Mullerian inhibiting substance, sex hormone binding globulin and sex hormone levels in stimulant-naïve, first-diagnosed prepubertal boys with attention-deficit/hyperactivity disorder: comparison with matched healthy controls as well as before and after oros-methylpenidate treatment.

Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder with strong male predominance. Since Müllerian Inhibiting Substance (MIS) produces sex-linked bias in animal studies, we aimed to investigate the role of MIS, Sex Hormone Binding Globulin (SHBG) and sex hormone levels in boys with ADHD.Methods: We compared prepubertal, psychostimulant-naïve boys with ADHD with age-matched healthy control boys (HCs). Patients were re-evaluated after 30 days of methylphenidate treatment assessing ADHD severity, and serum MIS, testosterone, estradiol, and albumin concentrations.Results: Compared to 30 HCs, with ADHD (n = 49, age = 6.9 ± 0.2 years) had lower SHBG (p = .014), and higher free testosterone (p = 0.006) and bioavailable testosterone (p = .002) percentages. Methylphenidate improved ADHD measures (all p < .0001) and abnormal baseline hormonal levels, increasing SHBG levels (p = .024), and lowering free (p = .001) and bioavailable testosterone (p = .016) percentages so that only free testosterone percentages remained higher versus HCs post-treatment (p = .02).Conclusions: Compared to age- and sex-matched HCs, prepubertal, stimulant-naïve boys with ADHD had significantly lower SHBG and higher free and bioavailable testosterone percentages, suggesting a possible contribution of sex hormones to ADHD. Osmotic-release oral system methylphenidate treatment for 30 days significantly improved ADHD symptoms and abnormal sex hormone levels, normalizing SHBG and bioavailable testosterone percentages that were similar to HCs while free testosterone remained elevated versus HCs.Key pointsCompare to healthy matched controls prepubertal stimulant-naïve boys with ADHD had significantly lower SHBG and higher free and bioavailable testosterone percentages, suggesting a possible effect on sex hormones to ADHD.After 30-day methylphenidate treatment, ADHD symptoms significantly improved, and SHBG and bioavailable testosterone percentages normalized which were similar to HCs, while free testosterone remained elevated versus HCs.We found a negative relationship between MIS levels and hyperactivity scores in ADHD boys. This finding suggests that MIS may contribute to hyperactivity symptoms, either directly by affecting behavior or indirectly by affecting sex hormone levels.

The Place of Calprotectin, Lactoferrin, and High-Mobility Group Box 1 Protein on Diagnosis of Acute Appendicitis with Children.

The purpose of this study is to investigate the role of serum calprotectin (CP), lactoferrin (LF), and high-mobility group protein B1 (HMGB-1) levels and fecal CP and LF levels in differential diagnosis of acute uncomplicated appendicitis from other causes of abdominal pain and further from complicated appendicitis. Totally, 120 children were included grouped into 4 as: healthy controls, patients with right lower quadrant pain with other than surgical causes, patients with uncomplicated appendicitis, and patients with complicated appendicitis. Serum CP, LF, HMGB-1, C-reactive protein (CRP) levels, and white blood cell (WBC) count were studied as well as the fecal CP and LF levels. There was a statistically significant difference between control group and both uncomplicated and complicated acute appendicitis groups, regarding all parameters. In diagnosis of complicated acute appendicitis, area under curve (AUC) for fecal LF, serum CP, and serum HMGB-1 were determined as 1.00 and the cutoff level was determined as 25 µg/g feces, 670 ng/mL, and 30 ng/mL, respectively. In differential diagnosis of uncomplicated and complicated AA, the most accurate parameter was fecal LF with an AUC of 0.977. At a 60 µg/g cutoff value for this variable, sensitivity, specificity, and accuracy were 96.7, 93.3, and 95.0 %, respectively. In conclusion, HMGB-1, calprotectin, and lactoferrin constitute novel markers in diagnosis of AA. Moreover, their levels may be helpful for the clinicians to judge about the severity of the condition. Larger studies are warranted to determine the diagnostic potential of HMGB-1, LF, and CP in AA diagnosis.

Relationship between soluble intercellular adhesion molecules and attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-oneset psychiatric disease, characterized by excessive overactivity, inattention, and impulsiveness. In recent studies, it is emphasized that inflammation may have a role in ADHD. In this study, we aimed to investigate whether there are associations between ADHD and serum levels of soluble intercellular adhesion molecules (s-ICAMs) which have important role in inflammatory diseases. We also measured the levels of these molecules after treatment with oros-methylphenidate. METHODS: Twenty-five patients diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders-IV-TR criteria and 18 healthy volunteer controls were included in this study. The levels of sICAMs were measured in the serum of the patients and healthy volunteers by ELISA kit as described. RESULTS: The levels of sICAM-1 and sICAM-2 were significantly higher in patients compared with controls. The level of sICAM-2 was decreased significantly in group treated with oros-methylphenidate. CONCLUSIONS: This is the first study pointing out the relationship between sICAMs and ADHD. The changes in sICAM-2 level may have a role in the effect mechanism of oros-methylphenidate, used for the treatment of ADHD.

A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers.

BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

Investigation of intercellular adhesion molecules (ICAMs) gene expressions in patients with Barrett's esophagus.

The adhesion molecules play a major role in inflammation as well as in neoplastic diseases. The aim of this study is to evaluate the expressions of the adhesion molecules, intercellular adhesion molecule 1 (ICAM-1), ICAM-2, and ICAM-3, in Barrett's esophagus, recognized as a premalign lesion for esophageal cancer and related to inflammation. Eighteen patients with Barrett's esophagus according to endoscopy and 25 volunteers without Barrett's esophagus disease were included in the study. Tissue samples were supplied by biopsy and used for both gene expression and immunohistochemical analysis. The significance of the differences between the two groups was assessed by Student's t test. The ICAM-1 expression level was fivefold higher in the patient group compared with that of the control. There was an increase in the serum level of ICAM-1 in patients compared to that of the controls, but this increase was not significant. ICAM-2 levels were also increased in the patient group, but it was not significant. There was no difference between controls and patients in ICAM-3 levels. Significantly higher levels of ICAM-1 gene expression make us think that ICAM-1 may play an important role in Barrett's esophagus. We think that more studies, with larger patient groups and preferably detailed histopathological and clinical evaluations, are needed to explain the severity of ICAM-1, ICAM-2, and ICAM-3 molecules in Barrett's esophagus.

The role of hepcidin and its related genes (BMP6, GDF-15, and HJV) in rats exposed to ischemia and reperfusion.

BACKGROUND/AIM: To determine the roles of hepcidin and its related genes in a renal ischemia/reperfusion model. MATERIALS AND METHODS: A total of 20 Wistar albino rats were equally divided into 2 groups: Group I was the control group and Group II was the ischemia and reperfusion (I/R) group (60 min of ischemia + 48 h of reperfusion). I/R was performed on the left kidneys of these rats and then the I/R-treated kidneys were removed. The levels of serum biochemical markers were evaluated after renal I/R. The expression levels of hepcidin-linked genes [growth differentiation factor 15 (GDF-15), bone morphogenetic protein 6 (BMP6), and hemojuvelin (HJV)] were also measured by RT-PCR technique. In addition, the tissues were evaluated histopathologically. RESULTS: No significant association was found between renal dysfunction and I/R when compared to biochemical parameters (P > 0.05). However, differences in platelet values were statistically significant (P < 0.05). Expression levels of GDF-15, BMP6, and HJV genes increased, but this increase was not statistically significant. In addition, histopathological evaluation was performed using hematoxylin and eosin stain. This showed a significant relationship between the control group and I/R group for ischemic and nonischemic kidney scoring. CONCLUSION: Hepcidin and BMP6, HJV, and GDF-15 should be taken into account when investigating the process of I/R.

Persistency of high proinflammatory cytokine levels from colostrum to mature milk in preeclampsia.

OBJECTIVES: Recent evidence suggests a role of an excessive maternal inflammatory response in the pathogenesis of preeclampsia. Whether this imbalance can be transferred from mother to breast milk remains to be established. DESIGN AND METHODS: 15 preeclamptic and 15 healthy pregnant women were recruited in this study. Colostrum and milk samples were collected postpartum in the first 48 h and at 30 days, respectively. Samples were analyzed for interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and soluble IL-2R (sIL-2R) levels with chemiluminescence enzyme immunometric assays. RESULTS: Colostrum cytokine levels corrected for gestational age and type of delivery were not significantly different in the two groups. Cytokine levels significantly decreased in mature milk versus colostrum in the control group (P < 0.05), but did not significantly decrease in the preeclampsia group (P > 0.05), except for TNF-alpha (P < 0.05). Mature milk IL-8 and TNF-alpha levels were higher in the preeclampsia group versus controls (P < 0.05). CONCLUSION: Results of this study show that proinflammatory cytokines in breast milk exhibit biological variation at different periods of human lactation. In preeclampsia, high cytokine levels persist at least for 30 days. These results suggest that preeclampsia may affect milk cytokine balance and offer an immunological signal for the host defense in high-risk neonates.

Decreased adrenomedullin and total nitrite levels in breast milk of preeclamptic women.

OBJECTIVE: To observe the adrenomedullin (AM) and total nitrite levels in the milk of preeclamptic and normal pregnant women. DESIGN AND METHODS: Fifteen women with preeclampsia and 15 normal pregnant women were included in the study. Total nitrite was quantitated by Griess reaction, while AM was measured by HPLC. RESULTS: The levels of AM and total nitrite in colostrum and 30th-day breast milk were decreased in preeclamptics. Total nitrite levels (micromol/l) were 56.09 +/- 11.18 vs. 82.20 +/- 12.01, P < 0.05, in colostrum of preeclamptics and controls, respectively. The level of total nitrite was 37.75 +/- 12.10 vs. 53.28 +/- 10.25, P < 0.05, in 30th-day milk of same patients. AM levels (pg/ml) were 11.18 +/- 1.11 vs. 16.59 +/- 1.24, P < 0.0001, in colostrum of preeclamptics and controls, respectively. In 30th-day milk of same patients, AM levels were 8.41 +/- 1.39 vs. 12.18 +/- 1.48, P < 0.005, respectively. CONCLUSION: This report shows for the first time that human milk has decreased levels of AM and total nitrite in preeclampsia.

Plasma lipid and lipoprotein concentrations in pregnancy induced hypertension.

OBJECTIVES: Aim of this study was to evaluate implication of pregnancy induced hypertension on maternal plasma lipid, lipoprotein, apolipoprotein concentrations and lipid peroxidation products by a comparison of normal pregnancy vs. preeclampsia. DESIGN AND METHODS: Thirty-four women with preeclampsia and 32 healthy pregnant women (controls) in the third trimester were recruited for this study. RESULTS: In the preeclamptic group plasma total triglyceride, low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA) and apolipoprotein B (apo-B) were significantly increased, while plasma high density lipoprotein cholesterol (HDL-C) was significantly decreased compared to that of control group. There was no significant difference in total cholesterol and apolipoprotein A1 (apo-A1) concentrations. CONCLUSION: Our findings suggest that preeclampsia share some metabolic characteristics with coronary artery disease such as dislipidemia and increased lipid peroxidation. However lipoprotein concentrations may be better biochemical markers of dislipidemia in the preeclamptic state than the corresponding apolipoproteins.

Acute effect of hemodialysis on serum levels of the proinflammatory cytokines.

Chronic inflammation is a common feature of end-stage renal disease, which carries a heightened risk of atherosclerosis and other co-morbid conditions. Dialysis treatment per se can bring additional risk factors for inflammation, such as increased risk of local graft and fistula infections, impure dialysate or bio-incompatible membranes. Our study was designed to determine whether a hemodialysis session leads to an acute substantial alteration in the plasma levels of the proinflammatory cytokines interleukin (IL)-6, IL-1beta and tumor necrosis factor (TNF)-alpha, the T-lymphocyte activation factor soluble IL-2 receptor (sIL-2R), and an inflammation mediator and chemotactic granulocyte factor, IL-8, in end-stage renal disease patients receiving chronic intermittent HD. In this study, 21 (12 male/nine female) patients undergoing chronic hemodialysis were enrolled. The acute effect of a hemodialysis session on serum cytokine concentrations was assessed by comparison of pre-hemodialysis and post-hemodialysis determinations. Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha levels were determined with chemiluminescence enzyme immunometric assays. A significant difference was not observed for IL-1beta, IL-6, TNF-alpha, and sIL-2R concentrations in pre-hemodialysis and post-hemodialysis specimens (p>0.05). Serum median (25th-75th percentiles) IL-8 concentration was 69.4 (34.9-110.3) pg/ml before hemodialysis, and decreased to 31.5 (18.0-78.8) pg/ml following hemodialysis (p: 0.006). Clearance of IL-8 increased by 0.47+/-0.08 pg/ml for each unit increase in pre-dialysis IL-8 (p<0.001) and decreased by 5.63+/-2.59 pg/ml for each unit increase in pre-dialysis urea mmol/l (p<0.05). In conclusion, the results of our study demonstrate that a hemodialysis session markedly decreases IL-8 concentration, which is significantly affected by pre-dialysis concentrations, indicating that removal of IL-8 is a concentration gradient-dependent action, but does not change the serum levels of IL-1beta, sIL-2R, IL-6, and TNF-alpha, underlining importance of the structural characteristics of the molecules.

Pediatric urolithiasis--evaluation of risk factors in 95 children.

OBJECTIVE: Pediatric urolithiasis is a rarely encountered pathology, except in endemic areas such as Turkey. As a recurrent pathology which may reveal functional as well and morphologic changes in the urinary tract, metabolic and environmental factors, in addition to urogenital abnormalities, should be evaluated thoroughly in each patient. In this prospective study, the patient and family histories of 95 children with stone disease were evaluated, together with serum and urine risk factors. MATERIAL AND METHODS: Between 1996 and 2001, 95 children (25 females, 70 males; mean age 7.3 years; age range 0.6-15 years) referred to our department with urolithiasis were evaluated. All patients were investigated with respect to stone localization, associated abnormalities, urinary tract infection (UTI), positive family history and serum and urine risk factors. In addition to standard risk factors (hypocitraturia, hypercalciuria, hyperoxaluria, hyperuricosuria, hypomagnesuria), diet and 24-h urine volume were also assessed in all children. Children with cystinuria were excluded from the study. RESULTS: Stone size ranged from 0.3 to 3.3 cm, with an average value of 2.0 cm. The localization of the stones was classified as unilateral single stone in 37 patients, multiple unilateral stones in six and bilateral multiple stones in 27. Hypocitraturia was the commonest risk factor detected in our patients. A positive family history was present in 51 cases (54%). In addition, UTI was present in 59 cases (62%) and 67 cases had a previous history of recurrent UTI. Associated urogenital abnormality was detected in nine cases (9.4%). There were significant correlations between stone size and urinary citrate excretion (p < 0.05) and between the presence of UTI and urinary phosphate excretion (r = 0.59, p = 0.047). Treatments used were open surgery in seven (7.3%) cases, extracorporeal shock-wave lithotripsy in 39 (41%) and endoscopic surgery in 20 (21%). Following these procedures, 39 (41%) patients were completely stone-free, 11 (11%) had residual stones (<5 mm in diameter) and 12 (14.8%) passed the stone(s) spontaneously. During follow-up, regrowth was seen in four (4.2%) patients and stone recurrence was noted in a further four (4.2%). CONCLUSIONS: In addition to stone removal, treatment of pediatric urolithiasis requires a thorough metabolic and environmental evaluation of all patients on an individual basis. Obstructive pathologies have to be corrected immediately and apparent metabolic abnormalities should also be treated. Children with a positive family history should be followed carefully with respect to stone recurrence. Urine volume increases in parallel with body mass index and medical therapeutic agents which increase urine citrate levels should be encouraged.

Triglycerides predict plasma fibronectin in children with type I diabetes mellitus rather than diabetes.

Fibronectins are adhesive proteins considered as markers of endothelial activation. Plasma fibronectin levels in diabetes mellitus (DM) have been found to be associated with atherosclerotic risk factors. This study was carried out to investigate plasma fibronectin and its relation with serum lipids, apolipoproteins AI, B100 and lp(a) in diabetic children. 35 children (19F/16M) with type I DM and 30 non-diabetic age and gender-matched controls were enrolled. Apolipoprotein and fibronectin concentrations were determined with nephelometric methods. Plasma fibronectin levels of the children with type I DM and the control group are not statistically different. HbA1c and triglycerides concentration are found to be significant predictors of plasma fibronectin in diabetic children, while effect of plasma cholesterol, apolipoprotein AI, B100 and lp(a) are insignificant. Diabetic children with triglycerides 1.13 mmol/l have elevated plasma fibronectin (median, 25th-75th percentiles; 29.6, 8.3-40.8 mg/dL) compared to the diabetic > or = 19.9, 8.6-30.7 mg/dL, p < 0.05) and non-diabetic children (16.6, 12.7-32.4 mg/dL, p < 0.01) with triglycerides < 1.13 mmol/L. On the other hand plasma fibronectin concentrations of diabetic and non-diabetic children with high triglycerides are not significantly different. In conclusion our data does not support the concept that plasma fibronectin is elevated in type I diabetes mellitus at least in children, but high plasma triglycerides secondary to diabetes or not is associated with higher FNp concentrations which may have implications on atherogenesis. Plasma cholesterol, apolipoproteins AI, B100 and lp(a) are not significant determinants of FNp in type I diabetic children.

Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus.

OBJECTIVES: Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation This study aimed to evaluate serum prolidase activity and urinary deoxypyridinoline cross links in type 2 diabetic subjects with and without osteoporosis assessed by bone mineral density. DESIGN AND METHODS: Seventy-five patients (54 F/21 M) with type 2 DM and 43 age and gender matched healthy subjects (30 F/13 M) were recruited for this study. Serum prolidase activity was assessed with colorimetric determination. Urinary deoxypyridinoline (Dpy) was determined with electrochemiluminesence immunoassay. RESULTS: Serum prolidase activity was significantly lower in patients with type 2 DM than in the healthy controls (mean +/- SEM; 43.3 +/- 1.4 U/L and 53.3 +/- 2.2 U/L respectively, p: 0.000). Non osteoporotic diabetic patients had lower serum prolidase activity (median: 25th-75th percentiles; 39.5: 30.3-50.5 U/L) than osteoporotic diabetic patients (50.0: 41.8-56.3 U/L, p: 0.030) and healthy controls (52.0: 43.0-58.0 U/L, p: 0.004). Urinary Dpy excretion was not different between osteoporotic and nonosteoporotic diabetic patients. However it was lower in both diabetic groups than the healthy controls. We did not observe a statistically significant difference between the serum prolidase activity of dislipidemic/normolipidemic, hypertensive/normotensive, obese/nonobese, insulin/OAD treated, poorly/well-controlled patients and patients with/without diabetic nephropathy and retinopathy (p > 0.05). CONCLUSION: This study shows a significant decrease in serum prolidase activity in patients affected with type 2 DM, which may be interpreted as evidence of decreased bone resorption. Our data also suggest that serum prolidase activity may be a better marker of osteoporosis in diabetic state than Dpy.

Diagnostic value of CRP and Lp(a) in coronary heart disease.

OBJECTIVES: Increased lipoprotein (a) [Lp(a)] concentration was reported to be an independent risk factor for coronary heart disease (CHD). Recent epidemiological studies affirmed the value of C-reactive protein (CRP) as the strongest, univariate predictor of the cardiovascular events. We decided to establish cut-off levels providing maximum diagnostic efficiency for CHD. METHODS: In this study we measured CRP and Lp(a) concentrations in patients with angiographically demonstrated CHD (group A, n: 120), patients without any angiographically demonstrable lesion (group B, n: 62) and a group of healthy subjects (group C, n: 41). Data were evaluated correcting for lipid and lipoprotein concentrations, diabetes mellitus, hypertension, smoking, age, and body mass index in men and women. ROC curve based cut-off values (comparing group A versus groups B and C) and associated diagnostic performances of the assays were evaluated. RESULTS: Significant increases were noted in serum CRP concentrations in men and women, in groups A vs. B,A vs. C, B vs. C. Lp(a) concentrations were not different among groups in men but were higher in group A vs. B and C in women. Optimal cut-off levels for CRP in women and men were found as 2.1 and 3.0 mg/l with the diagnostic values of 0.792 and 0.770, respectively. For Lp(a) optimal cut-off levels were found as 22.6 and 9.8 mg/dl with the diagnostic values of 0.612 and 0.596 in women and men, respectively. CONCLUSION: The CRP level is quite efficient for separation of patients from controls. Therefore keeping in mind the lack of specificity, the CRP level may be a useful tool in the diagnosis of coronary heart disease. However, the Lp(a) level is not efficient enough to support the use of Lp(a) measurement for management of coronary heart disease.