Suppression of preovulatory luteinizing hormone surges in heifers after intrauterine infusions of Escherichia coli endotoxin

A study was conducted to test the hypothesis that high cortisol concentrations associated with products of infections (endotoxin) cause derangement in the neuroendocrine mechanism controlling ovulation in heifers. Eight Holstein heifers were given 2 injections of prostaglandin (PG), 11 days apart, to synchronize estrus. Starting from 25 hours after the second injection of PG (PG-2), the uterus of each heifer was infused with 5 ml of pyrogen-free water (control, n = 3) or Escherichia coli endotoxin (5 micrograms/kg of body weight) in 5 ml of pyrogen-free water (treated, n = 5), once every 6 hours for 10 treatments. Blood samples were obtained every 15 minutes via indwelling jugular catheter for an hour before and 2 hours after each infusion, then hourly until an hour before the next infusion. Ultrasonography of the ovaries was performed every 12 hours, starting 24 hours after PG-2 injection until 96 hours after PG-2 injection. Serum concentrations of luteinizing hormone and cortisol were determined by validated radioimmunoassays. Changes in cortisol concentrations were not detected in control heifers with preovulatory luteinizing hormone surges at 60 to 66 hours after PG-2 injection, followed by ovulations 72 to 96 hours after PG-2 was injected. None of the treated heifers ovulated, and the resulting follicular cysts (14 to 18 mm diameter) persisted for 7 to 21 days. In all treated heifers, serum cortisol concentrations increased (4- to 10-fold) during the first 2 hours after each infusion and then decreased gradually until the next infusion. Luteinizing hormone concentrations remained at baseline values throughout the treatment period in all treated heifers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haematological changes in buffalo calves inoculated with Escherichia coli endotoxin and corticosteroids

Haematological studies were conducted on 10 clinically normal water buffalo calves to determine leucocytic responses to Escherichia coli endotoxin, prednisolone and dexamethasone. Intravenous injection of 10 micrograms endotoxin induced minimal decreases in leucocyte numbers, whereas 20, 50 and 100 micrograms produced a marked leucopenia within one hour. Moderate to marked leucopenia, neutropenia and lymphopenia persisted for three to 14 hours. Significant rebound neutrophilia was evident at six to eight hours after inoculation in calves given only 10 and 20 micrograms. Intramuscular injection of prednisolone (100 mg) and dexamethasone (5 mg) produced increases in total leucocyte counts and neutrophil numbers within two hours. Moderate to marked leucocytosis and neutrophilia persisted for eight to 24 hours. Lymphocyte response was unlike that in other species in that lymphopenia was not a consistent feature of the corticosteroid response. A transient monocytosis was seen following administration of prednisolone but not of dexamethasone, while eosinopenia and basopenia developed in both cases. In conclusion, endotoxin and corticosteroid induced changes in total and differential leucocyte counts in water buffalo were largely similar to those seen in cattle.     

Leucocytic changes in cows given intravenous injections of Escherichia coli endotoxin.

Single intravenous injections of Escherichia coli endotoxin into normal cows produced dose dependent leucocytic and febrile responses. Injections of 5 to 20 microgram endotoxin induced a neutrophilia between 4 and 8 h, whereas 50 to 500 microgram produced a severe neutropenia for 4 to 6 h followed by a gradual increase in neutrophils along with slight to moderate left shift. Higher doses caused progressively severe lymphopenia and greater increase in fever than the lower doses. It was concluded that blood leucocytic changes during the early part of endotoxin-induced mastitis are partly related to systemic absorption of endotoxin, and that the size of the bone marrow neutrophil reserve in the cow could be estimated by injecting 5 to 10 microgram of endotoxin intravenously.     

Acute phase response in reindeer after challenge with Escherichia coli endotoxin

The serum concentrations of two acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid-A (SAA), were monitored in reindeer after challenge with endotoxin. Four adult female reindeer received either 0.1 μg/kg Escherichia coli 0111:B4 lipopolysaccharide B or saline solution intravenously. At the second challenge, the treatments were reversed. In addition to the APPs, changes in blood chemistry and rectal temperature were monitored. The endotoxin challenge caused a significant increase in SAA (peak 48 h) and a sharp decrease (8–12 h) of serum iron concentrations in all animals. The mean Hp concentration increased at 8 h and remained elevated until 48 h, but no statistically significant differences were found. This investigation demonstrates that challenge with a single-bolus dose of E. coli endotoxin can activate the acute phase response (APR) and SAA appears to be a more sensitive indicator of the APR than Hp during bacterial infection in reindeer.     

Pharmacokinetics of gentamicin in cats given Escherichia coli endotoxin

Nineteen cats were given 3 mg of gentamicin sulfate/kg of body weight by rapid IV, SC, or IM injection for baseline values. Serum concentration of gentamicin vs time data were analyzed using a noncompartmental model based on statistical moment theory. One week later, each cat was given 0.5 microgram of Escherichia coli endotoxin/kg, IV. After cats had an increase in rectal temperature of at least 1 C, 3 mg of gentamicin/kg was administered by the same route used the previous week. Serum concentration of gentamicin vs time data were analyzed, and pharmacokinetic values were compared with base-line values. For IV studies, the half-life (t1/2) of gentamicin and the mean residence time were significantly different (P less than 0.05) compared with base line, whereas the total body clearance and apparent volume of distribution at steady state were not. The harmonic mean +/- pseudo SD for the t1/2 of gentamicin after IV administration was 76.8 +/- 12.6 minutes for base line and was 65.2 +/- 12.2 minutes in the same cats given endotoxin. The t1/2 of gentamicin after SC administration was 74.6 +/- 6.2 minutes for base line and was 65.2 +/- 13.6 minutes in the same cats given endotoxin. After IM administration, the t1/2 of gentamicin was 60.3 +/- 10 minutes for base line and was 59.7 +/- 13.6 minutes in the same cats given endotoxin. After IV administration of gentamicin, the arithmetic mean +/- SD for the mean residence time was 102.4 +/- 16.1 minutes for base line vs 79.2 +/- 18.4 minutes in the same cats given endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma concentration of sulphadimethoxine in pigs after multiple dosing and during injections of Escherichia coli endotoxin

The effect of endotoxin induced fever on the steady state concentration of sulphadimethoxine in pigs has been studied.Sulphadimethoxine 20 mg/kg b.wt. was injected at 9 a.m. in an ear vein each day for eleven days. From day 6 until the end of the experiment, endotoxin fromEscherichia coli 1.5 g/kg b.wt. was injected at 9 a.m. and at 3 p.m. The plasma concentration versus time curves were calculated by means of a computer program, assuming a two-compartment model. During the endotoxin injections the plasma concentrations were simulated and compared with those calculated.It was not possible to show any clinically significant changes in pharmacokinetics of sulphadimethoxine after the start of endotoxin injections.     

Dose-response of ponies to parenteral Escherichia coli endotoxin.

The response of the pony to increasing doses of Escherichia coli endotoxin was evaluated using intravenous and intraperitoneal administration models. Marked changes were seen in all parameters measured following endotoxin administration. Leukopenia (neutropenia, lymphopenia) and thrombocytopenia were not dose-dependent. Similarly, elevated plasma fibrinogen and altered glucose concentrations (hyperglycemia and hypoglycemia), pyrexia and increased lactate/pyruvate ratios were apparent at all endotoxin doses but were not dose related. The widely used packed cell volume and capillary refill time, we well as blood lactate and possibly serum beta-glucuronidase, were increased in a dose-related manner.     

Hemodynamics, plasma eicosanoid concentrations, and plasma biochemical changes in calves given multiple injections of Escherichia coli endotoxin

Twelve male neonatal calves (39 to 50 kg) were allotted to 3 groups of 4 calves each. All calves were anesthetized with halothane, and then Escherichia coli endotoxin was given intravenously (3 times) and intraperitoneally (3 times) during a 6-hour period. Group-1 calves were untreated, group-2 calves were pretreated with a low dose of flunixin meglumine (1.1 mg/kg of body weight), and group-3 calves were pretreated with a high dose of flunixin meglumine (4.4 mg/kg). In calves of group 1, the mean systemic arterial blood pressure (MABP) and cardiac output (CO) decreased, but pulmonary arterial pressure increased after the initial intravenous and intraperitoneal injections of endotoxin. In calves of this group, these changes were accompanied by increased plasma thromboxane B2 (TxB2) concentration. During this period, increased plasma TxB2 concentration or hemodynamic changes were not detected in calves of groups 2 and 3. Only calves of group 1 had altered hemodynamics early in the experiment; however, after 6 hours, calves of all 3 groups had similarly decreased CO and MABP. In calves of the untreated group, plasma 6-keto-prostaglandin (PG)F1 alpha concentration increased steadily from the beginning of the experiment until 3 hours later. The CO and MABP were low at the time when serum 6-keto-PGF1 alpha concentration was high; however, these 2 measurements also were low in treated calves who did not have correspondingly high plasma 6-keto-PGF1 alpha concentration. Regional blood flow analysis did not reveal correlations between prostanoid concentrations and altered blood flow to selected tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Study of the pathological effect of Escherichia coli endotoxin in rams

This experimental study was carried out on nine adult rams. Rams were injected intravenously with Escherichia coli endotoxin serotype 055:B5. The regimen of injections is described fully. Blood and semen samples were collected periodically to evaluate the changes in blood and semen picture. The reproductive as well as the visceral organs were collected and examined macroscopically and microscopically. The results of the study revealed that sperm cell abnormalities and serum testosterone level were increased, and sperm acrosomal abnormalities were significantly increased. The total leucocytic count was significantly decreased. The histopathological examination revealed severe testicular degeneration in addition to various other lesions in the visceral organs. Scanning electron microscope of the sperm cells revealed detached acrosomes, knobbed acrosomes and coiled tails.     

Clinical and clinico-pathological effects of Escherichia coli endotoxin in mature cattle.

The effects of intravenous administration of Escherichia coli endotoxin were studied in eight mature lactating cows. Three cows were studied following intrammary infection with E. coli. Significant clinical findings are presented. Significant clinico-pathological findings include leukopenia, decreased blood serum calcium concentrations and increased levels of serum glutamic-oxaloacetic transaminase and serum ornithine-carbamyl transferase. Significant elevations of plasma corticosteroids were also noted.     

Pharmacokinetics of ivermectin in sheep following pretreatment with Escherichia coli endotoxin

The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2 mg/kg. Ten Suffolk Down sheep, 55 ± 3.3 kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1 μg LPS/kg bw at ?24, ?16, and ?0.75 hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2 mg IVM/kg was administered 45 min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non‐compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half‐life (2.85 days), mean residence time (MRT) (2.27 days), area under the plasma concentration curve over time (AUC, 117.4 ng day^?1 ml^?1), volume of distribution (875.6 ml/kg), and clearance (187.1 ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E. coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.     

Gentamicin pharmacokinetics in horses given small doses of Escherichia coli endotoxin

The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 healthy horses and in 6 horses after they were given Escherichia coli endotoxin (0.113 microgram/kg). In the horses given endotoxin, there were a maximum temperature increase of 1.97 +/- 0.44 degrees (C) and a fever index (between the 2 groups) of 8.754 units. Other mild signs of endotoxemia also occurred. Statistically significant changes were not observed in the rate constants for distribution (alpha) or elimination (beta) or in body clearance (ClB) of gentamicin in the 2 groups of horses. In the horses given endotoxin, significant (P less than 0.05) increases were found in the serum concentration data (A, B, and CoS), and significant decreases were found in the apparent volume of distribution [Vd(area)] and in the volume of the central compartment (Vc). The alterations in gentamicin kinetics in the horses given endotoxin are believed to result from the decrease in Vc. This indicates that the extracellular fluid volume available for gentamicin distribution may be reduced by endotoxin.     

Morphologic changes in the intestine of swine after infection with verotoxin-producing Escherichia coli

Spontaneous morphologic lesions are described in 12 of 66 pigs submitted for necropsy. All 12 pigs were culture positive for Verotoxin-producing E. coli (VTEC). 10 of them were weaned pigs, one a suckling piglet and one a fattening hog. In 6 cases E. coli serovar 0139:H1 and in one case each the serovars 0139:H40; 0138:H-; 0125ac:H27 and 0154:H- were isolated. From the fecal samples of 2 animals E. coli ONT (O-group non typable):H- were cultured. Macroscopically there were cyanosis, edema of the eye lids, catarrhal enteritis and/or colitis as well as edema of the mesentery, swelling of the mesenteric lymph nodes and congestion of the lung to varying degrees. Histopathologic examination of 5 animals was carried out. In 3 animals atrophy and edema of the villi in the jejunum and ileum were discovered. In one animal an additional infection with corona virus was confirmed electron microscopically. Furthermore there was disseminated necrosis of lymphocytes in Peyer's patches of the small intestine and in secondary follicles of the mesenteric lymph nodes. In one of the animals a hemorrhagic-necrotising ileitis, occurred characterized by necrosis of villi and thrombosis of blood vessels in the mucosa. The highest number of VTEC with seven out of twelve animals was found in weaned pigs in association with the E. coli serovar 0139.     

The effects of Escherichia coli and its endotoxin on amyloidogenesis in ducks.

To compare the effects of two inocula on the induction of amyloidosis in normal and thymectomized ducks, 180 normal and 50 thymectomized ducks were injected intravenously weekly for up to 16 weeks with either crude endotoxin or crude whole cell extract of a virulent strain of Escherichia coli (O78), and another 60 ducks were injected with normal saline as study control. During the first 5 weekly injections, the initial doses of inducing agents were the smallest and then adjusted upward to the maximum study doses (1 or 2 mg/bird of crude endotoxin and 15-18 x 10(8) bacteria/bird of crude whole cell extract), which were then maintained over the course of the study. The incidence of amyloid deposition were: 50.00% (25/50) for thymectomized ducks that received 1 mg/bird/week of crude endotoxin, 61.67% (37/60) for intact ducks that received 15 x 10(8)-18 x 10(8) bacteria (crude whole cell extract)/bird/week, 53.33% (32/60) for intact ducks received 2 mg/bird/week of crude endotoxin, and 63.33% (38/60) for intact ducks received 1 mg/bird/week of crude endotoxin. The results suggest that crude whole cell extract and crude endotoxin induced amyloidosis in ducks at similar rates and that, in ducks, thymectomy has no appreciable effect on the occurrence of amyloidosis.     

Escherichia coli endotoxin as a stressor in the domestic fowl.

During 24 h after the injection of fowls (aged eight to 11 weeks) with Escherichia coli endotoxin (1 to 3 mg/kg) isolated from a pathogenic strain (O78) there were changes in the ascorbate content of the adrenal gland and increases in the plasma free fatty acid levels, indicating that the toxin behaves as a mild stressor.     

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)     

Effect of intrauterine infusion of Escherichia coli endotoxin in postpartum pony mares

Fifteen pony mares were assigned to 1 of 3 treatment groups after foaling: Group 1, 35 ml of sterile saline solution was infused into the uterine lumen within 24 hours after parturition (6 mares); group 2, 300 mg of Escherichia coli endotoxin was infused into the uterine lumen within 24 hours after parturition (6 mares); and group 3, 300 mg of E coli endotoxin was infused into the uterine lumen between 72 and 96 hours after parturition (3 mares). Rectal temperatures were taken at -1, -0.5, 0, 0.5, 1, 1.5, 2, 3, 4, and 5 hours after treatment. Venous blood samples were also taken at these times for routine WBC counts. Data were analyzed as a repeated measurement design with linear and quadratic orthogonal contrasts performed where significant time and interaction with time occurred. Pretreatment averages of total WBC and neutrophil counts were compared with their nadir posttreatment averages by a t test when treatment-by-time interaction was significant for the parameter. Rectal temperature (37.9 +/- 0.1 C) remained stable and did not vary among treatment groups after intrauterine infusions. In contrast, total WBC and neutrophil counts did vary among treatment groups across time. However, for treatment groups 1 and 3, neither blood total WBC count nor neutrophil count after intrauterine infusions was different from pretreatment observations. In group 2, total WBC count decreased (P less than 0.10) from a pretreatment average of 11.5 +/- 0.4 X 10(3) cells/mm3 to a nadir concentration of 10.0 +/- 0.6 X 10(3) cells/mm3 by 60 minutes after infusion of endotoxin into the uterus.(ABSTRACT TRUNCATED AT 250 WORDS)