Is downer cow syndrome related to chronic botulism?

The present work was directed to investigate the relationship between Downer cow syndrome (DCS) and chronic botulism in dairy cattle. For this purpose, a total of 52 fresh calving downer cows and 206 apparently healthy cows at 14 dairy farms were investigated for Clostridium botulinum ABE and CD antibody levels, C. botulinum and botulinum neurotoxin in rumen fluids as well as in faeces. Results indicated that the downer cows had higher IgG titers for C. botulinum ABE and CD than the healthy cows. All tested rumen fluids were negative for BoNT and C. botulinum. BoNT/D, however, and C. botulinum type D spores were detected in faecal samples of healthy and downer cows in the selected farms. In conclusion, the presence of a significantly higher C. botulinum ABE and CD antibody levels in DCS cows than in the healthy animals suggests that chronic C. botulinum toxico-infection could be a predisposing factor for DCS.

Clinical and anti-inflammatory effects of treating endotoxin-challenged pigs with meloxicam.

The clinical and anti-inflammatory effects of a single treatment of 0.4 mg meloxicam/kg bodyweight on pigs that had been challenged with Escherichia coli endotoxin were investigated. Significantly lower total clinical scores were recorded in pigs treated with meloxicam than in pigs treated with a placebo. Significantly higher mean serum concentrations of thromboxane B(2) were also recorded in pigs treated with a placebo for up to 24 hours after the challenge. The serum concentrations of acute phase proteins and specific antibody titres to E coli lipopolysaccharide were unaffected by the meloxicam. The meloxicam treatment was well tolerated.

Luminal salmonella endotoxin affects epithelial and mast cell function in the proximal colon of pigs.

BACKGROUND: Salmonellosis and systemic endotoxaemia affect intestinal function. However, little is known about the functional importance of luminal Salmonella (S.) endotoxin during intestinal infection. METHODS: Pigs were either given or not given lipopolysaccharide (LPS, 30 mg day(-1)) of S. Typhimurium DT-104 orally for 14 days. Blood samples were taken weekly. After slaughter (day 14), epithelia of the proximal colon were investigated in Ussing chambers. Bacterial translocations to lung, liver, spleen and several lymph nodes were determined by culture. RESULTS: Endotoxin feeding increased plasma C-reactive protein (CRP) and histamine levels without evoking clinical signs. Postmortem, proximal colonic epithelia of LPS-treated animals showed both a decreased histamine release after mast cell stimulation with A23187 and a smaller increase in short-circuit current after A23187 application. Addition of the nitric oxide donor, sodium nitroprusside (SNP), also elicited lower increases in short-circuit current in the proximal colon of endotoxin-treated pigs. Endotoxin pre-feeding decreased colonic ion conductance, although mannitol and histamine fluxes were high in some epithelia of this group. Luminal Salmonella endotoxin increased bacterial translocation to proximal jejunal lymph nodes. LPS applied to colonic epithelia in vitro had no electrophysiological effects. CONCLUSIONS: Luminal endotoxin elicits an acute phase response and affects intestinal electrolyte transport and mast cell function. Furthermore, LPS induces epithelial spots of increased mannitol permeability that could be identical to spots of enhanced bacterial translocation.

Results of an open, non-placebo controlled pilot study investigating the immunomodulatory potential of autovaccine.

Autovaccines are prepared from autologous, human, non-pathogenic, "rough" variants of E. coli derived from the stool flora of individuals according to a highly standardized procedure. As a fundamental concept within microbiological therapy, these autovaccines are mainly used to treat chronic inflammatory disorders associated with impaired immune reactions resistant to standard therapeutic treatments. Generally, immunomodulatory effects of outer membrane components or cell wall fragments of gram-negative bacteria on innate or adaptive immunity are widely accepted but nevertheless mechanisms of actions of these autovaccines remained obscure, despite some recent publication about other autovaccine preparations of different origin. Hence, immunomodulating properties of autovaccine were investigated in a pilot study with 78 outpatients with variable disorders ranging from recurrent respiratory infections to diffuse gastrointestinal complaints. Patients received their autologous bacteria parenterally in increasing doses. Before application and 4 to 6 weeks after application of autovaccine, blood samples of the patients were taken to investigate a range of immunological parameters such as acute phase proteins, serum antibodies and cytokines. The results revealed that autovaccines were able to modulate significantly the release of three potent immunoregulatory cytokines e.g. interferon-gamma, granulocyte-macrophage-colony stimulating factor and interleukin-1 beta, whereas specific humoral immunity remained largely unaffected. From these results it may be concluded that the autovaccine mainly act antigen non-specifically on the cytokine level rather than inducing a specific vaccination. Further studies with more detailed kinetic measurements of cytokines will have to verify these results.

The acute phase response following implantation of triclosan-bonded vascular prostheses.

OBJECTIVE: Infection of prosthetic material is a major complication of vascular surgery. Therapy for it includes implantation of antimicrobial prostheses bonded with different antimicrobial agents. These agents may, however, induce an acute phase reaction following implantation in the host, thus compromising follow-up of the infection. It is not known whether the antimicrobial agent triclosan induces a significant acute phase reaction when bonded to vascular prostheses. METHODS: To study this, 34 adult swine weighing 20-30 kg were allotted randomly to the following groups: (1) controls with untreated prostheses, (2) control group with triclosan-bonded prostheses, (3) therapy group with untreated prostheses, local infection with Staphylococcus aureus surgical revision, and exchange with new, untreated prostheses, and (4) therapy group with untreated prostheses, local infection with S. aureus, surgical revision, and exchange with triclosan-bonded prostheses. Serum C-reactive protein (CRP) and haptoglobin values were determined during the 28-day period after surgery. The study was performed at the Institute for Surgical Research of the Ludwig Maximilian University School of Medicine in Munich. RESULTS: Normal ranges of serum CRP and haptoglobin values were 10.7+/-1.4 microg/ml and 2.5+/-0.3 mg/ml, respectively. Following implantation of untreated and triclosan-bonded vascular prostheses, significantly elevated serum CRP and haptoglobin values were observed. No significant differences between results with triclosan-bonded and untreated prostheses were observed in control or treatment groups. No correlation was found between acute phase reaction and the absence or presence of infection. CONCLUSIONS: Triclosan is the only antimicrobial agent that bonds to vascular prosthetic material without the need of a sealant. Our data indicate that vascular prosthesis implantation, whether untreated and triclosan-bonded, results in a significant acute phase reaction. No differences between antimicrobial and untreated prostheses were observed, independently of the absence or presence of infection. The antimicrobial agent itself did not induce a severe acute phase response and may, therefore, be used in patients at risk of infection.

Candida albicans clinical isolates inactivated by formalin with different adherence to buccal epithelial cells induce proinflammatory and regulatory cytokines in human peripheral blood mononuclear cells.

Besides the activation of phagocytes, the release of cytokines is the most important immunological defence mechanism of an organism against infection with Candida albicans. On the other hand cytokines induced in the organism by the yeast itself are able to modulate the immune responses of the host. We investigated whether eight clinically isolated strains of C. albicans inactivated by formalin as well as a laboratory strain were able to induce proinflammatory and regulatory cytokines in peripheral blood mononuclear cells (PBMC) of four different donors. Under our assay conditions the yeast strains induced the cytokines interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in PBMC to varying extents, but not the cytokine interleukin-4 (IL-4). We observed a difference in the reaction of the individual donors to the stimulus C. albicans but on the other hand the extent of the cytokine signal seemed to be dependent on the yeast strain as well. No correlation was found between the ability of the individual C. albicans strains to induce cytokines in PBMC and their ability to adhere to buccal epithelial cells. Determination of the cytokine induction potential of C. albicans strains possibly may contribute to the detection of new virulence factors of this yeast.

[Determination of C-reactive protein and neopterin in serum of diseased and bacterially infected swine]. / Bestimmung von C-reaktivem Protein und Neopterin in Seren erkrankter und bakteriell infizierter Schweine.

The parameters C-reactive protein (CRP) and neopterin, which are associated with immunological reactions, were investigated in serum of healthy, diseased and with Haemophilus parasuis infected pigs. When comparing diseased young pigs with healthy young pigs significant increases of the CRP- and neopterin concentrations can be seen. The increase of the CRP-concentration was most remarkable. After the infection of SPF-piglets with Haemophilus parasuis, significantly decreased neopterin concentrations and increased CRP concentrations were determined in comparison with non-infected animals. The animals with the symptoms of arthritis and disorders of the central nervous system showed the lowest neopterin concentrations and the highest concentrations of CRP. It seems that CRP and neopterin are interesting serum parameters in pigs with regard to the recognition of immunological reactions after illness or infection.

Peptide design by artificial neural networks and computer-based evolutionary search.

A technique for systematic peptide variation by a combination of rational and evolutionary approaches is presented. The design scheme consists of five consecutive steps: (i) identification of a "seed peptide" with a desired activity, (ii) generation of variants selected from a physicochemical space around the seed peptide, (iii) synthesis and testing of this biased library, (iv) modeling of a quantitative sequence-activity relationship by an artificial neural network, and (v) de novo design by a computer-based evolutionary search in sequence space using the trained neural network as the fitness function. This strategy was successfully applied to the identification of novel peptides that fully prevent the positive chronotropic effect of anti-beta1-adrenoreceptor autoantibodies from the serum of patients with dilated cardiomyopathy. The seed peptide, comprising 10 residues, was derived by epitope mapping from an extracellular loop of human beta1-adrenoreceptor. A set of 90 peptides was synthesized and tested to provide training data for neural network development. De novo design revealed peptides with desired activities that do not match the seed peptide sequence. These results demonstrate that computer-based evolutionary searches can generate novel peptides with substantial biological activity.

[C-reactive protein as a new parameter of mastitis]. / Das C-reaktive Protein als ein neuer Parameter bei Mastitis.

The C-reactive protein (CRP) is an acute phase protein. Its deposit can be seen on several animal species. Following the development of a test system (enzyme-immunoassay/EIA) for the quantitative determination of bovine CRP, it was possible to detect this protein in bovine raw milk for the first time. It was shown in the first extensive investigations that the CRP concentration in raw milk was increased, sometimes as much as tenfold as a result of udder inflammation (mastitis). In several screening analyses of a herd of cows, the CRP-values were compared with the somatic cell number, fat, protein and lactose content. The degree of CRP concentrations in raw milk in cows suffering from mastitis during the antibiotic treatment was reflected in the treatment success. When CRP was used as an additional parameter of selection, a better average udder health could be seen after five months. The first results of our investigations demonstrate that CRP is a practicable indicator of inflammation and may be effectively used to determine and control udder illness in cows.

[C-reactive protein (CRP)--an acute-phase protein with importance in laboratory medicine in veterinary medicine]. / C-reaktives Protein (CRP)--ein Akute-Phase-Protein mit labormedizinischer Bedeutung in der Veterinärmedizin.

CRP is an acute phase protein (APP) formed by hepatic cells in acute phase reaction (APR). APR is initiated by a broad spectrum of cytokines of activated macrophages of blood and tissues. During the APR, plasma concentrations of APP are changed. Cytokines regulate APPs. CRP is a phylogenetically very old molecule. The degree of homology of amino acids in CRP is very high in a lot of species. CRP binding specificities depend on Ca++. The diagnostic importance of CRP in veterinary medicine is discussed.

Inhibition of platelet aggregation following chronic in vivo treatment of rats with nicotine: prevention by simultaneous application of propranolol.

Platelet aggregability is known to be enhanced and platelet-survival time shortened in smokers when compared with nonsmokers. Up to now it is unknown which of the substances in tobacco smoke are responsible for these effects. To evaluate a possible role of nicotine, rats were chronically treated with the alkaloid (10 mg/kg/day), continuously released from subcutaneously implanted osmotic minipumps. Surprisingly, after 8 weeks, platelet sensitivity toward the aggregating stimulus adenosine 5'-diphosphate (ADP) was markedly reduced. The mean ADP concentration required to induce half the maximum rate of aggregation (EC50) was 0.88 mumol/L in nicotine-treated animals, as compared with 0.67 mumol/L in controls (p less than 0.002). Platelet aggregability remained normal when the rats were treated simultaneously with nicotine and the beta blocker propranolol (3.5 mg/kg/day); for these animals, the mean EC50 for ADP was 0.73 mumol/L. These results are suggestive of a catecholamine-mediated action of nicotine. However, neither the basal levels of cAMP in platelet-rich plasma, nor the cAMP levels attained after stimulation of platelet adenylate cyclase with prostaglandin E1 (PGE1), were affected by 8 weeks of treatment with nicotine or nicotine plus propranolol. No effect on platelet aggregation was observed when the rats were treated with nicotine for only 2 weeks, or when nicotine or nicotine plus cotinine were added to platelet-rich plasma in vitro in concentrations equal to those attained in vivo after 8 weeks. Thus, prolonged application of nicotine in vivo caused an inhibition of ADP-induced rat platelet aggregation presumably mediated by beta-catecholaminergic stimulation of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic treatment with adrenaline or propranolol on platelet function and c-AMP levels in the rat.

Most of our knowledge about the modulation of platelet function by catecholamines is based on observations of acute in vitro actions. Little is known about the effects of chronically elevated or reduced adrenergic stimulation of the platelets. We therefore treated rats for 8 weeks with either adrenaline or the beta-blocker propranolol. Adrenaline (0.5 mg.kg-1.d-1) continuously administered from subcutaneously implanted osmotic mini pumps caused an increase in the sensitivity of the platelets towards ADP as stimulating agent. In contrast, chronic application of propranolol (10 mg.kg-1.d-1) via the drinking water led to a reduction in platelet aggregability. For animals treated with adrenaline, in accordance with the results of the aggregation experiments, the levels of c-AMP found in platelet rich plasma were reduced, both basally (by 33%) and after stimulation of platelet adenylate cyclase with prostaglandin E1 (by 39%). For the propranolol treated animals, the basal c-AMP concentrations remained unchanged. The levels of c-AMP attained after stimulation with prostaglandin E1 were diminished to a similar extent as for the adrenaline treated animals (by 38%). Although the in vitro addition of adrenaline to platelet rich plasma causes a beta-adrenoceptor mediated inhibition of platelet aggregation in the rat, the simulation seen after chronic adrenaline exposure in vivo, which is associated with decreases in both basal and stimulated c-AMP levels, suggests a functional preponderance of alpha-adrenoceptors over beta-adrenoceptors on the rat platelets. Although intraplatelet metabolic changes (blockade of stimulated c-AMP formation) after chronic application of propranolol should have resulted in enhancement of platelet aggregability, an inhibition of aggregation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)