The effect of oral metformin on insulin sensitivity in insulin-resistant ponies

Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion. To determine the effect of metformin on insulin and glucose dynamics in I-R ponies, six ponies were studied in a cross-over design by Minimal Model analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). Metformin was administered at 15. mg/kg bodyweight (BW), orally, twice-daily, for 21. days to the metformin-treated group. The control group received a placebo. A FSIGT was conducted before and after treatment. The Minimal Model of glucose and insulin dynamics rendered indices describing SI, glucose effectiveness (Sg), acute insulin response to glucose (AIRg) and the disposition index (DI). The body condition score (BCS), BW and cresty neck score (CNS) were also assessed. There was no significant change in SI, Sg, AIRg, DI, BW, BCS or CNS in response to metformin, or over time in the control group. There were no measurable benefits of metformin on SI, consistent with recent work showing that the bioavailability of metformin in horses is poor, and chronic dosing may not achieve therapeutic blood concentrations. Alternatively, metformin may only be effective in obese ponies losing weight or with hyperglycaemia.

Indigofera spicata (creeping indigo) poisoning of three ponies

Three ponies continuously grazed a pasture containing an estimated 24% Indigofera spicata (wet weight basis) for 4–6 weeks in April and May 2004. They developed ataxia, paresis, depression, muscle fasciculations, dysphagia, ptyalism and halitosis. Two also developed corneal opacity. One pony recovered with supportive treatment, but the other two were euthanased and necropsied. Neuropathology was not present in either case, but both livers had periacinar and periportal lymphocytic infiltrations and hydropic degeneration of mid-zonal hepatocytes, with mild to moderate periacinar necrosis also evident in one. The I. spicata contained 2.66 mg 3-nitropropionic acid (3-NPA)/g dry matter and 1.5 mg indospicine/g dry matter. Indospicine, but not 3-NPA, was detected in serum from both of the euthanased ponies and indospicine was detected in heart, liver and muscle from the one pony in which this assay was performed. The clinical syndrome closely resembled ‘Birdsville horse disease’ caused by I. linnaei and was similar to that reported in horses poisoned by the closely related species I. hendecaphylla and to 3-NPA poisoning of other animals, including humans. 3-NPA is thought to cause this neurological syndrome. To our knowledge, this is the first authenticated report of I. spicata poisoning in grazing animals. We also report here the first published evidence that 3-NPA and indospicine exist in naturalised I. spicata in Australia and of the formation of indospicine residues in tissues of animals grazing paddocks infested with I. spicata.

Plasmacytoid dendritic cells: one-trick ponies or workhorses of the immune system?

Plasmacytoid dendritic cells (pDCs) were first described as interferon-producing cells and, for many years, their overlapping characteristics with both lymphocytes and classical dendritic cells (cDCs) created confusion over their exact ontogeny. In this Viewpoint article, Nature Reviews Immunology asks five leaders in the field to discuss their thoughts on the development and functions of pDCs--do these cells serve mainly as a major source of type I interferons or do they also make other important contributions to immune responses?

Epidural analgesia with morphine or buprenorphine in ponies with lipopolysaccharide (LPS)-induced carpal synovitis

This study evaluated the analgesia effects of the epidural administration of 0.1 mg/kg bodyweight (BW) of morphine or 5 mu g/kg BW of buprenorphine in ponies with radiocarpal joint synovitis. Six ponies were submitted to 3 epidural treatments: the control group (C) received 0.15 mL/kg BW of a 0.9% sodium chloride (NaCl) solution; group M was administered 0.1 mg/kg BW of morphine; and group B was administered 5 mu g/kg BW of buprenorphine, both diluted in 0.9% NaCl to a total volume of 0.15 mL/kg BW administered epidurally at 10 s/mL. The synovitis model was induced by injecting 0.5 ng of lipopolysaccharide (LPS) in the left or right radiocarpal joint. An epidural catheter was later introduced in the lumbosacral space and advanced up to the thoracolumbar level. The treatment started 6 h after synovitis induction. Lameness, maximum angle of carpal flexion, heart rate, systolic arterial pressure, respiratory rate, temperature, and intestinal motility were evaluated before LPS injection (baseline), 6 h after LPS injection (time 0), and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h after treatments. Although the model of synovitis produced clear clinical signs of inflammation, the lameness scores in group C were different from the baseline for only up to 12 h. Both morphine and buprenorphine showed a reduction in the degree of lameness starting at 0.5 and 6 h, respectively. Reduced intestinal motility was observed at 0.5 h in group M and at 0.5 to 1 h in group B. Epidural morphine was a more effective analgesic that lasted for more than 12 h and without side effects. It was concluded that morphine would be a valuable analgesic option to alleviate joint pain in the thoracic limbs in ponies.

Cardiorespiratory and endocrine effects of endogenous opioid antagonism by naloxone in ponies anaesthetised with halothane

Halothane depresses cardiorespiratory function and activates the pituitary-adrenal axis, increasing beta endorphin. In horses, beta endorphin may enhance the anaesthetic-associated cardiorespiratory depression and mortality risk. The authors studied endogenous opioid effects on cardiorespiratory function and pituitary-adrenal activity in halothane-anaesthetised ponies by investigating opioid antagonism by naloxone. Six ponies were anaesthetised three times (crossover design). Anaesthesia was induced with thiopentone and maintained with 1.2 per cent halothane for 2 hours. Immediately after induction, naloxone was administered either intra venously (0.5 mg kg(-1) bolus then 0.25 mg kg(-1) hour(-1) for 2 hours) or intrathecally (0.5 mg) or was replaced by saline as control. Pulse and respiratory rates, arterial blood gases, cardiac output and plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were measured. All groups developed cardiorespiratory depression (40 per cent decrease in cardiac output) and plasma cortisol increased. Plasma ACTH concentration was higher in ponies treated with intrathecal naloxone. Endogenous opioids may inhibit ACTH Secretion, attenuating the stress response to halothane anaesthesia in equidae. (C) 2001 Harcourt Publishers Ltd.

Follicle profile and plasma gonadotropin concentration in pubertal female ponies

Twelve female ponies were examined daily for 30 days and classified as ovulating (OV; N = 6; 197 ± 6 kg) or prepubertal (PP; N = 6; 196 ± 9 kg). Follicles were detected by ultrasound and gonadotropins quantified by radioimmunoassay. The mean diameter of the largest follicles was significantly larger in OV (38 ± 1 mm) than in PP (26 ± 2 mm) but there was no difference between groups in the size of the second largest follicle. There were more small follicles (<24 mm) in the PP than in the OV group, but PP fillies had a smaller number of follicles >29 mm than the OV fillies. Follicle-stimulating hormone (FSH) levels did not differ between groups but PP fillies had lower luteinizing hormone (LH) peak (8 ± 1 ng/ml) and basal (4 ± 0.5 ng/ml) levels, lower peak magnitude (2 ± 0.2 ng/ml) and period average (5 ± 0.6 ng/ml) than OV fillies (32 ± 4.5, 8 ± 1.2, 17.1 ± 6, and 15 ± 2.3 ng/ml, respectively). The PP group, in contrast to the OV group, showed no relationship between FSH surge and follicle wave emergence. We conclude that an LH concentration higher than 8 ng/ml is needed for follicle growth to a preovulatory size. Wave emergence and FSH secretion seem to be independent events, probably due to an inhibitory neural system in these PP animals. PP fillies may provide a physiological model for the study of follicle wave emergence which apparently does not depend on gonadotropin levels.

Midazolam and ketamine induction before halothane anaesthesia in ponies: cardiorespiratory, endocrine and metabolic changes

Six Welsh gelding ponies were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) prior to induction of anaesthesia with midazolam at 0.2 mg/kg and ketamine at 2 mg/kg i.v.. Anaesthesia was maintained for 2 h using 1.2% halothane concentration in oxygen. Heart rate, electrocardiograph (EGG), arterial blood pressure, respiratory rate, blood gases, temperature, haematocrit, plasma arginine vasopressin (AVP), dynorphin, beta-endorphin, adrenocorticotropic hormone (ACTH), cortisol, dopamine, noradrenaline, adrenaline, glucose and lactate concentrations were measured before and after premedication, immediately after induction, every 20 min during anaesthesia, and at 20 and 120 min after disconnection. Induction was rapid, excitement-free and good muscle relaxation was observed. There were no changes in heart and respiratory rates, Decrease in temperature, hyperoxia and respiratory acidosis developed during anaesthesia and slight hypotension was observed (minimum value 76 +/- 10 mm Hg at 40 mins), No changes were observed in dynorphin, beta-endorphin, ACTH, catecholamines and glucose, Plasma cortisol concentration increased from 220 +/- 17 basal to 354 +/- 22 nmol/L at 120 min during anaesthesia; plasma AVP concentration increased from 3 +/- 1 basal to 346 +/- 64 pmol/L at 100 min during anaesthesia and plasma lactate concentration increased from 1.22 +/- 0.08 basal to 1.76 +/- 0.13 mmol/L at 80 min during anaesthesia, Recovery was rapid and uneventful with ponies taking 46 +/- 6 min to stand. When midazolam/ketamine was compared with thiopentone or detomidine/ketamine for induction before halothane anaesthesia using an otherwise similar protocol in the same ponies, it caused slightly more respiratory depression, but less hypotension. Additionally, midazolam reduced the hormonal stress response commonly observed during halothane anaesthesia and appears to have a good potential for use in horses.

Changes in plasma protein concentrations in ponies with experimentally induced alimentary laminitis

Objective-To determine whether plasma protein concentrations were altered in ponies with alimentary laminitis.Animals-12 adult ponies.Procedure-Acute laminitis was induced in 6 ponies by oral administration of carbohydrate (85% corn starch, 15% wood flour); the other 6 ponies were used as controls. A physical examination was performed and blood samples were collected immediately before and 4, 8, 12, 24, and 28 hours after administration of carbohydrate. Plasma protein concentrations were determined by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis.Results-19 plasma proteins ranging from a molecular weight of 24,000 to a molecular weight of 350,000 were identified in all 12 ponies. Plasma concentrations of proteins with molecular weights of 350,000 (fibrinogen), 130,000 (ceruloplasmin), 118,000 (c-reactive protein), 67,000 (alpha(1)-antitrypsin I), 65,000 (alpha(1)-antitrypsin II), 50,000 (haptoglobulin), and 45,000 (acid glycoprotein) were significantly increased in ponies with laminitis, compared with concentrations in control ponies.Conclusion-Changes in plasma protein concentrations are detectable within 4 hours after the onset of alimentary laminitis in ponies.Clinical Relevance-Measurement of plasma protein concentrations may be useful in monitoring the progression of laminitis in ponies.