Effects of pre‐operative administration of medetomidine on plasma insulin and glucose concentrations in healthy dogs and dogs with insulinoma

ObjectiveTo investigate the effect of medetomidine on plasma glucose and insulin concentrations in dogs with insulinoma and in healthy dogs undergoing anesthesia and surgery.AnimalsTwenty–five dogs with insulinoma and 26 healthy dogs.MethodsIn dogs with insulinoma, medetomidine (5 μg kg^?1) was randomly included (n = 12) or omitted (n = 13) from the pre–anesthetic medication protocol, which typically contained an opioid and an anticholinergic. Healthy dogs received medetomidine (5 μg kg^?1; n = 13) or acepromazine (0.04 mg kg^?1; n = 13) plus an opioid (morphine 0.5 mg kg^?1) and an anticholinergic (atropine 0.04 mg kg^?1) as pre–anesthetic medications. Pre–anesthetic medications were given intramuscularly. Plasma glucose and insulin concentrations were measured before (sample 1) and 30 minutes after pre–anesthetic medication (sample 2), and at the end of surgery in dogs with insulinoma or at 2 hours of anesthesia in healthy dogs (sample 3). Glucose requirement to maintain intra–operative normoglycemia in dogs with insulinoma was quantified and compared. Data were analyzed with anova and Bonferroni post–test, t–tests or chi–square tests as appropriate with p < 0.05 considered significant. Data are shown as mean ± SD.ResultsMedetomidine significantly decreased plasma insulin concentrations and increased plasma glucose concentrations in healthy dogs and those with insulinoma. These variables did not change significantly in the dogs not receiving medetomidine. In the dogs with insulinoma, intra–operative glucose administration rate was significantly less in the animals that received medetomidine compared to those that did not.ConclusionsPre–anesthetic administration of medetomidine significantly suppressed insulin secretion and increased plasma glucose concentration in dogs with insulinoma and in healthy dogs undergoing anesthesia and surgery.Clinical relevanceThese findings support the judicious use of medetomidine at low doses as an adjunct to the anesthetic management of dogs with insulinoma.     

Potential role of the CD38/cADPR signaling pathway as an underlying mechanism of the effects of medetomidine on insulin and glucose homeostasis

ObjectiveTo investigate the CD38/cADPR signaling pathway as possible underlying mechanism of the effects of medetomidine on insulin and glucose homeostasis.AnimalsThirty–two C57BL/6 mice of both sexes.MethodsWild–type (WT) and CD38–knockout (CD38^?/?) mice received medetomidine (50 μg kg^?1) or a similar volume of 0.9% NaCl (control) by intraperitoneal (IP) injection (each group n = 8). The mice were euthanized 45 minutes later with sodium pentobarbital IP and blood was sampled via cardiac puncture. Insulin and glucose concentrations were measured by radioimmunoassay and by the oxygen rate method, respectively. Data were analyzed with anova and Bonferroni post hoc (5% significance) and are shown as mean ± SD.ResultsPlasma insulin and glucose concentrations were similar between WT and CD38^?/? mice under control conditions. As compared to controls, medetomidine administration produced a statistically significant decrease in plasma insulin concentrations in the WT mice whereas the decrease in the CD38^?/? mice was not statistically significant. Correspondingly, medetomidine caused a significantly greater increase in plasma glucose concentrations in the WT than in the CD38^?/? mice.ConclusionThe CD38/cADPR signaling pathway may be one underlying mechanism of the glucose and insulin effects of the alpha–2 adrenergic receptor agonist medetomidine and likely other drugs of its’ class.     

Parthenocarpy restores fruitfulness in sterile triploid (3x) tomatoes artificially obtained by crossing 4x x 2x somaclones

Summary

To breed fruitful triploid tomatoes, diploid (2x) and tetraploid (4x) plants were regenerated from hypocotyl explants, using two pairs of near-isogenic lines differing respectively for the parthenocarpic fruit and parthenocarpic fruit-2 mutations. From 626 regenerated shoots, 53 were tetraploid. In the 4x plants, the mean number of fruits was lower than in the 2x class for all the genotypes, but in the two parthenocarpic lines it was higher than in the respective wild-types at the same ploidy level. Compared with 2x, the mean weight of 4x fruits was lower in wild-type and higher in parthenocarpic lines. Out of four cross combinations between tetraploid and diploid plants (within two parthenocarpic and two corresponding wild-type lines), only two yielded seeds (the parthenocarpic fruit line and its near-isogenic wild-type). Triploids were vegetatively propagated and evaluated in a field trial. Whereas wild-type triploids were completely sterile, the 3x parthenocarpic fruit plants had a fruit set that was not statistically different from that observed in 2x individuals. Mean fruit weight in 3x parthenocarpic plants was also higher than in 2x and comparable with 4x plants. Yield estimates in such triploids were not statistically different from those recorded in diploids, both wild-type and parthenocarpic. Triploid fruits had a soluble solids value higher than 2x fruits. The total seedlessness and the increased dry-matter content appeared traits peculiar to triploid parthenocarpic fruits. Therefore, triploids may deserve interest in breeding fresh market and processing tomatoes, providing that their commercial multiplication is ensured by micropropagation.     

Bryophyllum pinnatum poisoning of cattle

SUMMARY Two adult cattle died within 48 h of being fed a large amount of Bryophyllum pinnatum plants collected from a house garden. Clinical signs became apparent the day after feeding and included hypersalivation, ataxia, severe cardiac arrhythmia and laboured respiration. The main necropsy findings were acute rumenitis, reduction of bronchiolar lumens and emphysema.     

A neoproterozoic snowball earth

Negative carbon isotope anomalies in carbonate rocks bracketing Neoproterozoic glacial deposits in Namibia, combined with estimates of thermal subsidence history, suggest that biological productivity in the surface ocean collapsed for millions of years. This collapse can be explained by a global glaciation (that is, a snowball Earth), which ended abruptly when subaerial volcanic outgassing raised atmospheric carbon dioxide to about 350 times the modern level. The rapid termination would have resulted in a warming of the snowball Earth to extreme greenhouse conditions. The transfer of atmospheric carbon dioxide to the ocean would result in the rapid precipitation of calcium carbonate in warm surface waters, producing the cap carbonate rocks observed globally.     

Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis

HistoryA 4‐year old, 500 kg Thoroughbred female horse diagnosed with bilateral forelimb laminitis and cellulitis on the left forelimb became severely painful and refractory to non‐steroidal anti‐inflammatory therapy (flunixin meglumine on days 1, 2, 3 and 4; and phenylbutazone on days 5, 6 and 7) alone or in combination with gabapentin (days 6 and 7).Physical examinationPain scores assessed independently by three individuals with a visual analog scale (VAS; 0 = no pain and 10 = worst possible pain) were 8.5 on day 6, and it increased to 9.5 on day 7. Non‐invasive blood pressure monitoring revealed severe hypertension.ManagementAs euthanasia was being considered for humane reasons, a decision was made to add an experimental new drug, trans‐4‐{4‐[3‐(4‐Trifluoromethoxy‐phenyl)‐ureido]‐cyclohexyloxy}‐benzoic acid (t‐TUCB), which is a soluble epoxide hydrolase (sEH) inhibitor, to the treatment protocol. Dose and frequency of administration were selected based on the drug potency against equine sEH to produce plasma concentrations within the range of 30 nmol L^?1 and 2.5 μmol L^?1. Pain scores decreased sharply and remarkably following t‐TUCB administration and blood pressure progressively decreased to physiologic normal values. Plasma concentrations of t‐TUCB, measured daily, were within the expected range, whereas phenylbutazone and gabapentin plasma levels were below the suggested efficacious concentrations.Follow upNo adverse effects were detected on clinical and laboratory examinations during and after t‐TUCB administration. No new episodes of laminitis have been noted up to the time of writing (120 days following treatment).ConclusionsInhibition of sEH with t‐TUCB was associated with a significant improvement in pain scores in one horse with laminitis whose pain was refractory to the standard of care therapy. No adverse effects were noticed. Future studies evaluating the analgesic and protective effects of these compounds in painful inflammatory diseases in animals are warranted.