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Sample records for post-injury baicalein improves

  1. Post-Injury Administration of Mitochondrial Uncouplers Increases Tissue Sparing and Improves Behavioral Outcome following Traumatic Brain Injury in Rodents.

    PubMed

    Pandya, Jignesh D; Pauly, James R; Nukala, Vidya N; Sebastian, Andrea H; Day, Kristen M; Korde, Amit S; Maragos, William F; Hall, Edward D; Sullivan, Patrick G

    2007-05-01

    Following experimental traumatic brain injury (TBI), a rapid and significant necrosis occurs at the site of injury which coincides with significant mitochondrial dysfunction. The present study is driven by the hypothesis that TBI-induced glutamate release increases mitochondrial Ca(2+)cycling/overload, ultimately leading to mitochondrial dysfunction. Based on this premise, mitochondrial uncoupling during the acute phases of TBI-induced excitotoxicity should reduce mitochondrial Ca(2+) uptake (cycling) and reactive oxygen species (ROS) production since both are mitochondrial membrane potential dependent. In the present study, we utilized a cortical impact model of TBI to assess the potential use of mitochondrial uncouplers (2,4-DNP, FCCP) as a neuroprotective therapy. Young adult male rats were intraperitoneally administered vehicle (DMSO), 2,4-DNP (5 mg/kg), or FCCP (2.5 mg/kg) at 5 min post-injury. All animals treated with the uncouplers demonstrated a significant reduction in the amount of cortical damage and behavioral improvement following TBI. In addition, mitochondria isolated from the injured cortex at 3 or 6 h post-injury demonstrated that treatment with the uncouplers significantly improved several parameters of mitochondrial bioenergetics. These results demonstrate that post-injury treatment with mitochondrial uncouplers significantly (p < 0.01) increases cortical tissue sparing ( approximately 12%) and significantly (p< 0.01) improves behavioral outcome following TBI. The mechanism of neuroprotection most likely involves the maintenance of mitochondrial homeostasis by reducing mitochondrial Ca(2+) loading and subsequent mitochondrial dysfunction. These results further implicate mitochondrial dysfunction as an early event in the pathophysiology of TBI and that targeting acute mitochondrial events can result in long-term neuroprotection and improve behavioral outcome following brain injury. PMID:17518535

  2. Baicalein pretreatment reduces liver ischemia/reperfusion injury via induction of autophagy in rats

    PubMed Central

    Liu, Anding; Huang, Liang; Guo, Enshuang; Li, Renlong; Yang, Jiankun; Li, Anyi; Yang, Yan; Liu, Shenpei; Hu, Jifa; Jiang, Xiaojing; Dirsch, Olaf; Dahmen, Uta; Sun, Jian

    2016-01-01

    We previously demonstrated that baicalein could protect against liver ischemia/reperfusion (I/R) injury in mice. The exact mechanism of baicalein remains poorly understood. Autophagy plays an important role in protecting against I/R injury. This study was designed to determine whether baicalein could protect against liver I/R injury via induction of autophagy in rats. Baicalein was intraperitoneally injected 1 h before warm ischemia. Pretreatment with baicalein prior to I/R insult significantly blunted I/R-induced elevations of serum aminotransferase levels and significantly improved the histological status of livers. Electron microscopy and expression of the autophagic marker LC3B-II suggested induction of autophagy after baicalein treatment. Moreover, inhibition of the baicalein-induced autophagy using 3-methyladenine (3-MA) worsened liver injury. Furthermore, baicalein treatment increased heme oxygenase (HO)-1 expression, and pharmacological inhibition of HO-1 with tin protoporphyrin IX (SnPP) abolished the baicalein-mediated autophagy and the hepatocellular protection. In primary rat hepatocytes, baicalein-induced autophagy also protected hepatocytes from hypoxia/reoxygenation injury in vitro and the beneficial effect was abrogated by 3-MA or Atg7 siRNA, respectively. Suppression of HO-1 activity by SnPP or HO-1 siRNA prevented the baicalein-mediated autophagy and resulted in increased hepatocellular injury. Collectively, these results suggest that baicalein prevents hepatocellular injury via induction of HO-1-mediated autophagy. PMID:27150843

  3. The flavonoid baicalein promotes NMDA receptor-dependent long-term potentiation and enhances memory

    PubMed Central

    Wang, Wei; Wang, Fang; Yang, Yuan-Jian; Hu, Zhuang-Li; Long, Li-Hong; Fu, Hui; Xie, Na; Chen, Jian-Guo

    2011-01-01

    BACKGROUND AND PURPOSE There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long-term potentiation (LTP) in the hippocampal CA1 region and cognitive behavioural performance. EXPERIMENTAL APPROACH Effects of baicalein on LTP in rat hippocampal slices were investigated by electrophysiological methods. Phosphorylation of Akt (at Ser473), the extracellular signal-regulated kinase (ERK1/2) and the transcription factor cAMP response element-binding protein (CREB) (at Ser133) were analysed by Western blot. Fear conditioning was used to determine whether baicalein could improve learning and memory in rats. KEY RESULTS Baicalein enhanced the N-methyl-d-aspartate glutamate receptor-dependent LTP in a bell-shaped concentration-dependent manner. Addition of the lipoxygenase metabolites 12(S)-HETE and 12(S)-HPETE did not reverse these effects of baicalein. Baicalein treatment enhanced phosphorylation of Akt during induction of LTP with the same bell-shaped dose–response curve. LTP potentiation induced by baicalein was blocked by inhibitors of phosphoinositide 3-kinase. CREB phosphorylation was also increased in the CA1 region of baicalein-treated slices. Baicalein-treated rats performed significantly better than controls in a hippocampus-dependent contextual fear conditioning task. Furthermore, baicalein treatment selectively increased the phosphorylation of Akt and CREB in the CA1 region of hippocampus, but not in the prefrontal cortex, after fear conditioning training. CONCLUSIONS AND IMPLICATIONS Our results demonstrate that the flavonoid baicalein can facilitate memory, and therefore it might be useful in the treatment of patients with memory disorders. PMID:21133890

  4. The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer's disease.

    PubMed

    Gu, Xun-Hu; Xu, Li-Jun; Liu, Zhi-Qiang; Wei, Bo; Yang, Yuan-Jian; Xu, Guo-Gang; Yin, Xiao-Ping; Wang, Wei

    2016-09-15

    Increasing evidence suggests that disruptions of synaptic functions correlate with the severity of cognitive deficit in Alzheimer's disease (AD). Our previous study demonstrated that baicalein enhances long-term potentiation (LTP) in acute rat hippocampal slices and improves hippocampus-dependent contextual fear conditioning in rats. Given that baicalein possess various biological activities, especially its effects on synaptic plasticity and cognitive function, we examined the effect of baicalein on synaptic function both in vitro and in vivo in AD model. The effect of baicalein on Aβ42 oligomer impaired LTP was investigated by electrophysiological methods. Baicalein was administered orally via drinking water to the APP/PS1 mice and sex- and age-matched wild-type mice. Treatment started at 5 months of age and mice were assessed for cognition and AD-like pathology at 7-month-old. Cognition was analyzed by Morris water maze test, fear conditioning test, and novel object recognition test. Changes in hippocampal 12/15 Lipoxygenase (12/15LO) and glycogen synthase kinase 3β (GSK3β) activity, Aβ production, tau phosphorylation, synaptic plasticity, and dendritic spine density were evaluated. Baicalein prevented Aβ-induced impairments in hippocampal LTP through activation of serine threonine Kinase (Akt) phosphorylation. Long-term oral administration of baicalein inhibited 12/15LO and GSK3β activity, reduced β-secretase enzyme (BACE1), decreased the concentration of total Aβ, and prevented phosphorylation of tau in APP/PS1 mice. Meanwhile, baicalein restored spine number, synaptic plasticity, and memory deficits. Our results strengthen the potential of the flavonoid baicalein as a novel and promising oral bioactive therapeutic agent that prevents memory deficits in AD. PMID:27233830

  5. Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury

    PubMed Central

    Lloyd, Eric; Somera-Molina, Kathleen; Van Eldik, Linda J; Watterson, D Martin; Wainwright, Mark S

    2008-01-01

    Background Traumatic brain injury (TBI) with its associated morbidity is a major area of unmet medical need that lacks effective therapies. TBI initiates a neuroinflammatory cascade characterized by activation of astrocytes and microglia, and increased production of immune mediators including proinflammatory cytokines and chemokines. This inflammatory response contributes both to the acute pathologic processes following TBI including cerebral edema, in addition to longer-term neuronal damage and cognitive impairment. However, activated glia also play a neuroprotective and reparative role in recovery from injury. Thus, potential therapeutic strategies targeting the neuroinflammatory cascade must use careful dosing considerations, such as amount of drug and timing of administration post injury, in order not to interfere with the reparative contribution of activated glia. Methods We tested the hypothesis that attenuation of the acute increase in proinflammatory cytokines and chemokines following TBI would decrease neurologic injury and improve functional neurologic outcome. We used the small molecule experimental therapeutic, Minozac (Mzc), to suppress TBI-induced up-regulation of glial activation and proinflammatory cytokines back towards basal levels. Mzc was administered in a clinically relevant time window post-injury in a murine closed-skull, cortical impact model of TBI. Mzc effects on the acute increase in brain cytokine and chemokine levels were measured as well as the effect on neuronal injury and neurobehavioral function. Results Administration of Mzc (5 mg/kg) at 3 h and 9 h post-TBI attenuates the acute increase in proinflammatory cytokine and chemokine levels, reduces astrocyte activation, and the longer term neurologic injury, and neurobehavioral deficits measured by Y maze performance over a 28-day recovery period. Mzc-treated animals also have no significant increase in brain water content (edema), a major cause of the neurologic morbidity associated

  6. Characterization and Enhanced Antioxidant Activity of the Cysteinyl β-Cyclodextrin-Baicalein Inclusion Complex.

    PubMed

    Kim, Hwanhee; Yiluo, Hu; Park, Seyeon; Lee, Jae Yung; Cho, Eunae; Jung, Seunho

    2016-01-01

    Baicalein is a type of flavonoid isolated from the roots of a medicinal plant, Scutellaria baicalensis. Although it has attracted considerable attention due to its antiviral, anti-tumor, and anti-inflammatory activities, its limited aqueous solubility inhibits the clinical application of this flavonoid. The present study aimed to prepare and characterize a host-guest complex in an effort to improve the solubility and antioxidant activity of baicalein. The host molecule is a macrocyclic β-cyclodextrin (β-CD) functionalized with cysteine for a synergetic effect. The structure of the synthesized cysteinyl β-CD was analyzed using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The inclusion complex with baicalein was studied by UV-vis, NMR spectroscopy, scanning electron microscopy, and X-ray powder diffractometry. The formed cysteinyl β-CD/baicalein inclusion complex efficiently improved the solubility and antioxidant ability of baicalein. Therefore, we suggest that the present cysteinyl β-CD is a potential host molecule for inclusion complexation and for bioavailability augmentation. PMID:27240335

  7. Enhanced bioavailability after oral and pulmonary administration of baicalein nanocrystal.

    PubMed

    Zhang, Jianjun; Lv, Huixia; Jiang, Kun; Gao, Yuan

    2011-11-25

    The aim of the study was to investigate the potential of oral and pulmonary nanocrystal to enhance the bioavailability of baicalein, a bioactive flavonoid isolated from the root of Scutellaria baicalensis Georgi. So far, the nano-sized delivery system of baicalein and its pulmonary delivery have received no exploration. In the present investigation, the baicalein nanocrystal was prepared by anti-solvent recrystallization followed by high pressure homogenization. In vitro characterization was performed including particle size and distribution, Zeta potential, dissolution, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry. It was indicated that no crystalline change was observed after nanocrystal preparation. The baicalein nanocrystal containing only trace of stabilizer exhibited a significantly enhanced dissolution of baicalein. In vivo test was also carried out in rats and pharmacokinetic parameters of the baicalein crystal and the baicalein nanocrystal after gavage and pulmonary administration were compared, based on the simultaneous determination of baicalein and baicalin by high performance liquid chromatography. The mean relative bioavailability of oral baicalein nanocrystal was 1.67-fold that of oral baicalein crystal. The pulmonary baicalein nanocrystal had rapid and extensive absorption and had almost identical pharmacokinetic parameters to intravenous baicalein injection. PMID:21878378

  8. The Traditional Chinese Medicine Baicalein Potently Inhibits Gastric Cancer Cells

    PubMed Central

    Mu, Jiasheng; Liu, Tianrun; Jiang, Lin; Wu, Xiangsong; Cao, Yang; Li, Maolan; Dong, Qian; Liu, Yingbin; Xu, Haineng

    2016-01-01

    Baicalein, a traditional Chinese medicine, is a member of the flavone subclass of flavonoids. It has been reported to have anticancer activities in several human cancer cell lines in vitro. However, the therapeutic effects of baicalein on human gastric cancer and the mechanisms of action of baicalein have not been extensively studied. In the present study, we utilized a cell viability assay and an in vivo tumor growth assay to test the inhibitory effects of baicalein on gastric cancer. Analyses of the cell cycle, apoptosis and alterations in protein levels were performed to elucidate how baicalein functions in gastric cancer. We found that baicalein could potently inhibit gastric cancer cell growth and colony formation. Baicalein robustly induced arrest at the S phase in the gastric cancer cell line SGC-7901. It induced SGC-7901 cell apoptosis and disrupted the mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Analysis of protein expression levels in SGC-7901 cells showed downregulation of Bcl-2 and upregulation of Bax in response to baicalein treatment. These results indicate that baicalein induces apoptosis of gastric cancer cells through the mitochondrial pathway. In an in vivo subcutaneous xenograft model, baicalein exhibited excellent tumor inhibitory effects. These results indicate that baicalein may be a potential drug for gastric cancer therapy. PMID:26918059

  9. Exploring Therapeutic Potentials of Baicalin and Its Aglycone Baicalein for Hematological Malignancies

    PubMed Central

    Chen, Haijun; Gao, Yu; Wu, Jianlei; Chen, Yingyu; Chen, Buyuan; Hu, Jianda; Zhou, Jia

    2014-01-01

    Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized. PMID:25128647

  10. Inhibitory Effect of Baicalin and Baicalein on Ovarian Cancer Cells

    PubMed Central

    Chen, Jianchu; Li, Zhaoliang; Chen, Allen Y.; Ye, Xingqian; Luo, Haitao; Rankin, Gary O.; Chen, Yi Charlie

    2013-01-01

    Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant activity and possible anti-angiogenic, anti-cancer, anxiolytic, anti-inflammatory and neuroprotective activities. Two kinds of ovarian cancer (OVCAR-3 and CP-70) cell lines and a normal ovarian cell line (IOSE-364) were selected to be investigated in the inhibitory effect of baicalin and baicalein on cancer cells. Largely, baicalin and baicalein inhibited ovarian cancer cell viability in both ovarian cancer cell lines with LD50 values in the range of 45–55 μM for baicalin and 25–40 μM for baicalein. On the other hand, both compounds had fewer inhibitory effects on normal ovarian cells viability with LD50 values of 177 μM for baicalin and 68 μM for baicalein. Baicalin decreased expression of VEGF (20 μM), cMyc (80 μM), and NFkB (20 μM); baicalein decreased expression of VEGF (10 μM), HIF-1α (20 μM), cMyc (20 μM), and NFkB (40 μM). Therefore baicalein is more effective in inhibiting cancer cell viability and expression of VEGF, HIF-1α, cMyc, and NFκB in both ovarian cancer cell lines. It seems that baicalein inhibited cancer cell viability through the inhibition of cancer promoting genes expression including VEGF, HIF-1α, cMyc, and NFκB. Overall, this study showed that baicalein and baicalin significantly inhibited the viability of ovarian cancer cells, while generally exerting less of an effect on normal cells. They have potential for chemoprevention and treatment of ovarian cancers. PMID:23502466

  11. Novel antiviral activity of baicalein against dengue virus

    PubMed Central

    2012-01-01

    Background Dengue is a serious arboviral disease currently with no effective antiviral therapy or approved vaccine available. Therefore, finding the effective compound against dengue virus (DENV) replication is very important. Among the natural compounds, bioflavonoids derived mainly from plants are of interest because of their biological and medicinal benefits. Methods In the present study, antiviral activity of a bioflavonoid, baicalein, was evaluated against different stages of dengue virus type 2 (DENV-2) replication in Vero cells using focus forming unit reduction assay and quantitative RT-PCR. Results Baicalein inhibited DENV-2 replication in Vero cells with IC50= 6.46 μg/mL and SI= 17.8 when added after adsorption to the cells. The IC50 against DENV-2 was 5.39 μg/mL and SI= 21.3 when cells were treated 5 hours before virus infection and continuously up to 4 days post infection. Baicalein exhibited direct virucidal effect against DENV-2 with IC 50= 1.55 μg/mL and showed anti-adsorption effect with IC50 = 7.14 μg/mL. Conclusions Findings presented here suggest that baicalein exerts potent antiviral activity against DENV. Baicalein possesses direct virucidal activity against DENV besides its effects against dengue virus adsorption and intracellular replication of DENV-2. Baicalein, hence, should be considered for in vivo evaluation in the development of an effective antiviral compound against DENV. PMID:23140177

  12. Baicalein reduces β-amyloid and promotes nonamyloidogenic amyloid precursor protein processing in an Alzheimer’s disease transgenic mouse model

    PubMed Central

    Zhang, She-Qing; Obregon, Demian; Ehrhart, Jared; Deng, Juan; Tian, Jun; Hou, Huayan; Giunta, Brian; Sawmiller, Darrell; Tan, Jun

    2013-01-01

    Baicalein, a flavonoid isolated from the roots of Scutellaria baicalensis, is known to modulate γ-aminobutyric acid (GABA) type A receptors. Given prior reports demonstrating benefits of GABAA modulation for Alzheimer’s disease (AD) treatment, we wished to determine whether this agent might be beneficial for AD. CHO cells engineered to overexpress wild-type amyloid precursor protein (APP), primary culture neuronal cells from AD mice (Tg2576) and AD mice were treated with baicalein. In the cell cultures, baicalein significantly reduced the production of β-amyloid (Aβ) by increasing APP α-processing. These effects were blocked by the GABAA antagonist bicuculline. Likewise, AD mice treated daily with i.p. baicalein for 8 weeks showed enhanced APP α-secretase processing, reduced Aβ production, and reduced AD-like pathology together with improved cognitive performance. Our findings suggest that baicalein promotes nonamyloidogenic processing of APP, thereby reducing Aβ production and improving cognitive performance, by activating GABAA receptors. © 2013 Wiley Periodicals, Inc. PMID:23686791

  13. Anti-Bladder-Tumor Effect of Baicalein from Scutellaria baicalensis Georgi and Its Application In Vivo

    PubMed Central

    Wu, Jin-Yi; Li, Yi-Zhen; Chang, Yi-Sheng; Lai, Yi-Chien; Laio, Yu-Han; Wu, Jiann-Der; Liu, Yi-Wen

    2013-01-01

    Some phytochemicals with the characteristics of cytotoxicity and/or antimetastasis have generated intense interest among the anticancer studies. In this study, a natural flavonoid baicalein was evaluated in bladder cancer in vitro and in vivo. Baicalein inhibits 5637 cell proliferation. It arrests cells in G1 phase at 100 μM and in S phase below 75 μM. The protein expression of cyclin B1 and cyclin D1 is reduced by baicalein. Baicalein-induced p-ERK plays a minor role in cyclin B1 reduction. Baicalein-inhibited p65NF-κB results in reduction of cell growth. Baicalein-induced pGSK(ser9) has a little effect in increasing cyclin B1/D1 expression instead. The translation inhibitor cycloheximide blocks baicalein-reduced cyclin B1, suggesting that the reduction is caused by protein synthesis inhibition. On the other hand, neither cycloheximide nor proteasome inhibitor MG132 completely blocks baicalein-reduced cyclin D1, suggesting that baicalein reduces cyclin D1 through protein synthesis inhibition and proteasomal degradation activation. In addition, baicalein also inhibits cell invasion by inhibiting MMP-2 and MMP-9 mRNA expression and activity. In mouse orthotopic bladder tumor model, baicalein slightly reduces tumor size but with some hepatic toxicity. In summary, these results demonstrate the anti-bladder-tumor properties of the natural compound baicalein which shows a slight anti-bladder-tumor effect in vivo. PMID:23573134

  14. Evaluating predictive screening for children's post-injury mental health: New data and a replication

    PubMed Central

    Kassam-Adams, Nancy; Marsac, Meghan L.; García-España, J. Felipe; Winston, Flaura

    2015-01-01

    Background Recommended approaches for secondary prevention of posttrauma mental health difficulties in children require empirically sound predictive screening to determine which children require more intensive monitoring or targeted intervention. Although there are several promising screening tools for injured children, none has emerged as the gold standard, and little replication data are available regarding their performance. Objective To evaluate a predictive screening protocol for risk of later posttraumatic stress (PTS) and depression outcomes and address a crucial lack of replication studies by examining performance of two previously published screening tools (Screening Tool for Early Predictors of PTSD [STEPP] and Child Trauma Screening Questionnaire [CTSQ]). Method The study enrolled 290 children hospitalized after acute injury. A three-part screening protocol, including acute PTS and depression symptoms and other empirically derived risk factors, was administered in hospital as part of a stepped care study. PTS and depression symptoms and health-related quality of life (HRQoL) were assessed 6 months post-injury. Results The screening protocol demonstrated excellent sensitivity (1.00) and good specificity (0.73) for prediction of 6-month PTS, moderate sensitivity (0.64) and good specificity (0.74) for 6-month depression, and excellent negative predictive value for both outcomes. Among children screening at risk, HRQoL was poorer at 6 months post-injury. Replication analyses found predictive utility (sensitivity and specificity) was low for the STEPP and moderate for the CTSQ. Conclusions This study provides additional evidence that early post-injury screening could identify children at higher risk for persistent PTS symptoms and limited support for predicting post-injury depression. Findings support acute PTS symptoms as key early risk markers. The predictive value of a negative screening result (i.e., knowing who is not at risk) may be especially important

  15. Preparation and evaluation of self-microemulsifying drug delivery system of baicalein.

    PubMed

    Liu, Wenli; Tian, Rui; Hu, Wenjing; Jia, Yuntao; Jiang, Huiming; Zhang, Jingqing; Zhang, Liangke

    2012-12-01

    The main object of this work is to prepare self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, baicalein. SMEDDS is the mixture of surfactants, cosurfactants, and oils, which are emulsified in aqueous media under conditions of gentle agitation or gastrointestinal motility. Solubility of baicalein was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and droplet size distributions of the resultant microemulsions were determined using a particle size analyzer. Optimized SMEDDS formulations for baicalein were Cremophor RH40 (53.57%) as surfactant, Transcutol P (21.43%) as cosurfactant, and Caprylic capric triglyceride (ODO, 25%) as oil. The drug release rate of SMEDDS was significantly higher than that of the baicalein suspension. Comparison of the pharmacokinetics between baicalein-loaded SMEDDS and baicalein suspension was also performed in rats. The plasma concentrations of baicalein and baicalin, its mainly conjugated metabolite, were determined by HPLC method. The in vivo results showed that the absorption of baicalein from SMEDDS resulted in about 200.7% increase in relative bioavailability compared with that of the baicalein suspension. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as baicalein by the oral route. PMID:22982454

  16. Baicalein inhibits the migration and invasive properties of human hepatoma cells

    SciTech Connect

    Chiu, Yung-Wei; Lin, Tseng-Hsi; Huang, Wen-Shih; Teng, Chun-Yuh; Liou, Yi-Sheng; Kuo, Wu-Hsien; Lin, Wea-Lung; Huang, Hai-I; Tung, Jai-Nien; Huang, Chih-Yang; Liu, Jer-Yuh; Wang, Wen-Hung; Hwang, Jin-Ming

    2011-09-15

    Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24 h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-{beta}. In addition, baicalein reduced the phosphorylation levels of PKC{alpha} and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo. - Highlight: > Baicalein inhibits several essential steps in the onset of metastasis.

  17. Baicalein inhibits hepatocellular carcinoma cells through suppressing the expression of CD24.

    PubMed

    Han, Zhengquan; Zhu, Shengming; Han, Xiao; Wang, Zian; Wu, Shiwu; Zheng, Rongsheng

    2015-12-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death and is the most common type of liver cancer. Current therapies for hepatocellular carcinoma are still rather limited and novel therapeutic strategies are required. Baicalein, extracted from Scutellaria baicalensis, has anticancer effects on HCC in vitro and vivo. However, the detailed mechanisms are not well studied yet. In the present study, we evaluated anticancer effects of purified botanical extracts on HCC cells using high-throughput screening and investigated the effects of baicalein on HCC cells using proliferation and apoptosis assays, RT-PCR, and Western blot. Transfection was used to explore the underlying mechanisms of these effects. Our results showed that baicalein is the most efficient botanical extract in a HCC cell line as compared with the other 13 extracts. Baicalein significantly decreased the expression of c-Myc, a crucial regulator of cell proliferation, apoptosis and cellular transformation, in dose- and time-dependent manners in HCC cells. Moreover, baicalein inhibited HCC cell proliferation and induced apoptosis. The mRNA and protein expressions of CD24 were downregulated by baicalein in HCC cells and ectopic overexpression of CD24 reversed baicalein-induced inhibition of cell proliferation and survival. Taken together, our results demonstrate efficient anticancer effects of baicalein on HCC cells and indicate that baicalein suppresses cell growth and cell survival through downregulation of CD24. PMID:26548344

  18. Inclusion complexation between baicalein and β-cyclodextrin and the influence of β-cyclodextrin on the binding of baicalein with DNA: a spectroscopic approach.

    PubMed

    Sameena, Yousuf; Chandrasekaran, Sowrirajan; Israel V M V, Enoch

    2016-07-01

    This work deals with the commonly studied cyclic oligosaccharide and gains importance as it is entered on a drug delivering carbohydrate and provides insight into the oligosaccharide complex-biomolecular interaction. The binding of a flavone, baicalein, to β-cyclodextrin and calf thymus DNA is studied. The binding of baicalein to calf thymus DNA in the presence of β-cyclodextrin is analysed using the UV-vis absorption and fluorescence spectroscopy. The mode of binding and structure of the baicalein-β-cyclodextrin complex are reported. The role of the structure and the stoichiometry of the inclusion complex of baicalein-β-cyclodextrin in its influence on DNA binding are analysed. Highlights • This paper deals with the binding of a flavone, baicalein to β-cyclodextrin and/or DNA. • The inclusion complexation between baicalein and β-cyclodextrin is analysed. • The stoichiometry and the binding strength of the inclusion complex is reported. • The role of β-cyclodextrin in tuning the binding of baicalein to DNA is emphasized. • Spectroscopic and docking analysis are used to articulate the results. PMID:26308145

  19. Post-injury administration of NAAG peptidase inhibitor prodrug, PGI-02776, in experimental TBI.

    PubMed

    Feng, Jun-Feng; Van, Ken C; Gurkoff, Gene G; Kopriva, Christina; Olszewski, Rafal T; Song, Minsoo; Sun, Shifeng; Xu, Man; Neale, Joseph H; Yuen, Po-Wai; Lowe, David A; Zhou, Jia; Lyeth, Bruce G

    2011-06-13

    Traumatic brain injury (TBI) leads to a rapid and excessive increase in glutamate concentration in the extracellular milieu, which is strongly associated with excitotoxicity and neuronal degeneration. N-acetylaspartylglutamate (NAAG), a prevalent peptide neurotransmitter in the vertebrate nervous system, is released along with glutamate and suppresses glutamate release by actions at pre-synaptic metabotropic glutamate autoreceptors. Extracellular NAAG is hydrolyzed to N-acetylaspartate and glutamate by peptidase activity. In the present study PGI-02776, a newly designed di-ester prodrug of the urea-based NAAG peptidase inhibitor ZJ-43, was tested for neuroprotective potential when administered intraperitoneally 30 min after lateral fluid percussion TBI in the rat. Stereological quantification of hippocampal CA2-3 degenerating neurons at 24 h post injury revealed that 10 mg/kg PGI-02776 significantly decreased the number of degenerating neurons (p<0.05). Both average latency analysis of Morris water maze performance and assessment of 24-hour memory retention revealed significant differences between sham-TBI and TBI-saline. In contrast, no significant difference was found between sham-TBI and PGI-02776 treated groups in either analysis indicating an improvement in cognitive performance with PGI-02776 treatment. Histological analysis on day 16 post-injury revealed significant cell death in injured animals regardless of treatment. In vitro NAAG peptidase inhibition studies demonstrated that the parent compound (ZJ-43) exhibited potent inhibitory activity while the mono-ester (PGI-02749) and di-ester (PGI-02776) prodrug compounds exhibited moderate and weak levels of inhibitory activity, respectively. Pharmacokinetic assays in uninjured animals found that the di-ester (PGI-02776) crossed the blood-brain barrier. PGI-02776 was also readily hydrolyzed to both the mono-ester (PGI-02749) and the parent compound (ZJ-43) in both blood and brain. Overall, these findings

  20. Baicalein Reduces the Invasion of Glioma Cells via Reducing the Activity of p38 Signaling Pathway

    PubMed Central

    Lei, Xiaoming; Li, Siyuan; Zhang, Yong; Meng, Lihua; Xue, Rongliang; Li, Zongfang

    2014-01-01

    Baicalein, one of the major flavonids in Scutellaria baicalensis, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and related mechanism(s) in glioma are still unclear. In this study, we thus utilized glioma cell lines U87MG and U251MG to explore the effect of baicalein. We found that administration of baicalein significantly inhibited migration and invasion of glioma cells. In addition, after treating with baicalein for 24 h, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression as well as proteinase activity in glioma cells. Conversely, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 was increased in a dose-dependent manner. Moreover, baicalein treatment significantly decreased the phosphorylated level of p38, but not ERK1/2, JNK1/2 and PI3K/Akt. Combined treatment with a p38 inhibitor (SB203580) and baicalein resulted in the synergistic reduction of MMP-2 and MMP-9 expression and then increase of TIMP-1 and TIMP-2 expression; and the invasive capabilities of U87MG cells were also inhibited. However, p38 chemical activator (anisomycin) could block these effects produced by baicalein, suggesting baicalein directly downregulate the p38 signaling pathway. In conclusion, baicalein inhibits glioma cells invasion and metastasis by reducing cell motility and migration via suppression of p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for glioma. PMID:24587321

  1. Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine.

    PubMed

    Kim, Dong Hwan; Sung, Bokyung; Chung, Hae Young; Kim, Nam Deuk

    2014-09-01

    In this review, we will summarize the current understanding of modulation of colitis-associated colon tumorigenesis by two natural products, baicalein and betaine, which have anti-inflammatory activities. Baicalein and betaine have been shown to provide various health benefits to organism in many ways. Baicalein is a phenolic flavonoid derived originally from the root of Scutellaria baicalensis Georgi. From ancient times, baicalein has widely been used in oriental medicines as an anti-inflammatory and anti-cancer therapy. Betaine, trimethylglycine, is an essential biochemical molecule of the methionine/homocysteine cycle and is synthesized by conversion of choline. Betaine is an important human nutrient obtained from various foods including sugar beet and lycium. Betaine has provided various health benefits including disease prevention. However, the action mechanisms of their activity remain poorly understood. Recent studies reported the effects of baicalein and betaine on cytotoxicity against colon cancer cells and chemically induced colitis-associated colon tumorigenesis in mice. Administrations of baicalein and betaine containing diets significantly inhibited the incidence of tumors and hyperplasia with down-regulation of inflammation. Therefore, baicalein and betaine might be applicable to the prevention of inflammation-associated colon carcinogenesis. PMID:25337584

  2. Baicalein increases the cytotoxicity of cisplatin by enhancing gap junction intercellular communication.

    PubMed

    Wang, Yiwen; Wang, Qin; Zhang, Suzhi; Zhang, Yuan; Tao, Liang

    2014-07-01

    Drug resistance limits the clinical application of cisplatin, a widely used chemotherapeutic agent. Gap junction (GJ) is a channel that enhances cytotoxicity of certain chemotherapeutic agents. Baicalein is well known for its antitumor activity. This study investigated the effect of baicalein on cisplatin cytotoxicity and the relationship between this effect and the modulation of the GJ function in connexin 26 (Cx26)‑transfected HeLa cells. The sulforhodamine B (SRB) assay was used to examine the effect of baicalein on cell viability. A 'parachute' assay was used to investigate the effect of baicalein on GJ function. The effects of baicalein on cisplatin cytotoxicity and GJ function were assayed by standard colony‑forming assays. The expression of Cx26 was monitored by western blotting. It was observed that exposure of Cx26‑transfected cells to cisplatin reduced the number of colonies formed in low‑density cultures (no GJ formation) and in high‑density cultures (GJ formation), but the toxic effect was greater when cells were seeded at a high density. In the absence of connexin expression or with blockage of connexin channels however, cell density had no effect on cisplatin toxicity. Baicalein significantly enhanced cisplatin cytotoxicity, but this effect required the presence of functional GJs between the cells. In conclusion, the dependence of cisplatin toxicity on cell density is mediated by GJs. Baicalein increases cisplatin cytotoxicity through enhancing GJ intercellular communication. PMID:24736991

  3. Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine

    PubMed Central

    Kim, Dong Hwan; Sung, Bokyung; Chung, Hae Young; Kim, Nam Deuk

    2014-01-01

    In this review, we will summarize the current understanding of modulation of colitis-associated colon tumorigenesis by two natural products, baicalein and betaine, which have anti-inflammatory activities. Baicalein and betaine have been shown to provide various health benefits to organism in many ways. Baicalein is a phenolic flavonoid derived originally from the root of Scutellaria baicalensis Georgi. From ancient times, baicalein has widely been used in oriental medicines as an anti-inflammatory and anti-cancer therapy. Betaine, trimethylglycine, is an essential biochemical molecule of the methionine/homocysteine cycle and is synthesized by conversion of choline. Betaine is an important human nutrient obtained from various foods including sugar beet and lycium. Betaine has provided various health benefits including disease prevention. However, the action mechanisms of their activity remain poorly understood. Recent studies reported the effects of baicalein and betaine on cytotoxicity against colon cancer cells and chemically induced colitis-associated colon tumorigenesis in mice. Administrations of baicalein and betaine containing diets significantly inhibited the incidence of tumors and hyperplasia with down-regulation of inflammation. Therefore, baicalein and betaine might be applicable to the prevention of inflammation-associated colon carcinogenesis. PMID:25337584

  4. Baicalein exhibits anti-inflammatory effects via inhibition of NF-κB transactivation.

    PubMed

    Patwardhan, Raghavendra S; Sharma, Deepak; Thoh, Maikho; Checker, Rahul; Sandur, Santosh K

    2016-05-15

    NF-κB is a crucial mediator of inflammatory and immune responses and a number of phytochemicals that can suppress this immune-regulatory transcription factor are known to have promising anti-inflammatory potential. However, we report that inducer of pro-inflammatory transcription factor NF-κB functions as an anti-inflammatory agent. Our findings reveal that a plant derived flavonoid baicalein could suppress mitogen induced T cell activation, proliferation and cytokine secretion. Treatment of CD4+ T cells with baicalein prior to transfer in to lymphopenic allogenic host significantly suppressed graft versus host disease. Interestingly, addition of baicalein to murine splenic lymphocytes induced DNA binding of NF-κB but did not suppress Concanavalin A induced NF-κB. Since baicalein did not inhibit NF-κB binding to DNA, we hypothesized that baicalein may be suppressing NF-κB trans-activation. Thioredoxin system is implicated in the regulation of NF-κB trans-activation potential and therefore inhibition of thioredoxin system may be responsible for suppression of NF-κB dependent genes. Baicalein not only inhibited TrxR activity in cell free system but also suppressed mitogen induced thioredoxin activity in the nuclear compartment of lymphocytes. Similar to baicalein, pharmacological inhibitors of thioredoxin system also could suppress mitogen induced T cell proliferation without inhibiting DNA binding of NF-κB. Further, activation of cellular thioredoxin system by the use of pharmacological activator or over-expression of thioredoxin could abrogate the anti-inflammatory action of baicalein. We propose a novel strategy using baicalein to limit NF-κB dependent inflammatory responses via inhibition of thioredoxin system. PMID:27019135

  5. Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro

    PubMed Central

    Wang, Ke; Hou, Changchun; Cai, Shuangqi; Huang, Yingying; Du, Zhongye; Huang, Hong; Kong, Jinliang; Chen, Yiqiang

    2016-01-01

    Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections. PMID:27128436

  6. Baicalein induces apoptosis via ROS-dependent activation of caspases in human bladder cancer 5637 cells.

    PubMed

    Choi, Eun-Ok; Park, Cheol; Hwang, Hye-Jin; Hong, Su Hyun; Kim, Gi-Young; Cho, Eun-Ju; Kim, Wun-Jae; Choi, Yung Hyun

    2016-09-01

    Baicalein is a flavonoid derived originally from the root of Scutellaria baicalensis Georgi, which has been used in Oriental medicines for treating various diseases. Although this compound has been reported to have anticancer activities in several human cancer cell lines, the therapeutic effects of baicalein on human bladder cancer and its mechanisms of action have not been extensively studied. This study investigated the proapoptotic effects of baicalein in human bladder cancer 5637 cells. For this study, cell viability and apoptosis were evaluated using the 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue dye exclusion assay 4,6-diamidino-2-phenylindole staining, and flow cytometry. Measurements of the mitochondrial membrane potential (MMP), caspase activity assays and western blots were conducted to determine whether 5637 cell death occurred by apoptosis. Treatment with baicalein resulted in a concentration-dependent growth inhibition coupled with apoptosis induction, as indicated by the results of nuclei morphology examination and flow cytometry analyses. The induction of the apoptotic cell death of 5637 cells by baicalein exhibited a correlation with the downregulation of members of the inhibitor of apoptosis protein (IAP) family, including cIAP-1 and cIAP-2, and the activation of caspase-9 and -3 accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. The study also showed that baicalein decreases the expression of the proapoptotic protein Bax, increases antiapoptotic Bcl-2 expression, and noticeably aggravates the loss of MMP. Concomitantly, the data showed that baicalein increases the levels of death receptors and their associated ligands and enhances the activation of caspase-8 and truncation of Bid. However, the pan-caspase inhibitor can reverse baicalein-induced apoptosis, demonstrating that it is a caspase-dependent pathway. Moreover, it was found that baicalein can induce the production of reactive oxygen

  7. Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin

    PubMed Central

    WANG, CHONG-ZHI; ZHANG, CHUN-FENG; CHEN, LINA; ANDERSON, SAMANTHA; LU, FANG; YUAN, CHUN-SU

    2015-01-01

    Baicalin is a major constituent of Scutellaria baicalensis, which is a commonly used herbal medicine in many Asian countries. After oral ingestion, intestinal micro-biota metabolism may change parent compound's structure and its biological activities. However, whether baicalin can be metabolized by enteric microbiota and the related anti-cancer activity is not clear. In this study, using human enteric microbiome incubation and HPLC analysis, we observed that baicalin can be quickly converted to baicalein. We compared the antiproliferative effects of baicalin and baicalein using a panel of human cancer cell lines, including three human colorectal cancer (CRC) cell lines. In vitro antiproliferative effects on CRC cells were verified using an in vivo xenograft nude mouse model. Baicalin showed limited antiproliferative effects on some of these cancer cell lines. Baicalein, however, showed significant antiproliferative effects in all the tested cancer cell lines, especially on HCT-116 human colorectal cancer cells. In vivo antitumor results supported our in vitro data. We demonstrated that baicalein exerts potent S phase cell cycle arrest and pro-apoptotic effects in HCT-116 cells. Baicalein induced the activation of caspase 3 and 9. The in silico modeling suggested that baicalein forms hydrogen bonds with residues Ser251 and Asp253 at the active site of caspase 3, while interactions with residues Leu227 and Asp228 in caspase 9 through its hydroxyl groups. Data from this study suggested that baicalein is a potent anticancer metabolite derived from S. baicalensis. Enteric microbiota play a key role in the colon cancer chemoprevention of S. baicalensis. PMID:26398706

  8. Regulation of bone formation by baicalein via the mTORC1 pathway

    PubMed Central

    Li, Sheng-fa; Tang, Jia-jun; Chen, Jian; Zhang, Pei; Wang, Ting; Chen, Tian-yu; Yan, Bo; Huang, Bin; Wang, Liang; Huang, Min-jun; Zhang, Zhong-min; Jin, Da-di

    2015-01-01

    Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 μmol/L, 1 μmol/L, 10 μmol/L), to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX) mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day) in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen Iα1, and runt-related transcription factor 2 (RUNX2), in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months compared with OVX mice that were not treated with baicalein. We also found that expression of osteocalcin and RUNX2 was decreased in primary ossified tissue from the OVX group, and baicalein increased the levels of osteocalcin and RUNX2 in OVX mice. These data suggest that baicalein can stimulate MC3T3-E1 cells to differentiate into osteoblasts via activation of the mTORC1 signaling pathway, which includes protein kinases and transcription factors such as P-4E/BP1 and P-S6K1. PMID:26392752

  9. Structural Characteristics of the Alpha-Synuclein Oligomers Stabilized By the Flavonoid Baicalein

    SciTech Connect

    Hong, D.-P.; Fink, A.L.; Uversky, V.N.

    2009-05-18

    The flavonoid baicalein inhibits fibrillation of alpha-synuclein, which is a major component of Lewy bodies in Parkinson's disease. It has been known that baicalein induces the formation of alpha-synuclein oligomers and consequently prevents their fibrillation. In order to evaluate the structural properties of baicalein-stabilized oligomers, we purified oligomer species by HPLC and examined their stability and structure by CD, Fourier transform infrared spectroscopy, size exclusion chromatography HPLC, small-angle X-ray scattering, and atomic force microscopy. Baicalein-stabilized oligomers are beta-sheet-enriched according to CD and Fourier transform infrared spectroscopy analyses. They did not form fibrils even after very prolonged incubation. From small-angle X-ray scattering data and atomic force microscopy images, the oligomers were characterized as quite compact globular species. Oligomers were extremely stable, with a GdmCl C(m)=3.3 M. This high stability explains the previously observed inhibition properties of baicalein against alpha-synuclein fibrillation. These baicalein-stabilized oligomers, added to the solution of aggregating alpha-synuclein, were able to noticeably inhibit its fibrillation. After prolonged coincubation, short fibrils were formed, suggesting an effective interaction of oligomers with monomeric alpha-synuclein. Membrane permeability tests suggested that the baicalein-stabilized oligomers had a mild effect on the integrity of the membrane surface. This effect was rather similar to that of the monomeric protein, suggesting that targeted stabilization of certain alpha-synuclein oligomers might offer a potential strategy for the development of novel Parkinson's disease therapies.

  10. Baicalein induces CD4+Foxp3+ T cells and enhances intestinal barrier function in a mouse model of food allergy

    PubMed Central

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Kwon, Da-Ae; Shon, Dong-Hwa

    2016-01-01

    The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy. PMID:27561877

  11. Baicalein induces CD4(+)Foxp3(+) T cells and enhances intestinal barrier function in a mouse model of food allergy.

    PubMed

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Kwon, Da-Ae; Shon, Dong-Hwa

    2016-01-01

    The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy. PMID:27561877

  12. Latest research progress in the correlation between baicalein and breast cancer invasion and metastasis

    PubMed Central

    YAN, WAN-JUN; MA, XING-CONG; GAO, XIAO-YAN; XUE, XING-HUAN; ZHANG, SHU-QUN

    2016-01-01

    Breast cancer is one of the most commonly occurring female malignant tumors. According to the 2012 GLOBOCAN statistics, produced by the International Agency for Research On Cancer (‘IARC’), nearly 1.7 million women were diagnosed with breast cancer, with 522,000 related deaths: An increase in the incidence of breast cancer and associated mortality by nearly 18% from 2008. Metastasis is the final step in breast cancer progression, and represents the most common cause of mortality in patients with breast cancer. Therefore, a search for low-toxicity, safe and effective anti-breast cancer drugs in the form of natural compounds has become an intense focus of research. Baicalein, a widely used Chinese herbal medicine, has extensive antitumor activity. The present review briefly describes the research that has been performed on the association between baicalein and breast cancer metastasis, and further illustrates the influence of baicalein on the underlying mechanisms of breast cancer metastasis, adding a novel theory basis for baicalein antitumor research. In conclusion, baicalein may represent a promising target for the prevention and therapy of breast cancer. PMID:27073644

  13. γ-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein.

    PubMed

    Yamashita, Shuya; Baba, Kiwako; Makio, Akiko; Kumazoe, Motofumi; Huang, Yuhui; Lin, I-Chian; Bae, Jaehoon; Murata, Motoki; Yamada, Shuhei; Tachibana, Hirofumi

    2016-05-13

    Previous studies have identified biomolecules that mediate the physiological actions of food factors, such as amino acids, vitamins, fatty acids, minerals, plant polyphenols, and lactobacilli, suggesting that our bodies are equipped with an innate system that senses which food factors are required to maintain our health. However, the effects of environmental factors on food factor sensing (FFS) remains largely unknown. Tocotorienols (T3s), which belongs to the vitamin E family, possess several physiological functions, including cholesterol lowering and neuroprotective effects. Here, we investigated the effects of naturally abundant γ-T3 on FFS-related gene expressions in melanoma using a DNA chip. Our results showed that γ-T3 increased the expression level of aryl hydrocarbon receptor (AhR), a sensing molecule to plant polyphenol baicalein. The co-treatment with γ-T3 and baicalein enhanced the anti-proliferative activity of baicalein, accompanied by the downstream events of AhR-activation induced by baicalein. These data suggest that γ-T3 upregulates AhR expression and enhances its sensitivity to baicalein. PMID:27055589

  14. Vascular barrier protective effects of baicalin, baicalein and wogonin in vitro and in vivo

    SciTech Connect

    Kwak, Soyoung; Ku, Sae-Kwang; Han, Min-Su; Bae, Jong-Sup

    2014-11-15

    Inhibition of high mobility group box 1 (HMGB1) protein and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of sepsis. Here, three structurally related polyphenols found in the Chinese herb Huang Qui, baicalin (BCL), baicalein (BCN), and wogonin (WGN), were examined for their effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. According to our data, BCL, BCN, and WGN inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. BCL, BCN, and WGN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with BCL, BCN, and WGN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that BCL, BCN, and WGN could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway. - Highlights: • HMGB1 is an inflammatory mediator for vascular inflammation. • Baicalin, baicalein and wogonin inhibited HMGB1-induced hyperpermeability in vitro and in vivo. • Baicalin, baicalein and wogonin inhibited HMGB1-mediated inflammatory responses. • Baicalin, baicalein and wogonin suppressed the activation of NF-κB and ERK1/2 and production of TNF-α and IL-6. • Baicalin, baicalein and wogonin prevent CLP-induced septic mortality.

  15. Delayed Post-Injury Administration of Riluzole Is Neuroprotective in a Preclinical Rodent Model of Cervical Spinal Cord Injury

    PubMed Central

    Wu, Yongchao; Satkunendrarajah, Kajana; Teng, Yang; Chow, Diana S.-L.; Buttigieg, Josef

    2013-01-01

    Abstract Riluzole, a sodium/glutamate antagonist has shown promise as a neuroprotective agent. It is licensed for amyotrophic lateral sclerosis and is in clinical trial development for spinal cord injury (SCI). This study investigated the therapeutic time-window and pharmacokinetics of riluzole in a rodent model of cervical SCI. Rats were treated with riluzole (8 mg/kg) at 1 hour (P1) and 3 hours (P3) after injury or with vehicle. Afterward, P1 and P3 groups received riluzole (6 (mg/kg) every 12 hours for 7 days. Both P1 and P3 animals had significant improvements in locomotor recovery as measured by open field locomotion (BBB score, BBB subscore). Von Frey stimuli did not reveal an increase in at level or below level mechanical allodynia. Sensory-evoked potential recordings and quantification of axonal cytoskeleton demonstrated a riluzole-mediated improvement in axonal integrity and function. Histopathological and retrograde tracing studies demonstrated that delayed administration leads to tissue preservation and reduces apoptosis and inflammation. High performance liquid chromatography (HPLC) was undertaken to examine the pharmacokinetics of riluzole. Riluzole penetrates the spinal cord in 15 min, and SCI slowed elimination of riluzole from the spinal cord, resulting in a longer half-life and higher drug concentration in spinal cord and plasma. Initiation of riluzole treatment 1 and 3 hours post-SCI led to functional, histological, and molecular benefits. While extrapolation of post-injury time windows from rat to man is challenging, evidence from SCI-related biomarker studies would suggest that the post-injury time window is likely to be at least 12 hours in man. PMID:23517137

  16. Baicalein induces programmed cell death in Candida albicans.

    PubMed

    Dai, Bao-Di; Cao, Ying-Ying; Huang, Shan; Xu, Yong-Gang; Gao, Ping-Hui; Wang, Yan; Jiang, Yuan-Ying

    2009-08-01

    Recent evidence has revealed the occurrence of an apoptotic phenotype in Candida albicans that is inducible with environmental stresses such as acetic acid, hydrogen peroxide, and amphotericin B. In the present study, we found that the Chinese herbal medicine Baicalein (BE), which was one of the skullcapflavones, can induce apoptosis in C. albicans. The apoptotic effects of BE were detected by flow cytometry using Annexin V-FITC and DAPI, and it was confirmed by transmission electron microscopy analysis. After exposure to 4 microg/ml BE for 12 h, about 10% of C. albicans cells were apoptotic. Both the increasing intracellular levels of reactive oxygen species (ROS) and upregulation of some redox-related genes (CAP1, SOD2, TRR1) were observed. Furthermore, we compared the survivals of CAP1 deleted, wild-type, and overexpressed strains and found that Cap1p attenuated BE-initiated cell death, which was coherent with a higher mRNA level of the CAP1 gene. In addition, the mitochondrial membrane potential of C. albicans cells changed significantly ( p<0.001) upon BE treatment compared with control. Taken together, our results indicate that BE treatment induces apoptosis in C.albicans cells, and the apoptosis was associated with the breakdown of mitochondrial membrane potential. PMID:19734718

  17. Pre and post-injury environmental enrichment effects functional recovery following medial frontal cortical contusion injury in rats.

    PubMed

    Jacqmain, Justin; Nudi, Evan T; Fluharty, Sarah; Smith, Jeffrey S

    2014-12-15

    The rodent has been the preferred research model for evaluating the mechanisms related to, and potential treatments for, traumatic brain injury (TBI). Many therapies previously determined to be effective in pre-clinical investigations have failed to show the same effectiveness in clinical trials. The environment a rodent is housed in plays an important role in brain and behavioral development. Housing rodents in non-enriched environments significantly alters the development of the rodent brain and its behavioral profile, negatively impacting the ecological validity of the rodent model. This investigation employed 113 male Long-Evans rats assigned to either an enriched environment (EE) or standard environment (SE) from post-natal day 25. At four months of age, rats received either a controlled cortical impact (CCI) to the medial frontal cortex (mFC) or sham injury. Rats assigned to EE or SE pre-injury were re-assigned to remain in, or switch to, EE or SE post-injury. The open-field test (OFT), vermicelli handling test (VHT) Morris water maze (MWM), and rotor-rod (RR), were used to evaluate the animals response to TBI. The data from the current investigation indicates that the performance of TBI rats assigned to pre-injury EE was improved on the MWM compared to the TBI rats assigned to pre-injury SE. However, those that were reared in the EE performed better on the MWM if placed into a SE post-injury as compared to those placed into the EE after insult. The TBI and sham groups that were raised, and remained, in the SE performed worse than any of the EE groups on the RR. TBI rats that were placed in the EE had larger cortices and more cells in the hippocampus than the TBI rats housed in the SE. These data strongly suggest that the pre-injury housing environment should be considered as investigators refine pre-clinical models of TBI. PMID:25196632

  18. Carboxyfullerene neuroprotection post injury in parkinsonian nonhuman primates

    PubMed Central

    Dugan, Laura L.; Tian, LinLin; Quick, Kevin L.; Hardt, Josh I.; Karimi, Morvarid; Brown, Chris; Loftin, Susan; Flores, Hugh; Moerlein, Stephen M.; Polich, John; Tabbal, Samer D.; Mink, Jonathan W.; Perlmutter, Joel S.

    2014-01-01

    Objective We evaluated the efficacy of the potent antioxidant C3 to salvage nigrostriatal neuronal function after MPTP exposure in nonhuman primates. C3 is a first-in-class functionalized water-soluble fullerene which reduces oxygen radical species associated with neurodegeneration in in vitro studies. However, C3 has not been evaluated as a neuroprotective agent in a Parkinson model in vivo. Methods Macaque fascicularis monkeys were used in a double-blind, placebo-controlled study design. MPTP-lesioned primates were given systemic C3 (n = 8) or placebo (n = 7) for two months starting one week after MPTP. Outcomes included in vivo behavioral measures of motor parkinsonism using a validated non-human primate rating scale, kinematic analyses of peak upper extremity velocity, PET imaging of 6-[18F]fluorodopa (FD, reflects dopa decarboxylase) and [11C]dihydrotetrabenazine (DTBZ; reflects vesicular monoamine transporter type 2), as well as ex vivo quantification of striatal dopamine (DA) and stereologic counts of tyrosine hydroxylase (TH) immunostained neurons in substantia nigra. Results After two months, C3 treated monkeys had significantly improved parkinsonian motor ratings, greater striatal FD and DTBZ uptake, and higher striatal dopamine levels. None of the C3 treated animals developed any toxicity. Interpretation Systemic treatment with C3 reduced striatal injury and improved motor function despite administration after the MPTP injury process had begun. These data strongly support further development of C3 as a promising therapeutic agent for PD. PMID:25043598

  19. Baicalein increases keratin 1 and 10 expression in HaCaT keratinocytes via TRPV4 receptor activation.

    PubMed

    Huang, Kuo-Feng; Ma, Kuo-Hsing; Liu, Pei-Shan; Chen, Bo-Wei; Chueh, Sheau-Huei

    2016-08-01

    In this study, we characterized the effect of baicalein on the regulation of keratinocyte differentiation and proliferation, which are abnormal in atopic dermatitis or psoriasis. Treatment of HaCaT keratinocytes with 10 μm baicalein slightly inhibited cell growth, caused morphological differentiation and increased expression of keratins 1 and 10 (K1/K10) without affecting ROS generation, cytochrome c release or apoptosis. Baicalein treatment caused growth arrest in G0 /G1 phase and also induced Ca(2+) influx via TRPV4 receptor activation. Phosphorylation of ERK, Akt and p38 MAPK, but not JNK, was increased by baicalein, and inhibition of phosphorylation of ERK, but not that of Akt or p38 MAPK, blocked the baicalein-induced increase in K1/K10 expression, suggesting that ERK activation is involved in this increase. Removal of extracellular Ca(2+) or blockade of Ca(2+) influx by pharmacological inhibition or silencing of the TRPV4 receptor did not affect growth arrest, ROS generation or apoptosis, but inhibited baicalein-induced ERK phosphorylation and K1/K10 expression. Thus, baicalein treatment increases differentiation, and decreases proliferation, of keratinocytes. The mechanism of differentiation of keratinocytes is distinct from that of proliferation, the former being Ca(2+) dependent and the latter Ca(2+) independent. PMID:27060689

  20. Amylin Amyloid Inhibition by Flavonoid Baicalein: Key Roles of Its Vicinal Dihydroxyl Groups of the Catechol Moiety.

    PubMed

    Velander, Paul; Wu, Ling; Ray, W Keith; Helm, Richard F; Xu, Bin

    2016-08-01

    Amyloid formation of the 37-residue amylin is involved in the pathogenesis of type 2 diabetes and, potentially, diabetes-induced neurological deficits. Numerous flavonoids exhibit inhibitory effects against amylin amyloidosis, but the mechanisms of inhibition remain unclear. Screening a library of natural compounds uncovered a potent lead compound, the flavone baicalein. Baicalein inhibits amylin amyloid formation and reduces amylin-induced cytotoxicity. Analogue analyses demonstrated, for the first time, key roles of the vicinal hydroxyl groups on the A-ring. We provided mass spectrometric evidence that incubating baicalein and amylin leads to their conjugation, consistent with a Schiff base mechanism. PMID:27431615

  1. Baicalein Induces Caspase-dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells.

    PubMed

    Kim, Hong Jae; Park, Cheol; Han, Min-Ho; Hong, Su-Hyun; Kim, Gi-Young; Hoon Hong, Sang; Deuk Kim, Nam; Choi, Yung Hyun

    2016-03-01

    Preclinical Research Baicalein is one of the main bioactive flavonoids found in the roots of Scutellaria baicalensis Georgi. Here, we report that baicalein-induced growth inhibition was associated with the induction of apoptosis in human lung carcinoma A549 cells. Baicalein stimulated the expression of DR5, FasL, and FADD, and activated caspase-8 by reducing the levels of FLIPs (FLICE-inhibitory proteins). The apoptotic cell death was also connected with an activation of caspase-9 and -3, and cleavage of poly(ADP-ribose) polymerase; however, a blockage of caspase activation abolished baicalein-induced apoptotic potentials. Additionally, baicalein caused a mitochondrial membrane potential (MMP), the truncation of Bid, and the translocation of pro-apoptotic Bax to the mitochondria, thereby inducing the release of cytochrome c into the cytosol. In turn, baicalein increased the generation of reactive oxygen species (ROS); however, an ROS scavenger, N-acetylcysteine, notably attenuated baicalein-mediated loss of MMP and activation of caspases. Furthermore, baicalein activated the AMP-activated protein kinase (AMPK) signaling pathway. Consequently, baicalein-triggered cell death was attenuated by an AMPK inhibitor, but increased by an AMPK activator, compound C. Overall, the results suggest that the apoptotic activity of baicalein may be associated with caspase-dependent cascade through the activation of both intrinsic and extrinsic signaling pathways connected with ROS generation and AMPK activation. Drug Dev Res 77 : 73-86, 2016.   © 2016 Wiley Periodicals, Inc. PMID:26971531

  2. Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR).

    PubMed

    Carazo Fernández, Alejandro; Smutny, Tomas; Hyrsová, Lucie; Berka, Karel; Pavek, Petr

    2015-03-01

    The constitutive androstane receptor (CAR) is a crucial transcriptional regulator of key xenobiotic-metabolizing enzymes such as cytochrome P450 CYP3A4, CYP2C9 and CYP2B6. The flavonoids chrysin, baicalein and galangin have been reported to activate CAR and interfere with EGFR signaling. Nevertheless, it is not known if these flavonoids are direct CAR ligands or indirect phenobarbital-like CAR activators via the inhibition of epidermal growth factor receptor (EGFR) signaling. We analyze the interactions of chrysin, galangin and baicalein and its glycoside baicalin with human CAR. We have employed and validated methods that can study direct interaction with the CAR ligand binding pocket. Secondly, we determined if the compounds affect human EGFR signaling and interact with EGFR. Employing a TR-FRET coactivator assay with recombinant CAR or CAR assembly assay, a consistent activation of CAR with flavonoids and phenobarbital was not observed. It was determined, however, that galangin, chrysin, and baicalein may slightly repress EGFR-Tyr1068 autophosphorylation after EGF treatment, phosphorylation of downstream transcription factor ELK1 and stimulate EGFP-CAR nuclear translocation in primary human hepatocytes. These data suggest that flavonoids chrysin, galangin and baicalein are indirect human CAR activators. This study also demonstrates new approach how to test the direct CAR interaction with its ligands. PMID:25625231

  3. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus

    PubMed Central

    Moghaddam, Ehsan; Teoh, Boon-Teong; Sam, Sing-Sin; Lani, Rafidah; Hassandarvish, Pouya; Chik, Zamri; Yueh, Andrew; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    Baicalin, a flavonoid derived from Scutellaria baicalensis, is the main metabolite of baicalein released following administration in different animal models and human. We previously reported the antiviral activity of baicalein against dengue virus (DENV). Here, we examined the anti-DENV properties of baicalin in vitro, and described the inhibitory potentials of baicalin at different steps of DENV-2 (NGC strain) replication. Our in vitro antiviral experiments showed that baicalin inhibited virus replication at IC50 = 13.5 ± 0.08 μg/ml with SI = 21.5 following virus internalization by Vero cells. Baicalin exhibited virucidal activity against DENV-2 extracellular particles at IC50 = 8.74 ± 0.08 μg/ml and showed anti-adsorption effect with IC50 = 18.07 ± 0.2 μg/ml. Our findings showed that baicalin as the main metabolite of baicalein exerting in vitro anti-DENV activity. Further investigations on baicalein and baicalin to deduce its antiviral therapeutic effects are warranted. PMID:24965553

  4. Depletion of GGA1 and GGA3 mediates post-injury elevation of BACE1

    PubMed Central

    Walker, Kendall R.; Kang, Eugene L.; Whalen, Michael J.; Shen, Yong; Tesco, Giuseppina

    2012-01-01

    Traumatic brain injury (TBI) is one of the most robust environmental risk factors for Alzheimer’s disease (AD). Compelling evidence is accumulating that a single event of TBI is associated with increased levels of Aβ. However, the underlying molecular mechanisms remain unknown. We report here that the BACE1 interacting protein, GGA3, is depleted while BACE1 levels increase in the acute phase post-injury (48hrs) in a mouse model of TBI. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We next found that head trauma potentiates BACE1 elevation in GGA3 null mice in the acute phase post-TBI and discovered that GGA1, a GGA3 homologue, is a novel caspase-3 substrate depleted at 48 hrs post-TBI. Moreover, GGA1 silencing potentiates BACE1 elevation induced by GGA3 deletion in neurons in vitro indicating that GGA1 and GGA3 synergistically regulate BACE1. Accordingly, we found that levels of both GGA1 and GGA3 are depleted while BACE1 levels are increased in a series of post-mortem AD brains. Finally, we show that GGA3 haploinsufficiency results in sustained elevation of BACE1 and Aβ levels while GGA1 levels are restored in the subacute phase (7 days) post-injury. In conclusion, our data indicate that depletion of GGA1 and GGA3 engender a rapid and robust elevation of BACE1 in the acute phase post-injury. However, the efficient disposal of the acutely accumulated BACE1 solely depends on GGA3 levels in the sub-acute phase of injury. PMID:22836275

  5. Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism

    PubMed Central

    2012-01-01

    Background Two active compounds, baicalein and its glycoside baicalin were found in the dried root of Scutellaria baicalensis Georgi, and reported to be neuroprotective in vitro and in vivo. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism. Methods Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots. Results Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2. Conclusion The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells. PMID:22264378

  6. Synergistic Action of Flavonoids, Baicalein, and Daidzein in Estrogenic and Neuroprotective Effects: A Development of Potential Health Products and Therapeutic Drugs against Alzheimer's Disease

    PubMed Central

    Choi, Roy C. Y.; Zhu, Judy T. T.; Yung, Amanda W. Y.; Lee, Pinky S. C.; Xu, Sherry L.; Guo, Ava J. Y.; Zhu, Kevin Y.; Dong, Tina T. X.; Tsim, Karl W. K.

    2013-01-01

    Despite the classical hormonal effect, estrogen has been reported to mediate neuroprotection in the brain, which leads to the searching of estrogen-like substances for treating neurodegenerative diseases. Flavonoids, a group of natural compounds, are well known to possess estrogenic effects and used to substitute estrogen, that is, phytoestrogen. Flavonoid serves as one of the potential targets for the development of natural supplements and therapeutic drugs against different diseases. The neuroprotection activity of flavonoids was chosen for a possible development of anti-Alzheimer's drugs or food supplements. The estrogenic activity of two flavonoids, baicalein and daidzein, were demonstrated by their strong abilities in stimulating estrogen receptor phosphorylation and transcriptional activation of estrogen responsive element in MCF-7 breast cells. The neuroprotection effects of flavonoids against β-amyloid (Aβ) were revealed by their inhibition effects on in vitro Aβ aggregation and Aβ-induced cytotoxicity in PC12 neuronal cells. More importantly, the estrogenic and neuroprotective activities of individual flavonoid could be further enhanced by the cotreatment in the cultures. Taken together, this synergistic effect of baicalein and daidzein might serve as a method to improve the therapeutic efficacy of different flavonoids against Aβ, which might be crucial in developing those flavonoidsin treating Alzheimer's disease in the future. PMID:24058373

  7. Post-injury multiple organ failure: the role of the gut.

    PubMed

    Hassoun, H T; Kone, B C; Mercer, D W; Moody, F G; Weisbrodt, N W; Moore, F A

    2001-01-01

    Despite intensive investigation, the pathogenesis of post-injury multiple organ failure (MOF) remains elusive. Laboratory and clinical research strongly suggests that the gastrointestinal tract (i.e., the gut) plays a pivotal pathogenic role. Since its inception in 1988, the Trauma Research Center (TRC) at the University of Texas-Houston Medical School (UTHMS) has focused its efforts on elucidating the role of the gut in post-injury MOF. On the basis of our observations and those of others, we believe that 1) shock with resulting gut hypoperfusion is an important inciting event, 2) the reperfused gut is a source of proinflammatory mediators that can amplify the early systemic inflammatory response syndrome (SIRS) and thus contribute to early MOF, 3) early gut hypoperfusion causes an ileus in both the stomach and small bowel that sets the stage for progressive gut dysfunction so that the proximal gut becomes a reservoir for pathogens and toxins that contribute to late sepsis-associated MOF, and 4) late infections cause further worsening of this gut dysfunction. Thus, the gut can be both an instigator and a victim of MOF. The purpose of this article is to provide the rationale behind these beliefs and to provide a brief overview of the ongoing research projects in the TRC at UTHMS. PMID:11198350

  8. Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway

    PubMed Central

    Ma, Xingcong; Yan, Wanjun; Dai, Zhijun; Gao, Xiaoyan; Ma, Yinan; Xu, Quntao; Jiang, Jiantao; Zhang, Shuqun

    2016-01-01

    Background The flavonoid baicalein, a historically used Chinese herbal medicine, shows a wide range of biological and pharmaceutical effects, among which its potent antitumor activity has raised great interest in recent years. However, the molecular mechanism involved in the antimetastatic effect of baicalein remains poorly understood. This study aimed to verify the inhibitory effects of baicalein on metastasis of MDA-MB-231 human breast cancer cells both in vitro and in vivo, as well as to investigate the related mechanisms. Methods MTT assay was used to examine the inhibition of baicalein on proliferation of MDA-MB-231 cells. Wound healing assay and the in vitro invasion assay was carried out to investigate the effects of baicalein on migration and invasion of MDA-MB-231 cells, respectively. In order to explore the effects of baicalein on tumor metastasis in vivo, xenograft nude mouse model of MDA-MB-231 cells was established. Animals were randomly divided into four groups (control, therapy group, and low-dose and high-dose prevention group, n=6), and treated with baicalein as designed. Following sacrifice, their lungs and livers were collected to examine the presence of metastases. qRT-PCR and Western blot were performed to study the effects of baicalein on expression of SATB1, EMT-related molecules, and Wnt/β-catenin signaling components of MDA-MB-231 cells as well as the metastatic tissue. Effects of baicalein on the expression of target proteins in vivo were also analyzed by immunohistochemistry. Results Our results indicated that baicalein suppressed proliferation, migration, and invasion of MDA-MB-231 cells in a time- and dose-dependent manner. Based on assays carried out in xenograft nude mouse model, we found that baicalein inhibited tumor metastasis in vivo. Furthermore, baicalein significantly decreased the expression of SATB1 in MDA-MB-231 cells. It suppressed the expression of vimentin and SNAIL while enhancing the expression of E-cadherin. Baicalein

  9. Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

    PubMed

    Sun, Yu-Yo; Lin, Shang-Hsuan; Lin, Hung-Cheng; Hung, Chia-Chi; Wang, Chen-Yu; Lin, Yen-Chu; Hung, Kuo-Sheng; Lien, Cheng-Chang; Kuan, Chia-Yi; Lee, Yi-Hsuan

    2013-01-01

    The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo. PMID:23904909

  10. Panax Notoginseng Saponins as a Novel Nature Stabilizer for Poorly Soluble Drug Nanocrystals: A Case Study with Baicalein.

    PubMed

    Xie, Yuanbiao; Ma, Yueqin; Xu, Junnan; Liu, Yang; Yue, Pengfei; Zheng, Qin; Hu, Pengyi; Yang, Ming

    2016-01-01

    This study is aimed at seeking a nature saponin-based stabilizer for drug nanosuspensions. A poorly soluble drug (baicalein, BCL) was used as a model drug. BCL nanosuspensions with particle size of 156 nm were prepared by means of homogenization and converted into BCL nanocrystals (BCL-NC) stabilized with panax notoginseng saponins (PNS). It was found that PNS was able to prevent the aggregation of BCL-NS during storage and improve the redispersibility of BCL-NC after freeze-drying and spray-drying, compared with polymer stabilizer PVPK30. The freeze-dried and spray-dried BCL-NC with PNS exhibited excellent performance as evidenced by scanning_electron_microscope (SEM) analysis. It was the reason that PNS possessed the interfacial property (41.69 ± 0.32 mN/m) and electrostatic effect (-40.1 ± 1.6 mV), which could easily adsorb onto the surface of hydrophobic BCL nanocrystals and prevent from its aggregation. It is concluded that PNS can be used as an effective nature stabilizer for production of drug nanocrystals. PMID:27589712

  11. Development and extraction optimization of baicalein and pinostrobin from Scutellaria violacea through response surface methodology

    PubMed Central

    Subramaniam, Shankar; Raju, Ravikumar; Palanisamy, Anbumathi; Sivasubramanian, Aravind

    2015-01-01

    Objective: To develop a process that involves optimization of the amount of baicalein and pinostrobin from the hydro-methanolic extract of the leaves of Scutellaria violacea by response surface methodology (RSM). Materials and Methods: The combinatorial influence of various extraction parameters on the extraction yield was investigated by adopting Box–Behnken experimental design. Preliminary experiments carried out based on the traditional one variable at a time optimization revealed four such operational parameters to play a crucial role by influencing the yield. These four process parameters at three levels were considered to obtain the Box–Behnken experimental design. Results: RSM based model fitted to the resulting experimental data suggested that 52.3% methanol/water, 12.46:1 solvent-solid ratio, 285 rpm agitation and 6.07 h of extraction time are the optimal conditions which yielded a maximized amount of baicalein and pinostrobin of 2.9 and 4.05 mg/g DM. Analysis of variance revealed a high correlation coefficient (R2 = 0.999 for baicalein and 0.994 for pinostrobin), signifying a good fit between the regression model (second order) and the experimental observations. Conclusion: The present study signifies that both the metabolites have been extracted from S. violacea for the first time. Further, this study developed an optimized extraction procedure to obtain maximum yield of the metabolites, which is unique and better than conventional extraction methodology. The operational parameters under optimized conditions accounts for the lowest cost in extraction process thus, providing an efficient, rapid and cost-effective method for isolation and scale up of these commercially vital flavonoids. PMID:26109758

  12. Baicalein Triggers Mitochondria-Mediated Apoptosis and Enhances the Antileukemic Effect of Vincristine in Childhood Acute Lymphoblastic Leukemia CCRF-CEM Cells.

    PubMed

    Chen, Yun-Ju; Wu, Chieh-Shan; Shieh, Jeng-Jer; Wu, Jyh-Horng; Chen, Hsing-Yu; Chung, Ting-Wen; Chen, Yu-Kuo; Lin, Chi-Chen

    2013-01-01

    Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of childhood leukemia, and chemotherapy remains the mainstay therapy. Baicalein is an active flavonoid used in traditional Chinese medicine and has recently been found to have anticancer, anti-inflammatory, and antiallergic properties. This study aims to investigate the molecular apoptotic mechanisms of baicalein in CCRF-CEM leukemic cells and to evaluate the combined therapeutic efficacy of baicalein with several commonly used chemotherapeutic drugs in CCRF-CEM cells. Our results demonstrate that baicalein induces mitochondria-dependent cleavage of caspases-9 and -3 and PARP with concomitant decreases in IAP family proteins, survivin, and XIAP. Furthermore, our results present for the first time that baicalein triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the death receptor-caspase 8-tBid signaling cascade in CCRF-CEM cells. In addition, we also present for the first time that the combination of baicalein and vincristine results in a synergistic therapeutic efficacy. Overall, this combination strategy is recommended for future clinical trials in the treatment of pediatric leukemia owing to baicalein's beneficial effects in alleviating the vomiting, nausea, and skin rashes caused by chemotherapy. PMID:23476680

  13. Baicalein protects C6 glial cells against hydrogen peroxide-induced oxidative stress and apoptosis through regulation of the Nrf2 signaling pathway.

    PubMed

    Choi, Eun-Ok; Jeong, Jin-Woo; Park, Cheol; Hong, Su Hyun; Kim, Gi-Young; Hwang, Hye-Jin; Cho, Eun-Ju; Choi, Yung Hyun

    2016-03-01

    Baicalein, a flavonoid originally obtained from the roots of Scutellaria baicalensis Georgi, has been reported to possess various biological properties. Although several studies have demonstrated the anti-oxidative activity of baicalein, its neuroprotective mechanisms have not been clearly established. The present study aimed to detect the effects of baicalein against hydrogen peroxide (H2O2)-induced neuronal damage in C6 glial cells and to investigate the molecular mechanisms involved in this process. The results demonstrated that baicalein effectively inhibited H2O2-induced growth and reactive oxygen species (ROS) generation. We noted that Baicalein also attenuated the H2O2‑induced formation of comet tail, phosphorylation of p-γH2A.X, loss of mitochondrial membrane potential (MMP or ΔΨm), and changes to apoptosis‑related protein expression, which suggests that it can prevent H2O2‑induced cellular DNA damage and apoptotic cell death. Furthermore, treatment with baicalein effectively induced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as heme oxygenase-1 (HO-1) and thioredoxin reductase 1 (TrxR1) in a concentration and time-dependent manner. Moreover, the protective effects of baicalein against H2O2‑induced DNA damage and apoptosis were abolished by zinc protoporphyrin (ZnPP) IX, a HO-1 inhibitor, and auranofin, a TrxR inhibitor. In addition, we noted that the cytoprotective effects of baicalein were attenuated by transient transfection with Nrf2-specific small interfering RNA (siRNA). The findings of our present study suggest that baicalein enhances cellular antioxidant defense capacity through the inhibition of ROS generation and the activation of the Nrf2 signaling pathway, thus protecting C6 cells from H2O2-induced neuronal damage. PMID:26796879

  14. SUR1-Associated Mechanisms Are Not Involved in Ischemic Optic Neuropathy 1 Day Post-Injury

    PubMed Central

    Nicholson, James D.; Guo, Yan; Bernstein, Steven L.

    2016-01-01

    Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma. Glibenclamide, an SUR1 antagonist, appears to have neuroprotective effect against cerebral stroke in an open-label small clinical trial and great effectiveness in reducing damage after varied experimental CNS injury models. Despite its importance in CNS injuries, SUR1 upregulation appears to play no part in rodent anterior ischemic optic neuropathy (rAION) injury as tested by real-time PCR and immunohistochemical staining of rAION-injured rat optic nerve (ON). Furthermore, the SUR1 antagonist glibenclamide administered immediately after rAION injury provided no protection to proximal ON microvasculature 1 day post-injury but may reduce optic nerve head edema in a manner unrelated to ON SUR1 expression. Our results suggest that there may be fundamental differences between rAION optic nerve ischemia and other CNS white matter injuries where SUR1 appears to play a role. PMID:27560494

  15. SUR1-Associated Mechanisms Are Not Involved in Ischemic Optic Neuropathy 1 Day Post-Injury.

    PubMed

    Nicholson, James D; Guo, Yan; Bernstein, Steven L

    2016-01-01

    Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma. Glibenclamide, an SUR1 antagonist, appears to have neuroprotective effect against cerebral stroke in an open-label small clinical trial and great effectiveness in reducing damage after varied experimental CNS injury models. Despite its importance in CNS injuries, SUR1 upregulation appears to play no part in rodent anterior ischemic optic neuropathy (rAION) injury as tested by real-time PCR and immunohistochemical staining of rAION-injured rat optic nerve (ON). Furthermore, the SUR1 antagonist glibenclamide administered immediately after rAION injury provided no protection to proximal ON microvasculature 1 day post-injury but may reduce optic nerve head edema in a manner unrelated to ON SUR1 expression. Our results suggest that there may be fundamental differences between rAION optic nerve ischemia and other CNS white matter injuries where SUR1 appears to play a role. PMID:27560494

  16. [Preparation of baicalein using thermophilic and sugar-tolerant beta-glucosidase].

    PubMed

    Li, Shi-ping; Wen, Jian-hui; Zhao, Yi-wu; Huang, Wen-zhe; Pei, Jian-jun; Wang, Zhen-zhong; Zhao, Lin-guo; Xiao, Wei

    2015-12-01

    The reaction conditions of baicalin hydrolyzed into baicalein by a kind of thermophilic and sugar-tolerant beta-glucosidase were studied in this paper. The beta-glucosidase could catalyze baicalin into baicalein well in the acetic acid-sodium acetate buffer. The optimal enzyme activity was at 85 degrees C and pH 5.5. The enzyme was stable at the temperature less than 85 degrees C and pH range of 5-7.5. The maximum reaction rate V. and michaelis constant K. were 0.41 mmol x L(-1) x min(-1) and 3.31 mmol x L(-1) respectively. Different metal ions had different effects on the activity of enzyme. Na+ existing in acetic acid-sodium acetate buffer had an activation effect on enzyme. The enzyme activity was enhanced by the concentrations of glucose below 0.6 mol x L(-1), and was gradually inhibited when monosaccharide concentration was over 0.6 mol x L(-1). When the monosaccharide concentration reached 1.2 mol x L(-1), the inhibition rate of enzyme activity was about 50%, which showed good glucose tolerance. The good reaction conditions through the experiment have been determined as follows, the substrate: enzyme dose was 1 g: 0.2 mL, acetic acid-sodium acetate buffer pH 5.5, reaction temperature 85 degrees C, reaction time 10 h, and the enzymatic hydrolyzation ratio could reach 97%. PMID:27141672

  17. The impact of sport and active recreation injuries on physical activity levels at 12 months post-injury.

    PubMed

    Andrew, N; Wolfe, R; Cameron, P; Richardson, M; Page, R; Bucknill, A; Gabbe, B

    2014-04-01

    The aim of this study was to evaluate the impact of serious sport and active recreation injury on 12-month physical activity levels. Adults admitted to hospital with sport and active recreation-related injuries, and captured by the Victorian Orthopaedic Trauma Outcomes Registry were recruited to the study. Changes between preinjury and 12 month post-injury physical activity was assessed using the short International Physical Activity Questionnaire (IPAQ). Independent demographic, injury, and hospital variables were assessed for associations with changes in physical activity levels, using multivariate linear regression. A total of 324 patients were recruited, of which 98% were followed up at 12 months. Mean short IPAQ scores decreased from 7650 METS (95% CI: 7180, 8120) preinjury to 3880 METS; (95% CI: 3530, 4250) post-injury, independent of functional recovery. Education level and occupation group were the only variables independently associated with changes in physical activity levels post-injury. These results highlighted that sport and active recreation injuries lead to significant reductions in physical activity levels. Hence, the prevention of sport and active recreation injuries is important when considering promotion of activity at a population level. PMID:22937749

  18. Baicalein suppresses the viability of MG-63 osteosarcoma cells through inhibiting c-MYC expression via Wnt signaling pathway.

    PubMed

    He, Nengbin; Zhang, Zhichang

    2015-07-01

    The major reason responsible for the poor prognosis of osteosarcoma is the malignant proliferation of osteosarcoma cells. The activated Wnt/β-catenin signaling induces c-MYC gene transcription and results in osteocytes' carcinomatous change, which contributes to osteosarcoma development, so c-MYC gene is one of the therapeutic targets. The role of multiple botanical extracts in the expression of β-catenin's target gene c-MYC in osteosarcoma MG-63 cells was tested by cellomics high content screening. Baicalein was identified as the most effective one which can inhibit the proliferation and promote the apoptosis of MG-63 cells in a dose-dependent manner by cell counting kit-8 test and fluorescence-activated cell sorting, respectively. This process was associated with the decreased levels of β-catenin and its target gene c-MYC, identified by q-PCR and Western blotting, respectively. When MG-63 cells were treated with both baicalein and JNK inhibitor SP600125, the apoptosis and expression of c-MYC were not significantly decreased. After the construct pcDNA3.1-BANCR (BRAF-regulated lncRNA 1) was transfected into MG-63 cells, RT-PCR, Western blotting and CCK-8 assay showed that BANCR was positively correlated with baicalein. These results indicated that baicalein inhibited osteosarcoma cell proliferation and promoted apoptosis by targeting c-MYC gene through Wnt signaling, in which JNK and BANCR were also involved as well as β-catenin, suggesting a new potential mechanism for us to better understand the inhibiting effect of baicalein on osteosarcoma. PMID:25893737

  19. Post-injury Hyperfibrinogenemia Compromises Efficacy of Heparin-Based VTE Prophylaxis

    PubMed Central

    Harr, Jeffrey N.; Moore, Ernest E.; Chin, Theresa L.; Ghasabyan, Arsen; Gonzalez, Eduardo; Wohlauer, Max V.; Sauaia, Angela; Banerjee, Anirban; Silliman, Christopher C.

    2013-01-01

    Background Venous thromboembolism (VTE) prophylaxis remains debated following trauma, and recommendations have not been established. Although hyperfibrinogenemia is a marker of pro-inflammatory states, it is also contributes to thrombus formation. Post-injury hyperfibrinogenemia is common, but the effect of hypefibrinogenemia on VTE prophylaxis has not been fully elucidated. Therefore, we hypothesized that heparin is less effective for VTE prophylaxis following severe injury due to hyperfibrinogenemia. Methods In vitro studies evaluated TEG parameters in 10 healthy volunteers after the addition of fibrinogen concentrate and heparin. Data from a recent randomized controlled trial, conducted at an academic level-1 trauma center surgical intensive care unit, were reviewed. Critically injured patients were randomized to standard VTE prophylaxis (5,000 Units LMWH daily) or TEG-guided prophylaxis (up to 10,000 Units LMWH daily), and were followed for 5 days. Analysis was performed to evaluate the relationship between fibrinogen levels, measures of anticoagulation, and TEG parameters. Results In vitro studies revealed increased fibrinogen reversed the effects of heparin as measured by TEG. Fifty patients were enrolled in the clinical study with 25 in each arm. TEG parameters, fibrinogen, platelet count, and anti-Xa levels did not differ between groups despite treatment provided. Fibrinogen levels increased over the 5-day study period (597±24.0 to 689.3±25.0), as well as clot strength (9.8±0.4 to 14.5±0.6), which had a significant correlation coefficient (p<0.01). Moreover, there was a moderate inverse correlation between fibrinogen level and the effect of heparin (RF), which was significant on study days 1 and 3, implicating hyperfibrinogenemia in heparin resistance. Conclusion Hypercoagulablity and heparin resistance are common following trauma. The preclinical and clinical relationships between fibrinogen levels and hypercoagulability implicate hyperfibrinogenemia

  20. Anti-inflammatory activity of baicalein in LPS-stimulated RAW264.7 macrophages via estrogen receptor and NF-κB-dependent pathways.

    PubMed

    Fan, Guan-Wei; Zhang, Yuan; Jiang, Xiaorui; Zhu, Yan; Wang, Bingyao; Su, Lina; Cao, Wenjie; Zhang, Han; Gao, Xiumei

    2013-12-01

    Baicalein has been used for many years as a popular antiviral and antibacterial in China. Recent investigations revealed that baicalein also has anti-inflammatory activities. Our results indicated that baicalein increases ERE-luciferase activity in an estrogen receptor (ER)-dependent manner when either ERα or ERβ were coexpressed in Hela cells. This study examined whether baicalein exerts an anti-inflammatory effect in RAW264.7 cells through an estrogen receptor-dependent pathway and through regulation of NF-ĸB activation. In lipopolysaccharide (LPS)-induced RAW264.7 cells, baicalein exerts anti-inflammatory effects by inhibiting iNOS, COX-2, and TNF-α mRNA expression; NO production; as well as inflammatory cytokine (IL-1β, PGE2, and TNF-α) production through an ER-dependent pathway. These effects are accompanied with the inhibition of the transcription factor NF-ĸB activation and IκBα phosphorylation. We therefore conclude that baicalein inhibits LPS-induced inflammatory cytokine production via regulation of the NF-ĸB pathway and estrogen-like activity, suggesting that it may be useful for preventing inflammation-related diseases. PMID:23892998

  1. Structure-activity relationship study between baicalein and wogonin by spectrometry, molecular docking and microcalorimetry.

    PubMed

    Tu, Bao; Li, Rong-Rong; Liu, Zhi-Juan; Chen, Zhi-Feng; Ouyang, Yu; Hu, Yan-Jun

    2016-10-01

    Flavones (e.g. baicalein and wogonin) extensively used worldwide in food preparation and traditional medicine. In this study, a systematically comparative study of their structure-activity relationships (SAR) on their interaction with BSA, antioxidant activity and antibacterial activity has been carried out by spectrometry, molecular docking and microcalorimetry. Our results show that the skeleton structure of flavones, the number of hydroxyl groups, the type of functional group, conjugated system and the steric hindrance may be responsible for their different biological activity. These findings not only would lay a scientific foundation for discovering and designing flavones-based food and drug, may also help us to understanding the structure-activity relationship between flavones at the molecular level. PMID:27132840

  2. Baicalein Inhibits MCF-7 Cell Proliferation In Vitro, Induces Radiosensitivity, and Inhibits Hypoxia Inducible Factor.

    PubMed

    Gade, Shruti; Gandhi, Nitin Motilal

    2015-01-01

    Hypoxia inducible factor (HIF) is a key transcription factor responsible for imparting adaptability to the cancer cells growing in tumors. HIF induces the modulation of glucose metabolism, angiogenesis, and prosurvival signaling. Therefore, HIF is one of the attractive targets to treat solid tumors. Results presented in this study indicate that Baicalein (BA) inhibits HIF stabilization and also reduces its transcription activity in MCF-7 cells in vitro. Furthermore, BA was found to have antiproliferative ability as determined by the MTT assay and clonogenic survival. BA also induces apoptosis in MCF-7 cells at the concentration of 50 µM. We also report the radiosensitization of MCF-7 cells when they are treated with BA, resulting in higher γ-radiation-induced DNA damage. BA is extensively used in Chinese medicine and is known to be nontoxic at pharmacological doses. Our studies indicate that BA is one of the attractive natural compounds suitable for further evaluation as an adjuvant therapy. PMID:26756423

  3. Baicalein reverts L-valine-induced persistent sodium current up-modulation in primary cortical neurons.

    PubMed

    Caioli, Silvia; Candelotti, Elena; Pedersen, Jens Z; Saba, Luana; Antonini, Alessia; Incerpi, Sandra; Zona, Cristina

    2016-04-01

    L-valine is a branched-chain amino acid (BCAA) largely used as dietary integrator by athletes and involved in some inherited rare diseases such as maple syrup urine disease. This pathology is caused by an altered BCAA metabolism with the accumulation of toxic keto acids in tissues and body fluids with consequent severe neurological symptoms. In animal models of BCAA accumulation, increased oxidative stress levels and lipid peroxidation have been reported. The aim of this study was to analyze both whether high BCAA concentrations in neurons induce reactive oxygen species (ROS) production and whether, by performing electrophysiological recordings, the neuronal functional properties are modified. Our results demonstrate that in primary cortical cultures, a high dose of valine increases ROS production and provokes neuronal hyperexcitability because the action potential frequencies and the persistent sodium current amplitudes increase significantly compared to non-treated neurons. Since Baicalein, a flavone obtained from the Scutellaria root, has been shown to act as a strong antioxidant with neuroprotective effects, we evaluated its possible antioxidant activity in primary cortical neurons chronically exposed to L-valine. The preincubation of cortical neurons with Baicalein prevents the ROS production and is able to revert both the neuronal hyperexcitability and the increase of the persistent sodium current, indicating a direct correlation between the ROS production and the altered physiological parameters. In conclusion, our data show that the electrophysiological alterations of cortical neurons elicited by high valine concentration are due to the increase in ROS production, suggesting much caution in the intake of BCAA dietary integrators. PMID:26721313

  4. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    SciTech Connect

    Cheng, Ya-Hsin; Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan; Hung, Chein-Hui; Chang, Nai Wen; Lin, Chingju

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  5. Sodium cromolyn reduces expression of CTGF, ADAMTS1 and TIMP3 and modulates post-injury patellar tendon morphology

    PubMed Central

    Sharma, Aishwariya; Abraham, Thomas; Sampaio, Arthur; Cowan, Matthew; Underhill, Michael; Scott, Alex

    2014-01-01

    Objectives The purpose of this study was to determine whether administration of a mast cell inhibitor (sodium cromolyn, SC) would influence tendon repair and extracellular matrix gene expression following acute injury. Methods CD1 mouse patellar tendons were unilaterally injured and mast cell prevalence was determined. The effect of SC injection on tendon hypercellularity, cross-sectional area, collagen organization, and expression of extracellular matrix-related genes was examined. Results Mast cell prevalence was markedly increased in injured patellar tendons (p=0.009), especially at 8 weeks post injury (p=0.025). SC injection increased collagen organization compared to uninjected animals at 4 weeks and attenuated the development of tendon hypercellularity and tendon thickening post-injury. Expression of CTGF, ADAMTS1 and TIMP3 in injured tendon was reduced in the SC group. Conclusion SC injections moderated the structural alterations of healing tendon in association with downregulation of several genes associated with tendon fibrosis. This work corroborates previous findings pointing to a role of mast cells in tendon repair. PMID:21437947

  6. Baicalein Attenuates Oxidative Stress-Induced Expression of Matrix Metalloproteinase-1 by Regulating the ERK/JNK/AP-1 Pathway in Human Keratinocytes

    PubMed Central

    Kim, Ki Cheon; Kang, Sam Sik; Lee, Jongsung; Park, Deokhoon; Hyun, Jin Won

    2012-01-01

    The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [H2O2]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyflavone) was investigated for its in vitro activity against H2O2-induced damage using a human skin keratinocyte model. Baicalein pretreatment significantly inhibited H2O2-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway. PMID:24116275

  7. The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain.

    PubMed

    Hu, Shan; Chen, Yu; Wang, Zhi-Fu; Mao-Ying, Qi-Liang; Mi, Wen-Li; Jiang, Jian-Wei; Wu, Gen-Cheng; Wang, Yan-Qing

    2015-01-01

    Cancer-induced bone pain (CIBP) is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE), isolated from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi (or Huang Qin), has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could alleviate the mechanical allodynia in CIBP rats. Intrathecal 100 μg BE could inhibit the production of IL-6 and TNF-α in the spinal cord of CIBP rats. Moreover, intrathecal 100 μg BE could effectively inhibit the activation of p-p38 and p-JNK MAPK signals in CIBP rats. The analgesic effect of BE may be associated with the inhibition of the expression of the inflammatory cytokines IL-6 and TNF-α and through the activation of p-p38 and p-JNK MAPK signals in the spinal cord. These findings suggest that BE is a promising novel analgesic agent for CIBP. PMID:26649065

  8. The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain

    PubMed Central

    Hu, Shan; Chen, Yu; Wang, Zhi-Fu; Mao-Ying, Qi-Liang; Mi, Wen-Li; Jiang, Jian-Wei; Wu, Gen-Cheng; Wang, Yan-Qing

    2015-01-01

    Cancer-induced bone pain (CIBP) is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE), isolated from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi (or Huang Qin), has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could alleviate the mechanical allodynia in CIBP rats. Intrathecal 100 μg BE could inhibit the production of IL-6 and TNF-α in the spinal cord of CIBP rats. Moreover, intrathecal 100 μg BE could effectively inhibit the activation of p-p38 and p-JNK MAPK signals in CIBP rats. The analgesic effect of BE may be associated with the inhibition of the expression of the inflammatory cytokines IL-6 and TNF-α and through the activation of p-p38 and p-JNK MAPK signals in the spinal cord. These findings suggest that BE is a promising novel analgesic agent for CIBP. PMID:26649065

  9. In vitro potential modulation of baicalin and baicalein on P-glycoprotein activity and expression in Caco-2 cells and rat gut sacs.

    PubMed

    Miao, Qing; Wang, Zhiyong; Zhang, Yuanyuan; Miao, Peipei; Zhao, Yuanyuan; Zhang, Yujie; Ma, Shuangcheng

    2016-09-01

    Context Previous studies have shown that Scutellariae Radix, the dried root of Scutellaria baicalensis Georgi (Labiatae), has a certain inhibitory effect on P-glycoprotein (P-gp), but the effects of its main active constituents on P-gp are still ambiguous. Objectives In vitro studies were performed to investigate the effects of its main active constituents (baicalin and its aglycone, baicalein) on the activity and expression of P-gp in intestine using Caco-2 cells and rat gut sacs. Materials and methods In Caco-2 cell experiments, the effects of baicalin and baicalein on P-gp activity were investigated using a P-gp substrate, rhodamine 123 and non-substrate fluorescein Na, by determining their intracellular fluorescence accumulation, and their effects on P-gp expression were determined using flow cytometry. In addition, rat gut sac model was selected to investigate the effects of baicalin and baicalein on the transport of verapamil, a classical P-gp substrate. The gut sacs of male Sprague-Dawley rats were filled with 0.4 mL the test solution contained verapamil (0.2575 mg/mL) and the drugs [baicalin and baicalein, at concentrations of 1/8 IC50 (59.875, 41.5 μg/mL), 1/4 IC50 (119.75, 83 μg/mL) and 1/2 IC50 (239.5, 166 μg/mL)], and then incubated in Tyrode's solution for a period of time. After termination of the incubation, the incubated solution was processed for the subsequent detection. Results According to the results of MTT assay, the IC50 values of verapamil, baicalin and baicalein were 104, 479, 332 μg/mL, respectively. The obtained results from the two models were confirmed mutually. As a result, baicalin exhibited no obvious effect on intracellular accumulation of Rh-123, and almost had no effect on P-gp expression and verapamil transportation, while baicalein significantly increased intracellular accumulation of Rh-123 (p < 0.01), down-regulated P-gp expression (p < 0.01) and increased the transport of verapamil (p < 0

  10. Amino acid infusion fails to stimulate skeletal muscle protein synthesis up to one year post injury in children with severe burns

    PubMed Central

    Cotter, Matthew; Diaz, Eva C; Jennings, Kristofer; Herndon, David N; Børsheim, Elisabet

    2013-01-01

    Background Burn injury results in increased skeletal muscle protein turnover, where the magnitude of protein breakdown outweighs synthesis resulting in muscle wasting. The impact of increased amino acid (AA) provision on skeletal muscle fractional synthesis rate (FSR) in severely burned patients during their convalescence after discharge from hospital is not known. Subsequently, the purpose of this study was to determine skeletal muscle FSR in response to AA infusion in severely burned pediatric patients at discharge from hospital, and at six and twelve months post injury. Methods Stable isotope infusion studies were performed in the postprandial state and during intravenous AA infusion. Skeletal muscle biopsies were obtained and isotope enrichment determined in order to calculate skeletal muscle FSR. Patients were studied at discharge from hospital (n=11), and at six (n=15), and twelve months (n=14) post injury. Results The cohorts of patients studied at each time point post injury were not different with regards to age, body mass or burn size. AA infusion failed to stimulate FSR above basal values at discharge from hospital (0.27±0.04 vs. 0.26±0.06 %·hr−1), six months post injury (0.20±0.04 vs. 0.22±0.03 %·hr−1), and twelve months post injury (0.16±0.03 vs. 0.15±0.05 %·hr−1). Daily FSR was numerically lower at six months post burn (5.51±0.79 %·day−1) and significantly (P<0.05) lower at 12 months post burn (3.67±0.65 %·day−1) relative to discharge group (6.32±1.02 %·day−1). Discussion The findings of the current study suggest that the deleterious impact of burn injury on skeletal muscle AA metabolism persists for up to one year post injury. In light of these findings, nutritional and pharmacological strategies aimed at attenuating muscle protein breakdown post burn may be a more efficacious approach to maintaining muscle mass in severely burned patients. PMID:23694875

  11. RAGE signaling mediates post-injury arterial neointima formation by suppression of liver kinase B1 and AMPK activity

    PubMed Central

    Yu, Weifang; Liu-Bryan, Ru; Stevens, Stephanie; Damanahalli, Jagadeesha K.; Terkeltaub, Robert

    2012-01-01

    Objective Intima formation involves smooth muscle cell (SMC) proliferation and migration that ultimately drives arterial stenosis, thrombosis, and ischemia in atherosclerosis, hypertension, and arterial revascularization. Receptor for advanced glycation endproducts (RAGE) is a transmembrane signaling receptor implicated in diabetic renal and vascular complications, and post-injury intima formation, partly via Signal transducer and activator of transcription 3 (STAT3) activation. The metabolic super-regulator Adenosine monophosphate kinase (AMPK) inhibits SMC proliferation and intima formation. AMPK activation is promoted by liver kinase B1 (LKB1), and LKB1 inhibits STAT3 activation. Here, we tested the hypothesis that RAGE promotes arterial intima formation by modulating both LKB1 and AMPK. Methods and Results RAGE ligands (the calgranulin S100A11, and glycated albumin) suppressed AMPK activation in conjunction with increased proliferation and migration of cultured SMCs. These effects were inhibited both by RAGE deficiency and by prior AMPK activation. In SMCs, RAGE ligands decreased LKB1 activity. Moreover, knockdown of both LKB1 and AMPK were associated with increased STAT3 phosphorylation levels. In response to murine carotid artery ligation, expression of RAGE and S100A11 increased, whereas AMPK and LKB1 activity decreased in situ. Conversely, LKB1 and AMPK activity increased in situ, and neointima formation was attenuated in Rage−/− mice. Conclusion The linkage of decreased LKB1 and AMPK activity with increased STAT3 in SMCs mediates the capacity of RAGE ligand-induced signaling to promote neointima formation in response to arterial injury. PMID:22552116

  12. Skeletal Muscle Protein Breakdown Remains Elevated in Pediatric Burn Survivors up to One-Year Post-Injury.

    PubMed

    Chao, Tony; Herndon, David N; Porter, Craig; Chondronikola, Maria; Chaidemenou, Anastasia; Abdelrahman, Doaa Reda; Bohanon, Fredrick J; Andersen, Clark; Sidossis, Labros S

    2015-11-01

    Acute alterations in skeletal muscle protein metabolism are a well-established event associated with the stress response to burns. Nevertheless, the long-lasting effects of burn injury on skeletal muscle protein turnover are incompletely understood. This study was undertaken to investigate fractional synthesis (FSR) and breakdown (FBR) rates of protein in skeletal muscle of pediatric burn patients (n  =  42, >30% total body surface area burns) for up to 1 year after injury. Skeletal muscle protein kinetics were measured in the post-prandial state following bolus injections of C6 and N phenylalanine stable isotopes. Plasma and muscle phenylalanine enrichments were quantified using gas chromatography-mass spectrometry. We found that the FSR in burn patients was 2- to 3-fold higher than values from healthy men previously reported in the literature (P ≤ 0.05). The FBR was 4- to 6-fold higher than healthy values (P  <  0.01). Therefore, net protein balance was lower in burn patients compared with healthy men from 2 weeks to 12 months post-injury (P  <  0.05). These findings show that skeletal muscle protein turnover stays elevated for up to 1 year after burn, an effect attributable to simultaneous increases in FBR and FSR. Muscle FBR exceeds FSR during this time, producing a persistent negative net protein balance, even in the post-prandial state, which likely contributes to the prolonged cachexia seen in burned victims. PMID:26263438

  13. Kir2.1 regulates rat smooth muscle cell proliferation, migration, and post-injury carotid neointimal formation.

    PubMed

    Qiao, Yong; Tang, Chengchun; Wang, Qingjie; Wang, Dong; Yan, Gaoliang; Zhu, Boqian

    2016-09-01

    Phenotype switching of vascular smooth muscle cells (VSMC) from the contractile type to the synthetic type is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty. Inward rectifier K(+) channel 2.1 (Kir2.1) has been identified in VSMC. However, whether it plays a functional role in regulating cellular transformation remains obscure. In this study, we evaluated the role of Kir2.1 on VSMC proliferation, migration, phenotype switching, and post-injury carotid neointimal formation. Kir2.1 knockdown significantly suppressed platelet-derived growth factor BB-stimulated rat vascular smooth muscle cells (rat-VSMC) proliferation and migration. Deficiency in Kir2.1 contributed to the restoration of smooth muscle α-actin, smooth muscle 22α, and calponin and to a reduction in osteopontin expression in rat-VSMC. Moreover, the in vivo study showed that rat-VSMC switched to proliferative phenotypes and that knockdown of Kir2.1 significantly inhibited neointimal formation after rat carotid injury. Kir2.1 may be a potential therapeutic target in the treatment of cardiovascular diseases, such as atherosclerosis and restenosis following percutaneous coronary intervention. PMID:27387235

  14. Comparison of measures of comorbidity for predicting disability 12-months post-injury

    PubMed Central

    2013-01-01

    Background Understanding the factors that impact on disability is necessary to inform trauma care and enable adequate risk adjustment for benchmarking and monitoring. A key consideration is how to adjust for pre-existing conditions when assessing injury outcomes, and whether the inclusion of comorbidity is needed in addition to adjustment for age. This study compared different approaches to modelling the impact of comorbidity, collected as part of the routine hospital episode data, on disability outcomes following orthopaedic injury. Methods 12-month Glasgow Outcome Scale – Extended (GOS-E) outcomes for 13,519 survivors to discharge were drawn from the Victorian Orthopaedic Trauma Outcomes Registry, a prospective cohort study of admitted orthopaedic injury patients. ICD-10-AM comorbidity codes were mapped to four comorbidity indices. Cases with a GOS-E score of 7–8 were considered “recovered”. A split dataset approach was used with cases randomly assigned to development or test datasets. Logistic regression models were fitted with “recovery” as the outcome and the performance of the models based on each comorbidity index (adjusted for injury and age) measured using calibration (Hosmer-Lemshow (H-L) statistics and calibration curves) and discrimination (Area under the Receiver Operating Characteristic (AUC)) statistics. Results All comorbidity indices improved model fit over models with age and injuries sustained alone. None of the models demonstrated acceptable model calibration (H-L statistic p < 0.05 for all models). There was little difference between the discrimination of the indices for predicting recovery: Charlson Comorbidity Index (AUC 0.70, 95% CI: 0.68, 0.71); number of ICD-10 chapters represented (AUC 0.70, 95% CI: 0.69, 0.72); number of six frequent chronic conditions represented (AUC 0.70, 95% CI: 0.69, 0.71); and the Functional Comorbidity Index (AUC 0.69, 95% CI: 0.68, 0.71). Conclusions The presence of ICD-10 recorded comorbid

  15. Post-injury administration of allicin attenuates ischemic brain injury through sphingosine kinase 2: In vivo and in vitro studies.

    PubMed

    Lin, Jia-Ji; Chang, Ting; Cai, Wen-Ke; Zhang, Zhuo; Yang, Yong-Xiang; Sun, Chao; Li, Zhu-Yi; Li, Wei-Xin

    2015-10-01

    Allicin, one of the main biologically active compounds derived from garlic, has been shown to exert various pharmacological activities and is considered to have therapeutic potential for many pathologic conditions. In the present study, we investigated the potential post-ischemic neuroprotective effects of allicin and its underlying mechanisms. Using a rat middle cerebral artery occlusion (MCAO) model, we found that intraperitoneal treatment with 50 mg/kg allicin significantly reduced brain infarct volume, attenuated cerebral edema and decreased the neurological deficit score. Allicin treatment also diminished TUNEL positive cells and inhibited the activation of caspase-3 after MCAO. These protective effects could be observed even if the administration was delayed to 6 h after injury. In addition, we evaluated the in vitro protective effects of allicin against oxygen glucose deprivation (OGD) induced neuronal injury in primary cultured cortical neurons. Allicin (50 μM) increased neuronal viability, decreased lactate dehydrogenase (LDH) release and inhibited apoptotic neuronal death after OGD. These protective effects could be observed even if the administration was delayed to 4 h after injury. Furthermore, allicin significantly increased the expression of sphingosine kinases 2 (Sphk2) both in vivo and in vitro. Pretreatment with the Sphk2 inhibitor ABC294640 partially reversed the protective effects of allicin against MCAO and OGD injury, indicating that an Sphk2-mediated mechanism was involved in allicin-induced protection in our models. The combination of findings suggests that post-injury administration of allicin has potential as a neuroprotective strategy for ischemic stroke. PMID:26275594

  16. A novel molecularly imprinted method with computational simulation for the affinity isolation and knockout of baicalein from Scutellaria baicalensis.

    PubMed

    Li, Hong; He, Hongliang; Huang, Jiaojiao; Wang, Chong-Zhi; Gu, Xiaoli; Gao, Yankun; Zhang, Hongjuan; Du, Shuhu; Chen, Lina; Yuan, Chun-Su

    2016-02-01

    A novel molecularly imprinted polymer (MIP) was synthesized by precipitation polymerization with baicalein (BAI) as the template and used as solid-phase extraction (SPE) adsorbent, aiming at the affinity isolation and selective knockout of BAI from Scutellaria baicalensis Georgi (SB). We used computational simulation to predict the optimal functional monomer, polymerization solvent and molar ratio of template to functional monomer. Characterization and performance tests revealed that MIP exhibited uniform spherical morphology, rapid binding kinetics, and higher adsorption capacity for BAI compared with nonimprinted polymer (NIP). The application of MIP in SPE coupled with high-performance liquid chromatography to extract BAI from SB showed excellent recovery (94.3%) and purity (97.0%). Not only the single BAI compound, but also the BAI-removed SB extract was obtained by one-step process. This new method is useful for isolation and knockout of key bioactive compounds from herbal medicines. PMID:26037609

  17. Metabolism and pharmacokinetics of 8-hydroxypiperidinylmethyl-baicalein (BA-j) as a novel selective CDK1 inhibitor in monkey.

    PubMed

    Guo, Hong-Min; Sun, Yu-Ming; Zhang, Shi-Xuan; Ju, Xiu-Lan; Xie, Ai-Yun; Li, Jing; Zou, Liang; Sun, Xiao-Dan; Li, Hai-Liang; Zheng, Yang

    2015-12-01

    Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in the cell proliferation process and a new target in the research and development of anti-cancer drugs. 8-Hydroxypiperidinemethyl-baicalein (BA-j) is a Mannich base derivative of baicalein (BA) isolated from Scutellaria baicalensis, as a novel selective CDK1 inhibitor. 12 metabolites of BA-j in the monkey urine were identified by LC-MS-MS and (1)H NMR. The major metabolic pathways of BA-j, by capturing oxygen free radicals ((.)O2(-)) and releasing peroxides (H2O2), are degraded into active intermediate metabolite dihydroflavonol, then into main metabolite M179 by Shiff reaction, second metabolite M264 by sulfation, trace amount of metabolite M559 by glucuronidation UGT1A9, and without metabolism by CYP3A4. The metabolic process of BA-j by regulating intracellular reactive oxygen species (ROS) was related with BA-j selectively inducing apoptosis in cancer cells. Pharmacokinetics of 10mg/kg oral BA-j in monkey by HPLC-UV was best fitted to a two-compartment open model, with t1/2(β) of 4.2h, Cmax 25.4μM at 2h, and Vd 12.6L, meaning the drug distributing widely in body fluids with no special selectivity to certain tissues, and being able to permeate through the blood-brain barrier. The protein binding rate of BA-j was 91.8%. BA-j has excellent druggability for oral administration or injection, and it may be developed into a novel anti-cancer drug as a selective CDK1 inhibitor. PMID:26474673

  18. Baicalein attenuates the quorum sensing-controlled virulence factors of Pseudomonas aeruginosa and relieves the inflammatory response in P. aeruginosa-infected macrophages by downregulating the MAPK and NFκB signal-transduction pathways

    PubMed Central

    Luo, Jing; Kong, Jin-liang; Dong, Bi-ying; Huang, Hong; Wang, Ke; Wu, Li-hong; Hou, Chang-chun; Liang, Yue; Li, Bing; Chen, Yi-qiang

    2016-01-01

    Burgeoning antibiotic resistance and unfavorable outcomes of inflammatory injury after Pseudomonas aeruginosa infection have necessitated the development of novel agents that not only target quorum sensing (QS) but also combat inflammatory injury with the least risk of resistance. This study aimed to assess the anti-QS and anti-inflammatory activities of baicalein, a traditional herbal medicine that is widely used in the People’s Republic of China, against P. aeruginosa infection. We found that subminimum inhibitory concentrations of baicalein efficiently interfered with the QS-signaling pathway of P. aeruginosa via downregulation of the transcription of QS-regulated genes and the translation of QS-signaling molecules. This interference resulted in the global attenuation of QS-controlled virulence factors, such as motility and biofilm formation, and the secretion into the culture supernatant of extracellular virulence factors, including pyocyanin, LasA protease, LasB elastase, and rhamnolipids. Moreover, we examined the anti-inflammatory activity of baicalein and its mode of action via a P. aeruginosa-infected macrophage model to address its therapeutic effect. Baicalein reduced the P. aeruginosa-induced secretion of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNFα. In addition, baicalein suppressed P. aeruginosa-induced activation of the MAPK and NFκB signal-transduction pathways in cocultured macrophages; this may be the mechanism by which baicalein inhibits the production of proinflammatory cytokines. Therefore, our study demonstrates that baicalein represents a potential treatment for P. aeruginosa infection because it clearly exhibits both antibacterial and anti-inflammatory activities. PMID:26792984

  19. Repetitive concussive traumatic brain injury interacts with post-injury foot shock stress to worsen social and depression-like behavior in mice.

    PubMed

    Klemenhagen, Kristen C; O'Brien, Scott P; Brody, David L

    2013-01-01

    The debilitating effects of repetitive concussive traumatic brain injury (rcTBI) have been increasingly recognized in both military and civilian populations. rcTBI may result in significant neurological, cognitive, and affective sequelae, and is often followed by physical and/or psychological post-injury stressors that may exacerbate the effects of the injury and prolong the recovery period for injured patients. However, the consequences of post-injury stressors and their subsequent effects on social and emotional behavior in the context of rcTBI have been relatively little studied in animal models. Here, we use a mouse model of rcTBI with two closed-skull blunt impacts 24 hours apart and social and emotional behavior testing to examine the consequences of a stressor (foot shock fear conditioning) following brain injury (rcTBI). rcTBI alone did not affect cued or contextual fear conditioning or extinction compared to uninjured sham animals. In the sucrose preference test, rcTBI animals had decreased preference for sucrose, an anhedonia-like behavior, regardless of whether they experienced foot shock stress or were non-shocked controls. However, rcTBI and post-injury foot shock stress had synergistic effects in tests of social recognition and depression-like behavior. In the social recognition test, animals with both injury and shock were more impaired than either non-shocked injured mice or shocked but uninjured mice. In the tail suspension test, injured mice had increased depression-like behavior compared with uninjured mice, and shock stress worsened the depression-like behavior only in the injured mice with no effect in the uninjured mice. These results provide a model of subtle emotional behavioral deficits after combined concussive brain injury and stress, and may provide a platform for testing treatment and prevention strategies for social behavior deficits and mood disorders that are tailored to patients with traumatic brain injury. PMID:24058581

  20. Baicalein Protects Against Retinal Ischemia by Antioxidation, Antiapoptosis, Downregulation of HIF-1α, VEGF, and MMP-9 and Upregulation of HO-1

    PubMed Central

    Chuang, Min-Jay; Liu, Xiao-Qian; Ho, Li-Kang; Pan, Wynn H.T.; Zhang, Xiu-Mei; Liu, Chi-Ming; Tsai, Shen-Kou; Kong, Chi-Woon; Lee, Shou-Dong; Chen, Mi-Mi; Chao, Fang-Ping

    2013-01-01

    Abstract Purpose Retinal ischemia-associated ocular disorders are vision threatening. This study examined whether the flavonoid baicalein is able to protect against retinal ischemia/reperfusion. Methods Using rats, the intraocular pressure was raised to 120 mmHg for 60 min to induce retinal ischemia. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating dissociated retinal cells with 100 μM ascorbate and 5 μM FeSO4 (iron) for 1 h. The rats or the dissociated cells had been pretreated with baicalein (in vivo: 0.05 or 0.5 nmol; in vitro: 100 μM), vehicle (1% ethanol), or trolox (in vivo: 5 nmol; in vitro: 100 μM or 1 mM). The effects of these treatments on the retina or the retinal cells were evaluated by electrophysiology, immunohistochemistry, terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) staining, Western blotting, or in vitro dichlorofluorescein assay. In addition, real-time-polymerase chain reaction was used to assess the retinal expression of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), vascular endothelium growth factor (VEGF), and heme oxygenase-1 (HO-1). Results The retinal changes after ischemia included a decrease in the electroretinogram b-wave amplitude, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, an increase in vimentin immunoreactivity, which is a marker for Müller cells, an increase in apoptotic cells in the retinal ganglion cell layer linked to a decrease in the Bcl-2 protein, and changes in the mRNA levels of HIF-1α, VEGF, MMP-9, and HO-1. Of clinical importance, the ischemic detrimental effects were concentration dependently and/or significantly (0.05 nmol and/or 0.5 nmol) altered when baicalein was applied 15 min before retinal ischemia. Most of all, 0.5 nmol baicalein significantly reduced the upregulation of MMP-9; in contrast, 5 nmol trolox only had a weak

  1. Anti-fibrillation propensity of a flavonoid baicalein against the fibrils of hen egg white lysozyme: potential therapeutics for lysozyme amyloidosis.

    PubMed

    Fazili, Naveed Ahmad; Bhat, Imtiyaz Ahmad; Bhat, Waseem Feeroze; Naeem, Aabgeena

    2016-10-01

    More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3 M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20-fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in Congo red assay and appearance of a network of long rope-like fibrils in transmission electron microscope (TEM) analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose-dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150-μM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 and 450 nm, respectively, together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis. PMID:26555198

  2. Delivery of baicalein and paclitaxel using self-assembled nanoparticles: synergistic antitumor effect in vitro and in vivo

    PubMed Central

    Wang, Wei; Xi, Mei; Duan, Xuezhong; Wang, Yong; Kong, Fansheng

    2015-01-01

    Purpose Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance. The aim of the study reported here was to develop multifunctional, dual-ligand, modified, self-assembled nanoparticles (NPs) for the combination delivery of baicalein (BCL) and paclitaxel (PTX) prodrugs. Methods Prodrug of PTX and prodrug of BCL, containing dual-targeted ligands of folate (FA) and hyaluronic acid (HA), were synthesized. Multifunctional self-assembled NPs for combination delivery of PTX prodrug and BCL prodrug (PTX-BCL) were prepared and the synergistic antitumor effect was evaluated in vitro and in vivo. The in vitro transfection efficiency of the novel modified vectors was evaluated in human lung cancer A549 cells and drug-resistant lung cancer A549/PTX cells. The in vivo antitumor efficiency and systemic toxicity of different formulations were further investigated in mice bearing A549/PTX drug-resistant human lung cancer xenografts. Results The size of the PTX-BCL NPs was approximately 90 nm, with a positive zeta potential of +3.3. The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations. Conclusion The prepared PTX-BCL NP drug-delivery system was proven efficient by its targeting of drug-resistant human lung cancer cells and delivering of BCL and PTX prodrugs. Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine. PMID:26045664

  3. Comparative effects of low-level laser therapy pre- and post-injury on mRNA expression of MyoD, myogenin, and IL-6 during the skeletal muscle repair.

    PubMed

    Alves, Agnelo Neves; Ribeiro, Beatriz Guimarães; Fernandes, Kristianne Porta Santos; Souza, Nadhia Helena Costa; Rocha, Lília Alves; Nunes, Fabio Daumas; Bussadori, Sandra Kalil; Mesquita-Ferrari, Raquel Agnelli

    2016-05-01

    This study analyzed the effect of pre-injury and post-injury irradiation with low-level laser therapy (LLLT) on the mRNA expression of myogenic regulatory factors and interleukin 6 (IL-6) during the skeletal muscle repair. Male rats were divided into six groups: control group, sham group, LLLT group, injury group; pre-injury LLLT group, and post-injury LLLT group. LLLT was performed with a diode laser (wavelength 780 nm; output power 40 mW' and total energy 3.2 J). Cryoinjury was induced by two applications of a metal probe cooled in liquid nitrogen directly onto the belly of the tibialis anterior (TA) muscle. After euthanasia, the TA muscle was removed for the isolation of total RNA and analysis of MyoD, myogenin, and IL-6 using real-time quantitative PCR. Significant increases were found in the expression of MyoD mRNA at 3 and 7 days as well as the expression of myogenin mRNA at 14 days in the post-injury LLLT group in comparison to injury group. A significant reduction was found in the expression of IL-6 mRNA at 3 and 7 days in the pre-injury LLLT and post-injury LLLT groups. A significant increase in IL-6 mRNA was found at 14 days in the post-injury LLLT group in comparison to the injury group. LLLT administered following muscle injury modulates the mRNA expression of MyoD and myogenin. Moreover, the both forms of LLLT administration were able to modulate the mRNA expression of IL-6 during the muscle repair process. PMID:26914683

  4. Effect of low-energy laser irradiation and antioxidant supplementation on cell apoptosis during skeletal muscle post-injury regeneration in pigs.

    PubMed

    Otrocka-Domagała, I; Mikołajczyk, A; Paździor-Czapula, K; Gesek, M; Rotkiewicz, T; Mikiewicz, M

    2015-01-01

    The aim of this study was to evaluate the effect of low-energy laser irradiation, coenzyme Q10 and vitamin E supplementation on the apoptosis of macrophages and muscle precursor cells during skeletal muscle regeneration after bupivacaine-induced injury. The experiment was conducted on 75 gilts, divided into 5 experimental groups: I--control, II--low-energy laser irradiation, III--coenzyme Q10, IV--coenzyme Q10 and vitamin E, V--vitamin E. Muscle necrosis was induced by injection of 0.5% bupivacaine hydrochloride. The animals were euthanized on subsequent days after injury. Samples were formalin fixed and processed routinely for histopathology. Apoptosis was detected using the TUNEL method. The obtained results indicate that low-energy laser irradiation has a beneficial effect on macrophages and muscle precursor cell activity during muscle post-injury regeneration and protects these cells against apoptosis. Vitamin E has a slightly lower protective effect, limited mainly to the macrophages. Coenzyme Q10 co-supplemented with vitamin E increases the activity of macrophages and muscle precursor cells, myotube and young muscle formation. Importantly, muscle precursor cells seem to be more sensitive to apoptosis than macrophages in the environment of regenerating damaged muscle. PMID:26618584

  5. Baicalein protects against the development of angiotensin II-induced abdominal aortic aneurysms by blocking JNK and p38 MAPK signaling.

    PubMed

    Wang, Fang; Chen, Houzao; Yan, Yunfei; Liu, Yue; Zhang, Shuyang; Liu, Depei

    2016-09-01

    An abdominal aortic aneurysm (AAA) is a permanent, localized dilatation of the abdominal aorta. In western countries, the morbidity of AAA is approximately 8%. Currently, pharmacotherapies for AAA are limited. Here, we demonstrate that baicalein (BAI), the main component of the Chinese traditional drug "Huang Qin", attenuates the incidence and severity of AAA in Apoe (-/-) mice infused with angiotensin II (AngII). Mechanically, BAI treatment decreases AngII-induced reactive oxygen species (ROS) production in the aortic wall. Moreover, BAI inhibits inflammatory cell accumulation in the aortas of mice infused with AngII. It also inhibits AngII-induced activation of matrix metalloproteinase 2 (MMP-2) and MMP-9 to maintain elastin content in vivo. In addition, it blocks AngII cascade by downregulating angiotensin type 1 receptor (AT1R) and inhibiting mitogen-activated protein kinases (MAPKs). Taken together, our findings show that BAI is an effective agent for AAA prevention. PMID:27333787

  6. Analysis of baicalein, baicalin and wogonin in Scutellariae radix and its preparation by microemulsion electrokinetic chromatography with 1-butyl-3-methylimizolium tetrafluoborate ionic liquid as additive.

    PubMed

    Zhang, Huige; Tian, Kan; Tang, Jianghong; Qi, Shengda; Chen, Hongli; Chen, Xingguo; Hu, Zhide

    2006-10-01

    Microemulsion electrokinetic chromatography (MEEKC) using 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM-BF4) ionic liquid (IL) as additive was developed for the analysis of baicalin, wogonin and baicalein in Scutellariae radix and its preparation. After conducting a series of optimizations, baseline separation was obtained for the analytes within 5min under the optimum conditions (sodium dodecyl sulfate (SDS) 0.88% (m/v) ethyl acetate 0.8% (v/v) butan-1-ol 0.2% (v/v) and the buffer composition were 25% acetonitrile (v/v), 7.5 mM BMIM-BF4 and 10 mM NaH2PO4, pH 8.2, applied voltage 17.5 kV and detection at 254 nm), the method has been successfully applied to the determination and quantification of the analytes in the extracts of S. radix (cooked), S. radix (raw) and Qingfeiyihuowan which was the preparation including S. radix. PMID:16952364

  7. The PPAR gamma agonist Pioglitazone improves anatomical and locomotor recovery after rodent spinal cord injury

    PubMed Central

    McTigue, Dana M.; Tripathi, Richa; Wei, Ping; Lash, A. Todd

    2007-01-01

    Traumatic spinal cord injury (SCI) is accompanied by a dramatic inflammatory response, which escalates over the first week post-injury and is thought to contribute to secondary pathology after SCI. Peroxisome proliferator-activated receptors (PPAR) are widely expressed nuclear receptors whose activation has led to diminished pro-inflammatory cascades in several CNS disorders. Therefore, we examined the efficacy of the PPARγ agonist Pioglitazone in a rodent SCI model. Rats received a moderate mid-thoracic contusion and were randomly placed into groups receiving vehicle, low dose or high dose Pioglitazone. Drug or vehicle was injected i.p. at 15 min post-injury and then every 12h for the first 7d post-injury. Locomotor function was followed for 5 weeks using the BBB scale. BBB scores were greater in treated animals at 7d post-injury and significant improvements in BBB subscores were noted, including better toe clearance, earlier stepping and more parallel paw position. Stereological measurements throughout the lesion revealed a significant increase in rostral spared white matter in both Pioglitazone treatment groups. Spinal cords from the high dose group also had significantly more gray matter sparing and motor neurons rostral and caudal to epicenter. Thus, our results reveal that clinical treatment with Pioglitazone, an FDA-approved drug used currently for diabetes, may be a feasible and promising strategy for promoting anatomical and functional repair after SCI. PMID:17433295

  8. Reducing synuclein accumulation improves neuronal survival after spinal cord injury.

    PubMed

    Fogerson, Stephanie M; van Brummen, Alexandra J; Busch, David J; Allen, Scott R; Roychaudhuri, Robin; Banks, Susan M L; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Morgan, Jennifer R

    2016-04-01

    Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson's and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the "molecular tweezer" inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury. PMID:26854933

  9. Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6

    SciTech Connect

    Chen, Y.-C. . E-mail: yc3270@tmu.edu.tw; Chow, J.-M.; Lin, C.-W.; Wu, C.-Y.; Shen, S.-C.

    2006-10-15

    In the present study, we examined the protective mechanism of baicalein (BE) and its glycoside, baicalin (BI), on hydrogen-peroxide (H{sub 2}O{sub 2})-induced cell death in rat glioma C6 cells. Results of the MTT assay, LDH release assay, and morphological observation showed that H{sub 2}O{sub 2} addition reduced the viability of C6 cells, and this was prevented by the addition of BE but not BI. Incubation of C6 cells with BE significantly decreased the intracellular peroxide level induced by H{sub 2}O{sub 2} according to flow cytometric analysis using DCHF-DA as a fluorescent substrate. Suppression of H{sub 2}O{sub 2}-induced apoptotic events including DNA ladders, hypodiploid cells, and activation of caspases 3, 8, and, 9 by BE but not BI was identified in C6 cells. The cytotoxicity and phosphorylation of ERK proteins induced by H{sub 2}O{sub 2} were blocked by the ERK inhibitor PD98059. Catalase addition prevented H{sub 2}O{sub 2}-induced ROS production, ERKs protein phosphorylation, and cell death, and BE dose-dependently inhibited H{sub 2}O{sub 2}-induced ERK protein phosphorylation in C6 cells. These data suggest that ROS-scavenging activity is involved in BE prevention of H{sub 2}O{sub 2}-induced cell death via blocking ERKs activation. Additionally, BE but not BI induced heat shock protein 32 (HSP32; HO-1) protein expression in both time- and dose-dependent manners, but not heme oxygenase 2 (HO-2), heat shock protein 70 (HSP70), or heat shock protein 90 (HSP90) protein expression. In the absence of H{sub 2}O{sub 2}, BE induces ERKs protein phosphorylation, and HO-1 protein expression induced by BE was blocked by the addition of cycloheximide, actinomycin D, and the ERK inhibitor PD98059. The addition of the HO inhibitor ZnPP inhibited the protective effect of BE against H{sub 2}O{sub 2}-induced cytotoxicity in C6 cells according to the MTT assay and apoptotic morphology under microscopic observation, accompanied by blocking the ROS-scavenging activity of BE

  10. Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

    SciTech Connect

    Chandrashekar, Naveenkumar; Selvamani, Asokkumar; Subramanian, Raghunandhakumar; Pandi, Anandakumar; Thiruvengadam, Devaki

    2012-05-15

    The objective of the present study is to investigate the therapeutic efficacy of baicalein (BE) on inflammatory cytokines, which is in line with tumor invasion factors and antioxidant defensive system during benzo(a)pyrene [B(a)P] (50 mg/kg body weight) induced pulmonary carcinogenesis in Swiss albino mice. After experimental period, increased levels of total and differential cell count in bronchoalveolar lavage fluid were observed. Accompanied by marked increase in immature mast cell by toluidine blue staining and mature mast cell by safranin–alcian blue staining in B(a)P-induced lung cancer bearing animals. Protein expression levels studied by immunohistochemistry and immunoblot analysis of cytokines such as tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were also found to be significantly increased in lung cancer bearing animals. B(a)P-exposed mice lung exhibits activated expression of nuclear transcription factor kappa-B as confirmed by immunofluorescence and immunoblot analysis. Administration of BE (12 mg/kg body weight) significantly counteracted all the above deleterious changes. Moreover, assessment of tumor invasion factors on protein levels by immunoblot and mRNA expression levels by RT-PCR revealed that BE treatment effectively negates B(a)P-induced upregulated expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and cyclo-oxygenase-2. Further analysis of lipid peroxidation markers such as thiobarbituric acid reactive substances, hydro-peroxides and antioxidants such as glutathione-S-transferase and reduced glutathione in lung tissue was carried out to substantiate the antioxidant effect of BE. The chemotherapeutic effect observed in the present study is attributed to the potent anti-inflammatory and antioxidant potential by BE against pulmonary carcinogenesis. -- Highlights: ► BE treatment protects from inflammatory cells and mast-cells accumulation in lungs. ► BE altered the expressions of TNF

  11. Molecular neuroimaging of post-injury plasticity

    PubMed Central

    Jouroukhin, Yan; Nonyane, Bareng A. S.; Gilad, Assaf A.; Pelled, Galit

    2014-01-01

    Nerve injury induces long-term changes in neuronal activity in the primary somatosensory cortex (S1), which has often been implicated as the origin of sensory dysfunction. However, the cellular mechanisms underlying this phenomenon remain unclear. C-fos is an immediate early gene, which has been shown to play an instrumental role in plasticity. By developing a new platform to image real-time changes in gene expression in vivo, we investigated whether injury modulates the levels of c-fos in layer V of S1, since previous studies have suggested that these neurons are particularly susceptible to injury. The yellow fluorescent protein, ZsYellow1, under the regulation of the c-fos promoter, was expressed throughout the rat brain. A fiber-based confocal microscope that enabled deep brain imaging was utilized and local field potential were collected simultaneously. In the weeks following limb denervation in adult rats (n=10), sensory stimulation of the intact limb induced significant increases in c-fos gene expression in cells located in S1, both contralateral (affected, 27.6±3 cells) and ipsilateral (8.6±3 cells) to the injury, compared to controls (n=10, 13.4±3 and 1.0±1, respectively, p-value <0.05). Thus, we demonstrated that injury activates cellular mechanisms that are involved in reshaping neuronal connections and this may translate to neurorehabilitative potential. PMID:24909382

  12. A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury

    PubMed Central

    Peterson, Todd C.; McConomy, Keith S.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Kantor, Eric D.; Anderson, Gail D.

    2015-01-01

    Abstract Neuroprotection, recovery of function, and gene expression were evaluated in an animal model of traumatic brain injury (TBI) after a combination treatment of nicotinamide (NAM) and progesterone (Prog). Animals received a cortical contusion injury over the sensorimotor cortex, and were treated with either Vehicle, NAM, Prog, or a NAM/Prog combination for 72 h and compared with a craniotomy only (Sham) group. Animals were assessed in a battery of behavioral, sensory, and both fine and gross motor tasks, and given histological assessments at 24 h post-injury to determine lesion cavity size, degenerating neurons, and reactive astrocytes. Microarray-based transcriptional profiling was used to determine treatment-specific changes on gene expression. Our results confirm the beneficial effects of treatment with either NAM or Prog, demonstrating significant improvements in recovery of function and a reduction in lesion cavitation, degenerating neurons, and reactive astrocytes 24 h post-injury. The combination treatment of NAM and Prog led to a significant improvement in both neuroprotection at 24 h post-injury and recovery of function in sensorimotor related tasks when compared with individual treatments. The NAM/Prog-treated group was the only treatment group to show a significant reduction of cortical loss 24 h post-injury. The combination appears to affect inflammatory and immune processes, reducing expression of a significant number of genes in both pathways. Further preclinical trials using NAM and Prog as a combination treatment should be conducted to identify the window of opportunity, determine the optimal duration of treatment, and evaluate the combination in other pre-clinical models of TBI. PMID:25313690

  13. A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury.

    PubMed

    Peterson, Todd C; Hoane, Michael R; McConomy, Keith S; Farin, Fred M; Bammler, Theo K; MacDonald, James W; Kantor, Eric D; Anderson, Gail D

    2015-06-01

    Neuroprotection, recovery of function, and gene expression were evaluated in an animal model of traumatic brain injury (TBI) after a combination treatment of nicotinamide (NAM) and progesterone (Prog). Animals received a cortical contusion injury over the sensorimotor cortex, and were treated with either Vehicle, NAM, Prog, or a NAM/Prog combination for 72 h and compared with a craniotomy only (Sham) group. Animals were assessed in a battery of behavioral, sensory, and both fine and gross motor tasks, and given histological assessments at 24 h post-injury to determine lesion cavity size, degenerating neurons, and reactive astrocytes. Microarray-based transcriptional profiling was used to determine treatment-specific changes on gene expression. Our results confirm the beneficial effects of treatment with either NAM or Prog, demonstrating significant improvements in recovery of function and a reduction in lesion cavitation, degenerating neurons, and reactive astrocytes 24 h post-injury. The combination treatment of NAM and Prog led to a significant improvement in both neuroprotection at 24 h post-injury and recovery of function in sensorimotor related tasks when compared with individual treatments. The NAM/Prog-treated group was the only treatment group to show a significant reduction of cortical loss 24 h post-injury. The combination appears to affect inflammatory and immune processes, reducing expression of a significant number of genes in both pathways. Further preclinical trials using NAM and Prog as a combination treatment should be conducted to identify the window of opportunity, determine the optimal duration of treatment, and evaluate the combination in other pre-clinical models of TBI. PMID:25313690

  14. N-acetylcysteine amide confers neuroprotection, improves bioenergetics and behavioral outcome following TBI.

    PubMed

    Pandya, Jignesh D; Readnower, Ryan D; Patel, Samir P; Yonutas, Heather M; Pauly, James R; Goldstein, Glenn A; Rabchevsky, Alexander G; Sullivan, Patrick G

    2014-07-01

    Traumatic brain injury (TBI) has become a growing epidemic but no approved pharmacological treatment has been identified. Our previous work indicates that mitochondrial oxidative stress/damage and loss of bioenergetics play a pivotal role in neuronal cell death and behavioral outcome following experimental TBI. One tactic that has had some experimental success is to target glutathione using its precursor N-acetylcysteine (NAC). However, this approach has been hindered by the low CNS bioavailability of NAC. The current study evaluated a novel, cell permeant amide form of N-acetylcysteine (NACA), which has high permeability through cellular and mitochondrial membranes resulting in increased CNS bioavailability. Cortical tissue sparing, cognitive function and oxidative stress markers were assessed in rats treated with NACA, NAC, or vehicle following a TBI. At 15days post-injury, animals treated with NACA demonstrated significant improvements in cognitive function and cortical tissue sparing compared to NAC or vehicle treated animals. NACA treatment also was shown to reduce oxidative damage (HNE levels) at 7days post-injury. Mechanistically, post-injury NACA administration was demonstrated to maintain levels of mitochondrial glutathione and mitochondrial bioenergetics comparable to sham animals. Collectively these data provide a basic platform to consider NACA as a novel therapeutic agent for treatment of TBI. PMID:24792639

  15. N-acetylcysteineamide confers neuroprotection, improves bioenergetics and behavioral outcome following TBI

    PubMed Central

    Pandya, Jignesh D.; Readnower, Ryan D.; Patel, Samir P.; Yonutas, Heather M.; Pauly, James R.; Goldstein, Glenn A.; Rabchevsky, Alexander G.; Sullivan, Patrick G.

    2014-01-01

    Traumatic brain injury (TBI) has become a growing epidemic but no approved pharmacological treatment has been identified. Our previous work indicates that mitochondrial oxidative stress/damage and loss of bioenergetics play a pivotal role in neuronal cell death and behavioral outcome following experimental TBI. One tactic that has had some experimental success is to target glutathione using its precursor N-acetylcysteine (NAC). However, this approach has been hindered by the low CNS bioavailability of NAC. The current study evaluated a novel, cell permeant amide form of N-acetylcysteine (NACA), which has high permeability through cellular and mitochondrial membranes resulting in increased CNS bioavailability. Cortical tissue sparing, cognitive function and oxidative stress markers were assessed in rats treated with NACA, NAC, or vehicle following a TBI. At 15 days post-injury, animals treated with NACA demonstrated significant improvements in cognitive function and cortical tissue sparing compared to NAC or vehicle treated animals. NACA treatment also was shown to reduce oxidative damage (HNE levels) at 7 days post-injury. Mechanistically, post-injury NACA administration was demonstrated to maintain levels of mitochondrial glutathione and mitochondrial bioenergetics comparable to sham animals. Collectively these data provide a basic platform to consider NACA as a novel therapeutic agent for treatment of TBI. PMID:24792639

  16. Leucine supplementation improves regeneration of skeletal muscles from old rats.

    PubMed

    Pereira, Marcelo G; Silva, Meiricris T; da Cunha, Fernanda M; Moriscot, Anselmo S; Aoki, Marcelo S; Miyabara, Elen H

    2015-12-01

    The decreased regenerative capacity of old skeletal muscles involves disrupted turnover of proteins. This study investigated whether leucine supplementation in old rats could improve muscle regenerative capacity. Young and old male Wistar rats were supplemented with leucine; then, the muscles were cryolesioned and examined after 3 and 10 days. Leucine supplementation attenuated the decrease in the expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and eukaryotic translation initiation factor 4E (eIF4E) in young and old muscles on day 3 post-injury and promoted an increase in the cross-sectional area of regenerating myofibers from both young and old soleus muscles on day 10 post-injury. This supplementation decreased the levels of ubiquitinated proteins and increased the proteasome activity in young regenerating muscles, but the opposite effect was observed in old regenerating muscles. Moreover, leucine decreased the inflammation area and induced an increase in the number of proliferating satellite cells in both young and old muscles. Our results suggest that leucine supplementation improves the regeneration of skeletal muscles from old rats, through the preservation of certain biological responses upon leucine supplementation. Such responses comprise the decrease in the inflammation area, increase in the number of proliferating satellite cells and size of regenerating myofibers, combined with the modulation of components of the phosphoinositide 3-kinase/Akt-protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and ubiquitin-proteasome system. PMID:26481769

  17. N-acetylcysteine amide preserves mitochondrial bioenergetics and improves functional recovery following spinal trauma.

    PubMed

    Patel, Samir P; Sullivan, Patrick G; Pandya, Jignesh D; Goldstein, Glenn A; VanRooyen, Jenna L; Yonutas, Heather M; Eldahan, Khalid C; Morehouse, Johnny; Magnuson, David S K; Rabchevsky, Alexander G

    2014-07-01

    Mitochondrial dysfunction is becoming a pivotal target for neuroprotective strategies following contusion spinal cord injury (SCI) and the pharmacological compounds that maintain mitochondrial function confer neuroprotection and improve long-term hindlimb function after injury. In the current study we evaluated the efficacy of cell-permeating thiol, N-acetylcysteine amide (NACA), a precursor of endogenous antioxidant glutathione (GSH), on mitochondrial function acutely, and long-term tissue sparing and hindlimb locomotor recovery following upper lumbar contusion SCI. Some designated injured adult female Sprague-Dawley rats (n=120) received either vehicle or NACA (75, 150, 300 or 600mg/kg) at 15min and 6h post-injury. After 24h the total, synaptic, and non-synaptic mitochondrial populations were isolated from a single 1.5cm spinal cord segment (centered at injury site) and assessed for mitochondrial bioenergetics. Results showed compromised total mitochondrial bioenergetics following acute SCI that was significantly improved with NACA treatment in a dose-dependent manner, with maximum effects at 300mg/kg (n=4/group). For synaptic and non-synaptic mitochondria, only 300mg/kg NACA dosage showed efficacy. Similar dosage (300mg/kg) also maintained mitochondrial GSH near normal levels. Other designated injured rats (n=21) received continuous NACA (150 or 300mg/kg/day) treatment starting at 15min post-injury for one week to assess long-term functional recovery over 6weeks post-injury. Locomotor testing and novel gait analyses showed significantly improved hindlimb function with NACA that were associated with increased tissue sparing at the injury site. Overall, NACA treatment significantly maintained acute mitochondrial bioenergetics and normalized GSH levels following SCI, and prolonged delivery resulted in significant tissue sparing and improved recovery of hindlimb function. PMID:24805071

  18. N-acetylcysteineamide Preserves Mitochondrial Bioenergetics and Improves Functional Recovery Following Spinal Trauma

    PubMed Central

    Patel, Samir P.; Sullivan, Patrick G.; Pandya, Jignesh D.; Goldstein, Glenn A.; VanRooyen, Jenna L.; Yonutas, Heather M.; Eldahan, Khalid C.; Morehouse, Johnny; Magnuson, David S. K.; Rabchevsky, Alexander G.

    2014-01-01

    Mitochondrial dysfunction is becoming a pivotal target for neuroprotective strategies following contusion spinal cord injury (SCI) and the pharmacological compounds that maintain mitochondrial function confer neuroprotection and improve long-term hindlimb function after injury. In the current study we evaluated the efficacy of cell-permeating thiol, N-acetylcysteineamide (NACA), a precursor of endogenous antioxidant glutathione (GSH), on mitochondrial function acutely, and long-term tissue sparing and hindlimb locomotor recovery following upper lumbar contusion SCI. Some designated injured adult female Sprague-Dawley rats (n=120) received either Vehicle or NACA (75, 150, 300 or 600 mg/kg) at 15min and 6hrs post-injury. After 24hr the total, synaptic, and non-synaptic mitochondrial populations were isolated from a single 1.5cm spinal cord segment (centered at injury site) and assessed for mitochondrial bioenergetics. Results showed compromised total mitochondrial bioenergetics following acute SCI that was significantly improved with NACA treatment in a dose-dependent manner, with maximum effects at 300 mg/kg (n=4/group). For synaptic and non-synaptic mitochondria, only 300 mg/kg NACA dosage showed efficacy. Similar dosage (300mg/kg) also maintained mitochondrial GSH near normal levels. Other designated injured rats (n=21) received continuous NACA (150 or 300mg/kg/day) treatment starting at 15min post-injury for one week to assess long-term functional recovery over 6 weeks post-injury. Locomotor testing and novel gait analyses showed significantly improved hindlimb function with NACA that were associated with increased tissue sparing at the injury site. Overall, NACA treatment significantly maintained acute mitochondrial bioenergetics and normalized GSH levels following SCI, and prolonged delivery resulted in significant tissue sparing and improved recovery of hindlimb function. PMID:24805071

  19. Intravenous Administration of Simvastatin Improves Cognitive Outcome following Severe Traumatic Brain Injury in Rats.

    PubMed

    Mountney, Andrea; Boutté, Angela M; Gilsdorf, Janice; Lu, Xi-Chun; Tortella, Frank C; Shear, Deborah A

    2016-08-15

    Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly used to reduce serum cholesterol. The beneficial effects of oral simvastatin have been reported in pre-clinical models of traumatic brain injury (TBI). The current study was designed to evaluate the potential beneficial effects of simvastatin in a model of severe penetrating TBI using an intravenous (IV) route of administration. Rats were subjected to unilateral frontal penetrating ballistic-like brain injury (PBBI), and simvastatin was delivered intravenously at 30 min and 6 h post-injury and continued once daily for either 4 or 10 days post-PBBI. Motor function was assessed on the rotarod and cognitive performance was evaluated using the Morris water maze (MWM) task. Serum levels of inflammatory cytokines and the astrocytic biomarker, glial fibrillary acidic protein (GFAP), were quantified at 1 h, 4 h, and 24 h post-injury. Histopathological damage was assessed at the terminal end-point. Rotarod testing revealed significant motor deficits in all injury groups but no significant simvastatin-induced therapeutic benefits. All PBBI-injured animals showed cognitive impairment on the MWM test; however, 10-day simvastatin treatment mitigated these effects. Animals showed significantly improved latency to platform and retention scores, whereas the 4-day treatment regimen failed to produce any significant improvements. Biomarker and cytokine analysis showed that IV simvastatin significantly reduced GFAP, interleukin (IL)-1α, and IL-17 serum levels by 4.0-, 2.6-, and 7.0-fold, respectively, at 4 h post-injury. Collectively, our results demonstrate that IV simvastatin provides significant protection against injury-induced cognitive dysfunction and reduces TBI-specific biomarker levels. Further research is warranted to identify the optimal dose and therapeutic window for IV delivery of simvastatin in models of severe TBI. PMID:26542887

  20. H2O2 Improves Quality of Radix scutellariae Through Anti-oxidant Effect

    PubMed Central

    Qi, Song; Wu-lin, Cao; Hua, Jiang; Ai-hua, Zhang; Xiang-cai, Meng

    2016-01-01

    Introduction: The correlation between the quality and geographical origin of herbal medicine was traced back to Tang Dynasty in China, more than 1200 years, and the effects of ecological environments on the secondary metabolites such as flavonoids have been confirmed. However, little is known about how the adversity impacts on the quality. Reactive oxygen species (ROS) may be medium between the ecological environment and the secondary metabolism. Materials and Methods: The fresh roots of Scutellaria baicalensis Georgi were treated with 0.002 μmol/L, 0.2 μmol/L, and 20 μmol/L H2O2, respectively. A stress model was established to elucidate the change of secondary metabolism, anti-oxidant enzyme system, and enzymes relating to flavonoids. Results: The activities of superoxide dismutase, catalase and peroxidase decreased. Too much H2O2, firstly, boosted transformation of flavonoids glycoside into aglucon with the most remarkable activities through UDP-glucuronate baicalein 7-O-glucuronosyltransferase (UBGAT), and β-glucuronidase (GUS), then regulated the gene expression of phenylalanine ammonialyase, GUS, and UBGAT, and increased the contents of flavones, motivated the flavonoid glycoside converting into aglucon. With this action, the flavones displaced the anti-oxidant enzymes. The higher the dosage, the more baicalein and wogonin increased, the later they took action. Conclusion: The plant secondary metabolites to keep ROS constant are identical to the effective materials in clinic. They are closely linked. H2O2 can improve flavones, especially the aglucon, and further increased the quality of herbal medicine, which possesses very important value in medical practice. SUMMARY H2O2 decreasing the activities of CAT and POD lead to accumulation of more H2O2. Excess of H2O2 up-regulated PAL, BUG, promote biosynthesis of flavones, and enhance the nonenzyme system. “↑” and “↓” represent activity or content “up” and “down” respectively. PMID:27019566

  1. Progesterone and vitamin D: improvement after traumatic brain injury in middle-aged rats

    PubMed Central

    Tang, Huiling; Hua, Fang; Wang, Jun; Sayeed, Iqbal; Wang, Xiaojing; Chen, Zhengjia; Yousuf, Seema; Atif, Fahim; Stein, Donald G.

    2013-01-01

    Progesterone (PROG) and vitamin D hormone (VDH) have both shown promise in treating traumatic brain injury (TBI). Both modulate apoptosis, inflammation, oxidative stress, and excitotoxicity. We investigated whether 21 days of VDH deficiency would alter cognitive behavior after TBI and whether combined PROG and VDH would improve behavioral and morphological outcomes more than either hormone alone in VDH-deficient middle-aged rats given bilateral contusions of the medial frontal cortex. PROG (16 mg/kg) and VDH (5 µg/kg) were injected intraperitoneally 1 hour post-injury. Eight additional doses of PROG were injected subcutaneously over 7 days post-injury. VDH deficiency itself did not significantly reduce baseline behavioral functions or aggravate impaired cognitive outcomes. Combination therapy showed moderate improvement in preserving spatial and reference memory but was not significantly better than PROG monotherapy. However, combination therapy significantly reduced neuronal loss and the proliferation of reactive astrocytes, and showed better efficacy compared to VDH or PROG alone in preventing MAP-2 degradation. VDH+PROG combination therapy may attenuate some of the potential long-term, subtle, pathophysiological consequences of brain injury in older subjects. PMID:23896206

  2. Diffuse Brain Injury Elevates Tonic Glutamate Levels and Potassium-Evoked Glutamate Release in Discrete Brain Regions at Two Days Post-Injury: An Enzyme-Based Microelectrode Array Study

    PubMed Central

    Hinzman, Jason M.; Currier Thomas, Theresa; Burmeister, Jason J.; Quintero, Jorge E.; Huettl, Peter; Pomerleau, Francois; Gerhardt, Greg A.

    2010-01-01

    Abstract Traumatic brain injury (TBI) survivors often suffer from a wide range of post-traumatic deficits, including impairments in behavioral, cognitive, and motor function. Regulation of glutamate signaling is vital for proper neuronal excitation in the central nervous system. Without proper regulation, increases in extracellular glutamate can contribute to the pathophysiology and neurological dysfunction seen in TBI. In the present studies, enzyme-based microelectrode arrays (MEAs) that selectively measure extracellular glutamate at 2 Hz enabled the examination of tonic glutamate levels and potassium chloride (KCl)-evoked glutamate release in the prefrontal cortex, dentate gyrus, and striatum of adult male rats 2 days after mild or moderate midline fluid percussion brain injury. Moderate brain injury significantly increased tonic extracellular glutamate levels by 256% in the dentate gyrus and 178% in the dorsal striatum. In the dorsal striatum, mild brain injury significantly increased tonic glutamate levels by 200%. Tonic glutamate levels were significantly correlated with injury severity in the dentate gyrus and striatum. The amplitudes of KCl-evoked glutamate release were increased significantly only in the striatum after moderate injury, with a 249% increase seen in the dorsal striatum. Thus, with the MEAs, we measured discrete regional changes in both tonic and KCl-evoked glutamate signaling, which were dependent on injury severity. Future studies may reveal the specific mechanisms responsible for glutamate dysregulation in the post-traumatic period, and may provide novel therapeutic means to improve outcomes after TBI. PMID:20233041

  3. Distal biceps reconstruction 13 years post-injury

    PubMed Central

    Burrus, M. Tyrrell

    2015-01-01

    Distal biceps tendon ruptures are relatively rare injuries most commonly caused by an eccentric contraction of the biceps brachii. The majority of complete ruptures receive early surgical intervention, however, some patients do present in a delayed fashion. There are many surgical options at this time for acute and chronic injuries, and this case report describes an Achilles allograft reconstruction in a male who sustained a complete tear 13 years prior to presentation. At 12-month follow up, he had regained full function of his dominant extremity as evidence by returning to work with no limitations and by a Disabilities of the Arm, Shoulder, and Hand (DASH) score of zero. We are unaware of a successfully surgically reconstructed distal biceps tendon of this chronicity. As the literature on this subject is sparse, this case report gives credence to the idea that certain patients with a chronic distal biceps rupture should be considered for operative reconstruction and not relegated to continued failed conservative treatment. Discussed are the surgical treatment options and controversies for chronic distal biceps ruptures, and we review various outcome studies using different surgical techniques. PMID:25829956

  4. D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury.

    PubMed

    Yaka, Rami; Biegon, Anat; Grigoriadis, Nikolaos; Simeonidou, Constantina; Grigoriadis, Savvas; Alexandrovich, Alexander G; Matzner, Henri; Schumann, Johanna; Trembovler, Victoria; Tsenter, Jeanna; Shohami, Esther

    2007-07-01

    Traumatic brain injury triggers a massive glutamate efflux, activation of NMDA receptor channels, and cell death. Recently, we reported that NMDA receptors in mice are down-regulated from hours to days following closed head injury (CHI), and treatment with NMDA improved recovery of motor and cognitive functions up to 14 d post-injury. Here we show that a single injection of a low dose of D-cycloserine (DCS), a partial NMDA receptor agonist, in CHI mice 24 h post-injury, resulted in a faster and greater recovery of motor and memory functions as assessed by neurological severity score and object recognition tests, respectively. Moreover, DCS treatment of CHI mice led to a significant improvement of hippocampal long-term potentiation (LTP) in the CA1 region that was completely blunted in CHI control mice. However, DCS did not improve CHI-induced impairment in synaptic glutamate release measured by paired pulse facilitation (PPF) ratio in hippocampal CA1 region. Finally, CHI-induced reduction of brain-derived neurotrophic factor (BDNF) was fully restored following DCS treatment. Since DCS is in clinical use for other indications, the present study offers a novel approach to treat human brain injury. PMID:17351125

  5. Combining Enriched Environment, Progesterone, and Embryonic Neural Stem Cell Therapy Improves Recovery after Brain Injury.

    PubMed

    Nudi, Evan T; Jacqmain, Justin; Dubbs, Kelsey; Geeck, Katalin; Salois, Garrick; Searles, Madeleine A; Smith, Jeffrey S

    2015-07-15

    Millions of persons every year are affected by traumatic brain injury (TBI), and currently no therapies have shown efficacy in improving outcomes clinically. Recent research has suggested that enriched environments (EE), embryonic neural stem cells (eNSC), and progesterone (PROG) improve functional outcomes after TBI, and further, several investigators have suggested that a polytherapuetic approach may have greater efficacy than a single therapy. The purpose of the current study was to determine if varying combinations of post-injury EE, progesterone therapy, or eNSC transplantation would improve functional outcomes over just a single therapy. A controlled cortical impact was performed in rats to create a lesion in the medial frontal cortex. The rats were then placed in either EE or standard environments and administered 10 mg/kg progesterone or vehicle injections 4 h post-injury and every 12 h for 72 h after the initial injection. Seven days after the surgery, rats were transplanted with either eNSCs or media. Rats were then tested on the open field test, Barnes maze, Morris water maze, and Rotor-Rod tasks. Improved functional outcomes were shown on a majority of the behavioral tasks in animals that received a combination of therapies. This effect was especially prominent with therapies that were combined with EE. Immunohistochemistry showed that the transplanted eNSCs survived, migrated, and displayed neural phenotypes. These data suggest that a poly-therapeutic approach after TBI improves functional recovery to a greater magnitude. Moreover, when polytherapies are combined with EE, the effects on recovery are enhanced, leading to greater recovery of function. PMID:25268854

  6. Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury.

    PubMed

    Shultz, Sandy R; Wright, David K; Zheng, Ping; Stuchbery, Ryan; Liu, Shi-Jie; Sashindranath, Maithili; Medcalf, Robert L; Johnston, Leigh A; Hovens, Christopher M; Jones, Nigel C; O'Brien, Terence J

    2015-05-01

    Traumatic brain injury is a common and serious neurodegenerative condition that lacks a pharmaceutical intervention to improve long-term outcome. Hyperphosphorylated tau is implicated in some of the consequences of traumatic brain injury and is a potential pharmacological target. Protein phosphatase 2A is a heterotrimeric protein that regulates key signalling pathways, and protein phosphatase 2A heterotrimers consisting of the PR55 B-subunit represent the major tau phosphatase in the brain. Here we investigated whether traumatic brain injury in rats and humans would induce changes in protein phosphatase 2A and phosphorylated tau, and whether treatment with sodium selenate-a potent PR55 activator-would reduce phosphorylated tau and improve traumatic brain injury outcomes in rats. Ninety young adult male Long-Evans rats were administered either a fluid percussion injury or sham-injury. A proportion of rats were killed at 2, 24, and 72 h post-injury to assess acute changes in protein phosphatase 2A and tau. Other rats were given either sodium selenate or saline-vehicle treatment that was continuously administered via subcutaneous osmotic pump for 12 weeks. Serial magnetic resonance imaging was acquired prior to, and at 1, 4, and 12 weeks post-injury to assess evolving structural brain damage and axonal injury. Behavioural impairments were assessed at 12 weeks post-injury. The results showed that traumatic brain injury in rats acutely reduced PR55 expression and protein phosphatase 2A activity, and increased the expression of phosphorylated tau and the ratio of phosphorylated tau to total tau. Similar findings were seen in post-mortem brain samples from acute human traumatic brain injury patients, although many did not reach statistical significance. Continuous sodium selenate treatment for 12 weeks after sham or fluid percussion injury in rats increased protein phosphatase 2A activity and PR55 expression, and reduced the ratio of phosphorylated tau to total tau

  7. Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

    PubMed Central

    Garcia-Ovejero, Daniel; González, Susana; Paniagua-Torija, Beatriz; Lima, Analía; Molina-Holgado, Eduardo; De Nicola, Alejandro F.

    2014-01-01

    Abstract Progesterone is an anti-inflammatory and promyelinating agent after spinal cord injury, but its effectiveness on functional recovery is still controversial. In the current study, we tested the effects of chronic progesterone administration on tissue preservation and functional recovery in a clinically relevant model of spinal cord lesion (thoracic contusion). Using magnetic resonance imaging, we observed that progesterone reduced both volume and rostrocaudal extension of the lesion at 60 days post-injury. In addition, progesterone increased the number of total mature oligodendrocytes, myelin basic protein immunoreactivity, and the number of axonal profiles at the epicenter of the lesion. Further, progesterone treatment significantly improved motor outcome as assessed using the Basso-Bresnahan-Beattie scale for locomotion and CatWalk gait analysis. These data suggest that progesterone could be considered a promising therapeutical candidate for spinal cord injury. PMID:24460450

  8. Ketogenic Diet Improves Forelimb Motor Function after Spinal Cord Injury in Rodents

    PubMed Central

    Streijger, Femke; Plunet, Ward T.; Lee, Jae H. T.; Liu, Jie; Lam, Clarrie K.; Park, Soeyun; Hilton, Brett J.; Fransen, Bas L.; Matheson, Keely A. J.; Assinck, Peggy; Kwon, Brian K.; Tetzlaff, Wolfram

    2013-01-01

    High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (α-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited. PMID:24223849

  9. Suppressor of Cytokine Signaling-2 (SOCS2) Regulates the Microglial Response and Improves Functional Outcome after Traumatic Brain Injury in Mice

    PubMed Central

    Basrai, Harleen S.; Christie, Kimberly J.; Turbic, Alisa; Bye, Nicole; Turnley, Ann M.

    2016-01-01

    Traumatic brain injury (TBI) is frequently characterized by neuronal, axonal and myelin loss, reactive gliosis and neuroinflammation, often associated with functional deficits. Endogenous repair mechanisms include production of new neurons from precursor cells, but usually the new neurons fail to integrate and survive more than a few weeks. This is in part mediated by the toxic and inflammatory environment present in the injured brain which activates precursor cells to proliferate and differentiate but limits survival of the newborn progeny. Therefore, an understanding of mechanisms that regulate production and survival of newborn neurons and the neuroinflammatory response after brain injury may lead to therapeutic options to improve outcomes. Suppressor of Cytokine Signaling 2 (SOCS2) promotes hippocampal neurogenesis and survival of newborn neurons in the adult brain and regulates anti-inflammatory responses in the periphery, suggesting it may be a useful candidate to improve outcomes of TBI. In this study the functional and cellular responses of SOCS2 over-expressing transgenic (SOCS2Tg) mice were compared to wildtype littermates following mild or moderately severe TBI. Unlike wildtype controls, SOCS2Tg mice showed functional improvement on a ladder test, with a smaller lesion volume at 7d post injury and increased numbers of proliferative CD11b+ microglia/macrophages at 35d post-injury in the mild injury paradigm. At 7d post-moderately severe injury there was an increase in the area covered by cells expressing an anti-inflammatory M2 phenotype marker (CD206+) but no difference in cells with a pro-inflammatory M1 phenotype marker (CD16/32+). No effect of SOCS2 overexpression was observed in production or survival of newborn neurons, even in the presence of the neuroprotective agent erythropoietin (EPO). Therefore, SOCS2 may improve outcome of TBI in mice by regulating aspects of the neuroinflammatory response, promoting a more anti-inflammatory environment

  10. Suppressor of Cytokine Signaling-2 (SOCS2) Regulates the Microglial Response and Improves Functional Outcome after Traumatic Brain Injury in Mice.

    PubMed

    Basrai, Harleen S; Christie, Kimberly J; Turbic, Alisa; Bye, Nicole; Turnley, Ann M

    2016-01-01

    Traumatic brain injury (TBI) is frequently characterized by neuronal, axonal and myelin loss, reactive gliosis and neuroinflammation, often associated with functional deficits. Endogenous repair mechanisms include production of new neurons from precursor cells, but usually the new neurons fail to integrate and survive more than a few weeks. This is in part mediated by the toxic and inflammatory environment present in the injured brain which activates precursor cells to proliferate and differentiate but limits survival of the newborn progeny. Therefore, an understanding of mechanisms that regulate production and survival of newborn neurons and the neuroinflammatory response after brain injury may lead to therapeutic options to improve outcomes. Suppressor of Cytokine Signaling 2 (SOCS2) promotes hippocampal neurogenesis and survival of newborn neurons in the adult brain and regulates anti-inflammatory responses in the periphery, suggesting it may be a useful candidate to improve outcomes of TBI. In this study the functional and cellular responses of SOCS2 over-expressing transgenic (SOCS2Tg) mice were compared to wildtype littermates following mild or moderately severe TBI. Unlike wildtype controls, SOCS2Tg mice showed functional improvement on a ladder test, with a smaller lesion volume at 7d post injury and increased numbers of proliferative CD11b+ microglia/macrophages at 35d post-injury in the mild injury paradigm. At 7d post-moderately severe injury there was an increase in the area covered by cells expressing an anti-inflammatory M2 phenotype marker (CD206+) but no difference in cells with a pro-inflammatory M1 phenotype marker (CD16/32+). No effect of SOCS2 overexpression was observed in production or survival of newborn neurons, even in the presence of the neuroprotective agent erythropoietin (EPO). Therefore, SOCS2 may improve outcome of TBI in mice by regulating aspects of the neuroinflammatory response, promoting a more anti-inflammatory environment

  11. Salidroside Improves Behavioral and Histological Outcomes and Reduces Apoptosis via PI3K/Akt Signaling after Experimental Traumatic Brain Injury

    PubMed Central

    Chen, Szu-Fu; Tsai, Hsin-Ju; Hung, Tai-Ho; Chen, Chien-Cheng; Lee, Chao Yu; Wu, Chun-Hu; Wang, Pei-Yi; Liao, Nien-Chieh

    2012-01-01

    Background Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Methodology/Principal Findings Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside_significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside_also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Conclusions/Significance Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis

  12. Combat-Related Intradural Gunshot Wound to the Thoracic Spine: Significant Improvement and Neurologic Recovery Following Bullet Removal

    PubMed Central

    Louwes, Thijs M; Ward, William H; Lee, Kendall H

    2015-01-01

    The vast majority of combat-related penetrating spinal injuries from gunshot wounds result in severe or complete neurological deficit. Treatment is based on neurological status, the presence of cerebrospinal fluid (CSF) fistulas, and local effects of any retained fragment(s). We present a case of a 46-year-old male who sustained a spinal gunshot injury from a 7.62-mm AK-47 round that became lodged within the subarachnoid space at T9-T10. He immediately suffered complete motor and sensory loss. By 24-48 hours post-injury, he had recovered lower extremity motor function fully but continued to have severe sensory loss (posterior cord syndrome). On post-injury day 2, he was evacuated from the combat theater and underwent a T9 laminectomy, extraction of the bullet, and dural laceration repair. At surgery, the traumatic durotomy was widened and the bullet, which was laying on the dorsal surface of the spinal cord, was removed. The dura was closed in a water-tight fashion and fibrin glue was applied. Postoperatively, the patient made a significant but incomplete neurological recovery. His stocking-pattern numbness and sub-umbilical searing dysthesia improved. The spinal canal was clear of the foreign body and he had no persistent CSF leak. Postoperative magnetic resonance imaging of the spine revealed contusion of the spinal cord at the T9 level. Early removal of an intra-canicular bullet in the setting of an incomplete spinal cord injury can lead to significant neurological recovery following even high-velocity and/or high-caliber gunshot wounds. However, this case does not speak to, and prior experience does not demonstrate, significant neurological benefit in the setting of a complete injury. PMID:25705346

  13. Helium-neon laser improves skin repair in rabbits.

    PubMed

    Peccin, Maria Stella; Renno, Ana Claudia Muniz; de Oliveira, Flavia; Giusti, Paulo Ricardo; Ribeiro, Daniel Araki

    2012-12-01

    The purpose of this study was to evaluate the influence of helium-neon laser on skin injury in rabbits. For this purpose, 15 New Zealand rabbits underwent bilateral skin damage in leg. Helium-neon laser light, at a fluence of 6 J∕cm2 and wavelength of 632.8 nm, was applied on the left legs (laser group). The right leg lesions (control group) served as negative control. All sections were histopathologically analyzed using HE sections. The results showed little infiltration of inflammatory cells, with proliferation of fibroblasts forming a few fibrous connective tissue after 1 week post-injury. The lesion on the 3rd week was characterized by granulation tissue, which formed from proliferated fibrous connective tissue, congested blood vessels and mild mononuclear cell infiltration. On the 5th week, it was observed that debris material surrounded by a thick layer of connective tissue and dense collage, fibroblasts cells present in the dermis covered by a thick epidermal layer represented by keratinized epithelium. Taken together, our results suggest that helium-neon laser is able to improve skin repair in rabbits at early phases of recovery. PMID:23057697

  14. Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation.

    PubMed

    Bye, Nicole; Christie, Kimberly J; Turbic, Alisa; Basrai, Harleen S; Turnley, Ann M

    2016-05-01

    Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury. PMID:26896832

  15. Primed Mesenchymal Stem Cells Alter Healing and Improve Rat Medial Collateral Ligament Healing

    PubMed Central

    Saether, Erin E.; Chamberlain, Connie S.; Aktas, Erdem; Leiferman, Ellen M.; Brickson, Stacey L.; Vanderby, Ray

    2016-01-01

    Cell therapy with mesenchymal stem cells (MSCs) can improve tissue healing. It is possible, however, that priming MSCs prior to implantation can further enhance their therapeutic benefit. This study was then performed to test whether priming MSCs to be more anti-inflammatory would enhance healing in a rat ligament model, i.e. a medial collateral ligament (MCL). MSCs were primed for 48 hours using polyinosinic acid and polycytidylic acid (Poly (I:C)) at a concentration of 1µg/ml. Rat MCLs were surgically transected and administered 1×106 cells in a carrier solution at the time of injury. A series of healing metrics were analyzed at days 4 and 14 post-injury in the ligaments that received primed MSCs, unprimed MSCs, or no cells (controls). Applying primed MSCs beneficially altered healing by affecting endothelialization, type 2 macrophage presence, apoptosis, procollagen 1α, and IL-1Ra levels. When analyzing MSC localization, both primed and unprimed MSCs co-localized with endothelial cells and pericytes suggesting a supportive role in angiogenesis. Priming MSCs prior to implantation altered key ligament healing events, resulted in a more anti-inflammatory environment, and improved healing. PMID:26530282

  16. Aloe vera and Vitis vinifera improve wound healing in an in vivo rat burn wound model.

    PubMed

    Lin, Li-Xin; Wang, Peng; Wang, Yu-Ting; Huang, Yong; Jiang, Lei; Wang, Xue-Ming

    2016-02-01

    Aloe vera and Vitis vinifera have been traditionally used as wound healing agents. The present study aimed to investigate the effects of aloe emodin and resveratrol in the burn wound healing procedure. Burn wounds are common in developed and developing countries, however, in developing countries, the incidence of severe complications is higher and financial resources are limited. The results of the present study demonstrated that neither aloe emodin or resveratrol were cytotoxic to THP-1 macrophages at concentrations of 1, 100 and 500 ng/ml. A significant increase in wound-healing activity was observed in mice treated with the aloe emodin and resveratrol, compared with those which received control treatments. The levels of IL-1β in the exudates of the burn wound area of the treated mice increased in a time-dependent manner over 7 days following burn wound injury. At 10 days post-injury, steady and progressive wound healing was observed in the control animals. The present study confirmed that increased wound healing occurs following treatment with aloe emodin,, compared with resveratrol, providing support for the use of Aloe vera plants to improve burn wound healing. PMID:26677006

  17. Wound administration of M2-polarized macrophages does not improve murine cutaneous healing responses.

    PubMed

    Jetten, Nadine; Roumans, Nadia; Gijbels, Marion J; Romano, Andrea; Post, Mark J; de Winther, Menno P J; van der Hulst, Rene R W J; Xanthoulea, Sofia

    2014-01-01

    Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds. PMID:25068282

  18. Panax notoginseng saponins improve recovery after spinal cord transection by upregulating neurotrophic factors.

    PubMed

    Wang, Bo; Li, Yu; Li, Xuan-Peng; Li, Yang

    2015-08-01

    Saponins extracted from Panax notoginseng are neuroprotective, but the mechanisms underlying this effect remain unclear. In the present study, we established a rat model of thoracic (T10) spinal cord transection, and injected Panax notoginseng saponins (100 mg/kg) or saline 30 minutes after injury. Locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) scale from 1 to 30 days after injury, and immunohistochemistry was carried out in the ventral horn of the spinal cord at 1 and 7 days to determine expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Our results show that at 7-30 days post injury, the BBB score was higher in rats treated with Panax notoginseng saponins than in those that received saline. Furthermore, at 7 days, more NGF- and BDNF-immunoreactive neurons were observed in the ventral horn of the spinal cord of rats that had received Panax notoginseng saponins than in those that received saline. These results indicate that Panax notoginseng saponins caused an upregulation of NGF and BDNF in rats with spinal cord transection, and improved hindlimb motor function. PMID:26487862

  19. Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses

    PubMed Central

    Jetten, Nadine; Roumans, Nadia; Gijbels, Marion J.; Romano, Andrea; Post, Mark J.; de Winther, Menno P. J.; van der Hulst, Rene R. W. J.; Xanthoulea, Sofia

    2014-01-01

    Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds. PMID:25068282

  20. The Effect of Post-injury Depression on Quality of Life following Minor Injury

    PubMed Central

    Richmond, Therese S.; Guo, Wensheng; Ackerson, Theimann; Hollander, Judd; Gracias, Vicente; Robinson, Keith; Amsterdam, Jay

    2014-01-01

    Purpose To describe quality of life (QoL) in the year following minor injury and to test the hypothesis that individuals with depression in the postinjury year experience lower QoL than do individuals with no depression. Design Prospective, longitudinal, cohort design. A total of 275 adults were randomly selected from injured patients presenting to an urban emergency department. Methods All participants underwent structured psychiatric diagnostic interviews immediately after injury and at 3, 6, and 12 months. The primary outcome, QoL, was measured using the Quality of Life Index. Covariates included demographics, injury status, preinjury functional status, preinjury social support, and anticipation of problems postdischarge. The General Estimating Equation was used to compare changes in QoL between participants with and without depression over 3, 6, and 12 months, adjusting for covariates. Results An 18.1% proportion (95% confidence interval [CI] 13.3, 22.9%) of the sample met criteria for a mood disorder in the postinjury year. The depressed group reported a QoL that was 4.2 points (95% CI 2.8–5.6) lower in the year postinjury compared with that of the nondepressed group. Conclusions Depression after minor injury negatively affects QoL even a full year postinjury. Clinical Relevance The findings of this study show that patients who have injuries that are treated and discharged from an emergency department can have significantly lower QoL in the year after that injury that may be attributed to postinjury depression. Nurses should provide anticipatory guidance to patients that they may experience feelings of sadness or being “blue,” and that if they do, they should seek care. PMID:24354500

  1. CSF Proteomics of Secondary Phase Spinal Cord Injury in Human Subjects: Perturbed Molecular Pathways Post Injury

    PubMed Central

    Sengupta, Mohor Biplab; Basu, Mahashweta; Iswarari, Sourav; Mukhopadhyay, Kiran Kumar; Sardar, Krishna Pada; Acharyya, Biplab; Mohanty, Pradeep K.; Mukhopadhyay, Debashis

    2014-01-01

    Recovery of sensory and motor functions following traumatic spinal cord injury (SCI) is dependent on injury severity. Here we identified 49 proteins from cerebrospinal fluid (CSF) of SCI patients, eight of which were differentially abundant among two severity groups of SCI. It was observed that the abundance profiles of these proteins change over a time period of days to months post SCI. Statistical analysis revealed that these proteins take part in several molecular pathways including DNA repair, protein phosphorylation, tRNA transcription, iron transport, mRNA metabolism, immune response and lipid and ATP catabolism. These pathways reflect a set of mechanisms that the system may adopt to cope up with the assault depending on the injury severity, thus leading to observed physiological responses. Apart from putting forward a picture of the molecular scenario at the injury site in a human study, this finding further delineates consequent pathways and molecules that may be altered by external intervention to restrict neural degeneration. PMID:25350754

  2. Whole-body vibration improves functional recovery in spinal cord injured rats.

    PubMed

    Wirth, Felicitas; Schempf, Greta; Stein, Gregor; Wellmann, Katharina; Manthou, Marilena; Scholl, Carolin; Sidorenko, Malina; Semler, Oliver; Eisel, Leonie; Harrach, Rachida; Angelova, Srebrina; Jaminet, Patrick; Ankerne, Janina; Ashrafi, Mahak; Ozsoy, Ozlem; Ozsoy, Umut; Schubert, Harald; Abdulla, Diana; Dunlop, Sarah A; Angelov, Doychin N; Irintchev, Andrey; Schönau, Eckhard

    2013-03-15

    Whole-body vibration (WBV) is a relatively novel form of exercise used to improve neuromuscular performance in healthy individuals. Its usefulness as a therapy for patients with neurological disorders, in particular spinal cord injury (SCI), has received little attention in clinical settings and, surprisingly, even less in animal SCI models. We performed severe compression SCI at a low-thoracic level in Wistar rats followed by daily WBV starting 7 (10 rats) or 14 (10 rats) days after injury (WBV7 and WBV14, respectively) and continued over a 12-week post-injury period. Rats with SCI but no WBV training (sham, 10 rats) and intact animals (10 rats) served as controls. Compared to sham-treated rats, WBV did not improve BBB score, plantar stepping, or ladder stepping during the 12-week period. Accordingly, WBV did not significantly alter plantar H-reflex, lesion volume, serotonergic input to the lumbar spinal cord, nor cholinergic or glutamatergic inputs to lumbar motoneurons at 12 weeks after SCI. However, compared to sham, WBV14, but not WBV7, significantly improved body weight support (rump-height index) during overground locomotion and overall recovery between 6-12 weeks and also restored the density of synaptic terminals in the lumbar spinal cord at 12 weeks. Most remarkably, WBV14 led to a significant improvement of bladder function at 6-12 weeks after injury. These findings provide the first evidence for functional benefits of WBV in an animal SCI model and warrant further preclinical investigations to determine mechanisms underpinning this noninvasive, inexpensive, and easily delivered potential rehabilitation therapy for SCI. PMID:23157611

  3. Wound Healing Immediately Post-Thermal Injury Is Improved by Fat and Adipose Derived Stem Cell Isografts

    PubMed Central

    Loder, Shawn; Peterson, Jonathan R.; Agarwal, Shailesh; Eboda, Oluwatobi; Brownley, Cameron; DeLaRosa, Sara; Ranganathan, Kavitha; Cederna, Paul; Wang, Stewart C.; Levi, Benjamin

    2014-01-01

    Objectives Patients with severe burns suffer functional, structural, and aesthetic complications. It is important to explore reconstructive options given that no ideal treatment exists. Transfer of adipose and adipose-derived stem cells (ASCs) has been shown to improve healing in various models. We hypothesize that use of fat isografts and/or ASCs will improve healing in a mouse model of burn injury. Methods Twenty 6–8 week old C57BL/6 male mice received a 30% surface area partial-thickness scald burn. Adipose tissue and ASCs from inguinal fat pads were harvested from a second group of C57BL/6 mice. Burned mice received 500μl subcutaneous injection at burn site of 1) processed adipose, 2) ASCs, 3) mixed adipose (adipose and ASCs), or 4) sham (saline) injection (n=5/group) on the first day post-injury. Mice were followed by serial photography until sacrifice at days 5 and 14. Wounds were assessed for burn depth and healing by Hematoxylin and Eosin (H&E) and immunohistochemistry. Results All treated groups showed improved healing over controls defined by decreased wound depth, area, and apoptotic activity. After 5 days, mice receiving ASCs or mixed adipose displayed a non-significant improvement in vascularization. No significant changes in proliferation were noted at 5 days. Conclusions Adipose isografts improve some early markers of healing post-burn injury. We demonstrate that addition of these grafts improve specific structural markers of healing. This improvement may be due to an increase in early wound vascularity post-graft. Further studies are needed to optimize use of fat or ASC grafts in acute and reconstructive surgery. PMID:25185931

  4. SB203580, a p38 mitogen-activated protein kinase inhibitor, fails to improve functional outcome following a moderate spinal cord injury in rat.

    PubMed

    Stirling, D P; Liu, J; Plunet, W; Steeves, J D; Tetzlaff, W

    2008-07-31

    We examined the spatial and temporal expression patterns of active p38 mitogen-activated protein kinase (MAPK), an important regulator of immune cell function, following spinal cord injury (SCI). We further assessed whether administration of SB203580, an inhibitor of p38 MAPK activity, would reduce inflammation, improve tissue sparing, and improve functional outcome after SCI. Adult Wistar rats were subjected to a T9/10 SCI contusion of moderate severity and killed at several time points after injury, whereas sham-injured (control) animals only received a laminectomy. In control animals, active p38 MAPK expression was primarily localized to resting microglia within the spinal cord. Over the first 24 h after SCI, a continuing increase in active p38 MAPK expression was evident in neutrophils and activated microglia (OX42+) surrounding the spinal lesion site. At 15 days post-injury, active p38 MAPK was localized to macrophages (ED1+) that now dominated the lesion site. In addition, active p38 MAPK was localized to macrophages within white matter fiber tracts undergoing degeneration, several segments rostral and caudal to the injury site, which persisted for at least 6 weeks. Overall, our results demonstrate that active p38 MAPK is increased within resident and invading immune cells after SCI contusion injury and, therefore, may be an important target to regulate the inflammatory cascade after SCI. However, intrathecal application of SB203580 failed to improve functional outcome after a moderate SCI contusion. PMID:18562123

  5. Endothelin receptor-A (ETa) inhibition fails to improve neonatal hypoxic-ischemic brain injury in rats.

    PubMed

    Khatibi, Nikan H; Lee, Lillian K; Zhou, Yilin; Chen, Wanqiu; Rolland, William; Fathali, Nancy; Martin, Robert; Applegate, Richard; Stier, Gary; Zhang, John H

    2011-01-01

    Cerebral hypoxia-ischemia (HI) is an important cause of mortality and disability in newborns. It is a result of insufficient oxygen and glucose circulation to the brain, initiating long-term cerebral damage and cell death. Emerging evidence suggests that endothelin receptor-A (ETA) activation can play an important role in mediating brain damage. In this study, we investigated the role of ETA receptor inhibition using ABT-627 in neonatal HI injured rats. Postnatal day 10 Sprague-Dawley rat pups (n=91) were assigned to the following groups: sham (n=28), HI (vehicle, n=32), and HI with ABT-627 at 3 mg/kg (n=31). The Rice-Vannucci model was used to induce ischemia by ligating the right common carotid artery, followed by a 2 h hypoxic episode using 8% oxygen in a 37°C chamber. Postoperative assessment was conducted at 48 h after injury and again at 4 weeks. At the acute time point, investigative markers included cerebral edema, infarction volume, and body weight change. Neurobehavioral testing was measured at 4 weeks post-injury. Our findings indicated that ABT-627 had no effect on the measured parameters. This study suggests that ETA receptor blockade using ABT-627 post-treatment fails to improve neurological outcomes in neonatal HI injured rats. PMID:21725757

  6. Intravenous administration of Honokiol provides neuroprotection and improves functional recovery after traumatic brain injury through cell cycle inhibition.

    PubMed

    Wang, Haiquan; Liao, Zhengbu; Sun, Xiaochuan; Shi, Quanhong; Huo, Gang; Xie, Yanfeng; Tang, Xiaolan; Zhi, Xinggang; Tang, Zhaohua

    2014-11-01

    Recently, increasing evidence has shown that cell cycle activation is a key factor of neuronal death and neurological dysfunction after traumatic brain injury (TBI). This study aims to investigate the effects of Honokiol, a cell cycle inhibitor, on attenuating the neuronal damage and facilitating functional recovery after TBI in rats, in an attempt to unveil its underlying molecular mechanisms in TBI. This study suggested that delayed intravenous administration of Honokiol could effectively ameliorate TBI-induced sensorimotor and cognitive dysfunctions. Meanwhile, Honokiol treatment could also reduce the lesion volume and increase the neuronal survival in the cortex and hippocampus. The neuronal degeneration and apoptosis in the cortex and hippocampus were further significantly attenuated by Honokiol treatment. In addition, the expression of cell cycle-related proteins, including cyclin D1, CDK4, pRb and E2F1, was significantly increased and endogenous cell cycle inhibitor p27 was markedly decreased at different time points after TBI. And these changes were significantly reversed by post-injury Honokiol treatment. Furthermore, the expression of some of the key cell cycle proteins such as cyclin D1 and E2F1 and the associated apoptosis in neurons were both remarkably attenuated by Honokiol treatment. These results show that delayed intravenous administration of Honokiol could effectively improve the functional recovery and attenuate the neuronal cell death, which is probably, at least in part, attributed to its role as a cell cycle inhibitior. This might give clues to developing attractive therapies for future clinical trials. PMID:24973706

  7. Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice.

    PubMed

    Clausen, Fredrik; Hånell, Anders; Björk, Maria; Hillered, Lars; Mir, Anis K; Gram, Hermann; Marklund, Niklas

    2009-08-01

    Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1betain vitro. IL-1beta neutralization attenuated the CCI-induced cortical and hippocampal microglial activation (P < 0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1beta neutralization (P < 0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain-injured animals, IL-1beta neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL-1beta is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI. PMID:19614750

  8. Tome Improvement.

    ERIC Educational Resources Information Center

    Careless, James

    1994-01-01

    College catalogs can be made less costly by various techniques such as using inexpensive paper, keeping as much of the production as possible in-house, minimizing photographs and color, and printing separate catalogs for different divisions. Catalogs can be improved by providing greater visual appeal and ease of use. (MSE)

  9. Performance Improvement.

    ERIC Educational Resources Information Center

    1996

    This document contains four papers presented at a symposium on performance improvement moderated by Edward Schorer at the 1996 conference of the Academy of Human Resource Development (AHRD) "The Organizational Ecology of Ethical Problems: International Case Studies in the Light of HPT [Human Performance Technology]" (Peter J. Dean, Laurence…

  10. Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

    PubMed Central

    Figueroa, Johnny D.; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I.; Walker, Robert L.; Miranda, Jorge D.

    2012-01-01

    Abstract Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  11. An Intensive Locomotor Training Paradigm Improves Neuropathic Pain following Spinal Cord Compression Injury in Rats.

    PubMed

    Dugan, Elizabeth A; Sagen, Jacqueline

    2015-05-01

    Spinal cord injury (SCI) is often associated with both locomotor deficits and sensory dysfunction, including debilitating neuropathic pain. Unfortunately, current conventional pharmacological, physiological, or psychological treatments provide only marginal relief for more than two-thirds of patients, highlighting the need for improved treatment options. Locomotor training is often prescribed as an adjunct therapy for peripheral neuropathic pain but is rarely used to treat central neuropathic pain. The goal of this study was to evaluate the potential anti-nociceptive benefits of intensive locomotor training (ILT) on neuropathic pain consequent to traumatic SCI. Using a rodent SCI model for central neuropathic pain, ILT was initiated either 5 d after injury prior to development of neuropathic pain symptoms (the "prevention" group) or delayed until pain symptoms fully developed (∼3 weeks post-injury, the "reversal" group). The training protocol consisted of 5 d/week of a ramping protocol that started with 11 m/min for 5 min and increased in speed (+1 m/min/week) and time (1-4 minutes/week) to a maximum of two 20-min sessions/d at 15 m/min by the fourth week of training. ILT prevented and reversed the development of heat hyperalgesia and cold allodynia, as well as reversed developed tactile allodynia, suggesting analgesic benefits not seen with moderate levels of locomotor training. Further, the analgesic benefits of ILT persisted for several weeks once training had been stopped. The unique ability of an ILT protocol to produce robust and sustained anti-nociceptive effects, as assessed by three distinct outcome measures for below-level SCI neuropathic pain, suggests that this adjunct therapeutic approach has great promise in a comprehensive treatment strategy for SCI pain. PMID:25539034

  12. Combination of Eccentric Exercise and Neuromuscular Electrical Stimulation to Improve Quadriceps Function Post-ACL Reconstruction

    PubMed Central

    Lepley, Lindsey K.; Wojtys, Edward M.; Palmieri-Smith, Riann M.

    2014-01-01

    Background Neuromuscular electrical stimulation (NMES) has been shown to reduce quadriceps activation failure (QAF), and eccentric exercise has been shown lessen muscle atrophy post-ACL reconstruction. Given that these are two critical components of quadriceps strength, intervention combining these therapies may be effective at reinstituting quadriceps function post-anterior cruciate ligament (ACL) reconstruction. Objectives To evaluate the effectiveness of a combined NMES and eccentric exercise intervention to improve the recovery of quadriceps activation and strength post-reconstruction. Design Parallel longitudinal design. Setting Laboratory. Participants Thirty-six individuals post-injury were placed into four treatment groups (N&E, NMES and eccentrics; E-only, eccentrics only; N-only, NMES-only; STND, standard of care) and ten healthy controls participated. Intervention N&E and N-only received the NMES protocol 2x per week for the first six weeks post-reconstruction. N&E and E-only received the eccentric exercise protocol 2x per week beginning six weeks post-reconstruction. Main outcome measure Quadriceps activation was assessed via the superimposed burst technique and quantified via the central activation ratio. Quadriceps strength was assessed via maximal voluntary isomeric contractions (Nm/kg). Data was gathered on three occasions: pre-operative, 12-weeks-post-surgery and at return-to-play. Results No differences in pre-operative measures existed (P>0.05). E-only recovered quadriceps activation better than N-only or STND (P<0.05). N&E and E-only recovered strength better than N-only or the STND (P<0.05) and had strength values that were similar to healthy individuals at return-to-play (P>0.05). Conclusion Eccentric exercise was capable of restoring levels of quadriceps activation and strength that were similar to those of healthy adults and better than NMES alone. PMID:25819154

  13. Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats.

    PubMed

    Figueroa, Johnny D; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I; Walker, Robert L; Miranda, Jorge D; Leon, Marino De

    2012-02-10

    Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  14. D-Cycloserine improves functional outcome after traumatic brain injury with wide therapeutic window

    SciTech Connect

    Adeleye, A.; Biegon, A.; Adeleye, A.; Shohami, E.; Nachman, D.; Alexandrovich, A.; Trembovler, V.; Yaka, R.; Shoshan, Y.; Dhawan, J.; Biegon, A.

    2009-12-01

    It has been long thought that hyperactivation of N-methyl-D-aspartate (NMDA) receptors underlies neurological decline after traumatic brain injury. However, all clinical trials with NMDA receptor antagonists failed. Since NMDA receptors are down-regulated from 4 h to 2 weeks after brain injury, activation at 24 h, rather than inhibition, of these receptors, was previously shown to be beneficial in mice. Here, we tested the therapeutic window, dose regimen and mechanism of action of the NMDA receptor partial agonist d-cycloserine (DCS) in traumatic brain injury. Male mice were subjected to trauma using a weight-drop model, and administered 10 mg/kg (i.p.) DCS or vehicle once (8, 16, 24, or 72 h) twice (24 and 48 h) or three times (24, 48 and 72 h). Functional recovery was assessed for up to 60 days, using a Neurological Severity Score that measures neurobehavioral parameters. In all groups in which treatment was begun at 24 or 72 h neurobehavioral function was significantly better than in the vehicle-treated groups. Additional doses, on days 2 and 3 did not further improve recovery. Mice treated at 8 h or 16 h post injury did not differ from the vehicle-treated controls. Co-administration of the NMDA receptor antagonist MK-801 completely blocked the protective effect of DCS given at 24 h. Infarct volume measured by 2,3,5-triphenyltetrazolium chloride staining at 48 h or by cresyl violet at 28 days was not affected by DCS treatment. Since DCS is used clinically for other indications, the present study offers a novel approach for treating human traumatic brain injury with a therapeutic window of at least 24 h.

  15. Failure of Intravenous or Intracardiac Delivery of Mesenchymal Stromal Cells to Improve Outcomes after Focal Traumatic Brain Injury in the Female Rat

    PubMed Central

    Turtzo, L. Christine; Budde, Matthew D.; Dean, Dana D.; Gold, Eric M.; Lewis, Bobbi K.; Janes, Lindsay; Lescher, Jacob; Coppola, Tiziana; Yarnell, Angela; Grunberg, Neil E.; Frank, Joseph A.

    2015-01-01

    Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected dose) were found within 3 days of last dosage at the site of injury after either delivery route, with no mesenchymal stromal cells being detectable in brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model. PMID:25946089

  16. Improved professionalism

    SciTech Connect

    Not Available

    1990-03-01

    The availability of good technology does not automatically produce profit (or comparable goals). The necessary bridge between the two is how professionally the technology is used. Many people believe that the general level of professionalism must be elevated if we are to improve the health of the petroleum industry. The petroleum industry is not unique in this regard. This paper discusses professionalism issues from current and historical perspectives, then proposes concrete actions for industry, educators, and SPE to consider.

  17. Improving Photosynthesis

    PubMed Central

    Evans, John R.

    2013-01-01

    Photosynthesis is the basis of plant growth, and improving photosynthesis can contribute toward greater food security in the coming decades as world population increases. Multiple targets have been identified that could be manipulated to increase crop photosynthesis. The most important target is Rubisco because it catalyses both carboxylation and oxygenation reactions and the majority of responses of photosynthesis to light, CO2, and temperature are reflected in its kinetic properties. Oxygenase activity can be reduced either by concentrating CO2 around Rubisco or by modifying the kinetic properties of Rubisco. The C4 photosynthetic pathway is a CO2-concentrating mechanism that generally enables C4 plants to achieve greater efficiency in their use of light, nitrogen, and water than C3 plants. To capitalize on these advantages, attempts have been made to engineer the C4 pathway into C3 rice (Oryza sativa). A simpler approach is to transfer bicarbonate transporters from cyanobacteria into chloroplasts and prevent CO2 leakage. Recent technological breakthroughs now allow higher plant Rubisco to be engineered and assembled successfully in planta. Novel amino acid sequences can be introduced that have been impossible to reach via normal evolution, potentially enlarging the range of kinetic properties and breaking free from the constraints associated with covariation that have been observed between certain kinetic parameters. Capturing the promise of improved photosynthesis in greater yield potential will require continued efforts to improve carbon allocation within the plant as well as to maintain grain quality and resistance to disease and lodging. PMID:23812345

  18. Improving photosynthesis.

    PubMed

    Evans, John R

    2013-08-01

    Photosynthesis is the basis of plant growth, and improving photosynthesis can contribute toward greater food security in the coming decades as world population increases. Multiple targets have been identified that could be manipulated to increase crop photosynthesis. The most important target is Rubisco because it catalyses both carboxylation and oxygenation reactions and the majority of responses of photosynthesis to light, CO₂, and temperature are reflected in its kinetic properties. Oxygenase activity can be reduced either by concentrating CO₂ around Rubisco or by modifying the kinetic properties of Rubisco. The C₄ photosynthetic pathway is a CO₂-concentrating mechanism that generally enables C₄ plants to achieve greater efficiency in their use of light, nitrogen, and water than C₃ plants. To capitalize on these advantages, attempts have been made to engineer the C₄ pathway into C₃ rice (Oryza sativa). A simpler approach is to transfer bicarbonate transporters from cyanobacteria into chloroplasts and prevent CO₂ leakage. Recent technological breakthroughs now allow higher plant Rubisco to be engineered and assembled successfully in planta. Novel amino acid sequences can be introduced that have been impossible to reach via normal evolution, potentially enlarging the range of kinetic properties and breaking free from the constraints associated with covariation that have been observed between certain kinetic parameters. Capturing the promise of improved photosynthesis in greater yield potential will require continued efforts to improve carbon allocation within the plant as well as to maintain grain quality and resistance to disease and lodging. PMID:23812345

  19. NAAG peptidase inhibitor improves motor function and reduces cognitive dysfunction in a model of TBI with secondary hypoxia.

    PubMed

    Gurkoff, Gene G; Feng, Jun-Feng; Van, Ken C; Izadi, Ali; Ghiasvand, Rahil; Shahlaie, Kiarash; Song, Minsoo; Lowe, David A; Zhou, Jia; Lyeth, Bruce G

    2013-06-17

    Immediately following traumatic brain injury (TBI) and TBI with hypoxia, there is a rapid and pathophysiological increase in extracellular glutamate, subsequent neuronal damage and ultimately diminished motor and cognitive function. N-acetyl-aspartyl glutamate (NAAG), a prevalent neuropeptide in the CNS, is co-released with glutamate, binds to the presynaptic group II metabotropic glutamate receptor subtype 3 (mGluR3) and suppresses glutamate release. However, the catalytic enzyme glutamate carboxypeptidase II (GCP II) rapidly hydrolyzes NAAG into NAA and glutamate. Inhibition of the GCP II enzyme with NAAG peptidase inhibitors reduces the concentration of glutamate both by increasing the duration of NAAG activity on mGluR3 and by reducing degradation into NAA and glutamate resulting in reduced cell death in models of TBI and TBI with hypoxia. In the following study, rats were administered the NAAG peptidase inhibitor PGI-02776 (10mg/kg) 30 min following TBI combined with a hypoxic second insult. Over the two weeks following injury, PGI-02776-treated rats had significantly improved motor function as measured by increased duration on the rota-rod and a trend toward improved performance on the beam walk. Furthermore, two weeks post-injury, PGI-02776-treated animals had a significant decrease in latency to find the target platform in the Morris water maze as compared to vehicle-treated animals. These findings demonstrate that the application of NAAG peptidase inhibitors can reduce the deleterious motor and cognitive effects of TBI combined with a second hypoxic insult in the weeks following injury. PMID:23562458

  20. Intravenous Infusion of Magnesium Chloride Improves Epicenter Blood Flow during the Acute Stage of Contusive Spinal Cord Injury in Rats

    PubMed Central

    Muradov, Johongir M.

    2013-01-01

    Abstract Vasospasm, hemorrhage, and loss of microvessels at the site of contusive or compressive spinal cord injury lead to infarction and initiate secondary degeneration. Here, we used intravenous injection of endothelial-binding lectin followed by histology to show that the number of perfused microvessels at the injury site is decreased by 80–90% as early as 20 min following a moderate T9 contusion in adult female rats. Hemorrhage within the spinal cord also was maximal at 20 min, consistent with its vasoconstrictive actions in the central nervous system (CNS). Microvascular blood flow recovered to up to 50% of normal volume in the injury penumbra by 6 h, but not at the epicenter. A comparison with an endothelial cell marker suggested that many microvessels fail to be reperfused up to 48 h post-injury. The ischemia was probably caused by vasospasm of vessels penetrating the parenchyma, because repeated Doppler measurements over the spinal cord showed a doubling of total blood flow over the first 12 h. Moreover, intravenous infusion of magnesium chloride, used clinically to treat CNS vasospasm, greatly improved the number of perfused microvessels at 24 and 48 h. The magnesium treatment seemed safe as it did not increase hemorrhage, despite the improved parenchymal blood flow. However, the treatment did not reduce acute microvessel, motor neuron or oligodendrocyte loss, and when infused for 7 days did not affect functional recovery or spared epicenter white matter over a 4 week period. These data suggest that microvascular blood flow can be restored with a clinically relevant treatment following spinal cord injury. PMID:23302047

  1. Improved aethalometer

    DOEpatents

    Hansen, A.D.

    1988-01-25

    An improved aethalometer having a single light source and a single light detector and two light paths from the light source to the light detector. A quartz fiber filter is inserted in the device, the filter having a collection area in one light path and a reference area in the other light path. A gas flow path through the aethalometer housing allows ambient air to flow through the collection area of the filter so that aerosol particles can be collected on the filter. A rotating disk with an opening therethrough allows light for the light source to pass alternately through the two light paths. The voltage output of the detector is applied to a VCO and the VCO pulses for light transmission separately through the two light paths, are counted and compared to determine the absorption coefficient of the collected aerosol particles. 5 figs.

  2. Exercise-induced improvement in cognitive performance after traumatic brain-injury in rats is dependent on BDNF Activation

    PubMed Central

    Griesbach, Grace Sophia; Hovda, David Allen; Gomez-Pinilla, Fernando

    2009-01-01

    We have previously shown that voluntary exercise upregulates brain-derived neurotrophic factor (BDNF) within the hippocampus and is associated with an enhancement of cognitive recovery after a lateral fluid-percussion injury (FPI). In order to determine if BDNF is critical to this effect we used an immunoadhesin chimera (TrkB-IgG) that inactivates free BDNF. This BDNF inhibitor was administered to adult male rats two weeks after they had received a mild fluid percussion injury (FPI) or sham surgery. These animals were then housed with or without access to a running wheel (RW) from post-injury-day (PID) 14 to 20. On PID 21, rats were tested for spatial learning in a Morris Water Maze. Results showed that exercise counteracted the cognitive deficits associated with the injury. However this exercise-induced cognitive improvement was attenuated in the FPI-RW rats that were treated with TrkB-IgG. Molecules important for synaptic plasticity and learning were measured in a separate group of rats that were sacrificed immediately after exercise (PID 21). Western blot analyses showed that exercise increased the mature form of BDNF, synapsin I and cyclic-AMP response-element-binding protein (CREB) in the vehicle treated Sham-RW group. However, only the mature form of BDNF and CREB were increased in the vehicle treated FPI-RW group. Blocking BDNF (pre administration of TrkB-IgG) greatly reduced the molecular effects of exercise in that exercise-induced increases of BDNF, synapsin I and CREB were not observed. These studies provide evidence that BDNF has a major role in exercise's cognitive effects in traumatically injured brain. PMID:19555673

  3. Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.

    PubMed

    Schober, Michelle E; Requena, Daniela F; Abdullah, Osama M; Casper, T Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R

    2016-02-15

    Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI. PMID:26247583

  4. IL-10 Accelerates Re-Endothelialization and Inhibits Post-Injury Intimal Hyperplasia following Carotid Artery Denudation

    PubMed Central

    Verma, Suresh K.; Garikipati, Venkata Naga Srikanth; Krishnamurthy, Prasanna; Khan, Mohsin; Thorne, Tina; Qin, Gangjian; Losordo, Douglas W.; Kishore, Raj

    2016-01-01

    The role of inflammation on atherosclerosis and restenosis is well established. Restenosis is thought to be a complex response to injury, which includes early thrombus formation, acute inflammation and neo-intimal growth. Inflammatory cells are likely contributors in the host response to vascular injury, via cytokines and chemokines secretion, including TNF-alpha (TNF). We have previously shown that IL-10 inhibits TNF and other inflammatory mediators produced in response to cardiovascular injuries. The specific effect of IL-10 on endothelial cell (ECs) biology is not well elucidated. Here we report that in a mouse model of carotid denudation, IL-10 knock-out mice (IL-10KO) displayed significantly delayed Re-endothelialization and enhanced neo-intimal growth compared to their WT counterparts. Exogenous recombinant IL-10 treatment dramatically blunted the neo-intimal thickening while significantly accelerating the recovery of the injured endothelium in WT mice. In vitro, IL-10 inhibited negative effects of TNF on ECs proliferation, ECs cell cycle, ECs-monocyte adhesion and ECs apoptosis. Furthermore, IL-10 treatment attenuated TNF-induced smooth muscle cells proliferation. Our data suggest that IL-10 differentially regulate endothelial and vascular smooth cells proliferation and function and thus inhibits neo-intimal hyperplasia. Thus, these results may provide insights necessary to develop new therapeutic strategies to limit vascular restenosis during percutaneous coronary intervention (PCI) in the clinics. PMID:26808574

  5. Revisiting Early Post-Injury Mortality: Are They Bleeding Because They are Dying or Dying Because They Are Bleeding?

    PubMed Central

    Morton, Alexander P.; Moore, Ernest E.; Wohlauer, Max V.; Lo, Karen; Silliman, Chris C.; Burlew, Clay Cothren; Banerjee, Ani

    2014-01-01

    Background Intense debate continues in the search of the optimal ratio of blood components to deliver preemptively in the critically injured patient anticipated to require a massive transfusion. A major challenge is distinguishing patients with refractory coagulopathy versus those with overwhelming injuries who will perish irrespective of blood component administration. The hypothesis of this clinical study is that a predominant number of early deaths from hemorrhage are irretrievable despite an aggressive transfusion policy. Materials and Methods During the 7-yr period ending in December 2009, there were 772 in-hospital trauma deaths. Each of these deaths had been assigned a cause of death via concurrent review by the multi-disciplinary hospital trauma QI committee. ED deaths and patients arriving from outside facilities were excluded from this study. Results Of the 382 patients (49.5%) who died secondary to acute blood loss, (84/22.0 %) survived beyond the ED; (68/82%) were male, mean age was 31, and (30/36%) sustained blunt trauma. Cause of death was determined to be exsanguination in (63/75 %), coagulopathy in (13/15 %), metabolic failure in (5/6%), and indeterminate in (3/3.7%) patients. Conclusion These data indicate that 75% of patients who succumb to postinjury acute blood loss are bleeding because they are dying rather than dying because they are bleeding. Conversely, only 13 (2%) of hospital deaths were attributed to refractory coagulopathy. These critical facts need to be considered in designing studies to determine optimal massive transfusion protocols. PMID:23138049

  6. Schwann cell-derived Apolipoprotein D controls the dynamics of post-injury myelin recognition and degradation

    PubMed Central

    García-Mateo, Nadia; Ganfornina, Maria D.; Montero, Olimpio; Gijón, Miguel A.; Murphy, Robert C.; Sanchez, Diego

    2014-01-01

    Management of lipids, particularly signaling lipids that control neuroinflammation, is crucial for the regeneration capability of a damaged nervous system. Knowledge of pro- and anti-inflammatory signals after nervous system injury is extensive, most of them being proteins acting through well-known receptors and intracellular cascades. However, the role of lipid binding extracellular proteins able to modify the fate of lipids released after injury is not well understood. Apolipoprotein D (ApoD) is an extracellular lipid binding protein of the Lipocalin family induced upon nervous system injury. Our previous study shows that axon regeneration is delayed without ApoD, and suggests its participation in early events during Wallerian degeneration. Here we demonstrate that ApoD is expressed by myelinating and non-myelinating Schwann cells and is induced early upon nerve injury. We show that ApoD, known to bind arachidonic acid (AA), also interacts with lysophosphatidylcholine (LPC) in vitro. We use an in vivo model of nerve crush injury, a nerve explant injury model, and cultured macrophages exposed to purified myelin, to uncover that: (i) ApoD regulates denervated Schwann cell-macrophage signaling, dampening MCP1- and Tnf-dependent macrophage recruitment and activation upon injury; (ii) ApoD controls the over-expression of the phagocytosis activator Galectin-3 by infiltrated macrophages; (iii) ApoD controls the basal and injury-triggered levels of LPC and AA; (iv) ApoD modifies the dynamics of myelin-macrophage interaction, favoring the initiation of phagocytosis and promoting myelin degradation. Regulation of macrophage behavior by Schwann-derived ApoD is therefore a key mechanism conditioning nerve injury resolution. These results place ApoD as a lipid binding protein controlling the signals exchanged between glia, neurons and blood-borne cells during nerve recovery after injury, and open the possibility for a therapeutic use of ApoD as a regeneration-promoting agent. PMID:25426024

  7. N-Acetylaspartate reductions in brain injury: impact on post-injury neuroenergetics, lipid synthesis, and protein acetylation

    PubMed Central

    Moffett, John R.; Arun, Peethambaran; Ariyannur, Prasanth S.; Namboodiri, Aryan M. A.

    2013-01-01

    N-Acetylaspartate (NAA) is employed as a non-invasive marker for neuronal health using proton magnetic resonance spectroscopy (MRS). This utility is afforded by the fact that NAA is one of the most concentrated brain metabolites and that it produces the largest peak in MRS scans of the healthy human brain. NAA levels in the brain are reduced proportionately to the degree of tissue damage after traumatic brain injury (TBI) and the reductions parallel the reductions in ATP levels. Because NAA is the most concentrated acetylated metabolite in the brain, we have hypothesized that NAA acts in part as an extensive reservoir of acetate for acetyl coenzyme A synthesis. Therefore, the loss of NAA after TBI impairs acetyl coenzyme A dependent functions including energy derivation, lipid synthesis, and protein acetylation reactions in distinct ways in different cell populations. The enzymes involved in synthesizing and metabolizing NAA are predominantly expressed in neurons and oligodendrocytes, respectively, and therefore some proportion of NAA must be transferred between cell types before the acetate can be liberated, converted to acetyl coenzyme A and utilized. Studies have indicated that glucose metabolism in neurons is reduced, but that acetate metabolism in astrocytes is increased following TBI, possibly reflecting an increased role for non-glucose energy sources in response to injury. NAA can provide additional acetate for intercellular metabolite trafficking to maintain acetyl CoA levels after injury. Here we explore changes in NAA, acetate, and acetyl coenzyme A metabolism in response to brain injury. PMID:24421768

  8. High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death

    PubMed Central

    Fox, Jennifer T.; Sakamuru, Srilatha; Huang, Ruili; Teneva, Nedelina; Simmons, Steven O.; Xia, Menghang; Tice, Raymond R.; Austin, Christopher P.; Myung, Kyungjae

    2012-01-01

    Human ATAD5 is a biomarker for identifying genotoxic compounds because ATAD5 protein levels increase posttranscriptionally in response to DNA damage. We screened over 4,000 compounds with a cell-based quantitative high-throughput ATAD5-luciferase assay detecting genotoxic compounds. We identified 22 antioxidants, including resveratrol, genistein, and baicalein, that are currently used or investigated for the treatment of cardiovascular disease, type 2 diabetes, osteopenia, osteoporosis, and chronic hepatitis, as well as for antiaging. Treatment of dividing cells with these compounds induced DNA damage and resulted in cell death. Despite their genotoxic effects, resveratrol, genistein, and baicalein did not cause mutagenesis, which is a major side effect of conventional anticancer drugs. Furthermore, resveratrol and genistein killed multidrug-resistant cancer cells. We therefore propose that resveratrol, genistein, and baicalein are attractive candidates for improved chemotherapeutic agents. PMID:22431602

  9. Quality improvement techniques to improve patient satisfaction.

    PubMed

    Torres, E Joseph; Guo, Kristina L

    2004-01-01

    This paper describes several approaches for implementing quality improvement initiatives to improve patient satisfaction, which enables health-care organizations to position themselves for success in today's global and increasingly competitive environment. Specifically, measuring the views of patients, improving patient satisfaction through a community-wide effort, and using a Six Sigma program are discussed. Each of these programs can be an effective mechanism for quality improvement. A key component to quality improvement techniques involves collaborative efforts by all health-care professionals and managers as they seek to increase patient satisfaction. PMID:15552388

  10. Facilitating Mitochondrial Calcium Uptake Improves Activation-Induced Cerebral Blood Flow and Behavior after mTBI

    PubMed Central

    Murugan, Madhuvika; Santhakumar, Vijayalakshmi; Kannurpatti, Sridhar S.

    2016-01-01

    Mild to moderate traumatic brain injury (mTBI) leads to secondary neuronal loss via excitotoxic mechanisms, including mitochondrial Ca2+ overload. However, in the surviving cellular population, mitochondrial Ca2+ influx, and oxidative metabolism are diminished leading to suboptimal neuronal circuit activity and poor prognosis. Hence we tested the impact of boosting neuronal electrical activity and oxidative metabolism by facilitating mitochondrial Ca2+ uptake in a rat model of mTBI. In developing rats (P25-P26) sustaining an mTBI, we demonstrate post-traumatic changes in cerebral blood flow (CBF) in the sensorimotor cortex in response to whisker stimulation compared to sham using functional Laser Doppler Imaging (fLDI) at adulthood (P67-P73). Compared to sham, whisker stimulation-evoked positive CBF responses decreased while negative CBF responses increased in the mTBI animals. The spatiotemporal CBF changes representing underlying neuronal activity suggested profound changes to neurovascular activity after mTBI. Behavioral assessment of the same cohort of animals prior to fLDI showed that mTBI resulted in persistent contralateral sensorimotor behavioral deficit along with ipsilateral neuronal loss compared to sham. Treating mTBI rats with Kaempferol, a dietary flavonol compound that enhanced mitochondrial Ca2+ uptake, eliminated the inter-hemispheric asymmetry in the whisker stimulation-induced positive CBF responses and the ipsilateral negative CBF responses otherwise observed in the untreated and vehicle-treated mTBI animals in adulthood. Kaempferol also improved somatosensory behavioral measures compared to untreated and vehicle treated mTBI animals without augmenting post-injury neuronal loss. The results indicate that reduced mitochondrial Ca2+ uptake in the surviving populations affect post-traumatic neural activation leading to persistent behavioral deficits. Improvement in sensorimotor behavior and spatiotemporal neurovascular activity following kaempferol

  11. Baincalein alleviates early brain injury after experimental subarachnoid hemorrhage in rats: possible involvement of TLR4/NF-κB-mediated inflammatory pathway.

    PubMed

    Wang, Chun-xi; Xie, Guang-bin; Zhou, Chen-hui; Zhang, Xiang-sheng; Li, Tao; Xu, Jian-guo; Li, Ning; Ding, Ke; Hang, Chun-hua; Shi, Ji-xin; Zhou, Meng-liang

    2015-01-12

    Early brain injury (EBI) following subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes. Hence, effective therapeutic strategies targeting on EBI have recently become a major goal in the treatment of SAH patients. Baicalein is a flavonoid that has been shown to offer neuroprotection in kinds of brain injury models. This study investigated the effects of baicalein on EBI in rats following SAH. SAH was inducted in male Sprauge-Dawley rats by injection of fresh non-heparinized arterial blood into the prechiasmatic cistern. Baicalein (30 or 100 mg/kg) or vehicle were administrated 30 min after injury. Neurological deficit, brain edema, blood-brain barrier (BBB) permeability and neural cell apoptosis were assessed. To explore the further mechanisms, the change of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) signaling pathway and the levels of apoptosis associated proteins were also examined. Our study showed that treatment with baicalein (30 mg/kg) significantly improved neurological function at 24h after SAH and reduced brain edema at both 24h and 72 h after SAH. Baicalein also significantly reduced neural cell death, BBB permeability. These changes were associated with the remarkable reductions of TLR4 expression, IκB-α degradation, NF-κB translocation to nucleus, as well as the expressions of matrix metalloproteinase-9, tight junctions protein, interleukin-1β and tumor necrosis factor- ɑ. These findings suggest that baicalein may ameliorate EBI after SAH potentially via inhibition of inflammation-related pathway. PMID:25451085

  12. Making process improvement 'stick'.

    PubMed

    Studer, Quint

    2014-06-01

    To sustain gains from a process improvement initiative, healthcare organizations should: Explain to staff why a process improvement initiative is needed. Encourage leaders within the organization to champion the process improvement, and tie their evaluations to its outcomes. Ensure that both leaders and employees have the skills to help sustain the sought-after process improvements. PMID:24968631

  13. CHRONIC UCL INJURY: A MULTIMODAL APPROACH TO CORRECTING ALTERED MECHANICS AND IMPROVING HEALING IN A COLLEGE ATHLETE— A CASE REPORT

    PubMed Central

    Patrick, Rachel; McGinty, Josh; Lucado, Ann; Collier, Beth

    2016-01-01

    ABSTRACT Background Ulnar collateral ligament (UCL) tears and associated Tommy Johns surgical intervention from excessive and poor quality pitching has increased immensely—with more college and professional pitchers undergoing the surgery in 2014 alone than in the 1990s as a whole.1 Faulty mechanics developed at young ages are often well-engrained by the late adolescent years and the minimal healing ability of the largely avascular UCL often leads to delayed safe return to sport.2 Purpose The purpose of this case study was to describe an innovative, multimodal approach to conservative management of a chronic UCL injury in a college-aged baseball pitcher. This innovative approach utilizes both contractile and non-contractile dry needling to enhance soft tissue healing combined with standard conservative treatment to decrease pain and improve sport performance as measured by the Disabilities of Arm, Shoulder and Hand (DASH), Numeric Pain Report Scale (NPRS), and return to sport. Study Design Retrospective Case Report Case Description A collegiate athlete presented to an outpatient orthopedic physical therapy clinic for treatment of UCL sprain approximately six weeks post-injury and platelet-rich plasma injection. Diagnostic testing revealed chronic ligamentous microtrauma. Impairments at evaluation included proximal stabilizing strength deficits, myofascial trigger points throughout the dominant upper extremity, improper pitching form, and inability to pitch in game conditions due to severe pain. Interventions included addressing strength deficits throughout the body, dry needling, and sport-specific biomechanical training with pitching form analysis and correction. Outcomes Conventional DASH and Sport-Specific scale on the DASH and the numeric pain rating scale improved beyond both the minimally clinically important difference and minimal detectable change over the 12 week treatment3,4 At 24-week follow up, conventional DASH scores decreased from 34.20% disability

  14. Improving Your Game.

    ERIC Educational Resources Information Center

    Waggoner, Tom; Bredar, Randy

    2001-01-01

    Discusses ways a new athletic training facility can do more than just improve school sports programs. Explores the new facility's ability to increase functional and operational efficiencies, improve student academic performance, and recruit athletes. (GR)

  15. Embarking on performance improvement.

    PubMed

    Brown, Bobbi; Falk, Leslie Hough

    2014-06-01

    Healthcare organizations should approach performance improvement as a program, not a project. The program should be led by a guidance team that identifies goals, prioritizes work, and removes barriers to enable clinical improvement teams and work groups to realize performance improvements. A healthcare enterprise data warehouse can provide the initial foundation for the program analytics. Evidence-based best practices can help achieve improved outcomes and reduced costs. PMID:24968632

  16. Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

    PubMed

    Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

    2016-05-01

    Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as

  17. Improved technical specifications

    SciTech Connect

    Hoffman, D.R.

    1994-12-31

    Improved technical specifications for nuclear power plants are outlined. The objectives of this work are to improve safety, provide a clearer understanding of safety significance, and ease NRC and industry administrative burdens. Line item improvements, bases, and implementation of the specifications are discussed.

  18. Improving America's Schools Act

    NASA Technical Reports Server (NTRS)

    Cradler, John; Bridgforth, Elizabeth

    1995-01-01

    The Improving America's Schools ACT (IASA) emphasizes coherent systemic education reform, with Goals 2000 setting common standards for IASA and the recently authorized School-to-Work Program. IASA addresses the need to raise academic achievement, increase opportunities to learn, improve professional development, increase community involvement, utilize instructional applications of technology, and improve assessment, and allow more local flexibility in the use of funds.

  19. Improving College Freshman Retention

    ERIC Educational Resources Information Center

    Yu, Winnie Y.

    2012-01-01

    In recent years, access to higher education was greatly improved through public funding. This improvement is not matched by a similar increase in graduation rate. The purpose of this study is to examine what postsecondary institutions can do to improve college freshman retention. The conceptual framework was based on research on college student…

  20. Improving America's Schools.

    ERIC Educational Resources Information Center

    Joyce, Bruce R.

    This book presents an argument for school improvement and explains how it might be conducted. Three stages of evolutionary school improvement are identified and described: refinement, renovation, and redesign. It is suggested that the real task is not only innovating improvements; the real task is uniting teachers, administrators, and community…

  1. Improve Math Teaching with Incremental Improvements

    ERIC Educational Resources Information Center

    Star, Jon R.

    2016-01-01

    Past educational reforms have failed because they didn't meet teachers where they were. They expected major changes in practices that may have been unrealistic for many teachers even under ideal professional learning conditions. Instead of promoting broad scale changes, improvement may be more likely if they are composed of small yet powerful…

  2. Continual improvement plan

    NASA Technical Reports Server (NTRS)

    1994-01-01

    NASA's approach to continual improvement (CI) is a systems-oriented, agency-wide approach that builds on the past accomplishments of NASA Headquarters and its field installations and helps achieve NASA's vision, mission, and values. The NASA of the future will fully use the principles of continual improvement in every aspect of its operations. This NASA CI plan defines a systematic approach and a model for continual improvement throughout NASA, stressing systems integration and optimization. It demonstrates NASA's constancy of purpose for improvement - a consistent vision of NASA as a worldwide leader in top-quality science, technology, and management practices. The CI plan provides the rationale, structures, methods, and steps, and it defines NASA's short term (1-year) objectives for improvement. The CI plan presents the deployment strategies necessary for cascading the goals and objectives throughout the agency. It also provides guidance on implementing continual improvement with participation from top leadership and all levels of employees.

  3. How Performance Improves

    SciTech Connect

    Jerry L. Harbour; Julie L. Marble

    2005-09-01

    Countless articles and books have been written about and numerous programs have been developed to improve performance. Despite this plethora of activity on how to improve performance, we have largely failed to address the more fundamental question of how performance actually improves. To begin exploring this more basic question, we have plotted some 1,200 performance records to date and found that irrespective of venue, industry, or business, there seems to be a fundamental and repeatable set of concepts regarding how performance improves over time. Such gained insights represent both opportunities and challenges to the performance technologist. Differences in performance outcomes may, for example, be as much a function of the life cycle stage of a performance system as the efficacy of the selected improvement method itself. Accordingly, it may be more difficult to compare differing performance improvement methods than previously thought.

  4. Ergonomic Improvements for Foundries

    SciTech Connect

    Frank Peters; Patrick Patterson

    2002-06-18

    The goal of this project was to make improvements to the production systems of the steel casting industry through ergonomic improvements. Because of the wide variety of products, the wide range of product sizes, and the relatively small quantities of any particular product, manual operations remain a vital part of the production systems of the steel casting companies. Ergonomic improvements will assist the operators to more efficiently and consistently produce quality products.

  5. Improving College Teaching.

    ERIC Educational Resources Information Center

    Seldin, Peter; And Others

    This volume contains 20 papers providing practical, ready-to-use, research-based information to foster effective college teaching. Four sections group the papers under the following topics: (1) key influences on teaching quality; (2) programs to improve teaching; (3) strategies for teaching improvement; and (4) approaches to nontraditional…

  6. Improved wire chamber

    DOEpatents

    Atac, M.

    1987-05-12

    An improved gas mixture for use with proportional counter devices, such as Geiger-Mueller tubes and drift chambers. The improved gas mixture provides a stable drift velocity while eliminating wire aging caused by prior art gas mixtures. The new gas mixture is comprised of equal parts argon and ethane gas and having approximately 0.25% isopropyl alcohol vapor. 2 figs.

  7. Improvement of School Climate.

    ERIC Educational Resources Information Center

    Sierra Sands Unified School District, Ridgecrest, CA.

    THE FOLLOWING IS THE FULL TEXT OF THIS DOCUMENT: As a part of its School Improvement Program, James Monroe Junior High School planned to improve its school climate. Since the physical school environment was devoid of landscaping and did not provide places for student socialization, all interested groups (PTSA, student council, students, staff, and…

  8. Towards Whole System Improvement

    ERIC Educational Resources Information Center

    Glatter, Ron

    2012-01-01

    The relationship between academies, and school autonomy more generally, and the wider system is a crucial issue in the battle to improve school-level education. International experience indicates that emphasising choice and competition to drive improvement is not effective and that changing structures does not yield better results for students. A…

  9. Continuous Personal Improvement.

    ERIC Educational Resources Information Center

    Emiliani, M. L.

    1998-01-01

    Suggests that continuous improvement tools used in the workplace can be applied to self-improvement. Explains the use of such techniques as one-piece flow, kanban, visual controls, and total productive maintenance. Points out misapplications of these tools and describes the use of fishbone diagrams to diagnose problems. (SK)

  10. Automated Student Model Improvement

    ERIC Educational Resources Information Center

    Koedinger, Kenneth R.; McLaughlin, Elizabeth A.; Stamper, John C.

    2012-01-01

    Student modeling plays a critical role in developing and improving instruction and instructional technologies. We present a technique for automated improvement of student models that leverages the DataShop repository, crowd sourcing, and a version of the Learning Factors Analysis algorithm. We demonstrate this method on eleven educational…

  11. Improved solid aerosol generator

    DOEpatents

    Prescott, D.S.; Schober, R.K.; Beller, J.

    1988-07-19

    An improved solid aerosol generator used to produce a gas borne stream of dry, solid particles of predetermined size and concentration. The improved solid aerosol generator nebulizes a feed solution of known concentration with a flow of preheated gas and dries the resultant wet heated aerosol in a grounded, conical heating chamber, achieving high recovery and flow rates. 2 figs.

  12. Improving Disambiguation in FASIT.

    ERIC Educational Resources Information Center

    Burgin, Robert; Dillon, Martin

    1992-01-01

    Discussion of automatic indexing in information retrieval systems focuses on attempts to improve the indexing representation produced by the FASIT system. Concept selection and concept grouping are explained; improving disambiguation is discussed; and a retrieval experiment to test the effectiveness of the disambiguation using the cystic fibrosis…

  13. Improved nonlinear prediction method

    NASA Astrophysics Data System (ADS)

    Adenan, Nur Hamiza; Md Noorani, Mohd Salmi

    2014-06-01

    The analysis and prediction of time series data have been addressed by researchers. Many techniques have been developed to be applied in various areas, such as weather forecasting, financial markets and hydrological phenomena involving data that are contaminated by noise. Therefore, various techniques to improve the method have been introduced to analyze and predict time series data. In respect of the importance of analysis and the accuracy of the prediction result, a study was undertaken to test the effectiveness of the improved nonlinear prediction method for data that contain noise. The improved nonlinear prediction method involves the formation of composite serial data based on the successive differences of the time series. Then, the phase space reconstruction was performed on the composite data (one-dimensional) to reconstruct a number of space dimensions. Finally the local linear approximation method was employed to make a prediction based on the phase space. This improved method was tested with data series Logistics that contain 0%, 5%, 10%, 20% and 30% of noise. The results show that by using the improved method, the predictions were found to be in close agreement with the observed ones. The correlation coefficient was close to one when the improved method was applied on data with up to 10% noise. Thus, an improvement to analyze data with noise without involving any noise reduction method was introduced to predict the time series data.

  14. Synthesis of novel flavone derivatives possessing substituted benzamides and their biological evaluation against human cancer cells.

    PubMed

    Yun, Bo Hee; Lee, Young Hun; Park, Kyung Tae; Jung, Su Jin; Lee, Yong Sup

    2016-09-01

    Baicalein is a well-known flavone derivative that possesses diverse biological properties, such as anticancer, antioxidant and anti-inflammatory activities. Numerous baicalein derivatives, including 5,6,7-trimethoxyflavone, have been synthesized with the aim of enhancing its inherent biological activities. In the present work, new flavones, possessing an N-aroylamine-substituent on the B-ring, were synthesized to improve the cytotoxicity of baicalein and 5,6,7-trimethoxyflavone against human cancer cell lines. The majority of the flavones synthesized exhibited greater cytotoxicity than baicalein and 5,6,7-trimethoxyflavone against HepG2 and MCF-7 cells. Among them, compounds 5n, possessing a 3-methoxybenzoylamino group, exhibited great cytotoxic effects on HepG2 (GI50=7.06μM) and MCF-7 (GI50=7.67μM) cells. In contrast, N-aroylamine-substituted 5-hydroxy-6,7-dimethoxyflavone derivatives showed greater cytotoxicity against MCF-7 than HepG2 cells, indicating that the replacement of a 5-methoxy group on the A-ring with a 5-hydroxy group has a marked influence on the cytotoxicity profile. PMID:27503682

  15. Improving engineering effectiveness

    NASA Technical Reports Server (NTRS)

    Fiero, J. D.

    1985-01-01

    Methodologies to improve engineering productivity were investigated. The rocky road to improving engineering effectiveness is reviewed utilizing a specific semiconductor engineering organization as a case study. The organization had a performance problem regarding new product introductions. With the help of this consultant as a change agent the engineering team used a systems approach to through variables that were effecting their output significantly. Critical factors for improving this engineering organization's effectiveness and the roles/responsibilities of management, the individual engineers and the internal consultant are discussed.

  16. Improved Skin Friction Interferometer

    NASA Technical Reports Server (NTRS)

    Westphal, R. V.; Bachalo, W. D.; Houser, M. H.

    1986-01-01

    An improved system for measuring aerodynamic skin friction which uses a dual-laser-beam oil-film interferometer was developed. Improvements in the optical hardware provided equal signal characteristics for each beam and reduced the cost and complexity of the system by replacing polarization rotation by a mirrored prism for separation of the two signals. An automated, objective, data-reduction procedure was implemented to eliminate tedious manual manipulation of the interferometry data records. The present system was intended for use in two-dimensional, incompressible flows over a smooth, level surface without pressure gradient, but the improvements discussed are not limited to this application.

  17. Observatory Improvements for SOFIA

    NASA Technical Reports Server (NTRS)

    Peralta, Robert A.; Jensen, Stephen C.

    2012-01-01

    The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a joint project between NASA and Deutsches Zentrum fuer Luft- und Raumfahrt (DLR), the German Space Agency. SOFIA is based in a Boeing 747 SP and flown in the stratosphere to observe infrared wavelengths unobservable from the ground. In 2007 Dryden Flight Research Center (DFRC) inherited and began work on improving the plane and its telescope. The improvements continue today with upgrading the plane and improving the telescope. The Observatory Verification and Validation (V&V) process is to ensure that the observatory is where the program says it is. The Telescope Status Display (TSD) will provide any information from the on board network to monitors that will display the requested information. In order to assess risks to the program, one must work through the various threats associate with that risk. Once all the risks are closed the program can work towards improving the observatory.

  18. Improving Early School Success.

    ERIC Educational Resources Information Center

    Pianta, Robert C.; La Paro, Karen

    2003-01-01

    Several large-scale research efforts imply that improving instructional quality rather than assessing student readiness is a better way to promote student performance in the early grades. (Contains 12 references.) (Author/MLF)

  19. Improving a Good Thing.

    ERIC Educational Resources Information Center

    School Planning & Management, 2002

    2002-01-01

    Summarizes research from the Florida Solar Energy Center at the University of Central Florida which demonstrated that improvements in portable classrooms involving illumination and ventilation saved Florida 40 percent in electric use and $6 million in energy costs. (EV)

  20. Home Improvements Prevent Falls

    MedlinePlus

    ... on. Feature: Falls and Older Adults Home Improvements Prevent Falls Past Issues / Winter 2014 Table of Contents ... or home modification programs to help older people prevent falls. Check with your local health department, senior ...

  1. Improving Family Communications

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Listen Español Text Size Email Print Share Improving Family Communications Page Content Article Body How can I ...

  2. Improved Atomizer Resists Clogging

    NASA Technical Reports Server (NTRS)

    Dea, J. Y.

    1983-01-01

    Improved constant-output atomizer has conical orifice that permits air to sweep out all liquid thoroughly and prevent any buildup of liquid or dissolved solids. Capillary groove guides liquid to gas jet. Simple new design eliminates clogging.

  3. Productivity Improvement and Professionalism.

    ERIC Educational Resources Information Center

    Young, Benjamin I., Jr.

    1980-01-01

    The author presents a developmental model designed to help productivity improvement and professional development become an integral part of the natural everyday work experience. Examples and a summarized model are included. (CT)

  4. Proposal Improvements That Work

    NASA Technical Reports Server (NTRS)

    Dunn, F.

    1998-01-01

    Rocketdyne Propulsion and Power, an operating location of Boeing in Canoga Park, California is under contract with NASA's Marshall Space Flight Center (MSFC) in Huntsville, Alabama for design, development, production, and mission support of Space Shuttle Main Engines (SSMEs). The contract was restructured in 1996 to emphasize a mission contracting environment under which Rocketdyne supports the Space Transportation System launch manifest of seven flights a year without the need for a detailed list of contract deliverables such as nozzles, turbopumps, and combustion devices. This contract structure is in line with the overall Space Shuttle program goals established by the NASA to fly safely, meet the flight manifest, and reduce cost. Rocketdyne's Contracts, Pricing, and Estimating team has worked for the past several years with representatives from MSFC, the local Defense Contract Management Command, and the DCAA to improve the quality of cost proposals to MSFC for contract changes on the SSME. The contract changes on the program result primarily from engineering change proposals for product enhancements to improve safety, maintainability, or operability in the space environment. This continuous improvement team effort has been successful in improving proposal quality, reducing cycle time, and reducing cost. Some of the principal lessons learned are highlighted here to show how proposal improvements can be implemented to enhance customer satisfaction and ensure cost proposals can be evaluated easily by external customers.

  5. Mesh Quality Improvement Toolkit

    Energy Science and Technology Software Center (ESTSC)

    2002-11-15

    MESQUITE is a linkable software library to be used by simulation and mesh generation tools to improve the quality of meshes. Mesh quality is improved by node movement and/or local topological modifications. Various aspects of mesh quality such as smoothness, element shape, size, and orientation are controlled by choosing the appropriate mesh qualtiy metric, and objective function tempate, and a numerical optimization solver to optimize the quality of meshes, MESQUITE uses the TSTT mesh interfacemore » specification to provide an interoperable toolkit that can be used by applications which adopt the standard. A flexible code design makes it easy for meshing researchers to add additional mesh quality metrics, templates, and solvers to develop new quality improvement algorithms by making use of the MESQUITE infrastructure.« less

  6. Improved NASTRAN plotting

    NASA Technical Reports Server (NTRS)

    Chan, Gordon C.

    1991-01-01

    The new 1991 COSMIC/NASTRAN version, compatible with the older versions, tries to remove some old constraints and make it easier to extract information from the plot file. It also includes some useful improvements and new enhancements. New features available in the 1991 version are described. They include a new PLT1 tape with simplified ASCII plot commands and short records, combined hidden and shrunk plot, an x-y-z coordinate system on all structural plots, element offset plot, improved character size control, improved FIND and NOFIND logic, a new NASPLOT post-prosessor to perform screen plotting or generate PostScript files, and a BASIC/NASTPLOT program for PC.

  7. Novel improved PMR polyimides

    NASA Technical Reports Server (NTRS)

    Pater, R. H.

    1981-01-01

    A series of N-phenylnadimide (PN) modified PMR polyimide composites reinforced with graphite fibers was investigated. The improved flow matrix resins consist of N-phenylnadimide (PN), monomenthyl ester of 5-norbornene-2, 3-dicarboxylic acid (NE), dimethyl ester of 3,3, 4,4-benzophenonetetracarboxylic acide (BTDE), and 4,4 methylenedianiline (MDA). Five modified PMR resin systems were formulated by the addition of 4 to 20 mole percent N-phenylnadimide to the standard PMR-15 composition. These formulations and the control PMR resin were evaluated for rheological characteristics. The initial thermal and mechanical properties of the PN modified PMR and the control PMR/Celion 6000 composites were determined. The results show that the addition of N-phenylnadimide to PMR-15 significantly improved the resin flow characteristics without sacrificing the composites properties. Concentrations of 4 and 9 mole percent PN appear to improve the thermoxidative stability of PMR composites.

  8. Abuse Tolerance Improvements

    SciTech Connect

    Orendorff, Christopher J.; Nagasubramanian, Ganesan; Fenton, Kyle R.; Allcorn, Eric

    2015-10-01

    As lithium-ion battery technologies mature, the size and energy of these systems continues to increase (> 50 kWh for EVs); making safety and reliability of these high energy systems increasingly important. While most material advances for lithium-ion chemistries are directed toward improving cell performance (capacity, energy, cycle life, etc.), there are a variety of materials advancements that can be made to improve lithium-ion battery safety. Issues including energetic thermal runaway, electrolyte decomposition and flammability, anode SEI stability, and cell-level abuse tolerance continue to be critical safety concerns. This report highlights work with our collaborators to develop advanced materials to improve lithium-ion battery safety and abuse tolerance and to perform cell-level characterization of new materials.

  9. Improved limited discrepancy search

    SciTech Connect

    Korf, R.E.

    1996-12-31

    We present an improvement to Harvey and Ginsberg`s limited discrepancy search algorithm, which eliminates much of the redundancy in the original, by generating each path from the root to the maximum search depth only once. For a complete binary tree of depth d this reduces the asymptotic complexity from O(d+2/2 2{sup d}) to O(2{sup d}). The savings is much less in a partial tree search, or in a heavily pruned tree. The overhead of the improved algorithm on a complete binary tree is only a factor of b/(b - 1) compared to depth-first search. While this constant factor is greater on a heavily pruned tree, this improvement makes limited discrepancy search a viable alternative to depth-first search, whenever the entire tree may not be searched. Finally, we present both positive and negative empirical results on the utility of limited discrepancy search, for the problem of number partitioning.

  10. [Improving emergency department organisation].

    PubMed

    Yordanov, Youri; Beltramini, Alexandra; Debuc, Erwan; Pateron, Dominique

    2015-01-01

    Emergency departments use has been constantly increasing over the world. Overcrowding is defined as a situation which compromises patient safety because of delayed cares. This situation is often reached. Emergency departments have to continuously improve their organization to be able to ensure the same quality of care to a higher number of patients. Thus a good organization is essential: it doesn't always avoid overcrowding. The rest of the hospital has to be involved in this process to ensure efficiency. We examine the various interventions and procedures that can be found in medical literature for improving patients flow and management in emergency departments. PMID:25842427

  11. Improving designer productivity

    NASA Technical Reports Server (NTRS)

    Hill, Gary C.

    1992-01-01

    Designer and design team productivity improves with skill, experience, and the tools available. The design process involves numerous trials and errors, analyses, refinements, and addition of details. Computerized tools have greatly speeded the analysis, and now new theories and methods, emerging under the label Artificial Intelligence (AI), are being used to automate skill and experience. These tools improve designer productivity by capturing experience, emulating recognized skillful designers, and making the essence of complex programs easier to grasp. This paper outlines the aircraft design process in today's technology and business climate, presenting some of the challenges ahead and some of the promising AI methods for meeting those challenges.

  12. Strategies for Improving Access.

    ERIC Educational Resources Information Center

    Hore, Terry; Barwood, Bryan

    1989-01-01

    The development of the varied strategies that have been introduced in order to improve access for disadvantaged groups at Monash University is discussed. The Junior University Programme, the Monash Orientation Scheme for Aborigines, the Mature Age Special Admission Scheme, Special Entry Scheme, and the Schools Link Programme are described. (MLW)

  13. Improving: Services for Children

    ERIC Educational Resources Information Center

    Her Majesty's Inspectorate of Education, 2008

    2008-01-01

    This guide to self-evaluation and improvement builds upon the advice given in the publication "A Guide to Evaluating Services for Children and Young People Using Quality Indicators" (HMIE, 2006) (A summary of the quality indicators is reproduced in Appendix I). Local authorities, agencies and professionals who have responsibilities for providing…

  14. Improving Enterprise in Education

    ERIC Educational Resources Information Center

    Her Majesty's Inspectorate of Education, 2008

    2008-01-01

    "Improving Enterprise in Education" evaluates enterprise in education using a framework developed in direct response to a recommendation in "Determined to Succeed." The framework comprised quality indicators, chosen from the second edition of "How good is our school?" to focus on key features of enterprise in education: learners' experiences,…

  15. Improved Access to Learning.

    ERIC Educational Resources Information Center

    Miller, Sandra; Simkins, Michael

    2002-01-01

    Describes efforts by principal of the Willow Elementary School in the Charter Oak Unified School District (California) to provide students with technology-enhanced access to information and learning resources to improve reading and mathematics skills. Includes list of the Web addresses for the skills software used at the school. (PKP)

  16. Mutations in Lettuce Improvement.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mutations can make profound impact on the evolution and improvement of a self-pollinated crop such as lettuce. Since it is nontransgenic, mutation breeding is more acceptable to consumers. Combined with genomic advances in new technologies like TILLING, mutagenesis is becoming an even more powerfu...

  17. Improving Your Lecturing. Revised.

    ERIC Educational Resources Information Center

    Diamond, Nancy A.; And Others

    A guide for faculty who want to improve their lecturing skills is presented. After identifying advantages and disadvantages of the lecture method, suggestions are offered for effective lecture preparation, with attention to organizing the body of the lecture, and beginning and closing the lecture. Vocal aspects of lecture delivery are addressed,…

  18. Improving School Climate.

    ERIC Educational Resources Information Center

    Kelley, Edgar A.; And Others

    1989-01-01

    School climate improvements rely either on changes in the school's culture or changes in perceptions of the climate held by the school's employees and clients. To maintain and develop a culture that is supportive of school effectiveness, it is important to monitor the influence of the school's climate on student outcomes. The National Association…

  19. Improving boiler efficiency

    SciTech Connect

    Yost, L.

    1982-06-24

    Boilers and burners are designed to operate most efficiently at, or near, full load. This fact seems to indicate that on/off operation is more efficient; however, standby losses must be considered. This article examines various types of industrial boiler heat losses that reduce efficiency and discusses methods for improving operation.

  20. Improved Regression Calibration

    ERIC Educational Resources Information Center

    Skrondal, Anders; Kuha, Jouni

    2012-01-01

    The likelihood for generalized linear models with covariate measurement error cannot in general be expressed in closed form, which makes maximum likelihood estimation taxing. A popular alternative is regression calibration which is computationally efficient at the cost of inconsistent estimation. We propose an improved regression calibration…

  1. Improvements in agricultural sciences

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This editorial provides insight on investigations regarding advancements in agri-food quality and testing of eco-friendly organic farming methodologies. The discussion elaborates on the advantages of recent farming techniques and their impact on improved crop yield, crop quality, and minimization of...

  2. Improve Your Balance

    MedlinePlus

    ... My Go4Life Get Free Stuff Be a Partner Balance Improve Your Balance Each year, more than 2 million older Americans ... types of exercise — endurance , strength , balance, and flexibility . Balance Stand on One Foot Heel-to-Toe Walk ...

  3. MCNP Progress & Performance Improvements

    SciTech Connect

    Brown, Forrest B.; Bull, Jeffrey S.; Rising, Michael Evan

    2015-04-14

    Twenty-eight slides give information about the work of the US DOE/NNSA Nuclear Criticality Safety Program on MCNP6 under the following headings: MCNP6.1.1 Release, with ENDF/B-VII.1; Verification/Validation; User Support & Training; Performance Improvements; and Work in Progress. Whisper methodology will be incorporated into the code, and run speed should be increased.

  4. Improving Alaryngeal Speech Intelligibility.

    ERIC Educational Resources Information Center

    Christensen, John M.; Dwyer, Patricia E.

    1990-01-01

    Laryngectomized patients using esophageal speech or an electronic artificial larynx have difficulty producing correct voicing contrasts between homorganic consonants. This paper describes a therapy technique that emphasizes "pushing harder" on voiceless consonants to improve alaryngeal speech intelligibility and proposes focusing on the production…

  5. Improved traveling wave tubes

    NASA Technical Reports Server (NTRS)

    Buck, E.

    1980-01-01

    After a brief description of how a typical TWT works, multi-stage depressed collectors (MDC) are discussed. A quick method for computing the expected efficiency of a well engineered TWT is outlined to aid in estimating power supply needs. Applications of improved TWTs and a new power supply are suggested.

  6. Improved vortex reactor system

    DOEpatents

    Diebold, James P.; Scahill, John W.

    1995-01-01

    An improved vortex reactor system for affecting fast pyrolysis of biomass and Refuse Derived Fuel (RDF) feed materials comprising: a vortex reactor having its axis vertically disposed in relation to a jet of a horizontally disposed steam ejector that impels feed materials from a feeder and solids from a recycle loop along with a motive gas into a top part of said reactor.

  7. Improving Management Education

    ERIC Educational Resources Information Center

    Emiliani, M. L.

    2006-01-01

    Purpose: To present an outsider's view of how management education can be significantly improved. Design/methodology/approach: Focuses on correcting several obvious deficiencies in courses and degree programs to create highly differentiated educational experiences that are more relevant to student's needs and the organizations that employ…

  8. Globalisation, Effectiveness and Improvement.

    ERIC Educational Resources Information Center

    Mortimore, Peter

    This paper reports principally on two studies, prompted by research on school effectiveness in the United States and England, which indicate globalization is beginning to affect school improvement. The first study cites case studies of two schools--from working-class, multi-ethnic, poorly educated areas of Singapore and London--to determine if…

  9. Keeping Improvement in Mind

    ERIC Educational Resources Information Center

    Mielke, Paul; Frontier, Tony

    2012-01-01

    Like high-stakes student assessment, high-stakes teacher evaluation threatens to be an occasional event that is disconnected from day-to-day teaching and learning, producing results that do not help teachers improve their performance and placing teachers in a passive role as recipients of external judgment. For several years, the authors have…

  10. Improving Surface Irrigation Performance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Surface irrigation systems often have a reputation for poor performance. One key feature of efficient surface irrigation systems is precision (e.g. laser-guided) land grading. Poor land grading can make other improvements ineffective. An important issue, related to land shaping, is developing the pr...

  11. Improved Dispenser Cathodes

    NASA Astrophysics Data System (ADS)

    Ives, R. Lawrence; Falce, Lou

    2006-01-01

    Variations in emission current from dispenser cathodes can be caused by variations in temperature and work function over the surface. This paper described research to reduce these variations using improved mechanical designs and controlled porosity cathodes made from sintered tungsten wires. The program goal is to reduce current emission variations to less than 5% over the surface of magnetron injection guns operating temperature limited.

  12. Aerodynamics Improve Wind Wheel

    NASA Technical Reports Server (NTRS)

    Ramsey, V. W.

    1982-01-01

    Modifications based on aerodynamic concepts would raise efficiency of wind-wheel electric-power generator. Changes smooth airflow, to increase power output, without increasing size of wheel. Significant improvements in efficiency anticipated without any increase in size or number of moving parts and without departing from simplicity of original design.

  13. INNOVATIONS FOR INSTRUCTIONAL IMPROVEMENT.

    ERIC Educational Resources Information Center

    CUSHMAN, M.L.; STURGES, A.W.

    THE CATSKILL AREA PROJECT IN SMALL SCHOOL DESIGN, THE ROCKY MOUNTAIN AREA PROJECT FOR SMALL HIGH SCHOOLS, THE WESTERN STATES SMALL SCHOOLS PROJECT, AND THE TEXAS SMALL SCHOOLS PROJECT ARE DESCRIBED AND COMPARED. FINANCIAL SUPPORT COMPARISONS ARE MADE. METHODS OF IMPROVING INSTRUCTION ARE DIVIDED INTO TEACHER-CENTERED AND ADMINISTRATOR-CENTERED…

  14. Amplifier improvement circuit

    NASA Technical Reports Server (NTRS)

    Sturman, J.

    1968-01-01

    Stable input stage was designed for the use with a integrated circuit operational amplifier to provide improved performance as an instrumentation-type amplifier. The circuit provides high input impedance, stable gain, good common mode rejection, very low drift, and low output impedance.

  15. Teaching Behavior Improvement Program.

    ERIC Educational Resources Information Center

    Hoehn, Lilburn P., Ed.

    This document, intended for use by those who might wish to implement such a program, describes an inservice teacher self-improvement program based on goal setting by the teacher, practice of new skills, feedback about teaching performance, and self-analysis of the dissonance between goals and practice. Chapter 1 presents rationale and history of…

  16. Improving School Effectiveness.

    ERIC Educational Resources Information Center

    MacBeath, John, Ed.; Mortimore, Peter, Ed.

    School effectiveness is an issue that has preoccupied researchers and policymakers for 3 decades. To study how ineffective schools become effective and what constitutes an effective school, the Improving School Effectiveness Project was carried out in Scotland from 1995 to 1997. This project forms the basis of discussion in this book, which has 11…

  17. Improved compression molding process

    NASA Technical Reports Server (NTRS)

    Heier, W. C.

    1967-01-01

    Modified compression molding process produces plastic molding compounds that are strong, homogeneous, free of residual stresses, and have improved ablative characteristics. The conventional method is modified by applying a vacuum to the mold during the molding cycle, using a volatile sink, and exercising precise control of the mold closure limits.

  18. Dynamic balance improvement program

    NASA Technical Reports Server (NTRS)

    Butner, M. F.

    1983-01-01

    The reduction of residual unbalance in the space shuttle main engine (SSME) high pressure turbopump rotors was addressed. Elastic rotor response to unbalance and balancing requirements, multiplane and in housing balancing, and balance related rotor design considerations were assessed. Recommendations are made for near term improvement of the SSME balancing and for future study and development efforts.

  19. Performance Improvement Processes.

    ERIC Educational Resources Information Center

    1997

    This document contains four papers from a symposium on performance improvement processes. In "Never the Twain Shall Meet?: A Glimpse into High Performance Work Practices and Downsizing" (Laurie J. Bassi, Mark E. Van Buren) evidence from a national cross-industry of more than 200 establishments is used to demonstrate that high-performance work…

  20. Combining Biochemical and Imaging Markers to Improve Diagnosis and Characterization of Mild Traumatic Brain Injury in the Acute Setting: Results from a Pilot Study

    PubMed Central

    Kou, Zhifeng; Gattu, Ramtilak; Kobeissy, Firas; Welch, Robert D.; O’Neil, Brian J.; Woodard, John L.; Ayaz, Syed Imran; Kulek, Andrew; Kas-Shamoun, Robert; Mika, Valerie; Zuk, Conor; Tomasello, Francesco; Mondello, Stefania

    2013-01-01

    Background Mild traumatic brain injury (mTBI) is a significant healthcare burden and its diagnosis remains a challenge in the emergency department. Serum biomarkers and advanced magnetic resonance imaging (MRI) techniques have already demonstrated their potential to improve the detection of brain injury even in patients with negative computed tomography (CT) findings. The objective of this study was to determine the clinical value of a combinational use of both blood biomarkers and MRI in mTBI detection and their characterization in the acute setting (within 24 hours after injury). Methods Nine patients with mTBI were prospectively recruited from the emergency department. Serum samples were collected at the time of hospital admission and every 6 hours up to 24 hours post injury. Neuronal (Ubiquitin C-terminal Hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels were analyzed. Advanced MRI data were acquired at 9±6.91 hours after injury. Patients’ neurocognitive status was assessed by using the Standard Assessment of Concussion (SAC) instrument. Results The median serum levels of UCH-L1 and GFAP on admission were increased 4.9 folds and 10.6 folds, respectively, compared to reference values. Three patients were found to have intracranial hemorrhages on SWI, all of whom had very high GFAP levels. Total volume of brain white matter (WM) with abnormal fractional anisotropy (FA) measures of diffusion tensor imaging (DTI) were negatively correlated with patients’ SAC scores, including delayed recall. Both increased and decreased DTI-FA values were observed in the same subjects. Serum biomarker level was not correlated with patients’ DTI data nor SAC score. Conclusions Blood biomarkers and advanced MRI may correlate or complement each other in different aspects of mTBI detection and characterization. GFAP might have potential to serve as a clinical screening tool for intracranial bleeding. UCH-L1 complements MRI in injury

  1. Improved solar heating systems

    DOEpatents

    Schreyer, J.M.; Dorsey, G.F.

    1980-05-16

    An improved solar heating system is described in which the incident radiation of the sun is absorbed on collector panels, transferred to a storage unit and then distributed as heat for a building and the like. The improvement is obtained by utilizing a storage unit comprising separate compartments containing an array of materials having different melting points ranging from 75 to 180/sup 0/F. The materials in the storage system are melted in accordance with the amount of heat absorbed from the sun and then transferred to the storage system. An efficient low volume storage system is provided by utilizing the latent heat of fusion of the materials as they change states in storing ad releasing heat for distribution.

  2. Partnership for Continuous Improvement

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The proceedings are presented of the sixth annual conference on quality control between NASA and its contractors. The emphasis is placed on a commitment to quality and excellence that guarantees mission success. A forum is provided for representatives from government, industry, and academia to exchange ideas and experiences, encouraging total quality performance that results in high quality products and services. Key points are highlighted from the presentations and activities are described that have resulted in a broad range of improvements in products and services from government, industry, and academia. Long term commitment to quality is an essential requirement that ensures future success. That commitment reinterates the dedication to excellence in space exploration and to national quality and productivity improvement.

  3. Improved collecting apparatus

    SciTech Connect

    Duncan, C.P.

    1981-03-05

    An improved collecting apparatus for small aquatic or airborne organisms such as plankton, larval fish, insects, etc. The improvement constitutes an apertured removal container within which is retained a collecting bag, and which is secured at the apex of a conical collecting net. Such collectors are towed behind a vessel or vehicle with the open end of the conical net facing forward for trapping the aquatic or airborne organisms within the collecting bag, while allowing the water or air to pass through the apertures in the container. The container is readily removable from the collecting net whereby the collecting bag can be quickly removed and replaced for further sample collection. The collecting bag is provided with means for preventing the bag from being pulled into the container by the water or air following therethrough.

  4. Measuring to improve.

    PubMed

    Klein, R; Bobbitt, M

    1995-01-01

    Rush Prudential Health Plans, a managed care company located in Chicago, Illinois, is implementing a service quality improvement process across the three products it markets in the Chicago area: The Anchor Plan (a primarily staff model HMO), The Affiliates Plan (a network model HMO), and The Plus Plan (a point of service plan). In 1994, the company instituted an annual member satisfaction research study, conducted across the three plans, and began building a link between external customer requirements and internal operations. The research process consisted of three stages: determining external customer requirements, translating these customer-defined "symptoms" into underlying root causes, and developing a service quality improvement action plan. Rush Prudential determined that traditional "report card" surveys would not meet their goals for the information measurement process. A detailed diagnostic telephone survey was used to provide a picture of the entire clinical encounter, from scheduling an appointment through the time a member left the physician's office. PMID:10151598

  5. AGS preinjector improvement

    SciTech Connect

    Alessi, J.G.; Brennan, J.M.; Brown, H.N.; Brodowski, J.; Gough, R.; Kponou, A.; Prelec, K.; Staples, J.; Tanabe, J.; Witkover, R.

    1987-01-01

    In 1984, a polarized H/sup -/ source was installed to permit the acceleration of polarized protons in the AGS, using a low current, 750 keV RFQ Linear Accelerator as the preinjector. This RFQ was designed by LANL and has proved to be quite satisfactory and reliable. In order to improve the reliability and simplify maintenance of the overall AGS operations, it has been decided to replace one of the two 750 keV Cockcroft-Waltons (C-W) with an RFQ. The design of a new high current RFQ has been carried out by LBL and is also being constructed there. This paper describes the preinjector improvement project, centered around that RFQ, which is underway at BNL.

  6. Improving Vacuum Cleaners

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Under a Space Act Agreement between the Kirby company and Lewis Research Center, NASA technology was applied to a commercial vacuum cleaner product line. Kirby engineers were interested in advanced operational concepts, such as particle flow behavior and vibration, critical factors to improve vacuum cleaner performance. An evaluation of the company 1994 home care system, the Kirby G4, led to the refinement of the new G5 and future models. Under the cooperative agreement, Kirby had access to Lewis' holography equipment, which added insight into how long a vacuum cleaner fan would perform, as well as advanced computer software that can simulate the flow of air through fans. The collaboration resulted in several successes including fan blade redesign and continuing dialogue on how to improve air-flow traits in various nozzle designs.

  7. Improved Hall type thruster

    NASA Astrophysics Data System (ADS)

    Wetch, Joseph R.; See-pok Wong, Britt, Edward J.; McCracken, Kevin J.; Lin, Raymond; Petrosov, Valeri; Koroteev, Anatoli

    1995-01-01

    An improved design of the Hall type stationary plasma thruster has been tested in 1994. The test results are presented. The test measures performance, EMI and beam divergence of two models of thrusters from the Russian Keldysh Scientific-Research Institute of Thermal Processes. The first of these engines, T-100 produces 80 mN thruster with power of 1.35 kWe. The other thruster, T-160 is larger and produces 280 nM thrust with 4.5 kWe. Endurance testing of the T-100 for 2000 hours was completed at NIITP. Post operation wear measurements indicate that the insulator life expectency will exceed the 8000 hour design life objective. Improved efficiencies of 48 to 52% were measured for the T-100 and 58-62% (with elevated tank pressure) for the T-160 at specific impulse Isp of 1600 seconds and 2000 seconds respectively.

  8. Procedure improvement enterprises

    SciTech Connect

    Davis, P.L.

    1992-01-01

    At Allied-Signal's Kansas City Division (KCD), we recognize the importance of clear, concise and timely procedures for sharing information, promoting consistency and documenting the way we do business. For these reasons, the KCD has gathered a team of employees to analyze the process we currently use to publish procedures, identify the procedure needs of KCD employees, and design a system that meets or exceeds the requirements and expectations of DOE. The name of our group is the Procedure Improvement Enterprise Critical Process Team, or PIE CPT. The mission statement of Procedure Improvement Enterprise is to develop and implement within the Kansas City Division an effective nd flexible procedure system that will establish a model of excellence, will emphasize team work and open communication, and will ensure compliance with corporate/government requirements.

  9. Procedure improvement enterprises

    SciTech Connect

    Davis, P.L.

    1992-01-01

    At Allied-Signal`s Kansas City Division (KCD), we recognize the importance of clear, concise and timely procedures for sharing information, promoting consistency and documenting the way we do business. For these reasons, the KCD has gathered a team of employees to analyze the process we currently use to publish procedures, identify the procedure needs of KCD employees, and design a system that meets or exceeds the requirements and expectations of DOE. The name of our group is the Procedure Improvement Enterprise Critical Process Team, or PIE CPT. The mission statement of Procedure Improvement Enterprise is to develop and implement within the Kansas City Division an effective nd flexible procedure system that will establish a model of excellence, will emphasize team work and open communication, and will ensure compliance with corporate/government requirements.

  10. Process Improvement: Customer Service.

    PubMed

    Cull, Donald

    2015-01-01

    Utilizing the comment section of patient satisfaction surveys, Clark Memorial Hospital in Jeffersonville, IN went through a thoughtful process to arrive at an experience that patients said they wanted. Two Lean Six Sigma tools were used--the Voice of the Customer (VoC) and the Affinity Diagram. Even when using these tools, a facility will not be able to accomplish everything the patient may want. Guidelines were set and rules were established for the Process Improvement Team in order to lessen frustration, increase focus, and ultimately be successful. The project's success is driven by the team members carrying its message back to their areas. It's about ensuring that everyone is striving to improve the patients' experience by listening to what they say is being done right and what they say can be done better. And then acting on it. PMID:26571974

  11. Improved ephemerides of Pluto

    NASA Technical Reports Server (NTRS)

    Standish, E. M.

    1994-01-01

    The history of the Pluto ephemerides created at the Jet Propulsion Laboratory is given. The uncertainties of present and possible future ephemerides are illustrated, and it is shown how rapidly the error grows for any present-day ephemeris of Pluto which is extrapolated into the future--tens of thousands of kilometers after only a decade. Continuing the observations into the future not only will reduce the extrapolation time but will provide a substantial improvement to the ephemeris itself.

  12. Alumina fiber strength improvement

    NASA Technical Reports Server (NTRS)

    Pepper, R. T.; Nelson, D. C.

    1982-01-01

    The effective fiber strength of alumina fibers in an aluminum composite was increased to 173,000 psi. A high temperature heat treatment, combined with a glassy carbon surface coating, was used to prevent degradation and improve fiber tensile strength. Attempts to achieve chemical strengthening of the alumina fiber by chromium oxide and boron oxide coatings proved unsuccessful. A major problem encountered on the program was the low and inconsistent strength of the Dupont Fiber FP used for the investigation.

  13. Improving haul truck productivity

    SciTech Connect

    Fiscor, S.

    2007-06-15

    The paper reviews developments in payload management and cycle times. These were discussed at a roundtable held at the Haulage and Loading 2007 conference held in May in Phoenix, AZ, USA. Several original equipment manufacturers (OEMs) explaind what their companies were doing to improve cycle times for trucks, shovels and excavators used in surface coal mining. Quotations are given from Dion Domaschenz of Liebherr and Steve Plott of Cat Global Mining. 4 figs.

  14. Improved ranging systems

    NASA Technical Reports Server (NTRS)

    Young, Larry E.

    1989-01-01

    Spacecraft range measurements have provided the most accurate tests, to date, of some relativistic gravitational parameters, even though the measurements were made with ranging systems having error budgets of about 10 meters. Technology is now available to allow an improvement of two orders of magnitude in the accuracy of spacecraft ranging. The largest gains in accuracy result from the replacement of unstable analog components with high speed digital circuits having precisely known delays and phase shifts.

  15. CF6 performance improvement

    NASA Technical Reports Server (NTRS)

    Lennard, D. J.

    1978-01-01

    Potential CF6 engine performance improvements directed at reduced fuel consumption were identified and screened relative to airline acceptability and are reviewed. The screening process developed to provide evaluations of fuel savings and economic factors including return on investment and direct operating cost is described. In addition, assessments of development risk and production potential are made. Several promising concepts selected for full-scale development based on a ranking involving these factors are discussed.

  16. Teleophthalmology: improving patient outcomes?

    PubMed Central

    Sreelatha, Omana Kesary; Ramesh, Sathyamangalam VenkataSubbu

    2016-01-01

    Teleophthalmology is gaining importance as an effective eye care delivery modality worldwide. In many developing countries, teleophthalmology is being utilized to provide quality eye care to the underserved urban population and the unserved remote rural population. Over the years, technological innovations have led to improvement in evidence and teleophthalmology has evolved from a research tool to a clinical tool. The majority of the current teleophthalmology services concentrate on patient screening and appropriate referral to experts. Specialty care using teleophthalmology services for the pediatric group includes screening as well as providing timely care for retinopathy of prematurity (ROP). Among geriatric eye diseases, specialty teleophthalmology care is focused toward screening and referral for diabetic retinopathy (DR), glaucoma, age-related macular degeneration (ARMD), and other sight-threatening conditions. Comprehensive vision screening and refractive error services are generally covered as part of most of the teleophthalmology methods. Over the past decades, outcome assessment of health care system includes patients’ assessments on their health, care, and services they receive. Outcomes, by and large, remain the ultimate validators of the effectiveness and quality of medical care. Teleophthalmology produces the same desired clinical outcome as the traditional system. Remote portals allow specialists to provide care over a larger region, thereby improving health outcomes and increasing accessibility of specialty care to a larger population. A high satisfaction level and acceptance is reported in the majority of the studies because of increased accessibility and reduced traveling cost and time. Considering the improved quality of patient care and patient satisfaction reported for these telemedicine services, this review explores how teleophthalmology helps to improve patient outcomes. PMID:26929592

  17. Improved vortex reactor system

    DOEpatents

    Diebold, J.P.; Scahill, J.W.

    1995-05-09

    An improved vortex reactor system is described for affecting fast pyrolysis of biomass and Refuse Derived Fuel (RDF) feed materials comprising: a vortex reactor having its axis vertically disposed in relation to a jet of a horizontally disposed steam ejector that impels feed materials from a feeder and solids from a recycle loop along with a motive gas into a top part of said reactor. 12 figs.

  18. Teleophthalmology: improving patient outcomes?

    PubMed

    Sreelatha, Omana Kesary; Ramesh, Sathyamangalam VenkataSubbu

    2016-01-01

    Teleophthalmology is gaining importance as an effective eye care delivery modality worldwide. In many developing countries, teleophthalmology is being utilized to provide quality eye care to the underserved urban population and the unserved remote rural population. Over the years, technological innovations have led to improvement in evidence and teleophthalmology has evolved from a research tool to a clinical tool. The majority of the current teleophthalmology services concentrate on patient screening and appropriate referral to experts. Specialty care using teleophthalmology services for the pediatric group includes screening as well as providing timely care for retinopathy of prematurity (ROP). Among geriatric eye diseases, specialty teleophthalmology care is focused toward screening and referral for diabetic retinopathy (DR), glaucoma, age-related macular degeneration (ARMD), and other sight-threatening conditions. Comprehensive vision screening and refractive error services are generally covered as part of most of the teleophthalmology methods. Over the past decades, outcome assessment of health care system includes patients' assessments on their health, care, and services they receive. Outcomes, by and large, remain the ultimate validators of the effectiveness and quality of medical care. Teleophthalmology produces the same desired clinical outcome as the traditional system. Remote portals allow specialists to provide care over a larger region, thereby improving health outcomes and increasing accessibility of specialty care to a larger population. A high satisfaction level and acceptance is reported in the majority of the studies because of increased accessibility and reduced traveling cost and time. Considering the improved quality of patient care and patient satisfaction reported for these telemedicine services, this review explores how teleophthalmology helps to improve patient outcomes. PMID:26929592

  19. Improved Electrohydraulic Linear Actuators

    NASA Technical Reports Server (NTRS)

    Hamtil, James

    2004-01-01

    A product line of improved electrohydraulic linear actuators has been developed. These actuators are designed especially for use in actuating valves in rocket-engine test facilities. They are also adaptable to many industrial uses, such as steam turbines, process control valves, dampers, motion control, etc. The advantageous features of the improved electrohydraulic linear actuators are best described with respect to shortcomings of prior electrohydraulic linear actuators that the improved ones are intended to supplant. The flow of hydraulic fluid to the two ports of the actuator cylinder is controlled by a servo valve that is controlled by a signal from a servo amplifier that, in turn, receives an analog position-command signal (a current having a value between 4 and 20 mA) from a supervisory control system of the facility. As the position command changes, the servo valve shifts, causing a greater flow of hydraulic fluid to one side of the cylinder and thereby causing the actuator piston to move to extend or retract a piston rod from the actuator body. A linear variable differential transformer (LVDT) directly linked to the piston provides a position-feedback signal, which is compared with the position-command signal in the servo amplifier. When the position-feedback and position-command signals match, the servo valve moves to its null position, in which it holds the actuator piston at a steady position.

  20. Improved radioanalytical methods

    SciTech Connect

    Erickson, M.D.; Aldstadt, J.H.; Alvarado, J.S.; Crain, J.S.; Orlandini, K.A.; Smith, L.L.

    1995-12-31

    Methods for the chemical characterization of the environment are being developed under a multitask project for the Analytical Services Division (EM-263) within the US Department of Energy (DOE) Office of Environmental Management. This project focuses on improvement of radioanalytical methods with an emphasis on faster and cheaper routine methods. We have developed improved methods, for separation of environmental levels of technetium-99 and strontium-89/90, radium, and actinides from soil and water; and for separation of actinides from soil and water matrix interferences. Among the novel separation techniques being used are element- and class-specific resins and membranes. (The 3M Corporation is commercializing Empore {trademark} membranes under a cooperative research and development agreement [CRADA] initiated under this project). We have also developed methods for simultaneous detection of multiple isotopes using inductively coupled plasma-mass spectrometry (ICP-MS). The ICP-MS method requires less rigorous chemical separations than traditional radiochemical analyses because of its mass-selective mode of detection. Actinides and their progeny have been isolated and concentrated from a variety of natural water matrices by using automated batch separation incorporating selective resins prior to ICP-MS analyses. In addition, improvements in detection limits, sample volume, and time of analysis were obtained by using other sample introduction techniques, such as ultrasonic nebulization and electrothermal vaporization. Integration and automation of the separation methods with the ICP-MS methodology by using flow injection analysis is underway, with an objective of automating methods to achieve more reproducible results, reduce labor costs, cut analysis time, and minimize secondary waste generation through miniaturization of the process.

  1. Retaining caregivers, improving care.

    PubMed

    Bodwell, Wendy; Dent, Sara; Grant, Tracie; Hammerly, Milt; Mamula, Jeanie

    2006-01-01

    Text Summary In 2004, Centura Health's long-term care centers took part in a pilot project, sponsored by the Centers for Medicare & Medicaid Services, called "Improving Nursing Home Culture through Workforce Retention." A 30-member team comprising Centura leaders and long-term facility staff looked at Centura's eight participating facilities through residents' and employees' eyes. The goal of the team's reflection and subsequent changes was to create a culture in which decisions are focused on resident care and organizational policies are based on respect for employees. At the end of the first year, residents seemed happier and employee satisfaction and involvement increased at all eight Centura facilities. PMID:16519278

  2. Improved ion source

    DOEpatents

    Leung, K.N.; Ehlers, K.W.

    1982-05-04

    A magnetic filter for an ion source reduces the production of undesired ion species and improves the ion beam quality. High-energy ionizing electrons are confined by the magnetic filter to an ion source region, where the high-energy electrons ionize gas molecules. One embodiment of the magnetic filter uses permanent magnets oriented to establish a magnetic field transverse to the direction of travel of ions from the ion source region to the ion extraction region. In another embodiment, low energy 16 eV electrons are injected into the ion source to dissociate gas molecules and undesired ion species into desired ion species,

  3. Improved ion detector

    DOEpatents

    Tullis, A.M.

    1986-01-30

    An improved ion detector device of the ionization detection device chamber type comprises an ionization chamber having a central electrode therein surrounded by a cylindrical electrode member within the chamber with a collar frictionally fitted around at least one of the electrodes. The collar has electrical contact means carried in an annular groove in an inner bore of the collar to contact the outer surface of the electrode to provide electrical contact between an external terminal and the electrode without the need to solder leads to the electrode.

  4. Improving aircraft energy efficiency

    NASA Technical Reports Server (NTRS)

    Povinelli, F. P.; Klineberg, J. M.; Kramer, J. J.

    1976-01-01

    Investigations conducted by a NASA task force concerning the development of aeronautical fuel-conservation technology are considered. The task force estimated the fuel savings potential, prospects for implementation in the civil air-transport fleet, and the impact of the technology on air-transport fuel use. Propulsion advances are related to existing engines in the fleet, to new production of current engine types, and to new engine designs. Studies aimed at the evolutionary improvement of aerodynamic design and a laminar flow control program are discussed and possibilities concerning the use of composite structural materials are examined.

  5. Improving VHF Spectrum Utilization

    NASA Technical Reports Server (NTRS)

    Andro, Monty; Orr, Richard; Foore, Larry; Sheehe, Charles; Freeman, Mark; Nguyen, Thanh; Bretmersky, Steven; Laberge, Chuck; Buchanan, David

    2004-01-01

    Limited VHF communications system capacity and increasing air traffic results in congestion of the aviation VHF spectrum. The voice communications errors and delayed channel access create system congestion and air traffic delays. Regulatory subdivision of bands for specific functions limits flexibility in the frequency usage. The objective of this viewgraph presentation is to identify near/mid/far term technologies to improve the performance and spectrum efficiency of current and emerging VHF communications systems. Select technologies with the highest potential, perform research and development to bring them to implementation stage.

  6. Improving Carbon Fixation Pathways

    PubMed Central

    Ducat, Daniel C.

    2012-01-01

    A recent resurgence in basic and applied research on photosynthesis has been driven in part by recognition that fulfilling future food and energy requirements will necessitate improvements in crop carbon-fixation efficiencies. Photosynthesis in traditional terrestrial crops is being reexamined in light of molecular strategies employed by photosynthetic microbes to enhance the activity of the Calvin cycle. Synthetic biology is well-situated to provide original approaches for compartmentalizing and enhancing photosynthetic reactions in a species independent manner. Furthermore, the elucidation of alternative carbon-fixation routes distinct from the Calvin cycle raises possibilities that alternative pathways and organisms can be utilized to fix atmospheric carbon dioxide into useful materials. PMID:22647231

  7. Improving carbon fixation pathways

    SciTech Connect

    Ducat, DC; Silver, PA

    2012-08-01

    A recent resurgence in basic and applied research on photosynthesis has been driven in part by recognition that fulfilling future food and energy requirements will necessitate improvements in crop carbon-fixation efficiencies. Photosynthesis in traditional terrestrial crops is being reexamined in light of molecular strategies employed by photosynthetic microbes to enhance the activity of the Calvin cycle. Synthetic biology is well-situated to provide original approaches for compartmentalizing and enhancing photosynthetic reactions in a species independent manner. Furthermore, the elucidation of alternative carbon-fixation routes distinct from the Calvin cycle raises possibilities that novel pathways and organisms can be utilized to fix atmospheric carbon dioxide into useful materials.

  8. Improved Capacitive Liquid Sensor

    NASA Technical Reports Server (NTRS)

    Waldman, Francis A.

    1992-01-01

    Improved capacitive sensor used to detect presence and/or measure thickness of layer of liquid. Electrical impedance or admittance of sensor measured at prescribed frequency, and thickness of liquid inferred from predetermined theoretical or experimental relationship between impedance and thickness. Sensor is basically a three-terminal device. Features interdigitated driving and sensing electrodes and peripheral coplanar ground electrode that reduces parasitic effects. Patent-pending because first to utilize ground plane as "shunting" electrode. System less expensive than infrared, microwave, or refractive-index systems. Sensor successfully evaluated in commercial production plants to characterize emulsions, slurries, and solutions.

  9. Improved cycling cryopump

    DOEpatents

    Batzer, T.H.; Call, W.R.

    1984-12-04

    The present invention is designed to achieve continuous high efficiency cryopumping of a vacuum vessel by improving upon and combining in a novel way the cryopumping in a novel way the cryopumping methods. The invention consists of a continuous operation cryopump, with movable louvres, with a high efficiency pumping apparatus. The pumping apparatus includes three cryogenic tubes. They are constructed of a substance of high thermal conductivity, such as aluminum and their exterior surfaces are cryogenic condensing surfaces. Through their interior liquid or gaseous helium from two reservoirs can be made to flow, alternately promoting extreme cooling or allowing some warming.

  10. Improved tool grinding machine

    DOEpatents

    Dial, C.E. Sr.

    The present invention relates to an improved tool grinding mechanism for grinding single point diamond cutting tools to precise roundness and radius specifications. The present invention utilizes a tool holder which is longitudinally displaced with respect to the remainder of the grinding system due to contact of the tool with the grinding surface with this displacement being monitored so that any variation in the grinding of the cutting surface such as caused by crystal orientation or tool thicknesses may be compensated for during the grinding operation to assure the attainment of the desired cutting tool face specifications.