Workflow for Management of Gonadal Neoplasm in 2 Patients with Differences of Sex Development Enrolled in an Experimental Gonadal Tissue Cryopreservation Protocol.

OBJECTIVE: To outline our experimental gonadal tissue cryopreservation (GTC) protocol that does not disrupt the standard of care in medically-indicated gonadectomy for patients with differences of sex development, including highlighting the multidisciplinary collaborative protocol for when neoplasm is discovered in these cases. METHODS: Two patients with complete gonadal dysgenesis who were undergoing medically-indicated prophylactic bilateral gonadectomy elected to pursue GTC. Both were found to have germ cell neoplasia in situ on initial pathologic analysis, requiring recall of the gonadal tissue, which had been cryopreserved. RESULTS: Cryopreserved gonadal tissue was successfully thawed and transferred to pathology for complete analysis. No germ cells were identified in either patient nor were found to have malignancy, so further treatment beyond gonadectomy was not indicated. Pathologic information was communicated to each family, including that long-term GTC was no longer possible. CONCLUSION: Organizational planning and coordination between the clinical care teams, GTC laboratory, and pathology were key to handling these cases with neoplasia. Processes that anticipated the possibility of discovering neoplasia within tissue sent to pathology and the potential need to recall GTC tissue to complete staging included (1) documenting the orientation and anatomical position of tissue processed for GTC, (2) defining parameters in which tissue will be recalled, (3) efficiently thawing and transferring GTC tissue to pathology, and (4) coordinating release of pathology results with verbal communication from the clinician to provide context. GTC is desired by many families and at the time of gonadectomy and is (1) feasible for patients with DSD, and (2) did not inhibit patient care in 2 patients with GCNIS.

Prenatal detection and evaluation of differences of sex development: A qualitative interview study of parental perspectives and unmet needs.

OBJECTIVES: Prenatal diagnoses of differences of sex development (DSD) are increasing due to availability of cell-free DNA screening (cell-free DNA screening (cfDNA)). This study explores first-hand experiences of parents whose children had prenatal findings of DSD. METHODS: Eligible parents were identified through chart review at a pediatric center and interviewed about their prenatal evaluation, decision making, informational sources, and support systems. Interviews were coded using a combined inductive and deductive thematic analysis. Parents also completed quantitative measures of decisional regret. RESULTS: Seventeen parents (13 mothers; 4 fathers) of 13 children (with 7 DSD diagnoses) were recruited. Four children had discordance between sex predicted by cfDNA versus prenatal ultrasound, and 2 had non-binary appearing (atypical) genitalia on prenatal ultrasound. Of these 6, 3 were not offered additional prenatal testing or counseling. Most parents described tension between obtaining support through disclosure of their child's diagnosis and preserving their child's autonomy/privacy, highlighting the need for mental health support. CONCLUSION: This is the first study to gather qualitative data from parents whose children had prenatal findings of DSD. We identified multiple targets for intervention to improve care for patients with DSD across the lifespan, including improvements in clinician education, pre- and post-test counseling, and patient education materials.

A-TAPER: A Framework for Deprescribing Medications effectively.

Inappropriate medication use creates avoidable safety issues for older adults. Deprescribing medications that are high risk and/or of minimal benefit is important for reducing morbidity and adverse effects, especially in this population. A variety of deprescribing resources and algorithms are available, but a singular framework to effectively approach and implement the deprescribing of unnecessary medications in practice does not exist. An interprofessional team of pharmacists, geriatricians, and researchers developed a framework to guide providers in deprescribing medications. This framework is represented by the acronym A-TAPER, which stands for Assess medication use, Talk about risks versus benefits, select Alternatives, Plan next steps, Engage patient, and Reduce dose. Within this framework, comprehensive, medication-specific deprescribing toolkits can be created.

Chemical vapour deposition of graphene on copper-nickel alloys: the simulation of a thermodynamic and kinetic approach.

Chemical vapour deposition (CVD) of graphene on transition metals is generally believed to be the fabrication route best suited for the production of high-quality large-area graphene sheets. The mechanism of CVD graphene growth is governed by interactions in both the gas phase and at the surface. Here we present a simulation of the CVD graphene growth mechanism which includes thermodynamics, gas phase kinetics and the surface reaction in a sequential manner. The thermodynamic simulation shows that the deposition driving force is the greatest for high carbon to hydrogen ratios and reaches a maximum at around 850 °C. No graphene growth is observed below this temperature. The surface kinetic model also shows that below this temperature, the carbon surface concentration is less than the solubility limit, thus no film can grow. The effect of the reaction chamber geometry on the product concentrations was clear from the gas phase decomposition reactions. The gas residence times studied here (around 0.07 s) show that the optimum gas phase composition is far from that expected at thermodynamic equilibrium. The surface kinetics of CH4 reactions on Ni, Cu and Cu-Ni surfaces shows good agreement with the experimental results for different growth pressures (0.1 to 0.7 mbar), temperatures (600 to 1200 °C) and different Ni thicknesses (25-500 µm). Also, the model works well when substrates with various C solubilities are used. The thermodynamic and kinetic models described here can be used for the design of improved reactors to optimise the production of graphene with differing qualities, either single or multi-layer and sizes. More importantly, the transfer to a continuous process with a moving substrate should also be possible using the model if it is extended from 2D to 3D.

Sediment metal enrichment and ecological risk assessment of ten ports and estuaries in the World Harbours Project.

Ten global harbours were assessed for sediment quality by quantifying the magnitude of anthropogenic change and ecological risk. Anthropogenic change (enrichment) was high for Derwent River and Sydney estuary, moderate for Santander Harbour, Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin. All 10 enrichment indices used showed similar results. Derwent River sediment was rated at high ecological risk, followed by Sydney and Santander estuaries with moderate risk. Auckland and Darwin sediments exhibited minimal ecological risk and sediment in the remaining harbours (Dublin, Hong Kong, Ravenna, Ria de Vigo and Rio de Janeiro) were assessed at slight ecological risk. The extraordinary variety of environments and types/quantities/qualities of data investigated resulted in as much a critique and development of methodology, as an assessment of human impact, including unique techniques for elemental normalisation and contaminant classification. Recommendations for an improved technical framework for sediment quality assessment are provided.

Characterization of cold-induced remodelling reveals depot-specific differences across and within brown and white adipose tissues in mice.

AIM: Brown and beige adipose tissues dissipate energy in the form of heat via mitochondrial uncoupling protein 1, defending against hypothermia and potentially obesity. The latter has prompted renewed interest in understanding the processes involved in browning to realize the potential therapeutic benefits. To characterize the temporal profile of cold-induced changes and browning of brown and white adipose tissues in mice. METHODS: Male C57BL/6J mice were singly housed in conventional cages under cold exposure (4 °C) for 1, 2, 3, 4, 5 and 7 days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological, immunohistochemical, gene and protein expression analysis. RESULTS: Upon cold exposure, food intake increased, whilst body weight and adipocyte size were found to be transiently reduced. iBAT mass was found to be increased, whilst sWAT and eWAT were found to be transiently decreased. A combination of morphological, genetic (Ucp-1, Pgc-1α and Elov13) and biochemical (UCP-1, PPARγ and aP2) analyses demonstrated the depot-specific remodelling in response to cold exposure. CONCLUSION: Our results demonstrate the differential responses to cold-induced changes across discrete BAT and WAT depots and support the notion that the effects of short-term cold exposure are achieved by expansion, activation and increasing thermogenic capacity of iBAT, as well as browning of sWAT and, to a lesser extent, eWAT.

Monte Carlo simulations of ABC stacked kagome lattice films.

Properties of films of geometrically frustrated ABC stacked antiferromagnetic kagome layers are examined using Metropolis Monte Carlo simulations. The impact of having an easy-axis anisotropy on the surface layers and cubic anisotropy in the interior layers is explored. The spin structure at the surface is shown to be different from that of the bulk 3D fcc system, where surface axial anisotropy tends to align spins along the surface [1 1 1] normal axis. This alignment then propagates only weakly to the interior layers through exchange coupling. Results are shown for the specific heat, magnetization and sub-lattice order parameters for both surface and interior spins in three and six layer films as a function of increasing axial surface anisotropy. Relevance to the exchange bias phenomenon in IrMn3 films is discussed.

Outness, Stigma, and Primary Health Care Utilization among Rural LGBT Populations.

BACKGROUND: Prior studies have noted significant health disadvantages experienced by LGBT (lesbian, gay, bisexual, and transgender) populations in the US. While several studies have identified that fears or experiences of stigma and disclosure of sexual orientation and/or gender identity to health care providers are significant barriers to health care utilization for LGBT people, these studies have concentrated almost exclusively on urban samples. Little is known about the impact of stigma specifically for rural LGBT populations, who may have less access to quality, LGBT-sensitive care than LGBT people in urban centers. METHODOLOGY: LBGT individuals residing in rural areas of the United States were recruited online to participate in a survey examining the relationship between stigma, disclosure and "outness," and utilization of primary care services. Data were collected and analyzed regarding LGBT individuals' demographics, health care access, health risk factors, health status, outness to social contacts and primary care provider, and anticipated, internalized, and enacted stigmas. RESULTS: Higher scores on stigma scales were associated with lower utilization of health services for the transgender & non-binary group, while higher levels of disclosure of sexual orientation were associated with greater utilization of health services for cisgender men. CONCLUSIONS: The results demonstrate the role of stigma in shaping access to primary health care among rural LGBT people and point to the need for interventions focused towards decreasing stigma in health care settings or increasing patients' disclosure of orientation or gender identity to providers. Such interventions have the potential to increase utilization of primary and preventive health care services by LGBT people in rural areas.

Cloud condensation nucleation activities of calcium carbonate and its atmospheric ageing products.

Aerosol particles can serve as cloud condensation nuclei (CCN) to form cloud droplets, and its composition is a main factor governing whether an aerosol particle is an effective CCN. Pure mineral dust particles are poor CCN; however, changes in chemical composition of mineral dust aerosol particles, due to heterogeneous reactions with reactive trace gases in the troposphere, can modify their CCN properties. In this study we investigated the CCN activities of CaCO3 (as a surrogate for mineral dust) and its six atmospheric ageing products: Ca(NO3)2, CaCl2, CaSO4, Ca(CH3SO3)2, Ca(HCOO)2, and Ca(CH3COO)2. CaCO3 has a very low CCN activity with a hygroscopicity parameter (κ) of 0.001-0.003. The CCN activities of its potential atmospheric ageing products are significantly higher. For example, we determined that Ca(NO3)2, CaCl2 and Ca(HCOO)2 have κ values of ∼0.50, similar to that of (NH4)2SO4. Ca(CH3COO)2 has slightly lower CCN activity with a κ value of ∼0.40, and the κ value of CaSO4 is around 0.02. We further show that exposure of CaCO3 particles to N2O5 at 0% relative humidity (RH) significantly enhances their CCN activity, with κ values increasing to around 0.02-0.04. Within the experimental uncertainties, it appears that the variation in exposure to N2O5 from ∼550 to 15,000 ppbv s does not change the CCN activities of aged CaCO3 particles. This observation indicates that the CaCO3 surface may be already saturated at the shortest exposure. We also discussed the atmospheric implications of our study, and suggested that the rate of change in CCN activities of mineral dust particles in the troposphere is important to determine their roles in cloud formation.

Obesity and sex influence insulin resistance and total and multimer adiponectin levels in adult neutered domestic shorthair client-owned cats.

In this study, we estimated insulin sensitivity and determined plasma concentrations of total-, low-molecular-weight (LMW), and high-molecular-weight (HMW) adiponectin and leptin in 72 domestic shorthair, neutered, client-owned cats. Glucose tolerance was assessed with an intravenous glucose tolerance test and body fat percentage (BF%) was measured with dual-energy x-ray absorptiometry. Total adiponectin was measured with 2 different ELISAs. Low-molecular-weight and HMW adiponectin plasma concentrations were determined by Western blot analysis after sucrose-gradient velocity centrifugation, and the adiponectin multimer ratio [SA = HMW/(HMW + LMW)] was calculated. Differences in glucose tolerance, leptin, total adiponectin, and multimer ratio among lean (BF% <35; n = 26), overweight (35 45; n = 18) cats as well as between male (n = 34) and female (n = 38) neutered cats were evaluated by linear regression and 2-way ANOVA. Sex and age were included as covariates for analysis of BF%, whereas BF%, fat mass, and lean body mass were covariates for analysis of sex differences. Increased BF% was negatively correlated with multimer ratio (SA, r = -45; P < 0.002), whereas no differences were found in total adiponectin concentrations among BF% groups (P > 0.01). Male cats had indices of decreased insulin tolerance and significantly lower total adiponectin concentrations than did female cats (mean ± SEM, 3.7 ± 0.4 vs 5.4 ± 0.5 µg/mL; P < 0.02). Altered SAs could contribute to an obesity-associated decreasing glucose tolerance in cats, and low total adiponectin concentrations may relate to increased risk of diabetes mellitus in neutered male cats.

Remediation of dichloromethane (CH2Cl2) using non-thermal, atmospheric pressure plasma generated in a packed-bed reactor.

This work describes the application of a non-thermal plasma generated in a dielectric barrier packed-bed plasma reactor for the remediation of dichloromethane (CH2Cl2, DCM). The overall aim of this investigation is to identify the role of key process parameters and chemical mechanisms on the removal efficiency of DCM in plasma. The influence of process parameters, such as oxygen concentration, concentration of initial volatile organic compounds (VOCs), energy density, plasma residence time, and background gas, on the removal efficiency of 500 ppm DCM was investigated. Results showed a maximum removal efficiency with the addition of 2-4% oxygen into a nitrogen plasma. It is thought that oxygen concentrations in excess of 4% decreased the decomposition of chlorinated VOCs as a result of ozone and nitrogen oxide formation. Increasing the residence time and the energy density resulted in increasing the removal efficiency of chlorinated VOCs in plasma. A chemical kinetic model has been developed on the basis of the proposed reaction scheme, and the calculation of end product concentrations are in general good agreement with the observed values. With the understanding of the effect of the key parameters, it has been possible to optimize the remediation process.

Gas purification by nonthermal plasma: a case study of ethylene.

The destruction of ethylene in a dielectric barrier discharge plasma is investigated by the combination of kinetic modeling and experiments, as a case study for plasma-based gas purification. The influence of the specific energy deposition on the removal efficiency and the selectivity toward CO and CO2 is studied for different concentrations of ethylene. The model allows the identification of the destruction pathway in dry and humid air. The latter is found to be mainly initiated by metastable N2 molecules, but the further destruction steps are dominated by O atoms and OH radicals. Upon increasing air humidity, the removal efficiency drops by ± 15% (from 85% to 70%), but the selectivity toward CO and CO2 stays more or less constant at 60% and 22%, respectively. Beside CO and CO2, we also identified acetylene, formaldehyde, and water as byproducts of the destruction process, with concentrations of 1606 ppm, 15033 ppm, and 185 ppm in humid air (with 20% RH), respectively. Finally, we investigated the byproducts generated by the humid air discharge itself, which are the greenhouse gases O3, N2O, and the toxic gas NO2.

Monte Carlo simulations of intragrain spin effects in a quasi-2D Heisenberg model with uniaxial anisotropy.

A combination of Metropolis and modified Wolff cluster algorithms is used to examine the impact of uniaxial single-ion anisotropy on the phase transition to ferromagnetic order of Heisenberg macrospins on a 2D square lattice. This forms the basis of a model for granular perpendicular recording media where macrospins represent the magnetic moment of grains. The focus of this work is on the interplay between anisotropy D, intragrain exchange J' and intergrain exchange J on the ordering temperature T(C) and extends our previous reported analysis of the granular Ising model. The role of intragrain degrees of freedom in heat assisted magnetic recording is discussed.

Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib.

BACKGROUND: Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the 'Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targeted by DCA to induce myeloma growth inhibition. METHODS: Representative multiple myeloma cell lines and a myeloma-bearing mice were treated with DCA, alone and in combination with bortezomib. RESULTS: We found that aerobic glycolysis occurs in approximately half of MM cell lines examined, producing on average 1.86-fold more lactate than phorbol myristate acetate stimulated-peripheral blood mononuclear cells and is associated with low-oxidative capacity. Lower doses of DCA (5-10 mM) suppressed aerobic glycolysis and improved cellular respiration that was associated with activation of the pyruvate dehydrogenase complex. Higher doses of DCA (10-25 mM) induced superoxide production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest in MM cell lines. In addition, DCA increased MM cell line sensitivity to bortezomib, and combinatorial treatment of both agents improved the survival of myeloma-bearing mice. CONCLUSION: Myeloma cells display aerobic glycolysis and DCA may complement clinically used MM therapies to inhibit disease progression.

Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women.

OBJECTIVE: Evaluate the safety and tolerability of beloranib, a fumagillin-class methionine aminopetidase-2 (MetAP2) inhibitor, in obese women over 4 weeks. DESIGN AND METHODS: Thirty-one obese (mean BMI 38 kg/m2) women were randomized to intravenous 0.1, 0.3, or 0.9 mg/m2 beloranib or placebo twice weekly for 4 weeks (N = 7, 6, 9, and 9). RESULTS: The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9 mg/m2 beloranib was -3.8 kg (95% CI -5.1, -0.9; N = 8) versus -0.6 kg with placebo (-4.5, -0.1; N = 6). Weight change for 0.1 and 0.3 mg/m2 beloranib was similar to placebo. Beloranib (0.9 mg/m2) was associated with a significant 42 and 18% reduction in triglycerides and LDL-cholesterol, as well as improvement in C-reactive protein and reduced sense of hunger. Changes in ß-hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor-21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged. CONCLUSIONS: Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin.

Postprandial total and HMW adiponectin following a high-fat meal in lean, obese and diabetic men.

BACKGROUND/OBJECTIVES: Recent work suggests that macronutrients are pro-inflammatory and promote oxidative stress. Reports of postprandial regulation of total adiponectin have been mixed, and there is limited information regarding postprandial changes in high molecular weight (HMW) adiponectin. The aim of this study was to assess the effect of a standardised high-fat meal on metabolic variables, adiponectin (total and HMW), and markers of inflammation and oxidative stress in: (i) lean, (ii) obese non-diabetic and (iii) men with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: Male subjects: lean (n=10), obese (n=10) and T2DM (n=10) were studied for 6 h following both a high-fat meal and water control. Metabolic variables (glucose, insulin, triglycerides), inflammatory markers (interleukin-6 (IL6), tumour necrosis factor (TNF)α, high-sensitivity C-reactive protein (hsCRP), nuclear factor (NF)κB expression in peripheral blood mononuclear cells (p65)), indicators of oxidative stress (oxidised low density lipoprotein (oxLDL), protein carbonyl) and adiponectin (total and HMW) were measured. RESULTS: No significant changes in TNFα, p65, oxLDL or protein carbonyl concentrations were observed. Overall, postprandial IL6 decreased in subjects with T2DM but increased in lean subjects, whereas hsCRP decreased in the lean cohort and increased in obese subjects. There was no overall postprandial change in total or HMW adiponectin in any group. Total adiponectin concentrations changed over time following the water control, and the response was significantly different in lean subjects compared with subjects with T2DM (P=0.04). CONCLUSIONS: No consistent significant postprandial inflammation, oxidative stress or regulation of adiponectin was observed in this study. Findings from the water control suggest differential basal regulation of total adiponectin in T2DM compared with lean controls.

Overexpression of the adiponectin receptor AdipoR1 in rat skeletal muscle amplifies local insulin sensitivity.

Adiponectin is an adipokine whose plasma levels are inversely related to degrees of insulin resistance (IR) or obesity. It enhances glucose disposal and mitochondrial substrate oxidation in skeletal muscle and its actions are mediated through binding to receptors, especially adiponectin receptor 1 (AdipoR1). However, the in vivo significance of adiponectin sensitivity and the molecular mechanisms of muscle insulin sensitization by adiponectin have not been fully established. We used in vivo electrotransfer to overexpress AdipoR1 in single muscles of rats, some of which were fed for 6 wk with chow or high-fat diet (HFD) and then subjected to hyperinsulinemic-euglycemic clamp. After 1 wk, the effects on glucose disposal, signaling, and sphingolipid metabolism were investigated in test vs. contralateral control muscles. AdipoR1 overexpression (OE) increased glucose uptake and glycogen accumulation in the basal and insulin-treated rat muscle and also in the HFD-fed rats, locally ameliorating muscle IR. These effects were associated with increased phosphorylation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3ß. AdipoR1 OE also caused increased phosphorylation of p70S6 kinase, AMP-activated protein kinase, and acetyl-coA carboxylase as well as increased protein levels of adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif-1 and adiponectin, peroxisome proliferator activated receptor-γ coactivator-1α, and uncoupling protein-3, indicative of increased mitochondrial biogenesis. Although neither HFD feeding nor AdipoR1 OE caused generalized changes in sphingolipids, AdipoR1 OE did reduce levels of sphingosine 1-phosphate, ceramide 18:1, ceramide 20:2, and dihydroceramide 20:0, plus mRNA levels of the ceramide synthetic enzymes serine palmitoyl transferase and sphingolipid Δ-4 desaturase, changes that are associated with increased insulin sensitivity. These data demonstrate that enhancement of local adiponectin sensitivity is sufficient to improve skeletal muscle IR.

Structure, signalling and physiologic role of adiponectin-dietary and exercise- related variations.

Since its discovery in 1995 adiponectin has garnered considerable interest from the academic, clinical and biotech communities due to its proposed salutary anti-inflammatory, anti-diabetic, anti-atherogenic and cardioprotective properties. As a result our appreciation of adiponectin's structure and the importance of post-translational modifications (PTMs) in adiponectin production are now relatively advanced. So too, following the identification of a variety of adiponectin receptors, binding proteins and downstream signalling networks, is our understanding of adiponectin's intracellular signalling pathways that are implicated in mediating adiponectin's pleiotropic effects. Adiponectin's ability to moderate inflammation, which is recognised as a key protagonist in many modern diseases, may be the key to many of its beneficial effects. Recent insights indicate that adiponectin modulates cellular inflammation by affecting sphingolipid metabolism, with the adiponectin receptors displaying intrinsic ceramidase activity. In the current review we will summarise the molecular details of adiponectin, discuss key players and recent insights into adiponectin signalling and consider the physiologic role(s) of adiponectin. We will also review studies into the effects of diet or exercise on circulating adiponectin levels focusing largely on reports from human trials.

Adiposity and adiponectin in dogs: investigation of causes of discrepant results between two studies.

Although one study showed lower adiponectin concentrations in obese dogs, other recent studies indicate that adiponectin might not be decreased in obese dogs, raising the possibility that the physiology of adiponectin is different in dogs than in humans. The aim of this study was to investigate possible causes of the discrepancy between the two largest studies to date that assessed the association between adiposity and adiponectin concentration in dogs, including the validity of the assay, laboratory error, and the effects of breed, sex, and neuter status on the relationship between adiposity and adiponectin concentrations. Adiponectin concentrations measured with a previously validated adiponectin ELISA were compared with those estimated by Western blotting analysis of reduced and denatured plasma samples. The possibility of laboratory error and the effect of EDTA anticoagulant and aprotinin were tested. Adiponectin concentration was measured by ELISA in 20 lean dogs (10 male and 10 female, 5 neutered in each sex). There was close correlation between adiponectin concentrations measured by ELISA and those estimated by Western blotting analysis (r = 0.90; P < 0.001). There was no substantial effect of EDTA, aprotinin, or laboratory error on the results. There was confounding by neuter status of the relationship between adiposity and adiponectin concentrations, but adiponectin concentrations were not significantly lower in male than in female lean dogs (females, 36 mg/L; males, 26 mg/L; P > 0.20) and were not significantly lower in intact than in neutered lean male dogs (intact, 28 mg/L; neutered, 23 mg/L; P = 0.49). We conclude that the adiponectin ELISA previously validated for use in dogs appears to be suitable for determination of canine adiponectin concentrations and that testosterone does not appear to have a strong effect on plasma adiponectin concentrations in dogs. Obesity might decrease adiponectin concentrations in intact but not in neutered dogs.

Distinct adiponectin profiles might contribute to differences in susceptibility to type 2 diabetes in dogs and humans.

Dogs develop obesity-associated insulin resistance but not type 2 diabetes mellitus. Low adiponectin is associated with progression to type 2 diabetes in obese humans. The aims of this study were to compare total and high molecular weight (HMW) adiponectin and the ratio of HMW to total adiponectin (S(A)) between dogs and humans and to examine whether total or HMW adiponectin or both are associated with insulin resistance in naturally occurring obese dogs. We compared adiponectin profiles between 10 lean dogs and 10 lean humans and between 6 lean dogs and 6 age- and sex-matched, client-owned obese dogs. Total adiponectin was measured with assays validated in each species. We measured S(A) with velocity centrifugation on sucrose gradients. The effect of total and HMW adiponectin concentrations on MINMOD-estimated insulin sensitivity was assessed with linear regression. Lean dogs had total and HMW adiponectin concentrations three to four times higher than lean humans (total: dogs 32 ± 5.6 mg/L, humans 10 ± 1.3 mg/L, P<0.001; HMW: dogs 25 ± 4.5 mg/L, humans 6 ± 1.3 mg/L, P<0.001) and a higher S(A) (dogs: 0.78 ± 0.05; humans: 0.54 ± 0.08, P = 0.002). Adiponectin concentrations and S(A) were not lower in obese dogs (0.76 ± 0.05 in both groups; P=1). Total adiponectin, HMW adiponectin, and S(A) were not associated with insulin sensitivity in dogs. We propose that differences in adiponectin profiles between humans and dogs might contribute to the propensity of humans but not dogs to develop type 2 diabetes. Dogs with chronic, naturally occurring obesity do not have selectively reduced HMW adiponectin, and adiponectin does not appear to be important in the development of canine obesity-associated insulin resistance.