Abstract Community acquired pneumonia, mainly caused by Streptococcus pneumoniae ( S.pn.), is a common cause of death worldwide. Despite adequate antibiotic therapy, pneumococcal pneumonia can induce pulmonary endothelial hyperpermeability leading to acute lung injury, which often requires mechanical ventilation (MV) causing ventilator-induced lung injury (VILI). Endothelial stabilization is mediated by angiopoietin-1 induced Tie2 activation. PEGylated (polyethylene glycol) Tie2-agonist Vasculotide (VT) mimics Angiopietin-1 effects. Recently, VT has been shown to reduce pulmonary hyperpermeability in murine pneumococcal pneumonia. The aim of this study was to determine whether VT reduces lung damage in S.pn. infected and mechanically ventilated mice. Pulmonary hyperpermeability, immune response and bacterial load were quantified in S.pn. infected mice treated with Ampicillin + /−VT and undergoing six hours of MV 24 h post infection. Histopathological lung changes, Tie2-expression and -phosphorylation were evaluated. VT did not alter immune response or bacterial burden, but interestingly combination treatment with ampicillin significantly reduced pulmonary hyperpermeability, histological lung damage and edema formation. Tie2-mRNA expression was reduced by S.pn. infection and/or MV but not restored by VT. Moreover, Tie2 phosphorylation was not affected by VT. These findings indicate that VT may be a promising adjunctive treatment option for prevention of VILI in severe pneumococcal pneumonia.
Several families of functionally and structurally distinct ion channels have been identified throughout the last decade, resulting in a growing complexity in our understanding of ion transport across biological membranes. Here, we introduce a novel family of putative chloride channel proteins with nine bovine, murine, and human homologs identified to date. The gene family has been termed CLCA family (chloride channels, calcium-activated) based on observations that heterologous expression of several family members is associated with the appearance of a novel anion channel activity that depends on the concentration of intracellular calcium. The family members identified so far are the bovine calcium-activated chloride channel (CaCC or bCLCA1), the bovine lung endothelial cell adhesion molecule-1 (LuECAM-1), the murine calcium-activated chloride channels mCLCA1, mCLCA2, and mCLCA3 (previously termed gob-5), and four human homologs (hCLCA1, hCLCA2, hCLCA3, and hCaCC2). Each of these homologs is character ized by a unique cellular and tissue expression pattern with most consistent expression in secretory epithelia of the digestive, respiratory, and reproductive organs. Of special interest is the observation that several of these molecules seem to combine cell-cell adhesion properties with ion channel function. Structural analyses have revealed that a four- or five-transmembrane topography is conserved throughout the family. Their functional features as well as the cellular coexpression of several CLCA homologs with the cystic fibrosis transmembrane conductance regulator (CFTR) in numerous tissues raises the question whether CLCA family members may participate in the complex ion channel disorder of cystic fibrosis. Keywords: CLCA Gene Family, Putative Chloride Channels, Calcium Activated chloride channel, CaCC or bCLCA1, Bovin lung endothelial cell, Adhesion molecule, LuECAM, HCLCA1, MCLCA2, CLCA family Members
A novel Sarcocystis species has recently been reported in the domestic pigeon (Columba livia f. domestica) as intermediate host, causing severe central nervous signs similar to Paramyxovirus-1 or Salmonella Typhimurium var. cop. infection. Transmission of the parasite via the northern goshawk (Accipiter gentilis) as definitive host has been established. Experimental infection of domestic pigeons with sporocysts excreted by experimentally infected northern goshawks reproduced the natural infection in the pigeon, proving the causative role of the parasite in the disease. Here, we describe in greater detail the course of the fulminant biphasic disease depending on the infectious dose. Pigeons infected with 103 or 104 sporocysts showed clinical signs of polyuria and apathy around 10–11 days postinfection (dpi) and sudden neurological signs 51–57 dpi as a second phase of disease. Pigeons infected with higher doses died within 7–12 dpi, also showing polyuria and apathy but without nervous signs. At necropsy, livers and spleens had multifocal necroses and infestations with parasitic stages, namely, schizonts. Moreover, lesions and schizonts were also found in the lung, bone marrow, and next to blood vessels in the connective tissue of various organs. Pigeons infected with 102 sporocysts remained symptomless until 58–65 dpi, when sudden central nervous signs occurred. Major histopathologic findings of pigeons with neurological signs were encephalitis and myositis of virtually every skeletal muscle with high infestations of sarcocysts. Only mild myocarditis and very few cysts were found in the heart muscles. Importantly, a sentinel pigeon developed identical lesions when compared to those of low-dose infected pigeons, suggesting a risk of mechanical transmission of sporocysts from freshly infected to uninfected pigeons in a flock. By contrast, chickens failed to develop any clinical signs or pathologic lesions in the same experiment. The findings further characterize the new highly pathogenic disease in domestic pigeons, which clinically mimics paramyxovirosis and salmonellosis in both phases of the disease and exclude chickens as further intermediate host species.
The spectral behavior of single terrylene molecules at a hexadecane−silica interface structure is studied. Different sample preparation techniques indicate that molecules close to a silica substrate in a hexadecane matrix are subject to additional dephasing or spectral diffusion. The temperature activation of the homogeneous line width of these molecules shows much reduced activation energies as compared to those of molecules in bulk hexadecane. These low-lying activation energies may be attributed to surface phonon states or local phonon modes particular to the interface structure. With the aid of a low-temperature scanning confocal microscope, the distance of single terrylene molecules to the silica surface can be measured with a precision of 60 nm. A drastic increase of the homogeneous line width for molecules with distances less than 150 nm to the silica surface is found.
In 2012, a Dog circovirus (DogCV) was discovered in the USA, which was followed by further descriptions of the virus in the USA, Italy and Germany. The present study is the first to examine the prevalence of DogCV in faeces of dogs from Germany and other European countries.Faecal samples from 184 dogs with diarrhoea and from 82 clinically healthy dogs (control group) were analysed for the presence of DogCV by PCR. Furthermore, the detection of parvovirus, coronavirus, Giardia and Cryptosporidium was performed in all samples.In the group of dogs with diarrhoea the prevalence of DogCV was 20.1% (37/184), in the healthy control group it was 7.3% (6/82). Therefore, the virus could be detected significantly more frequently in dogs with diarrhoea. The detection frequency of DogCV is comparable with those of the other tested pathogens. In approximately 50% of the DogCV-positive dogs, infections with other enteropathogenic organisms were diagnosed.The role of co-infection in the pathogenesis of the disease remains unclear, but there appears to be an association between co-infection and disease severity. Evidence of DogCV in clinically healthy dogs appears important for the epidemiology and raises questions about its pathogenicity. Further studies are needed to clarify questions regarding the pathogenesis, causal relevance and possible interference by other diarrhoeal pathogens. Nevertheless, the results of this study are an important indication that DogCV should be considered as a differential diagnosis in dogs with diarrhoea.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of Intersystem Crossing Parameters via Observation of Quantum Jumps on Single MoleculesM. Vogel, A. Gruber, J. Wrachtrup, and C. von BorczyskowskiCite this: J. Phys. Chem. 1995, 99, 41, 14915–14917Publication Date (Print):October 1, 1995Publication History Published online1 May 2002Published inissue 1 October 1995https://pubs.acs.org/doi/10.1021/j100041a003https://doi.org/10.1021/j100041a003research-articleACS PublicationsRequest reuse permissionsArticle Views181Altmetric-Citations34LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
The pulmonary epithelial glycocalyx is rich in glycosaminoglycans such as hyaluronan and heparan sulfate. Despite their presence, the precise role of these glycosaminoglycans in bacterial lung infections remains elusive. To address this, we intranasally inoculated mice with Streptococcus pneumoniae in the presence or absence of enzymes targeting pulmonary hyaluronan and heparan sulfate, followed by characterization of subsequent disease pathology, pulmonary inflammation, and lung barrier dysfunction. Enzymatic degradation of hyaluronan and heparan sulfate exacerbated pneumonia in mice, as evidenced by increased disease scores and alveolar neutrophil recruitment. However, targeting epithelial hyaluronan further exacerbated systemic disease, indicated by elevated splenic bacterial load and plasma levels of pro-inflammatory cytokines. In contrast, enzymatic cleavage of heparan sulfate resulted in increased bronchoalveolar bacterial burden, lung damage and pulmonary inflammation in mice infected with Streptococcus pneumoniae. Accordingly, heparinase-treated mice also exhibited disrupted lung barrier integrity as evidenced by higher alveolar edema scores and vascular protein leakage into the airways. This finding was corroborated in a human alveolus-on-a-chip platform, confirming that heparinase treatment also disrupts the human lung barrier. Notably, enzymatic pre-treatment with either hyaluronidase or heparinase also rendered human epithelial cells more sensitive to pneumococcal-induced barrier disruption, as determined by transepithelial electrical resistance measurements, consistent with our findings in murine pneumonia. Taken together, these findings demonstrate the importance of intact hyaluronan and heparan sulfate in controlling pneumococcal virulence, pulmonary inflammation, and epithelial barrier function.
