COTSMod: A spatially explicit metacommunity model of outbreaks of crown-of-thorns starfish and coral recovery.

Outbreaks of the Pacific crown-of-thorns starfish (COTS; Acanthaster cf. solaris) have been responsible for 40% of the decline in coral cover on the GBR over the last 35 years. With the intensity and frequency of bleaching and cyclonic disturbances increasing, effectively managing these outbreaks may allow reefs an opportunity to recover from these cumulative impacts. Significant research effort has been directed toward developing regional scale models for COTS outbreaks, but these have yet to be fit explicitly to long term time series at the scale of the entire GBR, nor do previous research efforts incorporate explicit estimates of cumulative disturbance history. We developed a stage-based metapopulation model for COTS at a 1×1km resolution using long-term time series and modelled estimates of COTS larval connectivity, nutrient concentrations and important vital rates estimated from the literature. We coupled this metapopulation model to an existing spatially explicit model of coral cover growth, disturbance and recovery across the GBR from 1996 to 2017 to create a metacommunity model. Our results were validated against a spatially and temporally extensive dataset of COTS and coral cover across the GBR, predicting an average coral decline of 1.3% p.a. across the GBR, and accurately recreating coral cover trajectories (mean prediction error=7.1%) and COTS outbreak classification (accuracy=80%). Sensitivity analyses revealed that overall model accuracy was most sensitive to larval predation (boosted regression tree; relative importance=46.7%) and two parameters defining juvenile density dependent mortality (21.5% and 17.5%). The COTS model underestimated peak COTS densities particularly in the Swains and Townsville sectors of the reef, while overestimating COTS density during non-outbreak years. A better understanding of inter-annual variability in larval connectivity, and regionally variable density dependence for adult COTS life stages may improve model fit during these extreme outbreak events. Our model provides a platform to develop upon, and with improvements to estimates of larval connectivity and larval predation could be used to simulate the effects of implementing varying combinations of COTS interventions. This research highlights the importance of the early life history stages of COTS as drivers of outbreak dynamics, emphasizing the need for further empirical research to estimate these parameters.

Phase 1 study of MEDI3902, an investigational anti-Pseudomonas aeruginosa PcrV and Psl bispecific human monoclonal antibody, in healthy adults.

OBJECTIVES: MEDI3902 is a bivalent, bispecific human immunoglobulin G1κ monoclonal antibody that binds to both the Pseudomonas aeruginosa PcrV protein involved in host cell cytotoxicity and the Psl exopolysaccharide involved in P. aeruginosa colonization and tissue adherence. MEDI3902 is being developed for the prevention of nosocomial P. aeruginosa pneumonia in high-risk patients. METHODS: This phase 1 dose-escalation study (NCT02255760) evaluated the safety, pharmacokinetics, antidrug antibody (ADA) responses and ex vivo anticytotoxicity and opsonophagocytic killing activities of MEDI3902 after a single intravenous infusion in healthy adults aged 18 to 60 years. Fifty-six subjects were randomized in a 3:1 ratio to receive 250, 750, 1500 or 3000 mg of MEDI3902 or placebo and followed for 60 days afterwards. RESULTS: Treatment-emergent adverse events (TEAEs) were mild or moderate in severity; no serious TEAEs were observed. The most common TEAEs were infusion-related reactions. MEDI3902 exhibited approximately linear pharmacokinetics across the 250, 750 and 1500 mg doses and nonlinear pharmacokinetics between the 1500 and 3000 mg doses. One subject in the 3000 mg group tested positive for ADA on day 61 and had a lower MEDI3902 serum concentration from days 43 to 61 than ADA-negative subjects. Serum anticytotoxicity antibody concentrations and opsonophagocytic killing activity were correlated with MEDI3902 serum concentrations across all doses. CONCLUSIONS: Phase 1 study results of MEDI3902 in healthy subjects support further evaluation of its safety and efficacy in subjects at risk for P. aeruginosa pneumonia.

Strategies to optimize the performance of Robotic-assisted laparoscopic hysterectomy.

A hybrid technique of robot-assisted, laparoscopic hysterectomy using the ENSEAL(®) Tissue Sealing Device is described in a retrospective, consecutive, observational case series. Over a 45 month period, 590 robot-assisted total laparoscopic hysterectomies +/- oophorectomy for benign and malignant indications were performed by a single surgeon with a bedside assistant at a tertiary healthcare center. Patient demographics, indications for surgery, comorbidities, primary and secondary surgical procedures, total operative and surgical time, estimated blood loss (EBL), length of stay (LOS), complications, transfusions and subsequent readmissions were analyzed. The overall complication rate was 5.9% with 35 patients experiencing 69 complications. Mean (SD) surgery time, operating room (OR) time, EBL, and LOS for the entire cohort were 75.5 (39.42) minutes, 123.8 (41.15) minutes, 83.1 (71.29) millilitres, and 1.2 (0.93) days, respectively. Mean surgery time in the first year (2009) was 91.6 minutes, which declined significantly each year by 18.0, 19.0, and 24.3 minutes, respectively. EBL and LOS did not vary -significantly across the entire series. Using the cumulative sum method, an optimization curve for surgery time was evaluated, with three distinct optimization phases observed. In summary, the use of an advanced laparoscopic tissue-sealing device by a bedside surgical assistant provided an improved operative efficiency and reliable vessel sealing during robotic hysterectomy.

Aortic, cerebral and lower limb arterial and venous response to orthostatic stress after a 60-day bedrest.

The objective of this study is to assess by echography and Doppler the Cerebral (Vmca), Aortic (Vao) and Femoral (Vfem) arterial flow velocity and calf vein (Tibial, Gastrocnemius) section (Tib, Gast) during orthostatic intolerance (OI) test after a 60-day, head down tilt bed rest (HDBR). Twenty-four women (25-40 years) underwent a 60-day HDBR at -6°: eight as control (Con), eight with exercise against lower body negative pressure (Ex-Lb) and eight with nutrition supplement (Nut). Before and after (R0) HDBR, all subjects underwent a 10-min, 80° tilt followed by progressive LBNP until presyncope. After the post-HDBR Tilt + LBNP test, two groups were identified: finishers (F, n = 11) who completed the Tilt and non-finishers (NF, n = 13). A higher percentage decrease in Vao flow, higher percentage distension of Tib vein and a lack of increase in Vmca/Vfem ratio during the post-HDBR Tilt + LBNP compared to pre-HDBR were correlated to OI, but not all of these abnormal responses were present in each of the NF subjects. Abnormal responses were more frequent in Con and Nut than in Ex-Lb subjects. (1) HDBR did not affect the cardiac, arterial and venous responses to the orthostatic test to the same extent in each subject. (2) Exercise within LBNP partially preserved the cardiovascular response to Tilt, while Nutrition supplementation had no efficacy. (3) Cerebral/femoral flow ratio and aortic flow were the parameters most closely related to OI. (4) Reduction in aortic flow was not the major hemodynamic change preceding syncope.

Tibial and gastrocnemian vein response to LBNP after a 60 day bedrest with and without counter-measures (WISE study).

UNLABELLED: The objective was to quantify calf vein cross section area (CSA) maximal enlargement and the percent change in response to LBNP (lower body negative pressure) after a 60 day bedrest. METHOD: The 24 healthy volunteers (25-40 y) of the WISE 60 day HDT(-6 degree) bedrest, were divided into 3 groups: Control (Co), Exercise countermeasure (Ex: treadmill under LBNP and flywheel), Nutrition (Nut: daily protein supplement). All were studied at -45mmHg LBNP pre and at HDT day 55. Posterior Tibial (Tib), and Gastrocnemian (Gast) vein were investigated by echography using an echographic probe fixed at the upper and posterior part of the calf. From the post HDT CSE test the subjects were identified as finisher or non finisher to the 10-min tilt tolerance test. RESULTS: At LBNP-45mmHg, the maximal enlargement of the Tib and Gast veins remained constant pre, and at HDT day 55 in all group (Co, Ex, Nut, finisher, non finisher). For both veins there was a higher vein distension (percent change from supine rest to -45mmHg) in Co and Nut group compared to Ex group despite the maximal distension was similar in all groups. Also the vein distension was higher in non finisher than in finisher. CONCLUSION: The maximal distension of the vein were not affected nor by HDT nor by CM. The Ex counter-measure minimized the bed rest effect on leg vein distensibility (percent CSA change) while the Nut countermeasure had no effect. Higher leg vein distensibility was associated with reduced orthostatic tolerance.

Changes in cerebral oxygenation and blood flow during LBNP in spinal cord-injured individuals.

Spinal cord-injured (SCI) individuals, having a sympathetic nervous system lesion, experience hypotension during sitting and standing. Surprisingly, they experience few syncopal events. This suggests adaptations in cerebrovascular regulation. Therefore, changes in systemic circulation, cerebral blood flow, and oxygenation in eight SCI individuals were compared with eight able-bodied (AB) individuals. Systemic circulation was manipulated by lower body negative pressure at several levels down to -60 mmHg. At each level, we measured steady-state blood pressure, changes in cerebral blood velocity with transcranial Doppler, and cerebral oxygenation using near-infrared spectroscopy. We found that mean arterial pressure decreased significantly in SCI but not in AB individuals, in accordance with the sympathetic impairment in the SCI group. Cerebral blood flow velocity decreased during orthostatic stress in both groups, but this decrease was significantly greater in SCI individuals. Cerebral oxygenation decreased in both groups, with a tendency to a greater decrease in SCI individuals. Thus present data do not support an advantageous mechanism during orthostatic stress in the cerebrovascular regulation of SCI individuals.

Effects of pharmacological adrenergic and vagal modulation on fractal heart rate dynamics.

Breakdown of short-term fractal-like behaviour of HR indicates an increased risk for adverse cardiovascular events and mortality, but the pathophysiological background for altered fractal HR dynamics is not known. Our aim was to study the effects of pharmacological modulation of autonomic function on fractal correlation properties of heart rate (HR) variability in healthy subjects. Short-term fractal scaling exponent (alpha1) along with spectral components of HR variability were analysed during the following pharmacological interventions in healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12), (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation by low dose of atropine (n=10). Then alpha1 decreased progressively during the incremental doses of NE (from 0.85 +/- 0.250 to 0.55 +/- 0.23, P<0.0001). NE also decreased the average HR (P<0.001) and increased the high frequency spectral power (P<0.001). Vagal blockade with atropine increased the alpha1 value (from 0.82 +/- 0.22 to 1.24 +/- 0.41, P<0.05). Combined NE + EPI infusion and vagal activation with a low dose atropine did not result in any changes in alpha1, and alpha-adrenergic blockade by PHE did not completely reverse the effects of NE on alpha1. Increased levels of circulating NE result in reduction of short-term correlation properties of HR dynamics. The results suggest that coactivation of cardiac vagal outflow at the time of high levels of a circulating sympathetic transmitter explains the breakdown of fractal-like behaviour of human HR dynamics.

TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS.

BLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA. We show that mice treated with TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is blocked at the transitional T1 stage such that virtually no mature B cells are present, while B-1 cell numbers are relatively normal. These findings further elucidate the roles of BLyS and APRIL in modulating B cell development and suggest that BLyS is required for the development of most but not all mature B cell populations found in the periphery.

Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor.

We have characterized platelet-derived growth factor (PDGF) C, a novel growth factor belonging to the PDGF family. PDGF-C is a multidomain protein with the N-terminal region homologous to the extracellular CUB domain of neuropilin-1, and the C-terminal region consists of a growth factor domain (GFD) with homology to vascular endothelial growth factor (25%) and PDGF A-chain (23%). A serum-sensitive cleavage site between the two domains allows release of the GFD from the CUB domain. Competition binding and immunoprecipitation studies on cells bearing both PDGF alpha and beta receptors reveal a high affinity binding of recombinant GFD (PDGF-CC) to PDGF receptor-alpha homodimers and PDGF receptor-alpha/beta heterodimers. PDGF-CC exhibits greater mitogenic potency than PDGF-AA and comparable or greater mitogenic activity than PDGF-AB and PDGF-BB on several mesenchymal cell types. Analysis of PDGF-CC in vivo in a diabetic mouse model of delayed wound healing showed that PDGF-CC significantly enhanced repair of a full-thickness skin excision. Together, these studies describe a third member of the PDGF family (PDGF-C) as a potent mitogen for cells of mesenchymal origin in in vitro and in vivo systems with a binding pattern similar to PDGF-AB.

Molecular cloning, chromosome mapping and characterization of a testis-specific cystatin-like cDNA, cystatin T.

The cystatin superfamily of cysteine proteinase inhibitors consists of three major families. In the present study, we report the cloning of the cDNA for mouse cystatin T, which is related to family 2 cystatins. The deduced amino acid sequence of cystatin T contains regions of significant sequence homology including the four highly conserved cysteine residues in exact alignment with all cystatin family 2 members. However, cystatin T lacks some of the conserved motifs believed to be important for inhibition of cysteine proteinase activity. These characteristics are seen in two other recently cloned genes, CRES and Testatin. Thus, cystatin T appears to be the third member of the CRES/Testatin subgroup of family 2 cystatins. The mouse cystatin T gene was mapped on a region of chromosome 2 that contains a cluster of cystatin genes, including cystatin C and CRES. Northern blot analysis demonstrated that expression of mouse cystatin T is highly restricted to the mouse testis. Thus, a shared characteristic of the cystatin family 2 subgroup members is an expression pattern limited primarily to the male reproductive tract.

Solid phase synthesis of peptide aldehyde protease inhibitors. Probing the proteolytic sites of hepatitis C virus polyprotein.

The solid phase synthesis of a set of peptide aldehydes derived from the NS5A/NS5B junction of hepatitis C virus (HCV) viral polyprotein is demonstrated using an oxazolidine linker and the Multipin method. Deletion of the P6 and P5 residues results in a dramatic loss of inhibitory activity.

Serial effects of high-resistance and prolonged endurance training on Na+-K+ pump concentration and enzymatic activities in human vastus lateralis.

The purpose of this study was to compare two contrasting training models, namely high-resistance training and prolonged submaximal training on the expression of Na+-K+ ATPase and changes in the potential of pathways involved in energy production in human vastus lateralis. The high-resistance training group (VO2peak = 45.3 +/- 1.9 mL kg(-1) min(-1), mean +/- SE, n = 9) performed three sets of six to eight repetitions maximal, each of squats, leg presses and leg extensions, three times per week for 12 weeks, while the prolonged submaximal training group (VO2peak = 44.4 +/- 6.6 mL kg(-1) min(-1), n = 7) cycled 5-6 times per week for 2 h day(-1) at 68% VO2peak for 11 weeks. In the HRT group, Na+-K+ ATPase (pmol g(-1) wet wt), measured with the 3H-ouabain binding technique, showed no change from 0 (289 +/- 22) to 4 weeks (283 +/- 15), increased (P < 0.05) by 16% at 7 weeks and remained stable until 12 weeks (319 +/- 19). For prolonged submaximal training, a 22% increase (P < 0.05) was observed from 0 (278 +/- 31) until 3 weeks (339 +/- 29) with no further changes observed at either 9 weeks (345 +/- 25) or 11 weeks (359 +/- 34). In contrast to high-resistance training, where a 15% increase (P < 0.05) was observed, only in the maximal activity of phosphorylase, prolonged submaximal training resulted in increases in malate dehydrogenase, beta-hydroxyl-CoA dehydrogenase, hexokinase and phosphofructokinase. In contrast to high-resistance training which failed to result in an increase in VO2peak, prolonged submaximal training increased VO2peak by approximately 15%. Only for prolonged exercise training was a relationship observed for VO2peak and Na+-K+-ATPase (r = 0.59; P < 0.05). Correlations between VO2peak and mitochondrial enzyme activities were not significant (P > 0.05) for either training programme. It is concluded that although both training programmes stimulate an up-regulation in Na+-K+ ATPase concentration, only the prolonged submaximal training programme enhances the potential for beta-oxidation, oxidative phosphorylation and glucose phosphorylation.

Gender differences in the expression of endothelin receptors in human saphenous veins in vitro.

The contractile response to endothelin-1 (ET-1) appears to be modulated by the relative density of ETA and ETB receptors. To determine the effects of gender on the distribution of ET receptors, we analyzed the endothelin receptor subtypes on membrane fractions prepared from saphenous vein samples obtained from patients of different genders undergoing coronary artery bypass graft surgery. The contractile response to ET-1 in the presence and absence of 1 microM of the ETA receptor antagonist BQ-123 was also investigated. Similar studies were repeated with endothelium-denuded samples to study the role of endothelium- and smooth muscle-derived ETB receptors. Competitive binding experiments were performed on membrane fractions using [125I]ET-1 and unlabeled ligands ET-1, ET-3, sarafatoxin 6c and BQ-123. Analysis of the binding data with endothelium-intact samples yielded two classes of binding sites in both women and men. In women, the maximum binding capacities were 83 +/- 6 and 97 +/- 10 fmol/mg protein for ETA and ETB receptors, respectively; the corresponding values in men were 618 +/- 121 and 201 +/- 10 fmol/mg protein. In addition, ET-1-induced contractions were 2-fold greater in men than in women at high ET-1 concentrations. Competitive binding studies with endothelium-denuded saphenous veins demonstrated the presence of only ETA receptors in both female and male tissue. These results indicate that the ratio and the density of ET receptors are different in men and women, which might be an important factor in the regulation of the contractile response.

Exposure to heat shock affects thermosensitivity of the locust flight system.

The natural habitat of the migratory locust, Locusta migratoria, is likely to result in locusts being heat stressed during their normal adult life. It is known that locusts exhibit a heat-shock response: exposure to 45 degrees C for 3 h induces thermotolerance and the expression of heat-shock proteins. We investigated the effects of exposure to heat-shock conditions on the thermosensitivity of flight rhythm generation in tethered, intact animals and in deafferented preparations. Heat shock had no effect on wingbeat frequency measured at the start of flight sequences, nor did it affect the postimaginal maturation of this parameter. During sustained flight, heat shock slowed the characteristic asymptotic reduction of wingbeat frequency. Wingbeat frequency of heat-shocked animals was less sensitive to temperature in the range 24 degrees to 47 degrees C than that of control animals, and the upper temperature limit, above which flight rhythms could not be produced, was 6 degrees to 7 degrees C higher in heat-shocked animals. These results were mirrored in the response of deafferented preparations, indicating that modifications in the properties of the flight neuromuscular system were involved in mediating the response of the intact animal. We propose that exposure to heat shock had the adaptive consequences of reducing thermosensitivity of the neural circuits in the flight system and allowing them to operate at higher temperatures.

Discovery of nanomolar ligands for 7-transmembrane G-protein-coupled receptors from a diverse N-(substituted)glycine peptoid library.

Screening a diverse, combinatorial library of ca. 5000 synthetic dimer and trimer N-(substituted)glycine "peptides" yielded novel, high-affinity ligands for 7-transmembrane G-protein-coupled receptors. The peptoid library was efficiently assembled using readily available chemical building blocks. The choice of side chains was biased to resemble known ligands to 7-transmembrane G-protein-coupled receptors. All peptides were screened in solution-phase, competitive radioligand-binding assays. Peptoid trimer CHIR 2279 binds to the alpha 1-adrenergic receptor with a Ki of 5 nM, and trimer CHIR 4531 binds to the mu-opiate receptor with a Ki of 6 nM. This represents the first example of the discovery of high-affinity receptor ligands from a combinatorial library of non-natural chemical entities.

Pharmacokinetics, bioavailability, plasma protein binding and disposition of nalidixic acid in rainbow trout (Oncorhynchus mykiss).

1. The pharmacokinetics, disposition and bioavailability of nalidixic acid were examined in Rainbow Trout following i.v. and per os administration (5 mg/kg). 2. Nalidixic acid was biexponentially eliminated from plasma following i.v. dosing (t1/2 alpha = 0.06 h, t1/2 beta = 23.0 h). The volume of distribution (Vss) and total body clearance (Clb) were 964.7 ml/kg and 31.5 ml/kg/h, respectively. 3. In vitro plasma protein binding was specific and saturable over a range of concentrations from 0.43 microM to 20.0 mM. Binding was approx. 26% at kinetically relevant plasma concentrations. 4. Apparent oral bioavailability was determined to be > 100%, suggesting that nalidixic acid was largely bioavailable and non-linear pharmacokinetics were evoked. 5. Oral studies demonstrated the highest 14C nalidixic acid equivalent concentrations in bile, intestine and liver. Muscle contained intermediate concentrations but among all organs accounted for the greatest total amount of drug (12.2% of dose). Mass balance studies demonstrated composite values for per cent of dose administered of 23.7, 18.8, 8.5, 10.0, 7.4 and 2.3% for 1, 2, 3, 6, 9 and 15 days, respectively. 6. A glucuronic acid conjugate of nalidixic acid was identified by n.m.r. and mass spectral analysis as the single primary metabolite.

Effect of hypertonic and isotonic saline solutions on plasma constituents of conscious horses.

Blood constituents and vascular volume indices were determined in 5 standing horses by use of 2-period crossover experimental design. Horses were either administered hypertonic (2,400 mosm/kg of body weight, i.v.) or isotonic (300 mosm/kg, i.v.) saline solution. Each solution was administered at a dosage of 5 ml/kg (infusion rate, 80 ml/min). Samples for determination of PCV, plasma volume, blood volume, plasma osmolality, total amount of plasma protein and plasma concentrations of protein, Na, K, and Cl were collected at 0 hour (baseline, before fluid infusion) and 0.5 hour (at the end of fluid infusion), and subsequently, at 0.25- or 0.5-hour intervals for 4.5 hours. All horses were given the predetermined dose of fluids by 0.5 hour after beginning the saline infusion. Values of P < or = 0.05 were considered significant. Administration of hypertonic saline solution was associated with decreased mean body weight by 4.5 hours, but weight change after isotonic saline administration was not significant. Other than body weight and plasma protein concentration, between-trial difference (treatment effect) was not observed for any measured variable or index. The F values indicated that increasing the number of horses would have not changed these results. A time effect was evident across both trials, so that mean (+/- SD) plasma volume increased (12.3 +/- 1.07%) and mean plasma protein concentration (-12.1 +/- 1.03%) and PCV (-11.9 + 0.67%) decreased proportionately and transiently in association with administration of either fluid at that volume. Other time effects included increased plasma osmolality and Na and Cl concentrations. Blood volume estimates and total amount of plasma protein remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved insulin sensitivity in hyperinsulinaemic ponies through physical conditioning and controlled feed intake.

Ten hyperinsulinaemic ponies divided into conditioned (N = 5) and rested (N = 5) groups were evaluated for their insulin and glucose response following oral glucose administration at Weeks 0, 2, 4, and 6. All ponies received a controlled intake of a pelleted ration during the study. In both groups body weight had decreased from baseline by Week 4 and remained low. After 2 weeks of exercise, ponies in the conditioned group had significantly decreased insulin and glucose indices, including peak insulin response, area under the insulin curve from 0 to 210 min (TIS), and the TIS value: area under the glucose curve from 0 to 210 min. By Week 4 of conditioning, although the insulin and glucose indices continued to decrease in the exercised ponies, there was no significant difference between the groups. Over the first 6 weeks of the study all ponies improved their insulin sensitivity accompanied by a loss of body weight. The conditioned ponies were further evaluated during deconditioning at Weeks 8, 10 and 12. The improved insulin sensitivity was maintained during deconditioning.

Insulin and glucose response following oral glucose administration in well-conditioned ponies.

Twenty-three well-conditioned ponies were evaluated for insulin and glucose response following oral glucose administration (1 g/kg bodyweight [bwt] as a 20 per cent solution). Ponies were defined as normal if total insulin secretion (TIS) was less than 149 mu iu/ml h and the glucose concentration was below 11.1 +/- 0.11 mmol/litre (200 +/- 2 mg/dl) at all times following oral glucose administration. When glucose concentrations were maintained below 11.1 +/- 0.11 mmol/litre, the area under the glucose curve (TG) was less than 17.4 mmol/litre/h (314 mg/dl/h). The ponies were assigned to four groups based on insulin and glucose response: Group 1 (n = 7), normal; Group 2 (n = 5), high insulin, normal glucose; Group 3 (n = 8), high insulin, high glucose and Group 4 (n = 3), high glucose, normal insulin. This classification is an initial attempt to define normal insulin and glucose response in ponies. Additional data need to be accumulated to define further insulin resistance and diabetes in ponies.