Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

The All-Data-Based Evolutionary Hypothesis of Ciliated Protists with a Revised Classification of the Phylum Ciliophora (Eukaryota, Alveolata)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ The file attached is the published version of the article

A Theory-Based Meta-Analysis: Stress Management Interventions for College Students

The purpose of this study was to determine the combined average effect size for the efficacy of stress management interventions in randomized controlled trials with college students. A workplace stress intervention approach guided article selection. A single instrument measured stress. The analysis was a random effects model. The literature search in the spring of 2020 yielded eight qualifying studies, published from 2014-2020. The overall effect size was statistically significant (g = ‒0.41). Especially given pandemic-related stressors, this meta-analysis could serve as a baseline for future research comparisons. It mirrored results of other meta-analyses, discussed in the literature review. No prior meta-analysis to our knowledge has employed the same approach or framework

Spatially Explicit Decision Support for Watershed Management on Military Lands: Stream Integrity, Interactive Programming, and Best Management Practices

2012 S.C. Water Resources Conference - Exploring Opportunities for Collaborative Water Research, Policy and Managemen

Murfreesboro Addresses

https://digitalcommons.acu.edu/crs_books/1086/thumbnail.jp

ACTH-Bestimmungen im Plasma aus dem Bulbus cranialis venae jugularis

Der Anstieg der Corticosteroninkretion in das Nebennierenvenenblut frisch hypophysektomierter Ratten diente zur Bestimmung von ACTH-Spiegeln in 1 ml nativen, menschlichen Plasma. Normale ACTH-Plasmaspiegel sind sowohl bei Punktion der Vena cubitalis als auch des Bulbus cranialis venae jugularis durch diese Methode nicht oder nur ungenau zu erfassen. Bei Patienten mit pathologisch erhöhten ACTH-Spiegeln in der Vena cubitalis sind die ACTH-Spiegel im Bulbus cranialis venae jugularis signifikant höher. Es ließ sich eine Beziehung zwischen ACTH-Spiegel in der Peripherie (Vena cubitalis), Differenz der ACTH-Spiegel zwischen Bulbus cranialis venae jugularis und Vena cubitalis und biologischer Halbwertszeit von endogenem ACTH aufstellen. Nach den Ergebnissen der Bestimmung von ACTH-Spiegeln bei Nebennierengesunden läßt sich folgern, daß die biologische Halbwertszeit von endogenem ACTH größer als 4 min sein muß. Bei Patienten mit erhöhten ACTH-Spiegeln ließ sich die biologische Halbwertszeit von endogenem ACTH größenordnungsmäßig mit ca. 40 min berechnen. Bei diesen Patienten betrug die mittlere tägliche ACTH-Inkretion ca. 100 E.ACTH-contents of 1 ml specimens of human plasma were assayed by measurement of increases of corticosterone output in the adrenal vein of acutely hypophysectomized rats. This procedure is not sensitive enough to measure normal ACTH-levels acurately, neither when blood was drawn from the bulbus cranialis venae jugularis, nor from the vena cubitalis. In patients having pathologically elevated ACTH-levels, the ACTH-content of plasma is significantly higher in the bulbus cranialis venae jugularis than in peripheral venous blood. An equation is presented formulating the relation of peripheral ACTH-levels, differences of ACTH-levels between bulbus cranialis venae jugularis and vena cubitalis, and of the biological halflife of endogenous ACTH. On the basis of the results of the determinations of socalled normal ACTH-levels it can be concluded, that the biological halflife of endogenous ACTH is longer than 4 min. From the data of patients with elevated ACTH-levels a halflife of approximately 40 min and a mean ACTH-secretion of approx. 100 units per day could be calculated

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders