Insulin sensitivity indices: Fasting versus glucose-stimulated ýndices in pediatric non-alcoholic fatty liver disease

OBJECTIVE: We aimed to compare insulin sensitivity indices, fasting vs glucose stimulated, in children and adolescents with non-alcoholic fatty liver disease. PATIENTS AND METHODS: Two hundredeleven obese children with median age of 11.24 ± 2.65 years were evaluated. After initial clinical and anthropometric examination, B-mode ultrasonography (USG) was performed and all subjects underwent Oral Glucose Tolerance Test (OGTT). Quantitative insulin sensitivity check index (QUICKI), homeostatic model assessment for insulin resistance (Homa-IR), the insulinogenic index (IGI), the Matsuda index, and the oral glucose insulin sensitivity (OGIS) model were used to determine peripheral insulin sensitivity. RESULTS: 59.24% (68 boys, 57 girls) of obese children had NALFD. The prevalence of FLD in obese adolescents was significantly higher than in prepubertal children (65.8% vs. 51.5%). Fasting glucose, insulin, Homa-IR, QUICKI, and OGIS and Matsuda were significantly different between subjects with and without NALFD. Insulin and glucose indices were not found to be significantly different in the prepubertal group, whereas Homa-IR, QUICKI, Matsuda, and OGIS were significantly different in the pubertal group. Age, waist circumference, and OUICKI were found to be risk factors associated with the presence of NALFD in the logistic-regression analysis. CONCLUSIONS: Age, waist circumference, and OUICKI were found to be risk factors associated with NALFD. As the value of QUICKI decreases, the probability of having steatosis increases. Although OGTT results gave the information about the glucose tolerance of a subject, indices derived from OGTT were not found to be superior to the traditional surrogates such as Homa-IR or QUICKI

Vitamin A status of healthy children in Manisa, Turkey

<p>Abstract</p> <p>Background</p> <p>Vitamin A deficiency is a major public health nutrition problem in the developing world. Even subclinical Vitamin A deficiency is associated with increased childhood mortality. Severe maternal vitamin A deficiency may cause increased mortality in the first months of life. There have been a limited number of studies regarding vitamin A status in Turkey. The aim of this study was to assess vitamin A status of healthy children in Manisa, Turkey.</p> <p>Methods</p> <p>Vitamin A status of 100 healthy children aged 36-48 months is evaluated. The children were seen during routine examination. Serum retinol concentrations were measured by high-performance liquid chromatography. Duration of breast feeding, age solid foods introduced, use of supplementary vitamins, weight and height, and intake of specific groups of nutrients on a daily, weekly and monthly basis were collected from a questionnaire completed by the mothers. Height and weight z-scores were calculated according to national standards. Mothers of 20 of the 100 children were known to have normal serum and breast milk retinol concentrations. Children with normal serum retinol concentration were compared with the children with VAD. Student's t-test and Mann-Whitney test were used to compare independent variables. The Pearson correlation analysis test was used to test relation between numeric variables.</p> <p>Results</p> <p>Mean retinol concentration was 0.98 ± 0.32 μmol/L in the whole study group. Serum retinol concentrations were normal (>0.70 μmol/L) in 89% of the children. When children with normal serum retinol concentrations were compared with those with retinol concentrations lower than 0.70 μmol/L, there was no difference in terms of age, gender, weight and height at the time of study, z-scores, birth weight, birth length, duration of breast feeding, time to begin solid food, rate of supplementary vitamin use, and rate of infections (P > 0.05). There was not any relation between vitamin A concentrations and weight and height at the time of study, z-scores, birth weight, birth length, duration of breast feeding, time to begin solid food, vitamin use, and frequency of intake of specific groups of nutrients (P > 0.05).</p> <p>Conclusions</p> <p>This study showed that VAD is a moderate health problem in Manisa.</p

Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 Are Identified in Individuals with Congenital Hypogonadotropic Hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the &gt;15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ∼12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH

Nitric oxide and cyclic nucleotides: Their roles in junction dynamics and spermatogenesis

Spermatogenesis is a highly complicated process in which functional spermatozoa (haploid, 1n) are generated from primitive mitotic spermatogonia (diploid, 2n). This process involves the differentiation and transformation of several types of germ cells as spermatocytes and spermatids undergo meiosis and differentiation. Due to its sophistication and complexity, testis possesses intrinsic mechanisms to modulate and regulate different stages of germ cell development under the intimate and indirect cooperation with Sertoli and Leydig cells, respectively. Furthermore, developing germ cells must translocate from the basal to the apical (adluminal) compartment of the seminiferous epithelium. Thus, extensive junction restructuring must occur to assist germ cell movement. Within the seminiferous tubules, three principal types of junctions are found namely anchoring junctions, tight junctions, and gap junctions. Other less studied junctions are desmosome-like junctions and hemidesmosome junctions. With these varieties of junction types, testes are using different regulators to monitor junction turnover. Among the uncountable junction modulators, nitric oxide (NO) is a prominent candidate due to its versatility and extensive downstream network. NO is synthesized by nitric oxide synthase (NOS). Three traditional NOS, specified as endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS), and one testis-specific nNOS (TnNOS) are found in the testis. For these, eNOS and iNOS were recently shown to have putative junction regulation properties. More important, these two NOSs likely rely on the downstream soluble guanylyl cyclase/cGMP/protein kinase G signaling pathway to regulate the structural components at the tight junctions and adherens junctions in the testes. Apart from the involvement in junction regulation, NOS/NO also participates in controlling the levels of cytokines and hormones in the testes. On the other hand, NO is playing a unique role in modulating germ cell viability and development, and indirectly acting on some aspects of male infertility and testicular pathological conditions. Thus, NOS/NO bears an irreplaceable role in maintaining the homeostasis of the microenvironment in the seminiferous epithelium via its different downstream signaling pathways

ARCHIVES OF MEDICAL RESEARCH

Background. Recently it was proposed that nitric oxide metabolites (NO) may have a role in the pathophysiology of schizophrenia and major depressive disorders. The present study was performed to assess changes in serum nitric oxide metabolite levels in schizophrenic patients compared with healthy, controls. Our secondary aim was to further evaluate the impact of psychopharmacologic treatment on circulating NO levels not assessed previously. Methods. Serum NO levels of patients with schizophrenia (n = 20) before and after 6 weeks of treatment were compared with those of healthy controls (n = 20). Severity of schizophrenia and response to treatment were assessed with positive and negative symptoms of schizophrenia. NO levels were estimated by Griess method in serum samples. Results. In patients with schizophrenia, pre-treatment serum NO levels were higher than those of control subjects (39.15 +/- 18.24 vs. 25.40. +/- 5.83 mumol/L, p = 0.036) and also of post-treatment values (34.41 +/- 16.35 vs. 25.40 +/- 5.83 mumol/L, p = 0.049), respectively. However, no significant difference was found between serum NO levels in pre- and post-treatment values. Conclusions. Our findings of increased serum NO levels in schizophrenic patients confirmed the role of NO in the pathophysiology of schizophrenia. However, we found that antipsychotic drugs do not reveal significant effects on serum levels of NO in schizophrenia in a 6-week treatment regimen. Further studies with longer therapy periods may suggest some new clues for novel treatment strategies employing antioxidants and NOS inhibitors in schizophrenia. (C) 2004 IMSS. Published by Elsevier Inc

CLINICAL BIOCHEMISTRY

Objectives: The aim of the present study is to investigate the effect of obesity on testicular function by evaluating reproductive hormones, inhibinB, insulin-like 3(INSL3), and leptin, in obese and non-obese adolescents according to pubertal Tanner stages. Design and methods: Eighty adolescent boys were grouped (n = 20) as; Group1 : obese-Tanner2, Group2: non-obese-Tanner2, Group3: obese-Tanner4, Group4: non-obese-Tanner4. Serum INSL3, luteinizing hormone, follicle-stimulating hormone, total testosterone, free testosterone, estradiol, sex hormone binding globulin, inhibin B and leptin levels were assessed in all groups. Results: INSL3 levels were significantly lower in obese adolescents compared to non-obese boys (p = 0.003, Tanner2) and (p = 0.031, Tanner4). There was a negative correlation between INSL3 and leptin (r = -0.468, p = 0.001). The negative correlation between INSL3 and BMISDS indicates that pubertal obesity leads to Leydig cell impairment. Conclusions: This study demonstrated for the first time in the literature that obesity effects testicular Leydig cell function starting from Tanner stage 2. (C) 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved

CELL BIOCHEMISTRY AND FUNCTION

Polypropylene mesh is the most widely used material in inguinal hernia repair. Although polypropylene mesh is known as an inert material, it is experimentally proven that mesh generates a chronic inflammatory tissue reaction. The aim of the present study was to investigate the long-term effects of polypropylene mesh material used in inguinal hernia operations on testicular function, testicular nitric oxide (NO) metabolism and germ cell-specific apoptosis in rats. The study comprised 40 male rats that were randomly allocated into two groups. In group 1, the left spermatic cord was elevated and a 0.5 x 1 cm polypropylene mesh was placed behind the left inguinal spermatic cord and group 2 consisted of the sham-operated controls. Blood samples were taken at 6 months preoperatively and postoperatively after to assess luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels for hormonal evaluation. Testicular NO was evaluated by the Griess method, apoptosis by a TUNEL method and inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) expressions by immunohistochemical staining. Mild (+) eNOS expression was observed in all specimens. Mild (+) iNOS expression was only detected in ipsilateral testis of the mesh-implanted study group. Apoptotic cells were not detected in any samples. We are of the opinion that long-term polypropylene mesh implantation has no effect on testicular hormonal function and only a limited effect on nitric oxide levels and this effect is not sufficient to cause apoptosis in testis that could lead to infertility. It seems that mesh implantation is a reliable method in inguinal hernia repair; however, further work is required by more sensitive methods to fully elucidate the potential testicular damage. Copyright (c) 2004 John Wiley & Sons, Ltd

ANGIOLOGY

Leptin is an adipocytokine that is produced mainly by adipose tissue; it is also identified in atherosclerotic lesions in human coronary atherosclerosis. However, the relation of serum leptin concentrations to ischemic heart disease (IHD) is still obscure. The aims of the present study were to investigate serum leptin concentrations in patients with ST-elevated myocardial infarction (STEMI) and with chronic stable angina pectoris (CSAP) and to evaluate the possible correlations of leptin to other atherosclerotic risk factors; including serum high sensitive C-reactive protein (Hs-CRP), serum homocysteine, and fibrinogen concentrations. For this purpose, 35 patients with CSAP, 40 with acute STEMI, and 30 control subjects with normal findings from coronary angiography were taken into the study prospectively. Serum leptin concentrations were significantly higher in patients with CSAP and STEMI compared to the control group (7.74 +/- 1.34 vs 6.37 +/- 1.85 ng/mL, p=0.021 and 8.22 +/- 3.13 vs 6.37 1.85 ng/mL, p=0.023, respectively). In addition, serum homocysteine concentrations were significantly increased in patients with CSAP (15.23 +/- 5.96 vs 11.40 +/- 2.11 mu mol/L, p=0.025) and patients with STEMI (15.90 +/- 5.02 vs 11.40 +/- 2.11 mu mol/L, p=0.012) compared to the control group. Serum fibrinogen concentrations were significantly increased only in the CSAP group as compared to controls (4.15 +/- 1.39 vs 3.45 +/- 1.19 g/L, p = 0.025). No significant correlation was found between leptin levels and selected risk factors. In conclusion, serum leptin concentrations were significantly higher in both the CSAP and STEMI groups. However, owing to the lack of correlation between the leptin levels and selected classical coronary risk factors, it may be considered that leptin can be evaluated as one of the independent risk factors for IHD. Further randomized and controlled studies will be required to determine the pathophysiological meaning of the increased leptin levels and the central role between adipocyte function and atherosclerosis

UROLOGIA INTERNATIONALIS

Introduction: The Fowler-Stephens maneuver, a mode of spermatic vessel ligation, is a method of choice in the management of high testes. The aim of the present study is to investigate the effects of pre-ischemic administration of N-G-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase (NOS) inhibitor, in preventing testicular ischemic damage and germ cell-specific apoptosis in rats. Materials and Methods: 30 min before ligation of the spermatic vessels, L-NAME was administered intraperitoneally to a group of rats and saline was given to another group of rats (controls). Biochemical assessments of NO and germ cell-specific apoptosis were performed. Results: Testicular NO levels in the L-NAME group showed significant decreases in the ipsilateral (p = 0.004) and contralateral (p = 0.015) testes in relation to those of the control group. The apoptotic indices were found in 2.3% of the L-NAME group and 3.1% of the control group. Conclusion: Pre-ischemic administrations of the NOS inhibitor, L-NAME, effectively decreased NO production and to some degree caused a reduction in germ cell apoptosis in the rat testes after spermatic vessel ligation. Further studies are mandatory to confirm our preliminary results and to address the potential introduction of NOS inhibitors into clinical practice. Copyright (c) 2005 S. Karger AG, Basel