Erol Bolu

Increased oxidative stress and hypozincemia in male obesity

OBJECTIVES Antioxidants protect an organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Alterations in the levels of antioxidants and several essential trace elements in the plasma and various tissues of ob/ob mice have been reported previously. The aim of this study was to investigate oxidative status and trace elements in obese individuals. DESIGN AND METHODS Seventy-six obese men (body mass index (BMI) > 30 kg/m(2)) and 24 healthy, age-matched male control volunteers were enrolled in the study. Fasting plasma insulin, glucose, triglyceride (TG), total cholesterol, VLDL, and HDL levels, erythrocyte glutathione peroxidase (GSH-Px) and copper zinc-superoxide dismutase (CuZn-SOD) activities, and erythrocyte thiobarbituric acid reactive substances (TBARS) levels were measured in both groups. Erythrocyte copper (Cu), zinc (Zn) and iron (Fe) levels were also measured. RESULTS We found that the mean Cu and Fe levels in obese individuals were not significantly different than those in the control group, whereas the mean Zn levels were significantly lower than those of the control group (p = 0.023). The mean erythrocyte CuZn-SOD and GSH-Px levels in obese individuals were significantly lower than those in controls (p = 0.001) whereas erythrocyte TBARS levels were significantly higher (p = 0.001) than those of the control group. CONCLUSION We conclude that male obesity is associated with defective antioxidant status and hypozincemia, which may have implications in the development of obesity related health problems.

TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood

CONTEXT Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. OBJECTIVE A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. DESIGN AND SETTING The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. PATIENTS OR OTHER PARTICIPANTS 345 probands, 18 family members, and 292 controls were studied. INTERVENTION Reproductive phenotypes throughout reproductive life and before and after therapy were examined. MAIN OUTCOME MEASURE Rare sequence variants in TAC3/TACR3 were detected. RESULTS In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism. CONCLUSIONS Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time.

The relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy.

Abstract Objectives. Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of DM. The aim of the present study was to investigate the possible relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. Materials and methods. Plasma TNF-α and IL-6, pro-inflammatory cytokines, concentrations were measured in 25 patients with DN and in 30 diabetic control subjects. Also, we evaluated the markers of endothelial dysfunction such as flow mediated dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media thickness (CIMT). Results. TNF-α, IL-6 and high-sensitivity C-reactive protein concentrations were significantly higher (p = 0.012, p = 0.006 and p < 0.001, respectively) in the patients with DN than the controls. And, urinary protein concentrations were significantly higher (p < 0.001) but eGFR levels were significantly lower (p < 0.001) in the patients with DN. FMD was significantly lower in DN patients (p < 0.001). We have observed that FMD correlated negatively with body mass index (r = −0.424, p < 0.05). And there was also a positive correlation between TNF-α and urinary protein concentrations in the patients with DN (p < 0.05). Conclusion. TNF-α, IL-6, hsCRP and urinary protein concentrations are higher in the DN patients. There were no correlations among pro-inflammatory cytokines concentrations and markers of vascular endotelial disfunction. These findings did not show vascular endothelial dysfunction, but may indicate glomerular endothelial dysfunction.

Voice changes after androgen therapy for hypogonadotrophic hypogonadism.

Objectives/Hypothesis: Males with isolated hypogonadotropic hypogonadism (IHH) fail to undergo normal sexual development, including the lack of masculinization of the larynx. The objective of this study was to measure the mean vocal fundamental frequency (MF0) in IHH patients and determine the impact of androgen treatment. An additional aim was to compare the MF0 between IHH patients and controls.

Transsphenoidal approaches to the pituitary: a progression in experience in a single centre

BackgroundEvolving of a single centre by means of different transsphenoidal approaches during the survey of methodological advances in pituitary surgery is presented.Materials and methodsNinety-three consecutive patients with pituitary adenomas underwent transphenoidal pituitary operations at Gulhane Military Medical Academy from January 1996 to October 2007. Retrospective chart-based analysis of the surgical methods of transsphenoidal pituitary adenoma operations were done. Surgical methods were described. Outcomes and complications were presented. Attention is focused on the methodology of different surgical techniques of pituitary surgery.FindingsDuring the evaluation period, 12 Sublabial approaches (1996–1998), 13 transseptal transsphenoidal approaches (1999–2000), 15 endonasal transsphenoidal approaches (2000–2004), 25 endoscopy assisted endonasal approaches (2002–2006) and 28 pure endoscopic endonasal approaches (2006–2007) were performed.ConclusionsTechnologic advancements in endoscopy and gaining experience in pituitary surgery drives neurosurgeons toward less invasive approaches.

Metabolic syndrome and the effect of testosterone treatment in young men with congenital hypogonadotropic hypogonadism

OBJECTIVE The relationship between metabolic syndrome (MS) and hypogonadism has always been investigated in study groups confounded with aging, obesity or chronic metabolic disorders. So far, there has been no data about the presence of MS in young hypogonadal patients. Also, there is controversial data about the metabolic effects of testosterone replacement therapy. We investigated the frequency of MS in treatment-naïve, young men with congenital hypogonadal hypogonadism (CHH). We also searched for the effect of testosterone replacement on the metabolic profiles of this specific patient group. DESIGN Retrospective analysis. METHODS A total of 332 patients (age 21.68 ± 2.09 years) were enrolled. The control group included 395 age- and body mass index (BMI)-matched healthy young men (age 21.39 ± 1.49 years). Standard regimen of testosterone esters (250 mg/3 weeks) was given to 208 patients. RESULTS MS was more prevalent in CHH (P<0.001) according to healthy controls. The patients had higher arterial blood pressure, waist circumference (WC), triglyceride (P<0.001 for all), fasting glucose (P=0.02), fasting insulin (P=0.004), homeostatic model assessment of insulin resistance (HOMA-IR) (P=0.002) and lower high density lipoprotein (HDL) cholesterol (P<0.001) levels. After 5.63±2.6 months of testosterone treatment, the BMI, WC (P<0.001 for both), systolic blood pressure (P=0.002) and triglyceride level (P=0.04) were increased and the total and HDL cholesterol levels were decreased (P=0.02 and P<0.001 respectively). CONCLUSIONS This study shows increased prevalence of MS and unfavorable effects of testosterone replacement in young patients with CHH. Long-term follow-up studies are warranted to investigate the cardiovascular safety of testosterone treatment in this specific population.

Effects of leptin on intake of specific micro- and macronutrients in a woman with leptin gene deficiency studied off and on leptin at stable body weight

In this report, we examine the effects of leptin on the intake of specific macro- and micronutrients in a female patient with leptin gene deficiency. The patient was studied off and on leptin at stable body weight, within the normal to mildly overweight range. The data were obtained by detailed dietary assessments, measuring dietary intakes by weighed food and fluid consumption records, and analyzed using nutrition analysis software. Overall, significant differences were found in the off versus on leptin treatment periods in the following categories: (i) macronutrients: kilocalories, protein, carbohydrates, monounsaturated fats, MFA 18:1 oleic and total fiber; (ii) vitamins: vitamin C, pyridoxine and pantothenic acid; (iii) minerals: potassium, magnesium, copper and chromium; and amino acids: threonine, lysine and histidine. The nutritional data from this study indicates a direct link between the effects of leptin and ingestion of several specific micronutrients. The mechanisms underlying these effects warrant further investigation and study.

The effect of fatty pancreas on serum glucose parameters in patients with nonalcoholic steatohepatitis

OBJECTIVE Fatty pancreas (FP) is related to obesity, and may have some clinical implications on glucose metabolism. The frequency and importance of FP in patients with nonalcoholic steatohepatitis (NASH) are not clear. This study aimed to investigate: the frequency of FP in patients with NASH, and its effects on serum glucose parameters. METHODS FP was detected and graded by transabdominal ultrasonography (USG) in patients with biopsy-proven NASH and healthy controls. Body Mass Index and waist circumference were recorded, and serum lipids, fasting serum glucose, HbA1c, OGTT 2-h, insulin level, insulin resistance, type 2 diabetes mellitus (DM) and prediabetes rates were detected. RESULTS Eighty-four subjects with NASH and 35 healthy controls were enrolled in the study. There was no FP in 41 (48.8%) of the NASH patients according to the study criteria. Forty-three of the NASH patients and 5 of the controls had different grades of fat in their pancreas (51.2% vs. 14%, p=0.001). The HbA1c and OGTT 2-h results were significantly higher in NASH patients with FP compared to those without FP (p=0.003 and p=0.018). The rates of both prediabetes and DM were also found to be significantly increased in NASH patients with FP (p=0.004). The mean waist circumference was higher in patients with FP (p=0.027). Grade of FP by USG showed no effect on study parameters in subgroup analysis. CONCLUSION FP is common in patients with NASH and increases the rate of prediabetes and DM. The coexistence of both NASH and FP has a further impact on glucose metabolism and DM frequency.

Comparison of Electrocardiographic Repolarization Patterns between Hypogonad Males and Normal Subjects

Background: There is a significant difference in repolarization on the surface ECG between men and women. The effect of testosterone on repolarization of myocardium may provide a basis for the physiological and pathophysiological importance of these distinctions between sexes. The purpose of this study is to compare the repolarization characteristics of surface ECG in patients with secondary hypogonadotropic hypogonadism to those of healthy men and women.

Effects of three different medications on metabolic parameters and testicular volume in patients with hypogonadotropic hypogonadism: 3‐year experience

The aim of this study was to demonstrate the influences of three different treatment strategies on biochemical parameters and testicular volume (TV) in patients with idiopathic hypogonadotropic hypogonadism (IHH).