Plasma prolactin, thyroid-stimulating hormone, melanocyte-stimulating hormone, and adrenocorticotropin responses to thyrotropin-releasing hormone in mares treated with detomidine and butorphanol.

Stress or excitement is a concern when performing endocrine tests on fractious horses. Sedation may be a solution; however, perturbation of test results may preclude useful information. Thyrotropin-releasing hormone (TRH) is a known stimulator of prolactin, thyroid-stimulating hormone (TSH), melanocyte-stimulating hormone (MSH), and ACTH. Thyrotropin-releasing hormone-induced ACTH is a diagnostic tool for the assessment of endocrinopathies such as pituitary pars intermedia dysfunction. It is unknown if drugs commonly used for sedation alter endocrine responses. The objective of this study was to assess the effects of detomidine (DET) and butorphanol on endocrine responses to TRH. Nine light horse mares were used in a replicated 3 × 3 Latin square with the following treatments: saline, DET, and detomidine + butorphanol (DET/BUT), all administered intravenously at 0.01 mg/kg BW. A 1-wk washout period was allowed between phases, all of which were performed in December. Blood samples were collected at -10 and 0 min before treatment and 5 and 10 min post-treatment. Administration of 1 mg TRH occurred 10 min post-treatment, and blood sampling continued 5, 10, 20, and 30 min post-TRH. Data were analyzed by ANOVA as a replicated Latin square with repeated sampling. Plasma prolactin increased (P < 0.0001) after TRH in all groups, rapidly peaking at 5 min in drug-treated mares and 40 min in saline-treated mares. The peak prolactin response to TRH was 2-fold higher (P < 0.0001) in saline-treated mares compared with those drug-treated. A peak rise in plasma TSH was observed in DET/BUT-treated mares 10 min after TSH and was greater (P ≤ 0.007) compared with DET- and saline-treated mares. Plasma MSH was stimulated (P = 0.001) by DET and DET/BUT before TRH, and the peak MSH response to TRH was greater (P < 0.0001) in drug-treated mares, although not hastened as observed with prolactin and TSH. A peak rise in ACTH was observed in drug-treated mares 5 min after administration of TRH, whereas a peak rise was observed in control mares 10 min post-TRH and was almost 2-fold lower (P = 0.05) than the peak observed in DET and DET/BUT-treated mares. Basal ACTH concentrations were not affected by DET or DET/BUT, indicating that sedation with these compounds may be achieved when needing to measure basal plasma ACTH. Treatment with DET and DET/BUT did alter the prolactin, TSH, MSH, and ACTH responses to TRH; therefore, the use of these drugs may not be advisable when assessing endocrine responses to TRH stimulation.

Hemodynamics of the corpus luteum in mares during experimentally impaired luteogenesis and partial luteolysis.

The aim of the current project was to characterize the luteal vascularity and the plasma concentrations of progesterone (P4), prolactin (PRL) and 13,14-dihydro-15-keto-PGF2α (PGFM) in mares with luteal disturbances during early and mid-diestrus. In Experiment 1, twenty-one mares were treated with 2 mL of 0.9% NaCl, or 1 mg Dinoprost, or 10 mg Dinoprost on day two after ovulation (Control-D2, 1/10PGF-D2 and PGF-D2 groups, respectively; n = 7 mares/group). In Experiment 2, similar treatments were performed eight days post-ovulation using a different cohort of 21 mares (Control-D8, 1/10PGF-D8 and PGF-D8 groups, respectively; n = 7 mares/group). Blood samples were collected hourly and power-Doppler examinations of the corpus luteum (CL) were performed every 6 h from H0 (moment immediately before treatment) to H48. Data collection was also done once a day from D0 (day of ovulation) to D20. In Experiment 1, the PGF-D2 and 1/10PGF-D2 groups had lower increase of plasma concentration of P4 until H48 and reduced maximum P4 concentrations on D8-D11 than mares from the Control-D2 group. However, no differences among groups were detected for luteal vascularity during early and mid-diestrus. In Experiment 2, complete and partial luteolysis were detected in mares from the PGF-D8 and 1/10PGF-D8 groups, respectively. Luteal vascularity and plasma P4 concentrations differed among Control-D8, PGF-D8 and 1/10PGF-D8 groups on H48. Partially regressed CLs (1/10PGF-D8 group) generated more Doppler signals than completed regressed CLs (PGF-D8 group) between D10 and D13. In both experiments, a transient increase in PRL activity was observed in parallel to the PGFM pulse in mares receiving 1 or 10 mg Dinoprost. The use of prostaglandin on D2 at conventional or 1/10 of the dose impaired the luteal development in mares. Moreover, the low dose of prostaglandin lead to partial regression of mature CLs. The blood supply was reduced in partially regressed CLs, but not in CLs undergoing impaired luteogenesis.

Influence of two ovulation-inducing agents on the pituitary response and follicle blood flow in mares.

The objective of the current study was to evaluate the effects of deslorelin and hCG, two ovulation-inducing therapies, on LH surge and follicle vascularity in mares. Thirty mares were either treated with 1.5 mg IM of deslorelin, 2,500 IU IV of hCG or 2 mL IM of NaCl 0.9% (GnRH, hCG and Saline groups, respectively). Power-flow Doppler examination and blood collection were performed every hour during the first 12 hours after treatment (H0) and every six hours between hours 12 (H12) and 30 (H30) after treatment. Moreover, endpoints were evaluated every hour through the last six hours before ovulation (OV-6 to OV-1). In GnRH group, plasma LH concentration progressively increased (P < 0.001) during the first 6 hours after treatment and remained high (P > 0.1) until OV-1. A significant increase in LH concentrations was first detected (P < 0.05) at 24 hours after treatment in hCG group, while no changes (P > 0.1) on LH levels were found during H0-H30 and between OV-6 and OV-1 in the Saline group. Independent of the treatment, significant variations on the percentage of the follicle wall with Doppler signals were not observed (P > 0.1) throughout the entire experiment. A weak correlation between the preovulatory follicle vascularity and the plasma LH concentration was found in GnRH, hCG and Saline groups (r = +0.29, +0.29 and -0.23, respectively; P ˂ 0.0001). These results described for the first time the immediate and continuous pituitary response to ovulation-inducing therapy with injectable deslorelin. Moreover, spontaneous and induced ovulations were not preceded by an increased follicle vascularity, which differs from previous reports in large animals.

Real-time characterization of the uterine blood flow in mares before and after artificial insemination.

The present experiment was divided into two studies to investigate the effect of age and endometrial degeneration on uterine blood flow of mares throughout the immediate post-breeding period. In study 1, uterine blood flow was characterized in mares (n = 7 mares/group) with minimal, moderate or severe endometrial degenerative changes (GI, GII and GIII, respectively). In study 2, the effect of age was investigated using young (≤ 6 years) and old (≥ 15 years) mares (n = 7 mares/group). Uterine vascular perfusion and mesometrial pulsatility index (PI) were evaluated every hour from H0 (moment immediately before AI) to H12. In study 1, a pronounced and transitory increase on uterine vascular perfusion was detected (P < 0.001) between H1 and H3 in the three endometrial groups. In addition, GIII mares had greater (P < 0.05) mesometrial PI than GI mares during the post-breeding period, denoting reduced uterine blood flow. In study 2, a transitory increase on uterine vascular perfusion was also observed in both age groups during the first hour after mating. However, mesometrial PI of young and old mares was similar (P > 0.05) and constant (P > 0.7) through the first 12h after AI. Results demonstrated, for the first time, the immediate changes on uterine vascular perfusion and mesometrial PI in response to semen infusion. Moreover, reduced blood flow of the uterus during the post-breeding period was strongly associated with endometrial degenerative changes in mares, regardless of age.

Lithography and doping in strained Si towards atomically precise device fabrication.

We investigate the ability to introduce strain into atomic-scale silicon device fabrication by performing hydrogen lithography and creating electrically active phosphorus δ-doped silicon on strained silicon-on-insulator (sSOI) substrates. Lithographic patterns were obtained by selectively desorbing hydrogen atoms from a H resist layer adsorbed on a clean, atomically flat sSOI(001) surface with a scanning tunnelling microscope tip operating in ultra-high vacuum. The influence of the tip-to-sample bias on the lithographic process was investigated allowing us to pattern feature-sizes from several microns down to 1.3 nm. In parallel we have investigated the impact of strain on the electrical properties of P:Si δ-doped layers. Despite the presence of strain inducing surface variations in the silicon substrate we still achieve high carrier densities (>1.0 × 10(14) cm(-2)) with mobilities of ∼100 cm(2) V(-1) s(-1). These results open up the possibility of a scanning-probe lithography approach to the fabrication of strained atomic-scale devices in silicon.

Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares.

Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at -10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P < 0.01) to both sulpiride and TRH injection and were greater (P < 0.05) in insulin-insensitive mares than in sensitive mares. Plasma prolactin concentrations responded (P < 0.01) to both sulpiride and TRH injection, and the response was greater (P < 0.05) for sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P < 0.01) to TRH injection only and were higher (P < 0.05) in insulin-sensitive mares in almost all time periods. Plasma LH and FSH concentrations varied with time (P < 0.05), particularly in the first week of the experiment, but were not affected by treatment or insulin sensitivity category. Plasma GH concentrations were affected (P < 0.05) only by day of treatment. The greater MSH responses to sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are consistent with our previous observation of elevated plasma triiodothyronine concentrations in hyperleptinemic horses (later shown to be insulin insensitive as well).

Ohm's law survives to the atomic scale.

As silicon electronics approaches the atomic scale, interconnects and circuitry become comparable in size to the active device components. Maintaining low electrical resistivity at this scale is challenging because of the presence of confining surfaces and interfaces. We report on the fabrication of wires in silicon--only one atom tall and four atoms wide--with exceptionally low resistivity (~0.3 milliohm-centimeters) and the current-carrying capabilities of copper. By embedding phosphorus atoms within a silicon crystal with an average spacing of less than 1 nanometer, we achieved a diameter-independent resistivity, which demonstrates ohmic scaling to the atomic limit. Atomistic tight-binding calculations confirm the metallicity of these atomic-scale wires, which pave the way for single-atom device architectures for both classical and quantum information processing.

Relationships of occupational and non-occupational physical activity to abdominal obesity.

HYPOTHESIS: Physically active occupations may protect against the risk of abdominal obesity. OBJECTIVES: This study assessed the interaction between non-occupational physical activity (NOA) (leisure-time, transport and domestic activity) and occupational activity (OA) in relation to abdominal obesity. METHODS: A total of 3539 adults over the age of 20, with no work limitations, employed in one of the 17 occupations classified as low OA (LOA) or high OA (HOA) were identified in the 1999-2004 National Health and Nutrition Examination Survey. Waist circumference (WC) was used to categorize individuals into either non-obese or abdominally obese (WC>88 cm in women and >102 cm in men) categories. NOA was divided into three categories based upon physical activity guidelines: (1) no NOA; (2) insufficient NOA; and (3) sufficient NOA. Logistic regression was used to examine possible associations between NOA, OA and abdominal obesity. RESULTS: In those who are sedentary outside of work, a high-activity occupation reduces the odds risk ratio of being categorized with abdominal obesity to 0.37 in comparison with those who work in low-activity occupations. For people working in low-activity occupations, there was a clear association with activity outside of work and the odds risk ratio of being categorized with abdominal obesity. In these adults, a reduced odds ratio was found only among those who met the physical activity guidelines through NOA (odds ratio=0.55; 95% confidence interval (CI)=0.40-0.75). CONCLUSION: HOA is associated with a reduced risk of abdominal obesity. Thus, it is important to include OA in studies seeking to understand the association between physical activity and abdominal adiposity.

Hyperleptinemia in mares and geldings: assessment of insulin sensitivity from glucose responses to insulin injection.

Four experiments were conducted 1) to assess the use of glucose responses to insulin injections as a means of estimating insulin sensitivity in horses and 2) to compare the insulin sensitivities of normal horses vs. those displaying hyperleptinemia (HL). In Exp. 1, HL mares and geldings (n = 4 each) and 4 mares and geldings with normal leptin concentrations (NL) were injected intravenously with 20 and 100 mU/kg of BW of bovine insulin on 2 separate occasions in December 2008. In Exp. 2, the experimental protocol was repeated in late April 2009. In Exp. 1, the 20 mU/kg of BW dose of insulin caused a greater (P < 0.05) decline in glucose concentrations in NL mares and geldings compared with HL horses. The response of HL mares to the 100 mU/kg of BW dose was less (P < 0.05) than for the other groups. In Exp. 2, responses of all groups to the 20 mU/kg of BW dose were small and similar among groups (P > 0.1), whereas the greater dose revealed differences (P < 0.05) in sensitivity among groups consistent with those observed with the smaller dose in Exp. 1. Experiment 3 was conducted in June and July of 2009 to further examine the dose-response relationship in mares of potentially different insulin sensitivities in an attempt to standardize the approach for studying a wide range of sensitivities. Recombinant human insulin was used at doses of 8, 20, 50, and 125 mU/kg of BW, as needed, to estimate (by linear regression) the dose of insulin causing a 50% decline in glucose concentrations (ED50). Five mares each of reduced leptin concentrations (LL) and small BCS (3 to 5), LL and larger BCS (6 to 7.5), and increased leptin concentrations and increased BCS were studied. The ED50 was similar (P > 0.1) for LL mares, regardless of BCS, and was less (P < 0.01) than for mares with increased leptin concentrations. It was concluded that a dose of 50 mU/kg of BW of recombinant human insulin could be used safely to start the dose-response curve; smaller or larger doses could then be applied as appropriate to get sufficient data for estimation of ED50. Experiment 4, conducted in October of 2009, assessed the repeatability of the estimates for ED50 obtained in Exp. 3. Six mares with LL vs. increased leptin concentrations received the 50 mU/kg dose of insulin; appropriate larger or smaller doses were used to obtain estimates of ED50. Estimates obtained were highly correlated (r = 0.91) with those obtained in Exp. 3, with an average within-mare CV of 8.9%; this is equal to or better than the repetabilities of the currently used methods of assessing insulin sensitivity in horses. It was concluded that hyperleptinemic horses, which are also hyperinsulinemic and have exaggerated insulin responses to glucose injection, are indeed less sensitive to insulin than normal horses with reduced leptin concentrations of the same body condition.

Hyperleptinemia in horses: responses to administration of a small dose of lipopolysaccharide endotoxin in mares and geldings.

Mares and geldings in good body condition selected for hyperleptinemia vs. normal leptin concentrations were studied to determine whether the hyperleptinemic condition affected various characteristics of the hematologic and hormonal systems after a challenge with lipopolysaccharide endotoxin. Four mares and 4 geldings that were determined to be hyperleptinemic (mean plasma leptin concentrations of 10.0 to 15.5 ng/mL) and 4 mares and 4 geldings with mean plasma leptin concentrations between 2.4 and 5.5 ng/mL were administered Escherichia coli O55:B5 endotoxin (35 ng/kg of BW in 500 mL of saline over a 30-min infusion), or saline only, in pairs in a single-switchback design, with horses and treatments randomly assigned for the first infusion. Physiological variables and blood components were monitored for 24 h after the onset of infusions. Treatments were switched and the second infusions were administered 8 d later. Relative to vehicle infusion, endotoxin infusion increased (P < 0.01) the rectal temperature, heart rate, respiration rate, plasma total protein concentration, and blood packed cell volume; there was an interaction of leptin status, endotoxin treatment, and time for heart rate (P = 0.039), respiration rate (P = 0.018), and plasma total protein concentration (P = 0.054). Blood concentrations of leukocytes, lymphocytes, and neutrophils all decreased (P < 0.001) after endotoxin infusion; there was an interaction (P = 0.0057) between sex and leptin status for blood platelet concentration. Plasma leptin concentrations increased (P = 0.013) after endotoxin infusion in both hyperleptinemic horses and those with reduced leptin concentrations. There were interactions (P < 0.037) of sex with endotoxin treatment and time for plasma concentrations of cortisol and prolactin, whereas plasma GH concentrations were affected (increased; P < 0.001) only by time after infusion. Given that the effects of hyperleptinemia were generally minor, it was concluded that the hyperleptinemic condition, and its associated type-2 diabetic symptoms, has a minimal impact on the components of the hematologic and hormonal systems studied.

Validity of the Nike+ device during walking and running.

We determined the validity of the Nike+ device for estimating speed, distance, and energy expenditure (EE) during walking and running. Twenty trained individuals performed a maximal oxygen uptake test and underwent anthropometric and body composition testing. Each participant was outfitted with a Nike+ sensor inserted into the shoe and an Apple iPod nano. They performed eight 6-min stages on the treadmill, including level walking at 55, 82, and 107 m x min(-1), inclined walking (82 m x min(-1)) at 5 and 10% grades, and level running at 134, 161, and 188 m x min(-1). Speed was measured using a tachometer and EE was measured by indirect calorimetry. Results showed that the Nike+ device overestimated the speed of level walking at 55 m x min(-1) by 20%, underestimated the speed of level walking at 107 m x min(-1) by 12%, but closely estimated the speed of level walking at 82 m x min(-1), and level running at all speeds (p<0.05). Similar results were found for distance. The Nike+ device overestimated the EE of level walking by 18-37%, but closely estimated the EE of level running (p<0.05). In conclusion the Nike+ in-shoe device provided reasonable estimates of speed and distance during level running at the three speeds tested in this study. However, it overestimated EE during level walking and it did not detect the increased cost of inclined locomotion.

Hormonal patterns in normal and hyperleptinemic mares in response to three common feeding-housing regimens.

We previously reported that a rise in plasma leptin concentrations followed the rise in insulin and glucose in meal-fed horses, whereas horses maintained on pasture had little fluctuations in hormonal patterns. We have also described a hyperleptinemic-hyperinsulinemic condition that occurs in about 30% of our light horse mares of high body condition maintained on pasture. The present experiment was designed to 1) study the effect of 3 common feeding-housing regimens on leptin and other metabolic hormones in mares and 2) determine whether the hyperleptinemic condition interacted with these regimens. Six light horse mares with high body condition (average score = 7) were assigned to 2 simultaneous 3 x 3 Latin squares, 1 with normal mares (leptin = 0.1 to 6 ng/mL) and 1 with mares displaying hyperleptinemia (>10 ng/mL). Three feeding-housing regimens were compared: ad libitum pasture, ad libitum native grass hay in an outdoor paddock, and single morning feedings of a pelleted concentrate and hay at 0700 in a barn. Five days of acclimation to the feeding regimens were followed by a 36-h period of hourly blood collection to characterize the hormonal characteristics. Leptin concentrations were elevated (P < 0.001) in mares predetermined to be hyperleptinemic compared with normal mares, regardless of the feeding regimen. Leptin was greatest (P < 0.01) in mares on pasture and least in mares fed hay. Variations over time (P < 0.01) were present for all hormones and metabolites studied. Glucose and insulin concentrations were greatest (P < 0.01) in mares on pasture, with meal-fed mares exhibiting an immediate rise in plasma concentrations of both after feeding. Mares on hay had low and constant concentrations of glucose, insulin, and leptin, with no apparent fluctuations. Cortisol, prolactin, and IGF-I did not differ with leptin status, whereas GH differed due to feeding-housing regimen (P < 0.02); there was also an interaction of leptin status and feeding-housing regimen for GH concentrations (P = 0.094). It was concluded that 1) estimates of hormonal secretion in horses based on frequent sampling, depending upon the hormone in question, can be profoundly affected by the feeding-housing regimens, and 2) the hyperleptinemic condition persists under differing conditions of feeding-housing.

Leptin secretion in horses: effects of dexamethasone, gender, and testosterone.

Five experiments were performed to evaluate the effects of dexamethasone (DEX), gender, and testosterone on plasma leptin concentrations in horses. In experiment 1, plasma leptin, insulin, glucose, and IGF-1 concentrations were increased (P < 0.01) in stallions following five daily injections of DEX (125 microg/kg BW). In experiment 2, leptin concentrations increased (P < 0.01) in mares, geldings, and stallions following a single injection of DEX, and the response was greater (P < 0.01) in mares and geldings than in stallions. The gender effect was confounded by differences in body condition scores and diet; however, based on stepwise regression analysis, both BCS and gender were significant sources of variation in the best fit model for pre-DEX leptin concentrations (R(2) = 0.65) and for maximum leptin response to DEX (R(2) = 0.75). In experiment 3, in which mares and stallions were pair-matched based on age and body condition and fed similar diets, mares again had higher (P < 0.01) leptin concentrations than stallions after DEX treatment as used in experiment 2. In experiment 4, there was no difference (P > 0.1) in plasma leptin response in mares following four single-injection doses of DEX from 15.6 to 125 microg/kg BW. In experiment 5, treatment of mares with testosterone propionate every other day for 5 days did not alter (P > 0.1) plasma leptin concentrations or the leptin response to DEX. In conclusion, multiple injections of DEX increase leptin concentrations in stallions, as does a single injection in mares (as low as 15.6 microg/kg BW), geldings and stallions. The greater leptin levels observed in mares and geldings relative to stallions were due partially to their greater body condition and partially to the presence of hyperleptinemic individuals; however, even after accounting for body condition and diet, mares still had greater leptin concentrations than stallions after DEX administration. Elevation of testosterone levels in mares for approximately 10 days did not alter leptin concentrations in mares.

Effect of dexamethasone, feeding time, and insulin infusion on leptin concentrations in stallions.

Three experiments tested the hypotheses that daily cortisol rhythm, feeding time, and/or insulin infusion affect(s) leptin secretion in stallions. Ten mature stallions received ad libitum hay and water and were fed a grain concentrate once daily at 0700. In Exp. 1, stallions received either a single injection of dexamethasone (125 microg/kg BW i.m.; n = 5) or vehicle (controls; n = 5) at 0700 on d -1. Starting 24 h later, blood samples were collected every 2 h for 36 h via jugular venipuncture. Cortisol in control stallions varied (P < 0.01) with time, with a morning peak and evening nadir; dexamethasone suppressed (P < 0.01) cortisol concentrations. Leptin and insulin were greater (P < 0.01) in the treated stallions, as was the insulin response to feeding (P < 0.01). Leptin in control stallions varied (P < 0.01) in a diurnal pattern, peaking approximately 10 h after onset of eating. This pattern of leptin secretion was similar, although of greater magnitude (P < 0.01), in treated stallions. In Exp. 2, five stallions were fed the concentrate portion of their diet daily at 0700 and five were switched to feeding at 1900. After 14 d on these regimens, blood samples were collected every 4 h for 48 h and then twice daily for 5 d. Cortisol varied diurnally (P = 0.02) and was not altered (P = 0.21) by feeding time. Insulin and leptin increased (P < 0.01) after feeding, and the peaks in insulin and leptin were shifted 12 h by feeding at 1900. In Exp. 3, six stallions were used in two 3 x 3 Latin square experiments. Treatments were 1) normal daily meal at 0700; 2) no feed for 24 h; and 3) no feed and a bolus injection of insulin (0.4 mIU/kg BW i.v.) followed by infusion of insulin (1.2 mIU.kg BW(-1).min(-1)) for 180 min, which was gradually decreased to 0 by 240 min; sufficient glucose was infused to maintain euglycemia. Plasma insulin increased (P < 0.01) in stallions when they were meal-fed (to approximately 150 microIU/mL) or infused with insulin and glucose (to approximately 75 microIU/mL), but insulin remained low (10 microIU/mL or less) when they were not fed. The increases in insulin were paralleled by gradual increases (P < 0.01) in leptin concentrations 3 to 4 h later in stallions fed or infused with insulin and glucose. When stallions were not fed, leptin concentrations remained low. These results demonstrate that feeding time, and more specifically the insulin increase associated with a meal, not cortisol rhythm, drives the postprandial increase in plasma leptin concentrations in horses.

Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis and a primary cause of disability, however, there are no treatments that can slow disease progression or repair damaged joint cartilage. Fibroblast growth factor-18 (FGF18) has been reported to have significant anabolic effects on cartilage. We therefore examined its effects on repair of cartilage damage in a rat meniscal tear model of OA. DESIGN: Surgical damage to the meniscus in rats leads to joint instability and significant damage to the articular cartilage at 3 weeks post-surgery. At this time, animals received bi-weekly intra-articular injections of FGF18 for 3 weeks, and the knee joints were then harvested for histologic examination. RESULTS: FGF18-induced dose-dependent increases in cartilage thickness of the tibial plateau, due to new cartilage formation at the articular surface and the joint periphery. The generation of new cartilage resulted in significant reductions in cartilage degeneration scores. The highest dose of FGF18 also induced an increase in chondrophyte size and increased remodeling of the subchondral bone. CONCLUSIONS: The results of this study demonstrate that FGF18 can stimulate repair of damaged cartilage in a setting of rapidly progressive OA in rats.

Effects of body mass index on the accuracy of an electronic pedometer.

Electronic pedometers are accurate for assessing steps taken while walking in normal weight adults but the accuracy of these devices has not been tested in overweight and obese men and women. The primary purpose of this study was to assess the accuracy of an electronic pedometer for measuring steps taken at various walking speeds in groups of adults with variations in body mass index (BMI). The secondary purpose was to determine if the manufacturer recommended position is the best placement position for overweight and obese adults. Participants were categorized into one of three BMI categories identified by the World Health Organization: normal (N = 25; < 25 kg x m(-2)), overweight (N = 24; 25 - 29.9 kg x m(-2)), or obese (N = 17; > or = 30 kg x m(-2)). Participants walked on a treadmill for 3 min at 54, 67, 80, 94, and 107 m x min(-1) for a total of 15 min. During the treadmill walking, three electronic pedometers tallied steps taken. The pedometers were placed at the waist level, one on the anterior mid-line of the thigh (front; manufacturer recommended placement), one on the mid-axillary line (side), and one on the posterior mid-line of the thigh (back). Concurrently, a researcher counted steps using a hand-tally counter. Category of BMI did not affect the accuracy of the pedometer at any walking speed (54 m x min(-1), p = 0.991; 67 m x min(-1), p = 0.556; 80 m x min(-1), p = 0.591; 94 m x min(-1), p = 0.426; 107 m x min(-1), p = 0.869). At 54 m x min(-1), the front, side, and back pedometers significantly underestimated hand-tally counted steps by 20 % (p < 0.001), 33 % (p < 0.001), and 26 % (p < 0.001), respectively. At 67 m x min(-1) the front, side, and back pedometers significantly underestimated hand-tally counted steps by 7 % (p = 0.027), 13 % (p < 0.001), 11 % (p = 0.002), respectively. The steps recorded by the electronic pedometers placed at the front, side and back of the waist were not significantly different than steps counted by the hand-tally counter at speeds of 80 m x min(-1) and higher for all subjects combined. An electronic pedometer accurately quantified steps walked at speeds of 80 m x min(-1) or faster in persons with a normal BMI and those classified as overweight or obese. The placement of the pedometer on the front, side or back of the waistband did not affect accuracy of the pedometer for counting steps.

Endocrine responses in mares and geldings with high body condition scores grouped by high vs. low resting leptin concentrations.

Previous observations from this laboratory indicated that horses with high BCS could have resting plasma leptin concentrations ranging from low (1 to 5 ng/mL) to very high (10 to 50 ng/mL). To study the possible interactions of leptin secretion with other endocrine systems, BCS and plasma leptin concentrations were measured on 36 mares and 18 geldings. From mares and geldings that had a mean BCS of at least 7.5, five with the lowest (low leptin) and five with the highest (high leptin) leptin concentrations were selected. Jugular blood samples were collected twice daily for 3 d from the 20 selected horses to determine average resting hormone concentrations. Over the next 12 d, glucose infusion, injection of thyrotropin-releasing hormone (TRH), exercise, and dexamethasone treatment were used to perturb various hormonal systems. By design, horses selected for high leptin had greater (P < 0.0001) leptin concentrations than horses selected for low leptin (14.1 vs. 2.8 +/- 0.92 ng/mL, respectively). In addition, mares had greater (P = 0.008) leptin concentrations than geldings. Horses selected for high leptin had lower (P = 0.027) concentrations of GH but higher (P = 0.0005) concentrations of insulin and thriiodothyronine (T3) than those selected for low leptin. Mares had greater (P = 0.0006) concentrations of cortisol than geldings. There was no difference (P > 0.10) in concentrations of IGF-1, prolactin, or thyroid-stimulating hormone (TSH). Horses selected for high leptin had a greater (P = 0.0365) insulin response to i.v. glucose infusion than horses selected for low leptin. Mares had a greater (P = 0.0006) TSH response and tended (P = 0.088) to have a greater prolactin response to TRH than geldings; the T3 response was greater (P = 0.047) in horses selected for high leptin. The leptin (P = 0.0057), insulin (P < 0.0001), and glucose (P = 0.0063) responses to dexamethasone were greater in horses selected for high leptin than in those selected for low leptin. In addition, mares had a greater (P < 0.0001) glucose response to dexamethasone than geldings. Cortisol concentrations were decreased (P = 0.029) by dexamethasone equally in all groups. In conclusion, differences in insulin, T3, and GH associated with high vs. low leptin concentrations indicate a likely interaction of these systems with leptin secretion in horses and serve as a starting point for future study of the cause-and-effect nature of the interactions.

Thyrotropin releasing hormone interactions with growth hormone secretion in horses.

Light horse mares, stallions, and geldings were used to 1) extend our observations on the thyrotropin releasing hormone (TRH) inhibition of GH secretion in response to physiologic stimuli and 2) test the hypothesis that stimulation of endogenous TRH would decrease the normal rate of GH secretion. In Exp. 1 and 2, pretreatment of mares with TRH (10 microg/kg BW) decreased (P < 0.001) the GH response to exercise and aspartate infusion. Time analysis in Exp. 3 indicated that the TRH inhibition lasted at least 60 min but was absent by 120 min. Administration of a single injection of TRH to stallions in Exp. 4 increased (P < 0.001) prolactin concentrations as expected but had no effect (P > 0.10) on GH concentrations. Similarly, 11 hourly injections of TRH administered to geldings in Exp. 5 did not alter (P > 0.10) GH concentrations either during the injections or for the next 14 h. In Exp. 5, it was noted that the prolactin and thyroid-stimulating hormone responses to TRH were great (P < 0.001) for the first injection, but subsequent injections had little to no stimulatory effect. Thus, Exp. 6 was designed to determine whether the inhibitory effect of TRH also waned after multiple injections. Geldings pretreated with five hourly injections of TRH had an exercise-induced GH response identical to that of control geldings, indicating that the inhibitory effect was absent after five TRH injections. Retrospective analysis of pooled, selected data from Exp. 4, 5, and 6 indicated that endogenous GH concentrations were in fact lower (P < 0.01) from 45 to 75 min after TRH injection but not thereafter. In Exp. 7, 6-n-propyl-2-thiouracil was fed to stallions to reduce thyroid activity and hence thyroid hormone feedback, potentially increasing endogenous TRH secretion. Treated stallions had decreased (P < 0.01) concentrations of thyroxine and elevated (P < 0.01) concentrations of thyroid-stimulating hormone by d 52 of feeding, but plasma concentrations of GH and prolactin were unaffected (P > 0.10). In contrast, the GH response to aspartate and the prolactin response to sulpiride were greater (P < 0.05) in treated stallions than in controls. In summary, TRH inhibited exercise- and aspartate-induced GH secretion. The duration of the inhibition was at least 1 h but less than 2 h, and it waned with multiple injections. There is likely a TRH inhibition of endogenous GH episodes as well. Reduced thyroid feedback on the hypothalamic-pituitary axis did not alter basal GH and prolactin secretion.

Concentrations of nitric oxide in equine preovulatory follicles before and after administration of human chorionic gonadotropin.

In the present study, follicular fluids of estrous mares treated with saline solution (Control) or nitric oxide synthase (NOS) inhibitors were analyzed for nitric oxide (NO), estradiol-17beta (E2) and progesterone (P4) concentrations before and 36h after administration of human chorionic gonadotropin (hCG). Follicular fluids obtained before (0h) hCG administration from control mares had lower concentrations of NO than those obtained 36h after administration of hCG (58.3+/-17.8 micromol versus 340.4+/-57.7 micromol; P<0.05). A similar pattern was also noted for intrafollicular P4 in control mares, which had lower concentrations of intrafollicular P4 before hCG than 36h post-hCG administration (P<0.05). As expected, E2 concentrations of control follicles sampled before hCG administration were higher than those sampled 36h post-hCG administration (P<0.05). However, the E2 concentrations in follicles of mares treated with the NOS inhibitors N(omega)-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine (AG) did not decrease after hCG administration, unlike those in control mares (P>0.10). In addition, mares treated with NOS inhibitors had lower intrafollicular concentrations of NO and P4 than control mares, both before and after hCG administration (P<0.05). Increased intrafollicular concentrations of NO in control, hCG-stimulated mares provide evidence for the presence of an NO-generating system in the equine preovulatory follicle that is likely upregulated following administration of hCG.