Carbon monoxide may enhance bile secretion by increasing glutathione excretion and Mrp2 expression in rats

AbstractBackgroundNitric oxide (NO) donors have been reported to induce choleresis via an increased excretion of glutathione. The effects of another gas molecule, carbon monoxide (CO), on bile formation are, however, inconsistent among previous reports. We investigated the sequential changes of bile output and the biliary contents in rats with or without CO supplementation to elucidate the mechanism of CO on bile excretion.MethodsDichloromethane (DCM) was gastrically fed to male Sprague–Dawley rats to yield CO by liver biotransformation. The rats were divided into DCM-treated (n = 7), DCM plus L-NAME-treated (n = 6), and corn oil-treated-(n = 8) groups. Bile samples were collected hourly to examine the flow rate and bile content. Serum levels of nitrite and nitrate 4 hours after DCM supplementation with or without NO synthase (NOS) inhibition were measured by capillary electrophoresis. The expression of hepatic inducible NOS was evaluated by Western blotting 6 hours after DCM administration.ResultsLevels of carboxyhemoglobin rose to around 10% at 4 hours after DCM supplementation and were maintained until the end of the experiments. Bile flow increased after DCM supplementation and was associated with a concomitant increase of biliary glutathione and higher hepatic multidrug resistance-associated protein 2 (Mrp2) expression. Hepatic inducible NOS expression and serum nitrate/nitrite levels were also increased. Treatment with an NOS inhibitor (L-NAME) abolished the CO-induced glutathione excretion and choleresis, but not Mrp2 expression.ConclusionThe present study demonstrated that CO enhanced biliary output in conjunction with NO by increasing the biliary excretion of glutathione. The increment in biliary glutathione was associated with an increased expression of hepatic Mrp2

Transforming growth factor-β1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-κB pathways

<p>Abstract</p> <p>Background</p> <p>Transforming growth factor-β (TGF-β) and matrix metalloproteinases (MMPs) are the multifunctional factors during diverse physiological and pathological processes including development, wound healing, proliferation, and cancer metastasis. Both TGF-β and MMPs have been shown to play crucial roles in brain pathological changes. Thus, we investigated the molecular mechanisms underlying TGF-β1-induced MMP-9 expression in brain astrocytes.</p> <p>Methods</p> <p>Rat brain astrocytes (RBA-1) were used. MMP-9 expression was analyzed by gelatin zymography and RT-PCR. The involvement of signaling molecules including MAPKs and NF-κB in the responses was investigated using pharmacological inhibitors and dominant negative mutants, determined by western blot and gene promoter assay. The functional activity of MMP-9 was evaluated by cell migration assay.</p> <p>Results</p> <p>Here we report that TGF-β1 induces MMP-9 expression and enzymatic activity via a TGF-β receptor-activated reactive oxygen species (ROS)-dependent signaling pathway. ROS production leads to activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun-N-terminal kinase (JNK) and then activation of the NF-κB transcription factor. Activated NF-κB turns on transcription of the MMP-9 gene. The rat MMP-9 promoter, containing a NF-κB <it>cis</it>-binding site, was identified as a crucial domain linking to TGF-β1 action.</p> <p>Conclusions</p> <p>Collectively, in RBA-1 cells, activation of ERK1/2- and JNK-NF-κB cascades by a ROS-dependent manner is essential for MMP-9 up-regulation/activation and cell migration induced by TGF-β1. These findings indicate a new regulatory pathway of TGF-β1 in regulating expression of MMP-9 in brain astrocytes, which is involved in physiological and pathological tissue remodeling of central nervous system.</p

The effects of rear-wheel camber on the kinematics of upper extremity during wheelchair propulsion

BACKGROUND: The rear-wheel camber, defined as the inclination of the rear wheels, is usually used in wheelchair sports, but it is becoming increasingly employed in daily propulsion. Although the rear-wheel camber can increase stability, it alters physiological performance during propulsion. The purpose of the study is to investigate the effects of rear-wheel cambers on temporal-spatial parameters, joint angles, and propulsion patterns. METHODS: Twelve inexperienced subjects (22.3±1.6 yr) participated in the study. None had musculoskeletal disorders in their upper extremities. An eight-camera motion capture system was used to collect the three-dimensional trajectory data of markers attached to the wheelchair-user system during propulsion. All participants propelled the same wheelchair, which had an instrumented wheel with cambers of 0°, 9°, and 15°, respectively, at an average velocity of 1 m/s. RESULTS: The results show that the rear-wheel camber significantly affects the average acceleration, maximum end angle, trunk movement, elbow joint movement, wrist joint movement, and propulsion pattern. The effects are especially significant between 0° and 15°. For a 15° camber, the average acceleration and joint peak angles significantly increased (p < 0.01). A single loop pattern (SLOP) was adopted by most of the subjects. CONCLUSIONS: The rear-wheel camber affects propulsion patterns and joint range of motion. When choosing a wheelchair with camber adjustment, the increase of joint movements and the base of support should be taken into consideration

Natural orifice transluminal endoscopic surgery: A transtracheal approach for the thoracic cavity in a live canine model

BackgroundThe present study aimed to evaluate the performance of transtracheal thoracic exploration and pericardial window creation in a canine survival model.MethodsTransthoracic exploration was performed in 14 dogs. Under general anesthesia, after an incision in the right lateral wall of the middle–lower portion of the trachea was made, a 9-mm metal tube was advanced into the thoracic cavity. For thoracic cavity exploration and pericardial window creation, a flexible bronchoscope was introduced through the metal tube into the thoracic cavity. After thoracoscopy, a Dumon stent (Novatech, Grasse, France) was used to cover the tracheal incision site and facilitate healing. Animals were evaluated by endoscopy 1 and 2 weeks later. Animals were humanely killed, and necropsy was performed 2 weeks after the transtracheal natural orifice transluminal endoscopic surgery.ResultsFourteen dogs underwent transtracheal thoracic exploration lasting for an average of 110 minutes (range, 80–150), with 3 perioperative deaths. At 2 weeks after pericardial window creation, endoscopy revealed normal healing of the tracheal incision sites in all 11 surviving animals. Necropsy on the 11 animals at 2 weeks showed 9 adhesions around the pericardial window and 5 adhesions around the tracheal incision region. No mediastinitis or abscesses could be identified.ConclusionsTranstracheal thoracic exploration is technically feasible. Increasing surgical experience together with improvement in endoscopic techniques will further facilitate the development of natural orifice transluminal endoscopic surgery for thoracic diseases

Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy

Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH2 terminus and one or three LIM domains at their COOH terminus. Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles. Examination of striated muscle from the mutants revealed that Cypher is not required for sarcomerogenesis or Z-line assembly, but rather is required for maintenance of the Z-line during muscle function. In vitro studies demonstrated that individual domains within Cypher localize independently to the Z-line via interactions with α-actinin or other Z-line components. These results suggest that Cypher functions as a linker-strut to maintain cytoskeletal structure during contraction

SARS Exposure and Emergency Department Workers

Of 193 emergency department workers exposed to severe acute respiratory syndrome (SARS), 9 (4.7%) were infected. Pneumonia developed in six workers, and assays showed anti-SARS immunoglobulin (Ig) M and IgG. The other three workers were IgM-positive and had lower IgG titers; in two, mild illness developed, and one remained asymptomatic

Taiwanese Dermatological Association consensus for the management of atopic dermatitis

AbstractBackground/ObjectiveThis report describes the 2014 consensus of the Taiwanese Dermatological Association (TDA) regarding the treatment of atopic dermatitis (AD). The TDA consensus is distributed to practices throughout Taiwan to provide recommendations for therapeutic approaches for AD patients to improve their quality of life.MethodsThe information in the consensus was agreed upon by a panel of national experts at TDA AD consensus meetings held on March 16, May 4, and June 29, 2014. The consensus was in part based on the 2013 Asia–Pacific AD guidelines and the guidelines of the American Academy of Dermatology, with modification to reflect the clinical practice in Taiwan.ResultsThe amendments were drafted after scientific discussions focused on the quality of evidence, risk, and benefits; all the consensus contents were voted on by the participating dermatologists, with approval by at least 75% for inclusion.ConclusionThe consensus provides a comprehensive overview of treatment for AD, with some local and cultural considerations for practitioners in Taiwan, especially the use of wet dressings/wraps, systemic immunomodulatory agents, and complementary therapies

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente