Dysfunction of the canine respiratory muscle pump in ascites.

Ascites, a complicating feature of many diseases of the liver and peritoneum, commonly causes dyspnea. The mechanism of this symptom, however, is uncertain. In the present study, progressively increasing ascites was induced in anesthetized dogs, and the hypothesis was initially tested that ascites increases the impedance on the diaphragm and, so, adversely affects the lung-expanding action of the muscle. Ascites produced a gradual increase in abdominal elastance and an expansion of the lower rib cage. Concomitantly, the caudal displacement of the diaphragm and the fall in airway opening pressure during isolated stimulation of the phrenic nerves decreased markedly; transdiaphragmatic pressure during phrenic stimulation also decreased. To assess the adaptation to ascites of the respiratory system overall, we subsequently measured the changes in lung volume, the arterial blood gases, and the electromyogram of the parasternal intercostal muscles during spontaneous breathing. Tidal volume and minute ventilation decreased progressively as ascites increased, leading to an increase in arterial PCO2 and parasternal intercostal inspiratory activity. It is concluded that 1) ascites, acting through an increase in abdominal elastance and an expansion of the lower rib cage, impairs the lung-expanding action of the diaphragm; 2) this impairment elicits a compensatory increase in neural drive to the inspiratory muscles, but the compensation is not sufficient to maintain ventilation; and 3) dyspnea in this setting results in part from the dissociation between increased neural drive and decreased ventilation.     

Collagen-bound LDL modifies endothelial cell adhesion to type V collagen: Implications for atherosclerosis

Low density lipoprotein (LDL) is retained in the extracellular matrix of the arterial wall where it is considered to be atherogenic, but little is known about how cell adhesion to the matrix is affected by collagen-bound LDL. We tested the effect of native, oxidized and acetylated LDL reacted with adsorbed monomeric type I, III and V collagen on endothelial cell adhesion to collagen using a colorimetric adhesion assay. We found that none of the LDL species affected adhesion to type I and III collagen, but that collagen-bound native and acetylated LDL enhanced attachment to type V collagen, whereas bound oxidized LDL inhibited adhesion to this collagen. We therefore suggest that oxidized LDL associated with type V collagen in the arterial wall would favor de-endothelialization and contribute to atherogenesis and thrombosis.     

Stem cell-based photodynamic therapy

We have transfected murine neural stem cells (NSCs) and rat umbilical cord matrix-derived stem cells (RUCMSCs) with a plasmid expressing gaussia luciferase (gLuc). These cells are engineered to secrete the luciferase. We have used gLuc containing supernatant from culturing the NSCs to perform in vitro photodynamic therapy of murine melanoma cells (B16F10), and RUCMSCs to perform in vivo PDT of lung melanomas in C57BL/6 mice. The treatment system was comprised of aminolevulic acid as a prodrug for the synthesis of the photosensitizer protoporphyrin IX, gaussia luciferase, and its' substrate coelenterazine. A significant reduction of the number of live melanoma cells in vitro and a borderline significant retardation of tumour growth in vivo was observed after coelenterazine-mediated PDT.     

Mechanical advantage of the canine triangularis sterni

De Troyer, André, and Alexandre Legrand.Mechanical advantage of the canine triangularis sterni.J. Appl. Physiol. 84(2): 562-568, 1998.Recent studies on the canine parasternal intercostal,sternomastoid, and scalene muscles have shown that the maximal changesin airway opening pressure (Pao) obtained per unit muscle mass(Pao/m) during isolatedcontraction are closely related to the fractional changes in musclelength per unit volume increase of the relaxed chest wall. In thepresent study, we have examined the validity of this relationship for the triangularis sterni, an important expiratory muscle of the rib cagein dogs. Passive inflation above functional residual capacity (FRC)induced a virtually linear increase in muscle length, such that, with a1.0-liter inflation, the muscle lengthened by 17.9 ± 1.6 (SE) % of its FRC length. When the muscle in one interspace wasmaximally stimulated at FRC, Pao increased by 0.84 ± 0.11 cmH₂O. However, in agreement withthe length-tension characteristics of the muscle, when lung volume wasincreased by 1.0 liter before stimulation, the rise in Pao amounted to1.75 ± 0.12 cmH₂O. At thehigher volume, Pao/m thereforeaveraged + 0.53 ± 0.05 cmH₂O/g, such that the coefficientof proportionality between the change in triangularis sterni lengthduring passive inflation and Pao/m was the same as that previously obtained for the parasternalintercostal and neck inspiratory muscles. These observations,therefore, confirm that there is a unique relationship between thefractional changes in length of the respiratory muscles, bothinspiratory and expiratory, during passive inflation and theirPao/m. Consequently, the maximal effect of a particular muscle on the lung can be predicted on the basisof its change in length during passive inflation and its mass. Ageometric analysis of the rib cage also established that thelengthening of the canine triangularis sterni during passive inflationis much greater than the shortening of the parasternal intercostalsbecause, in dogs, the costal cartilages slope downward from thesternum.

     

Widespread triazole pesticide use affects infection dynamics of a global amphibian pathogen

The sixth mass extinction is a consequence of complex interplay between multiple stressors with negative impact on biodiversity. We here examine the interaction between two globally widespread anthropogenic drivers of amphibian declines: the fungal disease chytridiomycosis and antifungal use in agriculture. Field monitoring of 26 amphibian ponds in an agricultural landscape shows widespread occurrence of triazole fungicides in the water column throughout the amphibian breeding season, together with a negative correlation between early season application of epoxiconazole and the prevalence of chytrid infections in aquatic newts. While triazole concentrations in the ponds remained below those that inhibit growth of Batrachochytrium dendrobatidis, they bioaccumulated in the newts' skin up to tenfold, resulting in cutaneous growth-suppressing concentrations. As such, a concentration of epoxiconazole, 10 times below that needed to inhibit fungal growth, prevented chytrid infection in anuran tadpoles. The widespread presence of triazoles may thus alter chytrid dynamics in agricultural landscapes.     

The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (P_{HLA-A-aa-site-62} = 7.4×10⁻²⁹; P _{HLA-B-aa-site-116} = 6.5×10⁻¹⁹; P _{HLA-C-aa-site-156} = 6.8×10⁻⁸ respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.