Localized cutaneous calcinosis associated with leptospirosis in a 4-month-old beagle puppy.

A 4-month-old male beagle dog was presented for a 15-day history of firm cutaneous nodules. Histopathological examination of skin biopsies revealed calcinosis cutis. However, re-evaluation 40 d later confirmed spontaneous resolution of the lesions without specific treatment. Two weeks before development of the skin lesions, this dog had been hospitalized and treated for acute renal and hepatic disease attributed to leptospirosis, with both PCR and serology positive for Leptospira australis. Calcinosis cutis secondary to a systemic disease (leptospirosis, blastomycosis) has been rarely reported. In this case, the suspected pathogenesis included organic stress (cortisol hypersecretion) and abnormal calcium/phosphorus metabolism during acute renal failure. To our knowledge, this is the third published case of cutis calcinosis associated with leptospirosis in dogs. Key clinical message: Previous leptospirosis should be considered in a dog with calcinosis cutis. The cutaneous lesions appeared after acute leptospirosis and regressed spontaneously.

Calcinose cutanée localisée associée à une leptospirose chez un chiot Beagle de 4 mois. Un Beagle mâle de 4 mois a été présenté en consultation à la suite de l'apparition de nodules cutanés fermes 15 jours auparavant. L'examen histopathologique de biopsies cutanées a révélé une calcinose cutanée. Le contrôle à 40 jours a confirmé une résolution spontanée des lésions sans traitement spécifique. Deux semaines avant le développement des lésions cutanées, ce chien avait été hospitalisé et traité pour une maladie rénale et hépatique, attribuée à une leptospirose. Les examens PCR et sérologique étaient positifs pour Leptospira australis. La calcinose cutanée secondaire à une maladie systémique (leptospirose, blastomycose) est rarement rapportée et le mécanisme étiopathogénique suspecté comprenait un stress organique (hypersécrétion de cortisol) et un déséquilibre du métabolisme phosphocalcique lors de l'épisode d'insuffisance rénale aiguë. À notre connaissance, il s'agit du troisième cas publié de calcinose cutanée associée à la leptospirose chez le chien.Message clinique clé:Une potentielle leptospirose antérieure doit être mentionnée chez un chien atteint de calcinose cutanée. Les lésions cutanées semblent apparaître de manière décalée et régresser spontanément.(Traduit par Claude Muller).

Tannins from Hamamelis virginiana bark extract: characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus.

Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV) of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV) type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol) inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (<500 g/mol) such as gallic acid, epigallocatechin gallate or hamamelitannin inhibited neuraminidase but not hemagglutination. Average molecular weight of the compounds seemed to positively correlate with receptor binding (but not neuraminidase) inhibition. In general, neuraminidase inhibition seemed to contribute little to the antiviral activity. Importantly, antiviral use of the ultrafiltration fraction enriched in high molecular weight condensed tannins and, to a lesser extent, the unfractionated bark extract was preferable over individual isolated compounds. These results are of interest for developing and improving plant-based antivirals.

EPs® 7630 (Umckaloabo®), an extract from Pelargonium sidoides roots, exerts anti-influenza virus activity in vitro and in vivo.

A prodelphinidin-rich extract from Pelargonium sidoides DC, EPs® 7630 (Umckaloabo®), which is licensed to treat respiratory tract infections such as acute bronchitis, was investigated for its antiviral effects. EPs® 7630 showed dose-dependent anti-influenza activity at non-toxic concentrations against pandemic H1N1, oseltamivir-sensitive and -resistant seasonal H1N1, seasonal H3N2 and the laboratory H1N1 strain A/Puerto Rico/8/34, while it had no antiviral activity against adenovirus or measles virus. The extract inhibited an early step of influenza infection and impaired viral hemagglutination as well as neuraminidase activity. However, EPs® 7630 did not exhibit a direct virucidal effect, as virus preincubation (unlike cell preincubation) with the extract did not influence infectivity. Importantly, EPs® 7630 showed no propensity to resistance development in vitro. Analysis of EPs® 7630 constituents revealed that prodelphinidins represent the active principle. Chain length influenced antiviral activity, as monomers and dimers were less effective than oligo- and polymers. Importantly, gallocatechin and its stereoisomer epigallocatechin exert antiviral activity also in their monomeric form. In addition, EPs® 7630 administered by inhalation significantly improved survival, body weight and body temperature of influenza-infected mice, without obvious toxicity, demonstrating the benefit of EPs® 7630 in treatment of influenza.

Decreased expression of mineralocorticoid receptor mRNA and its splice variants in postmortem brain regions of patients with major depressive disorder.

Appropriate signaling in the brain by the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) is critical in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, emotional arousal and cognitive performance. To date, few data exist on MR (and GR) expression in the brain of patients suffering from major depressive disorder (MDD). With the help of quantitative PCR we assessed MR and GR mRNA expression, including the splice variants MRα and MRß, in tissue samples from the hippocampus, amygdala, inferior frontal gyrus, cingulate gyrus and nucleus accumbens. Expression levels were compared between tissue samples from six MDD patients and six non-depressed subjects. Relative to total GR, total MR mRNA expression was higher in hippocampus and lower in the amygdala, inferior frontal gyrus and nucleus accumbens. Both MRα and MRß could be detected in all brain regions that were analyzed, although MRß expression was low. Significantly lower expression levels (30-50%) were detected for MR or GR in hippocampal, inferior frontal gyrus and cingulate gyrus tissue from MDD patients (p < .05), while no differences were found in the amygdala or nucleus accumbens. The data show that both MRα and MRß mRNA are expressed throughout the human limbic brain with highest expressions in the hippocampus. A decreased expression of corticosteroid receptors in specific brain regions of MDD patients could underlie HPA hyperactivity, mood and cognitive disturbances often observed in patients suffering from stress-related psychopathologies.

Neutralising immunogenicity of a polyepitope antigen expressed in a transgenic food plant: a novel antigen to protect against measles.

Transgenic carrot plants were developed expressing a designer polyepitope combining tandem repeats of a protective loop-forming B cell epitope (H386-400) of the measles virus hemagglutinin protein with a human promiscuous, measles-unrelated T cell epitope (tt830-844). Despite the sensitivity of the loop conformation to its molecular environment, proper folding was confirmed by conformation-dependent monoclonal antibodies. The antibodies also reacted with the boiled antigen in Western blot. Immunisation of mice peritoneally with carrot plant extracts induced high titers of antibodies that crossreacted strongly with the virus. Furthermore, the sera neutralised field isolates of different geographic origins and genotypes in a modified plaque reduction neutralisation assay performed on CD150-transfected Vero cells. These results demonstrate that transgenic carrot plants can serve as an efficient expression system to produce highly immunogenic, randomly assembled polyepitope antigens. The combined features of the selected epitopes and the potential of the plant expression system may pave the way towards new vaccines against measles.