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Objective: To determine the virulence of a Brucella abortus mutant, BA25, lacking a major 25 kd outer membrane protein (Omp25) in cattle., Animals: 20 mixed-breed heifers in late gestation., Procedure: 10 heifers were inoculated with 1 x 10(7) colony-forming units of the Omp25 mutant via the conjunctival sac, and an equal number were infected with the virulent parental strain B. abortus 2308. The delivery status of the dams was recorded, and colonization was assessed following necropsy. The ability of BA25 to replicate inside bovine phagocytes and chorionic trophoblasts was also evaluated in vitro because of the propensity of virulent brucellae to replicate inside these cells in vivo., Results: The parental strain induced abortions in 5 of 10 inoculated cattle, whereas only 1 of 10 dams exposed to BA25 aborted. Brucella abortus strain 2308 colonized all of the cow-calf pairs and induced Brucella-specific antibodies in 100% of the dams. In contrast, BA25 was isolated by bacteriologic cultural technique from 30% of the calves and 50% of the inoculated dams (n = 10). Of the 10 heifers inoculated with BA25, 4 did not develop Brucella-specific antibodies nor were they colonized by the mutant strain. In bovine macrophages and chorionic trophoblasts, BA25 replicated in significantly lower numbers than the virulent parental strain (n = 3)., Conclusions and Clinical Relevance: The 25 kd outer membrane protein may be an important virulence factor for B. abortus in cattle. The attenuation of the Omp25 mutant in cattle may involve the inability of BA25 to replicate efficiently in bovine phagocytes and chorionic trophoblasts.

Effects of saline solution (groups 1, 2, and 3), xylazine (2.2 mg/kg of body weight, groups 4 and 5), acepromazine (0.1 mg/kg, groups 6 and 7), diazepam (1.0 mg/kg, groups 8 and 9), morphine (1.0 mg/kg, groups 10 and 11), or fentanyl-droperidol (0.055 ml/kg, groups 12 and 13), IM were compared in groups of atropinized dogs. Treated dogs were anesthetized to stage III, plane 2 with pentobarbital, IV. After stabilization of anesthesia, the dogs were given IV 0.5 mg of 4-aminopyridine (4-AP)/kg + 0.25 mg of yohimbine/kg (groups 2, 5, 7, and 9), or 4-AP + yohimbine + 0.04 mg of naloxone/kg (groups 3, 11, and 13). Groups 1, 4, 6, 8, 10, and 12 were given saline solution instead of test antagonists. Required dosage of pentobarbital, arousal and walk times (measured from injection of antagonists), respiratory rate, and heart rate were measured. Emergence phenomena were recorded and graded as smooth, fairly smooth, smooth in some dogs to rough in other dogs, rough, or very rough. In group 1 dogs, mean arousal time (MAT) was 279.5 minutes, mean walk time (MWT) was 583.3 minutes, and emergence was rough. In groups 4, 6, 8, 10, and 12, MAT was decreased by the sedatives to the range of 52 to 115.3 minutes and MWT was decreased to the range of 82.3 to 188.5 minutes. Emergence was smooth (groups 4 and 6), fairly smooth (groups 10 and 12), or smooth to rough (group 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Groups of atropinized cats (6/group) were given IM meperidine (5.5 mg/kg of body weight) plus acepromazine (0.25 mg/kg). Forty minutes later, the cats were anesthetized to disappearance of pedal reflexes with 1% pentobarbital IV. Volume of anesthetic was recorded. Five minutes later, the cats were given IV saline solution (2 ml; control group), the antagonists 4-aminopyridine (4-AP; 0.5 mg/kg), yohimbine (0.4 mg/kg), or a combination of 0.5 mg of 4-AP/kg plus 0.4 mg of yohimbine/kg. Mean arousal time (MAT), walk time (MWT), respiratory rate, and heart rate were measured. Emergence phenomena also were recorded. Meperidine plus acepromazine caused mydriasis and mild sedation without ataxia or marked protrusion of the 3rd eyelid. The cats did not resist restraint for venipuncture. The pooled mean dosage level of pentobarbital required for anesthesia was 12.3 mg/kg. Control group MAT and MWT were 66.2 minutes and 126 minutes, respectively. Marked residual sedation lasted several hours. In cats given 4-AP plus yohimbine, MAT and MWT were decreased to 4.4 minutes and 36.5 minutes, respectively. These values were not significantly shorter than those same values in cats given 4-AP or yohimbine alone (P greater than 0.05), but the combination of 4-AP plus yohimbine produced a qualitatively better reversal of anesthesia than did 4-AP or yohimbine alone. Emergence was smooth in all 4 groups; mild-to-moderate residual sedation lasted 2 to 4 hours in the principals. Relapses, drug side effects, and behavioral aberrations were not observed. Mean respiratory rates and heart rates decreased during anesthesia but these values were not excessively depressed or stimulated at any time. Cardiac irregularities were not detected by palpation or auscultation.(ABSTRACT TRUNCATED AT 250 WORDS)

In 2 separate experiments, groups of atropinized cats (6 cats/group) were given acepromazine (0.25 mg/kg of body weight) or xylazine (2.2 mg/kg) IM and anesthetized with pentobarbital. The mean dose of pentobarbital was decreased approximately 36% by acepromazine, and approximately 80% by xylazine, compared with published doses. Anesthetized cats were given IV saline solution (control groups) or were given the antagonists 4-aminopyridine (4-AP; 0.5 mg/kg), yohimbine (0.4 mg/kg), or 4-AP + yohimbine (0.5 mg/kg and 0.4 mg/kg, respectively). In acepromazine-treated cats, 4-AP + yohimbine was the most effective antagonist; arousal and walking occurred in an average of 10.4 minutes and 91.7 minutes, respectively. Yohimbine enhanced the antagonistic effects of 4-AP. In xylazine-treated cats, yohimbine was an effective antagonist; arousal and walking occurred in an average of 2.8 minutes and 12.8 minutes, respectively. Yohimbine did not enhance the antagonistic effects of 4-AP. Mean respiratory rates were decreased by acepromazine, but were increased by xylazine. Thus, respiratory rate depression by pentobarbital was not as marked with xylazine as it was with acepromazine. Changes in mean heart rate were not remarkable with either sedative, and cardiac irregularities were not palpated or auscultated. In healthy cats, the duration of pentobarbital anesthesia can be controlled by 4-AP + yohimbine (acepromazine-pretreated cats) or by yohimbine alone (xylazine-pretreated cats).

Groups of fasted atropinized crossbred dogs of both sexes were injected IM with a standard dosage of a xylazine-acepromazine combination (2.2 mg/kg and 0.5 mg/kg, respectively). Righting reflex was uniformly lost and considered to be the point of maximum sedation. After maximal sedation, dogs were injected IV with 4-amino-pyridine (4-AP, 0.5 mg/kg), yohimbine (0.25 mg/kg), or a combination of 4-AP and yohimbine. Controls were given (IV) 1 ml of saline solution. The 4-AP, yohimbine, and 4-AP + yohimbine significantly reduced walk times (time to arousal and ability to walk on a leash) from a control value of 43.1 minutes to 7.6, 4.4, and 1.9 minutes, respectively (P less than 0.05). Relapse to unconsciousness did not occur with any antagonist regimen and recovery was uneventful. In 3 dogs sedated with the xylazine-acepromazine combination supplemented with halothane having surgically placed cannulas and electrodes for measurement of electroencephalo-, electrocardio-, and electromyographic (EEG, ECG, and EMG) responses, arterial blood pressure, and respiratory rates and depth, IV injection of 4-AP + yohimbine caused transient femoral arterial hypotension with tachycardia, increases in respiratory rate, depth, and minute volume, increased EMG and EEG activities preceding and accompanying gross movements, slight speeding of ECG, and behavioral arousal within 3 minutes. Increased heart rate also was observed in intact dogs given yohimbine. Increased rate and depth of respiration also was seen in all intact dogs given antagonists. Curiously, the xylazine-acepromazine combination did not induce arterial hypotension as expected from the product literature. To what extent pretreatment with atropine sulfate may have counteracted this effect is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetics of 4-aminopyridine (4-AP), a drug capable of antagonizing nondepolarizing neuromuscular blocking drugs, as well as several classes of injectable sedative and anesthetic agents, were studied in 6 intact, awake horses. Plasma samples were assayed for 4-AP over a frequent sampling schedule for 8 hours after IV administration. The plasma 4-AP vs time data best fit a 2-compartment pharmacokinetic model. Distribution half-life was 7.4 minutes, elimination half-life was 259 minutes, volume of the central compartment was 0.89 L/kg, volume of distribution (area) was 1.98 L/kg, volume of distribution at steady state was 1.9 L/kg, and total clearance was 5.3 ml min(-1) kg(-1). The 259-minute elimination halflife observed in the present study is consistent with prolonged clinical effectiveness observed in a previous study of antagonism of xylazine/ketamine anesthesia by 4-AP in horses.

Five groups of 6 fasted crossbred steers were injected IM with standard dosages of xylazine hydrochloride (0.3 to 0.5 mg/kg). At maximal sedation, the steers were injected IV with the antagonists' doxapram (1.0 mg/kg), doxapram + yohimbine (0.125 mg of yohimbine/kg), doxapram + 4-aminopyridine (4-AP; 0.3 mg of 4-AP/kg), or 4-AP + yohimbine. One group was given 1.0 ml of saline solution IV instead of antagonists. Doxapram, doxapram + yohimbine, doxapram + 4-AP, and 4-AP + yohimbine decreased mean standing time (time from antagonist injection until animal could stand unaided) to 17.0, 4.3, 3.3, and 4.5 minutes, respectively--significantly (P less than 0.05) down from a control value of 49.8 minutes. Mean total recovery time (time from xylazine injection until animal resumed eating) was decreased to 78 minutes by doxapram and 81.6 minutes by doxapram + 4-AP--significantly (P less than 0.05) down from the control value of 142.9 minutes. Respiratory character was improved (depth of respiration was increased) only by doxapram + 4-AP. Relapses to recumbency and marked sedation were not seen in steers given doxapram + 4-AP or the saline solution. One steer given doxapram, 2 given doxapram + yohimbine, and 1 given 4-AP + yohimbine relapsed to recumbency and sedation. Recovery was relatively smooth in steers given doxapram + 4-AP or 4-AP + yohimbine. Animals given doxapram or doxapram + yohimbine had difficult recoveries.(ABSTRACT TRUNCATED AT 250 WORDS)

One-day-old White Leghorn chicks were fed graded levels (0, 10, 50, 100 and 1,000 ppm) of pentachloronitrobenzene (PCNB; quintozene) up to 8 weeks. Each treatment group consisted of 90 randomly selected birds (2 replications of 45 birds each). Body weight gains were significantly lower at the 1,000-ppm treatment level. Histopathologic examination of brain, liver, pancreas, small intestine, gizzard, spleen, kidney, lung, and heart failed to reveal lesions in either control or treated groups. Bioaccumulation of PCNB or its metabolites (pentachloroaniline and pentachlorophenylmethylsulfide) in tissues only occurred in trace or very low concentrations. However, trace contaminating of PCNB, eg, hexachlorobenzene (HCB) and pentachlorobenzene (PCB) accumulated in tissues to a significant degree. Tetrachloronitrobenzene, another contaminant of PCNB, was found in only the adipose and cardiac tissues following the feeding of 1,000 ppm PCNB. Storage of PCNB, HCB, and PCB in adipose and other tissues was linearly related to the amount of PCNB in the ration.

Concentrations of 4-aminopyridine hydrochloride in plasma of cattle were measured over an 8-hour period following a bolus IV injection (0.3 mg/kg). The drug was assayed by a gas-liquid chromatographic method using a nitrogen-phosphorus detector. Plasma 4-aminopyridine hydrochloride vs time data best fit a 2-compartment pharmacokinetic model. Distribution half-life was 12.08 minutes; elimination half-life, 128.96 minutes; volume of the central compartment, 1.48 L/kg; volume of distribution based on total area, 3.07 L/kg; volume of distribution at steady state, 2.75 L/kg; and body clearance, 16.57 ml/min/kg.

Thirty-six fasted, mixed horse breed geldings (6 groups of 6 animals each) were anesthetized with xylazine and ketamine, and when maximally sedated, were given 1 of the following antagonists: saline solution, 4-aminopyridine (4-AP), small-dose yohimbine, large-dose yohimbine, 4-AP plus low-dose yohimbine, or 4-AP plus high-dose yohimbine. Measured data included mean standing time (MST), heart rate, respiratory rate, rectal temperature, and mean total recovery time ( MTRT ). Emergence phenomena were also observed and recorded as smooth, fairly smooth, fairly rough, or rough. Groups given 4-AP alone, small-dose yohimbine alone, or large-dose yohimbine alone produced a significant (P less than 0.05) decrease in MST (9.9 +/- 1.6 minutes, 11.3 +/- 1.7 minutes, and 10.6 +/- 2.3 minutes, respectively) compared with that in the saline control group (24.3 +/- 9.2 minutes). The MTRT were not significantly (P greater than 0.05) different (47.2 +/- 10 minutes, 90.4 +/- 15.1 minutes, and 83.2 +/- 23 minutes, respectively) from control values (66.2 +/- 13.4 minutes). When the antagonists were combined, 4-AP plus small-dose yohimbine and 4-AP plus large-dose yohimbine produced significant (P less than 0.05) decreases (10.3 +/- 2 minutes and 8.3 +/- 2.6 minutes, respectively) in MST compared with that of saline controls. The MTRT was significantly longer in the combined antagonist group (4-AP + small-dose yohimbine--131.8 +/- 28.9 minutes; 4-AP + large-dose yohimbine--131.3 +/- 19.4 minutes) compared with that of control or any antagonist alone.(ABSTRACT TRUNCATED AT 250 WORDS)

The USDA has detected hexachlorobenzene (HCB) in the body fat of domestic animals and poultry in at least 14 states. In Louisiana, industrial contamination appeared to be largely responsible for the HCB residues detected in cattle. Following the episode in Louisiana, the Environmental Protection Agency (EPA) established an interim tolerance of 0.5 ppm for HCB in the fat of cattle, sheep, goats, and horses. Edible meat products containing HCB at higher concentrations are violative and cannot be used as a source of food for human consumption.

Yohimbine hydrochloride is an indole alkaloid which blocks alpha 2-adrenergic and dopamine receptors and stimulates serotonergic receptors. Yohimbine was selected for testing as a possible antagonist in fescue toxicosis. Reduced body weight gains in cattle with chronic fescue toxicosis may be due to ergot alkaloids produced by fungi which infect the fescue grass. Ergot alkaloids stimulate dopamine receptors, antagonize serotonin, and lower serum prolactin concentrations. It was hypothesized that yohimbine may reverse or counteract the effects of the toxic fescue. Investigation was made of the treatment effects of multiple doses of yohimbine given in rats by intraperitoneal and oral routes. Given intraperitoneally once a day for 8 days, yohimbine hydrochloride increased serum prolactin concentrations. When given orally in feed for 7 days, the drug decreased the serum prolactin concentration. The effects of yohimbine on prolactin concentrations were dependent on the dosages and routes of administration. The inability of yohimbine, when given orally, to increase serum prolactin levels decreased its potential usefulness for prolonged treatment of fescue toxicosis.

Twenty-four crossbred steers (4 groups of 6 steers each) were injected IM with a standard dosage range of xylazine hydrochloride (0.2 to 0.3 mg/kg of body weight). When the steers were maximally sedated, group I (control group) were given isotonic saline solution (1 ml, IV), group II were given 4-aminopyridine (4-AP, 0.3 mg/kg) IV, group III were given yohimbine hydrochloride (0.125 mg/kg) IV, and group IV were given 4-AP (0.3 mg/kg) plus yohimbine hydrochloride (0.125 mg/kg) IV. The 4-AP decreased mean standing time (MST; time until animal could stand unaided) from 94.3 minutes (control) to 13.4 minutes. Yohimbine decreased MST to 27 minutes. The combination of 4-AP + yohimbine decreased MST to 7.4 minutes. Mean total recovery time (MTRT; time from xylazine injection until normal behavior, including eating and drinking) was not significantly (P = greater than 0.05) decreased from control values by any of the antagonists tested. The combination of 4-AP + yohimbine decreased MST in animals given a 3X overdose of xylazine (0.6 mg/kg) from 124 minutes (control) to 30.3 min. The MTRT was not significantly (P greater than 0.05) decreased from control values. Two animals given a 5X overdose of xylazine (1 mg/kg) and then given 4-AP + yohimbine had a MST of 32.5 minutes and a MTRT of 3.7 hours. The combination of 4-AP + yohimbine produced marked antagonism of xylazine sedation in cattle. The combination of antagonists may prove to be useful for the arousal of animals sedated with xylazine alone or with a combination of sedatives including xylazine.

The alpha 2-adrenergic agonist clonidine hydrochloride, the serotonin agonist quipazine maleate, and the serotonin (5-HT2) antagonist LY 53857 were tested alone and in various combinations for their capabilities to increase mean serum prolactin (MSP) concentrations in rats given the synthetic ergot alkaloid CB-154 (2-bromo-alpha-ergocriptine), a known prolactin suppressor. The LY 53857 and the combination of clonidine, quipazine, and LY 53857 significantly decreased MSP concentrations. Quipazine given alone (10 mg/kg of body weight) was best able to increase MSP concentration and has potential to antagonize prolactin-depressant effects of ergot alkaloids.

Documentation in the literature indicates that death is as painless following the induction of hypoxia by rapid decompression as by other methods that lead to hypoxia, such as exposure to high altitude, carbon monoxide, and inert gases (nitrogen, xenon, and krypton). Many of the signs and symptoms of hypoxia are the same as those for alcoholic intoxication and inert gas narcosis. Moreover, there is good evidence that analogous relationships or mechanisms may exist for hypoxia, inert gas narcosis, and anesthesia.