Fatal propylene glycol toxicosis in a horse

Toxicosis attributable to propylene glycol (1,2-propanediol) was suspected in an 8-year-old 450- to 500-kg male Quarter Horse. Clinical signs of toxicosis developed within 15 minutes of the accidental iatrogenic oral administration of 3.8 L of propylene glycol. Clinical signs of toxicosis included salivation, sweating, ataxia, and signs of pain. Additionally, at 24 hours after propylene glycol ingestion, the horse became increasingly atactic, had an abnormal breath odor, developed rapid shallow breathing, and was cyanotic. The horse died of apparent respiratory arrest 28 hours after the propylene glycol ingestion. Analysis of serum and combined urine and blood from the kidneys confirmed the presence of propylene glycol. Propylene glycol is used for the treatment and prevention of bovine ketosis, and is similar in appearance to mineral oil. The accidental administration of propylene glycol to horses may result in fatal poisoning.     

Intoxication with propylene glycol in two horses

Two horses were accidentally administered propylene glycol instead of mineral oil. After discovery of the mistake intensive medical therapy with intravenous fluids, etc. was started, and both animals recovered fully from their clinical symptoms. Veterinarians use propylene glycol as well as paraffin routinely for the treatment of their patients. Mistakes are likely to be made because both medicines and sometimes their packing have a similar appearance. Several incidents have been reported in other countries. A large amount of propylene glycol given to a horse, but also to other animals, can be dangerous and immediate adequate intervention is necessary. The major cause of the problems in case of a propylene glycol intoxication is the high concentration of D-lactate that arises. Clinically, this primarily results in a depression of the central nervous system and in metabolic acidosis. Furthermore colic, diarrhoea and respiratory problems may occur.     

Effects of trenbolone acetate and propylene glycol on pregnancy toxaemia in ewes

Eleven ewes with pregnancy toxaemia were monitored clinically and biochemically after daily treatment with trenbolone acetate (30 mg) and propylene glycol (twice daily 100 ml), for at least one week. The clinical signs of pregnancy toxaemia at first examination were less severe than those described in ewes in other countries. After the first treatment, the appetite improved in nine ewes, blood glucose levels increased in 10 ewes and blood ketone body concentrations decreased in nine animals. A statistically significant decrease in mean ketone body levels was found between the day of first examination and the second day thereafter. Four animals recovered before lambing (group 1). One animal lambed one day after the first treatment and recovered. In the remaining ewes clinical and biochemical improvement did not last long. Three of these animals did not recover until after lambing (group 2) and three animals died (group 3). In three animals of group 2 and two animals of group 3 an increase of serum activities of lactate dehydrogenase, sorbitol dehydrogenase, gamma glutamyl transferase and alkaline phosphatase was found. In two necropsied animals of group 3 a severe fatty degeneration of the liver was found. Treatment of pregnancy toxaemia with trenbolone acetate and propylene glycol appeared to have some positive effect in mild cases. In more advanced cases the time of parturition is the crucial factor leading to recovery.     

The synovial response to exogenous phospholipid (synovial surfactant) injected into the equine radiocarpal joint compared with that to prilocaine, hyaluronan and propylene glycol

AIMS: To determine the effects of the intra-articular injection of surface-active phospholipid in a propylene glycol carrier on synovial fluid composition and joint function of horses, and to compare these effects with those observed after the intra-articular administration of prilocaine, hyaluronan and propylene glycol alone. METHODS: Twenty-four horses were randomly allocated to four treatment groups: Group 1 100 mg of surface-active phospholipid in 1 ml of propylene glycol; Group 2 1 ml of propylene glycol; Group 3 10 ml of prilocaine; Group 4 2 ml of hyaluronan. Left radiocarpal joints were injected with the treatments and the right radiocarpal joints were injected with volume-matched saline as controls. Examinations for lameness, arthrocenteses and synovial fluid analyses were performed before and at 1, 3 and 7 days after injection. RESULTS: No horses became lame but treated joints temporarily developed mild to moderate effusions. Synovial fluid analyses indicated significantly greater inflammation in treated compared to control joints and this difference was greatest 24 hours after injection. There were no differences between the four treatments based on synovial fluid analysis except for neutrophil counts and alkaline phosphatase activities, which were significantly higher in prilocaine-treated joints. CONCLUSION: In horses, the intra-articular injection of surface-active phospholipid in a propylene glycol carrier induces clinically insignificant, temporary abnormalities in synovial fluid. Surface-active phospholipid was no more injurious to the synovium than prilocaine or hyaluronan. None of the agents used in this experiment caused lameness when injected into the joints of horses. RELEVANCE: This dose and formulation appear suitable for use in future experiments investigating the efficacy of surface-active phospholipid in the treatment or prevention of osteoarthritis in horses.     

Taste responses of dogs to ethylene glycol, propylene glycol, and ethylene glycol-based antifreeze

Although it is widely believed that ethylene glycol-based antifreeze (AF) is an attractive tastant to dogs and other animals, empirical data on this point are not available. In experiment 1, we examined the propensity of 178 adult mixed-breed dogs to approach, sniff, and lick a concentration of AF commonly used in automotive cooling systems (50%). Despite the fact that most of the dogs approached and sniffed the AF in these 5-minute tests, only 9% initiated lick responses and most of these were brief and not followed by additional licking. In experiment 2, the lick responses of five gastric-cannulated dogs to aqueous solutions of 20% sucrose, 50% ethylene glycol, 50% propylene glycol, water, and 50% AF were examined in 14-minute tests before and after periods of food and water deprivation. Under the latter conditions, 2 of the 5 dogs drank amounts of ethylene glycol that would have been lethal to uncannulated dogs. None of the five dogs drank potentially lethal amounts of AF. The preference order for these tastants was sucrose greater than water greater than ethylene glycol greater than AF = propylene glycol. Although these findings question the general belief that AF is highly palatable to most dogs, they do imply that large individual differences in responsiveness exist and that AF ingestion is likely influenced by motivational state. Furthermore, they suggest the possibility that unpleasant-tasting additives could be successfully developed to eliminate the ingestion of AF, because the initial attractiveness of AF is relatively low. Such additives would have to be stable in vehicular cooling systems and not adversely affect the functional aspects of AF performance.     

Influence of experimentally induced theileriosis (Theileria annulata) on the pharmacokinetics of a long-acting formulation of oxytetracycline (OTC-LA) in calves

The effects of experimental Theileria annulata infection on the i.m. (20 mg/kg) pharmacokinetics of oxytetracycline were investigated in crossbred calves. The serum concentration-time curves of oxytetracycline (OTC-LA), before and after experimental infection, were best described by a one-compartment open model. The experimental infection by subcutaneous administration of ground-up tick supernate (GUTS), equivalent to 30 Hyalomma anatolicum anatolicum ticks infected with Theileria annulata, produced a clear temperature rise and signs of clinical disease in calves. Subsequently, haemoglobin, packed cell volume, total leucocyte count and serum Cu, Fe and Zn concentrations decreased after infection. The absorption and elimination half-lives (t1/2 Ka and t1/2 Ke), mean absorbance time (MAT), time to peak concentration (Tmax), mean residence time (MRT), area under the serum concentration time curve (AUC infinity) and the bioavailability (F) were significantly (P < 0.05) decreased. The peak serum concentration (Cmax), however, remained unchanged after infection. These changes may necessitate alterations in the dosage regimen of oxytetracycline used to treat Theileria annulata infections in cattle under field conditions.     

Study of serum drug levels in calves following intramuscular administration of three tetracycline drug preparations

Three antibiotic formulations, oxytetracycline (A) in propylene glycol and oxytetracycline (B) in polyvinyl pyrrolidine and pyrrolidino-methyltetracycline in an oil suspension were given to calves by the intramuscular route. Only oxytetracycline (A) appeared to cause much pain after injection.

The half-time elimination (t_½cl) for oxytetracycline (A) was 14.000 ± 3.580 h for oxytetracycline (B) 10.290 ±5.159 h and for pyrrolidinomethyltetracycline 8.160 ± 0.920 h. The rate of elimination `beta slope” for oxytetracycline (A) was 0.052 ± 0.012 h⁻¹ for oxytetracycline (B) 0.077 ± 0.261 h⁻¹ and for pyrrolidinomethyltetracycline 0.086 ± 0.010 h⁻¹. The Y intercept of the “beta” elimination slope C_os (μg/mL) for oxytetracycline (A) was 2.490 ± 1.040, for oxytetracycline (B) 3.463 ± 1.874 and for pyrrolidinomethyltetracycline 2.852 ± 1.360.

Pyrrolidinomethyltetracycline appeared to have a two component elimination curve, however, only the “beta slope” was used for the calculations.

     

Effects of experimentally induced Theileria annulata infection on the pharmacokinetics of oxytetracycline in cross-bred calves

The effects of an experimental Theileria annulata infection on the intravenous (10 mg kg-1) pharmacokinetics of oxytetracycline (OTC) were investigated in crossbred calves. The serum concentration-time curve of oxytetracycline before and after the experimental infection was best described by an open two-compartment model. The experimental infection was induced by a subcutaneous administration of ground-up tick supernate (GUTS) equivalent to 30 Hyalomma anatolicum anatolicum ticks infected with Theileria annulata. It produced a definite temperature rise and symptoms of clinical disease in the calves. The haemoglobin, packed cell volume (PCV), white blood cell (WBC) counts and serum Cu, Fe and Zn concentrations decreased after onset of the infection. The distribution and elimination half-lives (t1/2 alpha and t1/2 beta), volume of the central compartment (Vc), AUC0-infinity, AUMC and mean residence time (MRT), were significantly reduced (P < or = 0.05) and the hybrid rate constants K12, Kel, K12/K21 ratio and total body clearance (ClB) of oxytetracycline were significantly (P < or = 0.05) increased after infection. The infection, however, had no effect on the C0, K21, apparent and steady-state volumes of distribution (Vd(area) and Vdss) of the drug. The above changes may necessitate changes in the dosage regimen of oxytetracycline used to treat Theileria infections in cattle under field conditions.     

Hematologic alterations in adult cats fed 6 or 12% propylene glycol.

Cat foods containing propylene glycol (PG) induce Heinz body formation in feline erythrocytes. To further study the hematologic importance of dietary PG, 21 adult cats were allotted to 3 groups of 7 each and fed diets containing 0, 6, or 12% PG on a dry-weight basis. Cats fed PG had a dose-related increase in Heinz bodies within 2 weeks, and the increase persisted throughout the study. Although only slight changes occurred in PCV, hemoglobin concentration, and RBC count, punctate reticulocytes were significantly increased in the group fed 12% PG. Mean RBC survival was decreased in the groups fed 6 or 12% PG by 30 and 55%, respectively, compared with the control group. These data indicate that PG-containing diets cause a dose-dependent erythrocyte destruction, even when fed at concentrations as low as 6%.     

The effects of a β2-agonist (clenbuterol), and anti-bacterial drugs (trimethoprim with sulphadiazine; oxytetracycline) on calf mucociliary clearance

A non-invasive radio-aerosol technique was employed to study mucociliary clearance patterns in three groups of four calves of different ages. The initial clearance pattern, the percentage cleared in 1 h, and the percentage cleared between 1 and 19 h were used as indices of clearance efficiency. (Percentage retention at 19 h was used as an index of alveolar deposition.) These measurements were recorded in a series of experiments designed to investigate the effects of: clenbuterol (given as a single intravenous injection, 0.75 microgram/kg); a combination of trimethoprim and sulphadiazine-TMPS (administered by intramuscular injection twice daily for 3 days: 2.5 mg/kg trimethoprim; 12.5 mg/kg sulphadiazine) alone, or with a supplementary injection of clenbuterol; and oxytetracycline (administered by intramuscular injection twice daily for 3 days; 3 mg/kg). Clenbuterol alone tended to increase clearance rate, although this effect did not achieve statistical significance. The combination of TMPS with clenbuterol produced results similar to those of clenbuterol alone. Neither TMPS nor oxytetracycline had any significant effect on indices of mucociliary clearance. Differences were observed between calves of different age groups, particularly in clearance phases between 1 and 19 h.     

Ethylene glycol toxicosis in cattle.

A 1-month-old Jersey calf died of oxalate nephropathy. The calf had access to antifreeze (ethylene glycol) 3 days prior to death. Since ethylene glycol toxicosis had not been reported in cattle, the effects or oral administration of ethylene glycol were studied in 7 calves and 3 cows. The toxic dose ranged from 2 to 10 ml of ethylene glycol per kg of body weight. Clinical signs were increased respiration, staggering gait, paraparesis, depression and later, recumbency and death. Hemoglobinuria and epistaxis were seen at doses of 10mg/kg of body weight. Azotemia, hypocalcemia and neutrophilia were constant findings whereas acidosis, plasma hyperosmolality and hemolytic anemia were seen in the animals receiving the higher doses. A diagnosis of ethylene glycol toxicosis must be based upon a history of ingestion and the presence of calcium oxalate crystals in body tissues (especially the kidney and brain).     

Effects of propylene glycol on carcass traits and its related gene expression in Korean native steers

The effects of propylene glycol (PEG) on performance, ruminal fermentation, blood glucose and insulin, carcass traits, and abundance of IGF-1 mRNA in LM and leptin mRNA in adipose tissue were examined in 20 Korean native steers, with 10 each in control and PEG-fed groups, respectively. Propylene glycol mixed with concentrate diet was provided daily at a rate of 2.5 mL/kg BW(0.75). Experimental animals were fed a concentrate diet to 1.8% of BW twice daily plus rice straw ad libitum during the 4-mo period before marketing. Daily DMI and ADG did not differ between control and PEG-fed steers. Steers receiving PEG displayed an increase (P = 0.044) in propionate concentration, whereas acetate concentration decreased (P = 0.032). Although blood glucose was not affected, serum insulin was increased (P = 0.047) by PEG feeding. Propylene glycol did not affect carcass weight, 13th-rib fat depth, marbling score, or lipid content of LM. The backfat of PEG-fed steers did not differ in leptin mRNA from control steers, whereas increased leptin mRNA was found in i.m. fat with PEG feeding. There was no treatment effect on the level of IGF-1 mRNA in the LM of the tested steers. These results indicate that the amount of PEG fed to steers was not sufficient to improve marbling score through enhanced ruminal propionate and insulin. The role of increased i.m. leptin mRNA level in PEG-fed steers remains to be further elucidated.     

Chloramphenicol, lincomycin and oxytetracycline disposition in calves with experimental pneumonic pasteurellosis

The effects of pneumonia on the pharmacokinetics of chloramphenicol, lincomycin, and oxytetracycline were evaluated in two-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures directly through the thoracic wall into each lung. Six days prior to induction of pneumonia, the antibiotics were administered in a single i.v. dose. The antibiotics were administered again 48 (i.v.), 60 and 72 h (i.m.) following injection of P. haemolytica. The pharmacokinetics of chloramphenicol (25 mg/kg) and lincomycin (10 mg/kg) were not significantly different in calves with pneumonia. The hybrid rate constant beta for oxytetracycline was increased in calves with pneumonia from 0.0034 +/- 0.0003/min to 0.0048 +/- 0.0007/min between 2 h and 8 h. Thus the elimination half-life in serum was shortened from 212.4 +/- 20.3 min to 149.3 +/- 19.5 min. In addition, there was an apparent but not statistically significant decrease in K12 with pneumonia. These findings accentuate the need for observance of 12-h dose intervals with oxytetracycline.     

A comparative study of the effects of meloxicam and flunixin meglumine (NSAIDs) as adjunctive therapy on interferon and tumor necrosis factor production in calves suffering from enzootic bronchopneumonia

The study was performed on 18 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided into three groups and respectively treated with oxytetracycline and meloxicam--Group I (9 animals); oxytetracycline and flunixin meglumine--Group II (3 animals); and oxytetracycline only--Group III (6 animals--control). The following observations were recorded before treatment (1st day) and two days later (3rd day): body temperature, the serum level of interferon (IFN) and tumor necrosis factor (TNF) as well as cytokine production by bronchoalveolar lavage (BAL) cells. The treatment of calves with a combination of oxytetracycline and meloxicam (Group I) and especially with oxytetracycline and flunixin meglumine (Group II) caused a significantly faster, in comparison to the control group, normalization of body temperature. Both drugs, meloxicam and especially flunixin meglumine, inhibited excessive TNF production in the organism (measured as the serum level of cytokine). Moreover, BAL cells isolated from calves treated with both NSAIDs were still able, ex vivo, to release TNF, in contrast to the control group (treated only with tetracycline) which lost the ability to produce TNF. The treatment of the calves with meloxicam and flunixin meglumine did not significantly influence the levels of IFN in sera but normalized ex vivo IFN production in BAL cells. These results suggest that the combination of meloxicam with an antibiotic or flunixin meglumine with an antibiotic which does not exert an immunosuppressive influence on the organism of calves suffering from enzootic bronchopneumonia is equally effective in the treatment of calves and superior to the antibiotic alone.     

Effect of steroidal and non-steroidal anti-inflammatory drugs in combination with long-acting oxytetracycline on non-specific immunity of calves suffering from enzootic bronchopneumonia

The aim of this paper was to compare the effect of flumethasone and meloxicam in combination with oxytetracycline on clinical and immunological parameters of calves suffering from enzootic bronchopneumonia. The study was performed on 30 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided randomly into three equal groups and, respectively, treated with-Group I: oxytetracycline and meloxicam; Group II: oxytetracycline and flumethasone; Group III (control): oxytetracycline only. Treatment of calves with the combination of oxytetracycline and meloxicam (Group I) caused a significantly faster, in comparison to other groups, improvement in the clinical illness index score (CIIS: cough, nasal discharge, dyspnea, depression and anorexia) and a faster normalization of body temperature. A slow decrease in white blood cell (WBC) count, the number of neutrophils, MID (mixed number of monocytes, eosinophils and basophils) and in the individual number of monocytes (CD14/CD45 positive cells) was observed in Groups I and III. In the blood of the calves which received oxytetracycline and flumethasone (Group II), leukocytosis, neutrophilia and monocytosis with concomitant lymphopenia and a low number of T cells (CD2+) was observed. Moreover, the calves treated with flumethasone exhibited a decrease in gamma-globulin concentration, and phagocytic parameters. Both drugs, flumethasone and meloxicam slightly decreased tumor necrosis factor (TNF) but meloxicam slightly increased the levels of interferon (IFN) in sera and in bronchoalveolar lavages (BALs). These results suggest that the combination of meloxicam with an antibiotic in calves suffering from enzootic bronchopneumonia is superior to the antibiotic alone and also to the combination of the antibiotic with flumethasone.     

The effect of isoprinosine and levamisole on factors relevant to protection of calves against respiratory disease

Experiments to characterize the effects of two immunomodulators, namely, isoprinosine and levamisole, on factors relevant to the resistance of calves to respiratory infection were undertaken. Daily oral doses of isoprinosine decreased the influx of neutrophils into the respiratory tract, increased membrane immunoglobulin and complement receptor expression on cells from bronchoalveolar lavage samples and decreased the severity of respiratory disease. Additional intravenous doses produced similar effects on neutrophil migration to the respiratory tract and on membrane receptor expression, but the changes were no greater than those seen with oral isoprinosine alone. No significant changes in the anti-bacterial activity of cells in bronchoalveolar lavage samples followed isoprinosine treatment. In vitro incubation of pulmonary alveolar macrophages harvested from normal calves with isoprinosine increased their expression of immunoglobulin and complement receptors. Levamisole did not affect neutrophil migration to the lower respiratory tract or membrane receptor expression by pulmonary alveolar macrophages after in vivo or in vitro treatment. The immunomodulatory effects of isoprinosine beneficially increase the resistance of calves to respiratory disease, and are potentially useful in the control of infectious diseases of farm animals.     

Antipyrine, erythromycin and oxytetracycline disposition in experimental fasciolosis.

The effects of fasciolosis on drug disposition were studied by administration of antipyrine, erythromycin and oxytetracycline to sheep and cattle. Fasciolosis was produced by administration of 200 or 400 metacercariae (MC) of Fasciola hepatica to sheep and 500 MC to cattle. The disease was subsequently confirmed by determination of plasma glutamate dehydrogenase and gamma-glutamyl transferase and identification and quantitation of mature flukes in the liver at necropsy. Acute or subacute fasciolosis in sheep was accompanied by a significant decrease in the elimination rate constant (beta) and increase in the elimination half-time (t 1/2) for antipyrine and erythromycin when compared with controls or infected sheep which had been treated with the anthelmintic luxabendazole. An increase in apparent volume of distribution (Vd) was seen only for erythromycin in sheep given 400 MC. There were no changes in the disposition of oxytetracycline in sheep with either acute or subacute infection and no effects on disposition of the three test drugs in chronically infected sheep. With early chronic disease in calves, only the disposition of oxytetracycline was affected; not that of antipyrine or erythromycin.     

Prophylactic and therapeutic application of Propionibacterium avidum KP-40 in swine and calves with acute enzootic bronchopneumonia.

The usefulness of the prophylactic or therapeutic application of Propionibacterium avidum KP-40, a potent stimulator of the monocyte-macrophage-system, was demonstrated in piglets and calves. After a 3-month-period of observation PA-treated piglets showed a significantly improved development (decreased number of infections, gain of body weight). In piglets and calves the therapeutic use of PA together with oxytetracycline proved to be superior in the treatment of acute endemic enzootic bronchopneumonia (AEB) as compared to groups of animals receiving PA or oxytetracycline alone.     

Proton nuclear magnetic resonance spectroscopy based investigation on propylene glycol toxicosis in a Holstein cow

Background

It is unknown which metabolites are responsible for propylene glycol (PG)-induced toxicosis, and a better understanding of the underlying mechanisms explaining incidences of abnormal behaviour of dairy cows fed PG is therefore needed.

Methods

The study included three cows of which one developed PG toxicosis. In order to investigate how the metabolism of PG differed in the cow developing toxicosis, proton nuclear magnetic resonance (NMR) spectroscopy was applied on ruminal fluids and blood plasma samples obtained before and after feeding with PG.

Results

PG toxicosis was characterized by dyspnea and ruminal atony upon intake of concentrate containing PG. The oxygen saturation of arterial blood haemoglobin and the oxygen pressure in arterial blood decreased along with the appearance of the clinical symptoms. NMR revealed differences in plasma and ruminal content of several metabolites between the cow responding abnormally to PG and the two control cows.

Conclusion

It is concluded that PG-toxicosis is likely caused by pulmonary vasoconstriction, but no unusual metabolites directly related to induction of this condition could be detected in the plasma or the ruminal fluid.     

Effects of experimentally induced Pasteurella haemolytica pneumonia on the pharmacokinetics of erythromycin in the calf

Pneumonic pasteurellosis was produced experimentally in 3- to 4-month-old Holstein bull calves by bilateral intrapulmonary administration of 5 X 10(7) to 10(9) colony-forming units of Pasteurella haemolytica. Of 8 calves, 4 developed minor pulmonary changes, 1 died of an apparent bacteremia within 24 hours, and 3 developed extensive pneumonic changes. At 1 week before (1 dose) and at 48, 60, and 72 hours (3 doses) after Pasteurella administration, the calves were given erythromycin at a dosage of 15 mg/kg, and the pharmacokinetic values were determined. There were statistically (P less than or equal to 0.05) significant increases in the distribution and elimination rates associated with pneumonia. The elimination half life decreased from 132.7 +/- 9.6 minutes in prepneumonic calves to 111.1 +/- 13.8 minutes and 99.7 +/- 2.6 minutes in calves with minor and with moderate pneumonic changes, respectively. There also was a decrease in apparent volume of distribution with pneumonia. Erythromycin tissue concentrations were determined 2 hours after the last dose was given to the calves with pneumonia. Tissue concentrations in the pneumonic lung areas were as high or higher than those in nonaffected lung tissues in the same animals. Because of the increased rate of elimination from serum in pneumonic calves, it may be advisable to use shorter dosage intervals in calves with severe respiratory tract disease.