Heterogeneous Stitching of X-ray Images According to Homographic Evaluation.

The C-arm X-ray system is a common intraoperative imaging modality used to observe the state of a fractured bone in orthopedic surgery. Using C-arm, the bone fragments are aligned during surgery, and their lengths and angles with respect to the entire bone are measured to verify the fracture reduction. Since the field-of-view of the C-arm is too narrow to visualize the entire bone, a panoramic X-ray image is utilized to enlarge it by stitching multiple images. To achieve X-ray image stitching with feature detection, the extraction of accurate and densely matched features within the overlap region between images is imperative. However, since the features are highly affected by the properties and sizes of the overlap regions in consecutive X-ray images, the accuracy and density of matched features cannot be guaranteed. To solve this problem, a heterogeneous stitching of X-ray images was proposed. This heterogeneous stitching was completed according to the overlap region based on homographic evaluation. To acquire sufficiently matched features within the limited overlap region, integrated feature detection was used to estimate a homography. The homography was then evaluated to confirm its accuracy. When the estimated homography was incorrect, local regions around the matched feature were derived from integrated feature detection and substituted to re-estimate the homography. Successful X-ray image stitching of the C-arm was achieved by estimating the optimal homography for each image. Based on phantom and ex-vivo experiments using the proposed method, we confirmed a panoramic X-ray image construction that was robust compared to the conventional methods.

Navigation-assisted anchor insertion in shoulder arthroscopy: a validity study.

BACKGROUND: This study aimed to compare conventional and navigation-assisted arthroscopic rotator cuff repair in terms of anchor screw insertion. METHODS: The surgical performance of five operators while using the conventional and proposed navigation-assisted systems in a phantom surgical model and cadaveric shoulders were compared. The participating operators were divided into two groups, the expert group (n = 3) and the novice group (n = 2). In the phantom model, the experimental tasks included anchor insertion in the rotator cuff footprint and sutures retrieval. A motion analysis camera system was used to track the surgeons' hand movements. The surgical performance metric included the total path length, number of movements, and surgical duration. In cadaveric experiments, the repeatability and reproducibility of the anchor insertion angle were compared among the three experts, and the feasibility of the navigation-assisted anchor insertion was validated. RESULTS: No significant differences in the total path length, number of movements, and time taken were found between the conventional and proposed systems in the phantom model. In cadaveric experiments, however, the clustering of the anchor insertion angle indicated that the proposed system enabled both novice and expert operators to reproducibly insert the anchor with an angle close to the predetermined target angle, resulting in an angle error of < 2° (P = 0.0002). CONCLUSION: The proposed navigation-assisted system improved the surgical performance from a novice level to an expert level. All the experts achieved high repeatability and reproducibility for anchor insertion. The navigation-assisted system may help surgeons, including those who are inexperienced, easily familiarize themselves to of suture anchors insertion in the right direction by providing better guidance for anchor orientation. LEVEL OF EVIDENCE: A retrospective study (level 2).

A hands-free region-of-interest selection interface for solo surgery with a wide-angle endoscope: preclinical proof of concept.

BACKGROUND: A hands-free region-of-interest (ROI) selection interface is proposed for solo surgery using a wide-angle endoscope. A wide-angle endoscope provides images with a larger field of view than a conventional endoscope. With an appropriate selection interface for a ROI, surgeons can also obtain a detailed local view as if they moved a conventional endoscope in a specific position and direction. METHODS: To manipulate the endoscope without releasing the surgical instrument in hand, a mini-camera is attached to the instrument, and the images taken by the attached camera are analyzed. When a surgeon moves the instrument, the instrument orientation is calculated by an image processing. Surgeons can select the ROI with this instrument movement after switching from 'task mode' to 'selection mode.' The accelerated KAZE algorithm is used to track the features of the camera images once the instrument is moved. Both the wide-angle and detailed local views are displayed simultaneously, and a surgeon can move the local view area by moving the mini-camera attached to the surgical instrument. RESULTS: Local view selection for a solo surgery was performed without releasing the instrument. The accuracy of camera pose estimation was not significantly different between camera resolutions, but it was significantly different between background camera images with different numbers of features (P < 0.01). The success rate of ROI selection diminished as the number of separated regions increased. However, separated regions up to 12 with a region size of 160 × 160 pixels were selected with no failure. Surgical tasks on a phantom model and a cadaver were attempted to verify the feasibility in a clinical environment. CONCLUSIONS: Hands-free endoscope manipulation without releasing the instruments in hand was achieved. The proposed method requires only a small, low-cost camera and an image processing. The technique enables surgeons to perform solo surgeries without a camera assistant.

Pyranopyran-1,8-dione, an Active Compound from Vitices Fructus, Attenuates Cigarette-Smoke Induced Lung Inflammation in Mice.

Previously, we isolated and identified pyranopyran-1,8-dione (PPY) from Viticis Fructus, as a bioactive compound possessing anti-inflammatory properties. The present study was aimed to evaluate the preventive benefit of PPY on cigarette-smoke (CS)-induced lung inflammation. C57BL/6 mice were exposed to CS for 2 weeks while PPY was administrated by oral injection 2 h before CS exposure. To validate the anti-inflammatory effects of PPY, the numbers of immune cells in the bronchoalveolar lavage fluid were counted. Proinflammatory cytokines (Tumor necrosis factor-α: TNF-α, IL-6) and keratinocyte chemokine (KC/CXCL1) were also measured. Histopathologic analysis and cellular profiles showed that inflammatory cell infiltrations were significantly decreased in peribronchial and perivascular area by PPY treatment. The alveolar destruction by CS was markedly ameliorated by PPY treatment. In addition, the TNF-α, IL-6, and KC levels were declined in the PPY groups. These observations suggest that PPY has a preventive potential for lung inflammatory diseases.

A new wide-angle arthroscopic system: a comparative study with a conventional 30° arthroscopic system.

PURPOSE: To compare users' hand movements in performing validated shoulder arthroscopic tasks between a 30° and a wide-angle arthroscopic system, using phantom models with an optical motion analysis system. METHODS: Twelve orthopaedic residents were enrolled and randomly allocated into two groups. In order to compensate for any learning effect, a Latin square counterbalancing technique was used. An optical motion analysis system was used with markers affixed to pre-designed sites; each participant conducted four validated shoulder arthroscopic tasks using both arthroscopic systems. Each participant was instructed to perform the experiment three times with each arthroscope. The time taken, total path length, number of movements, and average acceleration were analysed. RESULTS: Significant differences were observed for the time taken, number of movements, and average acceleration between the two arthroscopic systems (P < 0.05 for all). However, the time taken was not significant. The mean total path length measured 53 ± 38 cm with the 30° arthroscope, while the mean with the wide-angle arthroscope was significantly shorter, at 36 ± 22 cm. The mean number of movements with the 30° and wide-angle arthroscopes were 1974 ± 1305 and 1233 ± 990, respectively, while the average accelerations were 2.6 ± 1.3 and 1.2 ± 0.6 cm/s(2), respectively. The mean time taken was 13 % faster when using the wide-angle arthroscopic system, although this was not statistically significant. CONCLUSION: The wide-angle arthroscopic system improved the arthroscope manoeuvre in terms of the total path length, number of movements, and average acceleration required for experimental arthroscopy. This system may help surgeons triangulate the arthroscope and surgical instruments during surgery by expanding the field of view.

Vitex rotundifolia L. prevented airway eosinophilic inflammation and airway remodeling in an ovalbumin-induced asthma mouse model.

Vitex rotundifolia L. (VR) as long been used in China and Korea in traditional medicine. This study was conducted to evaluate the ability of Vitex rotundifolia L. to prevent airway inflammation and remodeling in an ovalbumin (OVA)-induced murine asthma model. The total cell number and number of inflammatory cells in the bronchoalveolar lavage (BAL) fluid were counted. The levels of cytokines in the BAL fluid and serum IgE levels were measured using an ELISA. For histological analysis, hematoxylin and eosin staining, periodic acid-Schiff staining and immunohistochemistry were evaluated. The release of total cells into the BAL fluid was significantly inhibited in OVA-induced asthmatic mice treated with VR extract. In addition, eosinophilia and lymphocytosis were reduced significantly in mice that received VR extract. Furthermore, levels of the T(h)2 cytokines IL-4 and IL-5 and pro-inflammatory cytokine TNF-α in the BAL fluid and total IgE in serum were markedly suppressed by VR extract. OVA-specific IgE in the serum and IL-13 in the BAL fluid were decreased, but not significantly. The allergic effects of VR extract were accompanied by a reduction in airway hyperresponsiveness. Additionally, morphologic findings demonstrated that VR extract substantially inhibited OVA-induced eosinophilia, goblet cell hyperplasia and smooth muscle mass production. This finding suggests that VR extract may have pharmacological effects that would be useful for the treatment of asthma via the inhibition of the T(h)2 response and airway remodeling.

Comparison of extraction phases for a two-phase culture of a recombinant E. coli producing retinoids.

To prevent degradation of intracellular retinoids through in situ extraction from the cells, a two-phase culture system was performed. Several organic solvents, including n-alkanes, mineral oils and cosmetic raw materials, were applied as the extraction phase. Of the n-alkanes, n-decane had the highest retinoid production as 134 mg/l after 72 h. For mineral oil, light and heavy mineral oil gave retinoid productions of 158 and 174 mg/l after 96 h, respectively. Of other materials, isopropyl myristate gave the highest retinoid production of 181 mg/l. These results indicate that many types of oils can be applied for retinoid production, and optimization of the in situ extraction process will lead to further improve of economical production for the industrial purpose.

Inhibitory effects of Stemona tuberosa on lung inflammation in a subacute cigarette smoke-induced mouse model.

BACKGROUND: Stemona tuberosa has long been used in Korean and Chinese medicine to ameliorate various lung diseases such as pneumonia and bronchitis. However, it has not yet been proven that Stemona tuberosa has positive effects on lung inflammation. METHODS: Stemona tuberosa extract (ST) was orally administered to C57BL/6 mice 2 hr before exposure to CS for 2 weeks. Twenty-four hours after the last CS exposure, mice were sacrificed to investigate the changes in the expression of cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), chemokines such as keratinocyte-derived chemokine (KC) and inflammatory cells such as macrophages, neutrophils, and lymphocytes from bronchoalveolar lavage fluid (BALF). Furthermore, we compared the effect of ST on lung tissue morphology between the fresh air, CS exposure, and ST treatment groups. RESULTS: ST significantly decreased the numbers of total cells, macrophages, neutrophils, and lymphocytes in the BALF of mice that were exposed to CS. Additionally, ST reduced the levels of cytokines (TNF-α, IL-6) and the tested chemokine (KC) in BALF, as measured by enzyme-linked immunosorbent assay (ELISA). We also estimated the mean alveolar airspace (MAA) via morphometric analysis of lung tissues stained with hematoxylin and eosin (H&E). We found that ST inhibited the alveolar airspace enlargement induced by CS exposure. Furthermore, we observed that the lung tissues of mice treated with ST showed ameliorated epithelial hyperplasia of the bronchioles compared with those of mice exposed only to CS. CONCLUSIONS: These results indicate that Stemona tuberosa has significant effects on lung inflammation in a subacute CS-induced mouse model. According to these outcomes, Stemona tuberosa may represent a novel therapeutic herb for the treatment of lung diseases including COPD.

The standardized herbal formula, PM014, ameliorated cigarette smoke-induced lung inflammation in a murine model of chronic obstructive pulmonary disease.

BACKGROUND: In this study, we evaluated the anti-inflammatory effect of PM014 on cigarette smoke induced lung disease in the murine animal model of chronic obstructive pulmonary disease (COPD). METHODS: Mice were exposed to cigarette smoke (CS) for 2 weeks to induce COPD-like lung inflammation. Two hours prior to cigarette smoke exposure, the treatment group was administered PM014 via an oral injection. To investigate the effects of PM014, we assessed PM014 functions in vivo, including immune cell infiltration, cytokine profiles in bronchoalveolar lavage (BAL) fluid and histopathological changes in the lung. The efficacy of PM014 was compared with that of the recently developed anti-COPD drug, roflumilast. RESULTS: PM014 substantially inhibited immune cell infiltration (neutrophils, macrophages, and lymphocytes) into the airway. In addition, IL-6, TNF-α and MCP-1 were decreased in the BAL fluid of PM014-treated mice compared to cigarette smoke stimulated mice. These changes were more prominent than roflumilast treated mice. The expression of PAS-positive cells in the bronchial layer was also significantly reduced in both PM014 and roflumilast treated mice. CONCLUSIONS: These data suggest that PM014 exerts strong therapeutic effects against CS induced, COPD-like lung inflammation. Therefore, this herbal medicine may represent a novel therapeutic agent for lung inflammation in general, as well as a specific agent for COPD treatment.

Augmented reality-based surgical guidance for wrist arthroscopy with bone-shift compensation.

BACKGROUND AND OBJECTIVES: Intraoperative joint condition is different from preoperative CT/MR due to the motion applied during surgery, inducing an inaccurate approach to surgical targets. This study aims to provide real-time augmented reality (AR)-based surgical guidance for wrist arthroscopy based on a bone-shift model through an in vivo computed tomography (CT) study. METHODS: To accurately visualize concealed wrist bones on the intra-articular arthroscopic image, we propose a surgical guidance system with a novel bone-shift compensation method using noninvasive fiducial markers. First, to measure the effect of traction during surgery, two noninvasive fiducial markers were attached before surgery. In addition, two virtual link models connecting the wrist bones were implemented. When wrist traction occurs during the operation, the movement of the fiducial marker is measured, and bone-shift compensation is applied to move the virtual links in the direction of the traction. The proposed bone-shift compensation method was verified with the in vivo CT data of 10 participants. Finally, to introduce AR, camera calibration for the arthroscope parameters was performed, and a patient-specific template was used for registration between the patient and the wrist bone model. As a result, a virtual bone model with three-dimensional information could be accurately projected on a two-dimensional arthroscopic image plane. RESULTS: The proposed method was possible to estimate the position of wrist bone in the traction state with an accuracy of 1.4 mm margin. After bone-shift compensation was applied, the target point error was reduced by 33.6% in lunate, 63.3% in capitate, 55.0% in scaphoid, and 74.8% in trapezoid than those in preoperative wrist CT. In addition, a phantom experiment was introduced simulating the real surgical environment. AR display allowed to expand the field of view (FOV) of the arthroscope and helped in visualizing the anatomical structures around the bones. CONCLUSIONS: This study demonstrated the successful handling of AR error caused by wrist traction using the proposed method. In addition, the method allowed accurate AR visualization of the concealed bones and expansion of the limited FOV of the arthroscope. The proposed bone-shift compensation can also be applied to other joints, such as the knees or shoulders, by representing their bone movements using corresponding virtual links. In addition, the movement of the joint skin during surgery can be measured using noninvasive fiducial markers in the same manner as that used for the wrist joint.

Exogenous lactate intake immediately after endurance exercise increases time to exhaustion in VO2max measurements in mice.

PURPOSE: The purpose of the study was to investigate the effects of 4 weeks of lactate intake immediately after endurance exercise on maximal oxygen uptake (VO2max) in exercise performance. METHODS: Seven-week-old mice from the Institute of Cancer Research (ICR) were randomly divided into four groups: vehicle intake (SE/CON), lactate intake (SE/LAC), endurance exercise with vehicle intake (EX/ CON), and lactate intake with endurance exercise (EX/ LAC). Mice were subjected to 60-70% VO2max endurance exercise with or without oral lactate intake 5 days/ week for 4 weeks. VO2max measurements (VO2max, time to exhaustion (TTE), respiratory exchange rate, fat oxidation, and carbohydrate oxidation) were recorded at the end of the study period. After 48 h of VO2max measurement, the mice were sacrificed, and three different abdominal fat samples (epididymal, perirenal, and mesenteric) were collected. RESULTS: Body weight and abdominal fat mass did not differ between the groups. When measuring VO2max, endurance exercise raised VO2max, and lactate intake after endurance exercise increased TTE. The change in energy substrate utilization during VO2max measurement demonstrated that although the respiratory exchange rate and fat oxidation were enhanced by lactate intake, there were no synergistic effects of lactate intake and endurance exercise. CONCLUSION: Lactate intake immediately after endurance exercises can improve exercise performance, indicating the benefit of long-term exogenous lactate intake as an exercise supplement.

Validating a nondestructive optical method for apportioning colored particulate matter into black carbon and additional components.

Exposure of black carbon (BC) is associated with a variety of adverse health outcomes. A number of optical methods for estimating BC on Teflon filters have been adopted but most assume all light absorption is due to BC while other sources of colored particulate matter exist. Recently, a four-wavelength-optical reflectance measurement for distinguishing second hand cigarette smoke (SHS) from soot-BC was developed (Brook et al., 2010; Lawless et al., 2004). However, the method has not been validated for soot-BC nor SHS and little work has been done to look at the methodological issues of the optical reflectance measurements for samples that could have SHS, BC, and other colored particles. We refined this method using a lab-modified integrating sphere with absorption measured continuously from 350 nm to 1000 nm. Furthermore, we characterized the absorption spectrum of additional components of particulate matter (PM) on PM(2.5) filters including ammonium sulfate, hematite, goethite, and magnetite. Finally, we validate this method for BC by comparison to other standard methods. Use of synthesized data indicates that it is important to optimize the choice of wavelengths to minimize computational errors as additional components (more than 2) are added to the apportionment model of colored components. We found that substantial errors are introduced when using 4 wavelengths suggested by Lawless et al. to quantify four substances, while an optimized choice of wavelengths can reduce model-derived error from over 10% to less than 2%. For environmental samples, the method was sensitive for estimating airborne levels of BC and SHS, but not mass loadings of iron oxides and sulfate. Duplicate samples collected in NYC show high reproducibility (points consistent with a 1:1 line, R(2) = 0.95). BC data measured by this method were consistent with those measured by other optical methods, including Aethalometer and Smoke-stain Reflectometer (SSR); although the SSR looses sensitivity at filter loadings above 90 ng/mm(2). Furthermore, positive correlations (R(2) = 0.7) were observed between EC measured by NIOSH Method 5040 on quartz filters and BC measured in co-located Teflon filter samples collected from both heating and non-heating seasons. Overall, the validation data demonstrates the usefulness of this method to evaluate BC from archived Teflon filters while potentially providing additional component information.

Personal, indoor, and outdoor exposure to VOCs in the immediate vicinity of a local airport.

This study measures the effect of emissions from an airport on the air quality of surrounding neighborhoods. The ambient concentrations of benzene, toluene, ethylbenzene, and o-, m-, and p-xylene (BTEX) were measured using passive samplers at 15 households located close to the airport (indoor, outdoor, and personal), at the end of airport runways and an out-of-neighborhood location. Measurements occurred over a 48-h period during summer 2006 and winter 2006-2007. The average concentrations were 0.84, 3.21, 0.30, 0.99, and 0.34 µg/m3 at the airport runways and 0.84, 3.76, 0.39, 1.22, and 0.39 µg/m3 in the neighborhood for benzene, toluene, ethylbenzene, m-, p-, and o-xylene. The average neighborhood concentrations were not significantly different to those measured at the airport runways and were higher than the out-of-neighborhood location (0.48, 1.09, 0.15, 0.78, and 0.43 µg/m3, each BTEX). B/T ratios were used as a tracer for emission sources and the average B/T ratio at the airport and outdoors were 0.20 and 0.23 for the summer and 0.40 and 0.42 for the winter, suggesting that both areas are affected by the same emission source. Personal exposure was closely related to levels in the indoor environment where subjects spent most of their time. Indoor/outdoor (I/O) ratios for BTEX ranged from 1.13 to 2.60 and 1.41 to 3.02 for summer and winter. The seasonal differences in I/O ratios reflected residential ventilation patterns, resulting in increased indoor concentrations of volatile organic compounds during winter.

Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice.

Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

Adenovirus-mediated Foxp3 expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model.

Foxp3 is a master regulator of CD4(+)CD25(+) regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma. Th2 cytokine and immune cell profiles of bronchoalveolar lavage fluid (BALF), as well as serum IgE levels, were analyzed. Histological analyses were also conducted to demonstrate the effects of Foxp3 expression on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Adenoviral Foxp3 was expressed only in lung epithelial cells, and not in CD4(+) or CD8(+) cells. BALF from Foxp3 gene-delivered mice showed significantly reduced numbers of total immune cells, eosinophils, neutrophils, macrophages and lymphocytes in response to cockroach allergen or OVA. In addition, Foxp3 expression in the lung reduced the levels of Th2 cytokines and IgE in BALF and serum, respectively. Moreover, histopathological analysis also showed that Foxp3 expression substantially inhibited eosinophil infiltration into the airways, goblet cell hyperplasia and smooth muscle cell hypertrophy. Furthermore, when Tregs were depleted by diphtheria toxin in Foxp3(DTR) mice, the anti-asthmatic functions of Foxp3 were not altered in OVA-challenged asthma models. In this study, our results suggest that Foxp3 expression in lung epithelial cells, and not in Tregs, inhibited OVA- and cockroach extract-induced asthma.

The therapeutic effects of tuberostemonine against cigarette smoke-induced acute lung inflammation in mice.

Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking and is characterized by the destruction of lung parenchyma, structural alterations of the small airways, and systemic inflammation. Tuberostemonine (TS) is an alkaloid-type phytochemical from Stemona tuberosa. In the present study, we evaluated the anti-inflammatory effect of TS in a cigarette smoke (CS)-induced mouse model of acute lung inflammation. The mice were whole-body exposed to CS or fresh air for 7 days. TS was administered by an intraperitoneal (i.p.) injection 1h before exposure to CS. To test the effects of TS, the numbers of total cells, neutrophils, macrophages and lymphocytes in the bronchoalveolar lavage (BAL) fluid were counted. Furthermore, we measured the levels of several chemokines, such as GCP-2, MIP-3α, MCP-1 and KC, in the lung tissue. The cellular profiles and histopathological analysis demonstrated that the infiltration of peribronchial and perivascular inflammatory cells significantly decreased in the TS-treated groups compared with the CS-exposure group. The TS treatment significantly ameliorated the airway epithelial thickness induced by CS exposure and caused a significant decrement in the production of chemokines in the lung. These results suggest that TS has anti-inflammatory effects against CS-induced acute lung inflammation.

Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammation via Bee Venom Phospholipase A2 in Mice.

Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A2 (bvPLA2) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA2 in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA2 six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA2 treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA2 treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes' mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA2 on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA2 in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA2 are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA2 in radiation pneumonitis and fibrosis treatments.

Protective Effects of Intratracheally-Administered Bee Venom Phospholipase A2 on Ovalbumin-Induced Allergic Asthma in Mice.

Asthma is a common chronic disease characterized by bronchial inflammation, reversible airway obstruction, and airway hyperresponsiveness (AHR). Current therapeutic options for the management of asthma include inhaled corticosteroids and ß2 agonists, which elicit harmful side effects. In the present study, we examined the capacity of phospholipase A2 (PLA2), one of the major components of bee venom (BV), to reduce airway inflammation and improve lung function in an experimental model of asthma. Allergic asthma was induced in female BALB/c mice by intraperitoneal administration of ovalbumin (OVA) on days 0 and 14, followed by intratracheal challenge with 1% OVA six times between days 22 and 30. The infiltration of immune cells, such as Th2 cytokines in the lungs, and the lung histology, were assessed in the OVA-challenged mice in the presence and absence of an intratracheal administration of bvPLA2. We showed that the intratracheal administration of bvPLA2 markedly suppressed the OVA-induced allergic airway inflammation by reducing AHR, overall area of inflammation, and goblet cell hyperplasia. Furthermore, the suppression was associated with a significant decrease in the production of Th2 cytokines, such as IL-4, IL-5, and IL-13, and a reduction in the number of total cells, including eosinophils, macrophages, and neutrophils in the airway.

Tuberostemonine N, an active compound isolated from Stemona tuberosa, suppresses cigarette smoke-induced sub-acute lung inflammation in mice.

OBJECTIVE: Our previous study demonstrated that a Stemona tuberosa extract had significant effects on cigarette smoking (CS)-induced lung inflammation in mice. The present study evaluated the potential of tuberostemonine N (T.N) to prevent airway inflammation and suppress airway responses in a CS-induced in vivo COPD model. METHODS: T.N was isolated from the root of ST and analyzed using 1D and 2D NMR. The purity of T.N was accessed using HPLC-ELSD analysis. C57BL/6 mice in this study were whole-body exposed to mainstream CS or room air for 4 weeks, and T.N (1, 5 and 10 mg/kg body wt.) was administered to mice via intraperitoneal (i.p.) injection before CS exposure. The number of inflammatory cells, including neutrophils, macrophages and lymphocytes, and the amount of proinflammatory cytokines and chemokines were accessed from bronchoalveolar lavage fluid (BALF) to investigate the anti-inflammatory effects of T.N. Average alveoli size was also measured using histological analyses. RESULTS: Cellular profiles and histopathological analyses revealed that the infiltration of peribronchial and perivascular inflammatory cells decreased significantly in the T.N-treated groups compared to the CS-exposed control group. T.N significantly inhibited the secretion of proinflammatory cytokines and chemokines in BALF and decreased alveoli size in lung tissue. CONCLUSIONS: These data suggest that T.N exerts anti-inflammatory effects against airway inflammation, and T.N may be a novel therapeutic agent for lung diseases, such as COPD.

Casticin, an active compound isolated from Vitex Fructus, ameliorates the cigarette smoke-induced acute lung inflammatory response in a murine model.

The aim of this study was to determine of the effect of casticin, as an anti-inflammatory agent, on an acute lung inflammation in vivo model established through exposure to cigarette smoke (CS). Casticin is a phytochemical from Vitex species such as Vitex rotundifolia and Vitex agnus-castus that was recently shown to exert an anti-inflammatory effect in vivo. To demonstrate the effects of casticin, C57BL/6 mice were whole-body exposed to mainstream CS or fresh air for two weeks and treated with 1, 2, and 10mg/kg casticin via an i.p. injection. Immune cell infiltrations and cytokine productions were assessed from bronchoalveolar lavage Fluid (BALF), and lung histological analysis was performed. Treatment with casticin was observed to significantly inhibit the numbers of total cells, neutrophils, macrophages, and lymphocytes and reduce the levels of proinflammatory cytokines and chemokines in the BALF. In addition, casticin significantly decreased the infiltration of peribronchial and perivascular inflammatory cells and the epithelium thickness. The results of this study indicate that casticin has significant effects on the lung inflammation induced by CS in a mouse model. According to these outcomes, casticin may have therapeutic potential in inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD).