Beta-escin has potent anti-allergic efficacy and reduces allergic airway inflammation

<p>Abstract</p> <p>Background</p> <p>Type I hypersensitivity is characterized by the overreaction of the immune system against otherwise innocuous substances. It manifests as allergic rhinitis, allergic conjunctivitis, allergic asthma or atopic dermatitis if mast cells are activated in the respective organs. In case of systemic mast cell activation, life-threatening anaphylaxis may occur. Currently, type I hypersensitivities are treated either with glucocorticoids, anti-histamines, or mast cell stabilizers. Although these drugs exert a strong anti-allergic effect, their long-term use may be problematic due to their side-effects.</p> <p>Results</p> <p>In the course of a routine <it>in vitro </it>screening process, we identified beta-escin as a potentially anti-allergic compound. Here we tested beta-escin in two mouse models to confirm this anti-allergic effect <it>in vivo</it>. In a model of the early phase of allergic reactions, the murine passive cutaneous anaphylaxis model, beta-escin inhibited the effects of mast cell activation and degranulation in the skin and dose-dependently prevented the extravasation of fluids into the tissue. Beta-escin also significantly inhibited the late response after antigen challenge in a lung allergy model with ovalbumin-sensitized mice. Allergic airway inflammation was suppressed, which was exemplified by the reduction of leucocytes, eosinophils, IL-5 and IL-13 in the bronchoalveolar lavage fluid. Histopathological examinations further confirmed the reduced inflammation of the lung tissue. In both models, the inhibitory effect of beta-escin was comparable to the benchmark dexamethasone.</p> <p>Conclusions</p> <p>We demonstrated in two independent murine models of type I hypersensitivity that beta-escin has potent anti-allergic properties. These results and the excellent safety profile of beta-escin suggest a therapeutic potential of this compound for a novel treatment of allergic diseases.</p

The first RT-qPCR confirmed case of tick-borne encephalitis in a dog in Scandinavia

Background Tick-borne encephalitis (TBE) is a zoonotic neurological disease caused by tick-borne encephalitis virus (TBEV), a flavivirus endemic in parts of Europe and Asia. Seroconversion without signs of clinical disease is common in dogs and most of the cases previously described have been tentatively diagnosed by combining neurologic signs with serum antibody titres. Here, the first Scandinavian RT-qPCR-confirmed clinical case of TBE in a dog is reported. Case presentation A 4-year old castrated male Pointer Labrador cross was presented with acute-onset ataxia. During hospitalisation, the dog developed seizures. Despite aggressive treatment with steroids, antimicrobials and sedation/anaesthesia, there was continued deterioration during the following 24 h after admission and the dog was euthanised and submitted for necropsy. Histopathological changes in the brain were consistent with lymphoplasmacytic and histiocytic meningoencephalomyelitis. RT-qPCR examination of the brain was positive for TBEV, confirming infection. Conclusions Meningoencephalomyelitis caused by TBEV should be a diagnostic consideration in dogs presenting with clinical signs of central nervous system disease such as acute-onset ataxia and seizures in areas where TBEV-positive ticks are endemic. Clinical TBE may be underdiagnosed in dogs due to lack of specific testing

Evidence of Parvovirus Replication in Cerebral Neurons of Cats

The correlation between parvovirus infections and lesions in the central nervous system other than cerebellar hypoplasia was studied in 100 cats. The animals were necropsied with a history of various diseases, one third showing typical clinical and pathomorphological signs of panleukopenia. In 18 cats polyclonal antiserum against canine parvovirus consistently labeled neurons mainly in diencephalic regions, whereas the cerebellar cortex remained negative in all cases. In situ hybridization with digoxigenin-labeled minus-sense RNA probes, hybridizing with monomer-replicative form DNA or mRNA, revealed positive signals in nuclei of several neurons of the brain, again excluding the cerebellum. PCR applied to formalin-fixed and paraffin-embedded brain tissue and intestinal tissues of the diseased cats and subsequent DNA sequence analysis yielded canine parvovirus type 2 (CPV-2)-like sequences in the central nervous system. Two aspects of these findings are intriguing: (i) parvoviruses appear to be capable of replicating in neurons, cells that are considered to be terminally differentiated and (ii) CPV-like viruses of the old antigenic type CPV-2 appear to be able to infect cats

Emergence of Usutu virus, an African Mosquito-Borne Flavivirus of the Japanese Encephalitis Virus Group, Central Europe

During late summer 2001 in Austria, a series of deaths in several species of birds occurred, similar to the beginning of the West Nile virus (WNV) epidemic in the United States. We necropsied the dead birds and examined them by various methods; pathologic and immunohistologic investigations suggested a WNV infection. Subsequently, the virus was isolated, identified, partially sequenced, and subjected to phylogenetic analysis. The isolates exhibited 97% identity to Usutu virus (USUV), a mosquito-borne Flavivirus of the Japanese encephalitis virus group; USUV has never previously been observed outside Africa nor associated with fatal disease in animals or humans. If established in central Europe, this virus may have considerable effects on avian populations; whether USUV has the potential to cause severe human disease is unknown

Evaluation of a gene-directed enzyme-product therapy (GDEPT) in human pancreatic tumor cells and their use as in vivo models for pancreatic cancer.

BACKGROUND: Gene-directed enzyme prodrug therapy (GDEPT) is a two-step treatment protocol for solid tumors that involves the transfer of a gene encoding a prodrug-activating enzyme followed by administration of the inactive prodrug that is subsequently activated by the enzyme to its tumor toxic form. However, the establishment of such novel treatment regimes to combat pancreatic cancer requires defined and robust animal model systems. METHODS: Here, we comprehensively compared six human pancreatic cancer cell lines (PaCa-44, PANC-1, MIA PaCa-2, Hs-766T, Capan-2, and BxPc-3) in subcutaneous and orthotopical mouse models as well as in their susceptibility to different GDEPTs. RESULTS: Tumor uptake was 83% to 100% in the subcutaneous model and 60% to 100% in the orthotopical mouse model, except for Hs-766T cells, which did not grow orthotopically. Pathohistological analyses of the orthotopical models revealed an infiltrative growth of almost all tumors into the pancreas; however, the different cell lines gave rise to tumors with different morphological characteristics. All of the resultant tumors were positive for MUC-1 staining indicating their origin from glandular or ductal epithelium, but revealed scattered pan-cytokeratin staining. Transfer of the cytochrome P450 and cytosine deaminase suicide gene, respectively, into the pancreatic cancer cell lines using retroviral vector technology revealed high level infectibility of these cell lines and allowed the analysis of the sensitivity of these cells to the chemotherapeutic drugs ifosfamide and 5-fluorocytosine, respectively. CONCLUSION: These data qualify the cell lines as part of valuable in vitro and in vivo models for the use in defined preclinical studies for pancreas tumor therapy

Construction and Rescue of a Molecular Clone of Deformed Wing Virus (DWV)

<div><p>European honey bees are highly important in crop pollination, increasing the value of global agricultural production by billions of dollars. Current knowledge about virulence and pathogenicity of <i>Deformed wing virus</i> (DWV), a major factor in honey bee colony mortality, is limited. With this study, we close the gap between field research and laboratory investigations by establishing a complete <i>in vitro</i> model for DWV pathogenesis. Infectious DWV was rescued from a molecular clone of a DWV-A genome that induces DWV symptoms such as crippled wings and discoloration. The expression of DWV proteins, production of infectious virus progeny, and DWV host cell tropism could be confirmed using newly generated anti-DWV monoclonal antibodies. The recombinant RNA fulfills Koch’s postulates circumventing the need of virus isolation and propagation of pure virus cultures. In conclusion, we describe the development and application of a reverse genetics system for the study of DWV pathogenesis.</p></div