Interactions of fatty acids with the calcium release channel in malignant hyperthermia.
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Animals↗
Biomedical subjects
J Beech
Publications and source records attributed to J Beech.
Chronic obstructive pulmonary disease.
COPD continues to be a severe condition in horses. Despite increased understanding of its pathogenesis, there is relatively little information on effective treatment regimens. Management and prevention are critical, and more emphasis should be placed on improved housing, bedding, and feeding. More sophisticated accurate methods also are required for identifying specific causative allergens.
Allergens↗
Hepatocellular carcinoma associated with erythrocytosis and hypoglycemia in a yearling filly.
A yearling Arabian-type filly with a history of poor growth, erythrocytosis, hypoglycemia, and high liver enzyme activities was admitted to the hospital for evaluation. Three days after admission, the filly collapsed, deteriorated rapidly despite treatment, and was euthanatized. A metastatic hepatocellular carcinoma with capsular rupture and hemoperitoneum were found at necropsy. Primary liver tumors are rare in horses, and hepatocellular carcinoma has been reported in only 1 other horse. The systemic manifestations of the tumor in this filly included weakness, weight loss, inappetence, erythrocytosis with tumor production of erythropoietin, persistent hypoglycemia with normal serum insulin concentrations, serum alpha-fetoprotein (normally present only during fetal life), and terminal massive hemoperitoneum, all features of the syndrome in man.
Animals↗
Interactions in red blood cells between fatty acids and either snake venom cardiotoxin or halothane.
Phospholipase A2 (PLA2) activity enhances snake venom cardiotoxin (CTX)-induced and general anesthetic (halothane)-induced hemolysis of red blood cells. In the case of halothane-induced hemolysis, this effect appears to be related primarily to free fatty acids. In the present study, the interaction between CTXs and halothane and the effects of different free fatty acids on cardiotoxin and halothane-induced hemolysis were examined. The hemolytic actions of halothane and a CTX from Naja naja kaouthia venom were examined in erythrocytes with different phospholipid and free fatty acid composition from five species. The extent of hemolysis by CTX or halothane was dependent upon the species examined and appeared to be inversely related to the amount of saturated free fatty acid in the membrane. The order of susceptibility of red blood cells from five species to hemolysis was similar for halothane- and N. n. kaouthia CTX-induced hemolysis, but very different for osmotic fragility. The slope of the hemolysis dose-response curve was considerably steeper for halothane than for CTX. Hemolysis due to N. n. kaouthia CTX was greatly increased by halothane in erythrocytes from humans and horses and to a lesser extent in erythrocytes from sheep, goats and cows. Hemolysis induced by halothane and the N. n. kaouthia or Naja naja atra CTXs was enhanced by unsaturated fatty acids. In contrast, hemolysis induced by halothane was decreased and that caused by the two CTXs was relatively unaffected by saturated fatty acids. Halothane and CTXs differ in their exact mechanisms, but appear to act upon similar fatty acid-sensitive processes.
Animals↗
Fatty acids modulate calcium-induced calcium release from skeletal muscle heavy sarcoplasmic reticulum fractions: implications for malignant hyperthermia.
Based on studies in swine, the malignant hyperthermia syndrome has been postulated to result from an enhanced sensitivity (low threshold) of the Ca2(+)-induced Ca2(+)-release process. However, fatty acid production is elevated in homogenates of skeletal muscle from pigs and humans susceptible to malignant hyperthermia. In the present study, we demonstrate that the threshold of Ca2(+)-induced Ca2+ release is normal in susceptible humans and in susceptible swine depleted of triglycerides. Exogenously added unsaturated fatty acids decreased the threshold of Ca2(+)-induced Ca2+ release to a much greater extent in porcine and equine muscle than in human muscle. When triglyceride and free fatty acid values were reduced to about 40 and 60%, respectively, of control values, malignant hyperthermia-susceptible swine did not exhibit muscle rigidity when challenged in vivo with halothane and succinylcholine and the threshold of the Ca2(+)-induced Ca2(+)-release process in heavy sarcoplasmic reticulum fractions was normal. Despite the reduced triglyceride and fatty acid levels, these swine had a positive in vitro contracture test for malignant hyperthermia. A low Ca2(+)-induced Ca2(+)-release threshold is not essential for malignant hyperthermia susceptibility, but appears to be the result of excessive free fatty acids produced during organelle isolation.
Animals↗
Analysis of fatty acids in equine cerebrospinal fluid using gas chromatography with electron-capture detection.
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Animals↗
Hypertrophic osteopathy in a pony with a pituitary adenoma.
Hypertrophic osteopathy was diagnosed in a pony that had no antemortem or postmortem evidence of an intrathoracic lesion. With a history of hirsutism in an aged pony, a pituitary adenoma was suspected, and evaluation of plasma cortisol and insulin values and their response to thyrotropin-releasing hormone supported the diagnosis.
Adenoma↗
Autosomal trisomy in a Standardbred colt.
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Animals↗
Disseminated hemangiosarcoma in a horse.
A 6.5-year-old horse with a history of exercise-induced pulmonary hemorrhage was admitted because of acute onset of epistaxis, dyspnea, high respiratory rate, pale mucous membranes, and dark feces. There was no clinical or laboratory evidence of a bleeding disorder, and the horse's anemia was considered to be secondary to pulmonary hemorrhage. The cause of the hemorrhage was not found on thoracic sonograms or from cytologic examination of transtracheal aspirates. Despite supportive care, the horse's health deteriorated, and it was euthanatized. Necropsy revealed blood in the thoracic and peritoneal cavities and reddish black masses in many tissues. Histologic examination confirmed a diagnosis of hemangiosarcoma. Hemangiosarcoma is a rare tumor in horses; however, as this case demonstrates, it can cause pulmonary hemorrhage and respiratory distress and may be difficult to diagnose before death.
Animals↗
Pharmacokinetics of ticarcillin and clavulanic acid given in combination to adult horses by intravenous and intramuscular routes.
The pharmacokinetics of ticarcillin and clavulanic acid following administration by the intravenous (i.v.) and intramuscular (i.m.) routes were investigated in six normal adult horses. Following i.v. administration, the ticarcillin disposition data conformed to a two-compartment model with an elimination half-life of 1.0 h. The disposition of clavulanic acid was described by a one-compartment model with an elimination half-life of 0.40 h. Following i.m. administration, the half-lives of both drugs were prolonged (ticarcillin 1.8 h, clavulanic acid 1.2 h). The bioavailability of ticarcillin was 84.4% and clavulanic acid 94.3%.
Animals↗
Breathing strategy of the adult horse (Equus caballus) at rest.
To investigate the mechanism underlying the polyphasic airflow pattern of the equine species, we recorded airflow, tidal volum, rib cage and abdominal motion, and the sequence of activation of the diaphragm, intercostal, and abdominal muscles during quiet breathing in nine adult horses standing at rest. In addition, esophageal, abdominal, and transdiaphragmatic pressures were simultaneously recorded using balloon-tipped catheters. Analysis of tidal flow-volume loops showed that, unlike humans, the horse at rest breathes around, rather than from, the relaxed volume of the respiratory system (Vrx). Analysis of the pattern of electromyographic activities and changes in generated pressures during the breathing cycle indicate that the first part of expiration is passive, as in humans, with deflation toward Vrx, but subsequent abdominal activity is responsible for a second phase of expiration: active deflation to below Vrx. From this end-expiratory volume, passive inflation occurs toward Vrx, followed by a second phase of inspiration: active inflation to above Vrx, brought about by inspiratory muscle contraction. Under these conditions the abdominal muscles appear to share the principal pumping duties with the diaphragm. Adoption of this breathing strategy by the horse may relate to its peculiar thoracoabdominal anatomic arrangement and to its very low passive chest wall compliance. We conclude that there is a passive and active phase to both inspiration and expiration due to the coordinated action of the respiratory pump muscles responsible for the resting adult horse's biphasic inspiratory and expiratory airflow pattern. This unique breathing pattern perhaps represents a strategy of minimizing the high elastic work of breathing in this species, at least at resting breathing frequencies.
Animals↗
Effect of phenytoin on the clinical signs and in vitro muscle twitch characteristics in horses with chronic intermittent rhabdomyolysis and myotonia.
In vitro twitch characteristics of the semimembranosus muscle were evaluated in 9 clinically normal horses, in 15 horses with chronic intermittent rhabdomyolysis (CIR) and in 2 horses with myotonia. Effects of phenytoin on in vitro muscle twitch and clinical signs of CIR and myotonia were evaluated in these same horses. Times to 90% relaxation were prolonged in the horses with CIR (mean +/- SEM, 186 +/- 5.9 ms) and in 2 horses with myotonia (197 and 177 ms) compared with those in clinically normal horses (mean +/- SEM, 146 +/- 2.1 ms). Horses with CIR also had significantly (P less than 0.05) longer times to 50% relaxation, compared with clinically normal horses. In the group of horses with CIR, Standardbreds had significantly (P less than 0.05) longer times to 90% and 50% relaxation, compared with Thoroughbreds. Times to 100% peak tension did not differ among the groups. Administration of phenytoin directly into a muscle preparation bath solution had no effect on muscle twitch properties. After the initial muscle biopsy, phenytoin was administered orally for 7 to 10 days to 4 horses with CIR, 2 myotonic horses, and 2 clinically normal horses before repeat biopsy from the same site in the contralateral semimembranosus muscle. Times to 90% relaxation decreased from 197 and 177 ms to 144 and 126 ms, respectively, in the 2 myotonic horses, from a mean of 192 (+/- 9) ms to 170 (+/- 9) ms in the 4 horses with CIR and remained unchanged (154 and 140 ms before vs 155 and 139 ms after treatment) in the 2 clinically normal horses.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Pharmacokinetics of intravenously and intramuscularly administered ticarcillin and clavulanic acid in foals.
Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After intramuscular administration, the half-life of elimination was 2.9 hours, with bioavailability of 54.6%. For IV administered clavulanic acid, the elimination half-life was 0.65 hour for the low dosage and 0.74 hour for the high dosage. After intramuscular administration, the elimination half-life was 0.92 hour, and bioavailability was 68.1%. A combined dosage, 50 mg of ticarcillin/kg and 1.67 mg of clavulanic acid/kg, given every 6 hours is recommended.
Animals↗
Ectopic expression of Thy-1 in the kidneys of transgenic mice induces functional and proliferative abnormalities.
Hybrid human--mouse Thy-1.1 genes were injected into pronuclei of Thy-1.2 mice to produce transgenic animals. A hybrid gene composed of the 5' part of the mouse Thy-1.1 gene combined with the 3' human untranslated regions was expressed abnormally in the kidney podocytes, which resulted in severe protein-uria and subsequent death in several founder mice. A hybrid Thy-1 gene composed of the human coding region with the 5' and 3' flanking regions of the mouse gene was expressed abnormally in a different part of the kidney (the tubular epithelia), which resulted in a proliferative kidney disorder. In addition, a neoplasm was found in the brain of one of these mice. These results show that the Thy-1 protein can play an important role in the activation, proliferation, and differentiation of many different cell types.
Animals↗
Effects of cromolyn in horses with chronic obstructive pulmonary disease.
The effect of disodium cromoglycate (cromolyn) in preventing the pulmonary dysfunction caused by the inhalation of barn and hay dust was studied in 5 horses with confirmed chronic obstructive pulmonary disease (COPD). The horses were studied before (Con) and after exposure to hay and dust allergens (Expos) and after pretreatment with cromolyn followed by exposure (Cr-Expos). There was a significant reduction in PaO2 from 86.8 +/- 8.3 to 73.1 +/- 8.8 when the horses were exposed to hay and dust allergens. The PaO2 after pretreatment with cromolyn and exposures was 78.1 +/- 5.5. There were no significant changes in PaCO2, FRC, pH and A-aDO2 when the Con, Expos, and Cr-Expos periods were compared. There were significant increases in VE from a control value of 77.9 +/- 18.2 to 128.7 +/- 55.1 and 133.7 +/- 17.1 L/min during the exposures, which was due primarily to increases in respiratory frequency. Respiratory dead space (VD/VT) increased from 0.55 +/- 0.10 to 0.71 +/- 0.07 and 0.65 +/- 0.05, and alveolar ventilation (VA) remained constant. Pulmonary resistance (RL) and transpulmonary pressure (Ptr) increased from a control of 0.77 +/- 0.28 cm H2O/L/sec and 7.73 +/- 3.38 cm H2O to 2.93 +/- 1.01 and 20.17 +/- 4.81 during the Expos period and tidal volume (VT) fell from 7.5 +/- 1.0 to 5.7 +/- 1.3 L. The pre-treatment with cromolyn before exposures significantly reduced the increase in RL and Ptr and returned VT to Con levels.
Animals↗
Evaluation of thyroid, adrenal, and pituitary function.
The clinical signs and endocrinologic abnormalities that characterize horses with pituitary, thyroid, and adrenal dysfunction are described. Laboratory tests and hormonal assays useful for evaluating horses with suspected endocrinopathies are discussed.
Adrenal Glands↗
Equine degenerative myeloencephalopathy.
This article discusses the history and signalment, clinical signs, differential diagnosis, pathology, etiology and pathogenesis, and treatment and prevention of equine degenerative myeloencephalopathy.
Animals↗
Drug therapy of respiratory disorders.
The emphasis of this article is on the clinical application of drugs in therapy for treatment of disorders of the lower respiratory tract. Medications discussed include those used to enhance clearance of secretions and those employed to prevent and/or alleviate bronchoconstriction. Antimicrobial agents and respiratory stimulants are briefly mentioned.
Adjuvants, Immunologic↗