Intraepithelial but not lamina propria lymphocytes in the porcine gut are affected by dexamethasone treatment

It is well established that glucocorticoids are key regulators of the immune system and act as immunosuppressive agents in high concentrations. In the pig, effects on the gut immune system and trafficking of lymphocytes between tissues and blood plasma were not investigated so far. Twelve pigs of 70 kg were fed 0.4 mg portions of dexamethasone (Dexa) twice daily for 9 days or remained untreated (controls) and were sacrificed for tissue collection at the end of Dexa treatment. Another six pigs with jugular vein catheters were left untreated for 7 days (control period) and then received Dexa for 9 days. Blood was drawn twice during the control period and at days 3, 6 and 9 of the Dexa period for characterization of peripheral blood leukocytes. Cells were obtained from thymus, mesenteric lymph nodes, jejunal mucosa and Peyer's patches. Lymphoid cells from gut tissue were isolated from two fractions: the EDTA-fraction, containing the intraepithelial lymphocytes (IEL), and the Collagenase-fraction, containing the lamina propria lymphocytes (LPL). In all samples, cell counts and phenotypic characterization of cells by flow cytometry (FCM) were performed. In thymus, Dexa led to a more than 90% reduction of the absolute cell number, which was mainly found in the CD4+CD8+ subpopulation. Dexa effects on lymphocytes from mesenteric lymph nodes were less severe (50%) and led mainly to a decrease (71%) of B-lymphocytes. The number of lymphocytes in the EDTA-fraction (IEL) of the jejunal mucosa decreased significantly by 56% in the Dexa-treated animals compared to the controls, whereas the number of lymphocytes in the Collagenase-fraction (LPL) decreased only moderately. In the Peyer's patches, a decreasing tendency in the number of lymphocytes in the EDTA-fraction was observed which, however, was not significant. In blood, monocytes and granulocytes were significantly increased in an order of 60%. The data show that supraphysiological amounts of Dexa remarkably reduce cell numbers in thymus and also in the intraepithelial compartment of the jejunal mucosa and ileal Peyer's patches. In blood, a notable homeostasis was observed for several leukocyte populations whereas both monocytes and granulocytes increased.     

Luteoforol,a flavan 4-ol,is induced in pome fruits by prohexadione-calciumand shows phytoalexin-like properties against <Emphasis Type="Italic">Erwinia amylovora</Emphasis>and other plant pathogens

Treatments with prohexadione-calcium led to lowered incidence of fire blight, scab and other diseases in pome fruit trees and other crop plants. In addition to acting as a growth regulator, prohexadione-calcium interferes with flavonoid metabolism and induces the accumulation of the 3-deoxycatechin luteoliflavan in shoots of pome fruit trees. Luteoliflavan does not possess any remarkable antimicrobial activity. Therefore luteoforol, its unstable and highly reactive precursor, has been tested in vitro for its bactericidal and fungicidal activities. Luteoforol was found to be highly active against different strains of Erwinia amylovora, the causal agent of fire blight, and all other bacterial and fungal organisms tested. Phytotoxic effects were also observed in pear plantlets. The results obtained indicate that prohexadione-calcium induces luteoforol as an active principle with non-specific biocidal properties. It is proposed that luteoforol is released upon pathogen attack from its cellular compartment and inhibits further disease development by destroying pathogen cells as well as by inducing a hypersensitive-like reaction in the host plant tissue. This mechanism would be closely analogous to the one known for structurally related phytoalexins in sorghum.     

Auswirkungen von Weiden (Salix spp.) und Pappeln (Populus spp.) im Kurzumtrieb auf die biologische Vielfalt am Beispiel von Laufk?fern (Carabidae)

The increasing cultivation of energy crops in the last few years may have an impact on changes in the environment, biodiversity and the landscape. Due to a longer rest of soil and reduced application of pesticides, perennial crops such as short rotation coppice (SRC) offer benefits that can have a positive effect on the biodiversity. However, to assess the overall impact of SRC on biodiversity, information on the quality of SRC as a habitat for animals and plants, depending on the woody species over several years and the management is required. In the years 2010 and 2011, the diversity of ground beetles of willow and poplar in SRC were examined using pitfall traps at three sites in southwestern Germany. It was distinguished between species, variety and age of the SRC. At all sites ground beetle diversity was significantly higher in the studied poplar stands than in those of the willows. In addition, significant differences between the varieties could be observed depending on the location and the year of examination. The older stands of the SRC showed in general a higher level of diversity. Due to the different variety preference of ground beetles it is recommended to plant a mixture of varieties. Furthermore, SRC of different ages should be established side by side, as with increasing tree age species of the open area decrease and forest species settle. Overall, SRC offer the potential to increase biodiversity in natural landscapes.     

Compartmentalized control of skin immunity by resident commensals

Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.     

Establishment of diagnostic criteria for feline nonflea-induced hypersensitivity dermatitis

Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are usually caused by environmental, food and/or flea allergens. Affected cats normally present with one of the following clinical reaction patterns: head and neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin lesions or miliary dermatitis. Importantly, none of these clinical presentations is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD is usually based on the exclusion of other pruritic diseases and on a positive response to therapy. The objectives of this study were to propose sets of criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats with pruritus and skin lesions and compared clinical parameters between cats with NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea HD and other pruritic conditions. Using simulated annealing techniques, we established two sets of proposed criteria for the following two different clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats; and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These criteria sets were associated with good sensitivity and specificity and may be useful for homogeneity of enrolment in clinical trials and to evaluate the probability of diagnosis of NFHD in clinical practice. Finally, these criteria were not useful to differentiate cats with NFHD from those with food HD.     

Characterization of In Vitro Synthesized Equine Metabolites of the Selective Androgen Receptor Modulators S24 and S4

Several selective androgen receptor modulators (SARMs) have been synthesized and investigated in humans, rats, and dogs in the past, but no data are yet available concerning the metabolism of SARMs in horses. The aryl-propionamide-derived drug candidates S24 and S4 (andarine) have a strong androgen receptor binding affinity and show distinctive specific cell answers. Although no SARM drug candidate (aiming for testosterone replacement therapy) has completed clinical trials yet, S4 has been illicitly available via the Internet. These facts led to the prohibition of SARMs by the German equestrian federation, and the (mis)use of such compounds would further represent a doping rule violation in horse racing. In this study, the drug candidates S24 and S4 were subjected to in vitro metabolism experiments with equine liver microsomal preparations from a female Quarter Horse to obtain information about potential target analytes in equine doping control analysis. The enzymatically synthesized metabolites were characterized by liquid chromatography–tandem mass spectrometry and –high-resolution/high-accuracy mass spectrometry. All observed S24 and S4 equine metabolites are in agreement with earlier in vitro and in vivo studies in humans and dogs. Nevertheless, the relative percentage of generated equine metabolites (as determined from the analytes’ response in full-scan chromatography–tandem mass spectrometry and –high-resolution/high-accuracy mass spectrometry measurements) differs considerably from the reported profiles. Although the S24 metabolite pattern is comparably balanced concerning glucuronidated and sulfonated conjugates, the major S4 metabolite was found to be the unconjugated dephenylated compound, with a proportion of more than 90%.     

Clinical efficacy of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAP) in the treatment of feline immunodeficiency virus-infected cats

In in vitro studies, the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAP) inhibited the replication of feline immunodeficiency virus (FIV). No information about its clinical efficacy is available so far. The aim of this prospective placebo-controlled, double-blinded study was to evaluate the antiviral efficacy of PMPDAP in cats naturally infected with FIV. Twenty cats were randomly assigned to two treatment groups receiving either PMPDAP (25 mg/kg) or placebo twice per week subcutaneously for 6 weeks. The general health status (Karnofsky's score), clinical signs, laboratory, immunological, and surrogate parameters were evaluated. No significant differences were found between PMPDAP- and placebo-treated cats, although cats treated with PMPDAP showed a tendency for improvement in their Karnofsky's score and clinical signs. Haematological side effects were noted in the PMPDAP-treated cats. Thus, PMPDAP may be an option in treating cats if it becomes available for veterinarians, but side effects have been monitored.