Upfront denileukin diftitox as in vivo regulatory T-cell depletion in order to enhance vaccination effects in a canine allogeneic hematopoietic stem cell transplantation model     

Knueppel A  Lange S  Altmann S  Sekora A  Knuebel G  Vogel H  Lindner I  Freund M  Junghanss C 《Veterinary immunology and immunopathology》2012,145(1-2):233-240

Denileukin Diftitox (ONTAK^®, DAB₃₈₉ IL-2) is a recombinant DNA-derived fusion protein depleting cells that express high-affinity IL-2 receptor. Important cell targets are CD4⁺CD25⁺Foxp3⁺ regulatory T cells (T_reg). Elimination of immunosuppressive T_reg by Denileukin Diftitox may provide a way to modulate immune tolerance following stem cell transplantation. Here, we combined T_reg depletion with a vaccination approach to induce donor-specific immune reactions. To investigate this approach we chose the mixed chimerism canine stem cell transplantation model which represents a high state of tolerance between two hematopoietic systems. The aim was therefore to induce a graft versus hematopoiesis effect thereby converting mixed to full donor chimerism. Dog leukocyte antigen identical siblings that had developed a stable mixed chimerism after non-myeloablative stem cell transplantation received a single dose of Denileukin Diftitox (18 μg/kg, i.v.) followed by several cell-lysate vaccinations. Host peripheral blood mononuclear cell lysates combined with CpG-ODN, and Montanide^® ISA 51 were locally applied. In vitro studies demonstrated that canine T_reg are a target of Denileukin Diftitox. The suppression of T-cell proliferation by T_reg was abolished by addition of Denileukin Diftitox (10 nM). An increase of proliferation of median 300% (range: 200%–425%) was observed. No change in donor chimerism was observed after administration of Denileukin Diftitox and vaccination. This study highlights that application of Denileukin Diftitox resulted in a depletion of T_reg followed by an increase of immune response in vitro. This effect could not be confirmed in vivo even if the immune system was stimulated by vaccinations.  相似文献   

Gene transcription abnormalities in canine atopic dermatitis and related human eosinophilic allergic diseases     

Plager DA  Torres SM  Koch SN  Kita H 《Veterinary immunology and immunopathology》2012,149(1-2):136-142

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Estrus cycle effect on muscle tyrosine kinase activity in bitches     

Gomes Pöppl Á  Costa Valle S  Hilário Díaz González F  de Castro Beck CA  Kucharski LC  Silveira Martins Da Silva R 《Veterinary research communications》2012,36(1):81-84

Estrus cycle is a well recognized cause of insulin resistance in bitches. The insulin receptor (IR) as well as the insulin-like growth factor-I receptor belong to the same subfamily of tyrosine kinase (TK) receptors. The objective of this study was to evaluate basal TK activity in muscle tissue of bitches during the estrus cycle. Twenty-four bitches were used in the study (7 in anestrus, 7 in estrus, and 10 in diestrus). Muscle samples, taken after spaying surgery to determine TK activity, were immediately frozen in liquid nitrogen and then stored at −80°C until the membranes were prepared by sequential centrifugation after being homogenized. TK activity was determined by Poly (Glu 4:Tyr 1) phosphorylation and expressed in cpm/μg of protein. TK activity was significantly lower (P < 0.001) in the animals in estrus (104.5 ± 11.9 cpm/μg of protein) and diestrus (94.5 ± 16.9 cpm/μg of protein) when compared with bitches in anestrus (183.2 ± 39.2 cpm/μg of protein). These results demonstrate, for the first time, lower basal TK activity in the muscle tissue of female dogs during estrus and diestrus, which may represent lower insulin signaling capacity, opening a new field of investigation into the molecular mechanisms of insulin resistance in dogs.  相似文献   

Integrative approach for landscape-based graph connectivity analysis: a case study with the common frog (Rana temporaria) in human-dominated landscapes     

Samuel Decout  Stéphanie Manel  Claude Miaud  Sandra Luque 《Landscape Ecology》2012,27(2):267-279

Graph-based analysis is a promising approach for analyzing the functional and structural connectivity of landscapes. In human-shaped landscapes, species have become vulnerable to land degradation and connectivity loss between habitat patches. Movement across the landscape is a key process for species survival that needs to be further investigated for heterogeneous human-dominated landscapes. The common frog (Rana temporaria) was used as a case study to explore and provide a graph connectivity analysis framework that integrates habitat suitability and dispersal responses to landscape permeability. The main habitat patches influencing habitat availability and connectivity were highlighted by using the software Conefor Sensinode 2.2. One of the main advantages of the presented graph-theoretical approach is its ability to provide a large choice of variables to be used based on the study’s assumptions and knowledge about target species. Based on dispersal simulation modelling in potential suitable habitat corridors, three distinct patterns of nodes connections of differing importance were revealed. These patterns are locally influenced by anthropogenic barriers, landscape permeability, and habitat suitability. And they are affected by different suitability and availability gradients to maximize the best possible settlement by the common frog within a terrestrial habitat continuum. The study determined the key role of landscape-based approaches for identifying the “availability-suitability-connectivity” patterns from a local to regional approach to provide an operational tool for landscape planning.  相似文献   

Subtilase cytotoxin encoding genes are present in human, sheep and deer intimin-negative, Shiga toxin-producing Escherichia coli O128:H2     

Sánchez S  Beristain X  Martínez R  García A  Martín C  Vidal D  Díaz-Sánchez S  Rey J  Alonso JM  Herrera-León S 《Veterinary microbiology》2012,159(3-4):531-535

Shiga toxin-producing Escherichia coli (STEC) O128:H2 is recognised worldwide to be an important non-O157 STEC associated with human illness and in particular with causing haemolytic uraemic syndrome. This serotype is commonly isolated from sheep and is being increasingly isolated from deer. We determined the virulence profile and genetic relationships of one human, six sheep and five deer intimin-negative STEC O128:H2 strains isolated in Spain over a 7-year period. Our goals were to establish the presence of other virulence-associated factors, such as SubAB, in intimin-negative STEC O128:H2 strains involved in human disease and in that case, to determine if sheep and/or deer represent a reservoir of SubAB-positive STEC O128:H2. All the strains lacked the eae gene and carried subtilase cytotoxin (SubAB) encoding genes (subAB) and tia genes, but not saa gene, suggesting the presence of the recently identified new variant of SubAB, encoded on a putative pathogenicity island together with tia. We report for the first time the presence of subtilase cytotoxin encoding genes in intimin-negative STEC O128:H2 strains pathogenic for humans and how this finding might explain their clinical relevance despite neither carrying eae nor stx subtypes associated with severe clinical outcomes, but only stx1c and stx2b. Multilocus sequence typing analysis revealed that STEC O128:H2 strains from sheep and deer belong to the clonal lineage of STEC O128:H2 strains involved in diarrhoeal and haemorrhagic diseases in humans. Our results indicate that sheep and deer represent a reservoir of SubAB-positive STEC O128:H2 strains and thus a potential source of human infection.  相似文献   

Gastroprotective potential of frutalin, a D-galactose binding lectin, against ethanol-induced gastric lesions     

de Vasconcellos Abdon AP  Coelho de Souza G  Noronha Coelho de Souza L  Prado Vasconcelos R  Araújo Castro C  Moreira Guedes M  Pereira Lima RC  de Azevedo Moreira R  de Oliveira Monteiro-Moreira AC  Rolim Campos A 《Fitoterapia》2012,83(3):604-608

The present study was designed to verify whether frutalin (FTL) affords gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2 ml of ethanol (96%). Mice in groups were pretreated with FTL (0.25, 0.5 and 1 mg/kg; i.p.), cimetidine (100 mg/kg; p.o.), or vehicle (0.9% of NaCl, 10 mL/kg; p.o.), 30 min before ethanol administration. They were sacrificed 30 min later, the stomachs excised, and the mucosal lesion area (mm2) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide, sulphydryls, ATP-sensitive potassium channels, adrenoceptors, opioid receptors and calcium channels were analyzed. Treatments effects on ethanol-associated oxidative stress markers GSH and MDA were measured in gastric tissue. FTL afforded a dose-unrelated gastroprotection against the ethanol damage. However, it failed to prevent the ethanol-induced changes in the levels of GSH and MDA. It was observed that the gastroprotection by FTL was greatly reduced in animals pretreated with capsazepine, indomethacin, L-NAME or glibenclamide. Considering the results, it is suggested that the FTL could probably be a good therapeutic agent for the development of new medicine for the treatment of gastric ulcer.  相似文献   

Comparative evaluation of live marker vaccine candidates "CP7_E2alf" and "flc11" along with C-strain "Riems" after oral vaccination     

Blome S  Aebischer A  Lange E  Hofmann M  Leifer I  Loeffen W  Koenen F  Beer M 《Veterinary microbiology》2012,158(1-2):42-59

Due to the tremendous socio-economic impact of classical swine fever (CSF) outbreaks, emergency vaccination scenarios are continuously under discussion. Unfortunately, all currently available vaccines show restrictions either in terms of marker capacities or immunogenicity. Recent research efforts were therefore directed at the design of new modified live marker vaccines. Among the most promising candidates the chimeric pestiviruses "CP7_E2alf" and "flc11" were identified. Within an international research project, these candidates were comparatively tested in challenge experiments after a single oral vaccination. Challenge infection was carried out with highly virulent CSF virus strain "Koslov", 14 or 21 days post vaccination (dpv), respectively. Safety, efficacy, and marker potential were addressed. All assessments were done in comparison with the conventional "gold standard" C-strain "Riems" vaccine. In addition to the challenge trials, multiple vaccinations with both candidates were performed to further assess their marker vaccine potential. All vaccines were safe and yielded full protection upon challenge 21 days post vaccination. Neither serological nor virological investigations showed major differences among the three vaccines. Whereas CP7_E2alf also provided clinical protection upon challenge at 14 days post vaccination, only 50% of animals vaccinated with flc11, and 83% vaccinated with C-strain "Riems" survived challenge at this time point. No marked differences were seen in protected animals. Despite the fact that all multiple-vaccinated animals stayed sero-negative in the accompanying marker test, the discriminatory assay remains a weak point due to delayed or inexistent detection of some of the vaccinated and subsequently infected animals. Nevertheless, the potential as live marker vaccines could be confirmed for both vaccine candidates. Future efforts will therefore be directed at the licensing of "Cp7_E2alf" as the first live marker vaccine for CSF.  相似文献   

The effect of three anaesthetic protocols on the stress response in cane toads (Rhinella marina)     

Sandra E Hernández  Conrad Sernia  Adrian J Bradley 《Veterinary anaesthesia and analgesia》2012,39(6):584-590

ObjectiveThree anaesthetics (MS222, clove oil and a mixture of ketamine/diazepam) were administered to cane toads to determine their effect on the hypothalamic-pituitary-adrenal (HPA) axis. Time to induction and recovery and any adverse events were also evaluated.Study designProspective randomized experimental trial.AnimalsThirty adult male cane toads (Rhinella marina) with body mass ranging between 130 and 250 g were captured from the field.MethodsThree groups of 10 toads were anaesthetized with ketamine (200 mg kg^?1) and diazepam (0.2 mg kg^?1) by intramuscular injection, MS222 (3 g L^?1) or clove-oil (0.3 mL L^?1) both by immersion. Blood samples were collected to determine plasma corticosterone concentrations. Induction and recovery time were recorded in each treatment. After full recovery animals were euthanized and a complete post-mortem examination was performed.ResultsSignificant differences were found in the activation of the HPA axis and in the times of induction and recovery between treatments (p < 0.001). Animals anaesthetized with clove-oil had the highest levels of corticosterone in plasma (42.5 ± 21.6 ng mL^?1). No differences were found between ketamine/diazepam (15.0 ± 13.3 ng mL^?1) and MS222 (22.0 ± 13.6 ng mL^?1) groups. The mean ± SD induction (minutes) and recovery (hours) times respectively were; ketamine/diazepam 66.5 ± 11 and 8 ± 3, clove oil 39 ± 12 and 7.6 ± 3, and MS222 42.5 ± 11 and 1.5 ± 0.5. Clove oil exposure had 30% mortality. Death followed a period of respiratory distress with changes consistent with non-cardiogenic oedema observed at post-mortem examination.Conclusions and Clinical relevanceBased on shorter induction and recovery times and minimal activation of HPA, MS222 is the anaesthetic of choice in cane toads. If it is not possible to use immersion methods of anaesthesia, ketamine/diazepam can be used but induction and recovery times are prolonged. Clove oil had unacceptable mortality in this study and should be used with extreme caution.  相似文献   

Physicochemical and Enzyme Characterization of Small and Large Starch Granules Isolated from Two Maize Cultivars     

Rubí G. Utrilla‐Coello  Edith Agama‐Acevedo  Ana Paulina Barba de la Rosa  Sandra L. Rodríguez‐Ambriz  Luis Arturo Bello‐Prez 《Cereal Chemistry》2010,87(1):50-56

In this study, some morphological, physicochemical, and the initial characterization of the starch granule enzymes of blue and white maizes of small and large granules are described. Starch was isolated from blue and white maizes, and the small and large granules were separated. The efficiency of separation was higher in large granules than small of the blue maize starch. The amylose content was slightly greater (1.3%) in large granules than smaller in both starches studied. No differences in the average gelatinization temperature were found between large and small granules, but the enthalpy of gelatinization value was higher in the small granules. The electrophoretic pattern showed that the granule‐bound starch synthase (GBSSI) had higher expression in large than small granules and that explain the higher amylose content in the former granules. The differences showed in the starch biosynthesis enzymes in small and large granules might explain partially the physicochemical and functional properties of maize.  相似文献   

Brachial plexus block using electrolocation for pancarpal arthrodesis in a dog     

Wenger S 《Veterinary anaesthesia and analgesia》2004,31(4):272-275

Conduction blockade was achieved at the brachial plexus of a dog undergoing surgery for pancarpal arthrodesis. The lidocaine/bupivacaine mixture used was the sole analgesic treatment applied during surgery and for 3 hours post-operatively. Location of the plexus brachialis was facilitated using a nerve stimulator. A low volume of lidocaine and bupivacaine (0.26 mL kg(-1)) resulted in successful blockade, which was evident from stable cardiorespiratory variables at low end-tidal (1.3-1.4%) isoflurane concentrations. Pain scoring and examination of motor and sensory function indicated adequate pain relief for 7 hours. While localization of the plexus brachialis can be performed 'blindly', electrolocation improves the success rate for less experienced anaesthetists.  相似文献