Water hardness is a critical factor that affects oxytetracycline dissolution by chelation with cations. These interactions may lead to impaired dosing and consequently decrease absorption. Moreover, feed present in gastrointestinal tract may interact with antibiotic and alter pharmacokinetic parameters. In the present study, dissolution profiles of an oxytetracycline veterinary formulation were assessed in purified, soft and hard water. Furthermore, oxytetracycline absolute bioavailability, after oral administration of the drug dissolved in soft or hard water, was evaluated in fed and fasted piglets. A maximum dissolution of 86% and 80% was obtained in soft and hard water, respectively, while in purified water dissolution was complete. Results from in vivo study reconfirmed oxytetracycline's very low oral bioavailability. The greatest values were attained when antibiotic was dissolved in soft water and in fasted animals. Statistically significant lower absolute bioavailability was achieved when hard water was used and/or animals were fed. Moreover, Cmax attained in all treatments was lower than MIC90 of most important swine pathogens. For these reasons, the oral use of OTC formulations, that have demonstrated low oral bioavailability, should be avoided to treat systemic diseases in pigs.

Weaning is a challenging stage of pig farming. Animals undergo environmental, social and dietary changes leading to weaning stress syndrome. In order to compensate for the detrimental effects of weaning stress, antibiotics and natural extracts are used as feed additives, sometimes without fully understanding the interactions between them or even with low concentrations of mycotoxins that are frequently present in feed. The aim of this study was to evaluate the effect of fosfomycin (FOS), Cynara scolymus extract (CSE), deoxynivalenol (DON) and their combined administration on intestinal health of weaned piglets. The experiment was designed as a 2 × 2 × 2 factorial arrangement with 3 factors (FOS, CSE and DON treatments), 2 levels each (presence and absence) and 3 repeats. Weaned piglets (n = 24) were randomly divided in groups to receive the different treatments, namely DON administered in diet (50 μg/kg BW), FOS administered into the drinking water (30 mg/kg BW), CSE administered in diet (15 mg/kg BW) and all their combinations. After 15 d, the animals were euthanized and gastrointestinal tract samples were immediately taken to evaluate gastrointestinal pH, Enterobacteriaceae to lactic acid bacteria (E:L) ratio, volatile fatty acid (VFA) concentrations, disaccharidase (lactase, sucrase and maltase) activity, histology (intestinal absorptive area [IAA] and goblet cells count) and mucus ability to adhere pathogenic Escherichia coli. From our results, FOS and CSE treatments, individually or combined, produced a lower E:L ratio, an enhanced production of butyrate, increased disaccharidase activity (particularly maltase), and a greater IAA and goblet cells count along with an increase in pathogenic bacteria adherence to intestinal mucus. Deoxynivalenol did not show interactions with the other factors and its administration produced decreases on VFA, disaccharidase activity and goblet cells count. In conclusion, weaning piglets receiving diets containing FOS, CSE or both exhibited evident beneficial intestinal effects compared to animals receiving diets free from these compounds. On the contrary, the presence of DON at sub-toxic concentrations produced detrimental effects on intestinal health. The knowledge of the physiological and pathological gut changes produced by these compounds contributes to understand their potential productive consequences.

Many of the beneficial effects on productive performance observed when vegetable extracts are incorporated as feed additives in intensive farming can be explained by an increase in bile production. An experiment was conducted to study choleretic and cholagogue effect of a Cynara scolymus extract formulation and of silymarin in pigs. Pigs were cannulated with a T-tube catheter in the bile duct. Bile production was continuously measured and re-infused to the duodenum through Oddi's sphincter at the same production rate. Treatments: Group A (n = 6), commercial feed; Group B (n = 6), C. scolymus extract (300 g/tonne) and Group C (n = 6), silymarin (300 g/tonne). Bile production was recorded hourly for each animal during 24 h. Total bile acids' concentrations in bile, just before and one hour after meals were evaluated. Average daily bile production for pigs in group B was 66% higher than for pigs in groups A or C (P < .05). When bile acids' concentrations before and after meals were compared, only pigs from group B exhibited an increase (P = .0023). From this study, it was concluded that neither choleretic nor cholagogue effects are attained with silymarin supplementation. On the contrary, C. scolymus extract increases bile production and secretion in pigs.

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.

AIMS: To evaluate the effect of a novel method of practical oxygen therapy on physiological parameters related to survival, weaning weight and preweaning mortality of neonatal piglets under commercial farm conditions. METHODS: Piglets from hyperprolific sows born with signs of asphyxia, (n=109; <6 on a score of respiration, meconium staining and activity) or very low birth weight (VLBW; n=112; <1.05 kg) were selected for the study. Approximately half of each group (n=55 VLBW piglets and n= 57 piglets with asphyxia) received 100% oxygen immediately after birth using a specially designed facemask for 45 seconds (VLBW) or 1 minute (asphyxiated). Physiological parameters (peripheral blood oxygen saturation (SpO2) blood glucose concentration and rectal temperature) were measured before oxygen treatment 5 minutes after birth (SpO2) and 24 hours later (SpO2, blood glucose concentration, temperature). Weight at birth, at 24 hours and at 21 days of age, preweaning mortality, and estimated colostrum intake were also recorded. RESULTS: A significant treatment effect on SpO2 was observed (p=0.013 and p<0.001 for VLBW and asphyxiated piglets respectively). VLBW and asphyxiated piglets that received oxygen treatment had higher SpO2 after treatment (measured 5 minutes after birth, 97.7 and 97.8% respectively) compared to immediately after birth (93.3 and 86.8% respectively) while untreated piglets showed no variation. Blood glucose concentrations increased in all piglets between birth and 2 24 hours of age (p=0.003 and p<0.001 for asphyxiated and VLBW piglets respectively) and this was higher in asphyxiated piglets that received oxygen than those that did not (5.6 (SE 0.2) mmol/L; p<0.05). Estimated colostrum intake was higher in asphyxiated (401.6 (SD 24.4) g/kg) and VLBW (374.9 (SE 23.4 g/kg) piglets that received oxygen than those that did not (273.2 (SE 24.1) g/kg; p<0.001 and 249.0 (SE 22.5) g/kg; p<0.001 respectively). Similarly weight at weaning was higher in asphyxiated (5.8 (SE 0.2) kg) and VLBW (4.9 (SE 0.2) kg) piglets that received oxygen therapy than control animals (4.9 (SE 0.2) kg;=0.005 and 4.1 (SE 0.2) kg; p=0.008 respectively). Furthermore, oxygen treatment markedly reduced preweaning mortality from 9/52 (17%) untreated to 1/57 (1.7%) oxygen-treated piglets suffering asphyxia at birth (p=0.006). CONCLUSIONS: Oxygen therapy improves physiological and productive parameters in piglets born with signs of asphyxia or VLBW. The incorporation of this strategy as part of the farrowing routine enhances the advantages of rearing hyperprolific sows.

Fosfomycin (FOS) is an antibiotic used, mostly in Latin America, for the treatment of lung and enteric infections of pigs. Intracellular fluids of enterocytes can act as biophase for Lawsonia intracellularis, the causative agent of porcine proliferative enteropathy (PPE). The aim of this study was to determine whether the presence of L. intracellularis in the enterocytes modifies FOS penetration. Eight healthy pigs in growth-finishing stage were used to produce healthy (group A) and L. intracellularis-colonized (group B) intestinal explants. For both groups, treatment consisted of a 580 μg/ml concentration of calcium FOS, which was added to each explant (0.5-6 hr). For group B, the Enterisol Ileitis vaccine was used as source of the micro-organism. Previously to the assay, the time necessary for L. intracellularis to colonize the enterocytes was defined. Also, a PCR protocol was optimized to determine the presence of the pathogen in the explants. There were nonstatistical differences for the penetration of the antibiotic into healthy and L. intracellularis-colonized enterocytes. MIC of FOS for L. intracellularis is unknown; nevertheless, MIC of various antibiotics ranges between 0.125 and 128 μg/ml. FOS reaches inside the enterocyte concentrations which surpass the MICs of other antibiotics that also act by the inhibition of cell wall synthesis; however, further studies should be carried out to determine fosfomycin MIC for L. intracellularis to discern the usefulness of this antibiotic in the treatment of PPE.

The incorporation of natural essential oils to the pigsʼ diet in intensive production systems is a potential tool to improve gut health and prevent infections without using antibiotics. Nevertheless, different products, even containing the same compounds, coming from the same botanical species, may exert dissimilar biological effects due differences in the technological processes by which they are produced and preserved. For this reason, suitability of a given product based on natural extracts, intended for swine production must be thoroughly evaluated. In the present study, we assessed the effects of three additives containing oregano (Lippia origanoides) essential oil, alone or in combination with clover (Eugenia caryophillata) essential oil, with or without being microencapsulated, on gastrointestinal health and on some performance parameters in a commercial pig production farm. Recently weaned piglets were randomly divided in four groups, and basal diet or essential oil-supplemented diet (OCE; MOCE; MOE) was randomly assigned to each of the groups from weaning to finishing. Blood samples were collected at pre-established days after weaning. Intestinal sampling took place at 42 and 72 days of age. Pigs consuming the supplemented diets showed higher intestinal metabolic activity during the post-weaning period, decreasing the impact of weaning stress on enterocytesʼ metabolism. Intestinal barrier function was not affected in pigs consuming microencapsulated products. All treated groups showed improved intestinal architecture, increased digestive enzymes activity and caecal VFA concentrations. The incorporation of the dietary essential oils products brought beneficial effects on gastrointestinal health that were reflected in improved performance parameters.

29Intestinal health of weaning piglets was studied after oral treatments with . CC-BY 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . http://dx.doi.org/10.1101/323204 doi: bioRxiv preprint first posted online May. 15, 2018; 52 Introduction 53Weaning is considered one of the most critical periods of pig production because 54 of its highly negative impact on health and productive performance of piglets, mainly in 55 the first post-weaning days. During this period, the animals are exposed to are ascribable to bile action (9-12). CSE is used in intensive pig and avian productions. 73It is obtained from the leaves of the plant and contains caffeolquinic acid derivatives 74 which are known for their choleretic-cholagogue effect in different species (7,13,14), 75 including pigs (15). 76Among weaning stress factors, the presence of anti-nutritional compounds in 77 feed, such as mycotoxins, negatively influences the productive performance of animals.