Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforming growth factor (TGF)-beta1 has long been regarded as a central mediator of tissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-beta1 and its signaling pathways have been attractive therapeutic targets for the development of antifibrotic drugs. However, the essential biological functions of TGF-beta1 in maintaining normal immune and cellular homeostasis significantly limit the effectiveness of TGF-beta1-directed therapeutic approaches. Thus, targeting downstream mediators or signaling molecules of TGF-beta1 could be an alternative approach that selectively inhibits TGF-beta1-stimulated fibrotic tissue response while preserving major physiological function of TGF-beta1. Recent studies from our laboratory revealed that TGF-beta1 crosstalk with epidermal growth factor receptor (EGFR) signaling by induction of amphiregulin, a ligand of EGFR, plays a critical role in the development or progression of pulmonary fibrosis. In addition, chitotriosidase, a true chitinase in humans, has been identified to have modulating capacity of TGF-beta1 signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-beta1 effector function significantly enhance the effectiveness and flexibility in targeting pulmonary fibrosis in which TGF-beta1 plays a significant role.
Animals ; Drug Design ; Hexosaminidases/antagonists & inhibitors/metabolism ; Humans ; Lung/*drug effects/metabolism/pathology ; Molecular Targeted Therapy ; Pulmonary Fibrosis/*drug therapy/metabolism/pathology ; Receptor Cross-Talk ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/metabolism ; Receptors, Transforming Growth Factor beta/antagonists & inhibitors/metabolism ; Signal Transduction ; Transforming Growth Factor beta1/*antagonists & inhibitors/metabolism

BACKGROUND: Although the intrathecal (IT) administration of midazolam has been reported to have analgesic effect in humans, it is not clear whether IT midazolam can prolong the duration of sensory block to T10 dermatome that is required block level for lower extremity surgery. The effect of 1 or 2 mg of IT midazolam added to bupivacaine on the duration of spinal anesthesia to T10 were examined in orthopedic patients. METHODS: Sixty six adult patients were randomly allocated to receive 11 mg of intrathecal 0.5% hyperbaric bupivacaine alone (Group B, n = 22) or with 1 mg (Group BM-1, n = 22) or 2 mg (Group BM-2, n = 22) of midazolam. Both the patients and the observers were blinded to the drug solutions and patient groups. The onset and duration of sensory block to T10, BIS, OAA/S scale, hemodynamic variables, and side effects during the operation and recovery were compared among the groups. RESULTS: The onset of sensory and motor block were not different among the groups. However, the duration of sensory block to T10 in the Group BM-2 was prolonged more 52.2, 42.2 minutes than the Group B and the Group BM-1, respectively. The BIS scale of the Group BM-2 tended to be lower than the Group B and the Group BM-1 but there were no statistical significance. The OAA/S scale were significantly higher in the Group BM-2 than the Group B and the Group BM-1 during operation. There were no differences in hemodynamic variables and side effects among the groups. CONCLUSIONS: Intrathecal addition of midazolam 2 mg to bupivacaine prolonged the duration of spinal block to T10 in orthopedic patients.
Adult ; Anesthesia, Spinal ; Bupivacaine* ; Hemodynamics ; Humans ; Lower Extremity ; Midazolam* ; Orthopedics*

Allergic asthma is associated with persistent functional and structural changes in the airways and involves many different cell types. Many proteins involved in allergic asthma have been identified individually, but complete protein profiles (proteome) have not yet been reported. Here we have used a differential proteome mapping strategy to identify tissue proteins that are differentially expressed in mice with allergic asthma and in normal mice. Mouse lung tissue proteins were separated using two-dimensional gel electrophoresis over a pH range between 4 and 7, digested, and then analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MS). The proteins were identified using automated MS data acquisition. The resulting data were searched against a protein database using an internal Mascot search routine. This approach identified 15 proteins that were differentially expressed in the lungs of mice with allergic asthma and normal mice. All 15 proteins were identified by MS, and 9 could be linked to asthma-related symptoms, oxidation, or tissue remodeling. Our data suggest that these proteins may prove useful as surrogate biomarkers for quantitatively monitoring disease state progression or response to therapy.
Animals ; Asthma/genetics/immunology/*metabolism ; Comparative Study ; Disease Models, Animal ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression/immunology ; Gene Expression Profiling ; Lung/immunology/metabolism/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin/immunology ; Proteome/*analysis/genetics/immunology ; Proteomics/methods ; RNA, Messenger/genetics/metabolism ; Research Support, Non-U.S. Gov't ; Reverse Transcriptase Polymerase Chain Reaction ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

BACKGROUND: Two hundred seventy-eight patients undergoing thoracic surgery were retrospectively analyzed to determine whether which variable can predict the identification of patients at risk of arterial hypoxemia developing during one-lung ventilation (OLV). METHODS: According to the value of SpO2, the patients were divided two groups. Group L (n = 62) had SpO2 values of less than 95%, whereas group H (n = 216) those of more than 95%. Preoperative and intraoperative data, including past medical history, current therapy, and usual preoperative and intraoperative tests, were collected and used as predictable variables for arterial hypoxemia during OLV by binary logistic regression (forward conditional method) subsequent to independent t-test and Chi-square test, as appropriate. RESULTS: Preoperative (past medical history with pulmonary resection of a lobectomy in dependent lung, hypertension, arrhythmias, and predicted diffusion capacity for carbon monoxide < or = 70%) and intraoperative (arterial oxygen tension/inspiratory oxygen fraction during two-lung ventilation <528 mmHg, right thoracotomy) variables were considered as predictable factors that identified patients at risk of arterial hypoxemia during OLV. CONCLUSION: Caution to the increased risk of arterial hypoxemia during OLV is needed in patients that have aforementioned preoperative and intraoperative variables.
Anoxia* ; Arrhythmias, Cardiac ; Carbon Monoxide ; Diffusion ; Humans ; Hypertension ; Logistic Models ; Lung ; One-Lung Ventilation* ; Oxygen ; Retrospective Studies ; Thoracic Surgery ; Ventilation

Objective: : This study compared the quality of recovery (QoR) after minicraniotomy for clipping of unruptured intracranial aneurysms (UIAs) between patients with and without scalp nerve block (SNB). Methods: : Patients were randomly assigned to the SNB (SNB using ropivacaine with epinephrine, n=27) and control (SNB using normal saline, n=25) groups. SNB was performed at the end of surgery. To assess postoperative QoR, the QoR-40, a patient-reported questionnaire, was used. The QoR-40 scores were measured preoperatively, 1–3 days postoperatively, at hospital discharge, and 1 month postoperatively. Pain and intravenous patient-controlled analgesia (IV-PCA) consumption were evaluated 3, 6, 9, and 12 hours and 1–3 days postoperatively. Results: : All QoR-40 scores, including those measured 1 day postoperatively (primary outcome measure; 155.0 [141.0–176.0] vs. 161.0 [140.5–179.5], p=0.464), did not significantly differ between the SNB and control groups. The SNB group had significantly less severe pain 3 (numeric rating scale [NRS]; 3.0 [2.0–4.0] vs. 5.0 [3.5–5.5], p=0.029), 9 (NRS; 3.0 [2.0–4.0] vs. 4.0 [3.0–5.0], p=0.048), and 12 (NRS; 3.0 [2.0–4.0] vs. 4.0 [3.0–5.0], p=0.035) hours postoperatively. The total amount of IV-PCA consumed was significantly less 3 hours postoperatively in the SNB group (2.0 [1.0–4.0] vs. 4.0 [2.0–5.0] mL, p=0.044). Conclusion : After minicraniotomy for clipping of UIAs, SNB reduced pain and IV-PCA consumption in the early postoperative period but did not improve the QoR-40 scores.

Extracranial carotid stenosis is a well-established, modifiable risk factor for stroke. Asymptomatic extracranial carotid stenosis is increasingly being detected due to the introduction of less-invasive and more-sensitive advanced diagnostic technologies. For severe asymptomatic stenosis, earlier pivotal clinical trials demonstrated the benefit of carotid endarterectomy over the best medical therapy. Since then, great advances have been made in interventional and medical therapies as well as surgical techniques. The first edition of the Korean Stroke Clinical Practice Guidelines for primary stroke prevention for the management of asymptomatic carotid stenosis reflected evidences published before June 2007. After the publication of the first edition, several major clinical trials and observational studies have been published, and major guidelines updated their recommendation. Accordingly, the writing group of Korean Stroke Clinical Practice Guidelines (CPG) decided to provide timely updated evidence-based recommendations. The Korean Stroke CPG writing committee has searched and reviewed literatures related to the management of asymptomatic carotid stenosis including published guidelines, meta-analyses, randomized clinical trials, and nonrandomized studies published between June 2007 and Feb 2011. We summarized the new evidences and revised our recommendations. Key changes in the updated guidelines are the benefit of intensive medical therapy and further evidence of carotid artery stenting as an alternative to carotid endarterectomy. The current updated guidelines underwent extensive peer review by experts from the Korean Stroke Society, Korean Society of Intravascular Neurosurgery, Korean Society of Interventional Neuroradiology, Korean Society of Cerebrovascular Surgery, and Korean Neurological Association. New evidences will be continuously reflected in future updated guidelines.
Carotid Arteries ; Carotid Stenosis ; Constriction, Pathologic ; Endarterectomy, Carotid ; Neurosurgery ; Peer Review ; Primary Prevention ; Publications ; Risk Factors ; Stents ; Stroke ; Writing