Global importance of new treatment strategies to efforts to control hepatitis B virus.

Introduction: Hepatitis B Virus (HBV) infection can progress to chronic HBV (CHB) disease, thereby increasing the risk of severe forms of liver disease (i.e. liver cirrhosis and hepatocellular carcinoma) and resulting in a high global burden of morbidity, mortality, and health-care utilization.

A novel excisional wound pain model for evaluation of analgesics in rats.

Background: Management of pain from open wounds is a growing unmet healthcare need. However, the models available to study pain from wounds or to develop analgesics for the patients suffering from them have primarily relied on incisional models. Here, we present the first characterized and validated model of open wound pain.

Effect of prenatal waterpipe tobacco smoke on airway inflammation in murine model of asthma of adult offspring mice.

Objective: Worldwide popularity of waterpipe tobacco smoking has increased, including in pregnant women. This study investigates the effect of prenatal waterpipe tobacco smoke (WTS) exposure on airway inflammation in a murine model of asthma of adult offspring mice.

Materials And Methods: Pregnant BALB/c mice were exposed to fresh air or WTS, using a whole-body exposure system that mimics human use during WTS.

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase-Knockout Mice.

Mice lacking the endogenous β2-adrenoceptor (β2AR) agonist epinephrine (phenylethanolamine N-methyltransferase [PNMT]-knockout mice) are resistant to developing an "asthma-like" phenotype in an ovalbumin sensitization and challenge (Ova S/C) model, and chronic administration of β2AR agonists to PNMT-KO mice restores the phenotype. Based on these and other studies showing differential effects of various β2AR ligands on the asthma phenotype, we have speculated that the permissive effect of endogenous epinephrine and exogenous β2AR agonists on allergic lung inflammation can be explained by qualitative β2AR signaling. The β2AR can signal through at least two pathways: the canonical Gαs-cAMP pathway and a β-arrestin-dependent pathway.

Epinephrine Activation of the β2-Adrenoceptor Is Required for IL-13-Induced Mucin Production in Human Bronchial Epithelial Cells.

Mucus hypersecretion by airway epithelium is a hallmark of inflammation in allergic asthma and results in airway narrowing and obstruction. Others have shown that administration a TH2 cytokine, IL-13 is sufficient to cause mucus hypersecretion in vivo and in vitro. Asthma therapy often utilizes β2-adrenoceptor (β2AR) agonists, which are effective acutely as bronchodilators, however chronic use may lead to a worsening of asthma symptoms.

Ligand bias prevents class equality among beta-blockers.

β-Blockers are used for a wide range of diseases from hypertension to glaucoma. In some diseases/conditions all β-blockers are effective, while in others only certain subgroups are therapeutically beneficial. The best-documented example for only a subset of β-blockers showing clinical efficacy is in heart failure, where members of the class have ranged from completely ineffective, to drugs of choice for treating the disease.

Arrestin-dependent but G-protein coupled receptor kinase-independent uncoupling of D2-dopamine receptors.

We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G-protein gated inwardly rectifying potassium channels (K(ir)3) and directly compared the effects of co-expression of G-protein coupled receptor kinase (GRK) and arrestin on agonist-dependent desensitization of the receptor response. We found, as described previously, that co-expression of a GRK and an arrestin synergistically increased the rate of agonist-dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses.

β2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model.

β(2)-Adrenoceptor (β2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent β2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the β2AR, epinephrine. In this study, we demonstrate that activation of the β2AR by epinephrine is paradoxically required for development of the asthma phenotype.