure.ObjectiveThis study aimed to evaluate glycation and acetylation by ESI-MS of the separate chains of neonatal fetal hemoglobin in comparison with glycation of maternal hemoglobin, to assess the impact of maternal diabetes.MethodsTwenty-nine non-diabetic (31 neonates) and 15 diabetic women (15 neonates) were recruited. Whole blood was collected at delivery from the mothers and cord blood from their respective neonate. The blood samples were diluted in acetonitrile:water (50:50) and treated with a cation exchange resin to remove sodium and potassium adducts on the hemoglobin. The α- and β-chain glycated maternal hemoglobin and α- and γ-chain glycated and acetylated hemoglobin of the neonate were measured by ESI-MS. HbA1c was measured on the Menarini 8160.ResultsMean α- and γ-chain and overall glycated hemoglobin and acetylated fetal hemoglobin were 1.23 ± 0.41%, 1.62 ± 0.47%, 1.24 ± 0.37%, and 8.56 ± 0.84% in the infant of the non-diabetic mother (INDM) and 1.39 ± 0.21%, 1.92 ± 0.61%, 1.64 ± 0.59%, and 8.44 ± 0.63% in the infant of the diabetic mother (IDM). Mean maternal α- and β-chain, overall glycated hemoglobin and HbA1c were 1.98 ± 0.38%, 4.28 ± 0.76%, 3.13 ± 0.51%, 5.39 ± 0.39% (non-diabetic) and 2.40 ± 0.83%, 4.71 ± 0.90%, 3.58 ± 0.83%, 6.15 ± 0.71% (diabetic). Overall glycated hemoglobin levels were significantly higher in the IDM (p = 0.006) compared to the INDM. Maternal glycated hemoglobin was significantly higher than neonatal glycated hemoglobin in the control (p < 0.0001) and diabetic group (p < 0.0001). A significant correlation was observed between maternal glucose concentration and overall glycated fetal hemoglobin in the IDM (p = 0.02). Glucose concentrations in the diabetic mother and the IDM were not significantly different (p = 0.5) and were significantly correlated (p < 0.0001). HbA1c was not significantly different in the two maternal groups. No significant difference was observed between AcHbF in IDM or INDM (p = 0.61).ConclusionsMeasurement of overall glycated fetal hemoglobin, incorporating α- and γ-chain glycations, seems best to assess abnormal glucose homeostasis during pregnancy. Accurate assay of this parameter is critical for stratification of risk of possible post birth developmental complications.     

Influence of diabetes on homocysteine-lowering therapy in chronic hemodialysis patients

IntroductionThe effect of homocysteine (Hcy)-lowering therapy may be different in hemodialysis (HD) patients with and without diabetes mellitus (DM).MethodsStable HD patients with uremia were administered folic acid and vitamin B for 3 months. The impact of treatment was compared in patients with and without DM.ResultsA total of 61 patients (31 men and 30 women) aged 56 ± 13 y completed the study. Among these, 44 patients (72%) did not have DM and 17 (28%) had DM. At baseline, total Hcy and high-sensitivity C-reactive protein (hsCRP) levels were similar. After treatment, the levels of total Hcy and hsCRP were significantly decreased in the nondiabetic group (total Hcy level decreased from 33.63 ± 14.13 μmol/l to 18.94 ± 8.46 μmol/l, p < 0.001; hsCRP level decreased from 0.58 mg/dl [range, 0.21–1.05 mg/dl] to 0.22 mg/dl [range, 0.11–0.53 mg/dl], p < 0.001) but not in the diabetic group (total Hcy level decreased from 34.97 ± 17.12 μmol/l to 29.53 ± 11.36 μmol/l, p = 0.057; hsCRP level decreased from 0.80 mg/dl [range, 0.24–1.47 mg/dl] to 0.49 mg/dl [range, 0.45–0.98 mg/dl], p = 0.28). Serial monitoring of total Hcy level showed a more sustained effect of therapy on patients without DM.ConclusionFolic acid and vitamin B administration significantly lower total Hcy and hsCRP levels in HD patients without DM but not in those with DM.     

Laboratory investigation and follow-up of chronic kidney disease stage 3 in primary care

BackgroundTo explore how CKD stage 3 patients are examined and treated in primary care with emphasis on laboratory analyses.MethodsA total of 386 patients with CKD stage 3, and their physician (one patient per general practitioner (GP)) were selected from hospital laboratory databases. GPs received a questionnaire asking them to categorize their patients' renal function based on creatinine and eGFR results, denoting follow-up and what changes in creatinine and eGFR results were considered clinically important.ResultsThe response rate was 60%, and 210 patients were included. Patients' median creatinine values were 95 μmol/L (females) and 124 μmol/L (males), the median eGFR value was 52 ml/min/1.73 m². Only 27% of patients were assessed to have CKD stage 3. 2/3 had either a urine dip strip (59%) and/or a urine albumin measurement (42%) and 20% were diagnosed with albuminuria. Median changes to signal improvement or deterioration in renal function or indicate referral were 14 (12%), 20 (18%) and 40 (36%) μmol/L for creatinine and 8 (17%), 8 (17%) and 13 (26%) ml/min/1.73 m² for eGFR. Albuminuria did not influence follow-up strategy.ConclusionsCKD stage 3 patients were insufficiently examined for albuminuria and seemingly referred to hospital care after larger eGFR declines than recommended in guidelines.     

Closing the anion gap: contribution of D-lactate to diabetic ketoacidosis

BackgroundA high anion gap in diabetic ketoacidosis (DKA) suggests that some unmeasured anions must contribute to the generation of the anion gap. We investigated the contribution of d-lactate to the anion gap in DKA.MethodsDiabetic patients with and without DKA and high anion gap were recruited. Plasma d-lactate was quantified by HPLC. Plasma methylglyoxal was assayed by liquid chromatography-tandem mass spectrometry.ResultsThe plasma fasting glucose, β-hydroxybutyrate, and blood HbA1c levels were highly elevated in DKA. Plasma anion gap was significantly increased in DKA (20.59 ± 6.37) compared to either the diabetic (7.50 ± 1.88) or the control group (6.53 ± 1.75) (p < 0.001, respectively). Moreover, plasma d-lactate levels were markedly increased in DKA (3.82 ± 2.50 mmol/l) compared to the diabetic (0.47 ± 0.55 mmol/l) or the control group (0.25 ± 0.35 mmol/l) (p < 0.001, respectively). Regression analysis demonstrated that d-lactate was associated with acidosis and anion gap (r = 0.686, p < 0.001).ConclusionsPlasma d-lactate levels are highly elevated and associated with metabolic acidosis and the high anion gap in DKA. Laboratory monitoring of d-lactate will provide valuable information for assessment of patients with DKA.     

Serum tartrate-resistant acid phosphatase 5b (TRACP5b) activity as a biomarker for bone metastasis in non-small cell lung cancer patients

BackgroundDiagnosis and follow-up of bone metastasis (BMet) in non-small cell lung cancer (NSCLC) patients usually rely on symptoms and image studies. A serum marker of bone resorption may improve the quality of treatment in such patients. Tartrate-resistant acid phosphatase 5b (TRACP5b) is a specific marker for osteoclasts and we proposed it can be used as a marker of BMet in NSCLC patients.MethodsIn November 2002 till August 2008 serum samples were obtained from 141 newly diagnosed stage IIIA, IIIB or IV NSCLC patients and 41 normal subjects. All patients received baseline bone scintinography examination and evaluation of clinical symptoms as a standard of BMet diagnosis. Patients were divided into 2 groups by having BMet (Group I, n = 72) or not (Group II, n = 69). An in-house immunoassay using a TRACP-specific monoclonal antibody, 14G6, was used to measure the serum TRACP5b activity at pH 6.1.ResultsThe mean serum TRACP5b activities of Group I, Group II and normal subjects were 3.50 ± 2.23 U/l, 2.09 ± 0.72 U/l and 2.33 ± 0.52 U/l, respectively. After adjusting for age, stage, gender, and histology in a generalized linear model, Group I has significantly higher TRACP5b activity than Group II (p < 0.001). The receiver operating characteristic analysis established a cutoff value of 2.551 U/l to identify BMet in NSCLC patients with a sensitivity of 63.9% and a specificity of 76.8%. TRACP5b activity declined in patients who responded to treatment (p = 0.047), and elevated in patients who developed new BMet (p = 0.05).ConclusionsSerum TRACP5b activity test is a potentially useful adjunct in diagnosing and monitoring BMet in NSCLC. Further study is warranted to establish its real value in diagnosis and monitoring of BMet in NSCLC patients.     

Impaired GFR is the most important determinant for FGF-23 increase in chronic kidney disease

ObjectivesIt is unclear whether fibroblast growth factor-23 (FGF-23) increases in response to phosphate accumulation or to decrease clearance in chronic kidney disease (CKD) as is the case with other low molecular weight proteins such as cystatin C (CysC).Design and methodsThis cross-sectional study measured serum FGF-23, CysC, and other serum markers of bone metabolism in 69 patients, aged 18 months–24 years, with various stages of CKD (eGFR = 11–214 mL/min).ResultsFGF-23 levels were significantly correlated with CysC and parathyroid hormone levels (PTH) on univariate non-linear regression analysis. In multivariate linear regression analysis, log (CysC) (β = 0.660, p < 0.0001), log (PTH) (β = 0.038, p = 0.37), and phosphate (β = 0.222, p = 0.028) explained 69.1% of the variance of FGF-23.ConclusionsCysC had the largest unique contribution to FGF-23 variance in this model, supporting the hypothesis that renal clearance may be the most responsible factor for elevated FGF-23 levels in early stages of CKD.     

Cystatin C as a predictor of all-cause mortality and myocardial infarction in patients with non-ST-elevation acute coronary syndrome

ObjectivesTo investigate the predictive value of cystatin C among patients diagnosed with non-ST-elevation acute coronary syndrome (nSTE-ACS).Design and methodsAdmission serum samples from 245 nSTE-ACS patients were measured with a novel cystatin C immunoassay based on a dry-reagent, double monoclonal design. Creatinine concentrations, estimated glomerular filtration rates (eGFR) and one-year follow-up data were available for these patients.ResultsDuring the follow-up period, 34 (14%) of patients had myocardial infarction (MI) and 25 (11%) died. Increased serum cystatin C was an independent predictor of all-cause mortality and combined events (all-cause mortality and MI) after adjustment to non-biomarker baseline factors, hazard ratio (HR) 2.19 (per increase of 1 tertile; 95% Cl 1.28–3.78, p = 0.0046) and 1.75 (1.22–2.51, p = 0.0024), respectively. Corresponding values for eGFR were 2.56 (1.43–4.59, p = 0.0016) and 1.76 (1.23–2.53, p = 0.0022), respectively. Creatinine was not an independent predictor of endpoints (p > 0.05).ConclusionsCystatin C was associated with an increased risk of death and combined events in patients with nSTE-ACS.     

Anserine inhibits carnosine degradation but in human serum carnosinase (CN1) is not correlated with histidine dipeptide concentration

BackgroundWe reported an association of a particular allele of the carnosinase (CNDP1 Mannheim) gene with reduced serum carnosinase (CN1) activity and absence of nephropathy in diabetic patients. Carnosine protects against the adverse effects of high glucose levels but serum carnosine concentration was generally low.MethodsWe measured the concentration of two further histidine dipeptides, anserine and homocarnosine, via HPLC. CN1 activity was measured fluorometically and for concentration we developed a capture ELISA.ResultsWe found an association between the CNDP1 Mannheim allele and reduced serum CN1 activity for all three dipeptides but no correlation to serum concentrations although anserine and homocarnosine inhibited carnosinase activity. Patients with liver cirrhosis have low CN1 activity (0.24 ± 0.17 μmol/ml/h, n = 7 males; normal range: 3.2 ± 1.1, n = 104; p < 0.05) and CN1 concentrations (2.3 ± 1.5 μg/ml; normal range: 24.9 ± 8.9, p < 0.05) but surprisingly, histidine dipeptide concentrations in serum are not increased compared to controls.ConclusionsSerum histidine dipeptide concentrations are not correlated to CN1 activity. The protective effect of low CN1 activity might be related either to turnover of CN1 substrates or a protective function of dipeptides might be localized in other tissues.     

Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES-31)

ObjectiveTo assess the association of high sensitivity C-Reactive Protein [hsCRP] and Tumour Necrosis Factor-α [TNF-α] with IMT in Asian Indians with different grades of glucose intolerance.Design and methodsSubjects with normal glucose tolerance [NGT](n = 150), impaired glucose tolerance [IGT] (n = 150) and type 2 diabetes (DM) (n = 150) were recruited from the Chennai Urban Rural Epidemiology Study [CURES], in south India. hsCRP was estimated by nephelometry and TNF-α by enzyme linked immunosorbent assay. Carotid IMT was assessed by high resolution B-mode ultrasonography.ResultshsCRP and TNF-α levels were higher in those with DM [p < 0.001] and IGT [p < 0.001] compared to NGT. In linear regression analysis, both hsCRP [p = 0.003] and TNF-α [p =0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. Among IGT subjects, TNF-α was associated with IMT [p < 0.001], while no association was observed either with hsCRP or TNF-α in diabetic subjects. In NGT subjects, mean IMT was highest in those with high values [III tertile] of both TNF-α and hsCRP [0.83 ± 0.1 mm; p < 0.001] followed by those with high TNF-α + low hsCRP [0.74 ± 0.09 mm; p < 0.001], high hsCRP  low TNF-α [0.67 ± 0.09 mm; p < 0.001], and lowest in those with both low TNF-α and hsCRP [I tertile] [0.63 ± 0.05 mm.ConclusionWe conclude that in Asian Indians 1. Levels of hsCRP and TNF-α increase with increasing severity of glucose intolerance 2. Both hsCRP and TNF-α are associated with IMT in NGT subjects while TNF-α alone is associated with IMT in IGT subjects 3. hsCRP and TNF-α have a cumulative effect on mean IMT values in NGT subjects.     

Value of serum anti-p53 antibodies as a prognostic factor in Egyptian patients with hepatocellular carcinoma

Objectivep53 antigen is an oncoprotective antigen and when damaged, leads to production of anti-p53 and also predisposes to various cancers, including hepatocellular carcinoma (HCC). Serum anti-p53 has been proven to have a prognostic value in patients with HCC. The objective of this study was to determine the prevalence and prognostic utility of serum anti-p53 in Egyptian patients with HCC.MethodsForty one patients with HCC, 26 patients with liver cirrhosis and 29 healthy controls were included in this study. For all the studied groups, we studied the clinical data, abdominal ultrasound (US) findings, biochemical liver function tests, serum alpha-fetoprotein (AFP) levels detected by enzyme immunoassay (EIA) kit and anti-p53 antibody levels by a modified enzyme-linked immunosorbent assay (ELISA). The severity of liver disease was assessed by Child–Pugh and MELD scores. Tumor characteristics were detected by (US) with or without computed tomography (CT) scan. These characteristics included tumor size, number and site. Tumor staging was done using Okuda, Cancer Liver Italian Program (CLIP) and Tokyo staging systems. Also, the overall survival of patients with HCC with reference to p53 antibody level was studied.ResultsThe mean age of HCC patients was 57.95 ± 8.41. There was a male predominance among HCC patients with male-to-female ratio of 3.6:1. Anti-p53 antibodies were detected in the sera of 68.3% of HCC patients, 50% of liver cirrhosis patients and 17.2% of healthy control subjects. The data showed that HCC patients had a significantly higher mean anti-p53 antibody values (p = 0.0001), than both liver cirrhosis patients and healthy control groups. Our results revealed that anti-p53 has a positive significant correlation with AFP (p = 0.002), severity of liver disease [Child Pugh score (p = 0.02) and MELD score (p = 0.0003)], tumor size (p < 0.0001), tumor number (p = 0.003) and tumor staging systems [Okuda (p = 0.04), CLIP (p = 0.006) and Tokyo (p < 0.0001)]. Also, our results revealed that serum anti-p53 antibodies had a significant association with overall survival of patients with HCC (p = 0.019) with a shorter survival time in anti-p53 positive status patients and with higher anti-p53 antibody levels within 19 months follow up.ConclusionThe detection of anti-p53 antibodies may be suitable for assessing the prognosis of HCC patients. The higher percentage of positivity of anti-p53 antibodies in Egyptian control subjects than reported elsewhere needs further thorough investigation.     

Small dense LDL cholesterol is a robust therapeutic marker of statin treatment in patients with acute coronary syndrome and metabolic syndrome

BackgroundSmall dense low-density lipoprotein (sd-LDL) is an atherogenic LDL subfraction and often increased in metabolic syndrome (MetS). This study aimed to determine whether sd-LDL cholesterol (sd-LDL-C) is a therapeutic marker of statin treatment in patients with acute coronary syndrome (ACS) and MetS.MethodsWe examined 71 patients with ACS and 50 non-ACS subjects with normal coronary arteries (controls). The patients with ACS were treated with life-style modifications (n = 36) or those plus 20 mg atorvastatin daily (n = 35) for 6 months. We measured sd-LDL-C by a novel detergent-based homogenous assay and calculated buoyant LDL-C (b-LDL-C).ResultsThe patients with ACS had higher sd-LDL-C than did the controls (30 ± 14 vs. 22 ± 8 mg/dl, p < 0.001). Furthermore, sd-LDL-C was higher in the patients with ACS and MetS (n = 31) than in those without MetS (n = 40) (35 ± 17 vs. 27 ± 11 mg/dl, p < 0.05). Atorvastatin reduced LDL-C and sd-LDL-C by 31% (102 ± 23 to 70 ± 28 mg/dl, p < 0.0001) and 24% (29 ± 15 to 22 ± 13 mg/dl, p < 0.01). The reduction in sd-LDL-C by atorvastatin was 5.5-fold greater in the patients with ACS and MetS than in those without MetS (p < 0.001). Contrary, that in b-LDL-C was similar between the groups.Conclusionssd-LDL-C is a superior therapeutic marker of statin treatment in patients with ACS and MetS.     

Lack of association between paraoxonase 1 Q192R polymorphism and multiple sclerosis in relapse phase: A case-control study

ObjectivesThe aim of this study was to estimate the serum activity of paraoxonase 1(PON1) and assess the distribution of PON1 polymorphisms in MS patients in the relapse phase.Design and methodsPON1 and arylesterase (ARE) serum activities were measured in two equal groups (each group 63 cases) of relapsing–remitting MS patients and healthy individuals.ResultsMean values for serum PON1 and ARE activities were 90.3 ± 63.4 and 182.1 ± 128.7 IU/L for patients and 99.9 ± 73.3 and 190.8 ± 150.3 IU/L for controls. Those values were not statistically significant (p = 0.242 and p = 0.378), respectively. Comparing genotype distributions and allele frequencies in both groups for PON1 Q192R and PON L55M polymorphisms did not show any statistical difference.ConclusionIn a selected group of MS patients in relapsing phase no statistically significant difference in PON1 and ARE activities was detected but the mean values for the serum enzyme activities were lower in MS patients.     

Kidney impairment in primary aldosteronism

BackgroundKidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration.MethodsA prospectively defined survey was conducted on 602 patients who were suspected of PA in the multiple-center Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Estimated glomerular filtration rate (eGFR) was calculated and followed up at 1 yr after treatment.ResultsThe diagnosis of PA was confirmed in 330 patients. Among them 17% of these patients had kidney impairment (eGFR < 60 ml/min/1.73 m²). Patients with PA had a higher prevalence of estimated hyperfiltration than those with essential hypertension (EH) (14.5% vs. 7.0%, p = 0.005). The eGFR independently predicted PA (OR, 1.017) in the propensity-adjusted multivariate logistic model. In PA, plasma renin activity and lower serum potassium (p = 0.018) was correlated with kidney impairment (p = 0.001), while this relationship was not significant in patients with EH. Either unilateral adrenalectomy or treatment of spironolactone for PA patients caused a decrease of eGFR (p < 0.001). Pre-operative hypokalemia (p = 0.013) and the long latency of hypertension (p = 0.016) could enhance the significant decrease of eGFR after adrenalectomy.ConclusionsPatients with aldosteronism had relative estimated hyperfiltration than patients with EH. Calculation of eGFR may increase the specificity in identifying patients with PA. Our findings demonstrate the correlation of serum potassium and renin with estimated hyperfiltration in PA and their relationship to kidney damage. These results provide a high priority for future renal protective strategies and methods for the early diagnosis and prompt treatment of PA.     

History of diabetes mellitus as a neurologic predictor in comatose survivors of cardiac arrest of cardiac origin treated with mild hypothermia

AimTo investigate the impact of a history of diabetes mellitus on the neurologic outcome in comatose survivors of cardiac arrest of cardiac origin treated with mild hypothermia.MethodsA prospective observational study was performed between September 2003 and July 2008. Eighty comatose survivors of cardiac arrest of cardiac origin were treated with mild hypothermia. Neurologic outcome at the time of hospital discharge, 30-day survival, and complications were assessed.ResultsTwenty-four of the 80 patients (30%) had a history of diabetes. The rate of favorable neurologic outcome was significantly lower in diabetic (17%) than in nondiabetic patients (46%) (p = 0.01). The rate of 30-day survival was lower in diabetic (33%) than in nondiabetic patients (54%), but the difference was not significant (p = 0.10). Multivariate analysis suggested that a history of diabetes was an independent predictor of unfavorable neurologic outcome (odds ratio 7.00, 95% confidence interval 1.42–46.19, p = 0.03), but not for 30-day survival. There was no significant difference in the prevalence of complications.ConclusionA history of diabetes is associated with poor neurologic outcome in comatose survivors of cardiac arrest treated with mild hypothermia.     

Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity

ObjectiveInsulin resistance and type 2 diabetes are associated with an increased risk of neurodegenerative diseases. Decreased brain-derived neurotrophic factor (BDNF) levels might play a role in the pathogenesis of neuropsychiatric disorders. The aim of our study was to estimate serum BDNF concentration in nonobese women divided into subgroups according to their insulin sensitivity.Design and methodsWe studied 46 young, healthy, nonobese women. Insulin sensitivity was estimated with the euglycemic–hyperinsulinemic clamp technique. Then, participants were divided into subgroups of high (mean, 12.79 ± 2.01 mg/kg fat-free mass/min) and low insulin sensitivity (mean, 7.33 ± 1.66 mg/kg fat-free mass/min).ResultsWe observed decreased serum BDNF concentration in women with low insulin sensitivity in comparison to high insulin sensitivity group (3306.11 ± 603.10 vs 4141.91 ± 755.37 pg/mL, p = 0.001). Serum BDNF was positively related to insulin sensitivity (r = 0.43, p = 0.003). This correlation remained significant after adjustment for other estimated parameters.ConclusionsSerum BDNF is decreased in young nonobese women with low insulin sensitivity. Early detection and prevention of insulin resistance might be useful in the prevention of neurodegenerative disorders.     

Estimated glomerular filtration rate for drug dose adjustment: Cockcroft and Gault or abbreviated MDRD equation?

ObjectivesEvaluate if Cockcroft and Gault (CG) estimated glomerular filtration rate (eGFR) might be replaced by abbreviated MDRD eGFR for drug dose adjustment.Design and methodseGFR was determined in 140 hospitalized patients (median: 68 years, 65 kg) treated by nephrotoxic and/or renally cleared drugs.ResultsCG eGFR was 61 mL/min vs. 78 mL/min/1.73 m² for MDRD (p < 0.0001). CG-MDRD difference ranged from ? 93 to + 34 mL/min, influenced by patient age, weight, and gender (p < 0.001).ConclusionsCG eGFR cannot be easily replaced by abbreviated MDRD eGFR for drug dose adjustment.     

Carotid intima media thickness is related positively to plasma pre ß-high density lipoproteins in non-diabetic subjects

BackgroundLipid-poor or lipid-free high density lipoprotein (HDL) particles, designated pre ß-HDL, stimulate removal of cell-derived cholesterol to the extracellular compartment, which is an initial step in the reverse cholesterol transport pathway. Pre ß-HDL levels may be elevated in subjects with established cardiovascular disease. We determined the relationship of carotid intima media thickness (IMT), a marker of subclinical atherosclerosis, with pre ß-HDL in subjects without clinically manifest cardiovascular disease.MethodsIMT and plasma pre ß-HDL, assayed by crossed immuno-electrophoresis, were determined in 70 non-diabetic subjects (aged 56 ± 9 years; non-smokers only; 27 women).ResultsIMT was correlated positively with pre ß-HDL, both expressed as plasma apolipoprotein (apo) A-I concentration (r = 0.271, p = 0.023) and as% of apo A-I (r = 0.341, p = 0.004). In contrast, IMT was correlated inversely with HDL cholesterol (r = ? 0.253, p = 0.035). IMT was also related positively to pre ß-HDL after adjustment for age, sex, systolic blood pressure (in apoA-I concentration, ß = 0.203, p = 0.043; in% of plasma apoA-I, ß = 0.235, p = 0.023). IMT remained associated with pre ß-HDL after additional adjustment for either body mass index, plasma glucose, cholesterol, triglycerides, HDL cholesterol, apoA-I and apoB.ConclusionSubclinical atherosclerosis may relate to higher plasma pre ß-HDL independently of apoA-I and HDL cholesterol levels.     

Lipid transfers to HDL are predictors of precocious clinical coronary heart disease

BackgroundHigh-density-lipoprotein (HDL) has several antiatherogenic properties and, although the concentration of HDL-cholesterol negatively correlates with incidence of coronary artery disease (CAD), this is not sufficient to evaluate the overall HDL protective role. The aim was to investigate whether precocious CAD patients show abnormalities in lipid transfers to HDL, a fundamental step in HDL metabolism and function.MethodsThirty normocholesterolemic CAD patients aged < 50 y and 30 controls paired for sex, age and B.M.I. were studied. Fasting blood samples were collected for the in vitro lipid transfer assay and plasma lipid determination. A donor nanoemulsion labeled with radioactive free-cholesterol, cholesteryl esters, phospholipids and triglycerides was incubated with whole plasma and after chemical precipitation of non-HDL fractions, supernatant was counted for radioactivity in HDL.ResultsLDL and HDL-cholesterol and triglycerides were equal in both groups. Transfers of free-cholesterol (3.8 ± 1.2%vs 7.0 ± 3.3%,p < 0.0001) and triglycerides (3.7 ± 1.7%vs 4.9 ± 1.9%, p = 0.0125) were diminished in CAD patients whereas cholesteryl ester transfer increased (6.5 ± 1.9%vs 4.8 ± 1.8%, p = 0.0008); phospholipid transfer was equal (17.8 ± 3.5% vs19.5 ± 3.9%).ConclusionAlterations in the transfer of lipids to HDL may constitute a new marker for precocious CAD and relation of this metabolic alteration with HDL antiatherogenic function should be investigated in future studies.