Effects of Pasteurella multocida endotoxins on turkey poults

Studies of turkey poult responses to Pasteurella multocida endotoxins indicated that lipopolysaccharide (LPS) preparations from two highly pathogenic strains and free endotoxin from one of these strains were all similar in lethal toxicity. Lethal intravenous doses were generally high, 1 mg or more for 1-week-old poults (13.3 mg/kg). The toxic effects of LPS were not increased by repeated administration of small hourly doses. For both forms of endotoxin, the relationship between dose and response was considered erratic. Attempts to increase the susceptibility of poults to LPS by administering a liver-damaging substance (galactosamine) or a histamine-releasing substance (compound 48/80) or by performing surgical bursectomy were not effective. The LPS did not provoke a dermal Shwartzman reaction, even though doses used were 10 times those that produced a characteristic reaction in a rabbit.     

Equine Escherichia coli endotoxemia: comparison of intravenous and intraperitoneal endotoxin administration.

Certain physiologic and hematologic data were determined in ponies given Escherichia coli endotoxin by three routes: single IV dose, single intraperitoneal (IP) dose, and multiple IP boluses. In all ponies, the reaction was characterized by weakness, depression, peripheral circulatory abnormalities, and pyrexia. The pyrexia was more severe and was sustained in the ponies given multiple IP bolus endotoxin. Changes in packed cell volume, peripheral blood neutrophil, lymphocyte, and thrombocyte counts, and blood glucose were noticed in the three groups. Blood lactate and beta-glucuronidase values were determined and increases occurred only in the two IP endotoxin administration groups. A fibrinogen increase was observed in only the multiple IP bolus group. Attempts were made to correlate the lactate and beta-glucuronidase values with the severity and prognosis of the endotoxemia response. In general, the single IV bolus and, to a lesser extent, the single IP bolus endotoxin produced abrupt but transient responses. The multiple IP bolus endotoxin administration produced a more gradual and sustained response, which was more closely comparable with a clinical gastrointestinal disease problem than the other routes of administration produced.     

Alterations in clinical, hematological and metabolic variables in bovine neonatal endotoxemia.

Endotoxemia is an important cause of morbidity and mortality in the neonate. Although many models are used to study the problem, none completely simulates the natural disease. To more clearly define a bovine neonatal endotoxemia model we studied the effects of dose of endotoxin on clinical, hematological and biochemical variables. Thirty-four neonatal calves were administered Escherichia coli endotoxin (LPS) at 0 (0.9% saline solution), 0.2, 2.0 or 20 micrograms/kg, by either IV bolus or infusion over 50 minutes. Variables monitored included mean arterial blood pressure (MAP), leukocyte (WBC) count, plasma glucose and lactate concentrations and clinical status. All LPS-treated calves displayed similar clinical signs within one hour. Dose-dependent differences in response to LPS among groups became evident over time. Substantial dose-dependent changes in attitude, appetite, mucous membrane character, capillary refill time, MAP, plasma glucose and lactate concentrations, and WBC count were noted in LPS-treated calves. Higher doses of LPS induced a more prolonged clinical response and significantly (p < 0.05) greater hypotension, lacticemia and hypoglycemia. While dose altered the response to endotoxin, the method of administration had no overall effect on the variables measured.     

Effects on plasma endotoxin and eicosanoid concentrations and serum cytokine activities in horses competing in a 48-, 83-, or 159-km endurance ride under similar terrain and weather conditions

OBJECTIVE: To determine plasma endotoxin concentration in horses competing in a 48-, 83-, or 159-km endurance race and its importance with regard to physical, hematologic, or serum and plasma biochemical variables. ANIMAL: 3 horses. PROCEDURE: Weight and rectal temperature measurements and blood samples were obtained before, during, and after exercise. Blood samples were analyzed for plasma endotoxin concentration; serum antiendotoxin antibody titers; thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha (PGF1alpha) concentrations; tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) activities; WBC, plasma protein, lactate, serum electrolyte, and calcium concentrations; PCV; and creatine kinase activity. RESULTS: Detection of plasma endotoxin increased during exercise for horses competing at all distances but occurred more frequently in the 48- and 83-km groups. Plasma lactate concentration was significantly greater when endotoxin was concurrently detected. Endotoxin in plasma was not significantly associated with success of race completion. Plasma TxB2 and PGF1alpha concentrations and serum IL-6 activity significantly increased with exercise. Horses that had an excellent fitness level (as perceived by their owners) had greater decreases in serum antiendotoxin antibody titers during exercise than did horses perceived as less fit. In horses with better finish times, TxB2 and PGF1alpha concentrations were significantly greater and TNFalpha activity was significantly less than that of slower horses. CONCLUSIONS AND CLINICAL RELEVANCE: Endotoxemia developed during endurance racing, but was significantly correlated with increased plasma lactate concentration and not with other variables indicative of endotoxemia. Plasma TxB2 and PGF1alpha concentrations and serum TNFalpha activity may be associated with performance success.     

Effect of Escherichia coli endotoxin on tissue lipoprotein lipase activities in chickens

1. Four-week-old broiler chickens were injected intravenously with from 0.01 to 1 mg of E. coli endotoxin/kg body weight or with saline. 2. At all doses used endotoxin markedly depressed food intake and lipoprotein lipase activities in muscle and adipose tissue within 8 h. Heart lipoprotein lipase activity was significantly depressed only at doses of 0.1 mg endotoxin/kg body weight or greater. 3. Treatment of birds with 0.3 mg endotoxin/kg body weight reduced post-heparin lipoprotein lipase activity to 0.13 of that in control birds in 8 h. 4. Endotoxin generally depressed plasma very-low-density lipoprotein concentration. Plasma non-esterified fatty acid concentration was significantly elevated only in birds given 1 mg endotoxin/kg body weight. 5. Fatty acid synthetase activity in the liver of endotoxin-treated birds was significantly lower than in control birds 16 h after administration of endoxin, but not after 8 h. 6. These results show that tissue lipoprotein lipase activity in birds is very responsive to E. coli endotoxin, as in mammals. Hypertriglyceridaemia occurs only occasionally in endotoxin-treated chickens, most probably because of the particularly close relationship between food intake and hepatic lipoprotein synthesis in birds.     

Effects of inhalation of dust and endotoxin on respiratory tracts of pigs.

OBJECTIVE: To assess the effects of inhalation of feed flour dust and dustborne endotoxin on respiratory tracts of pigs. ANIMALS: 29 healthy Belgian Landrace pigs. PROCEDURE: Pigs housed in an environmental chamber were exposed for 6 days to feed flour dust (1 to 15 mg/m3) and dustborne endotoxins (50 to 2,500 ng/m3). Effects were evaluated by measuring albumin concentration, lactate dehydrogenase (LDH) activity, cell composition of nasal lavage (NL) and bronchoalveolar lavage (BAL) fluids and blood, and percentages of CD4+ and CD8+ T lymphocytes in blood and lavage fluids. Dustborne endotoxin was obtained by mixing endotoxins from Escherichia coli (serotype O127:B8) with feed flour before spraying the flour in the environmental chamber. RESULTS: Exposure did not affect cell composition of NL fluid or blood. Total cell counts of BAL fluids were increased in all groups exposed to dust. Macrophage counts were increased in pigs exposed to inhalable dust concentrations as low as 4.4 mg/m3, and lymphocyte counts were increased in groups exposed to high dust concentrations. Percentages of CD4+ and CD8+ T lymphocytes in blood and lavage fluids were unchanged. In all dust-exposed groups, albumin content of BAL fluid was increased, whereas LDH activity was unaffected. Macrophage and lymphocyte infiltration and edema in the bronchi were identified by light microscopy. Effects attributable to E. coli endotoxin exposure were not identified. CONCLUSIONS: Inhalation of feed flour dust did not affect nasal mucosa but did induce bronchial airway inflammation. Dustborne endotoxins did not have effects attributable to endotoxin alone.     

Effect of Escherichia coli endotoxin and thyrotropin-releasing hormone on prolactin in lactating sows

Primiparous gilts were given subcutaneous injections of saline solution or 8 mg of Escherichia coli endotoxin (055:B5 strain) in saline solution on postpartum days (PPD) 2 and/or 6 and saline solution at the same site on PPD 1, 3, 5, and 7 at 1000 hours. On PPD 1 to 3 and on PPD 5 to 7, pigs were given 100 micrograms of thyrotropin-releasing hormone (TRH) IV at 1300 hours to evaluate TRH-induced prolactin (PRL) release. Blood samples were analyzed for PRL, cortisol, triiodothyronine (T3), and tetraiodothyronine (T4) concentrations. Rectal temperatures were monitored at hourly intervals between 0800 and 1500 hours on PPD 2 and 6. The PRL declined after endotoxin administration on PPD 2, but a similar decline was not seen after saline solution administration on PPD 1, 2, or 3. The PRL concentrations remained unchanged on PPD 5, 6, and 7 in gilts exposed to endotoxin for the 1st or 2nd time on PPD 6 and to saline solution on PPD 5 and 7. The TRH injection caused increases in PRL in all animals, but the PRL increase after TRH injection was significantly lower (P less than 0.05) in gilts treated with endotoxin on PPD 2. Cortisol concentrations increased after endotoxin exposure on PPD 2 and 6. Rectal temperatures increased after endotoxin exposure on PPD 2 and 6 with peak temperatures of 41.8 C and 41.6 C seen 4 and 3 hours, respectively, after endotoxin injection. The T3 and T4 response, used as an indicator of TRH perfusion of the adenohypophysis, was unchanged after endotoxin or saline solution administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of arachidonic acid metabolism in endotoxic horses: comparison of flunixin meglumine, phenylbutazone, and a selective thromboxane synthetase inhibitor

Two cyclooxygenase inhibitors (flunixin meglumine and phenylbutazone) and a selective thromboxane synthetase inhibitor were assessed in the management of experimental equine endotoxemia. Drugs or saline solution were administered to 16 horses 15 minutes before administration of a sublethal dose of endotoxin (Escherichia coli 055:B5). Plasma concentrations of thromboxane B2 (TxB2), prostacyclin (6-keto PGF1 alpha), plasma lactate, and hematologic values and clinical appearance were monitored for 3 hours after endotoxin administration. Pretreatment with flunixin meglumine (1 mg/kg of body weight) prevented most of the endotoxin-induced changes and correlated with a significant decrease in plasma TxB2 and 6-keto PGF1 alpha concentrations, compared with concentrations in nontreated horses (ie, pretreated with saline solution). Pretreatment with phenylbutazone (2 mg/kg) attenuated the effects of endotoxin and was associated with a brief, early, significant increase in plasma TxB2 concentrations, but not in plasma 6-keto PGF1 alpha concentrations. Pretreatment with the thromboxane synthetase inhibitor did not appear to clinically benefit the horses involved; however, arachidonic acid metabolism was redirected to prostacyclin production.     

Mixed venous oxygen tension as an estimate of cardiac output in anesthetized horses

The relationship between mixed venous O2 tension and cardiac output was studied in six anesthetized horses breathing 100% O2. Cardiac output, O2 consumption, mean arterial pressure, heart rate, and arterial and venous blood gases were measured after administration of xylazine or dobutamine to horses in lateral, sternal, and dorsal recumbencies. After approximately 3 hours, Escherichia coli endotoxin was administered while horses were in dorsal recumbency, and all measurements were repeated. Relationships between cardiac index (CI) and PVO2, heart rate, mean arterial pressure, jugular PVO2, and PVO2 of blood from a superficial limb vein were evaluated by linear regression analysis. Mean arterial pressure was significantly (P less than 0.05) correlated with CI in horses in all positions and after endotoxin administration. However, data points were poorly grouped. Heart rate and CI were significantly correlated in horses in all positions, but not after endotoxin administration. Correlations between jugular PVO2 and PVO2 of blood from a superficial limb vein were not significant in horses in sternal recumbency, and PVO2 of blood from a superficial limb vein was not significantly correlated with CI in horses in lateral recumbency. There was a significant and tight correlation between PVO2 and CI in horses in all positions and after endotoxin administration.     

Effect of endotoxin administration on body fluid compartments in the horse

Plasma volume, extracellular fluid volume (ECFV), and total body water (TBW) were measured before and after endotoxin (Escherichia coli) administration in 6 conscious adult horses. Evan's blue dye, sodium thiocyanate, and antipyrine were the test substances used to estimate plasma volume, ECFV, and TBW, respectively. Pharmacokinetic analysis of plasma concentration vs time was used to determine changes in body fluid compartments. The pathophysiologic effects of endotoxin were monitored by clinical evaluation, blood chemical changes, and blood gas determinations. All horses became dyspneic within 15 minutes of endotoxin administration and clinical signs of colic were evident 30 to 45 minutes after endotoxin administration. After endotoxin administration, serum glucose and creatinine concentrations were significantly (P less than 0.05) elevated, and all horses became hypoxic and developed marked metabolic acidosis, and plasma volume decreased approximately 15% (P less than 0.05). A significant change in ECFV or TBW during the 300-minute experimental period was not observed.     

Acute phase response in calves following infection with Pasteurella haemolytica, Ostertagia ostertagi and endotoxin administration

The concentrations of bovine acute phase proteins were monitored in plasma following experimental infection with Pasteurella haemolytica and Ostertagia ostertagi and after endotoxin administration. Raised levels of haptoglobin, alpha 1 proteinase inhibitor and seromucoid were detected after pasteurella infection and endotoxin administration. Ceruloplasmin levels increased after endotoxin administration but not during pasteurella infection. Raised levels of the four acute phase proteins were found in eight of 19 calves infected with ostertagia but showed a variable pattern and did not correlate with plasma pepsinogen increases. Bovine alpha 1 antichymotrypsin and alpha 2 macroglobulin were identified as acute phase reactants.     

Pathologic changes and tissue gentamicin concentrations after intravenous gentamicin administration in clinically normal and endotoxemic cats

Hematologic and serum biochemical values, tissue gentamicin concentrations, and renal pathologic changes were determined in clinically normal and endotoxemic cats given 3 mg of gentamicin/kg of body weight, IV. Endotoxemia was induced by IV administration of 0.5 microgram of Escherichia coli endotoxin/kg of body weight. In experiment 1, 6 cats were given endotoxin. After rectal temperature increased at least 1 degree C, cats were given gentamicin. Blood samples were collected before and at 1 and 3 hours after administration of gentamicin. With the exception of severe leukopenia, other hematologic changes or changes in serum biochemical values were not observed. In experiment 2, 24 cats were allotted to 4 groups and were given gentamicin, endotoxin, gentamicin plus endotoxin, or neither substance. Three hours later, cats were euthanatized, and tissue and body fluid specimens were obtained and were assayed for gentamicin concentration. Kidney specimens were examined microscopically. Endotoxemic cats had more gentamicin in the renal medulla than did control cats, but none of the cats had detectable renal lesions. The possible nephrotoxic synergism between gentamicin and severe endotoxemia and the lack of major differences in gentamicin concentration in extrarenal tissues indicated that the dosage of gentamicin in endotoxemic cats does not have to exceed the dosage recommended for clinically normal cats. A single dose of gentamicin administered IV did not cause renal damage in mildly endotoxemic cats, but nephrotoxicity ascribed to multiple doses of gentamicin in more severely endotoxemic cats needs to be evaluated.     

Endotoxin release after antimicrobial treatment in sick foals is mediated by antimicrobial class

The objective of this study was to determine whether treatment with antimicrobials leads to increased serum endotoxin concentrations in sick foals and to further determine whether an effect of class of antimicrobial on endotoxin release occurs in sick foals in vivo. This was a prospective, observational study at a university equine hospital. Twenty-four foals aged 12 hours to 12 days admitted to the hospital in 2004 and 2005 were used. Blood was collected from all foals at time 0 (admission) and at 30 minutes, 8 hours, 12 hours, and 24 hours after treatment with an antimicrobial. The choice of antimicrobial was determined by the clinician caring for the foal, and any other treatment, as deemed necessary for appropriate care of the foal, was employed. For each serum sample, the endotoxin concentration was determined using the limulus amebocyte lysate assay. Those foals that received a beta-lactam alone, more specifically the cephalosporin ceftiofur, showed a significant increase in endotoxin concentration 12 hours after antibiotic administration (P = .005). An increase in serum endotoxin concentration was not seen in the first 24 hours after antimicrobial administration when foals were treated with a combination of beta-lactam and aminoglycoside antimicrobials. In conclusion, a significant increase in endotoxin concentration as a consequence of ceftiofur administration occurs in sick foals. Administration of a combination of a beta-lactam antimicrobial and an aminoglycoside did not result in a significant increase in endotoxin release. Consideration of these findings should be made when choosing antimicrobial therapy for the sick foal.     

Adverse effects of a proposed equine sublethal endotoxin model

Commercially available Escherichia coli 055: B5 lipopolysaccharide was administered intravenously experimentally at a dosage of 10 micrograms/kg to 2 horses. Various clinical and clinico-pathological parameters were monitored before and after the endotoxin administration. Because of a hopeless prognosis, and for humane reasons, euthanasia was applied on both horses 6 h after administration. Values recorded for the different parameters, including the blood lactate level, were consistent with a lethal condition. It would appear that an intravenous dose of 10 micrograms/kg of endotoxin is potentially lethal to horses.     

Influence of intramammary infusion of polymyxin B on the clinicopathologic course of endotoxin-induced mastitis

The influence of giving 1 dose of polymyxin B (1.6 X 10(6) U/quarter) by the intramammary route to dairy cows to modify the clinicopathologic course of mastitis induced by intramammary infusion of Escherichia coli endotoxin (1 mg/quarter) was examined. Pretreatment with polymyxin B or its simultaneous administration reduced and delayed the typical febrile and leukopenic responses to endotoxin infusion, prevented an increase in plasma lactate dehydrogenase activity and a reduction in plasma zinc concentration, but only marginally influenced the degree of udder inflammation and had no effect on leukocytosis in the milk. Intramammary infusion of polymyxin B at 30 or 60 minutes after endotoxin was infused prevented the increase in plasma lactate dehydrogenase activity and moderated the decrease in plasma zinc concentration, but otherwise failed to alter the clinicopathologic course of endotoxin-induced acute mastitis.     

Low dose flunixin meglumine: effects on eicosanoid production and clinical signs induced by experimental endotoxaemia in horses

The efficacy of low doses of flunixin meglumine in reducing eicosanoid generation and clinical signs in response to experimentally induced endotoxaemia was investigated. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in serum and plasma by radioimmunoassay. Plasma flunixin concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters derived non-compartmentally. In horses administered flunixin meglumine before endotoxin challenge, a significant suppression in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha generation was observed. Elevations in blood lactate were significantly suppressed in horses pretreated with 0.25 mg/kg bodyweight flunixin meglumine. Reduction of the clinical signs of endotoxaemia by flunixin meglumine was dose dependent. Low doses of flunixin inhibited eicosanoid production without masking all of the physical manifestations of endotoxaemia necessary for accurate clinical evaluation of the horse's status.     

Efficacy of flunixin meglumine for the treatment of endotoxin-induced bovine mastitis

The clinical effect of flunixin meglumine administration was determined in cows with acute mastitis induced by intramammary administration of endotoxin. In 12 lactating cows, 10 micrograms of Escherichia coli 026:B6 endotoxin were administered via a teat cannula into the teat cistern of single randomly selected rear quarters. Cows were challenge exposed as pairs. One cow in each pair was administered parenteral flunixin meglumine (6 cows) and 1 cow per pair was administered saline solution (6 cows). Multiple doses (7) of 1.1 mg of flunixin meglumine/kg of body weight or saline solution were administered at 8-hour intervals beginning 2 hours after endotoxin. Cow and quarter clinical signs as well as milk somatic cell concentrations, bovine serum albumin, electrical conductivity, and milk production were determined before and for 14 days after endotoxin inoculation. Intramammary endotoxin produced signs characteristic of acute coliform mastitis. Quarter and systemic abnormalities occurred and milk production was reduced by approximately 50% at 12 hours after endotoxin. Flunixin meglumine therapy significantly (P less than or equal to 0.05) reduced rectal temperatures and quarter signs of inflammation and improved clinically graded depression when compared with these signs in saline solution-treated controls. Milk production and laboratory indicators of inflammation in milk were not significantly (P greater than 0.05) different for flunixin meglumine vs saline solution controls. The clinical response observed was consistent with the antipyretic, analgesic, and anti-inflammatory properties of flunixin meglumine.     

Some effects of gram-negative bacterial endotoxin and its importance as a contaminator of biological preparations

The purpose of this study was to establish a model which can be used to examine the biological response to Salmonella typhimurium endotoxin in both anaesthetized and unanaesthetized rabbits, and then compare this response to that of rabbits injected with an endotoxin-contaminated biological preparation. The parameters used to evaluate the biological response included total white blood cell and differential counts, 15-ketodihydro-PGF2 alpha concentration, and rectal temperature. Unanaesthetized groups of rabbits received 1000, 100, 10, or 1 ng/kg of the endotoxin via intravenous injection (i.v.); the anaesthetized group of rabbits received 100 ng/kg endotoxin i.v. (anaesthesia induced with Hypnorm). In addition, groups of rabbits were treated under anaesthesia with Pharmacia-Chiron's recombinant human Cu/Zn superoxide dismutase (SOD) (10 mg/kg body weight = 1.6 endotoxin units (EU)/kg) or Grünenthal's bovine SOD (two doses: 10 mg/kg = 400 EU/kg, or 50 mg/kg = 2000 EU/kg). Results demonstrated that at the lower doses of endotoxin (10 and 1 ng/kg) and r-hSOD (10 mg/kg), no leukopenia was observed. There was however a slight shift in the leukocyte population so that polymorphonucleocytes increased and monocytes decreased in number. Rabbits treated with higher doses of endotoxin (1000 and 100 ng/kg) showed many of the common signs of endotoxemia, including leukopenia, increased prostaglandin metabolite levels, and increased body temperature, as did the rabbits treated with endotoxin-contaminated bSOD. There was a definite dose-dependency, with the higher dose of bSOD giving a more marked rise in all parameters. These findings indicate that use of this or other endotoxin-contaminated biological preparations in live-animal experiments could produce erratic, and therefore unreliable, results.     

A pharmacokinetic study of amoxycillin in febrile beagle dogs following repeated administrations of endotoxin

The pharmacokinetics of amoxycillin was studied in nine male beagle dogs under healthy and febrile conditions. In Period 1, dogs received 20 mg/kg of an oral suspension of amoxycillin. Intravenous doses of saline, 2 and 20 microg/kg of endotoxin (LPS from Escherichia coli serotype) were administered to dogs (three per group) prior to administration of 20 mg/kg of amoxycillin in Period 2. Rectal temperature and behavioral changes were recorded and blood samples were collected over 12 h for pharmacokinetic analysis. Amoxycillin was assessed in plasma using liquid chromatography coupled with mass spectrometry. Plasma concentrations were analysed using a one-compartment model with lag-time for absorption using an iterative two-stage method. As compared with control groups, amoxycillin clearance decreased significantly with preliminary treatments of 2 microg/kg endotoxin (0.209 vs. 0.140 L/h kg, P < 0.05) and 20 microg/kg endotoxin (0.214 vs. 0.075 L/h kg, P < 0.05). As a result of this, the area under curve for the 2 and 20 microg/kg endotoxin groups increased significantly 100.4 vs. 149.4 microg h/mL (P < 0.05) and 99.2 vs. 277.7 microg h/mL (P < 0.05), respectively. Other drugs currently used for the treatment of fever and septic shock should be re-evaluated using a febrile animal model to avoid improper dose administration.     

Effect of repeated administration of tirilazad mesylate on healthy and endotoxemic calves: a pilot study.

Tirilazad mesylate (TM:U74006F), a nonglucocorticoid 21-aminosteroid (lazaroid), is beneficial in the treatment of experimentally-induced ischemic injury following brain and spinal cord trauma, subarachnoid hemorrhage, hypovolemic shock and endotoxemia. This study investigated the effects of TM following repeated administration in sixteen healthy and endotoxemic calves. Group A calves received TM 3 mg/kg IV; group B calves received Escherichia coli endotoxin in increasing doses (0.1 to 20 micrograms/kg IV); group C calves received TM and endotoxin and group D calves received sterile saline (10 mL). Endotoxin, TM and saline were given every eight hours for five days. Mild, transient tachypnea was observed following TM administration. The drug suppressed clinical signs of endotoxemia until larger doses of endotoxin were given. At necropsy no substantial lesions were observed in groups A and D. Groups B and C had lesions consistent with endotoxemia but only group C calves had evidence of abomasal and ruminal ulceration. Although TM may be of benefit in the treatment of endotoxemia, further studies are needed to determine the optimal dosage and potential side effects in the endotoxic bovine neonate.