Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia

BackgroundStatins are normally the first-line therapy for hypercholesterolemia (HC); however, the lipid-lowering response shows high interindividual variation. We investigated the effect of four polymorphisms in CYP3A4, CYP3A5 and ABCB1 genes on response to atorvastatin and CYP3A4 activity in Chilean subjects with HC.MethodsA total of 142 hypercholesterolemic individuals underwent atorvastatin therapy (10 mg/day/1 month). Serum lipid levels before and after treatment were measured. Genetic variants in CYP3A4 (? 290A>G, rs2740574), CYP3A5 (6986A>G, rs776746) and ABCB1 (2677G>A/T, rs2032582 and 3435C>T, rs1045642) were analyzed by PCR-RFLP. CYP3A4 enzyme activity in urine samples was assessed through determination of 6β-hydroxycortisol/cortisol free ratio (6βOHC/FC).ResultsAfter 4 weeks of therapy, a significant reduction in total cholesterol (TC) and LDL-c was observed (P < 0.001). The G allele for ? 290A>G polymorphism was related to higher percentage of variation in TC and LDL-c (P < 0.001). Moreover, same allele was associated with higher HDL-c variation (P = 0.017). In addition, CYP3A4 enzyme activity was lower in subjects carrying this polymorphism (P = 0.009). No differences were observed for CYP3A5 and ABCB1 variants.ConclusionOur results suggest that presence of G allele for ? 290A>G polymorphism determines a better response to atorvastatin, being also associated with lower CYP3A4 activity in vivo, causing an increased atorvastatin activity.     

Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method

BackgroundThe measurement of serum hepcidin, a peptide hormone that regulates iron metabolism, is clinically important to the understanding of iron homeostasis in health and disease. To date, the quantification of serum hepcidin levels by conventional immunological detection methods has proven problematic due to challenges in obtaining high quality antibodies which demonstrate good reproducibility. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has been employed recently for more sensitive quantification of hepcidin; however, this method has high background levels and therefore less than optimal specificity.MethodsIn order to increase the specificity of the mass spectrometry based assay, we developed a robust, ultra-performance liquid-chromatography-tandem mass spectrometry (UPLC-MS/MS) protocol using multiple selected reaction monitoring (mSRM) for quantification of hepcidin levels in urine and serum of human subjects. With this assay, we assessed levels of hepcidin before and for up to 8 h after oral ingestion of ferrous sulfate in ten adult human subjects without known disease.ResultsThe linear response of hepcidin quantitation on each instrument was measured, and the correlation coefficients of these calibrations were r² = 0.9512 ± 0.0202 (n = 5) for urine and r² = 0.9709 ± 0.0291 (n = 5) for serum [r² = mean ± SD]. Compared to baseline, the levels of urinary hepcidin between 2–4 h and 4–8 h of both women and men showed significant increases with p < 0.05 and p < 0.001, respectively. The levels of serum hepcidin between 4 h and 8 h in both women and men showed significant increases, compared with baseline values, with both p < 0.01. Interestingly, we also observed some degree of oscillation of levels, occurring at later time points.ConclusionsWe have developed and validated a new method for measuring hepcidin concentrations in human serum and urine and used it to demonstrate early increases with iron supplement in both urinary and serum levels of hepcidin, which return to baseline levels, except in urine samples from men.     

Are preservatives necessary in 24-hour urine measurements?

Background24-h urine measurements are used in the routine diagnosis and follow-up of many diseases in the clinical laboratory. Calcium (Ca²⁺), magnesium (Mg²⁺), phosphate (PO₄^3?) and uric acid are frequently requested markers in 24-h urine samples. Because of the different solubilities of these parameters, different urine collection conditions – urine in base for uric acid and urine in acid for Ca²⁺, PO₄^3? and Mg²⁺ measurements – are recommended.MethodsWe aimed to test the effect of addition of preservatives and heating of the urine specimen on the results obtained for Ca²⁺, Mg²⁺, PO₄^3? and uric acid by comparison with untreated samples results. Spot (n = 20) and 24-h urine (n = 50) samples were obtained from patients for routine urine analysis. A single spot urine sample was divided into five aliquots of 10 mL each: one containing 200 µL of HCl (6 N), another containing 200 µL of sodium bicarbonate, NaHCO₃ (5 g/L), two others in which the same preservative agents were added 24 h after the collection, and one without any preservative (untreated). Ca²⁺, PO₄^3?, uric acid and Mg²⁺ were measured in triplicate and at three different time points during the study: at the time of sampling (0 h), 24 h after sampling, and after heating the samples. The 24-h urine samples were collected without preservatives and analytes were measured promptly before and after acidification/alkalinization.ResultsThere was no statistically significant difference between untreated and treated samples (p > 0.05). Heating also failed to show any difference in the results (p > 0.05).ConclusionAccording to our results, addition of preservatives is not necessary for measurement of Ca²⁺, Mg²⁺, PO₄^3? and uric acid in promptly assayed 24-h urine samples.     

Determination of creatine and guanidinoacetate by GC-MS: study of their stability in urine at different temperatures

ObjectivesEvaluation of a GC-MS method using N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) as the silylating agent for GC-MS. Study of the stability of creatine and guanidinoacetate in urine.Design and methods22 urines were kept at RT, 4 °C and ? 30 °C for 15 days.ResultsMTBSTFA produces a single chromatographic peak in contrast with other derivatizing agents. Creatine concentration increases at room temperature (326% on average), and at 4 °C (75%). However, detection decreases after freezing (? 37%). Guanidinoacetate is stable, but decreases after freezing (? 37%). Sonication before analysis is crucial to obtain repetitive results.ConclusionsA modified GC-MS method has been validated and the conditions for preservation of the urine have been established.     

Association among retinol-binding protein 4, small dense LDL cholesterol and oxidized LDL levels in dyslipidemia subjects

ObjectivesTo investigate retinol-binding protein 4 (RBP4), small dense low-density lipoprotein cholesterol (sdLDL-C) and oxidized low-density lipoprotein (ox-LDL) levels and their associations in dyslipidemia subjects.Design and methodsWe determined RBP4, sdLDL-C, ox-LDL levels in 150 various dyslipidemia subjects and 50 controls. The correlation analysis and multiple linear regression analysis were performed.ResultsThe RBP4, sdLDL-C and ox-LDL levels were found increased in various dyslipidemia subjects. The sdLDL-C levels were positively correlated with RBP4 (r = 0.273, P = 0.001) and ox-LDL (r = 0.273, P = 0.001). RBP4 levels were also correlated with ox-LDL (r = 0.167, P = 0.043). The multiple regression analysis showed that only sdLDL-C was a significant independent predictor for RBP4 (β coefficient = 0.219, P = 0.009; adjusted R² = 0.041) and ox-LDL (β coefficient = 0.253, P = 0.003; adjusted R² = 0.057) levels, respectively.ConclusionsThe independent associations of sdLDL-C with RBP4 and ox-LDL were observed in dyslipidemia subjects. RBP4 may play an important role in lipid metabolism of atherosclerosis, particularly in formation of sdLDL.     

Synergistic effects of the polymorphisms in the PAI-1 and IL-6 genes with smoking in determining their associated risk with coronary artery disease

ObjectivesTo assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.Design and methodThe study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.ResultsThe frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively).ConclusionsThere are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.     

Increased urinary level of oxidized nucleosides in patients with mild-to-moderate Alzheimer's disease

Objective:Oxidative stress may play an important role in the pathogenesis of Alzheimer's disease (AD).Design and methods:To investigate the possible role of oxidative DNA damage in the pathogenesis of AD, we measured the metabolite concentrations of oxidized nucleosides (pseudouridine, 1-methyladenosine, 5-methylcytidine, 5-methyl-2′-deoxycytidine, 3-methyluridine, N², N²-dimethylguanosine, 8-hydroxy-2′-deoxyguanosine, 5-deoxyadenosine and 2-deoxyguanosine) in urine between AD (n = 36) and control subjects (n = 34) using liquid chromatography-mass spectrometry (LC-MS) without urine preparation.Results:In AD, the 3-methyluridine, 1-methyladenosine, 8-hydroxy-2′-deoxyguanosine (p < 0.05, respectively), 2-deoxyguanosine (p < 0.01) and pseudouridine, N², N²-dimethylguanosine (p < 0.001, respectively) were significantly increased when compared with the control subjects.Conclusion:The results indicate that oxidized urinary nucleosides may be useful as biomarkers for AD in early stages.     

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome

BackgroundIt is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics.MethodsSeventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured.ResultsHS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = ?0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = ?0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic.ConclusionsSimple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition.     

Oxidative modification of patient's plasma proteins and its role in pathogenesis of multiple sclerosis

BackgroundOxidative stress plays an important role in multiple sclerosis (MS).Objective and methodsThe present study was designed to evaluate the modifications of plasma proteins by estimation markers of oxidative/nitrosative stress: carbonyl groups and 3-nitrotyrosines (3-NT) levels in relapsing-remitting (RR) (n = 10) and secondary progressive (SP) (n = 10) clinical course of multiple sclerosis. Moreover, we estimated the level of uric acid (UA) in plasma of MS patients.ResultsCompared to controls (n = 10), the levels of carbonyl groups in plasma proteins were elevated (P < 0.0001) as well in RRMS as in SPMS. The highest concentration of 3-NT was observed in plasma proteins obtained from SPMS patients (P < 0.0005). The level of uric acid in plasma was significantly lower in RRMS (P < 0.0001) than SPMS.ConclusionThis is the first report which presented differences between SPMS and RRMS patients in 3-NT and protein carbonyl groups in plasma proteins.     

Development of a score based on urinalysis to improve the management of urinary tract infection in children

BackgroundThe need for reducing unnecessary antibiotic treatment is being emphasized in the management of urinary tract infections (UTI), a disease frequent in childhood. An ideal test should provide early diagnosis without the waiting times of urine culture, but even a simple test of exclusion could significantly improve patient management.MethodsWe evaluated the sensitivity, specificity, negative and positive predictive value of automated microscopy IRIS iQ200 combined with the dipstick analyses in children with suspected UTI. Multivariable logistic regression analysis was used to identify the set of variables that best predict positive culture results and develop a numerical risk score.ResultsOf 474 consecutive urine samples retrospectively analyzed, 69 were positive at urine culture with prevalence of infection of 14.6%. Parameters significantly associated with the presence of infection in multivariable analysis were age < 1 year (p < 0.001), leukocyte esterase ≥ 15 × 10^6/L (p < 0.001), number of small particles (ASP) ≥ 5500 × 10^6/L (p < 0.001) and bacteria ≥ 3 × 10^6/L (p = 0.01). The derived score ranged from 0 to 10, with higher values indicating higher risk of UTI. The area under the score ROC curve was 79% (95% CI 0.72–0.85), and was better than those of the individual urinary chemical and microscopic analyses.ConclusionsThis routine method could improve the management of UTI in children by early identifying patients with low probability of infection, for whom antibiotic treatment can be withheld until the results of urine culture become available.     

Role of endogenous cortisol on Helicobacter pylori colonization

Background and aimsHelicobacter pylori infects the gastric mucosa and can lead to chronic gastritis, gastric ulcer and gastric cancer. Colonization of H. pylori in the gastric mucosa is influenced by a variety of host, bacterial and environmental factors. Host defense mechanisms have been affected by endogenous glucocorticoids. We aimed to investigate the relationship between H. pylori and endogenous glucocorticoid.Materials and methodsForty cases with endoscopically and histologically proven H. pylori and 26 patients who did not have H. pylori on gastric biopsy samples were enrolled in our study. Cortisol was tested from 24-h collected urine samples.ResultsH. pylori (+) and H. pylori (?) groups consisted of 40 (28 women, 12 men; aged 44.85 ± 12.52 years) and 26 (22 women, 4 men; aged 52.27 ± 15.15 years) patients, respectively. Age and gender were similar in both groups. Body mass index, C-reactive protein and erythrocyte sedimentation rate were not statistically different between the two groups (p > 0.05). 24-h urine cortisol amount was lower in patients with H. pylori (+) than H. pylori (?) cases.ConclusionsPresent study demonstrates that patients with gastric H. pylori colonization have significantly lower cortisol levels when compared with H. pylori negative cases. There is a negative correlation between H. pylori colonization and urine cortisol output.     

Saliva S100B in professional sportsmen: High levels at resting conditions and increased after vigorous physical activity

BackgroundNeurological dysfunction is a key medical concern in professional sportsmen (PSM). We investigated whether saliva S100B concentrations in PSM and healthy controls are modified before and after training.MethodsWe conducted a case–control-study in 75 patients (25 PSM vs 50 controls) in which S100B saliva concentrations were expressed as absolute values and percentage of change (%) from samples drawn before (T0) and after (T1) training.ResultsNo differences (P > 0.05) between groups were found regarding clinical, monitoring and laboratory parameters. S100B both in PSM and controls was higher at T1 when compared to T0 (P < 0.01). In PSM, S100B was higher than controls (P < 0.001) at T0 and T1. S100B% at T0–T1 was higher (P < 0.001) in PSM and in controls and between PSM and controls (P < 0.001).ConclusionsIncreased saliva S100B levels in PSM before and after training suggest a paracrine/autocrine protein's role connected to stressing activity, which becomes especially evident in PSMs.     

Urinary iodine and sodium status of urban Korean subjects: a pilot study

ObjectivesWe estimated iodine status of Korean population by determining the concentration of spot urinary iodine (UI) with a reliable method based on the Sandell–Kolthoff reaction.Materials and MethodsA total of 540 urine samples from apparently healthy subjects were collected, and UI, urinary sodium (UNa), and urinary creatinine (UCr) were determined from those samples and analyzed with age.ResultsThere were significant decreases in either UI (P < 0.0001), UI/UCr ratio (P = 0.0001), UNa (P < 0.0001), or UNa/Cr ratio (P = 0.0001) in younger subjects than older ones. The median value of UI was 267.6 μg/L, but the median UI of the younger group (191.8 μg/L) was significantly decreased compared to that of the older group (383.9 μg/L).ConclusionsThis study showed that the median of UI in Korean urban population was in a more than adequate iodine nutritional state, but UI was significantly different between the younger age group and the older age group.     

A new age-based formula for estimating weight of Korean children

ObjectivesThe objective of this study was to develop and validate a new age-based formula for estimating body weights of Korean children.MethodsWe obtained body weight and age data from a survey conducted in 2005 by the Korean Pediatric Society that was performed to establish normative values for Korean children. Children aged 0–14 were enrolled, and they were divided into three groups according to age: infants (<12 months), preschool-aged (1–4 years) and school-aged children (5–14 years). Seventy-five percent of all subjects were randomly selected to make a derivation set. Regression analysis was performed in order to produce equations that predict the weight from the age for each group. The linear equations derived from this analysis were simplified to create a weight estimating formula for Korean children. This formula was then validated using the remaining 25% of the study subjects with mean percentage error and absolute error. To determine whether a new formula accurately predicts actual weights of Korean children, we also compared this new formula to other weight estimation methods (APLS, Shann formula, Leffler formula, Nelson formula and Broselow tape).ResultsA total of 124,095 children's data were enrolled, and 19,854 (16.0%), 40,612 (32.7%) and 63,629 (51.3%) were classified as infants, preschool-aged and school-aged groups, respectively. Three equations, (age in months + 9)/2, 2 × (age in years) + 9 and 4 × (age in years) ? 1 were derived for infants, pre-school and school-aged groups, respectively. When these equations were applied to the validation set, the actual average weight of those children was 0.4 kg heavier than our estimated weight (95% CI = 0.37–0.43, p < 0.001). The mean percentage error of our model (+0.9%) was lower than APLS (?11.5%), Shann formula (?8.6%), Leffler formula (?1.7%), Nelson formula (?10.0%), Best Guess formula (+5.0%) and Broselow tape (?4.8%) for all age groups.ConclusionWe developed and validated a simple formula to estimate body weight from the age of Korean children and found that this new formula was more accurate than other weight estimating methods. However, care should be taken when applying this formula to older children because of a large standard deviation of estimated weight.     

Reference ranges for serum S100B protein during the first three years of life

ObjectiveClinical and diagnostic management of traumatic brain injuries is problematic in young children. To facilitate this management, we describe blood reference ranges for the well established biomarker S100B in children younger than 3 years.Design and methodsSerum S100B concentrations were determined by electro-chemiluminescence immunoassay in a population of 186 healthy children aged 0–3 years.ResultsFour age groups emerged, i.e. 0–3, 4–9, 10–24 and 25–36 months. We also found an interesting inverse correlation with head circumference.ConclusionThis study provides useful serum S100B values from the largest cohort of healthy children aged 0–3 years old.     

Urinary IL-18: A marker of contrast-induced nephropathy following percutaneous coronary intervention?

ObjectivesContrast-induced nephropathy (CIN) is a complication that is underestimated in clinical practice after cardiac catheterization. Recently, the value of interleukin (IL)-18 as a novel biomarker for the detection of acute renal failure has been highlighted. In the present study, we sought to investigate whether urine IL-18 may be an early diagnostic marker of CIN.Design and methodsWe performed a nested case-control study using a hospital based cohort of all patients (n = 157) admitted for elective PCI for stable angina to the Uludag University School of Medicine between February 2007 and June 2007. We identified 15 patients (9.5%) with CIN. Controls were matched with cases at an attempted 2.5:1 ratio by age and gender. Urinary IL-18 values were measured before as well as 24 and 72 h after the PCI.ResultsNo statistically significant differences in urine IL-18 were detected between cases (n = 15) and controls (n = 36) or between the patient samples obtained before PCI and after the invasive procedure in both study groups.ConclusionsThese findings argue against the hypothesis that urine IL-18 may be clinically useful as a biomarker of CIN after radiological procedures requiring intravascular administration of iodinated contrast media. Further studies with larger sample sizes are needed to validate our findings.     

Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease

ObjectivesWe sought to determine whether serum concentrations of fibroblast growth factor 19 (FGF19) – an ileum-derived enterokine which plays a role in the control of glucose and lipid homeostasis – are altered in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).Design and methodsSerum levels of FGF19 were measured using enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 74 controls.ResultsFGF19 levels were significantly lower in patients with biopsy-proven NAFLD (median: 130 pg/mL) than in controls (median: 210 pg/mL, P < 0.001). Serum FGF19 levels were significantly but modestly associated with hepatocyte ballooning scores in univariate analysis (r = ? 0.25, P < 0.05) but not after adjustment for potential confounders (β = ? 0.18; t = 1.78, P = 0.08).ConclusionsThis pilot study suggests that serum FGF19 levels are decreased in patients with NAFLD but are not independently associated with liver histology findings.     

Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women

BackgroundSerum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL.MethodsWe determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance.ResultsIn simple regression analyses, RBP4 levels had significant correlations with total cholesterol (r = 0.354, P = 0.029), LDL-cholesterol (r = 0.396, P = 0.014), and sdLDL-cholesterol (r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol (r = 0.402, P = 0.012), LDL-cholesterol (r = 0.627, P < 0.001) and triglycerides (r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient (ß) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R² = 0.240), whereas RBP4 (ß = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R² = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels.ConclusionsWe showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.     

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.     

Effects of spinal cord stimulation on cortical excitability in patients with chronic neuropathic pain: A pilot study

BackgroundDespite a broad clinical use, the mechanism of action of SCS is poorly understood. Current information suggests that the effects of SCS are mediated by a complex set of interactions at several levels of the nervous system including spinal and supraspinal mechanisms.AimsThe study was undertaken to investigate the influence of SCS on distinct parameters of cortical excitability using single- and paired-pulse transcranial magnetic stimulation (TMS).MethodsFive patients with chronic neuropathic pain were examined with the SCS stimulator on and off by means of TMS. Pain was assessed using a visual-analogue scale. Electrophysiological and pain parameters of patients during this procedure were compared by means of a linear mixed effect model.ResultsSCS induced a significant modulation of cortical excitability, especially by influencing the parameter “intracortical facilitation” (t = −2.657; df = 8; p = 0.029). A significant relationship between this parameter and “perceived pain” could be obtained (t = −4.798; df = 8; p = 0.002).ConclusionsThese results suggest that SCS is able to influence neurobiological processes at the supraspinal level and that clinical effects of SCS may be at least in part of cortical origin.