Fosfomycin residues in colostrum: Impact on morpho-physiology and microbiology of suckling piglets.

Fosfomycin is a broad-spectrum bactericidal antibiotic widely used in pig farms for the treatment of a wide variety of bacterial infections. In this study, the elimination of disodium fosfomycin in colostrum/milk of the sow and the impact of this antibiotic on the microbiota and intestinal morpho-physiology of suckling piglets were analyzed. The average amount of fosfomycin eliminated in colostrum (after administration of 15 mg/kg IM) during the first 10 hr postpartum was 0.85 µg/ml, and the mean residual amount ingested by the piglets was 0.26 mg/kg. The elimination profile of fosfomycin concentrations in colostrum occurs at a time of profound changes in the morpho-physiology of the gastrointestinal tract of the piglet. However, the studied concentrations did not produce imbalances on the microbiota or on the morpho-physiology of the gastrointestinal tract of the piglet. Concentrations of fosfomycin were maintained in the mammary gland above the MIC for more than 8 hr for pathogenic bacteria of productive importance. This would indicate that fosfomycin may be considered safe for the specific treatment of bacterial infectious processes in sows during the peri- and postpartum period. This first study with disodium fosfomycin stimulates awareness in the proper use of antimicrobials at farrowing.

Fosfomycin: Uses and potentialities in veterinary medicine.

Fosfomycin (FOS) is a natural bactericidal broad-spectrum antibiotic which acts on proliferating bacteria by inhibiting cell wall and early murein/peptidoglycan synthesis. Bactericidal activity is evident against Gram positive and Gram negative bacteria and can also act synergistically with other antibiotics. Bacterial resistance to FOS may be natural or acquired. Other properties of this drug include inhibition of bacterial adhesion to epithelial cells, exopolysaccharide biofilm penetration, immunomodulatory effect, phagocytosis promotion and protection against the nephrotoxicity caused by other drugs. FOS has chemical characteristics not typically observed in organic phosphoric compounds and its molecular weight is almost the lowest of all the antimicrobials. It tends to form salts easily due to its acidic nature (disodium salt, for intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration; calcium and trometamol salt: for oral (PO) administration). FOS has a very low protein binding (<0.5%) which, along with its low molecular weight and water solubility, contributes to its good diffusion into fluids (cerebrospinal fluid, aqueous and vitreous humor, interstitial fluid) and tissues (placenta, bone, muscle, liver, kidney and skin/fat). In all species, important differences in the bioavailability have been found after administration in relation to the various derivatives of FOS salts. Pharmacokinetic profiles have been described in humans, chickens, rabbits, cows, dogs, horses and weaning piglets. The low toxicity and potential efficacy of FOS are the main factors that contribute to its use in humans and animals. Thus, it has been used to treat a broad variety of bacterial infections in humans, such as localized peritonitis, brain abscesses, severe soft tissue infections, cystitis and other conditions. In veterinary medicine, FOS is used to treat infectious diseases of broiler chickens and pigs. In broilers, it is administered for the treatment of E. coli and Salmonella spp. infections. In piglets, the drug is prescribed to treat a wide variety of bacterial infections. FOS penetration is demonstrated in phagocytic, respiratory (HEP-2) and intestinal (IPEC-J2) cells. Although not widely used in animals, the drug has shown good results in human medicine. The potentialities of FOS suggest that this drug is a promising candidate for the treatment of infections in veterinary medicine. For these reasons, the aim of this work is to provide animal health practitioners with information on a drug that is not extensively recognized.

Efficacy of free glutathione and niosomal glutathione in the treatment of acetaminophen-induced hepatotoxicity in cats.

Acetaminophen (APAP) administration results in hepatotoxicity and hematotoxicity in cats. The response to three different treatments against APAP poisoning was evaluated. Free glutathione (GSH) (200mg/kg), niosomal GSH (14 mg/kg) and free amino acids (180 mg/kg of N-acetylcysteine and 280 mg/kg of methionine) were administered to cats that were intoxicated with APAP (a single dose of 150 mg/kg, p.o.). Serum concentration of alanine aminotransferase (ALT) along with serum, liver and erythrocyte concentration of GSH and methemoglobin percentage were measured before and 4, 24 and 72 hours after APAP administration. Free GSH (200 mg/kg) and niosomal GSH (14 mg/kg) were effective in reducing hepatotoxicity and hematotoxicity in cats intoxicated with a dose of 150 mg/kg APAP. We conclude that both types of treatments can protect the liver and haemoglobin against oxidative stress in APAP intoxicated cats. Furthermore, our results showed that treatment with niosomal GSH represents an effective therapeutic approach for APAP poisoning.

Disodium-fosfomycin pharmacokinetics and bioavailability in post weaning piglets.

Disodium-fosfomycin pharmacokinetics has been studied in different species after oral, intravenous, intramuscular and subcutaneous administration. At present there are neither documented clinical experiences of the use of fosfomycin in pigs nor any published studies in weaning piglets, although it is a period of high incidence of infectious diseases. The pharmacokinetics and the bioavailability of sodium fosfomycin were studied in post weaning piglets after intravenous and intramuscular administration of 15 mg/kg of body weight. Plasma concentrations were measured by a high-performance liquid ms/ms. After IV administration the area under the fosfomycin concentration:time curve in plasma was AUC(0-12) of 120.00 ± 23.12 µg h/ml and the volume of distribution (Vd) of 273.00 ± 40.70 ml/kg. The elimination was rapid with a plasma clearance of 131.50 ± 30.07 ml/kg/h and a T(1/2) of 1.54 ± 0.40 h. Peak serum concentration (Cmax), Tmax, AUC(0-12) and bioavailability for the IM administration were 43.00 ± 4.10 µg/ml, 0.75 ± 0.00 h, 99.00 ± 0.70 µg h/ml and 85.5 ± 9.90% respectively. Different authors have determined a minimum inhibitory concentration (MIC90) ranging from 0.25 µg/ml for Streptococcus sp. and 0.5 µg/ml for Escherichia coli. Considering the above, and according to the values of plasma concentration vs time profiles observed in this study, effective plasma concentrations of fosfomycin for sensitive bacteria can be obtained following IV and IM administration of 15 mg/kg in piglets.

Disposition of suprofen enantiomers in the cat.

Suprofen (SPF) is a non-steroidal anti-inflammatory drug (NSAID), which belongs to the 2-arylpropionic acids subclass. As a result of their chiral characteristics, these compounds have shown a marked enantioselective behaviour with a high degree of interspecies variation. They are mainly eliminated by glucuronidation. Plasma, biliary and urine disposition of SPF was investigated in the cat after intravenous administration of the racemate (dose 2 mg/kg). Both enantiomers exhibited similar disposition profiles in plasma with no evidence of chiral inversion. During bile sampling time, recovered acylglucuronides of R (-) and S (+) SPF were less than 1% of the total dose administered. Only free SPF was recovered in the urine, representing 0.12% of the administered racemic SPF dose. The results indicate that neither chiral inversion nor glucuronidation predominate in SPF disposition in cats.

Liver necrosis induced by Wedelia glauca in rats. A light and electron microscopy study.

Clinical, pathological and ultrastructural changes in rats injected ip with extracts of Wedelia glauca are described. Macroscopic changes were congested livers with accentuated centrilobular vascular patterns. Microscopic hepatic lesions had variable degrees of degeneration and lytic necrosis of centrilobular hepatocytes. Ultrastructural liver changes were condensation of nuclear chromatin with loss of perinuclear membranes, enlargement of mitochondria with alteration of limiting membranes, disappearance of cristae and matrical rarefaction. The endoplasmic reticulum was dilated with detachment of ribosomes. Serum activities of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were increased.

Effects of long-term zearalenone administration on spermatogenesis and serum luteinizing hormone, follicle-stimulating hormone, and prolactin values in male rats.

Body and testis weights, serum luteinizing hormone, follicle-stimulating hormone, and prolactin values and volume fractions of Sertoli cells, spermatogonia, early and late primary spermatocytes, and round and long spermatids were evaluated in 70-day-old male rates treated orally with 20 mg of zearalenone/kg of body weight daily for 5 weeks. Significant (P < 0.05) increase in serum prolactin concentration was consistently observed during the 5 weeks of treatment with zearalenone. Significant changes were not observed in any of the other variables evaluated.

An outbreak of hepatogenous photosensitization in sheep grazing Tribulus terrestris in Argentina.

An outbreak of hepatogenous photosensitization occurred in 40% of sheep grazing Tribulus terrestris in southern Buenos Aires province. Postmortem examinations revealed diffuse jaundice and ochre discoloration of the liver. Histopathological liver lesions consisted of fibroplasia, periductular lamellar fibrosis, hyperplasia of small bile ducts and diffuse swelling of hepatocytes. A crystalloid material was observed in some bile ducts. Aspartate aminotransferase and gamma glutamyltransferase serum activities were elevated in all tested animals while serum bilirubin content was elevated only in the most severely affected sheep. These findings are consistent with reports of geeldikkop, a photosensitivity of sheep which occurs in South Africa and Australia.

Experimental combined aflatoxin B1 and ochratoxin A intoxication in pigs.

Twenty-one pigs weighing approximately 18 kg were placed in 7 groups of 3 and given diets containing respectively aflatoxin B1 alone at 0.375 and 0.0750 mg/kg, ochratoxin A alone at 1 and 2 mg/kg, 0.375 mg/kg of aflatoxin B1 plus 1 mg/kg of ochratoxin A and 0.750 mg/kg aflatoxin B1 and 2 mg/kg of ochratoxin A. The remaining group served as untreated control. At the respective dose levels, pigs receiving similar doses of ochratoxin A alone or in combination with aflatoxin B1, were similarly affected, the clinical effects of aflatoxin having been mostly obscured by those due to ochratoxin A. Mild degenerative hepatic changes typical of aflatoxicosis were observed in pigs fed this toxin alone or in combination with ochratoxin A. In kidneys of pigs fed diet containing 1 and 2 mg of ochratoxin A alone changes included interstitial fibrosis of the vortex and dystrophy and degeneration of the tubular epithelium. Similar lesions but less pronounced fibrosis were found in kidneys of pigs receiving both toxins. The respective lower dose levels of mycotoxins selected were judged to be about the no-effect levels for each dosed separately under the conditions of the trial. Such levels have been found not infrequently on mould affected grain and stock foods. The result highlights the difficulties that may be experienced in the recognition of such multimycotoxicoses as they are likely to occur in the field and indicate the need for toxicological analysis as well as pathological investigation in establishing a diagnosis.

A quantitative thin layer chromatography method for the analysis of aflatoxins, ochratoxin A, zearalenone, T-2 toxin and sterigmatocystin in foodstuffs.

A simple multimycotoxin analytical method was devised for the assay of 8 mycotoxins in foodstuff samples. The procedure consisted in the extraction of the samples with acetonitrile-4% KCl with the addition of HCl, defating with hexane and final extraction with methylene chloride. The mycotoxins were separated by bidimensional thin layer chromatography. The recovery was higher than 80% for all the mycotoxins. The limits of detection were 1.2 micrograms aflatoxins, 5 micrograms ochratoxin A, 20 micrograms sterigmatocystin, 100 micrograms T-2 toxin and 100 micrograms zearalenone/kg.

A quantitative thin layer chromatography method for the analysis of aflatoxins, ochratoxin A, zearalenone, T-2 toxin and sterigmatocystin in foodstuffs

A simple multimycotoxin analytical method was devised for the assay of 8 mycotoxins in foodstuff samples. The procedure consisted in the extraction of the samples with acetonitrile-4

KCl with the addition of HCl, defating with hexane and final extraction with methylene chloride. The mycotoxins were separated by bidimensional thin layer chromatography. The recovery was higher than 80

for all the mycotoxins. The limits of detection were 1.2 micrograms aflatoxins, 5 micrograms ochratoxin A, 20 micrograms sterigmatocystin, 100 micrograms T-2 toxin and 100 micrograms zearalenone/kg.

A quantitative thin layer chromatography method for the analysis of aflatoxins, ochratoxin A, zearalenone, T-2 toxin and sterigmatocystin in foodstuffs.

A simple multimycotoxin analytical method was devised for the assay of 8 mycotoxins in foodstuff samples. The procedure consisted in the extraction of the samples with acetonitrile-4

KCl with the addition of HCl, defating with hexane and final extraction with methylene chloride. The mycotoxins were separated by bidimensional thin layer chromatography. The recovery was higher than 80

for all the mycotoxins. The limits of detection were 1.2 micrograms aflatoxins, 5 micrograms ochratoxin A, 20 micrograms sterigmatocystin, 100 micrograms T-2 toxin and 100 micrograms zearalenone/kg.

Experimental ochratoxicosis A in pigs.

Ochratoxin A was isolated from a culture of Aspergillus ochraceus grown on a cornmeal substrate. The mycotoxin was added to a grower ration for 14 kg young pigs at 2, 4, 8 and 16 mg/kg and fed to groups of 3 for periods ranging from 6 to 20 days. The highest dose rate group only became sick, with loss of appetite, weight loss, polydipsia, polyuria, proteinuria, glucosuria, elevation of serum creatinine, pale swollen kidneys, renal tubular degeneration and cortical fibrosis. The pigs on the 2 mg toxin/kg of diet appeared unaffected with only slight renal tubular degeneration present in one animal. Feeding diet contaminated with the intermediate doses of 4 and 8 mg toxin/kg diet lead to reduction of weight gain and/or reduced feed intake and feed conversion efficiency as well as mild renal lesions. Ochratoxin A has recently been reported on mould-affected grain in Queensland and some local strains of A. ochraceus in culture have been shown to be able to produce levels of ochratoxin A of up to 4000 mg/kg of substrate. Rare episodes of nephrotoxicity in pigs seen at slaughter in Queensland may thus be due to prior contamination of the diet with ochratoxin A.

[Identification of the mycotoxin zearalenone in Argentina]. / Identificación de la micotoxina zearalenona en la Argentina.

Zearalenone, an estrogenic toxin produced by several Fusarium sp., was detected by two chromatographic methods in grain and food samples from several farms of th Buenos Aires Province. Suspected zearalenone spots were identified by comparing their Rf against that of the pure substance, by their change of behaviour under ultraviolet light of different wavelengths, by comparing the Rf against a standard preparation after thin layer chromatography in four different solvent systems, and by color reactions obtained after spraying reagents on the thin layer chromatographic plates. Sixteen of 55 samples were positive, with concentrations of the toxin ranging from 200 ppb to 750 ppb. Only Fusarium graminearum was isolated from eleven of these samples, indicating that the fungus was inactivated by heat or antifungal treatments.

Identificación de la micotoxina zearalenona en la Argentina / [Identification of the mycotoxin zearalenone in Argentina]

Zearalenone, an estrogenic toxin produced by several Fusarium sp., was detected by two chromatographic methods in grain and food samples from several farms of th Buenos Aires Province. Suspected zearalenone spots were identified by comparing their Rf against that of the pure substance, by their change of behaviour under ultraviolet light of different wavelengths, by comparing the Rf against a standard preparation after thin layer chromatography in four different solvent systems, and by color reactions obtained after spraying reagents on the thin layer chromatographic plates. Sixteen of 55 samples were positive, with concentrations of the toxin ranging from 200 ppb to 750 ppb. Only Fusarium graminearum was isolated from eleven of these samples, indicating that the fungus was inactivated by heat or antifungal treatments.

Identificación de la micotoxina zearalenona en la Argentina. / [Identification of the mycotoxin zearalenone in Argentina]

Zearalenone, an estrogenic toxin produced by several Fusarium sp., was detected by two chromatographic methods in grain and food samples from several farms of th Buenos Aires Province. Suspected zearalenone spots were identified by comparing their Rf against that of the pure substance, by their change of behaviour under ultraviolet light of different wavelengths, by comparing the Rf against a standard preparation after thin layer chromatography in four different solvent systems, and by color reactions obtained after spraying reagents on the thin layer chromatographic plates. Sixteen of 55 samples were positive, with concentrations of the toxin ranging from 200 ppb to 750 ppb. Only Fusarium graminearum was isolated from eleven of these samples, indicating that the fungus was inactivated by heat or antifungal treatments.