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Pharmacokinetics and short-term clinicopathologic changes after intravenous administration of a high dose of methimazole in dogs
1994
Vail, D.M. | Elfarra, A.A. | Panciera, D.L. | Hutson, P.R.
A bolus dose of methimazole (MMI) was administered IV over 1 minute to 5 healthy adult dogs at a dosage (40 mg/kg of body weight) known to impart protection against cisplatin-induced renal disease. Blood and urine samples for pharmacokinetic analysis were collected over a 24-hour period. Physical examination, CBC, determination of serum thyroid hormone concentrations, and serum biochemistry analysis were performed over a 10-day period to evaluate short-term toxicoses. At this dosage, MMI appears to be safe and well tolerated in dogs; only 1 of the 5 dogs had mild and transient increases in serum activity of hepatic enzymes. In addition, MMI did not alter serum thyroid hormone concentrations. Half-life of 8.82 hours and mean residence time of 12.18 hours were determined for MMI. Renal clearance of native MMI, along with sulfate and glucuronide conjugates, represented only 20% of total systemic clearance. Results of this study provide further information concerning clinical use of MMI in dogs and may contribute to better understanding of the mechanism of MMI protection against chemically induced nephrotoxicosis.
Mostrar más [+] Menos [-]Rate of change of QT interval in response to a sudden change in the heart rate in dogs
1994
Oguchi, Y. | Hamlin, R.L.
Although it is known that the QT interval is dependent on the preceding RR interval, QT interval does not vary during respiratory sinus arrhythmia, despite a wide variation in heart rate. To assess the rate of change of the QT interval following an abrupt increase or decrease in heart rate, QT intervals were measured from ECG of healthy, anesthetized, thoracotomized dogs in which a junctional rhythm had been induced by destroying the sinoatrial node. Atria were paced at 800- or 600-millisecond cycle durations until a steady state was reached, and then the cycle duration was changed suddenly to a new cycle duration (600 or 800 milliseconds, respectively). The time and number of heart beats required until the QT interval achieved a value of 63% (1 time constant) of the new steady state were calculated. Time constants for change in QT interval vs the number of beats following the change were 2.8 (SD = 1.3 s) seconds when heart rate was accelerated and 4.7 (SD = 2.1 s) seconds when heart rate was slowed. Differences were not statistically significant. The time constants for change in QT interval duration vs duration after the sudden change in heart rate were 1.7 (SD = 0.8 s) seconds when heart rate was accelerated and 3.7 (SD = 1.7 s) seconds when heart rate was slowed. These time constants differed significantly (P < 0.01). Response of QT interval, therefore, depended on the number of heart beats following sudden change in heart rate, but not time, except as time determined the number of heart beats. The QT interval did not change until 3 to 5 beats after the heart rate was suddenly changed. This number of beats would be more than that which would occur in 1 respiratory cycle in dogs; therefore, QT interval memory would prohibit changes in QT intervals that occur during respiratory sinus arrhythmia.
Mostrar más [+] Menos [-]Polymerase chain reaction for detection of Borrelia coriaceae, putative agent of epizootic bovine abortion
1994
Zingg, B.C. | LeFebvre, R.B.
The nucleotide sequence of a chromosomally encoded antigen-expressing gene of Borrelia coriaceae was determined and used as a target for the polymerase chain reaction (PCR). Two primer sets were designed specifying the amplification of 269- and 701-bp DNA fragments. Primer set I, producing the short amplicon, was tenfold more sensitive than primer set II. As little as 10 fg of purified B coriaceae DNA could consistently be detected. The PCR assays, containing controlled numbers of whole spirochetes, allowed detectable amplification of 2 to 10 organisms. An internal, nonradioactively labeled gene-specific probe verified specificity of the PCR amplicons. Neither primer set cross-reacted with other related spirochetes. This PCR assay was adapted and found suitable for identification of B. coriaceae in biological samples, such as blood and thymus. Evidence for presence of B. coriaceae in biological samples was not found in tissue samples obtained from experimentally infected cows and their fetuses. These data failed to establish a definite association between B. coriaceae and epizootic bovine abortion.
Mostrar más [+] Menos [-]Efficacy of 4-methylpyrazole for treatment of ethylene glycol intoxication in dogs
1994
Dial, S.M. | Thrall, M.A.H. | Hamar, D.W.
4-Methylpyrazole (4-MP), an alcohol dehydrogenase inhibitor, was administered to dogs to treat ethylene glycol (EG) intoxication. Eleven dogs were given 10.6 g of EG/kg of body weight; 5 dogs were treated with 4-MP 5 hours after EG ingestion and 6 dogs were treated with 4-MP 8 hours after EG ingestion. 4-Methylpyrazole was administered IV as a 50-mg/dl solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 12 hours after initial dose, 15 mg/ kg; at 24 hours after initial dose, 10 mg/kg, and at 30 hours after initial dose, 5 mg/kg. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 hours, and at 1 week and 2 weeks after EG ingestion. Dogs of both groups developed clinicopathologic signs associated with EG intoxication, including CNS depression, hyperosmolality, high anion gap metabolic acidosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria. Fractional excretion of sodium was increased in all dogs between 1 and 9 hours after EG ingestion, but remained increased beyond 24 hours only in the 2 dogs treated at 8 hours after EG ingestion that developed acute renal failure. All dogs treated 5 hours after EG ingestion recovered without morphologic, biochemical, or clinical evidence of renal impairment. Of the 6 dogs treated 8 hours after EG ingestion, 2 developed acute renal failure. One of the dogs treated 8 hours after EG ingestion remained isosthenuric for 2 months, but did not manifest any other signs of renal impairment. Of the dogs treated 8 hours after EG ingestion, 3 recovered without morphologic, biochemical, or clinical evidence of renal impairment. Serum half-life of EG was prolonged in the dogs treated 8 hours after EG ingestion. Percentage of EG excreted unchanged was 84 +/- 2% in the dogs treated 5 hours after EG ingestion, and was 40 +/- 10% in the dogs treated 8 hours after EG ingestion. 4-Methylpyrazole was effective in preventing renal failure in all dogs given 10.6 g of EG/kg when treatment was initiated by 5 hours after EG ingestion, and in 4 of 6 dogs when treatment was initiated by 8 hours after EG ingestion.
Mostrar más [+] Menos [-]Immunomodulatory effects of staphylococcal antigen and antigen-antibody complexes on canine mononuclear and polymorphonuclear leukocytes
1994
DeBoer, D.J.
Staphylococcal antigens and immune complexes (IC) prepared from antigen and hyperimmune canine serum were tested for their effects on certain functions of mononuclear (MN) and polymorphonuclear (PMN) leukocytes (cells) obtained from healthy dogs. The effect on MN cells was studied by determining the ability of antigen or IC to augment or inhibit mitogenesis induced by phytohemagglutinin (PHA). The effect of antigen or IC on PHA cells was studied by measurement of H2O2 production as an indicator of respiratory burst. Neither the antigen nor the IC, when cultured with MN cells, was mitogenic. Coincubation of antigen or IC with MN cells and PHA resulted in a concentration-dependent decrease in mitogenesis. The decreased mitogenesis could not be overcome by addition of excess PHA, and may in part have been related to toxic effects of the antigen or IC on MN cells. When MN cells were instead preincubated with antigen or IC, then washed and stimulated with PHA, there was still a concentration-dependent inhibition of mitogenesis, although toxicity to the cells was not observed. Low concentrations of staphylococcal antigen or IC stimulated slight H2O2 production by PHA cells. When PHA cells were coincubated with IC and another stimulus (opsonized zymosan or phorbol myristate acetate), IC appeared to augment phorbol myristate acetate-, but not zymosan-induced stimulation. These results suggest that staphylococcal antigens, either alone or complexed with antibody, have the ability to stimulate PMN cells and inhibit MN cell function. Such actions may have a role in the pathogenesis of recurrent staphylococcal infection in canine patients.
Mostrar más [+] Menos [-]Cardiopulmonary effects of medetomidine in heartworm-infected and noninfected dogs
1994
Venugopalan, C.S. | Holmes, E.P. | Fucci, V. | Keefe, T.J. | Crawford, M.P.
Medetomidine, an investigational drug indicated for clinical use as a short-term chemical restraint in dogs, was evaluated for its cardiopulmonary effects, in 10 naturally heartworm-infected (HW+) and 10 noninfected (HW-) Beagles. The drug was randomly administered IV (30 microgram/kg of body weight) and IM (40 microgram/kg) in single injections to all dogs. Heart rate, respiratory rate, ECG, blood gas tensions, blood pH, central venous and arterial pressures were measured at 0, 15, 30, 60, 90, 120, and 180 minutes. Medetomidine induced an immediate significant (P less than or equal to 0.001) increase in mean arterial blood pressure followed by decreased blood pressure that remained below normal throughout the study in both groups, irrespective of route of administration. Medetomidine increased central venous pressure, over time, for both groups and both routes of administration. Heart and respiratory rates were significantly (P less than or equal 0.001) decreased after medetomidine administration and remained reduced for the duration of the study in all dogs. The ECG variables were not significantly different between groups or between routes of administration. The HW+ dogs tended to have higher mean PaO2 than did HW- dogs at several postinjection determination times, particularly when the drug was administered IM. The PaO2 decreased during the first 30 minutes in both groups and tended to increase gradually thereafter. The pH decreased over time for both groups and both routes. A significant (P less than or equal to 0.05) decrease in pH was seen in the HW- dogs, compared with HW+ dogs at each measuring time for both routes. The PaCO2 did not significantly change for groups or routes. In general, bradycardia was the predominant cardiovascular effect seen after medetomidine administration in all dogs, irrespective of route. Lowering of blood pressure and heart rate (after a transient blood pressure increase) was synchronized with sedation in these dogs. The overall clinical response with regard to cardiopulmonary effects in HW+ dogs was similar to that in HW- dogs.
Mostrar más [+] Menos [-]Evaluation of a technique for detection of pulmonary hemorrhage in horses, using carbon monoxide uptake
1994
Aquilera-Tejero, E. | Pascoe, J.R. | Smith, B.L. | Tyler, W.S. | Woliner, M.J.
The diffusing capacity for carbon monoxide (DLCO) and the functional residual capacity (FRC) of the lung were measured in 5 healthy Thoroughbreds before and after instillation of autologous blood into their lungs, in an attempt to develop a method to quantitate extravascular blood in the lungs of horses with exercise-induced pulmonary hemorrhage. Mean (+/- SD) baseline values of DLCO and FRC were 333.8 +/- 61.9 ml/min/mm of Hg and 21.464 +/- 4.156 L, respectively. Blood instillation resulted in decreases in DLCO and FRC. The paradoxic decrease in DLCO (we were expecting to find an increase owing to blood in the airspaces, as has been reported in people) appears to be associated with the bronchoscopic procedure and with presence of blood in the airways. We concluded that rebreathing DLCO measurements were not effective for detecting blood introduced bronchoscopically into the lungs of horses.
Mostrar más [+] Menos [-]Myoelectric activity of the cecum and proximal loop of the ascending colon in cows
1994
Steiner, A. | Roussel, A.J. | Brumbaugh, G.W. | Taylor, T.S.
Six Jersey cows were implanted with 8 pairs of bipolar electrodes: 1 in the jejunum, 1 in the ileum, 3 in the cecum, and 3 in the proximal loop of the ascending colon (PLAC). Myoelectric activity was recorded at 2- to 3-day intervals, 3 times for 8 hours or 4 times for 6 hours, using a computer-based oscillograph and data-acquisition program. Mean (+/- SD) duration of the migrating myoelectric complex (MMC) in the ileum was 84.52 +/- 4.87 minutes. Phases I and II of the MMC lasted significantly (P < 0.05) longer than phase III. Two types (A and B) of cyclic activity were found in the cecum and PLAC. Cyclic activity type A was observed predominantly in the cecum, and type B was observed exclusively in the PLAC. Phase III of the MMC in the ileum was accompanied by hyperactivity type A at the level of the ileocecocolic junction in 60.90 +/- 12.65% of the MMC. Twenty-seven types of orally and aborally propagated spike sequences, involving the cecum and PLAC, were found. They were most frequent when an MMC phase III was observed in the ileum, and least frequent when an MMC phase I was observed in the ileum (P < 0.05). All electrode sites of the cecum and PLAC served as pacemaker areas. Propagated and nonpropagated spikes were found at all electrode sites of the cecum and PLAC. Although propagated spikes lasted significantly (P < 0.05) longer than nonpropagated spikes, a clear distinction on the basis of duration could not be defined between the 2 spike types because broad overlapping of duration existed. Duration of cecocolic spiking activity per electrode (expressed as percentage of time) was significantly (P < 0.05) greater during MMC phase III in the ileum than during MMC phase I. It can be concluded that myoelectric activity of the cecum is well coordinated with the ileum and the PLAC. Phases of reduced and increased myoelectric activity in the cecum and PLAC are simultaneous with phases I and III of the MMC in the ileum.
Mostrar más [+] Menos [-]Tidal breathing flow-volume loops in horses with recurrent airway obstruction (heaves)
1994
Petsche, V.M. | Derksen, F.J. | Robinson, N.E.
Tidal breathing flow-volume (TBFV) loops were determined in a group of control horses and in horses affected with recurrent airway obstruction (heaves). The latter group was studied when the condition was in remission and under increasing amounts of airway obstruction as reflected by measurements of change in pleural pressure, pulmonary resistance, and dynamic compliance. The TBFV loops of control horses had biphasic inspiratory and expiratory patterns; peak inspiratory and peak expiratory flows were detected early in inspiration and expiration, respectively. Tidal volume was unaffected by heaves, but at all stages of heaves, respiratory frequency was increased principally because of shorter inspiratory time, and therefore, inspiratory flow rate was increased. In horses with heaves, TBFV loops did not have a biphasic pattern; peak inspiratory flow was observed late in inspiration, and peak expiratory flow was observed early in expiration. As airway obstruction became more severe, peak expiratory flow increased as pulmonary resistance increased so that, during severe airway obstruction, TBFV loops had a characteristic appearance with high peak expiratory flow early in expiration followed by low flow rate.
Mostrar más [+] Menos [-]Persistence of immunity to toxoplasmosis in pigs vaccinated with a nonpersistent strain of Toxoplasma gondii
1994
Dubey, J.P. | Baker, D.G. | Davis, S.W. | Urban, J.F. Jr | Shen, S.K.
Persistence of the vaccine RH strain of Toxoplasma gondii was studied by bioassay and histologically in 14 pigs. Pigs were euthanatized 2, 4, 7, 8, 14, 15, 21, 29, 36, 42, 52, 57, and 76 days after IM inoculation with 100,000 T gondii tachyzoites. Viable T gondii tachyzoites derived from the RH strain were isolated by bioassay in mice inoculated with tissues of pigs euthanatized up to 14 days after vaccination. Except for fever, pigs vaccinated IM with the RH strain remained clinically normal. Two other pigs inoculated IV with 100,000 T gondii tachyzoites of the RH strain became ill, and 1 pig was comatose by 4 days after inoculation. These findings indicate that route of inoculation may influence the response of pigs to T gondii. To evaluate protective immunity in pigs vaccinated with the RH strain, 16 age-matched pigs were allotted to 4 groups (A-D) of 4 pigs each. Eight pigs (groups A and C) were vaccinated IM with 100,000 RH strain tachyzoites and 8 pigs (groups B and D) were nonvaccinated controls. Pigs of groups A and C were challenge-inoculated orally with a lethal dose of T gondii oocysts (100,000 oocysts) 81 days after vaccination, pigs of groups B and D were inoculated similarly 220 days after vaccination. The concentration of T gondii at 3 days after challenge inoculation of pigs vaccinated 81 days earlier was reduced 100,000-fold in mesenteric lymph nodes, compared with that in a nonvaccinated pig euthanatized at 3 days after challenge inoculation. Another nonvaccinated pig became comatose and had to be euthanatized at 7 days after challenge inoculation, numerous tachyzoites were in its mesenteric lymph nodes, intestines, and liver. The vaccinated pigs generally remained clinically after challenge inoculation with oocysts. Toxoplasma gondii was not isolated by bioassays from tissues of 5 of 8 vaccinated pigs, but was recovered from all nonvaccinated pigs. Results indicate that protective immunity persisted in pigs for at least 7 months after vaccination with the nonpersistent RH strain of T gondii.
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