Pentoxifylline pretreatment fails to block the acute-phase response toEscherichia coli endotoxin in dwarf goats

The purpose of this study was to assess whether pentoxifylline, a drug that can inhibit the production and action of pro-inflammatory cytokines, had beneficial effects on the acute-phase response toE. coli endotoxin in the dwarf goat. First, the effects of 0.5 mg/kg per min pentoxifylline given intravenously over 15 min were examined in five goats. One week later, the clinical changes caused by i.v. injection ofE. coli endotoxin (LPS: 0.1 µg/kg) were determined. This endotoxin induced fever, tachycardia, inhibition of rumen motility, and decreases in plasma zinc and iron concentrations. Three weeks later, the effects ofE. coli LPS were again determined immediately after pentoxifylline infusion in the same group of animals. It was concluded that a pharmacological dose of pentoxifylline has no protective effects on the acute-phase response reactions induced by a pyrogenic dose ofE. coli LPS Abbreviations AMP adenosine phosphate - APR acute-phase response - GMP guanosine phosphate - IL interleukin - i.v. intravenous - LPS lipopolysaccharides - NO nitric oxide - POF pentoxifylline - r recombinant - SEM standard error of mean - TNF tumour necrosis factor     

The effects of glibenclamide,a blocker of K+ ATP-sensitive potassium channels,on diaphragmatic fatigue during endotoxaemia in pigs

An in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K⁺ ATP-sensitive potassium channel blocker. Escherichia coli lipopolysaccharides (LPS, 70 g/kg, i.v., as a bolus) were infused into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 120 min of endotoxaemia, glibenclamide was administered (10 mg/kg, i.v., over 5 min) to half the pigs. The steength at different frequencies of stimulation (10, 20, 30, 50 Hz, 20 V, 1 s) and the endurance capacity (10 Hz, 20 V, 30 s) of the diaphragm were evaluated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after drug infusion. Glibenclamide transiently increased the blood pressure without changing the decreased cardiac output and at the same time further impaired the diaphragmatic activity. The reduced ability of the diaphragm to generate force in response to different electrical stimulations was shown by a significant reduction in strength. The endurance index decreased 5 min after glibenclamide infusion, returning to the pre-glibenclamide values by 150 min. These results indicate that glibenclamide modifies the activity of vascular smooth muscle and of the diaphragm.Abbreviations BP blood pressure - CO cardiac output - LPS lipopolysaccharides - Glib glibenclamide - i.m. intramuscular - i.v. intravenous - SEM standard error of the mean - v/v volume/volume P _ab, abdominal pressure - P _di transdiaphragmatic pressure - P _oes oesophageal pressure     

The effect of induced fever on the biokinetics of norfloxacin and its interaction with probenecid in goats

The kinetic profiles of norfloxacin were evaluated in afebrile, febrile and probenecid pre-treated (70 mg/kg orally) febrile goats after a single intravenous (i.v) dose (5 mg/kg). Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.2 g/kg, i.v.) and repeating it in half the dose (0.1 g/kg) 5 h later. The plasma pharmacokinetic values for norfloxacin were best represented using a two-compartment open model. The peak norfloxacin plasma level of 90.52±3.18 g/ml attained in the probenecid pre-treated febrile goats was higher than that in the febrile (75.46±0.72 g/ml) or afebrile goats (62.25±1.23 g/ml). Cl_B and K _el values were significantly (p<0.01) decreased in febrile compared with afebrile goats. These values were further reduced in febrile goats after probenecid pre-treatment. However, t _1/2 was not affected by the fever-probenecid interaction. Norfloxacin may be used as an infusion with probenecid in caprine diseases where very high plasma levels are required to combat resistant organisms such as Bacteroides.Abbreviations MIC minimum inhibitory concentration - LPS lipopolysaccharide - i.v. intravenous(ly)     

The generalized Shwartzman reaction induced by a single injection of endotoxin in pigs fed 2 vitamin E deficient commercial diet.

An experimental generalized Shwartzman reaction (GSR) induced in pigs by endotoxin from Escherichia coli has been reported previously (Teige et al. 1973, Quast 1973). The diet given to the pigs seemed to influence the outcome of the experiments. It has been found difficult to provoke GSR in pigs fed a commercial diet, even when the E. coli endotoxin is given as a single, relatively large dose or as 2 properly spaced doses (Teige et al., Nordstoga 1976). Quast induced the GSR by continuous infusion of endotoxin. In connection with 1 experiment in pigs, changes indicative of GSR were observed among a group of animals fed a commercial diet and receiving a small single dose of endotoxin. These observations are presented in this paper.     

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.     

Effects of endotoxin,interleukin‐1/3 and prostaglandin injections on fever response in broilers

1. The effect of endotoxin, interleukin‐1β and prostaglandin on fever response was studied in 80 broilers (Hubbard strain). Endotoxin (E. coli, LPS) was injected iv (1.5 μg/kg) and icv (1.5 μg/bird); interleukin‐1 (human recombinant IL‐1β, 80 pg/bird) and prostaglandin E₂ (5 μg/bird) were injected icv. Indomethacin (10 mg/kg, iv) pretreatment was also used before iv endotoxin injection.

2. The results showed that indomethacin was able to block the fever response induced by iv endotoxin injection, and IL‐1β and PGE₂ were both effective in producing fever when injected icv. These data suggest a prostaglandin‐mediated fever response by broilers, and also a strong evidence of the involvement of endogenous pyrogen (interleukin‐1) in fever response in birds.     

Respiratory phagocytes are implicated in enhanced colibacillosis in chickens co-infected with influenza virus H9N2 and Escherichia coli

1. The aim of this study was to determine the most likely time interval after infection with influenza virus H9N2 for co-infection with Escherichia coli to cause colibacillosis, the importance of lung load of E. coli and the involvement of respiratory phagocytes.

2. Specific pathogen free chickens were inoculated intranasally with 10⁶EID₅₀ of influenza virus or uninfected. After specified time intervals, 10⁷ CFU E. coli or phosphate-buffered saline was inoculated. The presence of lesions, the number of respiratory phagocytes in the respiratory lavage fluid and the E. coli load in the lung were determined after different time intervals.

3. Compared with the number of lesions in chickens receiving only E. coli inoculation, the number lesions in co-infected chickens were increased at 0- and 3-d time intervals, but reduced in the groups at 6- and 9-d intervals between co-infection.

4. At 1–3 d after E. coli inoculation, the number of lesions chickens was correlated with the number of respiratory phagocytes harvested and related to the E. coli load in the lungs at 5 d.

5. These results suggest that the lesions caused by E. coli in chickens were increased within a 0–3 d interval following H9N2 virus inoculation and that this effect is related to the number of respiratory phagocytes.     

Immune-modulatory effects of dietary Saccharomyces cerevisiae cell wall in broiler chickens inoculated with Escherichia coli lipopolysaccharide

1. An experiment was conducted to study the effect of yeast (Saccharomyces cerevisiae) cell wall (YCW) supplemented in diets of broiler chickens challenged with Escherichia coli lipopolysaccharide (LPS).

2. One-day-old broiler chicks were randomly distributed into 24 cages (6 replicate cages; 8 birds/cage) and were inoculated with 0 or 1 mg/kg body weight E. coli-LPS (d 4 and 9) and 0 or 500 mg YCW/kg feed, resulting in a 2 × 2 factorial arrangement of treatments. Experimental diets did not include coccidiostats, in-feed antibiotics or enzymes.

3. On d 21, the inoculation of E. coli-LPS reduced weight gain and feed intake and increased feed conversion ratio (FCR) of birds, an effect maintained until 28 d. In contrast, chickens given diets with YCW improved the FCR at both 21 and 28 d of age.

4. E. coli-LPS challenge reduced the relative weight of bursa of Fabricius, except when chickens were given YCW, which resulted in an interaction. Supplementation of broiler diets with YCW exacerbated the cellular immune response as measured by the delayed cutaneous hypersensitivity response test.

5. The results of this study suggested a benefit on feed efficiency when YCW was added to diets fed to broiler chickens challenged with E. coli-LPS. Part of the mode of action of YCW might be related to better maintenance of immune status in response to microbial challenge.     

Studies on occurrence,characterisation and decontamination of emerging pathogenic Escherichia coli (STEC,ETEC and EIEC) in table eggs

1. Escherichia coli is one of the most common facultative anaerobic species present in the gastrointestinal tract of animals and human beings. Usually they occur as commensals, but some serotypes can cause significant illnesses in humans as well as mammals and birds.

2. The occurrence of E. coli in different categories of table eggs collected from markets was evaluated. Isolates were analysed for the presence of virulence genes, antibiotic susceptibility pattern and efficacy of peracetic acid and chlorine for the purpose of decontaminating table eggs.

3. Significant differences were observed in the occurrence of E. coli between different groups viz. processed (cleaned, washed, sanitised and packed eggs), unprocessed (un-cleaned, un-sanitised and loose eggs) and free range (eggs obtained from backyard poultry) table eggs. Overall, E. coli occurred in table eggs at 28.6% with 22.9, 29.2 and 50.0% occurrence in processed, unprocessed and free-range table eggs, respectively.

4. A total of 24 isolates of E. coli were obtained and screened for virulence genes viz. STH, SLT1/2 and INVE genes. Of the 24 isolates recovered, 10 typeable isolates belonged to O141, O119, O9, O120 and O101 serotypes, while the remaining 14 were untypeable. Antibiograms of the isolates showed multiple antimicrobial resistance (MAR) index in the range of 0.13–0.40.

5. Peracetic acid (PAA) and chlorine (CL) were studied for their sanitisation efficacy; concentrations of 100 mg/kg of PAA and 200 mg/kg of CL completely inactivated E. coli over the egg surface and also resulted in 2.58 and 2.38 log reduction in total viable counts (TVC), respectively.

6. The presence of virulence-associated shiga-like toxin (SLT1/2) and invasion E (INVE) genes and antimicrobial resistance among the emerging serotypes of pathogenic E. coli isolated from table eggs has public health implications. It underscores the need to implement better management practices across the production systems and marketing channels to produce E. coli-free wholesome eggs for consumers.     

Antimicrobial susceptibility and phylotyping profile of pathogenic <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Salmonella enterica</Emphasis> isolates from calves and pigs in Minas Gerais,Brazil

The aims of the present study were to determine (i) the profiles of phylogroup and (ii) the antimicrobial susceptibility of pathogenic Escherichia coli strains isolated from calves, and of Salmonella spp. strains isolated from calves and pigs in Minas Gerais State, Brazil. Sixty-one pathogenic E. coli strains and Salmonella spp. (n?=?24) strains isolated from fecal samples of calves and Salmonella spp. (n?=?39) strains previously isolated from fecal samples of growing/finishing pigs were tested. The minimum inhibitory concentration (MIC) using the agar dilution method was determined for nalidixic acid, amikacin, amoxicillin, ampicillin, cefoxitin, norfloxacin, gentamicin, tetracycline, and trimethoprim-sulfamethoxazole. All E. coli isolates were susceptible to amikacin. Tetracycline was the antimicrobial that presented the higher frequency of resistance among E. coli strains, followed by ampicillin, trimethoprim-sulfamethoxazole, amoxicillin, nalidixic acid, norfloxacin, gentamicin, and cefoxitin. E. coli (n?=?61) strains isolated from calves belonged to different phylogroup namely, phylogroup A (n?=?26), phylogroup B1 (n?=?31), phylogroup E (n?=?3), and phylogroup F (n?=?1). Phylogroups B2, C, and D were not identified among the E. coli in the present study. All Salmonella spp. (n?=?24) strains isolated from fecal samples of calves were susceptible to amikacin, amoxicillin, ampicillin, norfloxacin, gentamicin, tetracycline, and trimethoprim-sulfamethoxazole. Resistance to nalidixic acid and cefoxitin was detected in 16.66 and 8.33 % of the Salmonella spp. strains, respectively. Among the Salmonella spp. (n?=?39) strains isolated from fecal samples of pigs, the higher frequency of resistance was observed to tetracycline, followed by amoxicillin, gentamicin, ampicillin, trimethoprim-sulfamethoxazole, nalidixic acid, cefoxitin, and norfloxacin. All strains were susceptible to amikacin. Forty-eight (78.68 %) of the E. coli strains were classified as multidrug-resistant, whereas among Salmonella spp. strains, the percentage of multidrug resistance was 57.14 %, being all multidrug-resistant strains isolated from pigs (92.30 %). The results from the present study indicate a high frequency of antimicrobial resistance among pathogenic E. coli strains isolated from calves and Salmonella spp. strains isolated from pigs and a high rate of susceptibility to most antimicrobials tested among Salmonella spp. strains isolated from calves. Our study highlights the presence of multidrug-resistant strains of E. coli and Salmonella spp. isolated from food-producing animals in Minas Gerais, Brazil.     

Effects of dietary additives (potassium diformate/organic acids) as well as influences of grinding intensity (coarse/fine) of diets for weaned piglets experimentally infected with Salmonella Derby or Escherichia coli

The aim of this study was to examine whether and to what extent the addition of potassium diformate (pdf) or free organic acids (fpa) to the diet and the grinding intensity might affect the course of infection and the passage of orally applied Salmonella and Escherichia coli in pigs. Experiments were carried out using 80 reared piglets allotted to four groups. Pigs were fed pelleted diets ad libitum (except during a 15 h feed‐withholding‐period before infection). The control diet contained finely ground cereals (2 mm screen). To two test diets (also finely ground) 1.2% pdf, 0.9% organic acids (75% formic and 25% propionic acid, fpa) respectively were added. The fourth diet (without acids) was based on coarsely ground cereals (6‐mm screen). After experimental infection alternately with S. Derby or E. coli, the course of infection was examined (rectal swab technique). Pigs were sacrificed 4–5 h after a further oral application of ～10⁹–10¹⁰ CFU S. Derby or E. coli to determine the counts of Salmonella or E. coli in chyme (classical culture methods). Adding pdf or fpa to the diet led to reduced Salmonella shedding and resulted in significantly lower counts of Salmonella and E. coli in the stomach content indicating an improved efficacy of the stomach barrier. In the distal parts of the digestive tract, the effect was less obvious concerning counts of E. coli, whereas counts of Salmonella were reduced markedly as well. The diet based on coarsely ground cereals failed to demonstrate positive effects concerning infection and passage of orally applied bacteria as well, but this diet was also pelleted and showed unintentionally, comparable amounts of fine particles. Results obtained in this study allow the recommendation of using pdf or organic acids as additives when dietary measures against Salmonella or E. coli in pigs are required.     

Genotypic and phenotypic diversity differences of presumptive commensal and avian pathogenic E. coli

1. The objective of the experiment was to characterise the genotypic and phenotypic differences between presumptive commensal E. coli and avian pathogenic E. coli (APEC) of poultry.

2. DNA was extracted from 65 confirmed APEC E. coli from chicken, 100 presumptive commensal E. coli from healthy turkey and 35 from healthy chicken. Enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and virulence factors genotyping was performed to characterise genetic features.

3. Carbon source utilisation and antimicrobial susceptibility tests were performed to characterise phenotypic features of isolates.

4. The genetic divergence between E. coli strains tested by ERIC-PCR profiles and virulence-associated genes showed a clear genetic separation between E. coli APEC and turkey E. coli strains.

5. The carbon utilisation profile of turkey isolates was different from chicken and APEC strains; whereas antimicrobial susceptibility was highest for turkey isolates (53%), and lowest for APEC strains (33.8%).

6. The study showed a significant negative correlation between utilisation of arabitol and adonitol with different virulence determinants tested, which suggests that the ability to utilise some uncommon carbon sources may be used to discriminate between presumptive commensal E. coli and APEC.     

Pharmacokinetics of difloxacin in healthy and E. coli-infected broiler chickens

1. The pharmacokinetics of difloxacin were investigated in healthy and E. coli-infected broiler chickens following intravenous and oral administration of a single dose of 10 mg/kg bodyweight.

2. After intravenous injection of difloxacin, the serum concentration–time curves were best described by a two-compartment open model. The distribution and elimination half-lives (t_0.5α) and (t_0.5el), respectively, were 0.10 ± 0.016 h and 3.7 ± 0.08 h in healthy chickens compared with 0.05 ± 0.005 h and 6.42 ± 0.71 h in E. coli-infected birds. The volumes of distribution V_dss were 3.14 ± 0.11 and 9.25 ± 0.43 l/kg, with total body clearance (Cl_tot) of 0.65 ± 0.018 and 1.14 ± 0.1 ml/kg/h, respectively.

3. Following oral administration, difloxacin was absorbed with t_0.5(ab) of 0.57 ± 0.06 and 0.77 ± 0.04 h and was eliminated with t_0.5(el) of 4.7 ± 0.34 and 3.42 ± 0.19, respectively, in normal and infected chickens. The peak serum concentrations were 1.34 ± 0.09 and 1.05 ± 0.06 µg/ml and attained a T_max of 2.27 ± 0.07 and 2.43 ± 0.06 h, respectively. The systemic bioavailability of difloxacin following oral administration was 86.2% in healthy chickens and 90.6% in E. coli-infected birds. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of difloxacin against the field strain of E. coli O78 in vitro were 0.02 µg and 0.04 µg/ml, respectively.

4. These results show that administration of a therapeutic dose of difloxacin is effective in the treatment of E. coli infection in chickens. The serum concentration of the drug was much higher than the MIC of the E. coli O78 strain in both healthy and infected chickens.     

The antipyretic effect of polymyxin B in endotoxin-induced fever

LPSS. typhimurium (0.3 g per kg) injected intravenously into conscious goats induced an inhibition of the extrinsic ruminal contractions in association with pyrexia and changes in heart rate. Pretreatment with polymyxin B (3 mg per kg i.v.) antagonized the endotoxin-induced symptoms in this species. In rabbits, the intravenous administration of LPSE. coli (0.1 g per kg) resulted in a febrile response, which could be markedly reduced by pretreatment with polymyxin B. Unlike endotoxins, the febrile response to leucocytic pyrogen was not inhibited after pretreatment with this antibiotic. Moreover, polymyxin B caused only a minimal decline in the febrile response due to sodium nucleinate from yeast (10 mg per kg). These results strengthen the view that the antipyretic activity of polymyxin B is due to an interaction of this cationic macromolecule with the anionic endotoxin molecule.     

Comparison of continuous infusion with intermittent bolus administration of cefotaxime on blood and cavity fluid drug concentrations in neonatal foals

Hewson, J., Johnson, R., Arroyo, L. G., Diaz‐Mendez, A., Ruiz‐López, J. A., Gu, Y., del Castillo, J. R. E. Comparison of continuous infusion with intermittent bolus administration of cefotaxime on blood and cavity fluid drug concentrations in neonatal foals. J. vet. Pharmacol. Therap.  36 , 68–77. Healthy neonatal foals were treated with cefotaxime by bolus (40 mg/kg IV q6h for 12 doses; n = 10) or by infusion (loading dose of 40 mg/kg IV followed by continuous infusion of a total daily dose of 160 mg/kg per 24 h for 3 days; n = 5). Population pharmacokinetics was determined, and concentrations in cavity fluids were measured at steady state (72 h). Highest measured serum drug concentration in the bolus group was 88.09 μg/mL and minimum drug concentration (C_min) was 0.78 μg/mL at 6‐h postadministration (immediately before each next dose), whereas infusion resulted in a steady‐state concentration of 16.10 μg/mL in the infusion group. Mean cefotaxime concentration in joint fluid at 72 h was higher (P = 0.051) in the infusion group (5.02 μg/mL) compared to the bolus group (0.78 μg/mL). Drug concentration in CSF at 72 h was not different between groups (P = 0.243) and was substantially lower than serum concentrations in either group. Insufficient data on pulmonary epithelial lining fluid were available to compare the methods of administration for cefotaxime in this cavity fluid. Results support continuous drug infusion over bolus dosing in the treatment for neonatal foal septicemia to optimize time that cefotaxime concentration exceeds the minimum inhibitory concentration of common equine pathogens.     

Endotoxin in the conscious piglet: Its effects on some general and gastrointestinal myoelectrical parameters

The effect of an intravenous bolus injection of endotoxin, 0.1, 1 or 10 g/kg, on rectal temperature, clinical appearance, haematological parameters, and on gastrointestinal electrical activity was examined in 11 conscious piglets of 4–5 weeks of age, with implanted electrodes in the antrum pylori, duodenum, jejunum and ileum. All doses resulted in a significant and dose-dependent increase in rectal temperature, in pronounced clinical signs and in distinct changes in haematological values. These included shivering, depression, respiratory distress, a leukopenia (0.1 g/kg) or a leukocytosis (1 g/kg) with a shift to the left, an accelerated sedimentation rate and a decreased packed cell volume. Doses of 1 and 10 g/kg induced a transient inhibition of gastroduodenal electrical activity. These results suggest that, in the piglet, endotoxin primarily manifests general clinical signs and that the gastrointestinal effects coincide with these.     

Use of cis-atracurium to maintain moderate neuromuscular blockade in experimental pigs

Objective

To determine the dose of cis-atracurium needed to produce a moderate neuromuscular blockade (NMB) in pigs.

Effect of added dietary threonine on growth performance,health, immunity and gastrointestinal function of weaning pigs with differing genetic susceptibility to Escherichia coli infection and challenged with E. coli K88ac

Threonine (Thr) is important for mucin and immunoglobulin production. We studied the effect of added dietary Thr on growth performance, health, immunity and gastrointestinal function of weaning pigs with differing genetic susceptibility to E. coli K88ac (ETEC) infection and challenged with ETEC. Forty‐eight 24‐day‐old weaned pigs were divided into two groups by their ETEC susceptibility using mucin 4 (MUC4) gene as a marker (2 MUC4^?/?, not‐susceptible, and 2 MUC4^+/+, susceptible, pigs per litter). Within genotype, pigs were fed two different diets: 8.5 (LThr) or 9.0 (HThr) g Thr/kg. Pigs were orally challenged on day 7 after weaning and slaughtered on day 12 or 13 after weaning. Before ETEC challenge, HThr pigs ate more (p < 0.05). The diet did not affect post‐challenge growth, but HThr tended to increase post‐challenge feed efficiency (p = 0.087) and overall growth (p = 0.087) and feed efficiency (p = 0.055). Before challenge, HThr pigs excreted less E. coli (p < 0.05), while after challenge, diet did not affect the number of days with diarrhoea and ETEC excretion. MUC4^+/+ pigs responded to the challenge with more diarrhoea, ETEC excretion and anti‐K88 IgA in blood and jejunal secretion (p < 0.001). HThr pigs had a higher increase of anti‐K88 IgA values in jejunal secretion (p = 0.089) and in blood (p = 0.089, in MUC4^+/+ pigs only). Thr did not affect total IgA and IgM values, morphometry of jejunum, goblet cells count in colon, total mucin from jejunum and colon, but varied jejunal goblet cells counts (p < 0.05). In the first two post‐weaning weeks, 8.5 g Thr/kg diet may be not sufficient to optimize initial feed intake, overall feed efficiency and intestinal IgA secretion and to control the gut microbiota in the first post‐weaning week, irrespective of the pig genetic susceptibility to ETEC infection.     

Bacillus subtilis and yeast cell wall improve the intestinal health of broilers challenged by Clostridium perfringens

1. The objective was to investigate the effects of Bacillus subtilis, yeast cell wall (YCW) and their combination on intestinal health of broilers challenged by Clostridium perfringens over a 21-d period.

2. Using a 5 × 2 factorial arrangement of treatments, 800 1-d-old male Cobb 500 broilers were used to study the effects of feed additives (without additive or with zinc bacitracin, B. subtilis, YCW, and the combination of B. subtilis and YCW), pathogen challenge (without or with Clostridium perfringens challenge), and their interactive effects.

3. C. perfringens infection increased intestinal lesions scores, damaged intestinal histomorphology, increased serum endotoxin concentration, cytokine mRNA expression and intestinal population of C. perfringens and Escherichia coli and decreased ileal bifidobacteria numbers. The 4 additives decreased serum endotoxin. Zinc bacitracin tended to decrease cytokine mRNA expression and the intestinal number of C. perfringens and E. coli. B. subtilis, YCW and their combination increased cytokine mRNA expression. B. subtilis and YCW decreased the number of C. perfringens and E. coli in the ileum, and their combination decreased pathogens numbers in the ileum and caecum.

4. In conclusion, B. subtilis, YCW and their combination improved the intestinal health of NE-infected broilers, and could be potential alternatives to antibiotics.     

Effect of antisecretory drugs on experimentally induced weanling diarrhoea in piglets

In 45 newly-weaned 3 to 4-week-old piglets, diarrhoea was induced by a combined infection with transmissible gastroenteritis (TGE) virus and enterotoxigenic E. coli (ETEC) strains. In untreated control animals this dual inoculation resulted in profuse diarrhoea, vomiting, hypovolaemic shock and death of 77% of the animals within five days of TGE virus inoculation. Antisecretory drugs were administered intramuscularly for three consecutive days after experimental infection. The neurolepticum chlorpromazine, at 2 mg/kg/24 h, resulted in a significant inhibition of diarrhoea and vomiting, and in an increase in weight gain and survival. Sedation and hypothermia, however, were serious side-effects. The ₂ agonist clonidine, at 80 g/kg/12 h, induced a significant antidiarrhoeal effect and a reduction in mortality. The drug, however, provoked decreased activity of ₂-adrenergic excitation and incoordination. The -adrenergic antagonist propranolol, at 0.33 mg/kg/8 h, and the calcium channel blocker verapamil, at 2 mg/kg/8 h, had no beneficial effect on the experimentally induced diarrhoea.