Investigation of the value of hematological biomarkers in the clinical differential diagnosis of IgG4-RD.

BACKGROUND: IgG4- related disease (IgG4- RD) is a systemic fibroinflammatory disease whose pathogenesis has not been completely elucidated. Due to the novelty and complexity of the diagnostic criteria, it is difficult to distinguish from the diseases included in the differential diagnosis without tissue biopsy. This study aimed to discover new biomarkers that can help for disease diagnosis and its differential diagnosis by reviewing the relationships between neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). METHODS: Thirty IgG4- RD, 38 granulomatous polyangiitis (GPA), and 46 sarcoidosis patients presenting to the Rheumatology Clinic meeting the criteria of 2019 American College of Rheumatology, 2012 International Chapel Hill and 1999 American Thoracic Society meeting, respectively, and 27 healthy control subjects were included. We collected data on complete blood count with automated differential values including NLR, PLR, SII, and SIRI. RESULTS: The SII and PLR values were significantly higher in patients with IgG4-RD compared to healthy controls, (SII median (minmax) 572 (102-5583) vs. 434 (172-897), PLR median (min-max) 130 (56.8-546) vs. 104 (57.5- 253) p < 0.001). SII value was found to have a significant positive correlation with CRP in IgG4-RD disease (r = 0.371; p = 0.043). While SII, SIRI, NLR, PLR parameters were not significant between the IgG4-RD and sarcoidosis groups, SII, SIRI, NLR, PLR were significantly higher in patients with GPA than in IgG4-RD patients (p < 0.001). DISCUSSION: This is the first study to review the SII, SIRI, NLR, and PLR in IgG4-RD. The obtained results suggest that the SII could beused as a new tool, for differential diagnosis and activity of the IgG4-RD.

Prevalence and Time Course of Thiamine Deficiency in Critically Ill Children: A Multicenter, Prospective Cohort Study in Turkey.

OBJECTIVES: To determine the prevalence and time course of thiamine deficiency (TD) in PICU patients. DESIGN: Multicenter, prospective, cohort study between May 2019 and November 2019. SETTING: Three university-based tertiary care, mixed medical-surgical PICUs in Ankara, Turkey. PATIENTS: PICU patients 1 month to 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied 476 patients and grouped them by TD status on days 1 and 3 of the PICU admission. There might be a risk of unintended bias since we excluded 386 patients because of the absence of consent, inadequate blood samples, loss of identifier information, and recent vitamin supplementation. On day 1, TD was present in 53 of 476 patients (11.1%) and median (minimum-maximum) thiamine levels were 65.5 ng/mL (5-431 ng/mL). On day 3, TD was present in 27 of 199 patients (13.6%) with repeated measurement. The median (minimum-maximum) thiamine levels were 63 ng/mL (13-357 ng/mL). The time course of TD from day 1 to day 3 in these 199 patients was as follows. In 21 of 199 patients (10.6%) with TD on day 1, 11 of 21 (52%) continued to have TD on day 3 and the other 10 of 21 patients (48%) improved to no longer having TD. In 178 of 199 patients (89.4%) without TD on day 1, 16 of 178 (9%) went on to develop TD by day 3, and the other 162 of 178 (91%) continued to have normal thiamine status. CONCLUSIONS: In the PICU population in three centers in Turkey, the prevalence of TD in the sample of patients was 11.1%. In those TD patients who had serial studies, we also identified that by day 3 some continued to be TD, and some patients improved to normal thiamine status. Of concern, however, is the population who develop TD over the course of PICU stay.

Diagnostic utility of serum biomarkers in large vessel vasculitis and their correlation with positron emission tomography.

OBJECTIVES: To investigate the association between vascular inflammation, as detected by positron emission tomography (PET) imaging and interleukin-6 (IL-6), pentraxin3, and B-cell-activating factor (BAFF) in subjects with LVV. METHODS: The study included newly diagnosed giant cell arteritis (GCA, n = 27) or Takayasu arteritis (n = 9) patients and healthy control (HC, n = 31) subjects. PET scan and blood samples were obtained before the introduction of treatments. IL-6, PTX3, and BAFF levels were determined quantitatively by enzyme-linked immunosorbent assay kits. RESULTS: Thirty-six patients with LVV (20 females, 16 males; age 64.5 ± 16.6 years) and 31 HC (14 females, 17 males; age 37.1 ± 9.6 years) were included. Serum levels of IL-6, PTX3, and BAFF were increased in patients with newly diagnosed LVV compared with healthy control subjects. In receiver operating characteristics (ROC) analysis, serum IL-6 and BAFF provided excellent discrimination of newly diagnosed LVV patients from HC (area under the ROC curve of >0.90 and >0.80, respectively). None of the inflammatory markers correlated with vascular inflammatory activity determined by PET scanning. CONCLUSIONS: Our results suggest that IL-6 and BAFF may serve as markers of large vessel vasculitis, while PTX3 is not useful. None of the inflammatory markers correlated with PET assessed vasculitis activity.

The Effect of Smoking on Mitochondrial Biogenesis in Patients With Graves Ophthalmopathy.

PURPOSE: To evaluate the effects of cigarette smoking on oxidative stress (OS) and mitochondrial biogenesis related parameters in patients Graves Ophthalmopathy (GO). METHODS: Patients with moderate-to-severe GO according to the European Group on Graves Orbitopathy (EUGOGO) criteria were prospectively enrolled in this study. Age- and sex-matched healthy volunteers who applied to outpatient clinic due to refractive problems consisted the control group. Participants were divided into 4 groups based on their diagnosis and smoking status: group 1 (n = 30) smoker GO patients, group 2 (n = 30) nonsmoker GO patients, group 3 (n = 30) smoker healthy controls, and group 4 (n = 30) nonsmoker healthy controls. In the sera, total antioxidant status, total oxidant status and OS index values, peroxisome proliferator-activated receptor-γ coactivator 1-α, mitochondrial transcriptional factor A levels, and paraoxonase-1 enzyme activity were evaluated. RESULTS: Total oxidant status and OS index values were the highest in group 1 compared to other groups (p = 0.031, p = 0.042; respectively). There was no statistically significant difference in total antioxidant status and peroxisome proliferator-activated receptor-γ coactivator 1α levels among the groups (p = 0.521, p = 0.388; respectively). Paraoxonase-1 enzyme activity was the lowest in group 1 and highest in group 4 (p = 0.024). The levels of mitochondrial transcriptional factor A was the lowest in group 1 compared to other groups (p = 0.012). CONCLUSIONS: Cigarette smoking in GO patients seems to be a risk factor that increases OS, and therefore, it may have an unfavorable impact on the mitochondrial biogenesis.

The role of inflammatory biomarkers in CHD-associated pulmonary hypertension in children.

OBJECTIVE: The present study aims to identify the role of inflammatory markers such as C-reactive protein, interleukin-6, and fractalkine in CHD-associated pulmonary hypertension in children. METHODS: This is a prospective review of 37 children with CHD-related pulmonary hypertension, 21 children with congenital heart defects, and 22 healthy children. RESULTS: Serum C-reactive protein and interleukin-6 levels were significantly higher in the children with CHD-related pulmonary hypertension (respectively, p=0.049 and 0.026). Serum C-reactive protein concentrations correlated negatively with ejection fraction (r=-0.609, p=0.001) and fractional shortening (r=-0.452, p=0.007) in the pulmonary hypertension group. Serum fractalkine concentrations correlated negatively with ejection fraction (r=-0.522, p=0.002) and fractional shortening (r=-0.395, p=0.021) in the children with pulmonary hypertension. Serum interleukin-6 concentrations also correlated negatively with Qs (r=-0.572, p=0.021), positively with Rs (r=0.774, p=0.001), and positively with pulmonary wedge pressure (r=0.796, p=0.006) in the pulmonary hypertension group. A cut-off value of 2.2 IU/L for C-reactive protein was able to predict pulmonary hypertension with 77.5% sensitivity and 77.5% specificity. When the cut-off point for interleukin-6 concentration was 57.5 pg/ml, pulmonary hypertension could be predicted with 80% sensitivity and 75% specificity. CONCLUSION: Inflammation is associated with the pathophysiology of pulmonary hypertension. The inflammatory markers C-reactive protein and interleukin-6 may have a role in the clinical evaluation of paediatric pulmonary hypertension related to CHDs.

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

Association between Plasma Endothelin-1, Transforming Growth Factor-ß, Fibroblast Growth Factor, and Nitric Oxide Levels and Liver Injury in Hematopoietic Stem Cell Transplantation Recipients with Persistent Iron Overload after Transplantation.

Graft-versus-host disease, iron overload, and infections are the major causes of liver dysfunction in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. We investigated the relationship between serum iron parameters and the levels of transforming growth factor-ß (TGF-ß), fibroblast growth factor (FGF), endothelin-1 (ET-1), and nitric oxide (NO) as predictors of chronic liver injury in 54 AHSCT recipients who survived at least a year after transplantation. Serum samples from patients were obtained for the evaluation of ET-1, TGF-ß, FGF, NO, and nontransferrin bound iron at the first year follow-up visit using commercially available ELISA kits. Patients were categorized depending on serum ferritin and transferrin saturation levels. The parameters were compared between the groups, and survival analysis was also performed. Most of the AHSCT recipients (81.5%) were in complete remission during the study. After a median follow-up time of 73 months (range, 13 to 109 months), 72.2% of the patients were alive. Mean serum levels of ET-1, NO, TGF-ß, and FGF were 81.54 ± 21.62 µmol/mL, 31.82 ± 26.42 µmol/mL, 2.56 ± 0.77 ng/mL, and 50.31 ± 32.69 pg/mL, respectively. Nineteen patients (35.2% of the cohort) had serum ferritin levels higher than 1000 ng/mL. Mean serum levels of ET-1, NO, TGF-ß, and FGF were similar in patients with serum ferritin levels below or above 1000 ng/mL (P > .05). Serum ferritin levels were positively correlated with serum alanine aminotransferase (r = .284, P = .042) and γ-glutamyl transferase (r = .271, P = .05) levels and were negatively correlated with serum albumin levels (r = .295, P = .034). There was a significant positive correlation between serum transferrin saturation and alanine aminotransferase levels (r = .305, P = .03). Serum ET-1 level was positively correlated with alkaline phosphatase levels (r = .304, P = .026). In univariate Cox regression analysis serum levels of iron parameters, ET-1, NO, TGF-ß, and FGF did not have an impact on overall survival (P > .05). The probability of progression-free survival was also similar in patients with ferritin levels above or below 1000 ng/mL (P = .275). The probability of survival was similar in patients with transferrin saturation ≥70% and <70% (P > .05). Serum iron parameters showed a positive correlation with liver injury. However, there was no correlation between fibrogenic cytokines and liver transaminases. Our results suggest that iron overload at least with the current levels of ferritin might have a relatively benign course. Prospective randomized trials will guide the actual role of iron chelation in the post-transplantation setting.

Inflammatory markers, oxidative stress, and antioxidant capacity in healthy allo-HSCT donors during hematopoietic stem cell mobilization.

The aim of this study is to investigate the impact of mobilization with granulocyte colony stimulating factor (G-CSF) and apheresis procedure on inflammatory and oxidative stress markers, and antioxidant capacity in healthy allo-HSCT donors. The study was conducted in the Stem Cell Transplantation Unit of Gazi University Hospital between October 2010 and March 2011, and 25 consecutive allo-HSCT donors were included. The alteration in the serum levels of iron, iron binding capacity, albumin, ferritin, IL-6, hs-CRP, TAC, MDA, and AOPP were determined at five different time points. (1) Prior to the first dose of G-CSF (T0), (2) preapheresis (on the fourth day of G-CSF before the apeheresis procedure) (T1), (3) immediately postapheresis (T2), (4) 24 h postapheresis (T3), and (5) a week after apheresis (T4). Serum ferritin levels increased steadily after administration of G-CSF and remained high up toT4. Both serum IL-6 and hs-CRP levels began to increase in the T1 sampling and reached to a maximum level at T3 and decreased even below the basal levels at T4. Serum AOPP levels decreased at preapheresis and postapheresis time points, while they increased at T3 and T4 samples. Serum MDA levels decreased at T1, T2, T3, and T4 samples. Serum TAC increased significantly and steadily at all time points post G-CSF. In conclusion; mobilization with G-CSF and apheresis caused a transient inflammatory reaction and a protein limited oxidative stress in healthy allo-HCT donors.

Analysis of serum γ-glutamyl transferase levels in neonatal intensive care unit patients.

OBJECTIVES: Gamma-glutamyl transferase (GGT) is commonly measured in newborn infants as a sensitive liver function test; however, reference ranges are mostly based on early studies, including relatively small number of patients. The aim of this study was to emphasise recently changed GGT values because of changed newborns profile admitted to neonatal intensive care units (NICUs) and establish new cross-sectional reference ranges for the serum GGT levels in a cohort of neonates between 26 and 42 weeks' gestational age in 1 centre. METHODS: From January 1, 2010 to December 31, 2012, liver function tests including serum GGT measurements were performed in 705 newborns who were admitted to NICUs because of different aetiologies at Gazi University School of Medicine Hospital, Ankara, Turkey. Infants with Apgar score <8 at the fifth minute, any metabolic or liver disease, cholestasis, congenital infection, culture-proven sepsis, elevated serum aminotransferases, and who were treated with phenobarbital were excluded. Clinical and laboratory data of 583 neonates were analysed retrospectively. GGT was measured by enzymatic method using the Abbott Architect C16000 autoanalyser. Mean, 2.5th, and 97.5th percentiles were used to express the reference range data. RESULTS: Four hundred sixty-one GGT values of 200 preterm infants and 501 GGT values of 383 term infants during the first 28 days after birth were analysed. Serum GGT levels of preterm infants in the first 7 days and between 8 and 28 days after delivery were (mean±standard deviation; 141.81±88.56 U/L and 131.17±85.53 U/L) similar to term infants (139.90±86.46 U/L and 144.56±86.51 U/L), respectively (P=0.649 and P=0.087). Serum GGT levels were found to be significantly higher in male infants (no need of query) (145.98±93.68 U/L) than female infants (132.18±78.97 U/L) (P=0.035), and infants born vaginally (152.24±90.71 U/L) also had higher serum GGT activity than those born by caesarean section (135.38±85.37 U/L) (P=0.005). CONCLUSIONS: A new reference range for serum GGT levels that is higher than previous reference values can identify neonates with truly abnormal results and prevent unnecessary interventions.

The effects of iron on FGF23-mediated Ca-P metabolism in CKD patients.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is an important counterregulatory hormone for phosphate homeostasis. Since it has been reported that iron administration induces hypophosphatemic osteomalacia by triggering FGF23 synthesis, we hypothesized that iron administration might lead to a further increase in FGF23, resulting in alterations to Ca-P metabolism in a stage 5 CKD population. METHODS: This cross-sectional study was performed in a single center, and involved 73 hemodialysis patients (47.7 ± 15.74 years old, 68.5% men), 29 peritoneal dialysis patients (44.55 ± 15.05 years old, 62.1% men), and 55 healthy (43.57 ± 14.36 years old, 55.6% men) subjects. The dialysis group was subcategorized according to iron therapy administration into users and nonusers. RESULTS: The median iFGF23 level was significantly higher in the dialysis population than in the healthy controls [88.050 (25.2-1038.3) pg/ml versus 46.95 (2.4-356) pg/ml (p < 0.001)]. In the dialysis population, a significantly lower median iFGF23 level was observed in iron therapy users than in nonusers [87.6 (25.2-1038.3) versus 119 (51.6-1031); respectively, p = 0.045]. A significant negative association between iron administration and iFGF23 level was revealed by both univariate (r = -0.237, p = 0.016) and multivariate (ß = -0.221, p = 0.032) analysis. No association was found between iFGF23 and serum ferritin and iron levels. Also, there was no association between iron therapy and serum phosphate level. CONCLUSION: In contrast to what is seen for the general population, this study showed that there was a negative relationship between iron administration and serum iFGF23 level in a dialysis population. We can therefore conclude that if high levels of FGF23 are harmful, iron therapy may have a beneficial effect on bone metabolism by reducing FGF23 levels in a dialysis population.

Neutrophil to lymphocyte ratio in evaluation of inflammation in patients with chronic kidney disease.

AIM: The current data have proven the pivotal role of inflammation in the development of atherosclerosis and cardiovascular diseases in patients with chronic kidney disease (CKD). Neutrophil to lymphocyte (N/L) ratio has increasingly been reported as a measure of systemic inflammation. This study assessed N/L ratio and investigated its associations with standard inflammatory biomarkers in different stages of CKD patients. MATERIAL AND METHODS: This cross-sectional study included 30 predialysis, 40 hemodialysis, 35 peritoneal dialysis patients, and 30 healthy subjects. N/L ratio and important clinical and laboratory parameters were registered. Multivariate regression analyses were carried out to investigate the relations of N/L ratio. RESULTS: N/L ratio was significantly higher in each patient group compared to the healthy subjects (for all, p < 0.001). It was positively correlated with interleukin-6 (IL-6) (r = 0.393, p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.264, p = 0.002) levels and negatively correlated with hemoglobin (r = -0.271, p = 0.001), serum albumin (r = -0.400, p < 0.001), and high-density lipoprotein (HDL) cholesterol levels (r = -0.302, p < 0.001). In CKD patients with hypertension (HT), higher N/L ratio was detected when compared to those without HT (p = 0.006). Having CKD, the presence of HT, serum albumin, HDL-cholesterol, IL-6, and hs-CRP levels were found to be independent predictors of the ratio after adjusting for significant covariates (p < 0.001). CONCLUSION: An easy and inexpensive laboratory measure of N/L ratio might provide significant information regarding inflammation in CKD including predialysis and dialysis patients.

Volatile anesthetic preconditioning attenuated sepsis induced lung inflammation.

BACKGROUND: This study aimed to evaluate the differential protective effects of isoflurane or sevoflurane on lung inflammation in a rat model of cecal ligation and puncture (CLP) induced sepsis. METHODS: Seventy-two rats were assigned to control, sevoflurane, or isoflurane groups. At 2 and 4 h, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), nitrate/nitrate levels (NO), total antioxidant capacity (TAC), and intercellular cell adhesion molecule-1 (ICAM-1) were determined. At 12 and 24 h, malondialdehyde (MDA), myeloperoxidase (MPO), and histologic changes were evaluated. Survival was monitored for 7 d after CLP. RESULTS: Sevoflurane (75%) and isoflurane (63%) significantly improved survival rate compared with control rats (38%). When sevoflurane and isoflurane groups were compared, sevoflurane pretreatment showed significant decrease in NO at 2 h [1045 (803-1274)/1570 (1174-2239) and 4 h [817 (499-1171)/1493 (794-2080)]; increase in TAC at 4 h [580.0 (387-751)/320 (239-512)]; decrease in MDA at 12 h [2.5 (1.1-4.2)/5.4 (4-73)] and 24 h [10.8 (6.0-14.0)/15.9 (9-28)]; and decrease in MPO at 24 h [145.8 (81-260)/232 (148-346)]. The difference in the ICAM-1 expression of the isoflurane and sevoflurane groups was not significant at both measurement times. The architectural integrity of the alveoli was preserved in all the groups. The injury scores of the three groups at 12 and 24 h did not show any significant difference. CONCLUSIONS: Both sevoflurane and isoflurane attenuated inflammatory response, lipid peroxidation, and oxidative stress. Furthermore, sevoflurane was more effective in modulating sepsis induced inflammatory response at the chosen concentration in sepsis model.

Elevated homocysteine and asymmetric dimethyl arginine levels in pulmonary hypertension associated with congenital heart disease.

Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality among patients with congenital heart disease (CHD). This study was designed to determine biomarker levels in patients with PAH associated with CHD (PAH-CHD) and CHD patients without PAH and to investigate the relationship of these potential biomarkers with hemodynamic findings. In this prospective single-center study, patients with CHD were analyzed according to the presence or absence of PAH and compared with healthy control subjects. Cardiac catheterization and echocardiographs were performed. Plasma homocysteine, asymmetric dimethyl arginine (ADMA), and nitric oxide (NO) levels were determined by enzyme-linked immunosorbent assay. Homocysteine and ADMA levels were higher in the PAH-CHD group (n = 30) than among CHD patients with left-to-right shunting but no PAH (n = 20; P < 0.001) and healthy control subjects (n = 20; P < 0.001). There was no difference in NO levels. Cyanotic PAH-CHD patients had significantly higher homocysteine than acyanotic patients in the same group. No correlation was shown between echocardiographic/hemodynamic parameters and homocysteine, ADMA, and NO levels. Homocysteine and ADMA levels are increased in patients with PAH-CHD. These parameters have the potential to be used as biomarkers in the diagnosis and follow-up evaluation of patients with PAH-CHD. However, large, multicentered prospective studies are required to facilitate routine use of these biologic markers in the clinical setting.

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

OBJECTIVE: The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores. METHOD: Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively. RESULTS: Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r = - 0.675) and ITAS scores (r = - 0.385), as well as with CRP and CRI. CONCLUSION: Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.

Effects of nuclear factor-κB inhibitors on colon anastomotic healing in rats.

BACKGROUND: Nuclear factor (NF)-κB plays an essential role in inflammation. We tested this role by administering NF-κB-inhibitors into rats undergoing a well-established model of colonic anastomotic healing. METHODS: Wistar rats underwent laparotomy, descending colonic transection, and handsewn reanastomosis. The animals were randomized to receive either a selective NF-κB inhibitor (parthenolide 0.5 mg/kg or resveratrol 0.5 mg/kg) or an equal volume of water by gavages before operation and then daily after surgery. Animals were sacrificed either immediately after anastomotic construction (d 0) or at the third, fifth, or seventh postoperative day. RESULTS: Both parthenolide and resveratrol treatment led to early significant increases in plasma levels of IL-6. On d 7, hydroxyproline levels were significantly higher in the parthenolide and resveratrol groups. A similar pattern was observed with the bursting pressure. In contrast, gelatinase activity (MMP-2 and MMP-9 expression) was significantly higher in the control group on postoperative d 3. On d 3, expression of NF-κB activity was up-regulated in the anastomotic area. Both parthenolide and resveratrol completely attenuated NF-κB activity. Study groups also developed more marked inflammatory cell infiltration and collagen deposition on histology analysis. CONCLUSIONS: Parthenolide and resveratrol significantly improved healing and mechanical stability of colonic anastomoses in rats during the early postoperative period. Both agents may be acting to accelerate the host reparative process as well as to enhance protection of the anastomotic wound bed.

Protective effect of beta-glucan on contrast induced-nephropathy and a comparison of beta-glucan with nebivolol and N-acetylcysteine in rats.

BACKGROUND: It has been shown that beta-glucan (BG), which has antioxidant and immunomodulatory effects, attenuats renal ischemia-reperfusion injury. We aimed to investigate whether BG might have a preventive role against the development of contrast-induced nephropathy and to compare its effect with nebivolol (Nb) and N-acetylcysteine (NAC). METHODS: Thirty-six Wistar albino female rats were randomly divided into six groups (n = 6 each): control, contrast media (CM), BG, BG + CM, Nb + CM, and NAC + CM. With the exception of control and CM groups, the others were given drugs orally once a day for 5 days. Kidney function parameters, inflammatory parameters, and serum and renal tissue oxidative stress markers were measured. RESULTS: Increases of serum creatinine and blood urea nitrogen levels were significantly higher (p < 0.05) in the CM group only. Absolute changes of serum creatinine levels in BG, BG + CM and Nb + CM groups were significantly lower than those in the CM group (p < 0.05). Serum levels of advanced oxidation protein products and malondialdehyde were significantly less (p < 0.05) in the BG group compared to the CM group. Histopathological lesions in the CM group were more advanced (p < 0.05). No significant differences between the BG + CM, Nb + CM and NAC + CM groups were found with regard to histopathological findings. CONCLUSION: This study suggests that BG protects or ameliorates against contrast-induced nephropathy. Its beneficial effects may be similar to or greater than those of Nb or NAC.

The effects of delivery route and anesthesia type on early postnatal weight loss in newborns: the role of vasoactive hormones.

OBJECTIVE: To investigate the effects of delivery route and maternal anesthesia type and the roles of vasoactive hormones on early postnatal weight loss in term newborns. METHODS: Ninety-four term infants delivered vaginally (group 1, n=31), cesarean section (C/S) with general anesthesia (GA) (group 2, n=29), and C/S with epidural anesthesia (EA) (group 3, n=34) were included in this study. All infants were weighed at birth and on the second day of life and intravenous (IV) fluid infused to the mothers for the last 6 h prior to delivery was recorded. Serum electrolytes, osmolality, N-terminal proANP (NT-proANP), brain natriuretic peptide (BNP), aldosterone and plasma antidiuretic hormone (ADH) concentrations were measured at cord blood and on the second day of life. RESULTS: Our research showed that postnatal weight loss of infants was higher in C/S than vaginal deliveries (5.7% vs. 1.3%) (p < 0.0001) and in EA group than GA group (6.8% vs. 4.3%) (p < 0.0001). Postnatal weight losses were correlated with IV fluid volume infused to the mothers for the last 6 h prior to delivery (R = 0.814, p = 0.000) and with serum NT-proANP (R = 0.418, p = 0.000), BNP (R = 0.454, p = 0.000), and ADH (R = 0.509, p = 0.000) but not with aldosterone concentrations (p > 0.05). CONCLUSION: Large amounts of IV fluid given to the mothers who were applied EA prior to the delivery affect their offsprings' postnatal weight loss via certain vasoactive hormones.

The impact of dialysis type on biomarkers for cardiovascular diseases.

OBJECTIVES: The impact of dialysis type on the biomarkers that reflect the severity of cardiovascular diseases is not clearly known. We aimed to investigate the effect of dialysis type on biomarkers of cardiovascular diseases in patients with end-stage renal disease (ESRD). STUDY DESIGN: The study included 108 patients who had been on dialysis treatment (57 patients receiving hemodialysis, 51 patients receiving peritoneal dialysis) for ESRD for at least three months. Blood samples were collected just after the dialysis. Serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), cardiac troponin I (TnI), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and plasma fibrinogen levels were measured and compared between the two dialysis groups. RESULTS: The two dialysis groups were similar with respect to age and gender. The frequency of hypertension was significantly higher in patients receiving peritoneal dialysis. This group also had higher total cholesterol, HDL cholesterol, LDL cholesterol, and hemoglobin levels. Serum levels of NT-proBNP, hs-CRP, IL-6, and TNF-α, and plasma fibrinogen levels were similar in the two dialysis groups (p>0.05), but TnI was significantly higher in patients receiving peritoneal dialysis (p=0.04). Comparison of the patient subgroups based on the duration of dialysis (<12 months, 12-36 months, and >36 months) showed that longer dialysis duration was associated with significantly lower values of NT-proBNP, TNF-α, and hs-CRP (p<0.05). CONCLUSION: The dialysis type does not affect serum NT-proBNP, hs-CRP, IL-6, TNF-α, and plasma fibrinogen levels, but TnI level is higher in patients treated with peritoneal dialysis.

FGF23, alpha-Klotho and vitamin D mediated calcium-phosphate metabolism in haemodialysis patients.

BACKGROUND: Klotho is a prote˝in that acts as a co-receptor for FGF23. FGF23-Klotho axis has great importance regarding the regulation of mineral metabolism by kidneys. In this study, we analysed FGF23, Klotho, 1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D, parathormone, Calcium and Phosphate levels of haemodialysis patients in order to investigate the nature of the mineral metabolism disruption in chronic kidney diseases. METHODS: Sixty haemodialysis patients and 34 healthy controls were included in the study. Serum iFGF, cFGF, and soluble Klotho were analysed using ELISA kits. Moreover, 1,25-dihydroxyvitamin D3 was determined using LCMS/MS. Calcium, phosphate, iPTH and 25-hydroxyvitamin D were measured using autoanalyzers. RESULTS: In haemodialysis patients, iFGF23, cFGF23, iPTH and P levels were significantly higher, and 1,25-dihydroxyvitamin D3, Klotho and Ca levels were significantly lower compared with the control group. There was no significant difference in the 25-hydroxyvitamin D levels. CONCLUSIONS: Our study showed that lack of sufficient amounts of Klotho is crucial for mineral metabolism disruptions seen as a complication of chronic kidney diseases. Despite the high levels of the hormone, FGF23 is unable to accomplish its function properly, likely due to deteriorated kidney function in haemodialysis patients.

Probiotic agent Saccharomyces boulardii reduces the incidence of lung injury in acute necrotizing pancreatitis induced rats.

BACKGROUND: Acute necrotizing pancreatitis is a severe acute inflammatory disease of the pancreas that can lead to extrapancreatic organ involvement. Supervening lung injury is an important clinical entity determining the prognosis of the patient. Probiotics are dietary supplements known to reduce or alter inflammation and inflammatory cytokines. In the present study, we hypothesize that probiotics may reduce lung injury by reducing bacterial translocation, which results in reduced infection, inflammation, and generation of proinflammatory cytokines in an experimental model of acute necrotizing pancreatitis. METHODS: Pancreatitis was induced by concomitant intravenous infusion of cerulein and glycodeoxycholic acid infusion into the biliopancreatic duct. Saccharomyces boulardii was used as the probiotic agent. Rats were divided into three groups: sham, pancreatitis-saline, which received saline via gavage at 6 and 24 h following the pancreatitis, pancreatitis-probiotics, which received probiotics via gavage method at 6 and 24 h following the pancreatitis. The rats were sacrificed at 48 h, venous blood, mesenteric lymph node, pancreatic and lung tissue samples were obtained for analysis. RESULTS: Serum pancreatic amylase, lactate dehydrogenase, secretory phospholipase A(2), and IL-6 were found to be increased in pancreatitis-saline group compared with the other groups (P < 0.05). Histological analyses revealed that edema, inflammation, and vacuolization as well as polymorphonuclear leukocyte infiltration in the lung tissue was significantly reduced in the probiotic treated group. Bacterial translocation was significantly reduced in the probiotic treated group compared with the other groups (P < 0.05). CONCLUSION: These results suggest that Saccharomyces boulardii reduce the bacterial translocation. As a result of this, reduced proinflammatory cytokines and systemic inflammatory response was observed, which may be the reason underlying reduced lung injury in acute necrotizing pancreatitis.