The relationship between serum FGF-23 concentration and insulin resistance, prediabetes and dyslipidemia in obese children and adolescents.

Background Obesity is known to cause metabolic disturbances including insulin resistance, dyslipidemia and alters bone mineralization. The effects of obesity on fibroblast growth factor 23 (FGF-23), which is important in bone mineralization, have not yet been clarified. Our aim was to investigate the association between FGF-23 concentration and obesity-associated dysmetabolism. Methods Subjects comprised 46 obese children and adolescents. The same number of age-matched, healthy controls were recruited. Markers of bone mineralization and glucose metabolism were measured. Thyroid function and insulin resistance were investigated in both groups. In obese subjects; an oral glucose tolerance test (OGTT) was performed and hemoglobin A1c and lipid fractions were measured. Bone mineral density and hepatic steatosis were investigated. Results Serum FGF-23, α-klotho and 1,25(OH)2D3 concentrations were significantly lower while fasting insulin, fasting glucose, C-peptide and alkaline phosphatase (ALP) concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the obese group compared to controls. A significant negative correlation was observed between free tri-iodothyronine (fT3) and both FGF-23 and α-klotho in the obese group. Significant negative correlation was found between FGF-23 and C-peptide and a positive correlation was found between FGF-23 and high density lipoprotein-cholesterol (HDL-c) in the obese subjects with impaired glucose tolerance (IGT). Significant negative correlations were found between FGF-23 and both fasting insulin levels and C-peptide levels in the obese subjects with hepatic steatosis. Conclusions In our study, insulin resistance-associated hyperinsulinism and/or lower 1,25(OH)2D3 levels, both present in obese children and adolescents, may lead to decreased serum FGF-23 concentrations in obese subjects.

Atorvastatin exerts anti-nociceptive activity and decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in a rat endometriosis model.

PURPOSE: The purpose of this study was to examine the effects of atorvastatin in the treatment of experimental endometriosis. METHODS: Endometriosis was induced in 24 female rats. 4 weeks after the procedure dimensions of the foci were recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriotic foci were recorded. Biochemical, histopathological and immunohistochemical studies were performed and nociception was compared in groups. RESULTS: Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-α levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05). CONCLUSION: Atorvastatin treatment may have a therapeutic potential in the treatment of endometriosis through its anti-inflammatory and anti-nociceptive properties.

Nuclear transcription factor-kappa beta-dependent ultrastructural alterations within the placenta and systemic inflammatory activation in pregnant patients with hemolysis, elevated liver functions and low thrombocyte count (HELLP) syndrome: a case-control study.

OBJECTIVE: Preeclampsia appears to be associated with a higher extent of inflammation than in uncomplicated pregnancies. We aimed to test whether this was the case in patients with hemolysis, elevated liver functions and low platelet count (HELLP) syndrome and to clarify the contribution of placental and systemic inflammatory variables in the development of this syndrome. MATERIALS AND METHODS: Thirty healthy pregnant women (control group) and 20 patients with HELLP syndrome (study group) were included in the study. Placental inflammatory activity was evaluated by quantifying immunohistochemically the levels of p65/RelA expression of nuclear transcription factor-kappa beta (NF-kB) in paraffin-embedded tissue samples. In addition, ultrastructural changes in placental morphology in HELLP patients were evaluated by transmission electron microscopy (TEM). The serum concentrations of myeloperoxidase (MPO) and C-reactive protein (CRP) were also measured and compared. RESULTS: p65/RelA immunoexpression and serum MPO and CRP levels were significantly higher in patients with HELLP syndrome (p < 0.05). TEM of placenta in the study group revealed severely vacuolized syncytiotrophoblasts, irregular basal lamina and damaged capillary endothelium when compared with the placenta of control subjects. CONCLUSION: Our results suggest that over-expression of placental NF-kB is correlated with elevation of serum inflammatory markers and placental ultrastructural changes, which may point to an important role of local and systemic inflammatory activation in the pathogenesis of HELLP syndrome.

Amniotic fluid urocortin-1 concentrations for the prediction of preterm delivery.

AIM: The aim of this study was to analyze whether urocortin-1 concentration in midtrimester amniotic fluid could serve as an indicative marker of preterm labor. MATERIAL AND METHODS: A retrospective cohort study was conducted. Urocortin-1 concentrations in midtrimester amniotic fluid were measured in 22 pregnant women with preterm deliveries and 45 women who delivered at term using enzyme-linked immunosorbent assay. RESULTS: The median amniotic fluid urocortin-1 concentration was significantly lower in the women with preterm birth (40.06 pg/mL; range, 13.77-67.58 pg/mL) than in the women who gave birth at term (49.56 pg/mL; range, 26.25-175.9 pg/mL; P = 0.022). The result of receiver-operator curve analysis indicates that an amniotic fluid urocortin-1 concentration ≤ 57.88 pg/mL had an area under the curve of 0.673 (95% confidence interval, 0.55-0.78; P = 0.01) with a sensitivity of 81.8%, specificity of 40.0%, positive predictive value of 40%, and a negative predictive value of 82% in identifying which of the patients subsequently delivered prematurely. CONCLUSIONS: These results suggest that low urocortin-1 concentration in midtrimester amniotic fluid could be used as an indicative marker of preterm birth.

Prevalence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum in pregnant women.

BACKGROUND: Mycoplasma hominis and Ureaplasma urealyticum are important opportunistic pathogens implicated in urogenital infections and complicated pregnancy. We aimed to study the role of these pathogens in symptomatic and asymptomatic pregnant women and determine their clinical significance and antibiotic susceptibility. METHODS: One hundred pregnant women were included in the study, 50 symptomatic patients and 50 asymptomatic controls. Duplicate endocervical samples were taken from each individual and analyzed using the Mycoplasma IST-2 kit and A7 agar medium. Antimicrobial susceptibility was tested against doxycycline, josamycin, ofloxacin, erythromycin, tetracycline, ciprofloxacin, azithromycin, clarithromycin, and pristinamycin using the Mycoplasma IST-2 kit. RESULTS: Twelve symptomatic pregnant women had spontaneous abortions. Of these, eight (66.7%) cases had been colonized with M. hominis and/or U. urealyticum. Of the pregnant women infected with M. hominis and/or U. urealyticum, 40.7% delivered a low birth weight infant. M. hominis was successfully cultured in five women (5%) and U. urealyticum in 27 (27%). Among positive cultures, 15.6% and 84.4% of isolates were M. hominis and U. urealyticum, respectively. M. hominis and U. urealyticum were uniformly susceptible to doxycycline, tetracycline, and pristinamycin, which may be successfully used in the empirical therapy of infected individuals. CONCLUSIONS: It can be concluded that genital colonization with M. hominis and U. urealyticum may predispose to spontaneous abortion and low birth weight.

The role of ghrelin in weight gain and growth in epileptic children using valproate.

Ghrelin is a major hormone, regulating the energy balance of the body. Weight gain is a significant side effect of valproic acid, which has not been clearly identified pathogenetically. The aim of this study was to investigate the effect of valproic acid on ghrelin and its potential effects on weight gain and growth. Each patient and control group consisted of 35 children aged 3 to 15 years. Fasting serum glucose, insulin, C-peptide, leptin, ghrelin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels were measured in patients treated with valproic acid before and at month 6 of treatment. A significant increase in body weight, body mass index, height, and height standard deviation scores was observed in all patients after 6 months of treatment. Significant increases in growth velocity and weight gain were observed in the patient group compared with controls at 6 months of therapy. A significant increase in serum ghrelin levels (P < .01) was detected at the same time in the study group. A negative correlation of ghrelin with insulin-like growth factor-1 and insulin-like growth factor binding protein-3 was detected. Serum ghrelin levels were significantly increased (P < .05), and insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were significantly decreased (P < .01 and P < .05, respectively) in the prepubertal group at 6 months of treatment, but no significant change was observed in the pubertal group. Consequently, ghrelin levels significantly increase in the prepubertal children treated with valproic acid. The weight gain in using valproic acid may be associated with the increase in ghrelin level in the early treatment period.

The level of endothelin-1 and nitric oxide in patients with chronic viral hepatitis B and C and correlation with histopathological grading and staging.

BACKGROUND AND AIM: The aim of this study was to estimate the serum levels of endothelin-1 (ET-1) and nitric oxide (NO) and to analyze the correlation of their levels with histopathological grading and staging of the liver in patients with chronic hepatitis B (CHB) and C (CHC). METHODS: Eighty-nine patients who were either HBsAg positive (45 CHB patients, 34 inactive carriers (IC)) or had CHC (10 patients) and 36 healthy volunteers as a control group were included in this study. Fifty patients from the CHB (n=43) or CHC (n=7) groups with elevated serum alanine transaminase (ALT) levels underwent a liver biopsy. Histological activity was scored according to Ishak's activity and the fibrotic index. The ET-1 serum concentration was determined with a commercially available ELISA assay kit. Total nitrite was measured by the Griess reaction as an index for NO production. RESULTS: Serum levels of ET-1 and NO were significantly increased in CHB patients (7.67+/-4.00pg/ml and 172.44+/-50.30mumol/l, respectively) compared with the IC group (3.99+/-5.42pg/ml and 114.68+/-32.22mumol/l, respectively) and the control group (3.05+/-0.65pg/ml and 58.61+/-24.18mumol/l, respectively) (p<0.0001). The CHC patients also had significantly higher serum levels of ET-1 (5.92+/-4.24pg/ml) and NO (147.50+/-55.84mumol/l) compared to the control group (p<0.0001 and <0.001, respectively). Linear regression analysis identified that the level of ET-1 was an independent variable that correlated significantly with the stage score (r(2)=0.348, p<0.0001) in CHB patients but there was no correlation in the CHC group. CONCLUSION: ET-1 and NO levels were increased in chronic hepatitis and there was a significant correlation between the ET-1 level and the stage in CHB patients.

The prevalence and molecular typing of enterotoxigenic Escherichia coli strains isolated from diarrheic stools in Malatya, Turkey.

This study was performed from June 2002 to November 2003 year in Malatya, eastern Turkey. Stools of 172 diarrheic patients and 90 healthy controls were analysed for enterotoxigenic Escherichia coli (ETEC). Heat-labile (LT) and heat-stable (ST) toxins were investigated by passive latex agglutination and enzyme immunoassay, respectively. Nine ETEC strains were isolated from 172 diarrheic stools (5.2%). Seven of the ETEC strains (10.1%) were isolated from 69 children in the 0-5 year age group. Two of these pediatric isolates were ST positive (2.9%) and five were LT positive (7.2%). ETEC was not isolated in the 6-18 year age group. Two ST producing E. coli strains were detected in diarrheic adult patients (> 18 years). In the 90 controls, two ETEC strains were detected (2.2%). One of them was a LT producer (1.1%) and the other was a ST producer (1.1%). E. coli strains producing both toxins simultaneously were not observed. ETEC positivity was higher in the diarrheic group than in the control group but statistically not significant (p > 0.05). The rate of resistance among ETEC strains to cefuroxime axetil, ampicillin, piperacillin, and trimethoprim-sulfamethoxazole was 72.7%, 54.5%, 45.5%, and 36.4%, respectively whereas the resistance rate to the same antibiotics in non-ETEC strains was 14%, 62%, 54%, and 66%, respectively. All ETEC isolates were intermediately resistant to cephalothin and fully susceptible to other antibiotics tested. Typing of the ETEC strains was done by arbitrary primed polymerase chain reaction (AP-PCR). Only two LT strains of the 11 typed strains had a unique profile. The remaining nine were mixed LT and ST strains and divided into two groups. The first group had three strains having a similarity coefficient ranging from 70-90%. The other one had six strains, five of them were similar and one was subtype isolate. It can be concluded that ETEC strains might be considerably important enteropathogens especially in pediatric patients in the 0-5 year age group. High clonal relation indicated that ETEC strains were epidemiologically related.

The prevalence of fecal colonization of enterococci, the resistance of the isolates to ampicillin, vancomycin, and high-level aminoglycosides, and the clonal relationship among isolates.

The gastrointestinal tract carriage of enterococci was searched in 150 hospitalized patients and 100 outpatients, and clonal relatedness of the isolates and their resistance to ampicillin, vancomycin, and high-level streptomycin and gentamicin were investigated. A stool sample or rectal swab collected from each patient was inoculated into appropriate media within an hour. Enterococcus species were identified by using conventional biochemical tests, API-20 Strep assay, and BBL crystal kit. Antibiotic susceptibility tests were performed using Kirby-Bauer disk diffusion method. A polymerase chain reaction (PCR) was used to detect vanA and vanB genes. Pulsed-field gel electrophoresis (PFGE) and arbitrarily primed-polymerase chain reaction (AP-PCR) methods were used for molecular typing of the strains. Enterococci were isolated from 90 (60%) of the specimens collected from 150 inpatients. Of these 90 isolates, 37 (41%) had high-level gentamicin resistance, 36 (40%) had high-level streptomycin resistance, and 50 (55.6%) had ampicillin resistance. Fecal colonization was found in 30% of the outpatients. Resistances to ampicillin, high-level streptomycin, and gentamicin were 13%, 10%, and 3%, in these patients' isolates, respectively. No vancomycin-resistant enterococci were detected by both agar diffusion and PCR assays in our study. Both typing procedures were applied on 78 Enterococcus strains isolated from inpatients. AP-PCR typing showed that 30 (50.8%) of the 59 E. faecium and 5 (50%) of the 10 E. faecalis strains were clonally related. These values were found to be 12 (20.3%) and two (20%) by PFGE, respectively. The typing procedures did not find any clustered strains in the six E. durans and three E. avium isolates. Neither PFGE nor AP-PCR result was significantly different among the sensitive and resistant strains. Our results indicate that the high prevalence of colonization with ampicillin and highlevel aminoglycoside-resistant enterococci is an important problem in our medical center. The high clonal diversity among the isolates indicates limited spread of antibiotic-resistant strains between patients.

Homocysteine, lipid profile, nitric oxide, vitamin B12, and folate values in patients with premature coronary artery disease and their children.

The plasma concentrations of homocysteine and lipoprotein A are independent risk factors for atherosclerotic vascular disease. Nitric oxide (NO) and folate values are also important in atherogenesis. The authors aimed to evaluate these parameters in patients having coronary artery bypass surgery (CABS) before 50 years of age and in their children. In 31 patients having CABS, 47 children of these patients, and 28 normal control subjects, homocysteine, NO, vitamin B12, folate, lipoprotein A, triglyceride, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, apolipoprotein A1, and apolipoprotein B values were determined. Homocysteine values of the patients with premature coronary heart diseases and their children were significantly higher than those of controls (p < 0.031 and p < 0.006, respectively). Also, NO levels were significantly higher in both groups than in controls (p < 0.001 and p < 0.031, respectively). B12 values were significantly higher in both groups (p < 0.05 and p < 0.033, respectively). Lipoprotein A levels were higher in both groups but not significantly so.

[Investigation of serum IgG subclass distributions and anti-HBs response in healthy adults after hepatitis B vaccination]. / Hepatit B asilamasindan sonra saglikli eriskinlerde serum IgG alt tipleri ve anti-HBbs yanitinin arastirilmasi.

The aim of this study was to evaluate the distribution of serum total IgG (tIgG) subtypes before and after hepatitis B vaccinations in young adults and the relationship between anti-HBs titers and tIgG subtypes. Thirty-eight young adults (29 female, 9 male; age range: 18-20 years) who were the students of Malatya Health Care Profession High School were included in the study. Their anti-HBs and total anti-HBc markers' were negative. The study group were immunized with 20 microg/mL recombinant HBV vaccine intramuscularly (Engerix B) at 0, 1st, and 6th months. The tIgG subtype distributions before vaccination and anti-HBs and tlgG subtype distributions after vaccination were investigated. Serum samples were collected one month after the third dose vaccination, and anti-HBs were found negative (<10 IU/ml) in 8 subjects (21%), low positive (10-100 IU/ml) in 14 subjects (37%), and high positive (>100 IU/ml) in 16 subjects (42%). There was no difference between the response groups in terms of tIgG subtype distributions obtained before vaccination. After vaccination, while there was no increase in the tIgG subtypes in the unresponsive group, increased IgG1 levels were determined in low and high response groups. The IgG1 increment ratio was more evident in high response cases. We concluded that IgG1 subtype titer was the most important indicator for the evaluation of the efficacy of active HBV immunization.

Prevalence of group A streptococcal carriers in asymptomatic children and clonal relatedness among isolates in Malatya, Turkey.

In our study, the prevalence of nasopharyngeal Streptococcus pyogenes was 130 (14.3%) of 909 healthy children. Isolates were found to be susceptible to all antibiotics tested. Pulsed-field gel electrophoresis and arbitrarily primed PCR revealed that 34 (32.4%) of the 105 isolates and 41 (40.6%) of the 101 isolates typed, respectively, were clonally indistinguishable.

Primary drug resistance and molecular epidemiology of Mycobacterium tuberculosis isolates from patients in a population with high tuberculosis incidence in Turkey.

To determine the rate of primary drug resistance and compare the fingerprint pattern diversity of the resistant and sensitive Mycobacterium tuberculosis isolates, antituberculosis susceptibility testing and restriction fragment length polymorphism (RFLP) analysis were performed on 88 M. tuberculosis isolates of the patients who were diagnosed as new tuberculosis cases in 2000. Primary resistance to isoniazid, rifampicin, ethambutol, and streptomycin were determined by the BACTEC method. IS6110 and pTBN12 were used as molecular markers. The frequency of resistance to at least one drug was 32.95%, whereas 10.23% of the isolates were resistant to more than one drug. Single-drug resistance to isoniazid, streptomycin, ethambutol, and rifampicin was found in 9 (10.22%), 7 (7.95%), 4 (4.54%), and 0 (0.0%) strains, respectively. Two M. tuberculosis strains (2.26%) showed multiple drug resistance. The combination of two fingerprinting procedures on a total of 88 isolates identified 58 (65.9%) strains as unique and clustered 30 strains in 11 clusters (clustering = 34.1%). The clustering rate for resistant and sensitive isolates was 13.8% and 40.1%, respectively. In conclusion; drug susceptibility testing showed that the majority of the drug-resistant infections involved either isoniazid or streptomycin alone. In addition to the high tuberculosis incidence, elevated primary drug resistance and high clustering rate indicate problems in the present control programs. New control strategies supported by molecular typing might be more effective to reduce tuberculosis.