Decreased plasma nesfatin-1 levels in patients with acute myocardial infarction

Nesfatin-1 is a novel anorexigenic hormone which has close relationship with diabetes, obese, anorexia nervosa, psychiatric disorders and neurogenic diseases. The aim of our study was to evaluate levels of plasma nesfatin-1 among patients presenting with coronary artery disease and the correlation between nesfatin-1 levels and other clinical parameters. Fasting plasma levels of nesfatin-1 were tested in 48 acute myocardial infarction (AMI) patients, 74 stable angina pectoris (SAP) patients and 34 control subjects. All of them were examined by coronary angiography. The severity of coronary atherosclerosis was assessed using the Gensini score. Plasma nesfatin-1 levels were significantly lower in AMI group than SAP group or control group (0.91 ± 0.08 ng/mL vs. 0.98 ± 0.19 ng/mL and 1.09 ± 0.39 ng/mL, respectively, P < 0.05). In AMI patients, plasma nesfatin-1 levels were negatively correlated with high-sensitivity C-reactive protein, neutrophil% or Gensini scores. Such information implies that lower nesfatin-1 concentration may play a very important role in the development of AMI.     

C-type natriuretic peptide plasma levels are reduced in obese adolescents

The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age: 11.8 ± 0.4 years; BMI: 29.8 ± 0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP: 3.4 ± 0.2 vs 13.6 ± 2.3 pg/ml, p < 0.0001; BNP: 18.8 ± 2.6 vs 36.9 ± 5.5 pg/ml, p = 0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.     

Levothyroxine Replacement In Obese Hypothyroid Females After Total Thyroidectomy

Objective: Levothyroxine (LT4) replacement in hypothyroid obese patients is poorly understood. We assessed whether the LT4 regimen required to achieve euthyroidism differs between nonobese and obese hypothyroid females.Methods: We retrospectively identified nonobese and obese females who received LT4 starting with a standard dose of 1.6 μg/kg after total thyroidectomy for preoperative diagnosis of benign goiter. We examined the association between LT4 dosage required to achieve euthyroid state (thyroid-stimulating hormone [TSH] 0.4–2.5 mIU/L) and patient characteristics using linear regression models with and without adjustment for age, ethnicity, medication use, and postoperative hypoparathyroidism.Results: We identified 32 females (15 nonobese/17 obese) who achieved euthyroid state. Obese patients weighed more (104.1 ± 22.5 vs. 64.9 ± 10.0 kg, P<.0001) and required a higher final LT4 than nonobese (146 ± 38 vs. 102 ± 12 μg, P = .0002) but LT4 requirements per kg total body weight (TBW) were similar (1.60 ± 0.29 vs. 1.42 ± 0.38 μg/kg, P = .15). LT4 dose per kg ideal body weight (IBW) was higher in obese than in nonobese females (2.62 ± 0.67 vs. 1.88 ± 0.28 μg/kg, P = .0004) and this difference persisted after adjustments (P<.05). During LT4 titration, 47% and 20% of obese and nonobese patients had subnormal TSH episodes, respectively (P = .11). After taking LT4 compliance, malabsorption, and competing medication use into consideration, we found marked LT4 dose variability in obese patients. Patients who needed a mean daily LT4 dose ≤150 mg (124 ± 16 μg/day) compared with >150 μg (198 ± 4 μg/day) demonstrated lower LT4 per TBW (1.25 ± 0.18 vs. 1.84 ± 0.43 μg/kg, P = .03) and IBW (2.28 ± 0.47 vs. 3.44 ± 0.18 μg/kg, P<.0001), respectively.Conclusion: The standard approach to LT4 replacement in obese and nonobese females after thyroidectomy is imprecise. Mean daily LT4 doses in obese and nonobese patients were similar if expressed per kg TBW, though there was variability in the final LT4 among obese patients. We suggest initiating LT4 at a dose lower than that routinely recommended in obese females.Abbreviations:AACE = American Association of Clinical EndocrinologistsATA = American Thyroid AssociationBMI = body mass indexIBW = ideal body weightLT4 = levothyroxineTBW = total body weightTSH = thyroid-stimulating hormone     

The Association of Thyroid Hormones and Tsh with the Metabolic Syndrome in Euthyroid Taiwanese Individuals

Objective: There are conflicting studies in euthyroid males and females regarding associations between thyroidrelated hormones and parameters of the metabolic syndrome (MetS). We investigated the association between serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations and MetS in euthyroid men and women.Methods: Taiwanese subjects aged 20 to 65 years who had undergone a voluntary health examination at a preventive examination agency in Taipei were enrolled in this cross-sectional study. The definition of MetS was suggested by the Bureau of Health Promotion, Department of Health, Taiwan. Euthyroidism was defined as TSH and free thyroxine (FT4) levels within the normal reference ranges while not taking any thyroid medication. We conducted multiple logistic regression to identify the ability of serum triiodothyronine (T3), FT4, and TSH concentrations to identify the relative risk for the presence of MetS and components of the MetS in euthyroid Taiwanese individuals.Results: A total of 8,207 Taiwanese subjects (mean age: men, 45.3 ± 9.9 years; women, 43.5 ± 9.3 years) were enrolled in this study. A total of 1,672 subjects (20.4%) were defined as having MetS; these subjects had significantly higher (P<.0001) mean age (48.4 ± 9.1 years vs. 43.6 ± 10.7 years), prevalence of men (78.7% vs. 53.4%), and smoking (16.8% vs. 11.6%) than those without MetS. The median TSH, FT4, and T3 levels in all subjects were 1.70 mIU/L, 1.41 ng/dL, and 1.20 ng/mL, respectively. Higher T3 and lower FT4 values rather than TSH increased the odds ratio for MetS in men and women after adjusting for smoking and age, particularly for the association of T3 and MetS in women (uppermost quartile versus lowermost quartile: odds ratio, 2.4; 95% confidence interval, 1.6 to 3.5; P for trend <.0001).Conclusion: In euthyroid Taiwanese men and women, relatively high serum T3 concentrations was most strongly associated with the presence of the MetS; relatively low serum T4 was less strongly related, and serum TSH levels were not associated with the MetS. It is not known if the relationship of serum T3 and T4 to the MetS is causal.Abbreviations:BMI = body mass indexFT4 = free thyroxineMetS = metabolic syndromeOR = odds ratioT3 = triiodothyronineTSH = thyroid-stimulating hormoneWC = waist circumference     

Alterations of irisin concentrations in saliva and serum of obese and normal-weight subjects,before and after 45 min of a Turkish bath or running

The purpose of this study was to ascertain (1) whether human saliva contains irisin and whether its level correlates with serum irisin concentration, (2) whether salivary glands, eccrine glands and sebaceous glands in human skin produce irisin, (3) how the changes in saliva and serum irisin concentrations after the Turkish bath at 47 ± 3 °C compare with the changes caused by moderate exercise in obese and normal weight subjects. Seven obese male subjects and seven normal weight subjects were enrolled for Turkish bath. Seven obese male subjects and seven normal weight subjects were also enrolled for moderate outdoor exercise, and thirteen male normal weight subjects neither exercised nor showered at the Turkish bath. From each participant, 1.5 ml of saliva and 5 ml blood were collected simultaneously before and after the moderate exercise and Turkish bath. Salivary glands and eccrine and sebaceous glands in the skin were screened immunohistochemically for irisin while serum and saliva irisin were measured with an ELISA. Submandibular glands, eccrine glands and sebaceous glands in the human skin showed strong irisin immunoreactivity. Human saliva contained irisin and its level was significantly higher than the serum levels in both obese and normal weight subjects. However, irisin concentrations were more markedly increased in both saliva and serum samples from subjects who had showered at a Turkish bath than in obese subjects who had exercised or in normal weight subjects. Human submandibular glands, eccrine sweat glands and sebaceous glands synthesize irisin.     

Mechanical properties of the patellar tendon in adults and children

It is not currently known how the mechanical properties of human tendons change with maturation in the two sexes. To address this, the stiffness and Young's modulus of the patellar tendon were measured in men, women, boys and girls (each group, n=10). Patellar tendon force (F_pt) was calculated from the measured joint moment during a ramped voluntary isometric knee extension contraction, the antagonist knee extensor muscle co-activation quantified from its electromyographical activity, and the patellar tendon moment arm measured from magnetic resonance images. Tendon elongation was imaged using the sagittal-plane ultrasound scans throughout the contraction. Tendon cross-sectional area was measured at rest from ultrasound scans in the transverse plane. Maximal F_pt and tendon elongation were (mean±SE) 5453±307 N and 5±0.5 mm for men, 3877±307 N and 4.9±0.6 mm for women, 2017±170 N and 6.2±0.5 mm for boys and 2169±182 N and 5.9±0.7 mm for girls. In all groups, tendon stiffness and Young's modulus were examined at the level that corresponded to the maximal 30% of the weakest participant's F_pt and stress, respectively; these were 925–1321 N and 11.5–16.5 MPa, respectively. Stiffness was 94% greater in men than boys and 84% greater in women than girls (p<0.01), with no differences between men and women, or boys and girls (men 1076±87 N/mm; women 1030±139 N/mm; boys 555±71 N/mm and girls 561.5±57.4 N/mm). Young's modulus was 99% greater in men than boys (p<0.01), and 66% greater in women than girls (p<0.05). There were no differences in modulus between men and women, or boys and girls (men 597±49 MPa; women 549±70 MPa; boys 255±42 MPa and girls 302±33 MPa). These findings indicate that the mechanical stiffness of tendon increases with maturation due to an increased Young's modulus and, in females due to a greater increase in tendon cross-sectional area than tendon length.     

Regional brain and sex differences in the plasma progesterone concentration of sheep

Progesterone concentration was measured in specific brain regions of the ram and anestrous ewe to provide reference values for future studies to investigate if local CNS lesions resulting from neurodegenerative diseases of sheep are associated with progesterone loss. Using radioimmunoassay, plasma progesterone was recorded throughout all brain regions assayed. No significant differences were found between the ewe and ram for any brain regions. There were however, significant differences between the different regions of an individual brain (P < 0.05). Plasma progesterone concentration for the highest to the lowest value recorded was as follows: 2.93 ± 0.85 and 2.77 ± 0.51 ng/g in the frontal cortex; 2.33 ± 0.67 and 2.25 ± 0.48 ng/g in the parietal cortex; 1.32 ± 0.36 and 1.29 ± 0.35 ng/g in the temporal cortex; 1.25 ± 0.32 and 1.25 ± 0.31 ng/g in the occipital cortex; 1.24 ± 0.30 and 1.23 ± 0.31 ng/g in the corpus callosum; 1.16 ± 0.30 and 1.21 ± 0.38 ng/g in the cerebellum; 1.09 ± 0.30 and 1.12 ± 0.39 ng/g in the medulla oblongata of the ewe and ram, respectively. Plasma progesterone concentration in the ewe (0.28 ± 0.06 ng/ml) was significantly higher than that in the ram (0.10 ± 0.03 ng/ml) (P < 0.001). Furthermore, plasma progesterone concentration in all sheep was several times lower than that of any regions of the brain. The results indicate that the sheep brain accumulates progesterone in significant levels, which may be independent of the circulating progesterone. The brain progesterone concentration in CNS regions assayed was similar for the ram and anestrous ewe. Neurodegenerative processes in visna, border disease and enzootic ataxia should be questioned in further studies if they are associated with local progesterone loss.     

Levels of l-ascorbic acid and cadmium in the saphenous vein of patients with coronary artery disease are negatively correlated

BackgroundThe aim of this study was the simultaneous determination of levels of cadmium and l-ascorbic Acid (AA) in human saphenous vein (SV) used in coronary artery bypass grafting (CABG) and check whether there is a relationship between these levels.MethodsHuman SV were collected from 40 patients (20 men and 20 women; age, 40–75 years) at the time of routine coronary artery surgical revascularization. The concentration of cadmium in the tissue was determined according to the GF AAS—atomic absorption method. The concentration of AA was assayed in supernatant by FIA method with spectrophotometric detection.ResultsAA concentration (mean ± SD); men: 98,7 ± 13,18 μg/g tissue, women: 96,06 ± 11,98 μg/g tissue. Cadmium concentration(mean ± SD); men: 309 ± 103,71 ng/g tissue, women: 348,5 ± 255,71 ng/g tissue. Correlations among concentrations of AA and cadmium were insignificant negative in the group of men (Pearson r = −0,1504, p = 0,5269) and in the group women (Pearson r = −0339, p = 0144).ConclusionsNegative correlations among concentrations of AA and cadmium in human SV obtained in our study may indicate a protective effect of this vitamin in relation to toxic cadmium.     

Serum cytokine profiles of Khorasan veterans 23 years after sulfur mustard exposure

Sulfur mustard (SM) is an incapacitating chemical warfare agent that was used against Iranian soldiers during the period from 1983 to 1988. We have investigated serum cytokines profiles of Khorasan veterans who were exposed to SM >23 years earlier. Forty-four male Iranian veterans who had >40% disabilities due to delayed complications of SM poisoning and had disabilities were investigated. A total of 30 healthy male volunteers (relatives of the veterans) were selected as the control group. Cytokine levels were measured in the serum of case and control subjects using commercial ELISA kits. Hematologic parameters (white/red blood cell counts, hemoglobin levels, immune cell differentials) were also performed on blood samples from the study subjects. The results indicated that serum levels of ICAM-1 were significantly higher in the samples from SM-exposed veterans (772.8 [±15.1] ng/ml [p = 0.014] vs. control values of 710.2 [±20.0] ng/ml). On the other hand, serum IL-1β, IL-8 levels and TNFα, were significantly lower for the veterans than the controls (IL-1β: 3.8 [±0.1] vs. 4.3 [±0.2] pg/ml, p = 0.037; IL-8: 21.0 [±6.1] vs. 84.6 [±20.3] pg/ml, p = 0.002; TNFα: 4.5 [±0.1] vs. 5.5 [± 0.1] pg/ml, p = 0.027). Levels of other assayed cytokines, e.g., IL-2, -4, -5, -6, -10, and -12, IFNγ, TNFβ, and sVCAM-1 were not significantly different between the study populations. None of the assayed hematologic parameters appeared to differ as well. It seems possible that dysfunctions could have been induced in the innate immune functions of the SM-exposed veterans as a result of these changes in cytokine expression and that these, in turn, may have contributed to the increased incidence of a myriad of diseases that have been documented in these veterans, including cancers. Future studies must focus on examining the significance of these changes in circulating cytokines and their potential contribution to the development of different diseases in veterans exposed to SM.     

Signals from fat after injury: Plasma adipokines and ghrelin concentrations in the severely burned

IntroductionHypermetabolism is universal in the severely burned and is characterized by catabolism of lean mass and body fat with associated insulin resistance. Adipokines are likely to play a role in these changes but have not been identified to date in burn patients.MethodsFrom a single burn ICU, 17 burn patients with an expected stay >14 days were studied. Study period began within 14 days of admission. Over 7 days, plasma samples were collected for measurement of leptin, adiponectin, resistin, ghrelin, insulin, and cortisol by ELISA. For comparison, samples from 15 healthy controls of similar age, BMI, and blood glucose were obtained.ResultsMean age was 33 ± 17 years and BMI 26 ± 3.4. Average burn size was 45 ± 20% TBSA and ISS 32 ± 10 with 72% having inhalation injury; in-hospital mortality was 29%. Estimated energy needs were 3626 ± 710 kcal, of which 84 ± 21% were met by enteral feeding with intensive insulin treatment (glucose 80–110 mg/ml). Using the homeostasis model assessment of insulin resistance, burned subjects were more resistant than controls (17 ± 11.3 and 8 ± 10.0). Insulin levels were elevated (57 ± 35.6 μU/ml in burned subject vs. 26 ± 31.1 μU/ml in controls), and cortisol concentrations increased (50 ± 41.2 μg/dl vs. 12 ± 3.9 μg/dl). These traditional hormone changes were associated with increased resistin (16.6 ± 5.5 ng/ml vs. 3.8 ± 0.9 ng/ml) and decreased leptin (8.8 ± 8.9 ng/ml vs. 19.4 ± 23.5 ng/ml), adiponectin (9 ± 3.5 ng/ml vs. 17 ± 10.2 ng/ml), and ghrelin (0.37 ± 0.14 ng/ml vs.0.56 ± 0.26 ng/ml).ConclusionPatients with burns, who are characteristically hypermetabolic with hypercortisolism and insulin resistant, have significant changes in adipokine levels that appear independent of the magnitude of initial injury or metabolic derangement. In addition, suppression of ghrelin in the presence of decreased leptin and adiponectin levels in combination with increased insulin and resistin levels represent unexpected changes in the metabolic milieu of the injured patient possibly due to dramatic activation of inflammatory pathways, indicating strategies for treatment.     

Elevated plasma levels of soluble (pro)renin receptor in patients with obstructive sleep apnea syndrome: Association with polysomnographic parameters

(Pro)renin receptor ((P)RR) is a specific receptor for both renin and its precursor prorenin. (P)RR was shown to be involved in pathophysiology of cardiovascular and renal diseases. Soluble (pro)renin receptor (s(P)RR), which is generated by furin from full length (P)RR, is present in blood. The aim of the present study is to clarify the association of plasma s(P)RR levels and the severity of OSAS. Plasma levels of s(P)RR were measured by ELISA in 58 male patients diagnosed as OSAS based on polysomnography, and 14 age-matched male control subjects. Blood samples were obtained at 6:00 a.m. just after overnight polysomnography. Plasma s(P)RR levels were significantly higher in patients with OSAS (9.0 ± 2.0 ng/mL, mean ± SD) than in control subjects (7.4 ± 1.5 ng/mL) (P = 0.0026). Plasma s(P)RR levels showed a significant negative correlation with % stage rapid eye movement (REM) sleep (r = −0.377, p < 0.005), and significant positive correlations with % stage 1 (r = 0.374, p < 0.005), arousal index (r = 0.341, p < 0.01), apnea hypopnea index (AHI) (r = 0.352, p < 0.01) and desaturation index (r = 0.302, p < 0. 05). In 12 OSAS patients with AHI ≥20, plasma levels of s(P)RR were studied after 3-month treatment with nasal continuous positive airway pressure (nCPAP). Plasma s(P)RR levels were significantly decreased after the nCPAP treatment (p = 0.0016). The present study has shown for the first time elevated plasma s(P)RR levels in patients with OSAS. Plasma s(P)RR levels were associated with the severity of OSAS. Soluble (P)RR may serve as a plasma marker reflecting the severity of OSAS.     

Neuromuscular and psychological influences on range of motion recovery in anterior cruciate ligament reconstruction patients

To identify distinguishing characteristics for knee surgery patients who experience a protracted recovery process, we sought to determine if there is an association between the neuromuscular stretch reflex and psychological factors of pain perception and anxiety on the range of motion (ROM) recovery rate of post-operative anterior cruciate ligament reconstruction (ACLR) rehabilitation patients. The ACLR participants were categorized into a slow recovery group (SRG: >6 weeks to recover 0–125° knee flexion [n = 10]) and a normal recovery group (NRG: <6 weeks to recovery 0–125° knee flexion [n = 12]). Control participants (n = 22) were age, gender and activity-level matched to the surgical participants. Neuromuscular testing consisted of sagittal plane video kinematics of the Wartenberg Pendulum Test for determining lower limb stiffness indices and electromyography-monitored patellar tendon tap reflex responses. Psychological and health status assessments consisted of the State–Trait Anxiety Inventory and SF-36? Health Survey. Data revealed that neuromuscular reflex profiles, lower limb stiffness indices, pain, anxiety and SF-36? indices of function were not significantly different between the two surgical groups (SRG and NRG). The surgical groups exhibited significantly greater pain (2.67 ± 2.27 SRG, 1.49 ± 1.15 NRG) than the control group (p ? .05). SF-36? indices were significantly lower for the surgical groups for total score (546.55 ± 94.70 SRG, 577.57 ± 125.58 NRG), function 69.00 ± 20.24 SRG, 67.08 ± 19.12 NRG), role physical (53.75 ± 22.85 SRG, 53.12 ± 23.15 NRG), social (76.24 ± 25.31 SRG, 65.62 ± 27.24 NRG), and emotional (82.49 ± 19.81 SRG, 81.38 ± 23.02 NRG) subscales (p ? .05). These results suggest that neuromuscular reflex responses, visual analogue scale (VAS) pain, and anxiety are not distinguishing factors for ROM recovery rate between the SRG and NRG. Decreased SF-36? indices, including pain as it influences function, though clinically relevant factors, were not statistically associated with post-operative ROM recovery rate.     

Resistance exercise modulates lipid plasma profile and cytokine content in the adipose tissue of tumour-bearing rats

Cancer cachexia is a multifactorial syndrome characterised by progressive weight loss, frequently accompanied by anorexia, sarcopenia, and chronic systemic inflammation. The white adipose tissue is markedly affected by cachexia and contributes to this syndrome throught the secretion of pro-inflammatory factors which reach the adjacent tissues and the circulation. A nonpharmacologic intervention that may attenuate cancer cachexia is chronic physical activity, but the effect of resistance training upon adipose tissue inflammation in cachexia has never been examined. For that purpose we designed a protocol in which animals were randomly assigned to a control group (CT, n = 7), a Tumour bearing group (TB, n = 7), a Resistance Trained group (RT, n = 7) and a Resistance Trained tumour bearing group (RTTB, n = 7). Trained rats climbed a vertical ladder with an extra load attached to the tail, representing 75–90% of total body mass, 3 times per week, for 8 weeks. In the 6th week of resistance training, tumour cells (3 × 10⁷ Walker 256 carcinosarcoma) were inoculated in the tumour groups. Body, adipose tissue, muscle and tumour mass was determined, as well a blood biochemical parameters, and the hormone and cytokine profile assessed. The glycogen content of the liver and muscle was measured. IL-10, IL-6 and TNF-α protein expression was evaluated in the mesenteric adipose tissue (MEAT) examined. Resistance training increased by 9% body weight gain in RTTB (final weight 310.8 ± 9.8 g), when compared with TB (final weight 288.3 ± 4.9 g). LDL-c levels were decreased in RTTB (0.28 ± 0.9 mmol/L) by 43% when compared with TB (0.57 ± 0.1 mmol/L). HDL-c levels were increased in RTTB (1.31 ± 0.12 mmol/L) by 15% in regard to CT (1.13 ± 0.7 mmol/L) and 22% as compared with TB (1.07 ± 0.07 mmol/L). RTTB testosterone levels (577 ± 131 ng/mL) were 55% higher when compared with CT (254 ± 41.3 ng/mL) and 63% higher when compared with TB (221 ± 23.1 ng/mL). Adiponectin levels were augmented in RT (23 μg/mL) by 43% when compared with TB (11 μg/mL). Protein expression of IL-6 was increased 38% in TB MEAT (5.95 pg/μg), as compared with CT (3.64 pg/μg) and 50% compared with RTTB (2.91 pg/μg). Similar results with respect to TNF-α TB (7.18 pg/μg) were observed: 39% and 46%, higher protein expression in comparison with CT (4.63 pg/μg) and RTTB (3.8 pg/μg), respectively. IL-10 protein expression was found to be increased in TB (4.4 pg/μg) and RTTB (3.2 pg/μg) 50% and 47%, respectively, in comparison with CT (1.2 pu/μg). The IL-10/TNF-α ratio was higher in RTTB in relation to all others experimental groups. The results show a robust effect of resistance exercise training in preventing important symptoms of cancer cachexia, thus strongly suggesting it may appear as an alternative to endurance exercise as a non-pharmacological therapy in the management of this syndrome.     

The influence of androgens on hibernation phenology of free-living male arctic ground squirrels

Free-living ground squirrel species are sexually dimorphic in hibernation phenology. The underlying causes of these differences are not yet known. Androgens, testosterone (T) in particular, inhibit hibernation. To determine the influence of endogenous androgens on annual timing of hibernation we first measured circulating levels of T and dehydroepiandrosterone (DHEA), an adrenal androgen implicated in non-mating season aggression in other species, in free-living male arctic ground squirrels (Urocitellus parryii, AGS). We also manipulated endogenous androgen levels by surgical castration, and consequently compared body temperature records from intact (n = 24) and castrated (n = 9) males to elucidate the influence of endogenous androgens on annual body temperature cycles. The highest T levels (0.53 ± 0.10 ng/mL) were in reproductively mature male AGS in spring; whereas, both immature males in spring and all males in late summer had T levels an order of magnitude lower (0.07 ± 0.01 and 0.06 ± 0.00 ng/mL, respectively). DHEA levels were higher in males during the late summer compared to reproductively mature males in spring (120.6 ± 18.9 and 35.9 ± 2.3 pg/mL, respectively). Eliminating gonadal androgens via castration resulted in males delaying euthermy by extending heterothermy significantly in spring (Apr 22 ± 2.9) than reproductive males (Mar 28 ± 3.9) but did not change the timing of hibernation onset (castrate: Oct 12 ± 1.0 vs. intact: Oct 3 ± 3.1). We conclude that while androgens play a significant role in spring hibernation phenology of males, their role in fall hibernation onset is unclear.     

Serum reference levels of selenium,zinc and copper in healthy pregnant women at a prenatal screening program in southeastern mediterranean region of Turkey

ProjectThe aim of the study was to investigate the serum reference range for Selenium (Se), Zinc (Zn) and Copper (Cu) levels in women of 10–14 (group I) and 16–20 (group II) weeks of gestation and compare them with those in non-pregnant healthy women and healthy men.ProcedureThis cross-sectional study was performed in 351 pregnant women [group I (n: 177) and group II (n: 174)], 30 non-pregnant women and 30 men as controls. The levels of Se, Zn and Cu levels were determined on flame and furnace atomic absorption spectrophotometer using Zeeman background correction.ResultsIn the 10–14 weeks of gestation Se, Zn and Cu serum levels were 44.85±9.23, 81.30±31.94 and 132.33±38.24 ug/dl, in 16–20 weeks of gestation were 47.18±10.92, 74.25±22.47 and 164.86±39.69 ug/dl, in non-pregnant women were 55.38±8.81, 121.41±29.22 and 104.75±39.14 ug/dl also in men 72.24±9.28, 134.85±15.95 and 78.29±20.90 ug/dl, respectively.ConclusionA significant low level of serum Se, Zn and a high level of Cu in the pregnant women in the 10–14 and 16–20 weeks of gestation were detected when compared with that of non-pregnant women and men.     

Gender Determines Serum Free Cortisol: Higher Levels in Men

Objective: Because only the free fraction of serum cortisol can readily access glucocorticoid receptors, we investigated whether or not a gender-related difference in serum free cortisol (FC) exists in the basal and adrenocorticotropic hormone (ACTH)-stimulated state.Methods: Serum total cortisol (TC) and FC were measured in 323 subjects (175 men; 148 women). Additionally, the low-dose 1-μg ACTH test was performed in 56 subjects (30 women, 26 men). Subjects were healthy volunteers, recruited in a preventive medicine screening program and an outpatient clinic.Results: Overall, basal serum TC and FC level were ~18 and ~33%, respectively, higher in men than in women (TC, 14.5 ± 0.33 μg/dL vs. 12.3 ± 0.33 μg/dL; P<.0001; FC, 0.68 ± 0.02 μg/dL vs. 0.51 ± 0.02 μg/dL; P<.0001). The higher FC in men relative to women was apparent across a wide age range (17 to 86 years) and persisted after adjustment for age and body mass index. The FC fraction (%FC, out of TC) was concordantly higher in men (5.4 ± 0.09% vs. 4.8 ± 0.3%; P = .046). FC was not related to the estimated menopausal status (women age below and above 47, 50, or 53 years). ACTH-stimulated FC levels were significantly higher in men compared to women, as reflected by the area under the response curve (49.4 ± 3.4 μg × min vs. 39.6 ± 2.2 μg × min; P = .0014).Conclusion: Gender is an unrecognized determinant of serum FC in humans. The possibility of lifelong exposure to the higher bioactive fraction of cortisol under basal conditions or daily stress involving ACTH stimulation should be further investigated in the context of gender-related phenotypic features such as “android” (visceral) fat deposition and longevity.Abbreviations:ACTH = adrenocorticotropic hormoneBMI = body mass indexCBG = cortisol-binding globulinFC = free cortisolHPA = hypothalamic-pituitary-adrenalTC = total cortisol     

Marcadores bioquímicos,nutricionales y actividad antioxidante en el síndrome metabólico

Background and objectives1) Nutritional assessment of the diet followed by patients with metabolic syndrome, and 2) biochemical analysis of the oxidation-reduction level in patients with metabolic syndrome.Material and methodsA cross-sectional study was conducted in patients with metabolic syndrome in Murcia. Fifty-three patients, 33 with and 20 without (control group) metabolic syndrome, were selected. The intervention consisted of completion of a recall survey and a test to nutritionally assess dietary intake. Anthropometric and laboratory variables, including those related to antioxidant activity, were also tested.ResultsAntioxidant activity was within normal limits in both groups (1.7 ± 0.2 mmol/L in the control group and 1.8 ± 0.1 mmol/L in the metabolic syndrome group) (NS). Superoxide dismutase levels were not significantly different between the groups. Mean glutathione reductase levels (U/L) were higher in the control group as compared to patients with metabolic syndrome (P < .05). As regards oxidative stress biomarkers, mean isoprostane levels were higher in the control group (4.9 ± 6.2 ng/mL) than in metabolic syndrome patients (3.5 ± 3.9 ng/mL) (P < .05). Oxidized LDL values tended to be higher in metabolic syndrome patients (96 ± 23.2 U/L) as compared to the control group (86.2 ± 17.3  U/L), but differences were not significant.ConclusionsThere is a trend to a poorer nutritional and biochemical profile in patients with metabolic syndrome, who also tend to have a greater degree of oxidative stress.     

Improvement in Pancreatic β-Cell Function with Vitamin D and Calcium Supplementation in Vitamin D-Deficient Nondiabetic Subjects

ObjectiveThere are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency.MethodsNondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented.ResultsThirty-seven patients with 25-OHD deficiency participated in the study. The baseline and postvitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (− 0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (− 20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (− 4.88 ± 10.65 mg/dL); and homeostasis model assessment-2–percent β-cell function C-peptide secretion (HOMA-2–%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, − 3.751; P < .0001), 25-OHD (Z, − 4.9; P < .0001), intact PTH (Z, − 4.04; P < .0001), fasting plasma glucose (Z, − 2.7; P < .007), and HOMA-2–%B C-PEP (Z, − 1.923; P < .05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged.ConclusionOptimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and β-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis. (Endocr Pract. 2014;20:129-138)     

The ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) is present in human plasma and expressed dependent on body mass index

Ghrelin is the only known peripherally produced and centrally acting peptide hormone stimulating food intake. The acylation of ghrelin is essential for binding to its receptor. Recently, the ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) was identified in mice, rats and humans. In addition to gastric mucosal expression, GOAT was also detected in the circulation of rodents and its expression was dependent on metabolic status. We investigated whether GOAT is also present in human plasma and whether expression levels are affected under different conditions of body weight. Normal weight, anorexic and obese subjects with body mass index (BMI) 30–40, 40–50 and >50 were recruited (n = 9/group). In overnight fasted subjects GOAT protein expression was assessed by Western blot and ghrelin measured by ELISA. GOAT protein was detectable in human plasma. Anorexic patients showed reduced GOAT protein levels (−42%, p < 0.01) whereas obese patients with BMI > 50 had increased concentrations (+34%) compared to normal weight controls. Ghrelin levels were higher in anorexic patients compared to all other groups (+62–78%, p < 0.001). Plasma GOAT protein expression showed a positive correlation with BMI (r = 0.71, p < 0.001) and a negative correlation with ghrelin (r = −0.60, p < 0.001). Summarized, GOAT is also present in human plasma and GOAT protein levels depend on the metabolic environment with decreased levels in anorexic and increased levels in morbidly obese patients. These data may indicate that GOAT counteracts the adaptive changes of ghrelin observed under these conditions and ultimately contributes to the development or maintenance of anorexia and obesity as it is the only enzyme acylating ghrelin.     

Diabetes Status and Race are Associated With Cardiovascular Risk Markers in Obese Adolescents

ObjectiveThe objective of this study was to evaluate differences in cardiovascular disease (CVD) risk markers in obese adolescents based on diabetes status and race in order to improve risk-reduction intervention strategies.MethodsThis was a retrospective, cross-sectional study of obese adolescents, age 10 to 21 years, who were evaluated at Children’s of Alabama between 2000 and 2012. Subjects were classified by glycated hemoglobin (HbA_1c) as having normoglycemia, prediabetes, or type 2 diabetes mellitus (T2DM).ResultsThere were a total of 491 African American (AA) or Caucasian American (CA) subjects. Body mass index was not different between HbA_1c and racial groups. Compared to subjects with normoglycemia or prediabetes, subjects with T2DM had higher levels of total cholesterol (TC) (178.6 ± 43.8 mg/dL vs. 161.5 ± 32.5 mg/dL vs. 162.4 ± 30.6 mg/dL; P < .0001) and low-density-lipoprotein cholesterol (107.4 ± 39.2 mg/dL vs. 97.0 ± 31.0 mg/dL vs. 97.5 ± 26.9 mg/dL; P = .0073). Compared with AA subjects, CA subjects had lower high-density-lipoprotein cholesterol (HDL-C) levels (40.4 ± 10.4 mg/dL vs. 44.3 ± 11.9 mg/dL; P = .0005) and higher non-HDL-C levels (129.6 ± 36.2 mg/dL vs. 122.5 ± 37.5 mg/dL; P = .0490). Of the characteristics studied, HbA_1c had the most significant positive association with dyslipidemia and was strongly correlated with both TC (β, 4.21; P < .0001) and non-HDL-C (β, 4.3; P < .0001).ConclusionObese adolescents with T2DM have more abnormal lipoprotein profiles than those with normoglycemia or prediabetes. Obese CA adolescents have more abnormal lipids than obese AA adolescents. HbA_1c was the characteristic most highly associated with abnormal lipoprotein profiles in our subjects. Our results show that CVD risk markers in obese adolescents vary by race and HbA_1c concentration. (Endocr Pract. 2015;21:165-173)