Predictive value of soluble urokinase plasminogen activator receptor, soluble ST2, and IL-33 in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains an important complication of preterm births. The soluble form of ST2 (sST2), interleukin-33 (IL-33), and soluble form of the urokinase plasminogen activator receptor (suPAR) have attracted increasing attention as biomarkers for different diseases. The aim of the current study was to assess the predictive value of plasma sST2, IL-33, and suPAR levels in patients with risk of BPD development. METHODS: A total of 38 babies were studied prospectively on delivery to the neonatal intensive care unit. Serum levels of IL-33, sST2, and suPAR were measured using enzyme-linked immunosorbent assay. Serum samples were collected from umbilical cord (at the time of delivery, termed CB) and peripheral blood (on day 14, termed PB). RESULTS: Levels of suPAR (PB-suPAR) and sST2 (PB-sST2) in the peripheral blood of the BPD group were significantly higher than the corresponding levels in the non-BPD group (P < 0.001, P = 0.028, respectively. There was a statistically significant correlation between PB-suPAR levels and the severity of BPD (P < 0.001)) when the suPAR results were analyzed using the receiver operating characteristic curve. CONCLUSION: PB-suPAR and PB-sST2 levels are sensitive and specific independent predictive biomarkers in preterm babies with BPD.

Determination of oxidative stress and cellular inflammation in patients with diabetic nephropathy and non-diabetic nephropathy being administered hemodialysis treatment due to chronic renal failure.

OBJECTIVES: We aimed to evaluate oxidative stress [8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA)] endothelial damage [asymmetric dimethylarginine (ADMA)] and markers of cellular inflammation [interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), neopterin (NP) and high-sensitivity C-reactive protein (hsCRP)] in patients with diabetic nephropathy (DN) and non-diabetic nephropathy who were being administered hemodialysis treatment because of chronic renal failure. METHODS: In determining 8-OHdG, IL-6 and TNF-α levels, Enzyme-Linked Immuno-Sorbent Assay method was used. Serum MDA, ADMA and NP levels were determined by using high performance liquid chromatography (HPLC). And hs-CRP values were measured with nephelometric method. RESULTS: Serum 8-OHdG and MDA levels were found statistically to have increased when compared with those of the control group in patients groups after dialysis. However, serum ADMA and neopterin levels were observed statistically to have decreased when compared with those of the control group in patients groups after dialysis. But, decreases on ADMA and neopterin levels are still much higher than those of control. IL-6 and TNF-α levels were found to have increased when compared with those of control group in patients groups before dialysis. CONCLUSION: The oxidative stress in patients with DN, who were being treated with hemodialysis due to chronic renal failure, was higher than that of non-DN patients who were being treated with hemodialysis. In contrast with this, inflammation occurring in non-DN patients was found to have been higher than that of in patients with DN.

The effect of hyperbaric oxygen therapy on ischemia-modified albumin levels in people with diabetes with foot ulcers.

INTRODUCTION: Hyperbaric oxygen (HBO2) treatment accelerates the healing process of diabetic foot ulcers (DFU) by increasing tissue oxygenation in hypoxic tissues. Ischemia-modified albumin (IMA) is produced as a result of serum albumin flowing through ischemic tissues. We aimed to investigate the effect of HBO2 therapy on IMA levels in patients with DFU. METHODS: Thirty (22 male, eight female) patients with DFU were enrolled into this study. HBO2 therapy was performed five times a week. Blood samples were drawn before the first treatment, after the 10th (IMA10) and 20th (IMA20) hyperbaric sessions. RESULTS: Pretreatment IMA levels [median (25%-75% quartiles)] of the patients were 0.010 (0.002-0.150) absorbance units (ABSU). Compared to pretreatment values, IMA levels did not change significantly after the 10th session [0.006 (0.003-0.025) ABSU] and 20th session [0.009 (0.005-0.019) ABSU] (p = 0.527). We found statistically significant negative correlations between diabetic age and IMA10 (r = -0.448, p = 0.013) and IMA20 (r = -0.414, p = 0.023). CONCLUSION: In contrast to our expectations, IMA levels did not change with HBO2 therapy in patients with DFU. We think that IMA levels did not decrease due to the production of free oxygen radicals during HBO2 therapy. Further studies with larger groups may give more accurate results.

Soluble TWEAK plasma levels increase after renal transplantation and associate with the improvement of endothelial function.

BACKGROUND: Soluble TWEAK (sTWEAK) and asymmetric dimethyl arginine (ADMA) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). We tested the hypothesis that the improvement in endothelial function observed after renal transplantation is directly linked to the normalization of both sTWEAK and ADMA. MATERIALS AND METHODS: One hundred and seventy-five kidney transplant recipients (71% men; 31·6 ± 9·4 years) were studied immediately before and on the 180th day post-transplantation. At each visit, blood samples were taken to assess circulating levels of sTWEAK and ADMA. Brachial artery endothelium-dependent vasodilatation (FMD) assessments were also performed. RESULTS: Renal transplantation was followed by an improvement in FMD. This improvement was paralleled by an increase in sTWEAK and a reduction in ADMA after transplantation (P < 0·001 for all). Cross-sectionally, both molecules associated with FMD before as well as after transplantation (P < 0·001 for all). Longitudinally, the changes observed in sTWEAK (ß = 0·26, P < 0·001) and ADMA (ß = -0·44, P < 0·001) levels were independently associated with the improvement of FMD (r(2)  = 0·30). CONCLUSIONS: Renal transplantation is followed by an improvement of FMD that is independently associated with the normalization of both sTWEAK and ADMA concentrations. We identify two surrogate biomarkers of endothelial function with potential as therapeutic targets.

Longitudinal analysis of vascular function and biomarkers of metabolic bone disorders before and after renal transplantation.

BACKGROUND/AIMS: The role of chronic kidney disease-mineral bone disorder (CKD-MBD) reversibility in the amelioration of vascular function and in the reduction of the risk for cardiovascular events after renal transplantation is still unknown. METHODS: We investigated the longitudinal relationship between the main biomarkers of CKD-MBD and the evolution of vascular function [flow-mediated dilatation (FMD)] after transplantation in a series of 161 patients with kidney failure maintained on chronic dialysis (5D-CKD). RESULTS: Before transplantation, FMD in patients was markedly lower (-40%, p < 0.001) than in well-matched healthy subjects and increased by 27% after transplantation (p = 0.001). Fibroblast growth factor 23 (FGF23), 25-hydroxy-vitamin D (25OHVD) and serum phosphate (p < 0.01) were independently associated with simultaneous changes in FMD. Changes in classical risk factors and in risk factors related to CKD like the glomerular filtration rate, serum albumin, C-reactive protein and insulin resistance failed to independently explain the variability in FMD changes after transplantation. CONCLUSION: Endothelium-dependent vasodilatation improves after kidney transplantation, which is parallel to the dramatic fall in FGF23, the reduction in serum phosphorus and the increase in 25OHVD levels. If these associations are causal, a part of decline in cardiovascular risk after transplantation is related to partial resolution of CKD-MBD.

Comparative effects of nebivolol and metoprolol on red cell distribution width and neutrophil/lymphocyte ratio in patients with newly diagnosed essential hypertension.

High level of circulating red cell distribution width (RDW) and neutrophil/lymphocyte (N/L) ratio may reflect ongoing vascular inflammation and play an important role in pathophysiology of hypertension. We evaluate the effects of nebivolol and metoprolol on the RDW and N/L in new essential hypertensive patients. After baseline assessment, 72 patients were randomly allocated to 5 mg/d of nebivolol (n = 37, 20 men) or 100 mg/d of metoprolol (n = 35, 18 men) and treated for 6 months. Blood pressure (BP), heart rate (HR), RDW, and N/L were measured before and after treatment. BP significantly decreased with both drugs (P < 0.001). Analog reduction was observed for resting HRs (P < 0.001), but metoprolol caused greater HR fall as compared with nebivolol (P < 0.001). After 6 months of treatment, nebivolol significantly lowered not only RDW but also the total white blood cell and N/L (P < 0.001, P = 0.023, P = 0.017, respectively). No changes were observed in metoprolol group. Percent decrease in RDW was found to be significantly higher in nebivolol than in the metoprolol group (P = 0.001) and remained also after correction for confounders (P = 0.012). Nebivolol improved RDW and N/L to a greater extent than metoprolol in patients with hypertension. These favorable effects may participate, together with the BP reduction, at the favorable properties of the drug in hypertension.

Vascular inflammation and aortic stiffness relate to early left ventricular diastolic dysfunction in prehypertension.

Prehypertension is characterized by an increased cardiovascular risk and by an increased prevalence of target organ damage compared with the pure normotensive state. The present study was designed to assess in prehypertensive subjects the possible relationships between early left ventricular dysfunction, vascular inflammation and aortic stiffness. The study population consisted of 31 untreated prehypertensive subjects (age: 34 ± 6 years, mean ± SD) and 31 age-matched pure normotensive controls. Left ventricular function was assessed by echocardiography, aortic distensibility parameters were derived from aortic diameters measured by ultrasonography, and high-sensitivity C-reactive protein was assessed by latex-enhanced reagent. Prehypertensive subjects displayed a significantly lower E/A ratio and a significantly greater deceleration time and isovolumetric relaxation time compared with normotensive controls. They also displayed aortic systolic diameter, diastolic diameter and mean aortic stiffness index beta significantly increased while systo-diastolic diameter change, mean aortic distensibility and aortic strain were significantly reduced compared with controls. Values of inflammatory markers were increased. At multiple regression analysis, E/A ratio was significantly related to high-sensitivity C-reactive protein and aortic stiffness index beta, after correction for age, left ventricular mass index and mean blood pressure (ß coefficient = -0.49, overall r(2) = 0.24, p = 0.01 and ß coefficient =-0.46, overall r(2) = 0.21, p = 0.02, respectively). Thus, in prehypertension, left ventricular dysfunction is significantly related to vascular inflammation and aortic stiffness, suggesting that early cardiac and vascular alterations may have an increased inflammatory process as a common pathophysiological link.

The relationship between microalbuminuria, left ventricular hypertrophy, retinopathy, and sex hormone status in newly diagnosed hypertensive women.

An increased incidence of hypertension (HT) in postmenopausal female population has been shown in previous studies and this has been ascribed to an association with altered status of estrogen (E2) and other female sex hormones. Hypertension is associated with certain target organ damage (TOD) and related clinical conditions. The aim of this study was to determine the relationship between microalbuminuria, left ventricular hypertrophy (LVH), retinopathy, and sex hormone status in newly diagnosed hypertensive women. A total of 66 hypertensive women (39 postmenopausal and 27 premenopausal) were included in the study. Along with the tests recommended in the HT guidelines, LVH, hypertensive retinopathy, and microalbuminuria were investigated in all the patients. Sex hormones (follicle stimulating hormone, luteinizing hormone, progesterone, and E2) of the patients were also measured. The results show that there was no statistically significant difference between the two groups in regard to TOD except microalbuminuria. The frequency of microalbuminuria in premenopausal group patients was higher than that of the postmenopausal group patients (P = .038). This study suggests that TOD caused by HT is a very important health problem, seeming to be related with female sex hormones.

The comparative effects of valsartan and amlodipine on vascular microinflammation in newly diagnosed hypertensive patients.

Pentraxin 3 (PTX3) is a new candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors. We aimed to investigate the effects of valsartan and amlodipine on the PTX3 and C-reactive protein (CRP) levels in patients with essential hypertension. Patients with a newly diagnosed essential hypertension were admitted to our internal medicine outpatient clinic. Patients were randomized to one of the following intervention protocols: calcium channel blocker (amlodipine, 5-10 mg/day) as group A (n = 22; mean age ± standard deviation [SD]: 52 ± 11 year) and angiotensine II receptor blocker (valsartan, 80-320 mg/day) as group B (n = 28; mean age ± SD: 50 ± 14 year). Endothelial dysfunction and systemic inflammation were evaluated with PTX3 and CRP. There was a significant decrease in the level of PTX3 after treatment in two groups (P < .05). Although there was a significant decrease in the level of CRP after treatment in amlodipine group, there was no significant decrease in the levels of PTX3 and CRP after treatment in two groups. There were no significant differences in the systolic and diastolic blood pressure reduction between the two treatment groups. In the treatment of hypertension, prior knowledge of the level of plasma PTX3 could be important in antihypertensive drug choice. C-reactive protein and PTX3 are the markers that have role in vascular inflammation and are found associated with the prognosis of cardiovascular outcomes in many trials. In our study, PTX and CRP levels were decreased when compared to baseline levels.

Comparison of calcium acetate and sevelamer on vascular function and fibroblast growth factor 23 in CKD patients: a randomized clinical trial.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a marker of endothelial dysfunction and atherosclerotic complications in patients with chronic kidney disease (CKD). Because previous studies suggested that sevelamer may exert effects on FGF-23 level and endothelial function independently of its phosphate-lowering action, we tested the effect of sevelamer versus calcium acetate on vascular function and FGF-23 levels. STUDY DESIGN: Randomized prospective open-label trial. SETTING & PARTICIPANTS: Patients with stage 4 CKD with hyperphosphatemia (n = 100). INTERVENTION: An 8-week intervention with sevelamer (n = 47) and calcium acetate (n = 53). OUTCOMES: The primary study outcome was change in flow-mediated vasodilatation in the forearm. The secondary outcome was change in FGF-23 levels. RESULTS: Serum phosphate levels decreased in both treatment arms (P < 0.001), but more markedly in the sevelamer group (P < 0.001). Flow-mediated vasodilatation increased from 6.1% to 7.1% (P < 0.001) in sevelamer-treated patients, whereas it was unchanged in the calcium-acetate group (6.0% vs 6.0%). In a combined analysis, treatment-induced changes in flow-mediated vasodilatation were (P < 0.001) associated with simultaneous changes in FGF-23 levels (-27.1% [-33.2% to -8.8%] for the sevelamer group; 3.5% [-8.4% to 12.1%] for the calcium acetate group), as well as with C-reactive protein and fetuin A levels. These relationships were confirmed in multiple regression analysis adjusting for changes in serum phosphate levels and other factors. LIMITATIONS: Unblinded randomized controlled study that cannot establish mechanisms of effect. CONCLUSIONS: In hyperphosphatemic patients with stage 4 CKD, treatment with phosphate lowering induces measurable improvements in flow-mediated vasodilatation. Furthermore, independently of serum phosphate level, FGF-23 level changes induced by phosphate binders are associated with simultaneous changes in flow-mediated vasodilatation. These observations are compatible with the hypothesis that FGF-23 may contribute to vascular dysfunction in this population.

Relationship between serum magnesium levels and cardiovascular events in chronic kidney disease patients.

BACKGROUND: Magnesium is an essential ion for all living cells because over 300 enzymes require the presence of magnesium for their catalytic action. To date, no group has evaluated magnesium as a cardiovascular risk factor in chronic kidney disease (CKD) subjects, in which closely interrelated factors and potential confounders such as endothelial dysfunction, insulin resistance (the homeostasis model assessment (HOMA) index) and inflammation (expressed as serum C-reactive protein (CRP) levels) were also considered. METHODS: Between March 2006 and December 2010, 283 CKD patients were followed up for time-to-event analysis until the occurrence of fatal or nonfatal cardiovascular events. Endothelium-dependent vasodilatation (flow-mediated dilatation; FMD) and endothelium-independent vasodilatation (nitroglycerin-mediated dilatation) of the brachial artery were assessed noninvasively using high-resolution ultrasound. RESULTS: From the univariate analysis of FMD, it appears that a higher magnesium level is associated with less endothelial dysfunction. When a multivariate analysis was performed, magnesium and estimated glomerular filtration rates (eGFR) maintained a strong positive correlation with FMD, supporting the hypothesis that higher levels of magnesium may protect against endothelial damage. In univariate Cox proportional hazards models, FMD, magnesium, high sensitivity CRP, the HOMA index, eGFR, comorbid diabetes, hypertension, smoking status, systolic blood pressure, serum phosphate and intact parathormone emerged as significant predictors for cardiovascular outcomes. Kaplan-Meier curves showed significantly higher cardiovascular mortality rates in CKD patients whose serum magnesium levels were below 2.05 mg/dl. CONCLUSIONS: This observational cohort study showed that magnesium may be an independent predictor of future cardiovascular outcomes and is the first study demonstrating such a role in etiologically diagnosed CKD patients, across different stages.

Protective effects of melatonin and S-methylisothiourea on mechlorethamine induced nephrotoxicity.

BACKGROUND: In this study, we aimed to investigate the protective effects of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced nephrotoxicity. MATERIALS AND METHODS: A total of 36 male Sprague-Dawley rats were divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Three groups received single dose of MEC (3.5 mg/kg) via transdermal route. Control animals were given saline only via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC. RESULTS: The tissue TNF-α, IL-1ß, and NOx levels were found significantly different for all groups (P < 0.001). MEC application resulted in severe histopathological changes. Melatonin showed meaningful protection against kidney damage. But protection by SMT was weaker. TNF-α and IL-1ß levels increased significantly with MEC application, and MEL and SMT ameliorated these increases in kidney tissue. MEC also elevated NOx levels in kidney tissue. CONCLUSIONS: Both inflammation and oxidative stress may have an important role in the MEC induced nephrotoxicity. MEL and SMT may also have anti-inflammatory properties, as well as anti-oxidant properties.

Serum lactate dehydrogenase levels significantly correlate with radiological extent of disease and spirometric values in patients with silicosis due to denim sandblasting.

BACKGROUND: The aim of the present study was to investigate serum lactate dehydrogenase (LD) levels in patients with silicosis due to denim sandblasting (SDDS) and also to investigate possible correlations between serum LD levels and the degree of radiological extent of disease (RED) and pulmonary function tests. METHODS: Forty-four males with SDDS and 32 healthy male subjects were included in the study. Patients and healthy controls were compared for serum LD levels. Correlations between serum LD levels, RED and spirometric values were investigated. RESULTS: Patients with SDDS had significantly higher serum LD levels than healthy controls. Patients with complicated SDDS had significantly higher serum LD levels than patients with simple SDDS. Significant correlations were found between serum LD levels and RED values. Significant correlations were found between serum LD levels and spirometric parameters. CONCLUSIONS: High serum LD levels might be considered as a marker of pulmonary parenchymal involvement in patients with SDDS. This study also suggests that the increase in serum LD levels might be closely related to the degree of pulmonary involvement in SDDS patients.

Neopterin: a promising marker for the inflammation in polycystic ovary syndrome.

BACKGROUND: Several markers of low-grade chronic inflammation are altered in women with polycystic ovary syndrome (PCOS). Neopterin (NEO) is a marker of celullar immunity, and oxidative stress, mainly produced by activated macrophages. We aimed to evaluate the NEO levels in PCOS patients and correlate them with antropometric and biochemical parameters. METHODS: The study groups consisted of 69 women with PCOS and 46 healthy controls. Both groups were divided into two subgroups according to their body mass index (BMI): <25 = normoweight, >25 = overweight. The clinical and biochemical parameters and serum NEO levels were analyzed. RESULTS: Circulating levels of NEO were significantly (p < 0.001) higher in women with PCOS (normoweight: 15.9 ± 4.7 nmol/l; overweight 13.3 ± 8.1 nmol/l) compared to controls (normoweight: 8.6 ± 2.0 nmol/l; overweight 9.2 ± 1.8 nmol/l) regardless of their weight classes. Waist-to-hip ratio (WHR) (p < 0.05), free and total testosterone (p < 0.001) were significantly elevated in women with PCOS compared to controls after controlling for the effect of obesity. CONCLUSION: Circulating NEO level s are elevated in PCOS independent of body mass index supporting the suggestion of PCOS is a low-grade chronic inflammatory state.

Serum ischemia modified albumin levels in pregnancies with neural tube defects.

OBJECTIVE: To evaluate ischemia-modified albumin (IMA) in women who had been pregnant with a child suffering from neural tube defect. STUDY DESIGN: Samples from 50 women who had been pregnant with an affected child (25 spina bifida, 25 anencephaly) and 25 controls matched for age, gestational age, and body mass index were studied. We measured serum IMA by enzyme-linked immunosorbent assay. RESULTS: Serum IMA was significantly higher in the study group compared to normal pregnancies (p < 0.05). The area under the receiver operating curve was 0.858 for IMA (95% CI, 0.769-0.947), whereas the optimal threshold value of IMA to discriminate between affected children and controls was 0.409 (sensitivity 88%, specificity 80%). The risk for increased IMA in mothers who have conceived a fetus with neural tube defect is 24.5 times higher than in the control group (rr = 24.5, 6.9-86.9, 95% CI) (p = 0.001). CONCLUSION: This study indicates that serum IMA in women who have conceived a fetus with neural tube defect is significantly higher than that in normal pregnant women.

Simultaneous determination of cyclosporine A, tacrolimus, sirolimus, and everolimus in whole-blood samples by LC-MS/MS.

OBJECTIVES: Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples. MATERIALS AND METHODS: We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients. RESULTS: System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes. CONCLUSION: This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.

Passive smoke exposure of female rats caused aortic atherosclerotic precursor lesions in their offspring.

The aim of this study was to evaluate the presence and degree of preclinical atherosclerosis in pups of pregnant rats exposed to cigarette smoke. Abdominal aorta examined for atherosclerotic lesions and intimal medial thickness of the abdominal aorta was measured by image analysis. The study groups showed endothelial cellular losses, marked intimal injuries, elastic fiber damages, mononuclear cellular infiltration, and irregularities in internal elastic membrane, with pronounced damages as integrity losses and local fragmentations. The results provide evidence for development of an atherosclerotic process in the neonatal period, even in prenatal stage, long before the formation of smoke-related cardiovascular diseases.

Comparison of hemodynamic and metabolic stress responses caused by endotracheal tube and Proseal laryngeal mask airway in laparoscopic cholecystectomy.

BACKGROUND: We aimed to compare hemodynamic and endocrine alterations caused by stress response due to Proseal laryngeal mask airway and endotracheal tube usage in laparoscopic cholecystectomy. MATERIALS AND METHODS: Sixty-three ASA I-II patients scheduled for elective laparoscopic cholecystectomy were included in the study. Patients were randomly allocated into two groups of endotracheal tube and Proseal laryngeal mask airway. Standard general anaesthesia was performed in both groups with the same drugs in induction and maintenance of anaesthesia. After anaesthesia induction and 20 minutes after CO(2) insufflations, venous blood samples were obtained for measuring adrenalin, noradrenalin, dopamine and cortisol levels. Hemodynamic and respiratory parameters were recorded at the 1(st), 5(th), 15(th), 30(th) and 45(th) minutes after the insertion of airway devices. RESULTS: No statistically significant differences in age, body mass index, gender, ASA physical status, and operation time were found between the groups (p > 0.05). Changes in hemodynamic and respiratory parameters were not statistically significant when compared between and within groups (p > 0.05). Although no statistically significant differences were observed between and within groups when adrenalin, noradrenalin and dopamine values were compared, serum cortisol levels after CO(2) insufflation in PLMA group were significantly lower than the ETT group (p = 0.024). When serum cortisol levels were compared within groups, cortisol levels 20 minutes after CO(2) insufflation were significantly higher (46.1 (9.5-175.7) and 27.0 (8.3-119.4) in the ETT and PLMA groups, respectively) than cortisol levels after anaesthesia induction (11.3 (2.8-92.5) and 16.6 (4.4-45.4) in the ETT and PLMA groups, respectively) in both groups (p = 0.001). CONCLUSION: PLMA usage is a suitable, effective and safe alternative to ETT in laparoscopic cholecystectomy patients with lower metabolic stress.

Low triiodothyronine alters flow-mediated vasodilatation in advanced nondiabetic kidney disease.

BACKGROUND/AIMS: Subclinical or frank hypothyroidism is causally implicated in endothelial dysfunction. Since the plasma concentration of the active form of thyroid hormone, triiodothyronine (T3), is reduced in chronic kidney disease (CKD), where endothelial function is frequently altered, low T3 may be a factor implicated in this disturbance in CKD patients. METHODS: We investigated the relationship between flow-mediated vasodilatation (FMD) and thyroid hormones in a series of 217 nondiabetic patients with stage 3-4 CKD. RESULTS: The plasma concentration of free T3 (fT3) was closely associated with FMD (r = 0.38; p < 0.001). fT3 was also inversely associated with hemoglobin (r = -0.41; p < 0.001), systolic pressure (r = -0.28; p < 0.001) and the plasma concentration of the endogenous inhibitor of NO synthase, asymmetric dimethylarginine (ADMA; r = -0.18; p = 0.007). However, adjustment for ADMA markedly attenuated the fT3-FMD link, a phenomenon suggesting that raised plasma ADMA, possibly driven by low fT3, at least in part mediates the adverse effects of low T3 on endothelial function in CKD. CONCLUSIONS: Low T3 in patients with moderate-to-severe CKD is a marker of endothelial dysfunction. This study sets a solid rationale for designing specific intervention studies aimed at clarifying the nature (causal or not causal) of the endothelial function-T3 link in CKD.

Vascular health, systemic inflammation and progressive reduction in kidney function; clinical determinants and impact on cardiovascular outcomes.

INTRODUCTION: Systemic inflammation, endothelial dysfunction and arterial thickening contribute to the elevated cardiovascular risk of dialysis patients. However, the course of these derangements and their relative contribution to the cardiovascular risk of nondialysed chronic kidney disease (CKD) are scarcely investigated. METHODS: Flow-mediated dilatation (FMD) and intima-media thickness (IMT) were assessed in 304 nondialysed CKD patients Stages 1-5 (mean age 46 ± 12 years, 158 men), together with routine biochemical measurements, C-reactive protein (CRP) and insulin resistance. Patients were then followed for time-to-event analysis of cardiovascular outcomes (fatal and nonfatal). RESULTS: CRP and IMT increased, while FMD decreased in parallel with estimated glomerular filtration rate (eGFR) decline (P < 0.001 for all). CRP and intact parathormone, as well as eGFR, appeared as strong determinants of FMD and IMT in multivariate analyses. After a median follow-up of 41 (range 6-46) months, 30 fatal and 59 nonfatal cardiovascular events occurred. In univariate analysis, FMD, IMT and CRP were significant predictors of outcome. In a multivariate Cox model excluding IMT, both FMD [hazard ratios 0.52 (95% confidence intervals 0.37-0.73) per %] and CRP [1.07 (1.03-1.11) per mg/L] predicted cardiovascular outcomes independently of confounders. In a model excluding FMD, only CRP (and not IMT) was a significant predictor. CONCLUSIONS: Endothelial dysfunction, arterial thickening and inflammation occur in parallel with the decline in eGFR, contributing to the increased cardiovascular risk of nondialysed CKD. Our results support the use of FMD over IMT measurements to monitor nondialysed CKD patients at risk.