[Sarcoptes scabiei var. suis in a closed pig breeding and fattening herd and control possibilities after treatment]. / Sarcoptes scabiei var. suis in einem geschlossenen Schweinezucht- und Mast- betrieb und Kontrollmöglichkeiten nach der Behandlung.

On an Austrian pig breeding and finishing farm containing 13,000 pigs a mange prevalence of 38.7% according to the results of the skin scraping and 28.2% based on serology was determined. Due to the insufficient treatment (single treatment of the sows using Phoxim [Sebacil pour on]), sustainable control was impossible. That could be confirmed by the high number of mange positive gilts and finishing pigs. Before eradication started the following prevalences of mange could be found: sows 6.74% (skin scrapings), respectively 6.18% (serologically), gilts 18.18% resp 28.67%, finishing pigs 54.35% and 38.58%. The breeding stock for eradication was treated with doramectin (Dectomax) injectable solution and the finishing pigs with Ivomec-praemix, both applied twice. The success of treatment of the different farm units and of different age groups was controlled for the following ten months by combined diagnostic methods. In addition to skin scrapings, serum and colostral samples were carried out using a commercially available ELISA licensed for investigation of blood serum and colostrum. After treatment antibodies in the serum of the sows and gilts and Sarcoptes mites in their skin scrapings were detectable for up to four months after treatment. In serum samples of piglets and colostrum samples antibodies against Sarcoptes mites were detectable up to five months after final treatment. Due to the higher level and longer verifiability of antibodies in blood samples of piglets for five months after treatment and high prevalences their use as a diagnostic tool can be recommended. In contrast the use of colostral samples for routine diagnosis should be investigated more thoroughly. The comparison of the results of different diagnostic methods showed that for reliable mange diagnosis combined methods are recommended.

Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal peptide drug delivery system.

PURPOSE: Intravenous application of pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified as a promising strategy for the treatment of type 2 diabetes. To generate a more applicable formulation, it was the aim of this study to develop a sustained buccal delivery system for this promising therapeutic peptide. METHODS: 2-Iminothiolane was covalently bound to chitosan to improve the mucoadhesive and permeation-enhancing properties of chitosan used as drug carrier matrix. The resulting chitosan-4-thiobutylamidine conjugate was homogenized with the enzyme inhibitor and permeation mediator glutathione (gamma-Glu-Cys-Gly), Brij 35, and PACAP (formulation A). The mixture was lyophilized and compressed into flat-faced discs (18 mm in diameter). One formulation was additionally coated on one side with palm wax (formulation B). Tablets consisting of unmodified chitosan and PACAP (formulation C) or of unmodified chitosan, Brij 35, and PACAP (formulation D) served as controls. Bioavailability studies were performed in pigs by buccal administration of these test formulations. Blood samples were analyzed via an ELISA method. RESULTS: Formulations A and B led to an absolute bioavailability of 1%, whereas PACAP did not reach the systemic circulation when administered via formulations C and D. Moreover, in the case of formulations A and B, a continuously raised plasma level of the peptide drug being in the therapeutic range could be maintained over the whole period of application (6 h). Formulations A and B were removed by moderate force from the buccal mucosa after 6 h, whereas formulations C and D detached from the mucosa 4 h after application. CONCLUSION: The study reveals this novel mucoadhesive delivery system to be a promising approach for buccal delivery of PACAP.

The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept.

It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

[Oesophagogastroduodenoscopy in swine--technique, methods, indications]. / Osophagogastroduodenoskopie beim Schwein--Technik, Methode, Indikationen.

The aim of this study was to investigate in 20 healthy pigs the practicability of the oesophagogastroduodenoscopic examination technique in regard to equipment, method of examination, indications and its suitability as a diagnostical tool for the assessment of the oesophagus, stomach and upper duodenum in one procedure. Preparation of the patient for endoscopy, the procedure of the endoscopic examination as well as the topographical findings of the upper intestinal tract including the duodenum until the flexura duodenojejunalis are described. Flexible oesophagogastroduodenoscopy is a suitable method for the observation and natural visualisation of mucosal surfaces and for the digital documentation of peristaltic movements. The procedure is easy to perform in anaesthetized animals, is in most cases completed within 15 min, and can be repeated in the same animal. Indications of this interesting diagnostic imaging technique are discussed.

Impact of extracorporeal membrane oxygenation modality on cytokine release during rescue from infant hypoxia.

The treatment of acute respiratory failure in infants by means of extracorporeal membrane oxygenation (ECMO) is thought to be associated with a treatment-related inflammatory reaction, which may deteriorate the underlying disease process. The aim of this study was to compare the venoarterial (VA) and venovenous (VV) modality of ECMO with regard to their pulmonary and serological cytokine release during rescue from acute hypoxia. The inflammatory response was measured in piglets undergoing hypoxic ventilation with a gas mixture of 92% N2 and 8% O2, which were then rescued through VA- (n = 5) or VV-ECMO (n = 5). The effect of cannulation and anesthesia on the inflammatory response was deducted from regularly ventilated control animals (n = 5). The concentrations of the proinflammatory interleukins (IL)-1beta and IL-8 increased in the bronchoalveolar lavage fluid of all groups over a study period of 5 h but were significantly higher (P < 0.05) during VA-ECMO treatment, whereas the anti-inflammatory IL-10 concentrations were significantly higher in the bronchoalveolar lavage fluid of VV-treated animals (P < 0.001). No statistical difference between groups was found in the serum concentrations of cytokines. We conclude that in this animal model rescue from hypoxia by means of the VA modality of ECMO leads to a more pronounced inflammatory reaction of the lung than when applying the VV modality.

Metabolic profiles of the mycotoxin zearalenone and of the growth promoter zeranol in urine, liver, and muscle of heifers.

A group of five heifers were fed for 84 days with 2 kg of zearalenone-contaminated oats (1370 microg/kg) resulting in an average daily intake of 2740 microg of zearalenone per animal. In a parallel experiment five heifers were implanted with two 25 mg zeranol pellets, one at the beginning of the study and one after 42 days, and fed with 2 kg of "blank" control oats (79 microg/kg, daily intake = 158 microg). A third group of five animals were also fed with 2 kg of "blank" oats and served as control. Urine samples of all animals were collected every 5-6 days during the whole period of the study. Animals of all three groups were killed 84 days after the beginning of the feeding study. Tissue samples (back, femoral region, liver, and residues of implanted pellets) were taken during post-mortem investigations. The content of zearalenone and zeranol and their metabolites in urine and tissue samples was established by an analytical method combining solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry. Urinary excretion rates of zeralenone and zeranol were calculated from these results.

Concentration levels of zearalenone and its metabolites in urine, muscle tissue, and liver samples of pigs fed with mycotoxin-contaminated oats.

The content of zearalenone and its metabolites in urine and tissue samples from pigs fed zearalenone-contaminated oats was established by analytical methods combining solid-phase extraction cleanup of the samples with highly selective liquid chromatography-mass spectrometry (LC-MS)/MS detection. Investigation of the urine samples revealed that approximately 60% of zearalenone was transformed in vivo to alpha-zearalenol and its epimer beta-zearalenol in a mean ratio of 3:1. Zeranol and taleranol as further metabolites could only be detected in trace amounts. Zearalanone was identified at considerable concentrations, though only in a couple of samples. In contrast, liver samples contained predominantly alpha-zearalenol, and to a minor extent beta-zearalenol and zearalenone, with a mean ratio of alpha-/beta-zearalenol of 2.5:1, while zeranol, taleranol, or zearalanone could not be identified in any of the investigated samples. The degree of glucoronidation was established for zearalenone as 27% in urine and 62% in liver; for alpha-zearalenol as 88% in urine and 77% in liver; and for beta-zearalenol as 94% in urine and 29% in liver. Analyses of muscle tissue revealed relatively high amounts of nonglucuronidated zeranol and alpha-zearalenol together with traces of taleranol and zearalenone, indicating that the metabolism of zearalenone and its metabolites is not restricted to hepatic and gastrointestinal metabolic pathways.