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Sample records for pulp improves survival

  1. Açai palm fruit (Euterpe oleracea Mart.) pulp improves survival of flies on a high fat diet.

    PubMed

    Sun, Xiaoping; Seeberger, Jeanne; Alberico, Thomas; Wang, Chunxu; Wheeler, Charles T; Schauss, Alexander G; Zou, Sige

    2010-03-01

    Reducing oxidative damage is thought to be an effective aging intervention. Açai, a fruit indigenous to the Amazon, is rich in phytochemicals that possesses high anti-oxidant activities, and has anti-inflammatory, anti-cancer and anti-cardiovascular disease properties. However, little is known about its potential anti-aging properties especially at the organismal level. Here we evaluated the effect of açai pulp on modulating lifespan in Drosophila melanogaster. We found that açai supplementation at 2% in the food increased the lifespan of female flies fed a high fat diet compared to the non-supplemented control. We measured transcript changes induced by açai for age-related genes. Although transcript levels of most genes tested were not altered, açai increased the transcript level of l(2)efl, a small heat-shock-related protein, and two detoxification genes, GstD1 and MtnA, while decreasing the transcript level of phosphoenolpyruvate carboxykinase (Pepck), a key gene involved in gluconeogenesis. Furthermore, açai increased the lifespan of oxidative stressed females caused by sod1 RNAi. This suggests that açai improves survival of flies fed a high fat diet through activation of stress response pathways and suppression of Pepck expression. Açai has the potential to antagonize the detrimental effect of fat in the diet and alleviate oxidative stress in aging. PMID:20080168

  2. Improving the Odds of Surviving Sepsis

    MedlinePlus

    ... Improving the Odds of Surviving Sepsis Inside Life Science View All Articles | Inside Life Science Home Page Improving the Odds of Surviving Sepsis ... Threatening Bacterial Infection Remains Mysterious This Inside Life Science article also appears on LiveScience . Learn about related ...

  3. Application of enzyme for improvement of Acacia APMP pulping and refining of mixed pulp for printing papermaking in Vietnam.

    PubMed

    Dien, Le Quang; Hoang, Phan Huy; Tu, Do Thanh

    2014-02-01

    This study assesses the influence of commercial enzyme (FibreZyme LBR) treatment applied to APMP pulp and to the mixture of 55% Acacia CTMP75 pulp, 30% soft-wood bleached chemical pulp (LBKP 90 from Chile) and 15% hard-wood bleached chemical pulp (NPKP 90 from Indonesia). The treatment was conducted at different temperatures, reaction times and enzyme dosages. The APMP and mixed pulp treated with the enzyme showed a significant decrease of refining time to achieve the same refining degree (Schopper-Riegler freeness, °SR) and better mechanical-physical properties due to the development of fibrillation. The fibre morphology difference between before and after treatment was revealed by the microscopic observations performed by a scanning electron microscope (SEM). The SEM analysis showed that the surface of the enzyme-treated fibre had some swelling and fibrillar phenomenon that lead to strong paper properties such as tear index, tensile index and burst index. PMID:24222497

  4. Improving the performance of enzymes in hydrolysis of high solids paper pulp derived from MSW

    PubMed Central

    2013-01-01

    Background The research aimed to improve the overall conversion efficiency of the CTec® family of enzymes by identifying factors that lead to inhibition and seeking methods to overcome these through process modification and manipulation. The starting material was pulp derived from municipal solid waste and processed in an industrial-scale washing plant. Results Analysis of the pulp by acid hydrolysis showed a ratio of 55 : 12 : 6 : 24 : 3 of glucan : xylan : araban/galactan/mannan : lignin : ash. At high total solids content (>18.5% TS) single-stage enzyme hydrolysis gave a maximum glucan conversion of 68%. It was found that two-stage hydrolysis could give higher conversion if sugar inhibition was removed by an intermediate fermentation step between hydrolysis stages. This, however, was not as effective as direct removal of the sugar products, including xylose, by washing of the residual pulp at pH 5. This improved the water availability and allowed reactivation of the pulp-bound enzymes. Inhibition of enzyme activity could further be alleviated by replenishment of β-glucosidase which was shown to be removed during the wash step. Conclusions The two-stage hydrolysis process developed could give an overall glucan conversion of 88%, with an average glucose concentration close to 8% in 4 days, thus providing an ideal starting point for ethanol fermentation with a likely yield of 4 wt%. This is a significant improvement over a single-step process. This hydrolysis configuration also provides the potential to recover the sugars associated with residual solids which are diluted when washing hydrolysed pulp. PMID:23885832

  5. Wet strength improvement of unbleached kraft pulp through laccase catalyzed oxidation.

    PubMed

    Lund, M; Felby, C

    2001-06-01

    Previous investigations have shown that laccase catalyzed oxidation of lignin containing wood fibers can enhance the strength of medium density fiberboards. In the present work it was investigated if laccase treatment had any impact on the tensile strength of a high yield unbleached kraft pulp. Treatment with laccase alone had only a very little effect on the wet strength of the pulp, whereas addition of lignin rich extractives increased the wet strength after the enzyme treatment significantly. A mediated oxidation gave a similar improvement of the wet tensile strength although no lignin was added to the fiber suspension. Furthermore, it was found that a heat treatment combined with a mediated oxidation gave a higher improvement in wet tensile strength than could be accounted for by the individual treatments. No change in dry tensile strength from the laccase treatment was observed. It is suggested that the observed improvement in wet tensile strength is related to polymerization of lignin on fibers in the hand sheet and/or coupling of phenoxy radicals on lignin associated to adjacent fibers. For the different mediators studied, a correlation was found between oxygen consumption upon mediated oxidation and generation of wet strength in the pulp. PMID:11397456

  6. Yield Improvement and Energy Savings Uing Phosphonates as Additives in Kraft pulping

    SciTech Connect

    Ulrike W. Tschirner; Timothy Smith

    2007-03-31

    Project Objective: Develop a commercially viable modification to the Kraft process resulting in energy savings, increased yield and improved bleachability. Evaluate the feasibility of this technology across a spectrum of wood species used in North America. Develop detailed fundamental understanding of the mechanism by which phosphonates improve KAPPA number and yield. Evaluate the North American market potential for the use of phosphonates in the Kraft pulping process. Examine determinants of customer perceived value and explore organizational and operational factors influencing attitudes and behaviors. Provide an economic feasibility assessment for the supply chain, both suppliers (chemical supply companies) and buyers (Kraft mills). Provide background to most effectively transfer this new technology to commercial mills.

  7. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells.

    PubMed

    Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

    2016-01-01

    Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment. PMID:26775677

  8. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells

    PubMed Central

    Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

    2016-01-01

    Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment. PMID:26775677

  9. Understanding the Nature and Reactivity of Residual Lignin for Improved Pulping and Bleaching Efficiency

    SciTech Connect

    Yuan-Zong Lai

    2001-11-30

    One of the most formidable challenges in kraft pulping to produce bleached chemical pulps is how to effectively remove the last 5-10% of lignin while maintaining the fiber quality. To avoid a severe fiber degradation, kraft pulping is usually terminated in the 25-30 kappa number range and then followed by an elementally chlorine free (ECF) or a totally chlorine free (TCF) bleaching sequence to reduce the environmental impacts.

  10. Analysis of reasons for decline of bioleaching efficiency of spent Zn-Mn batteries at high pulp densities and exploration measure for improving performance.

    PubMed

    Xin, Baoping; Jiang, Wenfeng; Li, Xin; Zhang, Kai; Liu, Changhao; Wang, Renqing; Wang, Yutao

    2012-05-01

    The reasons for decline of bioleaching efficiency of Zn and Mn from spent batteries at high pulp densities were analyzed; the measures for improving bioleaching efficiency were investigated. The results showed that extraction efficiency of Zn dropped from 100% at 1% of pulp density to 29.9% at 8% of pulp density, with Mn from 94% to only 2.5%. It was almost the linear reduction of the activity of the sulfur-oxidizing bacteria with increase of pulp density that witnessed declined bioleaching efficiency of Zn; it was the complete inactivation of the iron-oxidizing bacteria at 2% of pulp density or higher that witnessed declined bioleaching dose of Mn. By means of reducing initial pH value of leaching media, increasing concentration of energy matters and exogenous acid adjustment of media during bioleaching, the maximum extraction efficiency of almost 100% for Zn and 89% for Mn at 4% of pulp density was attained, respectively. PMID:22437046

  11. Improved Survival of Patients with Cystic Fibrosis

    MedlinePlus

    ... 50 years. What were the limitations of the study? It is not possible to know whether current estimates of survival will continue to be valid. In addition, the results reported are estimates for ...

  12. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  13. Improvement of Pulping Uniformity by Measurement of Single Fiber Kappa Number

    SciTech Connect

    Richard R. Gustafson; James B. Callis

    2001-11-20

    A method to measure the kappa of single fibers by staining with a fluorescent dye, Acridine Orange (AO), has been developed. This method is now applied to develop and automated flow-through instrument that permits routine kappa analysis on thousands of images of AO stained fibers to give the fiber kappa number distribution of a pulp sample in a few minutes. The design and operation of the instrument are similar to that of a flow cytometer but with the addition of extensive fiber imaging capability. Fluorescence measurements in the flow-through instrument are found to be consistent with those made with fluorescence microscope provided the signal processing in the flow-thou instrument is handled propertly. The kappa distributions of pulps that were analyzed by means of a density gradient column are compared to those measured with the flow-through instrument with good results. The kappa distributions of various laboratory pulps and commercial pulps have been measured. It has been found that all pulps are non-uniform but that ommercial pulps generally have broader kappa distributions thatn their laboratory counterparts. The effects of different pulping methods and chip pretreatments on pulp uniformity are discussed in the report. Finally, the application of flow-through fluorescence technology to other single fiber measurements are presented.

  14. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H.; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-01-01

    Abstract The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  15. Method for improving separation of carbohydrates from wood pulping and wood or biomass hydrolysis liquors

    DOEpatents

    Griffith, William Louis; Compere, Alicia Lucille; Leitten, Jr., Carl Frederick

    2010-04-20

    A method for separating carbohydrates from pulping liquors includes the steps of providing a wood pulping or wood or biomass hydrolysis pulping liquor having lignin therein, and mixing the liquor with an acid or a gas which forms an acid upon contact with water to initiate precipitation of carbohydrate to begin formation of a precipitate. During precipitation, at least one long chain carboxylated carbohydrate and at least one cationic polymer, such as a polyamine or polyimine are added, wherein the precipitate aggregates into larger precipitate structures. Carbohydrate gel precipitates are then selectively removed from the larger precipitate structures. The method process yields both a carbohydrate precipitate and a high purity lignin.

  16. Opportunities to improve energy efficiency in the U.S. pulp and paper industry

    SciTech Connect

    Worrell, Ernst; Martin, Nathan; Anglani, Norma; Einstein, Dan; Krushch, Marta; Price, Lynn

    2001-02-02

    This paper analyzes the energy efficiency and carbon dioxide emissions reductions potential of the U.S. pulp and paper industry, one of the largest energy users in the U.S. manufacturing sector. We examined over 45 commercially available state-of-the-art technologies and measures. The measures were characterized, and then ordered on the basis of cost-effectiveness. The report indicates that there still exists significant potential for energy savings and carbon dioxide emissions reduction in this industry. The cost-effective potential for energy efficiency improvement is defined as having a simple pay-back period of three years or less. Not including increased recycling the study identifies a cost-effective savings potential of 16% of the primary energy use in 1994. Including increased recycling leads to a higher potential for energy savings, i.e. a range of cost-effective savings between 16% and 24% of primary energy use. Future work is needed to further elaborate on key energy efficiency measures identified in the report including barriers and opportunities for increased recycling of waste paper.

  17. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    MedlinePlus

    ... Cancer Screening Research Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival For some women with breast ... took it for 5 years. (See the table.) Breast Cancer Recurrence and Death 5 to 14 Years after ...

  18. Eribulin Improves Survival of Women with Metastatic Breast Cancer

    Cancer.gov

    Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE.

  19. New Approaches in Vital Pulp Therapy in Permanent Teeth

    PubMed Central

    Ghoddusi, Jamileh; Forghani, Maryam; Parisay, Iman

    2014-01-01

    Vitality of dental pulp is essential for long-term tooth survival. The aim of vital pulp therapy is to maintain healthy pulp tissue by eliminating bacteria from the dentin-pulp complex. There are several different treatment options for vital pulp therapy in extensively decayed or traumatized teeth. Pulp capping or pulpotomy procedures rely upon an accurate assessment of the pulp status, and careful management of the remaining pulp tissue. The purpose of this review is to provide an overview of new approaches in vital pulp therapy in permanent teeth. PMID:24396371

  20. Solid-State Fermentation: an Alternative to Improve the Nutritive Value of Coffee Pulp

    PubMed Central

    Peñaloza, Walter; Molina, Mario R.; Brenes, Roberto Gomez; Bressani, Ricardo

    1985-01-01

    Coffee pulp was subjected to a solid-state fermentation process, using Aspergillus niger. The initial moisture content of the pulp, as well as the fermentation time and temperature, had a significant effect on the increase in total amino acid content of the material. The increase in total amino acids showed a significant correlation with the dry matter recovered (r = −0.98) and the increase in pH during the process (r = 0.98). With a moisture content of 80%, a pH of 3.5, a temperature of 35°C, and an aeration of 8 liters/min per kg as fermentation conditions, it was found that the maximum concentration of total amino acids was attained after 43 h. The fermented product had a higher total amino acid content and a lower cell wall constituent value (primarily cellulose and hemicellulose) than the original pulp. A growing chicken's ration containing 10% of the fermented product had a feed efficiency (2.14) similar to that of the standard ration (2.19) and was significantly better than that of the diet containing 10% of the original pulp (2.53). The difference observed in feed intake and weight gain between the standard diet and that with 10% of the fermented product is considered to be due to palatability factors which should be studied further. PMID:16346724

  1. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    PubMed Central

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2013-01-01

    Purpose To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p <.01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors. PMID:21658855

  2. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    SciTech Connect

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  3. Improving the hydrogen peroxide bleaching efficiency of aspen chemithermomechanical pulp by using chitosan.

    PubMed

    Li, Zongquan; Dou, Hongyan; Fu, Yingjuan; Qin, Menghua

    2015-11-01

    The presence of transition metals during the hydrogen peroxide bleaching of pulp results in the decomposition of hydrogen peroxide, which decreases the bleaching efficiency. In this study, chitosans were used as peroxide stabilizer in the alkaline hydrogen peroxide bleaching of aspen chemithermomechanical pulp (CTMP). The results showed that the brightness of the bleached CTMP increased 1.5% ISO by addition of 0.1% chitosan with 95% degree of deacetylation during peroxide bleaching. Transition metals in the form of ions or metal colloid particles, such as iron, copper and manganese, could be adsorbed by chitosans. Chitosans could inhibit the decomposition of hydrogen peroxide catalyzed by different transition metals under alkaline conditions. The ability of chitosans to inhibit peroxide decomposition depended on the type of transition metals, chitosan concentration and degree of deacetylation applied. The addition of chitosan slightly reduced the concentration of the hydroxyl radical formed during the hydrogen peroxide bleaching of aspen CTMP. PMID:26256367

  4. 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

  5. Improving survival after endometrial cancer: the big picture

    PubMed Central

    2015-01-01

    To improve survival in women with endometrial cancer, we need to look at the "big picture" beyond initial treatment. Although the majority of women will be diagnosed with early stage disease and are cured with surgery alone, there is a subgroup of women with advanced and high-risk early stage disease whose life expectancy may be prolonged with the addition of chemotherapy. Immunohistochemistry will help to identify those women with Lynch syndrome who will benefit from more frequent colorectal cancer surveillance and genetic counseling. If they happen to be diagnosed with colorectal cancer, this information has an important therapeutic implication. And finally, because the majority of women will survive their diagnosis of endometrial cancer, they remain at risk for breast and colorectal cancer, so these women should be counselled about screening for these cancers. These three interventions will contribute to improving the overall survival of women with endometrial cancer. PMID:26197859

  6. Surviving Performance Improvement "Solutions": Aligning Performance Improvement Interventions

    ERIC Educational Resources Information Center

    Bernardez, Mariano L.

    2009-01-01

    How can organizations avoid the negative, sometimes chaotic, effects of multiple, poorly coordinated performance improvement interventions? How can we avoid punishing our external clients or staff with the side effects of solutions that might benefit our bottom line or internal efficiency at the expense of the value received or perceived by…

  7. VEGF improves survival of mesenchymal stem cells in infarcted hearts

    SciTech Connect

    Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

    2008-11-14

    Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16{sup INK}, p21 and p19{sup ARF}. VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI.

  8. Improved survival with simendan after experimental myocardial infarction in rats.

    PubMed

    Levijoki, J; Pollesello, P; Kaheinen, P; Haikala, H

    2001-05-11

    This study compared the effects of simendan, a calcium sensitizer, with those of milrinone and enalapril on survival of rats with healed myocardial infarction. Seven days after ligation-induced myocardial infarction, the rats were randomized to control, milrinone, enalapril, or simendan groups. All compounds were administered via the drinking water for 312 days, at which time there was 80% mortality in the control group--the study's primary endpoint. The infarct sizes were similar across all groups. At endpoint, the mortality rates were: 63% (milrinone), 56% (enalapril) and 53% (simendan); the risk reductions were 25% (P = 0.04 vs. control) and 28% (P = 0.02 vs. control) with enalapril and simendan, respectively. Milrinone had no statistically significant effect on the survival rate. These findings suggest that, like enalapril, simendan improved survival in rats with healed myocardial infarction. PMID:11426847

  9. Interdisciplinary ICU Cardiac Arrest Debriefing Improves Survival Outcomes

    PubMed Central

    Wolfe, Heather; Zebuhr, Carleen; Topjian, Alexis A.; Nishisaki, Akira; Niles, Dana E.; Meaney, Peter A.; Boyle, Lori; Giordano, Rita T.; Davis, Daniela; Priestley, Margaret; Apkon, Michael; Berg, Robert A.; Nadkarni, Vinay M.; Sutton, Robert M.

    2014-01-01

    Objective In-hospital cardiac arrest is an important public health problem. High-quality resuscitation improves survival but is difficult to achieve. Our objective is to evaluate the effectiveness of a novel, interdisciplinary, postevent quantitative debriefing program to improve survival outcomes after in-hospital pediatric chest compression events. Design, Setting, and Patients Single-center prospective interventional study of children who received chest compressions between December 2008 and June 2012 in the ICU. Interventions Structured, quantitative, audiovisual, interdisciplinary debriefing of chest compression events with front-line providers. Measurements and Main Results Primary outcome was survival to hospital discharge. Secondary outcomes included survival of event (return of spontaneous circulation for ≥ 20 min) and favorable neurologic outcome. Primary resuscitation quality outcome was a composite variable, termed “excellent cardiopulmonary resuscitation,” prospectively defined as a chest compression depth ≥ 38 mm, rate ≥ 100/min, ≤ 10% of chest compressions with leaning, and a chest compression fraction > 90% during a given 30-second epoch. Quantitative data were available only for patients who are 8 years old or older. There were 119 chest compression events (60 control and 59 interventional). The intervention was associated with a trend toward improved survival to hospital discharge on both univariate analysis (52% vs 33%, p = 0.054) and after controlling for confounders (adjusted odds ratio, 2.5; 95% CI, 0.91–6.8; p = 0.075), and it significantly increased survival with favorable neurologic outcome on both univariate (50% vs 29%, p = 0.036) and multivariable analyses (adjusted odds ratio, 2.75; 95% CI, 1.01–7.5; p = 0.047). Cardiopulmonary resuscitation epochs for patients who are 8 years old or older during the debriefing period were 5.6 times more likely to meet targets of excellent cardiopulmonary resuscitation (95% CI, 2.9–10

  10. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    PubMed Central

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  11. Improving rotorcraft survivability to RPG attack using inverse methods

    NASA Astrophysics Data System (ADS)

    Anderson, D.; Thomson, D. G.

    2009-09-01

    This paper presents the results of a preliminary investigation of optimal threat evasion strategies for improving the survivability of rotorcraft under attack by rocket propelled grenades (RPGs). The basis of this approach is the application of inverse simulation techniques pioneered for simulation of aggressive helicopter manoeuvres to the RPG engagement problem. In this research, improvements in survivability are achieved by computing effective evasive manoeuvres. The first step in this process uses the missile approach warning system camera (MAWS) on the aircraft to provide angular information of the threat. Estimates of the RPG trajectory and impact point are then estimated. For the current flight state an appropriate evasion response is selected then realised via inverse simulation of the platform dynamics. Results are presented for several representative engagements showing the efficacy of the approach.

  12. Improving Oral Cancer Survival: The Role of Dental Providers

    PubMed Central

    MESSADI, DIANA V.; WILDER-SMITH, PETRA; WOLINSKY, LAWRENCE

    2010-01-01

    Oral cancer accounts for 2 percent to 4 percent of all cancers diagnosed each year in the United States. In contrast to other cancers, the overall U.S. survival rate from oral cancer has not improved during the past 50 years, mostly due to late-stage diagnosis. Several noninvasive oral cancer detection techniques that emerged in the past decade will be discussed, with a brief overview of most common oral cancer chemopreventive agents. PMID:19998655

  13. Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

    PubMed Central

    Ayub, Ahmar; Poulose, Ninu; Raju, Raghavan

    2015-01-01

    Resveratrol has been shown to potentiate mitochondrial function and extend longevity; however, there is no evidence to support whether resveratrol can improve survival or prolong life following hemorrhagic shock. We sought to determine whether (a) resveratrol can improve survival following hemorrhage and resuscitation and (b) prolong life in the absence of resuscitation. Using a hemorrhagic injury (HI) model in the rat, we describe for the first time that the naturally occurring small molecule, resveratrol, may be an effective adjunct to resuscitation fluid. In a series of three sets of experiments we show that resveratrol administration during resuscitation improves survival following HI (p < 0.05), resveratrol and its synthetic mimic SRT1720 can significantly prolong life in the absence of resuscitation fluid (<30 min versus up to 4 h; p < 0.05), and resveratrol as well as SRT1720 restores left ventricular function following HI. We also found significant changes in the expression level of mitochondria-related transcription factors Ppar-α and Tfam, as well as Pgc-1α in the left ventricular tissues of rats subjected to HI and treated with resveratrol. The results indicate that resveratrol is a strong candidate adjunct to resuscitation following severe hemorrhage. PMID:25879628

  14. Ten case history studies of energy efficiency improvements in pulp and paper mills. Final report

    SciTech Connect

    Not Available

    1981-01-01

    The ten technologies chosen for case history development are: sonic sootblowing in boilers, boiler operation on oil-water emulsified fuel, energy efficient motors, computerized control of excess air for boilers, boiler control and load allocation, driving of waste-activated sludge by multiple effect evaporation, pre-drying of hog fuel, lime kiln computerization, heat wheel for process heat recovery, and organic Rankine bottoming cycle for thermomechanical pulping heat recovery. For each case study, there is given: the company name, employee contact, plant summary, a description of the energy consuming process and of the energy-saving action, an assessment of energy savings, and the decision process leading to the adoption of the measure. A data summary for discounted cash flow analysis is tabulated for each case. (LEW)

  15. Lipopolysaccharide stimulation improves the odontoblastic differentiation of human dental pulp cells.

    PubMed

    Huang, Yihua; Jiang, Hongwei; Gong, Qimei; Li, Xuyan; Ling, Junqi

    2015-05-01

    Lipopolysaccharide (LPS) is one of the causative agents of pulpitis and previous studies have demonstrated that the LPS stimulation of human aortic valve interstitial cells induces inflammatory mediators and the gene expression of osteogenic factors. Therefore, in the present study, it was hypothesized that LPS affects the odontoblastic differentiation of human dental pulp cells (hDPCs). In order to investigate this, an in vitro study using hDPCs was performed. Increased alkaline phosphatase (ALP) activity was observed in the hDPCs treated with LPS, which was more marked when the cells were costimulated with odontogenic induction medium (OM). LPS also appeared to increase the gene expression levels of dentin sialophosphoprotein and dentin matrix protein‑1 and the protein expression level of dental sialoprotein in the hDPCs, particularly in combination with OM. In addition, the size and the number of nodules formed in the hDPCs exposed to OM and LPS were increased compared to those stimulated by OM alone. To determine the role of nuclear factor κB (NF‑κB) during the LPS‑induced odontoblastic differentiation of hDPCs, immunofluorescence was performed. The nuclear translocation of NF‑κB, induced by LPS was confirmed, suggesting its involvement in the LPS‑induced increase in odontoblastic differentiation of hDPCs. In conclusion, there may be an association between LPS stimulation, with or without OM, and odontoblastic differentiation. PMID:25528991

  16. Biotransformation and improved enzymatic extraction of chlorogenic acid from coffee pulp by filamentous fungi.

    PubMed

    Torres-Mancera, María Teresa; Baqueiro-Peña, Itzamná; Figueroa-Montero, Arturo; Rodríguez-Serrano, Gabriela; González-Zamora, Eduardo; Favela-Torres, Ernesto; Saucedo-Castañeda, Gerardo

    2013-01-01

    The highest enzymatic extraction of covalent linked chlorogenic (36.1%) and caffeic (CA) (33%) acids from coffee pulp (CP) was achieved by solid-state fermentation with a mixture of three enzymatic extracts produced by Aspergillus tamarii, Rhizomucor pusillus, and Trametes sp. Enzyme extracts were produced in a practical inexpensive way. Synergistic effects on the extraction yield were observed when more than one enzyme extract was used. In addition, biotransformation of chlorogenic acid (ChA) by Aspergillus niger C23308 was studied. Equimolar transformation of ChA into CA and quinic acids (QA) was observed during the first 36 h in submerged culture. Subsequently, after 36 h, equimolar transformation of CA into protocatechuic acid was observed; this pathway is being reported for the first time for A. niger. QA was used as a carbon source by A. niger C23308. This study presents the potential of using CP to produce enzymes and compounds such as ChA with biological activities. PMID:23341203

  17. Improved survival in a multidisciplinary short bowel syndrome program

    PubMed Central

    Modi, Biren P.; Langer, Monica; Ching, Y. Avery; Valim, Clarissa; Waterford, Stephen D.; Iglesias, Julie; Duro, Debora; Lo, Clifford; Jaksic, Tom; Duggan, Christopher

    2011-01-01

    Purpose Pediatric short bowel syndrome (SBS) remains a management challenge with significant mortality. In 1999, we initiated a multidisciplinary pediatric intestinal rehabilitation program. The purpose of this study was to determine if the multidisciplinary approach was associated with improved survival in this patient population. Methods The Center for Advanced Intestinal Rehabilitation includes dedicated staff in surgery, gastroenterology, nutrition, pharmacy, nursing, and social work. We reviewed the medical records of all inpatients and outpatients with severe SBS treated from 1999 to 2006. These patients were compared to a historical control group of 30 consecutive patients with severe SBS who were treated between 1986 and 1998. Results Fifty-four patients with severe SBS managed by the multidisciplinary program were identified. Median follow-up was 403 days. The mean residual small intestinal length was 70 ± 36 vs 83 ± 67 cm in the historical controls (P = NS). Mean peak direct bilirubin was 8.1 ± 7.9 vs 9.0 ± 7.4 mg/dL in controls (P = NS). Full enteral nutrition was achieved in 36 (67%) of 54 patients with severe SBS vs 20 (67%) of 30 patients in the control group (P = NS). The overall survival rate, however, was 89% (48/54), which is significantly higher than in the historical controls (70%, 21/30; P < .05). Conclusions A multidisciplinary approach to intestinal rehabilitation allows for fully integrated care of inpatients and outpatients with SBS by fostering coordination of surgical, medical, and nutritional management. Our experience with 2 comparable cohorts demonstrates that this multidisciplinary approach is associated with improved survival. PMID:18206449

  18. Bombesin improves survival from methotrexate-induced enterocolitis.

    PubMed Central

    Chu, K U; Higashide, S; Evers, B M; Rajaraman, S; Ishizuka, J; Townsend, C M; Thompson, J C

    1994-01-01

    OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents. Images Figure 5. Figure 7. PMID:7944667

  19. Advanced Quality Control System for the Thermomechanical Pulping Process Improves Quality and Reduces Energy Costs for Augusta Newsprint

    SciTech Connect

    Not Available

    2002-02-01

    In July 2001, the Augusta Newsprint Company partnered with Invensys' Pacific Simulation group to implement an advanced quality control (AQC) solution for the thermomechanical pulping (TMP) process at Augusta Newsprint's Augusta, Georgia, site. The goal of the project is to decrease energy and raw material costs while maintaining final pulp quality. The project involves coordinating AQC in 3 areas of the paper mill to reduce the amount of energy required for manufacturing. In addition, a time-of-day production (TODP) feature will use current power market pricing data to adjust production rates in the pulping operation to minimize the average cost of purchased energy. The AQC implementation is currently in progress.

  20. Improved oil-off survivability of tapered roller bearings

    NASA Technical Reports Server (NTRS)

    Kreider, Gary E.; Lee, Peter W.

    1987-01-01

    The aim of this program is to improve the oil-off survivability of a tapered roller bearing when applied to a helicopter transmission, since the tapered bearing has shown a performance advantage in this application. However, the critical roller end-rib conjunction is vulnerable to damage in an oil-off condition. Three powdered metal materials were selected to use as the rib material for oil-off evaluation. These were: M2 steel to a 65% density, CBS 1000M 65% density, and CBS 1000M 75% density. The bearing styles tested were ribbed cone (inner race) and ribbed cup (outer race). Carburized solid CBS 600 was also used as a ribbed material for comparison of oil-off results. The tests were conducted at six speeds from 4000 rpm (0.26 million DN) through 37000 rpm (2.4 million DN).The ribbed cup style bearing achieved longer lives than the ribbed cone style. A standard bearing lasted only 10 minutes at 4000 rpm; however, the 30-min oil-off goal was achieved through 11000 rpm using the survivable ribbed cup bearing. The oil-off lives at 37000 rpm were less than 10 seconds. The grinding of the powder metal materials and surface preparation to achieve an open porosity is extremely critical to the oil-off performance of the powder metal component.

  1. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    SciTech Connect

    Gerber, Naamit Kurshan; Wexler, Leonard H.; Singer, Samuel; Alektiar, Kaled M.; Keohan, Mary Louise; Shi, Weiji; Zhang, Zhigang; Wolden, Suzanne

    2013-05-01

    Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

  2. Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function

    PubMed Central

    Izumoto-Akita, Takako; Tsunekawa, Shin; Yamamoto, Akihito; Uenishi, Eita; Ishikawa, Kota; Ogata, Hidetada; Iida, Atsushi; Ikeniwa, Makoto; Hosokawa, Kaori; Niwa, Yasuhiro; Maekawa, Ryuya; Yamauchi, Yuichiro; Seino, Yusuke; Hamada, Yoji; Hibi, Hideharu; Arima, Hiroshi; Ueda, Minoru; Oiso, Yutaka

    2015-01-01

    Objective Many studies have reported that stem cell transplantation promotes propagation and protection of pancreatic β-cells in streptozotocin (STZ)-induced diabetic mice without the differentiation of transplanted cells into pancreatic β-cells, suggesting that the improvement is due to a paracrine effect of the transplanted cells. We investigated the effects of factors secreted by dental pulp stem cells from human exfoliated deciduous teeth (SHED) on β-cell function and survival. Research design and methods Conditioned medium from SHED (SHED-CM) was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM). The insulin levels in SHED-CM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BM-CM) were undetectable. STZ-induced diabetic male C57B/6J mice were injected with DMEM as a control, SHED-CM, exendin-4 (Ex-4), or BM-CM for 14 days. Mouse pancreatic β-cell line MIN6 cells were incubated with different concentrations of STZ with SHED-CM, DMEM, Ex-4, or BM-CM for 6 h. Results Administration of 1 mL of SHED-CM twice a day improved glucose intolerance in STZ-induced diabetic mice and the effect continued for 20 days after the end of treatment. SHED-CM treatment increased pancreatic insulin content and β-cell mass through proliferation and an intraperitoneal glucose tolerance test revealed enhanced insulin secretion. Incubation of MIN6 cells (a mouse pancreatic β-cell line) with SHED-CM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZ-induced cell death, indicating that the amelioration of hyperglycemia was caused by the direct effects of SHED-CM on β-cell function and survival. These effects were more pronounced than with the use of Ex-4, a conventional incretin-based drug, and BM-CM, which is a medium derived from other stem cells. Conclusions These findings suggest that SHED-CM provides direct protection and encourages the propagation of

  3. Improved survival after liver transplantation in patients with hepatopulmonary syndrome.

    PubMed

    Gupta, S; Castel, H; Rao, R V; Picard, M; Lilly, L; Faughnan, M E; Pomier-Layrargues, G

    2010-02-01

    Hepatopulmonary syndrome (HPS) is present in 10-32% of chronic liver disease patients, carries a poor prognosis and is treatable by liver transplantation (LT). Previous reports have shown high LT mortality in HPS and severe HPS (arterial oxygen (PaO(2)) < or =50 mmHg). We reviewed outcomes in HPS patients who received LT between 2002 and 2008 at two transplant centers supported by a dedicated HPS clinic. We assessed mortality, complications and gas exchange in 21 HPS patients (mean age 51 years, MELD score 14), including 11/21 (52%) with severe HPS and 5/21 (24%) with living donor LT (median follow-up 20.2 months after LT). Overall mortality was 1/21 (5%); mortality in severe HPS was 1/11 (9%). Peritransplant hypoxemic respiratory failure occurred in 5/21 (24%), biliary complications in 8/21 (38%) and bleeding or vascular complications in 6/21 (29%). Oxygenation improved in all 19 patients in whom PaO(2) or SaO(2) were recorded. PaO(2) increased from 52.2 +/- 13.2 to 90.3 +/- 11.5 mmHg (room air) (p < 0.0001) (12 patients); a higher baseline macroaggregated albumin shunt fraction predicted a lower rate of postoperative improvement (p = 0.045) (7 patients). Liver transplant survival in HPS and severe HPS was higher than previously demonstrated. Severity of HPS should not be the basis for transplant refusal. PMID:19775311

  4. Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates.

    PubMed

    Hankey, Kim G; Farese, Ann M; Blaauw, Erica C; Gibbs, Allison M; Smith, Cassandra P; Katz, Barry P; Tong, Yan; Prado, Karl L; MacVittie, Thomas J

    2015-06-01

    Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 μg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/μL, ANC ≥1,000/μL and platelet (PLT) count ≥20,000/μL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data

  5. Improving halva quality with dietary fibres of sesame seed coats and date pulp, enriched with emulsifier.

    PubMed

    Elleuch, Mohamed; Bedigian, Dorothea; Maazoun, Bouthaina; Besbes, Souhail; Blecker, Christophe; Attia, Hamadi

    2014-02-15

    Supplementation of halva with waste products of manufacturing, for example defatted sesame seed coats (testae) and date fibre concentrate, can improve its nutritional and organoleptic qualities. These constituents provide high fibre content and technological potential for retaining water and fat. Standard halva supplemented with date fibre concentrate, defatted sesame testae and emulsifier was evaluated for oil separation, texture and colour changes, sensory qualities and acceptability to a taste panel. Addition of both fibres with an emulsifier, improved emulsion stability and increased the hardness of halva significantly. The functional properties of sesame testae and date fibres promote nutrition and health, supplying polyphenol antioxidants and laxative benefits. PMID:24128542

  6. Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer

    MedlinePlus

    ... Prevention Lung Cancer Screening Research Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer ( ... starting treatment without their disease getting worse (progression-free survival), as assessed by radiologic review. Results Progression- ...

  7. Improving wet and dry strength properties of recycled old corrugated carton (OCC) pulp using various polymers.

    PubMed

    Hamzeh, Yahya; Sabbaghi, Sanaz; Ashori, Alireza; Abdulkhani, Ali; Soltani, Farshid

    2013-04-15

    In this study, the application of different dosages of low and high molecular weights (MW) of chitosan (Ch), cationic starch (CS) and poly vinyl alcohol (PVA) were systematically investigated using old corrugated carton (OCC) furnishes. Various sequences of above-mentioned polymeric additives were also examined to find out the optimal combination for improving both wet and dry tensile strength. For each treatment, 4 handsheets, each having basis weight of 100 g/m(2), were made. In general, the tensile strength of handsheets was significantly affected by the addition of polymeric agents. The enhancing effect of additives on dry tensile property was much higher than wet condition. The results also showed that the tensile strength of the samples made from OCC furnishes were improved upon the addition of high molecular weight chitosan (ChI) compared to the untreated ones (control). The low MW chitosan did not change the properties of handsheets dramatically. Application of polymeric agents moderately decreased the stretch to rupture, however with increasing dosage the stretch was improved. Sequential addition of used polymers showed that triple application of polymers was beneficial to both dry and wet tensile strength, although the effect was larger for dry. The best results in wet and dry tensile strengths were achieved using sequential of PVA-ChI-CS. Sequential addition of oppositely charged polymers forms a macromolecular layered structure of polyelectrolytes. PMID:23544577

  8. [Hope for improvement of survival in ovarian cancer].

    PubMed

    Högberg, Thomas; Bergfeldt, Kjell; Borgfeldt, Christer; Holmberg, Erik; Åvall Lundqvist, Elisabeth

    2015-01-01

    Ovarian cancer is the most common cause of death from a gynecologic cancer. Every year around 700 women contracts ovarian cancer in Sweden. The overall survival is among the highest in Europe, but still long term relative survival is only 46%. It is a long-held myth that ovarian cancer is a disease without symptoms. Almost 90% of women have symptoms, even in the early stages. Symptoms that should arise suspicion of ovarian cancer and initiate diagnostic work-up are continuous abdominal extension, early feeling of satiety, pelvic or abdominal pain, urinary urge and postmenopausal bleeding. Women's awareness of symptoms and willingness to seek medical advice and the organization of the health care system are important factors determining cancer survival. Ovarian cancer is a heterogeneous group of diseases with different tumor traits and prognosis. Personalized medicine and preventive measures recognizing recent knowledge about tumor biology will positively affect survival. PMID:26646961

  9. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Cancer.gov

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  10. Method of freezing living cells and tissues with improved subsequent survival

    DOEpatents

    Senkan, Selim M.; Hirsch, Gerald P.

    1980-01-01

    This invention relates to an improved method for freezing red blood cells, ther living cells, or tissues with improved subsequent survival, wherein constant-volume freezing is utilized that results in significantly improved survival compared with constant-pressure freezing; optimization is attainable through the use of different vessel geometries, cooling baths and warming baths, and sample concentrations.

  11. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  12. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  13. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  14. A histologic assessment of a HYBENX® oral tissue decontaminant in vital pulp therapy in dogs.

    PubMed

    Rohrer, M D; Prasad, H S; Savord, E G

    2016-01-01

    The aim of this study was to assess HYBENX® Oral Tissue Decontaminant (HOTD) in treating vital pulp exposure in a canine model. The use of HOTD solution was compared to an accepted and standard regimen for vital pulp exposure, an application of a commercial calcium hydroxide product (Ca(OH)2). Both control and experimental treatments were followed by restoration with a commercial zinc oxide and eugenol obtundant intermediate restorative material and thermal insulator (ZOE). At 7 days there was 100% pulp vitality with HOTD and 50% with Ca(OH)2. New dentin formation was seen in 62.5% of the HOTD treated pulps and none of the Ca(OH)2 treatment group. The vital pulp exposures at day 21 post treatment with HOTD also showed significant improvement over Ca(OH)2 in the presence of odontoblasts, new dentin formation and pulp survivability. The presence of odontoblasts and new dentin was noted in 71% of the HOTD cases versus 50% of the survivable Ca(OH)2 cases. Furthermore, 100% of HOTD cases had vital pulps versus 62.5% of Ca(OH)2 cases. The 60-day specimens of both experimental and control techniques exhibited histologically similar appearances and were similar in outcomes. HOTD treatment at day 7 showed a significant positive difference, both in the formation of new dentin and tooth vitality. HOTD proved better for the post 21-day specimens and equivalent for the 60-day pulp specimens with no evidence of untoward tissue reactions or results. PMID:27469568

  15. Pulp Regeneration: Current Approaches and Future Challenges

    PubMed Central

    Yang, Jingwen; Yuan, Guohua; Chen, Zhi

    2016-01-01

    Regenerative endodontics aims to replace inflamed/necrotic pulp tissues with regenerated pulp-like tissues to revitalize teeth and improve life quality. Pulp revascularization case reports, which showed successful clinical and radiographic outcomes, indicated the possible clinical application of pulp regeneration via cell homing strategy. From a clinical point of view, functional pulp-like tissues should be regenerated with the characterization of vascularization, re-innervation, and dentin deposition with a regulated rate similar to that of normal pulp. Efficient root canal disinfection and proper size of the apical foramen are the two requisite preconditions for pulp regeneration. Progress has been made on pulp regeneration via cell homing strategies. This review focused on the requisite preconditions and cell homing strategies for pulp regeneration. In addition to the traditionally used mechanical preparation and irrigation, antibiotics, irrigation assisted with EndoVac apical negative-pressure system, and ultrasonic and laser irradiation are now being used in root canal disinfection. In addition, pulp-like tissues could be formed with the apical foramen less than 1 mm, although more studies are needed to determine the appropriate size. Moreover, signaling molecules including stromal cell derived factor (SDF-1α), basic Fibroblast Growth Factor (bFGF), Platelet Derived Growth Factor (PDGF), stem cell factor (SCF), and Granulocyte Colony-Stimulating Factor (G-CSF) were used to achieve pulp-like tissue formation via a cell homing strategy. Studies on the cell sources of pulp regeneration might give some indications on the signaling molecular selection. The active recruitment of endogenous cells into root canals to regenerate pulp-like tissues is a novel concept that may offer an unprecedented opportunity for the near-term clinical translation of current biology-based therapies for dental pulp regeneration. PMID:27014076

  16. Improving Survival of Pancreatic Cancer. What Have We Learnt?

    PubMed

    Singh, Tanveer; Chaudhary, Adarsh

    2015-10-01

    Pancreatic adenocarcinoma still ranks high among cancer-related deaths worldwide. In spite of substantial strides in preoperative staging, surgery, perioperative care, and adjuvant treatment, the survival still remains dismal. A number of patient-, disease-, and surgeon-related factors play a role in deciding the eventual outcome of the patient. The aim of this commentary is to review the current knowledge of various factors and the recent advances that impact the survival of patients with pancreatic adenocarcinoma. A search of scientific literature using Embase and MEDLINE, for the years 1985-2015, was carried out for search terms "pancreatic cancer" and "survival." Further search was based on the various specific prognostic factors that contribute towards survival of patients with pancreatic cancer found in the literature. Most of the studies used for this review include those that deal with pancreatic head cancers, some include patients with pancreatic cancers in all locations while very few included patients with tumors of body and tail only. In spite of significant developments in pre- and perioperative management, increased rates of margin-negative resections, and use of adjuvant treatment, the survival rates of pancreatic cancer patients remains poor. A paradigm shift with more effective adjuvant regimen and genetic interventions may help change the outcomes of patients with pancreatic cancer. PMID:26722209

  17. Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

    PubMed Central

    Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin

    2014-01-01

    Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis. PMID:24590482

  18. Opportunities to improve energy efficiency and reduce greenhouse gas emissions in the U.S. pulp and paper industry

    SciTech Connect

    Martin, Nathan; Anglani, N.; Einstein, D.; Khrushch, M.; Worrell, E.; Price, L.K.

    2000-07-01

    The pulp and paper industry accounts for over 12% of total manufacturing energy use in the U.S. (U.S. EIA 1997a), contributing 9% to total manufacturing carbon dioxide emissions. In the last twenty-five years primary energy intensity in the pulp and paper industry has declined by an average of 1% per year. However, opportunities still exist to reduce energy use and greenhouse gas emissions in the manufacture of paper in the U.S. This report analyzes the pulp and paper industry (Standard Industrial Code (SIC) 26) and includes a detailed description of the processes involved in the production of paper, providing typical energy use in each process step. We identify over 45 commercially available state-of-the-art technologies and measures to reduce energy use and calculate potential energy savings and carbon dioxide emissions reductions. Given the importance of paper recycling, our analysis examines two cases. Case A identifies potential primary energy savings without accounting for an increase in recycling, while Case B includes increasing paper recycling. In Case B the production volume of pulp is reduced to account for additional pulp recovered from recycling. We use a discount rate of 30% throughout our analysis to reflect the investment decisions taken in a business context. Our Case A results indicate that a total technical potential primary energy savings of 31% (1013 PJ) exists. For case A we identified a cost-effective savings potential of 16% (533 PJ). Carbon dioxide emission reductions from the energy savings in Case A are 25% (7.6 MtC) and 14% (4.4 MtC) for technical and cost-effective potential, respectively. When recycling is included in Case B, overall technical potential energy savings increase to 37% (1215 PJ) while cost-effective energy savings potential is 16%. Increasing paper recycling to high levels (Case B) is nearly cost-effective assuming a cut-off for cost-effectiveness of a simple payback period of 3 years. If this measure is included, then

  19. Opportunities to improve energy efficiency and reduce greenhouse gas emissions in the US pulp and paper industry

    SciTech Connect

    Martin, Nathan; Anglani, N.; Einstein, D.; Khrushch, M.; Worrell, E.; Price, L.K.

    2000-07-01

    The pulp and paper industry accounts for over 12% of total manufacturing energy use in the US (US EIA 1997a), contributing 9% to total manufacturing carbon dioxide emissions. In the last twenty-five years primary energy intensity in the pulp and paper industry has declined by an average of 1% per year. However, opportunities still exist to reduce energy use and greenhouse gas emissions in the manufacture of paper in the US This report analyzes the pulp and paper industry (Standard Industrial Code (SIC) 26) and includes a detailed description of the processes involved in the production of paper, providing typical energy use in each process step. We identify over 45 commercially available state-of-the-art technologies and measures to reduce energy use and calculate potential energy savings and carbon dioxide emissions reductions. Given the importance of paper recycling, our analysis examines two cases. Case A identifies potential primary energy savings without accounting for an increase in recycling, while Case B includes increasing paper recycling. In Case B the production volume of pulp is reduced to account for additional pulp recovered from recycling. We use a discount rate of 30% throughout our analysis to reflect the investment decisions taken in a business context. Our Case A results indicate that a total technical potential primary energy savings of 31% (1013 PJ) exists. For case A we identified a cost-effective savings potential of 16% (533 PJ). Carbon dioxide emission reductions from the energy savings in Case A are 25% (7.6 MtC) and 14% (4.4 MtC) for technical and cost-effective potential, respectively. When recycling is included in Case B, overall technical potential energy savings increase to 37% (1215 PJ) while cost-effective energy savings potential is 16%. Increasing paper recycling to high levels (Case B) is nearly cost-effective assuming a cut-off for cost-effectiveness of a simple payback period of 3 years. If this measure is included, then the

  20. Multi-hospital Community NICU Quality Improvement Improves Survival of ELBW Infants.

    PubMed

    Owens, Jack D; Soltau, Thomas; McCaughn, Danny; Miller, Jason; O'Mara, Patrick; Robbins, Kenny; Temple, David M; Wender, David F

    2015-08-01

    Quality improvement or high reliability in medicine is an evolving science where we seek to integrate evidence-based medicine, structural resources, process management, leadership models, culture, and education. Newborn Associates is a community-based neonatology practice that staffs and manages neonatal intensive care units (NICU's) at Central Mississippi Medical Center, Mississippi Baptist Medical Center, River Oaks Hospital, St Dominic's Hospital and Woman's Hospital within the Jackson, Mississippi, metropolitan area. These hospitals participate in the Vermont-Oxford Neonatal Network (VON), which is a voluntary national network of about 1000 NICU groups that submit data allowing them to benchmark their patient outcome. This network currently holds data on 1.5 million infants. Participation may also include the Newborn Improvement Quality Collaborative (NICQ) which is an intensive quality improvement program where 40-60 of the almost 1000 VON centers participate each year or the iNICQ, which is an internet-based collaborative involving about 150 centers per year. From 2008-2009, our group concentrated efforts on quality improvement which included consolidating resources of three corporately managed hospitals to allow focused care of babies under 800-1000 grams at a single center, expanding participation in the VON NICQ to include all physicians and centers, and establishing a group QI focused committee aimed at sharing practice bundles and adopting quality improvement methodology. The goal of this article is to report the impact of these QI activities on survival of the smallest preterm infants who weigh less than 1500 grams at birth. Two epochs were compared: 2006-2009, and 2010-2013. 551 VLBW (< 1 500 grams) infants from epoch I were compared to 583 VLBW infants from epoch 2. Mortality in this group decreased from 18% to 11.1% (OR 0.62,95% CI 0.44-0.88). Mortality in the 501-750 grams birth weight category decreased from 45.7% to 18% (OR 0.39,95% CI 0

  1. Thymic Stromal Lymphopoietin Improves Survival and Reduces Inflammation in Sepsis.

    PubMed

    Piliponsky, Adrian M; Lahiri, Asha; Truong, Phuong; Clauson, Morgan; Shubin, Nicholas J; Han, Hongwei; Ziegler, Steven F

    2016-08-01

    The mechanisms that contribute to homeostasis of the immune system in sepsis are largely unknown. One study suggests a potential detrimental role for thymic stromal lymphopoietin (TSLP) in sepsis; however, the immune-regulatory effects of TSLP on myeloid cells within the intestinal microenvironment suggest the contrary. Our objective was to clarify TSLP's role in sepsis. Cecal ligation and puncture was performed in mice with total or myeloid-specific deficiency in the TSLP receptor (TSLPR). Survival was monitored closely, peritoneal fluids and plasma were analyzed for markers of inflammation, and myeloid cell numbers and their ability to produce inflammatory mediators was determined. The interaction of TSLP with TSLPR in myeloid cells contributed to mouse survival after septic peritonitis. Mice with TSLPR deficiency in myeloid cells displayed excessive local and systemic inflammation levels (e.g., increased inflammatory cell and cytokine levels) relative to control mice. Moreover, hepatic injury was exacerbated in mice with TSLPR deficiency in their myeloid cells. However, the enhanced inflammatory response did not affect the ability of these mice to clear bacteria. Resident neutrophils and macrophages from septic mice with TSLPR deficiency exhibited an increased ability to produce proinflammatory cytokines. Collectively, our findings suggest that the effects of TSLP on myeloid cells are crucial in reducing the multiple organ failure that is associated with systemic inflammation, which highlights the significance of this cytokine in modulating the host response to infection and in reducing the risks of sepsis development. PMID:26934097

  2. Sperm Count Improvement in a Cancer-Surviving Patient

    PubMed Central

    Pereira, Maria Conceição; Vieira, Margarida M.; Pereira, Joana Simões

    2015-01-01

    Objective To describe the case of a cancer-surviving patient who was treated with an aromatase inhibitor for fertility reasons with successful results. Clinical Case A 30-year-old patient from our institute who had been submitted to bone marrow transplantation in the past as part of treatment for Hodgkin's disease had revealed oligospermia several times. His sperm count mean value was 33,500 cells/ml. He was treated with an aromatase inhibitor (letrozole, 2 mg/day) for 8 months. After this period, his sperm count had increased significantly to 1,000,000 cells/ml. Conclusion A large number of cancer survivors express a wish for having babies. After their cure, a lot of them have a low count of spermatozoids, and we think that our results show an easy way of helping them. PMID:26351438

  3. Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.

    PubMed

    Wood, William A; Lee, Stephanie J; Brazauskas, Ruta; Wang, Zhiwei; Aljurf, Mahmoud D; Ballen, Karen K; Buchbinder, David K; Dehn, Jason; Freytes, Cesar O; Lazarus, Hillard M; Lemaistre, Charles F; Mehta, Paulette; Szwajcer, David; Joffe, Steven; Majhail, Navneet S

    2014-06-01

    Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children. PMID:24607554

  4. Improving village poultry's survival rate through community-based poultry health management: evidence from Benin.

    PubMed

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto Delphin

    2013-01-01

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of "poultry interest groups" in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due to the fact that village poultry farming is practiced in a total or partial scavenging system which gives the impression that all the birds in the village belong to the same flock. Accordingly, actions that target all farmers of the same village may have a larger impact on the village poultry's survival rate than actions that target individual producers. The objective of this study is to assess the impact of CBM on the survival rate of village poultry. Based on data collected on 353 poultry keepers, the study shows that CBM significantly improves the survival rate of village poultry. The adoption of technologies--poultry vaccination, construction of henhouses, and improved feed--disseminated through the CBM also significantly improves the survival rate. The access to markets for inputs and veterinary services is also important in improving the survival rate of poultry. Finally, the study suggests that governments and development agencies can improve village poultry survival rates by investing in the dissemination of information regarding best husbandry management practices through approaches that rely on the community such as CBM because CBM groups serve as channels for the dissemination of village poultry improvement technologies. PMID:22618192

  5. Metallic ions catalysis for improving bioleaching yield of Zn and Mn from spent Zn-Mn batteries at high pulp density of 10.

    PubMed

    Niu, Zhirui; Huang, Qifei; Wang, Jia; Yang, Yiran; Xin, Baoping; Chen, Shi

    2015-11-15

    Bioleaching of spent batteries was often conducted at pulp density of 1.0% or lower. In this work, metallic ions catalytic bioleaching was used for release Zn and Mn from spent ZMBs at 10% of pulp density. The results showed only Cu(2+) improved mobilization of Zn and Mn from the spent batteries among tested four metallic ions. When Cu(2+) content increased from 0 to 0.8 g/L, the maximum release efficiency elevated from 47.7% to 62.5% for Zn and from 30.9% to 62.4% for Mn, respectively. The Cu(2+) catalysis boosted bioleaching of resistant hetaerolite through forming a possible intermediate CuMn2O4 which was subject to be attacked by Fe(3+) based on a cycle of Fe(3+)/Fe(2+). However, poor growth of cells, formation of KFe3(SO4)2(OH)6 and its possible blockage between cells and energy matters destroyed the cycle of Fe(3+)/Fe(2+), stopping bioleaching of hetaerolite. The chemical reaction controlled model fitted best for describing Cu(2+) catalytic bioleaching of spent ZMBs. PMID:26057441

  6. Improved survival in limited scleroderma-related pulmonary artery hypertension.

    PubMed

    Marini, Carlo; Formichi, Bruno; Bauleo, Carolina; Michelassi, Claudio; Pancani, Roberta; Prediletto, Renato; Miniati, Massimo; Catapano, Giosuè; Monti, Simonetta; Mannucci, Francesca; Tavoni, Antonio; D'Ascanio, Anna; Pastormerlo, Luigi Emilio; Giannoni, Alberto; Giuntini, Carlo

    2014-06-01

    Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO2) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO2 <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO2 are predictors of survival and may assist in planning treatment. PMID:23361526

  7. Improved survival of newborns receiving leukocyte transfusions for sepsis

    SciTech Connect

    Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.

    1984-11-01

    To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions.

  8. Filial cannibalism improves survival and development of beaugregory damselfish embryos.

    PubMed Central

    Payne, Adam G; Smith, Carl; Campbell, Andrew C

    2002-01-01

    Cannibalism of small numbers of offspring by a parent has been proposed as an adaptive parental strategy, by providing energy to support parental care. However, there are few empirical studies to support this hypothesis. We conducted field and laboratory experiments to investigate partial filial cannibalism in Stegastes leucostictus, a coral reef fish with paternal care. Partial cannibalism was shown to be common, and males were found to remove developing embryos from throughout a clutch in a random pattern, rather than in the more aggregated pattern seen during embryo predation. Males that received a diet supplement grew faster than control males, but did not engage in less cannibalism. Also, males did not concentrate cannibalism on early embryonic stages with the highest energetic value. Experimental reduction of embryo densities was found to significantly increase embryo development rate and survival from egg deposition to hatching, and experimental reduction of oxygen levels significantly increased rates of partial filial cannibalism by males. Artificial spawning sites with low oxygen levels were avoided by spawning females, and cannibalism rates by males were higher. We propose that partial filial cannibalism serves as an adaptive parental strategy to low oxygen levels in S. leucostictus by increasing the hatching success of embryos. PMID:12396483

  9. Filial cannibalism improves survival and development of beaugregory damselfish embryos.

    PubMed

    Payne, Adam G; Smith, Carl; Campbell, Andrew C

    2002-10-22

    Cannibalism of small numbers of offspring by a parent has been proposed as an adaptive parental strategy, by providing energy to support parental care. However, there are few empirical studies to support this hypothesis. We conducted field and laboratory experiments to investigate partial filial cannibalism in Stegastes leucostictus, a coral reef fish with paternal care. Partial cannibalism was shown to be common, and males were found to remove developing embryos from throughout a clutch in a random pattern, rather than in the more aggregated pattern seen during embryo predation. Males that received a diet supplement grew faster than control males, but did not engage in less cannibalism. Also, males did not concentrate cannibalism on early embryonic stages with the highest energetic value. Experimental reduction of embryo densities was found to significantly increase embryo development rate and survival from egg deposition to hatching, and experimental reduction of oxygen levels significantly increased rates of partial filial cannibalism by males. Artificial spawning sites with low oxygen levels were avoided by spawning females, and cannibalism rates by males were higher. We propose that partial filial cannibalism serves as an adaptive parental strategy to low oxygen levels in S. leucostictus by increasing the hatching success of embryos. PMID:12396483

  10. Refining of Polysulfide Pulps

    NASA Astrophysics Data System (ADS)

    Copur, Yalcin

    This study compares the modified kraft process, polysulfide pulping, one of the methods to obtain higher pulp yield, with conventional kraft method. More specifically, the study focuses on the refining effects of polysulfide pulp, which is an area with limited literature. Physical, mechanical and chemical properties of kraft and polysulfide pulps (4% elemental sulfur addition to cooking digester) cooked under the same conditions were studied as regards to their behavior under various PFI refining (0, 3000, 6000, 9000 revs.). Polysulfide (PS) pulping, compared to the kraft method, resulted in higher pulp yield and higher pulp kappa number. Polysulfide also gave pulp having higher tensile and burst index. However, the strength of polysulfide pulp, tear index at a constant tensile index, was found to be 15% lower as compared to the kraft pulp. Refining studies showed that moisture holding ability of chemical pulps mostly depends on the chemical nature of the pulp. Refining effects such as fibrillation and fine content did not have a significant effect on the hygroscopic behavior of chemical pulp.

  11. Optimizing hemodialysis practices in Canada could improve patient survival.

    PubMed

    Yeates, Karen E; Mendelssohn, David C; Ethier, Jean; Trpeski, Lilyanna; Na, Jingbo; Bragg-Gresham, Jennifer L; Eichleay, Margaret A; Pisoni, Ronald L; Port, Fritz K

    2007-01-01

    Data from the Canadian Organ Replacement Registry (CORR) and the Dialysis Outcomes and Practice Patterns Study (DOPPS) were used to determine whether practice patterns have changed in Canada since the introduction of the Canadian Society of Nephrology (CSN) Guidelines in 1999. DOPPS data were then used to calculate the impact of not meeting the proposed guideline targets and to estimate the potential life years gained if all Canadian hemodialysis patients achieved guideline targets. For dialysis dose and hemoglobin targets, Canadian facility performance has significantly improved over time. The vascular access use patterns show trends toward a worse pattern with increased catheter use. A calculation of the percentage of attributable risk suggests that 49% of deaths could possibly be averted if all patients currently outside the guidelines achieved them over the next five years. This corresponds to a decrease in the annual death rate from 18 to 10.1 per hundred patient years. These data support the need for improved adherence to guidelines. If Canadian caregivers were to optimize practice patterns, patient outcomes could be improved. PMID:17691708

  12. Sex, Race, and Age Disparities in the Improvement of Survival for Gastrointestinal Cancer over Time

    PubMed Central

    Wan, Jue-feng; Yang, Li-feng; Shen, Yun-zhu; Jia, Hui-xun; Zhu, Ji; Li, Gui-chao; Zhang, Zhen

    2016-01-01

    There have been notable improvements in survival over the past 2 decades for gastrointestinal (GI) cancer. However, the degree of improvement by age, race, and sex remains unclear. We analyzed data from 9 population-based cancer registries included in the SEER program of the National Cancer Institute (SEER 9) in 1990 to 2009 (n = 288,337). The degree of survival improvement over time by age, race, and sex was longitudinally measured. From 1990 to 2009, improvements in survival were greater for younger age groups. For patients aged 20 to 49 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.74 (95% CI, 0.66–0.83), 0.49 (95% CI, 0.37–0.64), 0.69 (95% CI, 0.65–0.76), 0.62 (95% CI, 0.54–0.69), and 0.56 (95% CI, 0.42–0.76), for cancer of the stomach, small intestine, colon, rectum and anus, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. Compared with African Americans, whites experienced greater improvement in small intestinal and anal cancer survival. Female anal cancer and regional anal cancer patients experienced no improvement. Our data suggest that different improvement in survival in age, sex and race exists. PMID:27406065

  13. Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival Over Five Decades.

    PubMed

    Kirchoff, Daniel D; Deutsch, Gary B; Foshag, Leland J; Lee, Ji Hey; Sim, Myung-Shin; Faries, Mark B

    2016-01-01

    Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized. PMID:26802836

  14. Bio-conventional bleaching of kadam kraft-AQ pulp by thermo-alkali-tolerant xylanases from two strains of Coprinellus disseminatus for extenuating adsorbable organic halides and improving strength with optical properties and energy conservation.

    PubMed

    Lal, Mohan; Dutt, Dharm; Tyagi, C H

    2012-04-01

    Two novel thermo-alkali-tolerant crude xylanases namely MLK-01 (enzyme-A) and MLK-07 (enzyme-B) from Coprinellus disseminatus mitigated kappa numbers of Anthocephalus cadamba kraft-AQ pulps by 32.5 and 34.38%, improved brightness by 1.5 and 1.6% and viscosity by 5.75 and 6.47% after (A)XE(1) and (B)XE(1)-stages, respectively. The release of reducing sugars and chromophores was the highest during prebleaching of A. cadamba kraft-AQ pulp at enzyme doses of 5 and 10 IU/g, reaction times 90 and 120 min, reaction temperatures 75 and 65°C and consistency 10% for MLK-01 and MLK-07, respectively. MLK-07 was more efficient than MLK01 in terms of producing pulp brightness, improving mechanical strength properties and reducing pollution load. MLK-01 and MLK-07 reduced AOX by 19.51 and 42.77%, respectively at 4% chlorine demands with an increase in COD and colour due to removal of lignin carbohydrates complexes. A. cadamba kraft-AQ pulps treated with xylanases from MLK-01 to MLK-07 and followed by CEHH bleaching at half chlorine demand (2%) showed a drastic reduction in brightness with slight improvement in mechanical strength properties compared to pulp bleached at 4% chlorine demand. MLK-01 reduced AOX, COD and colour by 43.83, 39.03 and 27.71% and MLK-07 by 38.34, 40.48 and 30.77%, respectively at half chlorine demand compared to full chlorine demand (4%). pH variation during prebleaching of A. cadamba kraft-AQ pulps with strains MLK-01 and MLK-07 followed by CEHH bleaching sequences showed a decrease in pulp brightness, AOX, COD and colour with an increase in mechanical strength properties, pulp viscosity and PFI revolutions to get a beating level of 35 ± 1 °SR at full chlorine demand. PMID:22805918

  15. Does removal of the original pulp tissue before autotransplantation influence ingrowth of new tissue in the pulp chamber?

    PubMed

    Laureys, Wim G M; Dermaut, Luc R; Cuvelier, Claude A; De Pauw, Guy A M

    2010-10-01

    In an attempt to extend the indication area for autotransplantation of vital teeth, two possibilities can be proposed: (i) The enlargement of the apical foramen, with the aim to facilitate revascularization and ingrowth of new tissue. The ingrowth of tissue will eliminate the need for endodontic treatment when mature teeth are transplanted and (ii) the cryopreservation of teeth in case they cannot be transplanted immediately to the receptor site. Teeth with an ideal stage of root formation can be cryopreserved to perform transplantation later. Although pulpcell cultures survive crypreservation in vitro, the pulp tissue cannot survive the cryopreservation procedures when it is kept inside the pulpchamber. Therefore, the pulp tissue has to be removed before cryopreservation. It has been demonstrated that revascularization and ingrowth of new tissue can occur in an empty pulp chamber (1). The aim of this study was to find out if revascularization and ingrowth of new pulp tissue is influenced by removal of the original pulp tissue before autotransplantation. Twenty nine single-rooted teeth from three adult beagle dogs were transplanted after resection of the root tip. One group of teeth (n = 14) had the pulp tissue removed before transplantation. The other group (n = 15) had the original pulp left in situ. The transplanted teeth were histologically analysed 90 days post-transplantation. In the group with the tissue left in situ, 12 teeth (80%) showed a pulp chamber totally filled or at least 1/3 to 2/3 filled with viable tissue. In the group with the pulp tissue removed, 11 teeth (79%) had no or little vital tissue in the pulp chamber. The necrotic masses that develop in the original pulp tissue immediately after transplantation are a possible stimulating factor in the repair process of the pulp. As a conclusion, it can be stated that in case of autotransplantation of teeth, it is advisable to leave the pulp tissue in situ to stimulate the revascularization and

  16. Pulp and paper program fact sheets

    SciTech Connect

    1995-07-01

    Summaries are presented of Argonne technology transfer research projects in: sustainable forest management, environmental performance, energy performance, improved capital effectiveness, recycling, and sensors and controls. Applications in paper/pulp industry, other industries, etc. are covered.

  17. Are Global and Regional Improvements in Life Expectancy and in Child, Adult and Senior Survival Slowing?

    PubMed Central

    Hum, Ryan J.; Verguet, Stéphane; Cheng, Yu-Ling; McGahan, Anita M.; Jha, Prabhat

    2015-01-01

    Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health–primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest. PMID:25992949

  18. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Improved pension rates-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.24 Improved...

  19. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Improved pension rates-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.24 Improved...

  20. Combination of soya pulp and Bacillus coagulans lilac-01 improves intestinal bile acid metabolism without impairing the effects of prebiotics in rats fed a cholic acid-supplemented diet.

    PubMed

    Lee, Yeonmi; Yoshitsugu, Reika; Kikuchi, Keidai; Joe, Ga-Hyun; Tsuji, Misaki; Nose, Takuma; Shimizu, Hidehisa; Hara, Hiroshi; Minamida, Kimiko; Miwa, Kazunori; Ishizuka, Satoshi

    2016-08-01

    Intestinal bacteria are involved in bile acid (BA) deconjugation and/or dehydroxylation and are responsible for the production of secondary BA. However, an increase in the production of secondary BA modulates the intestinal microbiota due to the bactericidal effects and promotes cancer risk in the liver and colon. The ingestion of Bacillus coagulans improves constipation via the activation of bowel movement to promote defaecation in humans, which may alter BA metabolism in the intestinal contents. BA secretion is promoted with high-fat diet consumption, and the ratio of cholic acid (CA):chenodeoxycholic acid in primary BA increases with ageing. The dietary supplementation of CA mimics the BA environment in diet-induced obesity and ageing. We investigated whether B. coagulans lilac-01 and soya pulp influence both BA metabolism and the maintenance of host health in CA-supplemented diet-fed rats. In CA-fed rats, soya pulp significantly increased the production of secondary BA such as deoxycholic acid and ω-muricholic acids, and soya pulp ingestion alleviated problems related to plasma adiponectin and gut permeability in rats fed the CA diet. The combination of B. coagulans and soya pulp successfully suppressed the increased production of secondary BA in CA-fed rats compared with soya pulp itself, without impairing the beneficial effects of soya pulp ingestion. In conclusion, it is possible that a combination of prebiotics and probiotics can be used to avoid an unnecessary increase in the production of secondary BA in the large intestine without impairing the beneficial functions of prebiotics. PMID:27464459

  1. Biomechanical pulping: A mill-scale evaluation

    SciTech Connect

    Akhtar, M.; Scott, G.M.; Swaney, R.E.; Shipley, D.F.

    1999-07-01

    Mechanical pulping process is electrical energy intensive and results in low paper strength. Biomechanical pulping, defined as the fungal treatment of lignocellulosic materials prior to mechanical pulping, has shown at least 30% savings in electrical energy consumption, and significant improvements in paper strength properties compared to the control at a laboratory scale. In an effort to scale-up biomechanical pulping to an industrial level, fifty tons of spruce wood chips were inoculated with the best biopulping fungus in a continuous operation and stored in the form of an outdoor chip pile for two weeks. The pile was ventilated with conditioned air to maintain the optimum growth temperature and moisture throughout the pile. The control and fungus-treated chips were refined through a thermomechanical pulp mill (TMP) producing lightweight coated paper. The fungal pretreatment saved 33% electrical energy and improved paper strength properties significantly compared to the control. Since biofibers were stronger than the conventional TMP fibers, the authors were able to reduce the amount of bleached softwood kraft pulp by at least 5% in the final product. Fungal pretreatment reduced brightness, but brightness was restored to the level of bleached control with 60% more hydrogen peroxide. The economics of biomechanical pulping look attractive.

  2. Improved survival following surgery and radiation therapy for olfactory neuroblastoma: analysis of the SEER database

    PubMed Central

    2011-01-01

    Background Olfactory Neuroblastoma is a rare malignant tumor of the olfactory tract. Reports in the literature comparing treatment modalities for this tumor are limited. Methods The SEER database (1973-2006) was queried by diagnosis code to identify patients with Olfactory Neuroblastoma. Kaplan-Meier was used to estimate survival distributions based on treatment modality. Differences in survival distributions were determined by the log-rank test. A Cox multiple regression analysis was then performed using treatment, race, SEER historic stage, sex, age at diagnosis, year at diagnosis and SEER geographic registry. Results A total of 511 Olfactory Neuroblastoma cases were reported. Five year overall survival, stratified by treatment modality was: 73% for surgery with radiotherapy, 68% for surgery only, 35% for radiotherapy only, and 26% for neither surgery nor radiotherapy. There was a significant difference in overall survival between the four treatment groups (p < 0.01). At ten years, overall survival stratified by treatment modality and stage, there was no significant improvement in survival with the addition of radiation to surgery. Conclusions Best survival results were obtained for surgery with radiotherapy. PMID:21518449

  3. Does External Beam Radiation Therapy Improve Survival Following Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma?

    PubMed Central

    Cupino, Andrew C.; Hair, Clark D.; Angle, John F.; Caldwell, Stephen H.; Rich, Tyvin A.; Berg, Carl L.; Northup, Patrick G.; Al-Osaimi, Abdullah M. S.

    2012-01-01

    ABSTRACT Background: Transcatheter arterial chemoembolization (TACE) improves survival in patients with unresectable hepatocellular carcinoma (HCC). Partial liver radiotherapy with modern techniques has been shown to be safe. The purpose of this study was to evaluate the survival value of external beam radiation therapy (EBRT) with concurrent chemotherapy combined with TACE. Methods: A University of Virginia Interventional Radiology patient log was used to identify patients treated with TACE ± another modality from 1999 through 2005. During this time, 44 patients received TACE for unresectable HCC, and 7 of these received adjuvant EBRT. Univariate analysis and multivariable proportional hazards survival modeling were used to identify factors impacting survival. Results: We compared 37 patients receiving TACE alone to 7 receiving TACE and EBRT (5 with concurrent capecitabine). Unadjusted mean transplant-free survival times were TACE only = 376 days (standard error [SE] = 63 days), TACE + EBRT = 879 days (SE = 100 days). EBRT, TNM stage, and MELD score were important predictors for survival on univariate analysis (p < .10). The adjusted hazard ratio for transplant or death in the TACE + EBRT group was 0.15 (0.02–0.95, p = .026). Conclusion: EBRT with concurrent chemotherapy following TACE is feasible and well tolerated with modern treatment techniques. Further research should be directed toward determining the potential overall survival benefit of adjuvant EBRT with chemotherapy following TACE for hepatocellular carcinoma. PMID:22574232

  4. Donor Oversizing Results in Improved Survival in Patients with Left Ventricular Assist Device.

    PubMed

    Schumer, Erin M; Black, Matthew C; Rogers, Michael P; Trivedi, Jaimin R; Birks, Emma J; Lenneman, Andrew J; Cheng, Allen; Slaughter, Mark S

    2016-01-01

    Donor to recipient undersizing can result in diminished graft survival. The United Network for Organ Sharing database was retrospectively queried from January 2008 to December 2013 to identify adult patients who underwent heart transplantation. This population was divided into those without and with a left ventricular assist device (LVAD) at the time of transplant. Both groups were further subdivided into three groups: donor:recipient body mass index (BMI) ratio <0.8 (undersized), ≥0.8 and ≤1.2 (matched), and >1.2 (oversized). Kaplan-Meier analysis was used to compare graft survival. Cox regression analysis was used to identify factors affecting graft survival time. There was no difference in mean graft survival between undersized, matched, and oversized groups in patients without an LVAD (p = 0.634). Mean graft survival was significantly worse for undersized patients with an LVAD when compared with matched and oversized patients (p = 0.032). Cox regression revealed age, creatinine, waitlist time, United Network for Organ Sharing status, BMI ratio, and total bilirubin as significant factors affecting graft survival time. A donor to recipient BMI ratio of ≥1.2 results in significantly improved long-term graft survival for patients with an LVAD at the time of heart transplantation compared with patients with a BMI ratio of <1.2. An oversized organ should be considered for patients supported with an LVAD. PMID:27258226

  5. Improving survival of probiotic bacteria using bacterial poly-γ-glutamic acid.

    PubMed

    Bhat, A R; Irorere, V U; Bartlett, T; Hill, D; Kedia, G; Charalampopoulos, D; Nualkaekul, S; Radecka, I

    2015-03-01

    A major hurdle in producing a useful probiotic food product is bacterial survival during storage and ingestion. The aim of this study was to test the effect of γ-PGA immobilisation on the survival of probiotic bacteria when stored in acidic fruit juice. Fruit juices provide an alternative means of probiotic delivery, especially to lactose intolerant individuals. In addition, the survival of γ-PGA-immobilised cells in simulated gastric juice was also assessed. Bifidobacteria strains (Bifidobacteria longum, Bifidobacteria breve), immobilised on 2.5% γ-PGA, survived significantly better (P<0.05) in orange and pomegranate juice for 39 and 11 days respectively, compared to free cells. However, cells survived significantly better (P<0.05) when stored in orange juice compared to pomegranate juice. Moreover, both strains, when protected with 2.5% γ-PGA, survived in simulated gastric juice (pH2.0) with a marginal reduction (<0.47 log CFU/ml) or no significant reduction in viable cells after 4h, whereas free cells died within 2h. In conclusion, this research indicates that γ-PGA can be used to protect Bifidobacteria cells in fruit juice, and could also help improve the survival of cells as they pass through the harsh conditions of the gastrointestinal tract (GIT). Following our previous report on the use of γ-PGA as a cryoprotectant for probiotic bacteria, this research further suggests that γ-PGA could be used to improve probiotic survival during the various stages of preparation, storage and ingestion of probiotic cells. PMID:25506798

  6. SynCAM 1 improves survival of adult-born neurons by accelerating synapse maturation.

    PubMed

    Doengi, Michael; Krupp, Alexander J; Körber, Nils; Stein, Valentin

    2016-03-01

    The survival of adult-born dentate gyrus granule cells critically depends on their synaptic integration into the existing neuronal network. Excitatory inputs are thought to increase the survival rate of adult born neurons. Therefore, whether enhancing the stability of newly formed excitatory synapses by overexpressing the synaptic cell adhesion molecule SynCAM 1 improves the survival of adult-born neurons was tested. Here it is shown that overexpression of SynCAM 1 improves survival of adult-born neurons, but has no effect on the proliferation rate of precursor cells. As expected, overexpression of SynCAM 1 increased the synapse density in adult-born granule neurons. While adult-born granule neurons have very few functional synapses 15 days after birth, it was found that at this age adult-born neurons in SynCAM 1 overexpressing mice exhibited around three times more excitatory synapses, which were stronger than synapses of adult-born neurons of control littermates. In summary, the data indicated that additional SynCAM 1 accelerated synapse maturation, which improved the stability of newly formed synapses and in turn increased the likelihood of survival of adult-born neurons. © 2015 Wiley Periodicals, Inc. PMID:26332750

  7. Pulp and paper mills

    SciTech Connect

    Not Available

    1980-10-14

    The various hazards present in the many steps used in the production of products from pulp and paper mills were reviewed and discussed. The biological effects of 43 chemical, physical and dust hazards were detailed in the report. Dust hazards included exposures to wood dust, mold and bagasse dusts and fibrogenic dusts. Physical hazards included high heat and humidity, and noise. Raw materials and chemical intermediates discussed included calcium-oxide (1305788), magnesium-oxide (1309484), pulping liquors, sodium-hydroxide (1310732), sulfate, sulfites, sulfides, sulfur (7704349) and sulfuric-acid (7664939). Pulp bleaching agents were discussed along with papermaking additives, contaminants and/or byproducts, and pulping or combustion effluents. Sampling and analytical techniques for physical and chemical hazards were discussed. Engineering controls for hazards in pulp and paper mills were reviewed. OSHA regulations governing pulp and paper mills were evaluated.

  8. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  9. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  10. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency...

  11. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency...

  12. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency...

  13. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  14. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  15. 38 CFR 3.23 - Improved pension rates-Veterans and surviving spouses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Improved pension rates-Veterans and surviving spouses. 3.23 Section 3.23 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General §...

  16. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Improved pension elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency...

  17. Vemurafenib Improves Survival for Patients with Metastatic Melanoma | Division of Cancer Prevention

    Cancer.gov

    Patients with metastatic melanoma whose tumors harbor a specific genetic mutation have improved overall survival with the targeted therapy vemurafenib (Zelboraf), according to longer-term follow-up data from a phase II clinical tria |

  18. Biochemical Control With Radiotherapy Improves Overall Survival in Intermediate and High-Risk Prostate Cancer Patients Who Have an Estimated 10-Year Overall Survival of >90%

    SciTech Connect

    Herbert, Christopher; Liu, Mitchell; Tyldesley, Scott; Morris, W. James; Joffres, Michel; Khaira, Mandip; Kwan, Winkle; Moiseenko, Vitali; Pickles, Thomas

    2012-05-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51-176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%-94.1%) and 62.1% (95% CI 52.9%-71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%-100%) and 79.8% (95% CI 68.0%-91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p < 0.001) were statistically significant. Conclusion: Biochemical control translates into improved overall survival in patients with high or intermediate risk disease and an estimated 10-year overall survival of >90%.

  19. Prior infection does not improve survival against the amphibian disease Chytridiomycosis.

    PubMed

    Cashins, Scott D; Grogan, Laura F; McFadden, Michael; Hunter, David; Harlow, Peter S; Berger, Lee; Skerratt, Lee F

    2013-01-01

    Many amphibians have declined globally due to introduction of the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Hundreds of species, many in well-protected habitats, remain as small populations at risk of extinction. Currently the only proven conservation strategy is to maintain species in captivity to be reintroduced at a later date. However, methods to abate the disease in the wild are urgently needed so that reintroduced and wild animals can survive in the presence of Bd. Vaccination has been widely suggested as a potential strategy to improve survival. We used captive-bred offspring of critically endangered booroolong frogs (Litoria booroolongensis) to test if vaccination in the form of prior infection improves survival following re exposure. We infected frogs with a local Bd isolate, cleared infection after 30 days (d) using itraconazole just prior to the onset of clinical signs, and then re-exposed animals to Bd at 110 d. We found prior exposure had no effect on survival or infection intensities, clearly showing that real infections do not stimulate a protective adaptive immune response in this species. This result supports recent studies suggesting Bd may evade or suppress host immune functions. Our results suggest vaccination is unlikely to be useful in mitigating chytridiomycosis. However, survival of some individuals from all experimental groups indicates existence of protective innate immunity. Understanding and promoting this innate resistance holds potential for enabling species recovery. PMID:23451076

  20. Interact to Survive: Phyllobacterium brassicacearum Improves Arabidopsis Tolerance to Severe Water Deficit and Growth Recovery

    PubMed Central

    Bresson, Justine; Vasseur, François; Dauzat, Myriam; Labadie, Marc; Varoquaux, Fabrice; Touraine, Bruno; Vile, Denis

    2014-01-01

    Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR) are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (Fv/Fm), was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture. PMID:25226036

  1. Improved survival of young donor age dopamine grafts in a rat model of Parkinson's disease.

    PubMed

    Torres, E M; Monville, C; Gates, M A; Bagga, V; Dunnett, S B

    2007-06-01

    In an attempt to improve the survival of implanted dopamine cells, we have readdressed the optimal embryonic donor age for dopamine grafts. In a rat model of Parkinson's disease, animals with unilateral 6-hydroxydopamine lesions of the median forebrain bundle received dopamine-rich ventral mesencephalic grafts derived from embryos of crown to rump length 4, 6, 9, or 10.5 mm (estimated embryonic age (E) 11, E12, E13 and E14 days post-coitus, respectively). Grafts derived from 4 mm embryos survived poorly, with less than 1% of the implanted dopamine cells surviving. Grafts derived from 9 mm and 10.5 mm embryos were similar to those seen in previous experiments with survival rates of 8% and 7% respectively. The best survival was seen in the group that received 6 mm grafts, which were significantly larger than all other graft groups. Mean dopamine cell survival in the 6 mm group (E12) was 36%, an extremely high survival rate for primary, untreated ventral mesencephalic grafts applied as a single placement, and more than fivefold larger than the survival rate observed in the 10.5 mm (E14) group. As E12 ventral mesencephalic tissues contain few, if any, differentiated dopamine cells we conclude that the large numbers of dopamine cells seen in the 6 mm grafts must have differentiated post-implantation. We consider the in vivo conditions which allow this differentiation to occur, and the implications for the future of clinical trials based on dopamine cell replacement therapy. PMID:17478050

  2. Familiarity with breeding habitat improves daily survival in colonial cliff swallows

    PubMed Central

    BROWN, CHARLES R.; BROWN, MARY BOMBERGER; BRAZEAL, KATHLEEN R.

    2008-01-01

    One probable cost of dispersing to a new breeding habitat is unfamiliarity with local conditions such as the whereabouts of food or the habits of local predators, and consequently immigrants may have lower probabilities of survival than more experienced residents. Within a breeding season, estimated daily survival probabilities of cliff swallows (Petrochelidon pyrrhonota) at colonies in southwestern Nebraska were highest for birds that had always nested at the same site, followed by those for birds that had nested there in some (but not all) past years. Daily survival probabilities were lowest for birds that were naïve immigrants to a colony site and for yearling birds that were nesting for the first time. Birds with past experience at a colony site had monthly survival 8.6% greater than that of naïve immigrants. All colonies where experienced residents did better than immigrants were smaller than 750 nests in size, and in colonies greater than 750 nests, naïve immigrants paid no survival costs relative to experienced residents. Removal of nest ectoparasites by fumigation resulted in higher survival probabilities for all birds, on average, and diminished the differences between immigrants and past residents, probably by improving bird condition to the extent that effects of past experience were relatively less important and harder to detect. The greater survival of experienced residents could not be explained by condition or territory quality, suggesting that familiarity with a local area confers survival advantages during the breeding season for cliff swallows. Colonial nesting may help to moderate the cost of unfamiliarity with an area, likely through social transfer of information about food sources and enhanced vigilance in large groups. PMID:19802326

  3. Continuing improvement in survival for children with acquired immunodeficiency syndrome in Brazil.

    PubMed

    Matida, Luiza H; Ramos, Alberto N; Heukelbach, Jorg; Hearst, Norman

    2009-10-01

    This retrospective cohort study examined a nationally representative sample of 945 Brazilian children (ages 0-12 years) diagnosed with AIDS in 1999 to 2002 and followed through 2007. The probability of survival to 60 months was 86.3% (95% CI, 84.1%-88.5%). This compares with 52.8% (95% CI, 41.9%-60.8%) in a study of cases diagnosed in 1983 to 1998. These results demonstrate substantial improvement in survival for children with AIDS in Brazil. PMID:19672214

  4. Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress.

    PubMed

    Logan, Suzanna J; Yin, Liya; Geldenhuys, Werner J; Enrick, Molly K; Stevanov, Kelly M; Carroll, Richard T; Ohanyan, Vahagn A; Kolz, Christopher L; Chilian, William M

    2015-03-01

    Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD. Accordingly, manipulation of stem cell mitochondrial metabolism may be an effective strategy to improve survival of stem cells under oxidative stress. MitoNEET is a redox-sensitive, mitochondrial target of thiazolidinediones (TZDs), and influences cellular oxidative capacity. Pharmacological targeting of mitoNEET with the novel TZD, mitoNEET Ligand-1 (NL-1), improved cardiac stem cell (CSC) survival compared to vehicle (0.1% DMSO) during in vitro oxidative stress (H2O2). 10 μM NL-1 also reduced CSC maximal oxygen consumption rate (OCR) compared to vehicle. Following treatment with dexamethasone, CSC maximal OCR increased compared to baseline, but NL-1 prevented this effect. Smooth muscle α-actin expression increased significantly in CSC following differentiation compared to baseline, irrespective of NL-1 treatment. When CSCs were treated with glucose oxidase for 7 days, NL-1 significantly improved cell survival compared to vehicle (trypan blue exclusion). NL-1 treatment of cells isolated from mitoNEET knockout mice did not increase CSC survival with H2O2 treatment. Following intramyocardial injection of CSCs into Zucker obese fatty rats, NL-1 significantly improved CSC survival after 24 h, but not after 10 days. These data suggest that pharmacological targeting of mitoNEET with TZDs may acutely protect stem cells following transplantation into an oxidative environment. Continued treatment or manipulation of mitochondrial metabolism may be necessary to produce long-term benefits related to stem cell therapies. PMID:25725808

  5. Application of neural networks and sensitivity analysis to improved prediction of trauma survival.

    PubMed

    Hunter, A; Kennedy, L; Henry, J; Ferguson, I

    2000-05-01

    The performance of trauma departments is widely audited by applying predictive models that assess probability of survival, and examining the rate of unexpected survivals and deaths. Although the TRISS methodology, a logistic regression modelling technique, is still the de facto standard, it is known that neural network models perform better. A key issue when applying neural network models is the selection of input variables. This paper proposes a novel form of sensitivity analysis, which is simpler to apply than existing techniques, and can be used for both numeric and nominal input variables. The technique is applied to the audit survival problem, and used to analyse the TRISS variables. The conclusions discuss the implications for the design of further improved scoring schemes and predictive models. PMID:10699681

  6. Improvement of survival and prospect of cure in patients with metastatic breast cancer.

    PubMed

    Cheng, Yee Chung; Ueno, Naoto T

    2012-07-01

    Patients with metastatic breast cancer have traditionally been considered incurable with conventional treatment. However, 5-10% of those patients survive more than 5 years, and 2-5% survive more than 10 years. Recent studies suggest that the survival of patients with metastatic breast cancer has been slowly improving. In this review, we examine the possible curative approach for a certain group of patients with metastatic breast cancer. We identify that patients most likely to benefit from such an aggressive approach are young and have good performance status, adequate body functional reserve, long disease-free interval before recurrence, oligometastatic disease, and low systemic tumor load. An aggressive multidisciplinary approach including both local treatment of macroscopic disease and systemic treatment of microscopic disease can result in prolonged disease control in certain patients with metastatic breast cancer. Whether patients with prolonged disease control are "cured" remains controversial. PMID:21567170

  7. Innovative endodontic therapy for anti-inflammatory direct pulp capping of permanent teeth with a mature apex

    PubMed Central

    Komabayashi, Takashi; Zhu, Qiang

    2010-01-01

    Direct pulp capping is a treatment of an exposed vital pulp with a dental material to facilitate the formation of reparative dentin and maintenance of vital pulp. It has been studied as an alternate way to avoid vital pulp extirpation. However, the success rate of pulp capping is much lower than that of vital pulp extirpation. Therefore, direct pulp capping is currently considered controversial by many clinicians. To increase success rate, a critical need exists to develop new biologically-based therapeutics that reduce pulp inflammation, promote the continued formation of new dentin-pulp complex, and restore vitality by stimulating the regrowth of pulpal tissue. Bioengineered anti-inflammatory direct pulp capping materials, together with adhesive materials for leakage prevention, have great potential to improve the condition of the existing pulp from an inflamed to a non-inflamed status and lead to a high rate of long-term success. PMID:20416524

  8. A Systematic Case Study of the Course, Offshore Survival Systems Training, To Improve the Practice of Marine Survival Training.

    ERIC Educational Resources Information Center

    Zambon, Franco

    A major applied research project evaluated the effectiveness of a novel course, Offshore Survival Systems Training. The major course outcome that was evaluated was the increase in frequency with which offshore personnel correctly launched the covered powered survival craft on offshore drilling rigs. The evaluation methodology included the 628…

  9. Bioceramic Materials and the Changing Concepts in Vital Pulp Therapy.

    PubMed

    Cao, Yangpei; Bogen, George; Lim, Jung; Shon, Won-Jun; Kang, Mo K

    2016-05-01

    Vital pulp therapy (VPT) is devised to preserve and maintain vitality of pulpally involved teeth challenged by a variety of intraoral conditions. Notable progress has been made in this field due to a better understanding of pulp physiology, improved clinical protocols and advanced bioceramic materials paired with adhesive technology. With focused case selection, conservative VPT can provide reliable treatment options for permanent teeth diagnosed with normal pulps or reversible pulpitis. PMID:27290822

  10. Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis

    PubMed Central

    Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

    2007-01-01

    Targeted Interleukin (IL)-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild type (WT) littermates (n=127) were subjected to cecal ligation and puncture with a 27-gauge needle. Seven-day survival was 45% in transgenic animals and 30% in WT animals (p≤0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals, regardless of whether they expressed the transgene. Local parameters of injury including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines and stimulated cytokines from intraepithelial lymphocytes were similar between transgenic and wildtype mice. However, in stimulated splenocytes, pro-inflammatory cytokines MCP-1 (189 ± 43 pg/ml vs. 40 ± 8 pg/ml) and IL-6 (116 ± 28 pg/ml vs. 34 ± 9 pg/ml) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (p<0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the two groups as were circulating LPS levels. Transgenic mice also had lower white blood cell counts, associated with lower absolute neutrophil counts (0.5 ± 0.1 103/mm3 vs. 1.0 ± 0.2 103/mm3, p<0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage. PMID:17998890

  11. Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis.

    PubMed

    Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

    2008-04-01

    Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage. PMID:17998890

  12. Radiotherapy Improves Survival in Unresected Stage I-III Bronchoalveolar Carcinoma

    SciTech Connect

    Urban, Damien; Mishra, Mark; Onn, Amir; Dicker, Adam P.; Symon, Zvi; Pfeffer, M. Raphael; Lawrence, Yaacov Richard

    2012-11-01

    Purpose: To test the hypothesis that radiotherapy (RT) improves the outcome of patients with unresected, nonmetastatic bronchoalveolar carcinoma (BAC) by performing a population-based analysis within the Surveillance, Epidemiology, and End Results (SEER) registry. Methods and Materials: Inclusion criteria were as follows: patients diagnosed with BAC, Stage I-III, between 2001 and 2007. Exclusion criteria included unknown stage, unknown primary treatment modality, Stage IV disease, and those diagnosed at autopsy. Demographic data, treatment details, and overall survival were retrieved from the SEER database. Survival was analyzed using the Kaplan-Meier method and log-rank test. Results: A total of 6933 patients with Stage I-III BAC were included in the analysis. The median age at diagnosis was 70 years (range, 10-101 years). The majority of patients were diagnosed with Stage I (74.4%); 968 patients (14%) did not undergo surgical resection. Unresected patients were more likely to be older (p < 0.0001), male (p = 0.001), black (p < 0.0001), and Stage III (p < 0.0001). Within the cohort of unresected patients, 300 (31%) were treated with RT. The estimated 2-year overall survival for patients with unresected, nonmetastatic BAC was 58%, 44%, and 27% in Stage I, II, and III, respectively. Factors associated with improved survival included female sex, earlier stage at diagnosis, and use of RT. Median survival in those not receiving RT vs. receiving RT was as follows: Stage I, 28 months vs. 33 months (n = 364, p = 0.06); Stage II, 18 months vs. not reached (n = 31, nonsignificant); Stage III, 10 months vs. 17 months (n = 517, p < 0.003). Conclusions: The use of RT is associated with improved prognosis in unresected Stage I-III BAC. Less than a third of patients who could have potentially benefited from RT received it, suggesting that the medical specialists involved in the care of these patients underappreciate the importance of RT.

  13. Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

    PubMed Central

    Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

    2010-01-01

    Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

  14. Pancreatectomy Predicts Improved Survival for Pancreatic Adenocarcinoma: Results of an Instrumental Variable Analysis

    PubMed Central

    McDowell, Bradley D.; Chapman, Cole G.; Smith, Brian J.; Button, Anna M.; Chrischilles, Elizabeth A.; Mezhir, James J.

    2014-01-01

    Background and Objective Pancreatic resection is the standard therapy for patients with stage I/II pancreatic ductal adenocarcinoma (PDA), yet many studies demonstrate low rates of resection. The objective of this study is to evaluate whether increasing resection rates would result in an increase in average survival in patients with stage I/II PDA. Methods SEER data were analyzed for patients with stage I/II pancreatic head cancers treated from 2004–2009. Pancreatectomy rates were examined within Health Service Areas (HSA) across 18 SEER regions. An instrumental variables (IV) analysis was performed, using HSA rates as an instrument, to determine the impact of increasing resection rates on survival. Results Pancreatectomy was performed in 4,322 of the 8,323 patients evaluated with stage I/II PDA (overall resection rate=51.9%). The resection rate across HSAs ranged from an average of 38.6% in the lowest quintile to 67.3% in the highest quintile. Median survival was improved in HSAs with higher resection rates. IV analysis revealed that, for patients whose treatment choices were influenced by the rates of resection in their geographic region, pancreatectomy was associated with a statistically significant increase in overall survival. Conclusions When controlling for confounders using IV analysis, pancreatectomy is associated with a statistically significant increase in survival for patients with resectable PDA. Based on these results, if resection rates were to increase in select patients, then average survival would also be expected to increase. It is important that this information be provided to physicians and patients so they can properly weigh the risks and advantages of pancreatectomy as treatment for PDA. PMID:24979599

  15. Strategies to improve health coverage and narrow the equity gap in child survival, health, and nutrition.

    PubMed

    Chopra, Mickey; Sharkey, Alyssa; Dalmiya, Nita; Anthony, David; Binkin, Nancy

    2012-10-13

    Implementation of innovative strategies to improve coverage of evidence-based interventions, especially in the most marginalised populations, is a key focus of policy makers and planners aiming to improve child survival, health, and nutrition. We present a three-step approach to improvement of the effective coverage of essential interventions. First, we identify four different intervention delivery channels--ie, clinical or curative, outreach, community-based preventive or promotional, and legislative or mass media. Second, we classify which interventions' deliveries can be improved or changed within their channel or by switching to another channel. Finally, we do a meta-review of both published and unpublished reviews to examine the evidence for a range of strategies designed to overcome supply and demand bottlenecks to effective coverage of interventions that improve child survival, health, and nutrition. Although knowledge gaps exist, several strategies show promise for improving coverage of effective interventions-and, in some cases, health outcomes in children-including expanded roles for lay health workers, task shifting, reduction of financial barriers, increases in human-resource availability and geographical access, and use of the private sector. Policy makers and planners should be informed of this evidence as they choose strategies in which to invest their scarce resources. PMID:22999430

  16. The development of advanced hydroelectric turbines to improve fish passage survival

    SciTech Connect

    Cada, Glenn F.

    2001-09-01

    Recent efforts to improve the survival of hydroelectric turbine-passed juvenile fish have explored modifications to both operation and design of the turbines. Much of this research is being carried out by power producers in the Columbia River basin (U.S. Army Corps of Engineers and the public utility districts), while the development of low impact turbines is being pursued on a national scale by the U.S. Department of Energy. Fisheries managers are involved in all aspects of these efforts. Advanced versions of conventional Kaplan turbines are being installed and tested in the Columbia River basin, and a pilot scale version of a novel turbine concept is undergoing laboratory testing. Field studies in the last few years have shown that improvements in the design of conventional turbines have increased the survival of juvenile fish. There is still much to be learned about the causes and extent of injuries in the turbine system (including the draft tube and tailrace), as well as the significance of indirect mortality and the effects of turbine passage on adult fish. However, improvements in turbine design and operation, as well as new field, laboratory, and modeling techniques to assess turbine-passage survival, are contributing toward resolution of the downstream fish passage issue at hydroelectric power plants.

  17. Greatly improved survival and neuroprotection in aquaporin-4-knockout mice following global cerebral ischemia.

    PubMed

    Katada, Ryuichi; Akdemir, Gokhan; Asavapanumas, Nithi; Ratelade, Julien; Zhang, Hua; Verkman, A S

    2014-02-01

    Aquaporin-4 (AQP4), the principal water channel in astrocytes, is involved in brain water movement, inflammation, and neuroexcitation. In this study, there was strong neuroprotection in mice lacking AQP4 in a model of global cerebral ischemia produced by transient, bilateral carotid artery occlusion (BCAO). Survival and neurological outcome were greatly improved in the AQP4(-/-) vs. AQP4(+/+) mice after occlusion, with large and robust differences in both outbred (CD1) and inbred (C57bl/6) mouse strains without or with mechanical ventilation. Improved survival was also seen in mice lacking the scaffold protein α-syntrophin, which manifest reduced astrocyte water permeability secondary to defective AQP4 plasma membrane targeting. Intracranial pressure elevation and brain water accumulation were much reduced in the AQP4(-/-) vs. AQP4(+/+) mice after carotid artery occlusion, as were blood-brain barrier (BBB) disruption and neuronal loss. Brain slices from AQP4(-/-) mice showed significantly reduced cell swelling and cytotoxicity in response to oxygen-glucose deprivation, compared with slices from AQP4(+/+) mice. Our findings suggest that the neuroprotective effect of AQP4 deletion in global cerebral ischemia involves reduced astrocyte swelling and brain water accumulation, resulting in reduced BBB disruption, inflammation, and neuron death. AQP4 water transport inhibition may improve survival and neurological outcome after cardiac arrest and in other conditions associated with global cerebral ischemia. PMID:24186965

  18. Second Hepatectomy Improves Survival in Patients With Microvascular Invasive Hepatocellular Carcinoma Meeting the Milan Criteria

    PubMed Central

    Hou, Yi-Fu; Li, Bo; Wei, Yong-Gang; Yang, Jia-Yin; Wen, Tian-Fu; Xu, Ming-Qing; Yan, L.V.-Nan; Chen, Ke-Fei

    2015-01-01

    Abstract Microvascular invasion (MVI) is a strong risk factor for patients with hepatocellular carcinoma (HCC) meeting the Milan criteria and who have received curative hepatectomy. The relevance of a second hepatectomy in patients with MVI-positive recurrent HCC remains controversial. We had 329 cases of HCC hepatectomy meeting the Milan criteria and compared data on patient demographics, liver function, and tumor pathology between MVI-positive and MVI-negative group. We analyzed potential risk factors of overall survival (OS) and disease-free survival (DFS). Furthermore, newly developed pathological features following the second hepatectomy were also analyzed. The median OS and DFS were significantly superior in the MVI-negative group than in the MVI-positive group, 61 (10–81) versus 49 (11–82) months (P < 0.01) and 41 (7–75) versus 13 (3–69) months (P < 0.01), respectively. The presence of MVI and a total tumor diameter >3 cm were independent risk factors associated with both OS and DFS. Overall survival was significantly improved by a second hepatectomy in the MVI-positive group compared with the original MVI-positive group, 60 (26–82) versus 49 (11–82) months, respectively. This was now comparable to the MVI-negative group, 60 (26–82) versus 61 (10–81) months (P = 0.72). A second hepatectomy was consistently associated with better survival in the MVI-negative group as compared to the MVI-positive group. A second hepatectomy improves survival in patients with MVI HCC meeting the Milan criteria. The biology of MVI may change following a second hepatectomy. The absence of MVI is a good prognostic sign for patients undergoing second hepatectomy. PMID:26632890

  19. Glucosamine administration improves survival rate after severe hemorrhagic shock combined with trauma in rats.

    PubMed

    Nöt, Laszlo G; Marchase, Richard B; Fülöp, Norbert; Brocks, Charlye A; Chatham, John C

    2007-09-01

    We have previously shown that glucosamine administration resulted in higher cardiac output and improved tissue perfusion after trauma-hemorrhage with resuscitation in rats, which was associated with the increased levels of protein O-linked-N-acetylglucosamine (O-GlcNAc). The purpose of the study was to evaluate the effect of glucosamine on the survival, without resuscitation, in rats. Adult male rats underwent midline laparotomy and 55% of total blood volume was withdrawn for 25 min under isoflurane anesthesia. At the end of the hemorrhage period, 2.5 mL of 150 mM glucosamine or equivalent osmolarity of mannitol solution was injected intravenously for 10 min. The survival time, mean blood pressure, heart rate, and central body temperature were monitored continuously; then, the O-GlcNAc levels in heart, brain, liver, and muscle were measured by means of Western blot analysis. Glucosamine administration significantly increased the survival rate in comparison with mannitol administration (percentage of survival after 2 h, 47% vs. 20%; P < 0.05). The mean arterial pressure was significantly higher in the glucosamine group for 18 min after treatment. The protein O-GlcNAc levels, assessed 30 min after glucosamine treatment, were significantly increased in the heart, brain, and liver. These data demonstrate that i.v. glucosamine administration improves the survival rate after trauma-hemorrhage without resuscitation; this effect may be related to the glucosamine-induced increase in protein O-glycosylation. Furthermore, the increase in mean arterial pressure may suggest a vasoactive and/or positive inotropic effect of glucosamine in hypovolemic shock. PMID:17545939

  20. DIETARY BILE ACID SUPPLEMENTATION IMPROVES INTESTINAL INTEGRITY AND SURVIVAL IN A MURINE MODEL

    PubMed Central

    Perrone, Erin E.; Chen, Chen; Longshore, Shannon W.; Okezie, Oneybuchi; Warner, Brad W.; Sun, Chen-Chih; Alaish, Samuel M.; Strauch, Eric D.

    2010-01-01

    Purpose In vitro supplementation of the bile salt, taurodeoxycholic acid (TDCA), has been shown to stimulate proliferation and prevent intestinal apoptosis in IEC-6 cells. We hypothesize that addition of TDCA to a rodent liquid diet will be protective against induced intestinal injury. Methods C57Bl6 mice were fed a liquid diet with or without 50mg/kg/day TDCA supplementation. After 6 days, the mice were injected with LPS (10mg/kg) to induce intestinal injury. Specimens were obtained 24 hours later and evaluated for intestinal apoptosis, crypt proliferation, and villus length. A separate cohort of animals were injected with LPS (25mg/kg) and followed 7 days for survival. Results Mice whose diet was supplemented with TDCA had significantly increased survival. After LPS-induced injury, mice supplemented with TDCA showed decreased intestinal apoptosis by both H&E and caspase-3. They also had increased intestinal proliferation by BrdU-staining and increased villus length. Conclusions Dietary taurodeoxycholic acid supplementation alleviates mucosal damage and improves survival after LPS-induced intestinal injury. TDCA is protective of the intestinal mucosa by increasing resistance to injury-induced apoptosis, stimulating enterocyte proliferation and increasing villus length. TDCA supplementation also results in an increased survival benefit. Therefore, bile acid supplementation may potentially protect the intestine from injury or infection. PMID:20620329

  1. Effect of Residual Lignin Type and Amount on Bleaching of Kraft Pulp by Trametes versicolor

    PubMed Central

    Reid, Ian D.; Paice, Michael G.

    1994-01-01

    The white rot fungus Trametes (Coriolus) versicolor can delignify and brighten unbleached hardwood kraft pulp within a few days, but softwood kraft pulps require longer treatment. To determine the contributions of higher residual lignin contents (kappa numbers) and structural differences in lignins to the recalcitrance of softwood kraft pulps to biobleaching, we tested softwood and hardwood pulps cooked to the same kappa numbers, 26 and 12. A low-lignin-content (overcooked) softwood pulp resisted delignification by T. versicolor, but a high-lignin-content (lightly cooked) hardwood pulp was delignified at the same rate as a normal softwood pulp. Thus, the longer time taken by T. versicolor to brighten softwood kraft pulp than hardwood pulp results from the higher residual lignin content of the softwood pulp; possible differences in the structures of the residual lignins are important only when the lignin becomes highly condensed. Under the conditions used in this study, when an improved fungal inoculum was used, six different softwood pulps were all substantially brightened by T. versicolor. Softwood pulps whose lignin contents were decreased by extended modified continuous cooking or oxygen delignification to kappa numbers as low as 15 were delignified by T. versicolor at the same rate as normal softwood pulp. More intensive O2 delignification, like overcooking, decreased the susceptibility of the residual lignin in the pulps to degradation by T. versicolor. PMID:16349246

  2. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

    PubMed Central

    Yeo, C J; Abrams, R A; Grochow, L B; Sohn, T A; Ord, S E; Hruban, R H; Zahurak, M L; Dooley, W C; Coleman, J; Sauter, P K; Pitt, H A; Lillemoe, K D; Cameron, J L

    1997-01-01

    of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis. PMID:9193189

  3. PcrV antibody-antibiotic combination improves survival in Pseudomonas aeruginosa-infected mice.

    PubMed

    Song, Y; Baer, M; Srinivasan, R; Lima, J; Yarranton, G; Bebbington, C; Lynch, S V

    2012-08-01

    The type III secretion system (TTSS) of Pseudomonas aeruginosa, associated with acute infection, facilitates the direct injection of cytotoxins into the host cell cytoplasm. Mab166, a murine monoclonal antibody against PcrV, a protein located at the tip of the injectisome, has demonstrated efficacy against P. aeruginosa infection, resulting in reduced lung injury and increased survival in murine models of infection. We hypothesised that the administration of Mab166 in combination with an antibiotic would further improve the survival of P. aeruginosa-infected mice. A murine model of P. aeruginosa acute infection, three clinically relevant antibiotics (ciprofloxacin, tobramycin and ceftazidime) and the Mab166 antibody were used for this study. Consistently, compared to other treatment groups (antibiotic or antibody administered in isolation), the combination of Mab166 and antibiotic significantly improved the survival of mice infected with three times the lethal dose (LD(90)) of the highly cytotoxic ExoU-secreting strain, PA103. This synergistic effect was primarily due to enhanced bactericidal effect and protection against lung injury, which prevented bacterial dissemination to other organs. Hence, the combination of Mab166 with antibiotic administration provides a new, more effective strategy against P. aeruginosa airway infection, especially when large numbers of highly virulent strains are present. PMID:22187351

  4. Erythropoietin Improves the Survival of Fat Tissue after Its Transplantation in Nude Mice

    PubMed Central

    Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

    2010-01-01

    Background Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Methodology/Principal Findings Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Conclusions/Significance Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment. PMID:21085572

  5. Application of bacterial lipopolysaccharide to improve survival of the black tiger shrimp after Vibrio harveyi exposure.

    PubMed

    Rungrassamee, Wanilada; Maibunkaew, Sawarot; Karoonuthaisiri, Nitsara; Jiravanichpaisal, Pikul

    2013-10-01

    This study investigates an effect of bacterial lipopolysaccharide (LPS) as feed supplement to improve immunity of the black tiger shrimp (Penaeus monodon). LPS was coated to commercial feed pellets and given to the shrimp once or twice a day for 10 days before an exposure with shrimp pathogenic bacterium Vibrio harveyi. The growth rates, percent weight gains, total hemocyte and granulocyte counts and survival rates of shrimp between the LPS-coated pellet fed groups and a control group where shrimp fed with commercial feed pellets were compared. After 10 days of the feeding trials, growth rates were not significantly different in all groups, suggesting no toxicity from LPS supplement. To determine beneficial effect of LPS diets, each group was subsequently exposed to V. harveyi by immersion method and the survival rates were recorded for seven days after the immersion. Regardless of the dosages of LPS, the shrimp groups fed with LPS-coated pellets showed higher survival rates than the control group. There was no significant difference in survival rates between the two LPS dosages groups. In addition to survival under pathogen challenge, we also determine effect of LPS on immune-related genes after 10-day feeding trial. Gene expression analysis in the P. monodon intestines revealed that antilipopolysaccharide factor isoform 3 (ALF3), C-type lectin, and mucine-like peritrophin (mucin-like PM) were expressed significantly higher in a group fed with LPS supplemental diet once or twice a day than in a control group. The transcript levels of C-type lectin and mucin-like PM had increased significantly when LPS was given once a day, while significant induction of ALF3 transcripts was observed when shrimp were fed with LPS twice a day. The up-regulation of the immune gene levels in intestines and higher resistance to V. harveyi of the shrimp fed with LPS provide the evidence for potential application of LPS as an immunostimulant in P. monodon farming. PMID:23751331

  6. Bypass system modification at Bonneville Dam on the Columbia River improved the survival of juvenile salmon

    USGS Publications Warehouse

    Ferguson, J.W.; Sandford, B.P.; Reagan, R.E.; Gilbreath, L.G.; Meyer, E.B.; Ledgerwood, R.D.; Adams, N.S.

    2007-01-01

    From 1987 to 1992, we evaluated a fish bypass system at Bonneville Dam Powerhouse 2 on the Columbia River. The survival of subyearling Chinook salmon Oncorhynchus tshawytscha released into the system ranged from 0.774 to 0.911 and was significantly lower than the survival of test fish released into turbines and the area immediately below the powerhouse where bypass system flow reentered the river. Yearling and subyearling Chinook salmon and yearling coho salmon O. kisutch released into the bypass system were injured or descaled. Also, levels of blood plasma cortisol and lactate were significantly higher in yearling and subyearling Chinook salmon that passed through the bypass system than in fish released directly into a net located over the bypass exit. This original system was then extensively modified using updated design criteria, and the site where juvenile fish reentered the river was relocated 2.8 km further downstream to reduce predation on bypassed fish by northern pikeminnow Ptychocheilus oregonensis. Based on studies conducted from 1999 to 2001, the new bypass system resulted in high fish survival, virtually no injuries to fish, fish passage times that were generally similar to water travel times, and mild stress responses from which fish recovered quickly. The mean estimated survival of subyearling Chinook salmon passing through the new bypass system was 0.946 in 2001, which was an usually low-flow year. Survival, physical condition, passage timing, and blood physiological indicators of stress were all useful metrics for assessing the performance of both bypass systems and are discussed. The engineering and hydraulic criteria used to design the new bypass system that resulted in improved fish passage conditions are described.

  7. Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer's disease.

    PubMed

    Mita, Tsuneyuki; Furukawa-Hibi, Yoko; Takeuchi, Hideyuki; Hattori, Hisashi; Yamada, Kiyofumi; Hibi, Hideharu; Ueda, Minoru; Yamamoto, Akihito

    2015-10-15

    Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by a decline in cognitive abilities and the appearance of β-amyloid plaques in the brain. Although the pathogenic mechanisms associated with AD are not fully understood, activated microglia releasing various neurotoxic factors, including pro-inflammatory cytokines and oxidative stress mediators, appear to play major roles. Here, we investigated the therapeutic benefits of a serum-free conditioned medium (CM) derived from the stem cells of human exfoliated deciduous teeth (SHEDs) in a mouse model of AD. The intranasal administration of SHEDs in these mice resulted in substantially improved cognitive function. SHED-CM contained factors involved in multiple neuroregenerative mechanisms, such as neuroprotection, axonal elongation, neurotransmission, the suppression of inflammation, and microglial regulation. Notably, SHED-CM attenuated the pro-inflammatory responses induced by β-amyloid plaques, and generated an anti-inflammatory/tissue-regenerating environment, which was accompanied by the induction of anti-inflammatory M2-like microglia. Our data suggest that SHED-CM may provide significant therapeutic benefits for AD. PMID:26210934

  8. Factors associated with improved survival following surgery for renal cell carcinoma spinal metastases.

    PubMed

    Petteys, Rory J; Spitz, Steven M; Goodwin, C Rory; Abu-Bonsrah, Nancy; Bydon, Ali; Witham, Timothy F; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Sciubba, Daniel M

    2016-08-01

    OBJECTIVE Renal cell carcinoma (RCC) frequently metastasizes to the spine, causing pain or neurological dysfunction, and is often resistant to standard therapies. Spinal surgery is frequently required, but may result in high morbidity rates. The authors sought to identify prognostic factors and determine clinical outcomes in patients undergoing surgery for RCC spinal metastases. METHODS The authors searched the records of patients who had undergone spinal surgery for metastatic disease at a single institution during a 12-year period and retrieved data for 30 patients with metastatic RCC. The records were retrospectively reviewed for data on preoperative conditions, treatment, and survival. Statistical analyses (i.e., Kaplan-Meier survival analysis and log-rank test in univariate analysis) were performed with R version 2.15.2. RESULTS The 30 patients (23 men and 7 women with a mean age of 57.6 years [range 29-79 years]) had in total 40 spinal surgeries for metastatic RCC. The indications for surgery included pain (70%) and weakness (30%). Fourteen patients (47%) had a Spinal Instability Neoplastic Score (SINS) indicating indeterminate or impending instability, and 6 patients (20%) had a SINS denoting instability. The median length of postoperative survival estimated with Kaplan-Meier analysis was 11.4 months. Younger age (p = 0.001) and disease control at the primary site (p = 0.005), were both significantly associated with improved survival. In contrast, visceral (p = 0.002) and osseous (p = 0.009) metastases, nonambulatory status (p = 0.001), and major comorbidities (p = 0.015) were all significantly associated with decreased survival. Postoperative Frankel grades were the same or had improved in 78% of patients. Major complications occurred in 9 patients, and there were 3 deaths (10%) during the 30-day in-hospital period. Three en bloc resections were performed. CONCLUSIONS Resection and fixation may provide pain relief and neurological stabilization in patients

  9. IL-15 Prevents Apoptosis, Reverses Innate and Adaptive Immune Dysfunction, and Improves Survival in Sepsis

    PubMed Central

    Inoue, Shigeaki; Unsinger, Jacqueline; Davis, Christopher G.; Muenzer, Jared T.; Ferguson, Thomas A.; Chang, Katherine; Osborne, Dale F.; Clark, Andrew T.; Coopersmith, Craig M.; McDunn, Jonathan E.; Hotchkiss, Richard S.

    2010-01-01

    L-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2×2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-γ, as well as the percentage of NK cells that produced IFN-γ. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder. PMID:20026737

  10. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.

    PubMed

    Inoue, Shigeaki; Unsinger, Jacqueline; Davis, Christopher G; Muenzer, Jared T; Ferguson, Thomas A; Chang, Katherine; Osborne, Dale F; Clark, Andrew T; Coopersmith, Craig M; McDunn, Jonathan E; Hotchkiss, Richard S

    2010-02-01

    IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder. PMID:20026737

  11. Do Increased Doses to Stem-Cell Niches during Radiation Therapy Improve Glioblastoma Survival?

    PubMed Central

    Adeberg, Sebastian; Harrabi, Semi Ben; Mohr, Angela; Rieber, Juliane; Rieken, Stefan; Debus, Juergen

    2016-01-01

    Background and Purpose. The reasons for the inevitable glioblastoma recurrence are yet understood. However, recent data suggest that tumor cancer stem cells (CSCs) in the stem-cell niches, with self-renewing capacities, might be responsible for tumor initiation, propagation, and recurrence. We aimed to analyze the effect of higher radiation doses to the stem-cell niches on progression-free survival (PFS) and overall survival (OS) in glioblastoma patients. Materials and Methods. Sixty-five patients with primary glioblastoma treated with radiation therapy were included in this retrospective analysis. The SVZ and DG were segmented on treatment planning magnetic resonance imaging, and the dose distributions to the structures were calculated. The relationship of dosimetry data and survival was evaluated using the Cox regression analysis. Results. Conventionally fractionated patients (n = 54) who received higher doses (Dmean ≥ 40 Gy) to the IL SVZ showed improved PFS (8.5 versus 5.2 months; p = 0.013). Furthermore, higher doses (Dmean ≥ 30 Gy) to the CL SVZ were associated with increased PFS (10.1 versus 6.9 months; p = 0.025). Conclusion. Moderate higher IL SVZ doses (≥40 Gy) and CL SVZ doses (≥30 Gy) are associated with improved PFS. Higher doses to the DG, the second stem-cell niche, did not influence the survival. Targeting the potential cancer stem cells in the SVZ might be a promising treatment approach for glioblastoma and should be addressed in a prospective randomized trial. PMID:27429623

  12. High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT

    PubMed Central

    Danby, R D; Zhang, W; Medd, P; Littlewood, T J; Peniket, A; Rocha, V; Roberts, D J

    2016-01-01

    Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3+CD4+CD25+FOXP3+CD127dim/−) dose transplanted was 4.7 × 106/kg, with Tregs accounting for a median of 2.96% of CD4+ T cells. Patients transplanted with grafts containing a Treg/CD4+ T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4+ T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4+ T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation. PMID:26389831

  13. DENTAL PULP TISSUE ENGINEERING

    PubMed Central

    Demarco, FF; Conde, MCM; Cavalcanti, B; Casagrande, L; Sakai, V; Nör, JE

    2013-01-01

    Dental pulp is a highly specialized mesenchymal tissue, which have a restrict regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article will review the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and providing insightful information to readers about the different aspects enrolled in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The finds collected in our review showed that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable and the next decade will certainly be an exciting time for dental and craniofacial research. PMID:21519641

  14. Improvement of survival of the house fly (Musca domestica L.) larvae under mass-rearing conditions.

    PubMed

    Cičková, H; Kozánek, M; Takáč, P

    2013-02-01

    improve larval survival and increase the weight of produced fly biomass may decrease demand for production of house fly eggs and, therefore, reduce the maintenance costs of adult colony, as well as increase the revenue earned by selling the products. PMID:23089286

  15. Neoadjuvant chemotherapy improves survival of patients with upper tract urothelial carcinoma

    PubMed Central

    Porten, Sima; Siefker-Radtke, Arlene O.; Xiao, Lianchun; Margulis, Vitaly; Kamat, Ashish M.; Wood, Christopher G.; Jonasch, Eric; Dinney, Colin P. N.; Matin, Surena F.

    2015-01-01

    Background High-grade upper tract urothelial carcinoma (UTUC) is frequently upstaged after surgery and is associated with uniformly poor survival. Neoadjuvant chemotherapy may offer a way to improve clinical outcomes. We compare the survival rates of UTUC patients who received neoadjuvant chemotherapy prior to surgery with patients who did not. Methods Retrospective review of patients with high-risk UTUC who received neoadjuvant chemotherapy followed by surgery in 2004–2008 (study group), compared to a matched cohort who underwent initial surgery in 1993–2003 (control group). The Fisher exact, Wilcoxon rank-sum, and Kaplan-Meier methods were used. The log-rank test and Cox proportional hazards model were used to evaluate association of these two outcomes with patient, treatment, and tumor characteristics in univariate and multivariate models. Results Of 112 patients, 31 were in the study group and 81 in the control group. Patients who received neoadjuvant chemotherapy had improved OS and DSS with a 5-year DSS of 90.1% and 5-year OS rate 80.2%, versus a 5-year DSS and OS of 57.6% for those treated with initial surgery (p = 0.0204 and p = 0.0015, respectively). In multivariate analyses the neoadjuvant group had a lower risk of mortality (OS hazard ratio 0.42 [p = 0.035]; DSS hazard ratio 0.19 [p = 0.006]). Conclusions Neoadjuvant chemotherapy improves survival in patients with UTUC compared with a matched historical cohort of patients treated with initial surgery. Patients with high-risk UTUC should be considered for neoadjuvant chemotherapy, in view of the limited opportunity to administer effective cisplatin-based chemotherapy after nephroureterectomy. PMID:24633966

  16. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    PubMed

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

  17. Oxygen cycling to improve survival of stem cells for myocardial repair: A review.

    PubMed

    Dall, Christopher; Khan, Mahmood; Chen, Chun-An; Angelos, Mark G

    2016-05-15

    Heart disease represents the leading cause of death among Americans. There is currently no clinical treatment to regenerate viable myocardium following myocardial infarction, and patients may suffer progressive deterioration and decreased myocardial function from the effects of remodeling of the necrotic myocardium. New therapeutic strategies hold promise for patients who suffer from ischemic heart disease by directly addressing the restoration of functional myocardium following death of cardiomyocytes. Therapeutic stem cell transplantation has shown modest benefit in clinical human trials with decreased fibrosis and increased functional myocardium. Moreover, autologous transplantation holds the potential to implement these therapies while avoiding the immunomodulation concerns of heart transplantation. Despite these benefits, stem cell therapy has been characterized by poor survival and low engraftment of injected stem cells. The hypoxic tissue environment of the ischemic/infracting myocardium impedes stem cell survival and engraftment in myocardial tissue. Hypoxic preconditioning has been suggested as a viable strategy to increase hypoxic tolerance of stem cells. A number of in vivo and in vitro studies have demonstrated improved stem cell viability by altering stem cell secretion of protein signals and up-regulation of numerous paracrine signaling pathways that affect inflammatory, survival, and angiogenic signaling pathways. This review will discuss both the mechanisms of hypoxic preconditioning as well as the effects of hypoxic preconditioning in different cell and animal models, examining the pitfalls in current research and the next steps into potentially implementing this methodology in clinical research trials. PMID:27091653

  18. Dry Kraft Pulping at Ambient Pressure for Cost Effective Energy Saving and Pollution Deduction

    SciTech Connect

    Yulin Deng; Art Ragauskas

    2012-08-28

    evaporated first under vacuum condition at low temperature. Then, the dry woodchips were baked at high temperature (120-130 C) at atmospheric pressure. The qualities of the pulp made with this method were improved compared to that made with method one. The pulp shows higher brightness and lower bulk than Kraft pulping. The tensile strength is significantly higher than the pulp made from the first method. Although the pulp is stronger than that of TMP pulp, it is still lower than conventional Kraft fiber. Method Three: The third dry method was done in a Kraft pulping digester at elevated pressure but without free liquid in the digester. With this method, pulp that has almost the same qualities as conventional Kraft pulp could be produced. The screen yield, Kappa number, fiber brightness, pulp strength and pulp bulk are almost identical to the conventional Kraft pulp. The key advantages of this dry pulping method include ca. 55 % of cooking energy saved during the pulping process, as high as 50 wt% of NaOH saving as well as 3 wt% of Na2S saving comparing to Kraft one. By analyzing fiber properties, yields, chemical and energy consumptions, we concluded that the dry pulping method based on Liquid Free Chemical Pulping, LFCP, could be very attractive for the pulp and paper industry. More fundamental studies and scale up trials are needed to fully commercialize the technology. We expect to conduct pilot trials between 12 to 24 months of period if the DOE or industry can provide continual research funding. Based on the technology we demonstrated in this report, several pilot trial facilities in the United States will be available after small modifications. For example, the Herty Foundation in Savannah, Georgia is one of these potential locations. DOE funding for continuous study and final lead to commercialization of the technique is important.

  19. Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice

    PubMed Central

    Turner, Bradley J.; Alfazema, Neza; Sheean, Rebecca K.; Sleigh, James N.; Davies, Kay E.; Horne, Malcolm K.; Talbot, Kevin

    2014-01-01

    Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1G93A mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1G93A mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1G93A mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. PMID:24210254

  20. STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma

    SciTech Connect

    Geng Ling; Shinohara, Eric T.; Kim, Dong; Tan Jiahuai; Osusky, Kate; Shyr, Yu; Hallahan, Dennis E. . E-mail: Dennis.Hallahan@mcmail.vanderbilt.edu

    2006-01-01

    Purpose: Glioblastoma multiforme (GBM) is a devastating brain neoplasm that is essentially incurable. Although radiation therapy prolongs survival, GBMs progress within areas of irradiation. Recent studies in invertebrates have shown that STI571 (Gleevec; Novartis, East Hanover, NJ) enhances the cytotoxicity of ionizing radiation. In the present study, the effectiveness of STI571 in combination with radiation was studied in mouse models of GBM. Methods and Materials: Murine GL261 and human D54 GBM cell lines formed tumors in brains and hind limbs of C57BL6 and nude mice, respectively. GL261 and D54 cells were treated with 5 {mu}mol/L of STI571 for 1 h and/or irradiated with 3 Gy. Protein was analyzed by Western immunoblots probed with antibodies to caspase 3, cleaved caspase 3, phospho-Akt, Akt, and platelet-derived growth factor receptor (PDGFR) {alpha} and {beta}. Tumor volumes were assessed in mice bearing GL261 or D54 tumors treated with 21 Gy administered in seven fractionated doses. Histologic sections from STI571-treated mice were stained with phospho-Akt and phospho-PDGFR {beta} antibodies. Kaplan-Meier survival curves were used to study the response of mice bearing intracranial implants of GL261. Results: STI571 penetrated the blood-brain barrier, which resulted in a reduction in phospho-PDGFR in GBM. STI571-induced apoptosis in GBM was significantly enhanced by irradiation. STI571 combined with irradiation induced caspase 3 cleavage in GBM cells. Glioblastoma multiforme response to therapy correlated with an increase in tumor growth delay and survival when STI571 was administered in conjunction with daily irradiation. Conclusion: These findings suggest that STI571 has the potential to augment radiotherapy and thereby improve median survival.

  1. Cell-Deposited Matrix Improves Retinal Pigment Epithelium Survival on Aged Submacular Human Bruch's Membrane

    PubMed Central

    Sugino, Ilene K.; Gullapalli, Vamsi K.; Sun, Qian; Wang, Jianqiu; Nunes, Celia F.; Cheewatrakoolpong, Noounanong; Johnson, Adam C.; Degner, Benjamin C.; Hua, Jianyuan; Liu, Tong; Chen, Wei; Li, Hong

    2011-01-01

    Purpose. To determine whether resurfacing submacular human Bruch's membrane with a cell-deposited extracellular matrix (ECM) improves retinal pigment epithelial (RPE) survival. Methods. Bovine corneal endothelial (BCE) cells were seeded onto the inner collagenous layer of submacular Bruch's membrane explants of human donor eyes to allow ECM deposition. Control explants from fellow eyes were cultured in medium only. The deposited ECM was exposed by removing BCE. Fetal RPE cells were then cultured on these explants for 1, 14, or 21 days. The explants were analyzed quantitatively by light microscopy and scanning electron microscopy. Surviving RPE cells from explants cultured for 21 days were harvested to compare bestrophin and RPE65 mRNA expression. Mass spectroscopy was performed on BCE-ECM to examine the protein composition. Results. The BCE-treated explants showed significantly higher RPE nuclear density than did the control explants at all time points. RPE expressed more differentiated features on BCE-treated explants than on untreated explants, but expressed very little mRNA for bestrophin or RPE65. The untreated young (<50 years) and African American submacular Bruch's membrane explants supported significantly higher RPE nuclear densities (NDs) than did the Caucasian explants. These differences were reduced or nonexistent in the BCE-ECM-treated explants. Proteins identified in the BCE-ECM included ECM proteins, ECM-associated proteins, cell membrane proteins, and intracellular proteins. Conclusions. Increased RPE survival can be achieved on aged submacular human Bruch's membrane by resurfacing the latter with a cell-deposited ECM. Caucasian eyes seem to benefit the most, as cell survival is the worst on submacular Bruch's membrane in these eyes. PMID:21398292

  2. Differential improvement in survival among patients with AIDS after the introduction of HAART.

    PubMed

    Couzigou, C; Semaille, C; Le Strat, Y; Pinget, R; Pillonel, J; Lot, F; Cazein, F; Vittecoq, D; Desenclos, J-C

    2007-04-01

    We explored changes in the survival of patients with AIDS (PWA) according to the availability of antiretroviral drugs (1994-2002). We tested whether changes in the hazard ratio of progression to death (HR) have been homogeneous among various groups of PWA. We included 4158 PWA diagnosed in Paris, notified to the French National Surveillance Institute by 2002. Four calendar periods were defined: monotherapy (1994-95), bitherapy-HAART transition (1996), early HAART (1997-99), late HAART (2000-October 2002). HR were calculated with Cox models, including the calendar period, modelled as a time dependent covariate. Models were stratified by age, transmission category, CD4 cell count, and AIDS-defining illnesses (ADI) group. Cumulative survival at 60 months increased from 44.0% (before July 1996) to 75.6% (after July 1996) and median survival increased from 31.9 months to >76 months. Adjusted HR reached a minimum in the late HAART period (HR 0.22, 95% CI: 0.19-0.26). No difference in the decrease of the HR has been found by age. HR decreased and was marked during the late HAART period across all HIV transmission categories, including intravenous drug use. HR decreased significantly for all ADIs groups, including tumours. Among PWA diagnosed with tuberculosis, the HR decreased significantly only in the late HAART period. HR decrease was stronger for PWA with a CD4 cell count < or =200/mm(3). Substantial improvements in survival after the introduction of HAART were found for all PWA but varied by specific ADIs and the degree of immunosuppression. PMID:17453593

  3. Surgical Stabilization Improves Survival of Spinal Fractures Related to Ankylosing Spondylitis

    PubMed Central

    Robinson, Yohan; Willander, Johan; Olerud, Claes

    2015-01-01

    Study Design. National registry cohort study. Objective. The aim of this study was to investigate the effect of surgical stabilization on survival of spinal fractures related to ankylosing spondylitis (AS). Summary of Background Data. Spinal fractures related to AS are associated with considerable morbidity and mortality. Multiple studies suggest a beneficial effect of surgical stabilization in these patients. Methods. In the Swedish patient registry, all patients treated in an inpatient facility are registered with diagnosis and treatment codes. The Swedish mortality registry collects date and cause of death for all fatalities. Registry extracts of all patients with AS and spinal fractures including date of death and treatment were prepared and analyzed for epidemiological purposes. Results. Seventeen thousand two hundred ninety-seven individual patients with AS were admitted to treatment facilities in Sweden between 1987 and 2011. Nine hundred ninety patients with AS (age 66 ± 14 years) had 1131 spinal fractures, of which 534 affected cervical, 352 thoracic, and 245 lumbar vertebrae. Thirteen percent had multiple levels of injuries during the observed period. Surgically treated patients had a greater survival than those treated nonsurgically [hazard ratio (HR) 0.79, P = 0.029]. Spinal cord injury was the major factor contributing to mortality in this cohort (HR 1.55, P < 0.001). The proportion of surgically treated spinal fractures increased linearly during the last decades (r = 0.92, P < 0.001) and was 64% throughout the observed years. Conclusions. Spinal cord injury threatened the survival of patients with spinal fractures related to AS. Even though surgical treatment is associated with a considerable complication rate, it improved the survival of spinal fractures related to AS. Level of Evidence: 3 PMID:26267824

  4. Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis

    PubMed Central

    Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I; Serralde-Zúñiga, Aurora E; Cruz-Herrera, Javier; Pérez-Torres, Eduardo; Abdo-Francis, Juan M; Salas-Gordillo, Francisco; Pérez-Hernández, José L

    2015-01-01

    AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH). METHODS: This study was an open-label clinical trial, performed at the “Hospital General de México, Dr. Eduardo Liceaga”. We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d. RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02). CONCLUSION: MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX. PMID:25945012

  5. Invited review: Improving neonatal survival in small ruminants: science into practice.

    PubMed

    Dwyer, C M; Conington, J; Corbiere, F; Holmøy, I H; Muri, K; Nowak, R; Rooke, J; Vipond, J; Gautier, J-M

    2016-03-01

    Neonatal mortality in small ruminant livestock has remained stubbornly unchanging over the past 40 years, and represents a significant loss of farm income, contributes to wastage and affects animal welfare. Scientific knowledge about the biology of neonatal adaptation after birth has been accumulating but does not appear to have had an impact in improving survival. In this paper, we ask what might be the reasons for the lack of impact of the scientific studies of lamb and kid mortality, and suggest strategies to move forward. Biologically, it is clear that achieving a good intake of colostrum, as soon as possible after birth, is crucial for neonatal survival. This provides fuel for thermoregulation, passive immunological protection and is involved in the development of attachment between the ewe and lamb. The behaviour of the lamb in finding the udder and sucking rapidly after birth is a key component in ensuring sufficient colostrum is ingested. In experimental studies, the main risk factors for lamb mortality are low birthweight, particularly owing to poor maternal nutrition during gestation, birth difficulty, litter size and genetics, which can all be partly attributed to their effect on the speed with which the lamb reaches the udder and sucks. Similarly, on commercial farms, low birthweight and issues with sucking were identified as important contributors to mortality. In epidemiological studies, management factors such as providing assistance with difficult births, were found to be more important than risk factors associated with housing. Social science studies suggest that farmers generally have a positive attitude to improving neonatal mortality but may differ in beliefs about how this can be achieved, with some farmers believing they had no control over early lamb mortality. Facilitative approaches, where farmers and advisors work together to develop neonatal survival strategies, have been shown to be effective in achieving management goals, such as

  6. Does social feeding improve larval survival of the two-spotted lady beetle, Adalia bipunctata?

    PubMed

    Moore, Michael P; Burt, Charles R; Whitney, Thomas D; Hastings, Steven A; Chang, Gary C

    2012-01-01

    Lady beetles typically lay eggs in clusters, and clutch-mates that emerge near to each other might benefit in multiple ways. For example, lady beetle larvae are attracted to the pheromone released by aphids under attack. Thus, one potential advantage to larvae emerging as a group is if one larva captures an aphid, others can share in consuming the same aphid. Sharing a meal likely reduces the per capita food intake of a hatchling, but it might also provide enough nutrition to prevent death by starvation during a particularly vulnerable stage. In an assay of the behavior of two-spotted lady beetles (Adalia bipunctata), larvae were attracted to chemical cues from damaged aphids, corroborating previous research. Densities of A. bipunctata hatchlings were then manipulated to test whether the presence of clutch-mates increasesed the probability of capturing prey, and the survivorship of hatchlings. In one experiment, a single aphid was placed with a number of lady beetle hatchlings ranging from 1 to 10 in a small arena for 72 hours to evaluate prey capture effectiveness and hatchling survival. As the initial density of lady beetle hatchlings increased, their prey capture rate increased. At the same time, survival of the hatchlings was not affected by their initial density. Five experiments were performed on individual fava bean plants by varying densities of aphids and lady beetle hatchlings to evaluate lady beetle survivorship measured after five days. In all five on-plant experiments, increasing the initial number of lady beetle larvae did not improve their survival. Lady beetle larvae shared meals during the small scale experiments, but that behavior did not improve their survivorship under any of the experimental conditions. PMID:23425121

  7. Bipap improves survival and rate of pulmonary function decline in patients with ALS.

    PubMed

    Kleopa, K A; Sherman, M; Neal, B; Romano, G J; Heiman-Patterson, T

    1999-03-15

    Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neuron disease that frequently causes death within five years of diagnosis. The majority of deaths are due to pulmonary complications resulting from respiratory muscle weakness and bulbar involvement. A promising respiratory intervention is the recently introduced bi-level intermittent positive pressure (Bipap), which is a noninvasive ventilator modality shown to reduce the work of breathing and improve not only gas exchange, but also exercise tolerance and sleep quality. The aim of this study was to assess the utility of Bipap in prolonging survival in ALS. We retrospectively analyzed the results of Bipap use in 122 patients followed at Hahnemann University. All patients in this study were offered Bipap when their forced vital capacity (FVC) dropped below 50% of predicted value. Group 1 (n=38) accepted Bipap and used it more than 4 h/day. Group 2 (n=32) did not tolerate Bipap well and used it less than 4 h/day. Group 3 (n=52) refused to try Bipap. There was a statistically significant improvement in survival from initiation of Bipap in Group 1 (14.2 months) compared to Group 2 (7.0 months, P=0.002) or 3 (4.6 months, P<0.001) respectively. Furthermore, when the slope of vital capacity decline was examined, the group that used Bipap more than 4 h/day had slower decline in vital capacity (-3.5% change/month) compared to Group 2 (-5.9% change/month, P=0.02) and Group 3 (-8.3% change/month, P<0.001). We conclude that Bipap can significantly prolong survival and slow the decline of FVC in ALS. Our results suggest that all patients with ALS be offered Bipap when their FVC drops below 50%, at the onset of dyspnea, or when a rapid drop in %FVC is noted. PMID:10385053

  8. Fibrinogen Concentrate Improves Survival During Limited Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

    PubMed Central

    White, Nathan J.; Wang, Xu; Liles, W. Conrad; Stern, Susan

    2014-01-01

    The purpose of this study was to evaluate the effect of fibrinogen concentrate, as a hemostatic agent, on limited resuscitation of uncontrolled hemorrhagic shock. We use a swine model of hemorrhagic shock with free bleeding from a 4mm aortic tear to test the effect of adding a one-time dose of fibrinogen concentrate given at the onset of limited fluid resuscitation. Immature female swine were anesthetized and subjected to catheter hemorrhage and aortic tear to induce uniform hemorrhagic shock. Animals (N=7 per group) were then randomized to receive either; 1. No fluid resuscitation (Neg Control), 2. Limited resuscitation in the form of two boluses of 10ml/kg of 6% hydroxyethyl starch solution (HEX) given 30 minutes apart, or 3. The same fluid regimen with one dose of 120mg/kg fibrinogen concentrate given with the first HEX bolus (FBG). Animals were then observed for a total of 6 hours with aortic repair and aggressive resuscitation with shed blood taking place at 3 hours. Survival to 6 hours was significantly increased with FBG (7/8, 86%) vs. HEX (2/7, 29%), and Neg Control (0/7, 0%) (FBG vs. HEX, Kaplan Meier LR p=0.035). Intraperitoneal blood loss adjusted for survival time was increased in HEX (0.4ml/kg/min) when compared to FBG (0.1mg/kg/min, p=0.047) and Neg Control (0.1ml/kg/min, p=0.041). Systemic and cerebral hemodynamics also showed improvement with FBG vs. HEX. Fibrinogen concentrate may be a useful adjunct to decrease blood loss, improve hemodynamics, and prolong survival during limited resuscitation of uncontrolled hemorrhagic shock. PMID:25337778

  9. Does Social Feeding Improve Larval Survival of the Two-Spotted Lady Beetle, Adalia bipunctata?

    PubMed Central

    Moore, Michael P.; Burt, Charles R.; Whitney, Thomas D.; Hastings, Steven A.; Chang, Gary C.

    2012-01-01

    Lady beetles typically lay eggs in clusters, and clutch-mates that emerge near to each other might benefit in multiple ways. For example, lady beetle larvae are attracted to the pheromone released by aphids under attack. Thus, one potential advantage to larvae emerging as a group is if one larva captures an aphid, others can share in consuming the same aphid. Sharing a meal likely reduces the per capita food intake of a hatchling, but it might also provide enough nutrition to prevent death by starvation during a particularly vulnerable stage. In an assay of the behavior of two-spotted lady beetles (Adalia bipunctata), larvae were attracted to chemical cues from damaged aphids, corroborating previous research. Densities of A. bipunctata hatchlings were then manipulated to test whether the presence of clutch-mates increasesed the probability of capturing prey, and the survivorship of hatchlings. In one experiment, a single aphid was placed with a number of lady beetle hatchlings ranging from 1 to 10 in a small arena for 72 hours to evaluate prey capture effectiveness and hatchling survival. As the initial density of lady beetle hatchlings increased, their prey capture rate increased. At the same time, survival of the hatchlings was not affected by their initial density. Five experiments were performed on individual fava bean plants by varying densities of aphids and lady beetle hatchlings to evaluate lady beetle survivorship measured after five days. In all five on-plant experiments, increasing the initial number of lady beetle larvae did not improve their survival. Lady beetle larvae shared meals during the small scale experiments, but that behavior did not improve their survivorship under any of the experimental conditions. PMID:23425121

  10. Bubble Size Control to Improve Oxygen-Based Bleaching: Characterization of Flow Regimes in Pulp-Water-Gas Three-Phase Flows

    SciTech Connect

    S.M. Ghiaasiaan and Seppo Karrila

    2006-03-20

    Flow characteristics of fibrous paper pulp-water-air slurries were investigated in a vertical circular column 1.8 m long, with 5.08 cm diameter. Flow structures, gas holdup (void fraction), and the geometric and population characteristics of gas bubbles were experimentally investigated, using visual observation, Gamma-ray densitometry, and flash X-ray photography. Five distinct flow regimes could be visually identified: dispersed bubbly, layered bubbly, plug, churn-turbulent, and slug. Flow regime maps were constructed, and the regime transition lines were found to be sensitive to consistency. The feasibility of using artificial neural networks (ANNs) for the identification of the flow regimes, using the statistical characteristics of pressure fluctuations measured by a single pressure sensor, was demonstrated. Local pressure fluctuations at a station were recorded with a minimally-intrusive transducer. Three-layer, feed-forward ANNs were designed that could identify the four major flow patterns (bubbly, plug, churn, and slug) well. The feasibility of a transportable artificial neural network (ANN) - based technique for the classification of flow regimes was also examined. Local pressures were recorded at three different locations using three independent but similar transducers. An ANN was designed, trained and successfully tested for the classification of the flow regimes using one of the normalized pressure signals (from Sensor 1). The ANN trained and tested for Sensor 1 predicted the flow regimes reasonably well when applied directly to the other two sensors, indicating a good deal of transportability. An ANN-based method was also developed, whereby the power spectrum density characteristics of other sensors were adjusted before they were used as input to the ANN that was based on Sensor 1 alone. The method improved the predictions. The gas-liquid interfacial surface area concentration was also measured in the study. The gas absorption technique was applied

  11. Quantifying and Improving International Space Station Survivability Following Orbital Debris Penetration

    NASA Technical Reports Server (NTRS)

    Williamsen, Joel; Evans, Hilary; Bohl, Bill; Evans, Steven; Parker, Nelson (Technical Monitor)

    2001-01-01

    The increase of the orbital debris environment in low-earth orbit has prompted NASA to develop analytical tools for quantifying and lowering the likelihood of crew loss following orbital debris penetration of the International Space Station (ISS). NASA uses the Manned Spacecraft and Crew Survivability (MSCSurv) computer program to simulate the events that may cause crew loss following orbital debris penetration of ISS manned modules, including: (1) critical cracking (explosive decompression) of the module; (2) critical external equipment penetration (such as hydrazine and high pressure tanks); (3) critical internal system penetration (guidance, control, and other vital components); (4) hazardous payload penetration (furnaces, pressure bottles, and toxic substances); (5) crew injury (from fragments, overpressure, light flash, and temperature rise); (6) hypoxia from loss of cabin pressure; and (7) thrust from module hole causing high angular velocity (occurring only when key Guidance, Navigation, and Control (GN&C) equipment is damaged) and, thus, preventing safe escape vehicle (EV) departure. MSCSurv is also capable of quantifying the 'end effects' of orbital debris penetration, such as the likelihood of crew escape, the probability of each module depressurizing, and late loss of station control. By quantifying these effects (and their associated uncertainties), NASA is able to improve the likelihood of crew survivability following orbital debris penetration due to improved crew operations and internal designs.

  12. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    PubMed Central

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  13. Xuebijing Injection Promotes M2 Polarization of Macrophages and Improves Survival Rate in Septic Mice

    PubMed Central

    Liu, Yan-Cun; Yao, Feng-Hua; Chai, Yan-Fen; Dong, Ning; Sheng, Zhi-Yong; Yao, Yong-Ming

    2015-01-01

    Xuebijing (XBJ) injection, a concoction of several Chinese herbs, has been widely used as an immunomodulator for the treatment of severe sepsis in China. However, the precise mechanisms responsible for its efficacy have not been fully elucidated. In our study, we determined the flow cytometry markers (F4/80, CD11c, and CD206), the levels of secreted cytokines (TNF-α, IL-6, and IL-10), and the expression of specific proteins of M2 (Ym1, Fizz1, and Arg1) to assess macrophage polarization. Treatment with XBJ lowered M1 associated cytokine levels and increased the level of M2 associated cytokine level. The percentage of M2 phenotype cells of XBJ group was much higher than that of the control group. Expressions of phosphorylated Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6) were markedly enhanced after the administration of XBJ; on the other hand, the M2 associated cytokines and proteins were decreased following treatment with JAK1 or STAT6 inhibitor. In addition, the treatment of XBJ significantly improved the survival rate of septic mice. These studies demonstrate that XBJ can markedly promote M2 polarization and improve the survival rate of septic mice, thereby contributing to therapeutic effect in the treatment of septic complications. PMID:26064161

  14. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma

    PubMed Central

    Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A.; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A. Keith; Obreja, Mihaela; Moreau, Philippe

    2016-01-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. PMID:27439911

  15. Dental Pulp Testing: A Review

    PubMed Central

    Chen, Eugene; Abbott, Paul V.

    2009-01-01

    Dental pulp testing is a useful and essential diagnostic aid in endodontics. Pulp sensibility tests include thermal and electric tests, which extrapolate pulp health from sensory response. Whilst pulp sensibility tests are the most commonly used in clinical practice, they are not without limitations and shortcomings. Pulp vitality tests attempt to examine the presence of pulp blood flow, as this is viewed as a better measure of true health than sensibility. Laser Doppler flowmetry and pulse oximetry are examples of vitality tests. Whilst the prospect is promising, there are still many practical issues that need to be addressed before vitality tests can replace sensibility tests as the standard clinical pulp diagnostic test. With all pulp tests, the results need to be carefully interpreted and closely scrutinised as false results can lead to misdiagnosis which can then lead to incorrect, inappropriate, or unnecessary treatment. PMID:20339575

  16. Novel Pulping Technology: Directed Green Liquor Utilization (D-GLU) Pulping

    SciTech Connect

    Lucian A. Lucia

    2005-11-15

    The general objectives of this new project are the same as those described in the original proposal. Conventional kraft pulping technologies will be modified for significant improvements in pulp production, such as strength, bleachability, and yield by using green liquor, a naturally high, kraft mill-derived sulfidity source. Although split white liquor sulfidity and other high sulfidity procedures have the promise of addressing several of the latter important economic needs of pulp mills, they require considerable engineering/capital retrofits, redesigned production methods, and thus add to overall mill expenditures. Green liquor use, however, possesses the required high sulfidity to obtain in general the benefits attributable to higher sulfidity cooking, without the required capital constraints for implementation. Before introduction of green liquor in our industrial operations, a stronger understanding of its fundamental chemical interaction with the lignin and carbohydrates in US hardwood and softwoods must be obtained. In addition, its effect on bleachability, enhancement of pulp properties, and influence on the overall energy and recovery of the mill requires further exploration before the process witnesses widespread mill use in North America. Thus, proof of principle will be accomplished in this work and the consequent effect of green liquor and other high sulfide sources on the pulping and bleaching operations will be explored for US kraft mills. The first year of this project will generate the pertinent information to validate its ability for implementation in US pulping operations, whereas year two will continue this work while proceeding to analyze pulp bleachability and final pulp/paper properties and develop a general economic and feasibility analysis for its eventual implementation in North America.

  17. Statin Use is Associated with Improved Survival in Patients Undergoing Surgery for Renal Cell Carcinoma

    PubMed Central

    Kaffenberger, Samuel D.; Lin-Tsai, Opal; Stratton, Kelly L.; Morgan, Todd M.; Barocas, Daniel A.; Chang, Sam S.; Cookson, Michael S.; Herrell, S. Duke; Smith, Joseph A.; Clark, Peter E.

    2014-01-01

    Purpose To determine whether statin use at time of surgery is associated with survival following nephrectomy or partial nephrectomy for renal cell carcinoma (RCC). Statins are thought to exhibit a protective effect on cancer incidence and possibly cancer survival in a number of malignancies; to date, no studies have shown an independent association between statin use and mortality in RCC. Methods A retrospective cohort study of 916 patients who underwent radical or partial nephrectomy for RCC from 2000–2010 at a single institution was performed. Primary outcomes were overall (OS) and disease-specific survival (DSS). Univariable survival analyses were performed using the Kaplan-Meier and log-rank methods. Multivariable analysis was performed using a Cox proportional hazards model. The predictive discrimination of the models was assessed with Harrell’s c-index. Results Median follow-up of the entire cohort was 42.5 months. The three-year OS estimate was 83.1% (95%CI, 77.6–87.3%) for statin users and 77.3% (95%CI, 73.7–80.6%) for non-statin users (p=0.53). Three-year DSS was 90.9% (95%CI, 86.3–94.0%) for statin users and 83.5% (95%CI, 80.1–86.3%) for non-statin users (p=0.015). After controlling for age, ASA class, pT stage, pN stage, metastatic status, pre-operative anemia and corrected hypercalcemia, and blood type, statin use at time of surgery was independently associated with improved OS (HR 0.62, 95%CI 0.43–0.90; p=0.011) and DSS (HR 0.48, 95%CI 0.28–0.83; p=0.009). The multivariable model for DSS had excellent predictive discrimination with a c-index of 0.91. Conclusions These data suggest that statin usage at time of surgery is independently associated with improved OS and DSS in patients undergoing surgery for RCC. PMID:25456998

  18. Dentin barrier test with transfected bovine pulp-derived cells.

    PubMed

    Schmalz, G; Schuster, U; Thonemann, B; Barth, M; Esterbauer, S

    2001-02-01

    Growth kinetics of SV40 large T-antigen-transfected bovine pulp-derived cells on dentin were investigated. These cells were used in a dentin barrier test device, and the system was evaluated by testing a set of dental filling materials. Cells (120 cells/mm2) were seeded on dentin slices and incubated for up to 21 days. Cell proliferation was recorded using MTT assay. For cytotoxicity tests 3500 cells/mm2 were seeded on dentin discs, which were then incorporated into the dentin barrier test device. After 72 h preincubation test materials were applied. After a 24 h exposure with or without perfusion of the pulpal part of the test device, cell survival was evaluated using MTT assay. The cells revealed similar growth kinetics on dentin slices and on tissue culture plates. In cytotoxicity tests the cells were more sensitive toward the test materials than previously used three-dimensional cultures of human foreskin fibroblasts and as anticipated from clinical experience. Further improvement is expected by using three-dimensional cultures of pulp-derived cells. PMID:11491647

  19. Has the survival of the graft improved after renal transplantation in the era of modern immunosuppression?

    PubMed

    Moreso, Francesc; Hernández, Domingo

    2013-01-18

    The introduction of new immunosuppressant drugs in recent years has allowed for a reduction in acute rejection rates along with highly significant improvements in short-term kidney transplantation results. Nonetheless, this improvement has not translated into such significant changes in long-term results. In this manner, late graft failure continues to be a frequent cause of readmission onto dialysis programmes and re-entry onto the waiting list. Multiple entities of immunological and non-immunological origin act together and lead to chronic allograft dysfunction. The characteristics of the transplanted organ are a greater determinant of graft survival, and although various algorithms have been designed as a way of understanding the risk of the transplant organ and assigning the most adequate recipient accordingly. They are applied in the clinical setting only under exceptional circumstances. Characterising, for each patient, the immune factors (clinical and subclinical rejection, reactivation of dormant viral infections, adherence to treatment) and non-immune factors (hypertension, diabetes, anaemia, dyslipidaemia) that contribute to chronic allograft dysfunction could allow us to intervene more effectively as a way of delaying the progress of such processes. Therefore, identifying the causes of graft failure and its risk factors, applying predictive models, and intervening in causal factors could constitute strategies for improving kidney transplantation results in terms of survival. This review analyses some of the evidences conditioning graft failure as well as related therapeutic and prognostic aspects: 1) magnitude of the problem and causes of graft failure; 2) identification of graft failure risk factors; 3) therapeutic strategies for reducing graft failure, and; 4) graft failure prediction. PMID:23364624

  20. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    PubMed

    Jung, Enjae; Perrone, Erin E; Brahmamdan, Pavan; McDonough, Jacquelyn S; Leathersich, Ann M; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Hotchkiss, Richard S; Coopersmith, Craig M

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

  1. Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007.

    PubMed

    Bartelheim, Kerstin; Nemes, Karolina; Seeringer, Angela; Kerl, Kornelius; Buechner, Jochen; Boos, Joachim; Graf, Norbert; Dürken, Matthias; Gerss, Joachim; Hasselblatt, Martin; Kortmann, Rolf-Dieter; Teichert von Luettichau, Irene; Nagel, Inga; Nygaard, Randi; Oyen, Florian; Quiroga, Eduardo; Schlegel, Paul-Gerhardt; Schmid, Irene; Schneppenheim, Reinhard; Siebert, Reiner; Solano-Paez, Palma; Timmermann, Beate; Warmuth-Metz, Monika; Frühwald, Michael Christoph

    2016-08-01

    Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials. PMID:27228363

  2. Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury

    PubMed Central

    Jung, Enjae; Perrone, Erin E.; Brahmamdan, Pavan; McDonough, Jacquelyn S.; Leathersich, Ann M.; Dominguez, Jessica A.; Clark, Andrew T.; Fox, Amy C.; Dunne, W. Michael; Hotchkiss, Richard S.; Coopersmith, Craig M.

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

  3. HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia

    PubMed Central

    Wang, Libing; Gao, Lei; Lü, Shuqin; Xi, Hao; Qiu, Huiying; Chen, Li; Chen, Jie; Ni, Xiong; Xu, Xiaoqian; Zhang, Weiping; Yang, Jianmin; Wang, Jianmin; Song, Xianmin

    2016-01-01

    Background Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. Design and Methods We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Results Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). Conclusions The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients. PMID:26497216

  4. Improvement of Cell Survival During Human Pluripotent Stem Cell Definitive Endoderm Differentiation.

    PubMed

    Wang, Han; Luo, Xie; Yao, Li; Lehman, Donna M; Wang, Pei

    2015-11-01

    Definitive endoderm (DE) is a vital precursor for internal organs such as liver and pancreas. Efficient protocol to differentiate human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) to DE is essential for regenerative medicine and for modeling diseases; yet, poor cell survival during DE differentiation remains unsolved. In this study, our use of B27 supplement in modified differentiation protocols has led to a substantial improvement. We used an SOX17-enhanced green fluorescent protein (eGFP) reporter hESC line to compare and modify established DE differentiation protocols. Both total live cell numbers and the percentages of eGFP-positive cells were used to assess differentiation efficiency. Among tested protocols, three modified protocols with serum-free B27 supplement were developed to generate a high number of DE cells. Massive cell death was avoided during DE differentiation and the percentage of DE cells remained high. When the resulting DE cells were further differentiated toward the pancreatic lineage, the expression of pancreatic-specific markers was significantly increased. Similar high DE differentiation efficiency was observed in H1 hESCs and iPSCs through the modified protocols. In B27 components, bovine serum albumin was found to facilitate DE differentiation and cell survival. Using our modified DE differentiation protocols, satisfactory quantities of quality DE can be produced as primary material for further endoderm lineage differentiation. PMID:26132288

  5. Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis

    PubMed Central

    Liang, DongYu; Hou, YanQiang; Lou, XiaoLi; Chen, HongWei

    2015-01-01

    Purpose Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP)-induced sepsis in mice. Methods C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation. Results Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05). Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis. Conclusions Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis. PMID:26121476

  6. Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative Bacterial Infections

    PubMed Central

    Brown, Anthony E.; Baumbach, Janina; Cook, Peter E.; Ligoxygakis, Petros

    2009-01-01

    Background Primary immunodeficiencies are inborn errors of immunity that lead to life threatening conditions. These predispositions describe human immunity in natura and highlight the important function of components of the Toll-IL-1- receptor-nuclear factor kappa B (TIR-NF-κB) pathway. Since the TIR-NF-κB circuit is a conserved component of the host defence in higher animals, genetically tractable models may contribute ideas for clinical interventions. Methodology/Principal Findings We used immunodeficient fruit flies (Drosophila melanogaster) to address questions pertaining to survival following bacterial infection. We describe here that flies lacking the NF-κB protein Relish, indispensable for countering Gram-negative bacteria, had a greatly improved survival to such infections when subject to dietary short-term starvation (STS) prior to immune challenge. STS induced the release of Nitric Oxide (NO), a potent molecule against pathogens in flies, mice and humans. Administering the NO Synthase-inhibitory arginine analog N-Nitro-L-Arginine-Methyl-Ester (L-NAME) but not its inactive enantiomer D-NAME increased once again sensitivity to infection to levels expected for relish mutants. Surprisingly, NO signalling required the NF-κB protein Dif, usually needed for responses against Gram-positive bacteria. Conclusions/Significance Our results show that NO release through STS may reflect an evolutionary conserved process. Moreover, STS could be explored to address immune phenotypes related to infection and may offer ways to boost natural immunity. PMID:19221590

  7. Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival

    PubMed Central

    Mantel, Hendrik T. J.; Westerkamp, Andrie C.; Adam, René; Bennet, William F.; Seehofer, Daniel; Settmacher, Utz; Sánchez-Bueno, Francisco; Fabregat Prous, Joan; Boleslawski, Emmanuel; Friman, Styrbjörn; Porte, Robert J.

    2016-01-01

    Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five–year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience. PMID:27276221

  8. Ascorbic acid improves embryonic cardiomyoblast cell survival and promotes vascularization in potential myocardial grafts in vivo.

    PubMed

    Martinez, Eliana C; Wang, Jing; Gan, Shu Uin; Singh, Rajeev; Lee, Chuen Neng; Kofidis, Theo

    2010-04-01

    Organ restoration via cell therapy and tissue transplantation is limited by impaired graft survival. We tested the hypothesis that ascorbic acid (AA) reduces cell death in myocardial grafts both in vitro and in vivo and introduced a new model of autologous graft vascularization for later transplantation. Luciferase (Fluc)- and green fluorescent protein (GFP)-expressing H9C2 cardiomyoblasts were seeded in gelatin scaffolds to form myocardial artificial grafts (MAGs). MAGs were supplemented with AA (5 or 50 mumol/L) or plain growth medium. Bioluminescence imaging showed increased cell photon emission from day 1 to 5 in grafts supplemented with 5 mumol/L (p < 0.001) and 50 mumol/L (p < 0.01) AA. The amount of apoptotic cells in plain MAGs was significantly higher than in AA-enriched grafts. In our in vitro model, AA also enhanced H9C2 cell myogenic differentiation. For in vivo studies, MAGs containing H9C2-GFP-Fluc cells and enriched with AA (n = 10) or phosphate-buffered saline (n = 10) were implanted in the renal pouch of Wistar rats. At day 6, postimplantation bioluminescence signals decreased by 74% of baseline in plain MAGs versus 36% in AA-enriched MAGs (p < 0.0001). AA grafts contained significantly higher amounts of blood vessels, GFP(+) donor cells, and endothelial cells. In this study, we identified AA as a potent supplement that improves cardiomyoblast survival and promotes neovascularization in bioartificial grafts. PMID:19908964

  9. Effective treatment for improving the survival rate of raccoon dogs infected with Sarcoptes scabiei.

    PubMed

    Kido, Nobuhide; Omiya, Tomoko; Kamegaya, Chihiro; Wada, Yuko; Takahashi, Maya; Yamamoto, Yasuhiko

    2014-08-01

    Sarcoptes scabiei is one of the important external parasites. Although ivermectin is the recommended treatment, many raccoon dogs (Nyctereutes procyonoides) that were rescued and brought to the Kanazawa Zoological Gardens (Yokohama, Japan) have died because of S. scabiei, even after receiving single ivermectin treatment. Therefore, supportive treatment should be required. The present study revealed the number of animals that survived was greater after the administration of ivermectin along with an antibiotic for all raccoon dogs, as well as following the administration of fluid therapy to the debilitated raccoon dogs infected with S. scabiei, immediately after the rescue. During the initial period, treatment to improve the general clinical condition was required prior to deworming treatment for S. scabiei. PMID:24813465

  10. Metallofullerene-Nanoplatform-Delivered Interstitial Brachytherapy Improved Survival in a Murine Model of Glioblastoma Multiforme

    PubMed Central

    Wilson, John D.; Broaddus, William C.; Dorn, Harry C.; Fatouros, Panos P.; Chalfant, Charles E.; Shultz, Michael D.

    2012-01-01

    Fullerenes are used across scientific disciplines because of their diverse properties gained by altering encapsulated or surface bound components. In this study, the recently developed theranostic agent based on a radiolabeled functionalized metallofullerene (177Lu-DOTA-f-Gd3N@C80) was synthesized with high radiochemical yield and purity. The efficacy of this agent was demonstrated in two orthotopic xenograft brain tumor models of glioblastoma multiforme (GBM). A dose-dependent improvement in survival was also shown. The in vivo stability of the agent was verified through dual label measurements of biological elimination from the tumor. Overall, these results provide evidence that nanomaterial platforms can be used to deliver effective interstitial brachytherapy. PMID:22881865

  11. Effective Treatment for Improving the Survival Rate of Raccoon Dogs Infected with Sarcoptes scabiei

    PubMed Central

    KIDO, Nobuhide; OMIYA, Tomoko; KAMEGAYA, Chihiro; WADA, Yuko; TAKAHASHI, Maya; YAMAMOTO, Yasuhiko

    2014-01-01

    ABSTRACT Sarcoptes scabiei is one of the important external parasites. Although ivermectin is the recommended treatment, many raccoon dogs (Nyctereutes procyonoides) that were rescued and brought to the Kanazawa Zoological Gardens (Yokohama, Japan) have died because of S. scabiei, even after receiving single ivermectin treatment. Therefore, supportive treatment should be required. The present study revealed the number of animals that survived was greater after the administration of ivermectin along with an antibiotic for all raccoon dogs, as well as following the administration of fluid therapy to the debilitated raccoon dogs infected with S. scabiei, immediately after the rescue. During the initial period, treatment to improve the general clinical condition was required prior to deworming treatment for S. scabiei. PMID:24813465

  12. The growing prevalence of type 2 diabetes: increased incidence or improved survival?

    PubMed

    Maruthur, Nisa M

    2013-12-01

    Approximately 347 million persons were estimated to have diabetes worldwide in 2008, an increase of 194 million cases from 1980. Diabetes now affects both high- and low-income countries, with low-income countries bearing the majority of the burden. The epidemiologic transition from traditional health risks, such as poor hygiene, to modern health risks, such as sedentary lifestyle, has facilitated the increase in incidence in diabetes, especially in developing countries. The effect of these risk factors may be especially pronounced in some racial and ethnic populations. Increased surveillance for diabetes has contributed to increased diabetes prevalence in higher-income countries. Survival with and some risk factors for diabetes have improved in developed countries, but global diabetes mortality has increased by 20 % since 1990. Population growth and aging will only increase the burden of diabetes, and public health interventions are needed to address diabetes risk factors to stem the tide of this epidemic. PMID:24072478

  13. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives

    PubMed Central

    Bayanzay, Karim; Alzoebie, Lama

    2016-01-01

    Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. PMID:27540317

  14. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease

    SciTech Connect

    Lindvall, O.; Brundin, P.; Widner, H.; Rehncrona, S.; Gustavii, B.; Frackowiak, R.; Leenders, K.L.; Sawle, G.; Rothwell, J.C.; Marsden, C.D. )

    1990-02-02

    Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-({sup 18}F)fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the on-off phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

  15. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives.

    PubMed

    Bayanzay, Karim; Alzoebie, Lama

    2016-01-01

    Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. PMID:27540317

  16. Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!

    PubMed Central

    Hailer, Nils P; Lazarinis, Stergios; Mäkelä, Keijo T; Eskelinen, Antti; Fenstad, Anne M; Hallan, Geir; Havelin, Leif; Overgaard, Søren; Pedersen, Alma B; Mehnert, Frank; Kärrholm, Johan

    2015-01-01

    Background and purpose It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients and methods We identified 152,410 THA procedures using uncemented stems that were performed between 1995 and 2011 and registered in the Nordic Arthroplasty Register Association (NARA) database. We excluded 19,446 procedures that used stem brands less than 500 times in each country, procedures performed due to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed for the endpoint stem revision. Unadjusted survival rates were calculated according to Kaplan-Meier, and Cox proportional hazards models were fitted in order to calculate hazard ratios (HRs) for the risk of revision with 95% confidence intervals (CIs). Results Unadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8–92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4–99.0) to 99.9% (CI: 99.6–100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5–1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8–1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was

  17. Gacyclidine improves the survival and reduces motor deficits in a mouse model of amyotrophic lateral sclerosis

    PubMed Central

    Gerber, Yannick N.; Privat, Alain; Perrin, Florence E.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder typified by a massive loss of motor neurons with few therapeutic options. The exact cause of neuronal degeneration is unknown but it is now admitted that ALS is a multifactorial disease with several mechanisms involved including glutamate excitotoxicity. More specifically, N-methyl-D-aspartate (NMDA)-mediated cell death and impairment of the glutamate-transport has been suggested to play a key role in ALS pathophysiology. Thus, evaluating NMDAR antagonists is of high therapeutic interest. Gacyclidine, also named GK11, is a high affinity non-competitive NMDAR antagonist that may protect against motor neuron death in an ALS context. Moreover, GK11 presents a low intrinsic neurotoxicity and has already been used in two clinical trials for CNS lesions. In the present study, we investigated the influence of chronic administration of two doses of GK11 (0.1 and 1 mg/kg) on the survival and the functional motor activity of hSOD1G93A mice, an animal model of ALS. Treatment started at early symptomatic age (60 days) and was applied bi-weekly until the end stage of the disease. We first confirmed that functional alteration of locomotor activity was evident in the hSOD1G93A transgenic female mice by 60 days of age. A low dose of GK11 improved the survival of the mice by 4.3% and partially preserved body weight. Improved life span was associated with a delay in locomotor function impairment. Conversely, the high dose treatment worsened motor functions. These findings suggest that chronic administration of GK11 beginning at early symptomatic stage may be beneficial for patients with ALS. PMID:24409117

  18. Intravenous Mesenchymal Stem Cells Improve Survival and Motor Function in Experimental Amyotrophic Lateral Sclerosis

    PubMed Central

    Uccelli, Antonio; Milanese, Marco; Principato, Maria Cristina; Morando, Sara; Bonifacino, Tiziana; Vergani, Laura; Giunti, Debora; Voci, Adriana; Carminati, Enrico; Giribaldi, Francesco; Caponnetto, Claudia; Bonanno, Giambattista

    2012-01-01

    Despite some advances in the understanding of amyotrophic lateral sclerosis (ALS) pathogenesis, significant achievements in treating this disease are still lacking. Mesenchymal stromal (stem) cells (MSCs) have been shown to be effective in several models of neurological disease. To determine the effects of the intravenous injection of MSCs in an ALS mouse model during the symptomatic stage of disease, MSCs (1 × 106) were intravenously injected in mice expressing human superoxide dismutase 1 (SOD1) carrying the G93A mutation (SOD1/G93A) presenting with experimental ALS. Survival, motor abilities, histology, oxidative stress markers and [3H]d-aspartate release in the spinal cord were investigated. MSC injection in SOD1/G93A mice improved survival and motor functions compared with saline-injected controls. Injected MSCs scantly home to the central nervous system and poorly engraft. We observed a reduced accumulation of ubiquitin agglomerates and of activated astrocytes and microglia in the spinal cord of MSC-treated SOD1/G93A mice, with no changes in the number of choline acetyltransferase– and glutamate transporter type 1–positive cells. MSC administration turned around the upregulation of metallothionein mRNA expression and of the activity of the antioxidant enzyme glutathione S-transferase, both associated with disease progression. Last, we observed that MSCs reverted both spontaneous and stimulus-evoked neuronal release of [3H]d-aspartate, a marker of endogenous glutamate, which is upregulated in SOD1/G93A mice. These findings suggest that intravenous administration of MSCs significantly improves the clinical outcome and pathological scores of mutant SOD1/G93A mice, thus providing the rationale for their exploitation for the treatment of ALS. PMID:22481270

  19. Daumone fed late in life improves survival and reduces hepatic inflammation and fibrosis in mice

    PubMed Central

    Park, Jong Hee; Chung, Hae Young; Kim, Minkyu; Lee, Jung Hwa; Jung, Mankil; Ha, Hunjoo

    2014-01-01

    The liver is one of the most susceptible organs to aging, and hepatic inflammation and fibrosis increase with age. Chronic inflammation has been proposed as the major molecular mechanism underlying aging and age-related diseases, whereas calorie restriction has been shown to be the most effective in extending mammalian lifespan and to have anti-aging effects through its anti-inflammatory action. Thus, it is necessary to develop effective calorie restriction mimetics. Daumone [(2)-(6R)-(3,5-dihydroxy-6-methyltetrahydropyran-2-yloxy)heptanoic acid], a pheromone secreted by Caenorhabditis elegans, forces them to enter the dauer stage when facing inadequate conditions. Because Caenorhabditis elegans live longer during the dauer stage under energy deprivation, it was hypothesized that daumone may improve survival in mammals by mimicking calorie restriction. Daumone (2 mg kg−1 day−1) was administered orally for 5 months to 24-month-old male C57BL/6J mice. Daumone was found to reduce the risk of death by 48% compared with age-matched control mice, and the increased plasma insulin normally presented in old mice was significantly reduced by daumone. The increased hepatic hypertrophy, senescence-associated β-galactosidase activity, insulin resistance, lipid accumulation, inflammation, oxidative stress, and fibrosis in old mice were significantly attenuated by daumone. From a mechanistic view, daumone reduced the phosphorylation of the IκBα and upregulation of Rela and Nfkbia mRNA in the livers of old mice. The anti-inflammatory effect of daumone was confirmed in lipopolysaccharide-induced liver injury model. Oral administration of daumone improves survival in mice and delivers anti-aging effects to the aged liver by modulating chronic inflammation, indicating that daumone could be developed as an anti-aging compound. PMID:24796965

  20. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades.

    PubMed

    Carbonell, Nicolas; Pauwels, Arnaud; Serfaty, Lawrence; Fourdan, Olivier; Lévy, Victor George; Poupon, Raoul

    2004-09-01

    Over the past two decades, new treatment modalities have been introduced for the management of variceal bleeding. The aim of this retrospective study in a single center was to assess whether these treatments have improved the prognosis for cirrhotic patients with variceal bleeding. We reviewed the clinical records of all patients with cirrhosis admitted to our Liver Intensive Care Unit due to variceal bleeding during the years 1980, 1985, 1990, 1995, and 2000. Whereas balloon tamponade was still the first-line treatment in 1980, patients treated in 2000 received a vasoactive agent, an endoscopic treatment, and an antibiotic prophylaxis in, respectively, 90%, 100%, and 94% of cases. The in-hospital mortality rate steadily decreased over the study period: 42.6%, 29.9%, 25%, 16.2%, and 14.5% in 1980, 1985, 1990, 1995, and 2000, respectively (P < .05). Mortality decreased from 9% in 1980 to 0% in 2000 in Child-Turcotte-Pugh class A patients, from 46% to 0% in class B patients, and from 70% to 32% in class C patients. This improved survival was associated with a decrease of rebleeding (from 47% in 1980 to 13% in 2000) and bacterial infection rates (from 38% to 14%). On multivariable analysis, endoscopic therapy and antibiotic prophylaxis were independent predictors of survival. In conclusion, in-hospital mortality of patients with cirrhosis and variceal bleeding decreased threefold over the past two decades, in concurrence with an early and combined use of pharmacological and endoscopic therapies and short-term antibiotic prophylaxis. PMID:15349904

  1. Recognition and management of atlanto-occipital dislocation: improving survival from an often fatal condition

    PubMed Central

    Fisher, Charles G.; Sun, John C.L.; Dvorak, Marcel

    2001-01-01

    Objective To provide an overview of atlanto-occipital dislocation and associated occipital condyle fractures so as to alert physicians to this rare injury and potentially improve patient outcome. The pertinent anatomy, mechanism of injury, clinical and radiologic evaluation and the management of these rare injuries are discussed in an attempt to alert physicians to this type of injury and to improve outcome. Data sources The data were obtained from a MEDLINE search of the English literature from 1966 to 1999 and the experience of 4 spine surgeons at a quaternary care acute spinal cord injury unit. Study selection Detailed anatomic and epidemiologically sound radiology studies were identified and analyzed. Only small retrospective studies or case series were available in the literature. Data extraction Valid anatomic, biomechanical and radiologic evaluation was extracted from studies. Clinical data came from limited studies and expert opinion. Data synthesis Early diagnosis is essential and is facilitated by a detailed clinical examination and strict adherence to an imaging algorithm that includes CT and MRI scanning. When the dislocation is identified, timely gentle reduction and prompt stabilization throuigh nonoperative or operative means is found to optimize patient outcome. Conclusions Atlanto-occipital dislocation should be suspected in any patient involved in a high speed motor vehicle or pedestrian collision. Once suspected, proper imaging and appropriate management of these once fatal injuries can improve survival and neurologic outcome. PMID:11764873

  2. Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer.

    PubMed

    Cerullo, Marcelo; Gani, Faiz; Chen, Sophia Y; Canner, Joe; Pawlik, Timothy M

    2016-09-01

    Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD = 9.1 years). Roughly one half of patients were female (n = 1735, 51.1 %); 49.1 % (n = 1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n = 664) had diabetes. At the time of surgery, 60.0 % (n = 2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n = 1212) a partial/distal pancreatectomy, while 4.3 % (n = 147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p = 0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4-67.3 %] vs. 69.2 % [95 % CI 64.2-73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR] = 0.79, 95 % CI 0.67-0.93, p

  3. [Endodontic treatment of primary teeth. Pulp exposure and pulp necrosis].

    PubMed

    Gruythuysen, R J M

    2005-11-01

    With management of the deep caries in primary teeth we have to take account into the coping strategies of the patient and the state of the development of the dentition. That's why in most cases a root canal treatment of primary incisors or even a pulpotomy is not indicated. Often Intellectual Decision Not To Restore is a good alternative for treatment of deep caries in primary incisors. In deep caries lesions of primary canines and molars preferably minimal invasive techniques as indirect pulp capping are performed. In case of a exposure, the dentist can choose between several types of treatment. Improved techniques have lead to clinical satisfying results of the calcium hydroxide pulpotomy. A partial pulpotomy is if possible the treatment of choice. A resin modified glass ionomer cement is used to cover the pulp wound because it has good sealing properties and it is easy to handle. To limit the burden in young children a root canal treatment in primary teeth is seldom indicated. Overfilling with calcium hydroxide in root canal treatment of primary teeth never causes problems. PMID:16320568

  4. Tissue Engineering Considerations in Dental Pulp Regeneration

    PubMed Central

    Nosrat, Ali; Kim, Jong Ryul; Verma, Prashant; S. Chand, Priya

    2014-01-01

    Regenerative endodontic procedure is introduced as a biologically based treatment for immature teeth with pulp necrosis. Successful clinical and radiographic outcomes following regenerative procedures have been reported in landmark case reports. Retrospective studies have shown that this conservative treatment allows for continued root development and increases success and survival rate of the treated teeth compared to other treatment options. Although the goal of treatment is regeneration of a functional pulp tissue, histological analyses show a different outcome. Developing predictable protocols would require the use of key elements for tissue engineering: stem cells, bioactive scaffolds, and growth factors. In this study we will review the evidence based steps and outcomes of regenerative endodontics. PMID:24396373

  5. 38 CFR 3.712 - Improved pension elections; surviving spouses of Spanish-American War veterans.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... elections; surviving spouses of Spanish-American War veterans. 3.712 Section 3.712 Pensions, Bonuses, and... spouses of Spanish-American War veterans. (a) General. A surviving spouse of a Spanish-American War... and attendance. A surviving spouse of a Spanish-American War veteran who is receiving or entitled...

  6. Improved Posttreatment Functional Outcome is Associated with Better Survival in Patients Irradiated for Metastatic Spinal Cord Compression

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Veninga, Theo; Stalpers, Lukas J.A.; Basic, Hiba; Hoskin, Peter J.; Karstens, Johann H.; Schild, Steven E.; Dunst, Juergen

    2007-04-01

    Purpose: To evaluate the potential prognostic impact of the effect of radiotherapy (RT) on motor function and of the post-RT ambulatory status on survival in metastatic spinal cord compression (MSCC) patients. Methods and Materials: Of 1,852 patients irradiated for MSCC, 778 patients (42%) received short-course RT and 1,074 (58%) received long-course RT. The effect of RT on motor function (improvement vs. no change vs. deterioration) and the ambulatory status after RT (ambulatory vs. nonambulatory) were evaluated with respect to survival. Results: The actuarial survival rate of the entire cohort was 56% at 6 months, 43% at 12 months, and 32% at 24 months. The patients in whom motor function improved after RT had a significantly better 1-year survival rate than those who had no change or deterioration of motor function (75% vs. 40% and 3%, p < 0.001). The 1-year survival rate of the patients who were ambulatory after RT was significantly better than for those who were not ambulatory (63% vs. 4%, p < 0.001). The results were confirmed in multivariate analysis. Conclusions: The response to RT and the post-RT ambulatory status are important predictors for survival in MSCC patients. This finding can be used by physicians to stratify future studies, plan further therapy, and improve follow-up strategy in these patients.

  7. Improving male mating competitiveness and survival in the field for medfly, Ceratitis capitata (Diptera: Tephritidae) SIT programs.

    PubMed

    McInnis, D O; Shelly, T E; Komatsu, J

    2002-09-01

    The success of the sterile insect technique (SIT) depends critically upon mating between released sterilized males and wild females. In Hawaii, improvements in the efficiency of sterile males were attempted on two separate fronts--mating enhancement and survival improvement. In the former, two methods have been investigated--selective breeding and aromatherapy. In the latter, flies which survived in field cages for several days were selected and bred to produce progeny with enhanced survival ability compared to control flies. Regarding mating selection, standard laboratory-reared males that successfully mated with wild females in field cages were allowed to breed. F1 offspring were inbred, then the selection procedure was repeated for four additional cycles. In the aromatherapy procedure, laboratory-reared males were exposed to ginger root oil for several hours 1 day prior to testing in field cages. Compared to controls, the selected flies improved the mating competitiveness of male flies ca. 3-fold, irradiation reduced this increase to ca. 2.5-fold. Exposing the selected, hybrid strain raised the fitness of the lab males to ca. 9-fold that of wild males. In the ongoing survival selection study, we have obtained lines in which the selected males survived ca. 2-fold better than laboratory control males over several days in an outdoor field cage, with food and water provided. The goal is to combine the traits of higher survival and mating ability into a single strain for SIT release. PMID:12484531

  8. Prone positioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis.

    PubMed

    Gattinoni, L; Carlesso, E; Taccone, P; Polli, F; Guérin, C; Mancebo, J

    2010-06-01

    Prone positioning has been used for over 30 years in the management of patients with acute respiratory distress syndrome (ARDS). This maneuver has consistently proven capable of improving oxygenation in patients with acute respiratory failure. Several mechanisms can explain this observation, including possible intervening net recruitment and more homogeneously distributed alveolar inflation. It is also progressively becoming clear that prone positioning may reduce the nonphysiological stress and strain associated with mechanical ventilation, thus decreasing the risk of ventilator-induced lung injury, which is known to adversely impact patient survival. The available randomized clinical trials, however, have failed to demonstrate that prone positioning improves the outcomes of patients with ARDS overall. In contrast, the individual patient meta-analysis of the four major clinical trials available clearly shows that with prone positioning, the absolute mortality of severely hypoxemic ARDS patients may be reduced by approximately 10%. On the other hand, all data suggest that long-term prone positioning may expose patients with less severe ARDS to unnecessary complications. PMID:20473258

  9. Resveratrol improves health and survival of mice on a high-calorie diet

    PubMed Central

    Baur, Joseph A.; Pearson, Kevin J.; Price, Nathan L.; Jamieson, Hamish A.; Lerin, Carles; Kalra, Avash; Prabhu, Vinayakumar V.; Allard, Joanne S.; Lopez-Lluch, Guillermo; Lewis, Kaitlyn; Pistell, Paul J.; Poosala, Suresh; Becker, Kevin G.; Boss, Olivier; Gwinn, Dana; Wang, Mingyi; Ramaswamy, Sharan; Fishbein, Kenneth W.; Spencer, Richard G.; Lakatta, Edward G.; Le Couteur, David; Shaw, Reuben J.; Navas, Placido; Puigserver, Pere; Ingram, Donald K.; de Cabo, Rafael; Sinclair, David A.

    2016-01-01

    Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor- γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing. PMID:17086191

  10. Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

    PubMed

    Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

    2016-09-01

    The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. PMID:27343465

  11. Improved Survival and Hematopoietic Differentiation of Murine Embryonic Stem Cells on Electrospun Polycaprolactone Nanofiber

    PubMed Central

    Dehdilani, Nima; Shamsasenjan, Karim; Movassaghpour, Aliakbar; Akbarzadehlaleh, Parvin; Amoughli Tabrizi, Bahram; Parsa, Hamed; Sabagi, Fatemeh

    2016-01-01

    differentiation between the PCL and TCP culture systems. There were more CD34+(Sca1+) and CD133+cells subpopulations in the PCL group compared to the conventional TCP culture system. Conclusion The nanofiber scaffold, as an effective surface, improves survival and differentiation of mESCs into mHSCs compared to gelatin coated TCP. More studies are necessary to understand how the topographical features of electrospun fibers af- fect cell growth and behavior. This can be achieved by designing biomimetic scaffolds for tissue engineering. PMID:26862522

  12. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    SciTech Connect

    Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  13. Chloroquine improves survival and hematopoietic recovery following lethal low dose- rate radiation

    PubMed Central

    Lim, Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang, Yonggang; Yu, Hsiang-Hsuan M; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-01-01

    Purpose We have previously shown that the anti-malarial agent chloroquine can abrogate the lethal cellular effects of low dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials C57BL/6 mice were irradiated with total of 12.8 Gy delivered at 9.4 cGy/hr. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hrs and 4 hrs before irradiation. Bone marrow cells isolated from tibia, fibula and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retro orbital injection. Chimerism was assessed by flow cytometry. In vitro methyl cellulose colony forming assay of whole bone marrow cells as well as FACS analysis of lineage depleted cells was used to assess the effect of chloroquine on progenitor cells. Results Mice pretreated with chloroquine prior to radiation exhibited a significantly higher survival rate compared to mice treated with radiation alone (80 vs.31 percent, p=0.0026). Chloroquine administration prior to radiation did not impact the survival of ATM null mice (p=0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after the transplantation (4.2 percent vs. 0.4 percent, p=0.015). Conclusion Chloroquine administration prior to radiation had a significant effect on the survival of normal but not ATM null mice strongly suggesting that the in vivo effect like the in vitro effect is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection against the

  14. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer.

    PubMed

    Liu, Jui-Ming; Lin, Po-Hung; Hsu, Ren-Jun; Chang, Ying-Hsu; Cheng, Kuan-Chen; Pang, See-Tong; Lin, Shun-Ku

    2016-08-01

    More than 50% of prostate cancer patients have used traditional Chinese medicine (TCM) in Taiwan. However, the long-term clinical efficacy of TCM in prostate cancer patients remains unclear. Here, we investigated the relationship between TCM use and the survival of prostate cancer patients.A retrospective nationwide cohort study of prostate cancer patients was conducted between 1998 and 2003 using the Taiwan National Health Insurance Research Database. Patients were classified as TCM users or nonusers, and monitored from the day of prostate cancer diagnosis to death or end of 2012. The association between death risk and TCM use was determined using Cox proportional-hazards models and Kaplan-Meier curves.Of the 1132 selected prostate cancer patients, 730 (64.5%) and 402 (35.5%) were TCM users and nonusers, respectively. The mean follow-up period was 8.38 years, and 292 (25.8%) deaths were reported. TCM users had a decreased mortality rate (21.9%) compared with nonusers (32.8%). A lower death risk was observed with longer TCM use, especially in patients who used TCM for ≧200 days (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.44-0.84). TCM users with metastatic prostate cancer had a significant lower HR than nonusers (aHR 0.70, 95% CI 0.51-0.95). Chai-Hu-Jia-Long-Gu-Mu-Li-Tang was the most significant TCM formulae for improving survival in metastatic prostate cancer (aHR 0.18, 95% CI 0.04-0.94).The result suggested that complementary TCM therapy might be associated with a reduced risk of death in metastatic prostate cancer patients. PMID:27495088

  15. A new cluster-based oversampling method for improving survival prediction of hepatocellular carcinoma patients.

    PubMed

    Santos, Miriam Seoane; Abreu, Pedro Henriques; García-Laencina, Pedro J; Simão, Adélia; Carvalho, Armando

    2015-12-01

    Liver cancer is the sixth most frequently diagnosed cancer and, particularly, Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers. Clinicians assess each patient's treatment on the basis of evidence-based medicine, which may not always apply to a specific patient, given the biological variability among individuals. Over the years, and for the particular case of Hepatocellular Carcinoma, some research studies have been developing strategies for assisting clinicians in decision making, using computational methods (e.g. machine learning techniques) to extract knowledge from the clinical data. However, these studies have some limitations that have not yet been addressed: some do not focus entirely on Hepatocellular Carcinoma patients, others have strict application boundaries, and none considers the heterogeneity between patients nor the presence of missing data, a common drawback in healthcare contexts. In this work, a real complex Hepatocellular Carcinoma database composed of heterogeneous clinical features is studied. We propose a new cluster-based oversampling approach robust to small and imbalanced datasets, which accounts for the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing procedures of this work are based on data imputation considering appropriate distance metrics for both heterogeneous and missing data (HEOM) and clustering studies to assess the underlying patient groups in the studied dataset (K-means). The final approach is applied in order to diminish the impact of underlying patient profiles with reduced sizes on survival prediction. It is based on K-means clustering and the SMOTE algorithm to build a representative dataset and use it as training example for different machine learning procedures (logistic regression and neural networks). The results are evaluated in terms of survival prediction and compared across baseline approaches that do not consider clustering and/or oversampling using the

  16. Wnt Agonist Attenuates Liver Injury and Improves Survival after Hepatic Ischemia/Reperfusion

    PubMed Central

    Kuncewitch, Michael; Yang, Weng-Lang; Molmenti, Ernesto; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2012-01-01

    The Wnt/β-catenin signaling pathway is well characterized in stem cell biology and plays a critical role in liver development, regeneration, and homeostasis. We hypothesized that pharmacological activation of Wnt signaling protects against hepatic ischemia/reperfusion (I/R) injury through its known proliferative and anti-apoptotic properties. Sprague-Dawley rats underwent 70% hepatic ischemia by microvascular clamping of the hilum of the left and median lobes of the liver for 90 min, followed by reperfusion. Wnt agonist (2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine, 5 mg/kg BW) or vehicle (20% DMSO in saline) in 0.5 ml was injected intraperitoneally (i.p.) 1 h prior to ischemia or infused intravenously over 30 min right after ischemia. Blood and tissue samples from the pre-treated groups were collected 24 h after reperfusion, and a survival study was performed. Hepatic expression of β-catenin and its downstream target gene Axin2 were decreased after I/R while Wnt agonist restored their expression to sham levels. Wnt agonist blunted I/R-induced elevations of AST, ALT, and LDH and significantly improved the microarchitecture of the liver. The cell proliferation determined by Ki67 immunostaining significantly increased with Wnt agonist treatment and inflammatory cascades were dampened in Wnt agonist-treated animals, as demonstrated by attenuations in IL-6, myeloperoxdase, iNOS and nitrotyrosine. Wnt agonist also significantly decreased the amount of apoptosis, as evidenced by decreases in both TUNEL staining as well as caspase-3 activity levels. Finally, the 10-day survival rate was increased from 27% in the vehicle group to 73% in the pre-treated Wnt agonist group and 55% in the Wnt agonist post-ischemia treatment group. Thus, we propose that direct Wnt/β-catenin stimulation may represent a novel therapeutic approach in the treatment of hepatic I/R. PMID:23143067

  17. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer

    PubMed Central

    Liu, Jui-Ming; Lin, Po-Hung; Hsu, Ren-Jun; Chang, Ying-Hsu; Cheng, Kuan-Chen; Pang, See-Tong; Lin, Shun-Ku

    2016-01-01

    Abstract More than 50% of prostate cancer patients have used traditional Chinese medicine (TCM) in Taiwan. However, the long-term clinical efficacy of TCM in prostate cancer patients remains unclear. Here, we investigated the relationship between TCM use and the survival of prostate cancer patients. A retrospective nationwide cohort study of prostate cancer patients was conducted between 1998 and 2003 using the Taiwan National Health Insurance Research Database. Patients were classified as TCM users or nonusers, and monitored from the day of prostate cancer diagnosis to death or end of 2012. The association between death risk and TCM use was determined using Cox proportional-hazards models and Kaplan–Meier curves. Of the 1132 selected prostate cancer patients, 730 (64.5%) and 402 (35.5%) were TCM users and nonusers, respectively. The mean follow-up period was 8.38 years, and 292 (25.8%) deaths were reported. TCM users had a decreased mortality rate (21.9%) compared with nonusers (32.8%). A lower death risk was observed with longer TCM use, especially in patients who used TCM for ≧200 days (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.44–0.84). TCM users with metastatic prostate cancer had a significant lower HR than nonusers (aHR 0.70, 95% CI 0.51–0.95). Chai-Hu-Jia-Long-Gu-Mu-Li-Tang was the most significant TCM formulae for improving survival in metastatic prostate cancer (aHR 0.18, 95% CI 0.04–0.94). The result suggested that complementary TCM therapy might be associated with a reduced risk of death in metastatic prostate cancer patients. PMID:27495088

  18. Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice.

    PubMed

    Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin; Clausen, Bettina H; Lambertsen, Kate L; Valero-Esquitino, Veronica; Thöne-Reineke, Christa; Müller, Susanne; Widdop, Robert E; Denton, Kate M; Horiuchi, Masatsugu; Iwai, Masaru; Boato, Francesco; Dahlöf, Björn; Hallberg, Anders; Unger, Thomas; Steckelings, U Muscha

    2016-08-01

    This study investigated the effect of post-stroke, direct AT2-receptor (AT2R) stimulation with the non-peptide AT2R-agonist compound 21 (C21) on infarct size, survival and neurological outcome after middle cerebral artery occlusion (MCAO) in mice and looked for potential underlying mechanisms. C57/BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21 significantly improved survival after MCAO when compared to vehicle-treated mice. C21 treatment had no impact on infarct size, but significantly attenuated neurological deficits. Expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB) (receptor for BDNF) and growth-associated protein 43 (GAP-43) were significantly increased in the peri-infarct cortex of C21-treated mice when compared to vehicle-treated mice. Furthermore, the number of apoptotic neurons was significantly decreased in the peri-infarct cortex in mice treated with C21 compared to controls. There were no effects of C21 on neurological outcome, infarct size and expression of BDNF or GAP-43 in AT2-KO mice. From these data, it can be concluded that AT2R stimulation attenuates early mortality and neurological deficits after experimental stroke through neuroprotective mechanisms in an AT2R-specific way. Key message • AT2R stimulation after MCAO in mice reduces mortality and neurological deficits.• AT2R stimulation increases BDNF synthesis and protects neurons from apoptosis.• The AT2R-agonist C21 acts protectively when applied post-stroke and peripherally. PMID:26983606

  19. Autologous endothelial progenitor cells improve allograft survival in porcine lung transplantation with prolonged ischemia

    PubMed Central

    Yen, Yi-Ting; Roan, Jun-Neng; Fang, Shih-Yuan; Chang, Shi-Wei; Tseng, Yau-Lin

    2016-01-01

    Background As endothelial progenitor cells (EPCs) attenuated acute lung injury (ALI) in rabbit model, we hypothesized that autologous EPCs preserved lung graft function during the acute reperfusion period of lung transplantation and tested the therapeutic potential of EPCs in a porcine model of lung transplantation with prolonged graft ischemia. Methods Day-7 EPCs isolated from the recipient subjects or plain culture media were administered into the left pulmonary artery immediately before restoration of pulmonary blood flow in a porcine lung allotransplantation model, with the transplantation surgeons blinded to the content of injection. Hemodynamics and arterial blood gas were recorded, and the right pulmonary artery was occluded 30 min after reperfusion to evaluate the lung graft function. The lung grafts were sectioned for histological examination at the end of experiments. The total ischemic time for lung graft was approximately 14 h. Results All animals receiving plain medium died within 40 min after reperfusion, but 3 out of 5 (60%) piglets receiving EPCs survived up to 4 h after diversion of the entire cardiac output into the lung graft (P<0.01). The donor body weight, recipient body weight, cold ischemic time, and time for anastomosis were comparable between the EPC and control group (P=0.989, 0.822, 0.843, and 0.452, respectively). The mean aortic pressure decreased, and the cardiac output and mean pulmonary artery pressure elevated after right pulmonary artery occlusion. All these parameters were gradually compensated in the EPC group but decompensated in the control group. Better preservation of gas exchange function, reduced thrombi formation in the terminal pulmonary arterioles, and attenuated interstitial hemorrhage of the lung graft were observed in the EPC group. Conclusions We concluded autologous EPCs significantly enhanced the function of lung allograft and improved survival in a porcine model of lung transplantation with prolonged ischemia

  20. Adult neural precursor cells form connexin-dependent networks that improve their survival.

    PubMed

    Ravella, Ajaya; Ringstedt, Thomas; Brion, Jean-Pierre; Pandolfo, Massimo; Herlenius, Eric

    2015-10-21

    Establishment of cellular networks and calcium homeostasis are essential for embryonic stem cell proliferation and differentiation. We also hypothesized that adult neural progenitor cells form functional cellular networks relevant for their development. We isolated neuronal progenitor cells from the subventricular zone of 5-week-old mice to investigate the role of gap junctions, calcium homeostasis, and cellular networks in cell differentiation and survival. Western blotting and reverse transcription-PCR showed that the cells expressed the gap junction components connexin 26, 36, 43, and 45, and that expression of connexin 43 increased in early (8 days) differentiated cells. Transmission electron microscopy and immunocytochemistry also indicated that gap junctions were present. Scrape-loading experiments showed dye transfer between cells that could be prevented by gapjunction blockers; thus, functional intercellular gap junctions had been established. However, dye transfer was four times stronger in differentiated cultures, correlating with the increased connexin 43 expression. During time-lapse calcium imaging, both differentiated and undifferentiated cultures showed spontaneous calcium activity that was reduced by gap junction blockers. Cross-correlation analysis of the calcium recordings showed that the cells were interconnected through gap junctions and that the early-differentiated cells were organized in small-world networks. Gap junction blockers did not affect proliferation and differentiation, but resulted in twice as many apoptotic cells. mRNAi knockdown of connexin 43 also doubled the number of apoptotic cells. We conclude that adult neural progenitor cells form networks in vitro that are strengthened during early differentiation by increased expression of connexin 43. The networks are functional and improve cell survival. PMID:26351758

  1. mRNA-based dendritic cell immunization improves survival in ret transgenic mouse melanoma model.

    PubMed

    Sharbi-Yunger, Adi; Grees, Mareike; Tzehoval, Esther; Utikal, Jochen; Umansky, Viktor; Eisenbach, Lea

    2016-06-01

    Malignant melanoma is characterized by a rapid progression, metastasis to distant organs and resistance to chemo and radiotherapy. Although melanoma is capable of eliciting an immune response, the disease progresses and the overall results of immunotherapeutic clinical studies are not satisfactory. Recently, we have developed a novel genetic platform for improving an induction of peptide-specific CD8(+) T cells by dendritic cell (DC) based on membrane-anchored β2-microglobulin (β2m) linked to a selected antigenic peptide at the N-terminus and to the cytosolic domain of TLR4 at the C-terminus. In vitro transcribed mRNA transfection of antigen-presenting cells (APCs) resulted in an efficient coupling of peptide presentation and cell activation. In this research, we utilize the chimeric platform to induce an immune response in ret transgenic mice that spontaneously develop malignant skin melanoma and to examine its effect on the overall survival of tumor-bearing mice. Following immunization with chimeric construct system, we observe a significantly prolonged survival of tumor-bearing mice as compared to the control group. Moreover, we see elevations in the frequency of CD62L(hi)CD44(hi) central and CD62L(lo)CD44(hi) effector memory CD8(+) T-cell subsets. Importantly, we do not observe any changes in frequencies of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the vaccinated groups. Our data suggest that this novel vaccination approach could be efficiently applied for the immunotherapy of malignant melanoma. PMID:27471629

  2. Morphological and mechanical effects of extended beating on EFB pulp web

    NASA Astrophysics Data System (ADS)

    Zukeri, Mohd Ridzuan Hafiz Mohd; Ghazali, Arniza; Lazin, Mohd Azli Khairil Mat

    2012-09-01

    The pulp extracted from the alkaline peroxide pulping (APP) of EFB was beaten from 500 revolutions to 10000 revolutions using PFI mill to investigate the morphological changes undergone by the pulp and the resultant effect on paper sheet properties. As a result of beating, pulp elements were observed as intensely fibrillated, reducing the amounts of fibre bundles and thus, reducing interruption in the inter-fiber bonding. To a defined extent, beating was also seen as unwinding the structure of vessel element to a single strand of loose spiral body. These fibrillated vessel elements of APP pulp from EFB, plus the fines element germinating from further segmentation of the vessels, were the factors contributing to the overall strength improvement of the produced EFB pulp network. The applied increment in beating revolution had apparently widened the known broad spectrum quality of APP pulp from EFB. This demonstrates EFB potential for application in specialty paper production.

  3. A2B Adenosine Receptor Blockade Enhances Macrophage-Mediated Bacterial Phagocytosis and Improves Polymicrobial Sepsis Survival in Mice

    PubMed Central

    Belikoff, Bryan G.; Hatfield, Stephen; Georgiev, Peter; Ohta, Akio; Lukashev, Dmitriy; Buras, Jon A.; Remick, Daniel G.; Sitkovsky, Michail

    2013-01-01

    Antimicrobial treatment strategies must improve to reduce the high mortality rates in septic patients. In noninfectious models of acute inflammation, activation of A2B adenosine receptors (A2BR) in extracellular adenosine-rich microenvironments causes immunosuppression. We examined A2BR in antibacterial responses in the cecal ligation and puncture (CLP) model of sepsis. Antagonism of A2BR significantly increased survival, enhanced bacterial phagocytosis, and decreased IL-6 and MIP-2 (a CXC chemokine) levels after CLP in outbred (ICR/CD-1) mice. During the CLP-induced septic response in A2BR knockout mice, hemodynamic parameters were improved compared with wild-type mice in addition to better survival and decreased plasma IL-6 levels. A2BR deficiency resulted in a dramatic 4-log reduction in peritoneal bacteria. The mechanism of these improvements was due to enhanced macrophage phagocytic activity without augmenting neutrophil phagocytosis of bacteria. Following ex vivo LPS stimulation, septic macrophages from A2BR knockout mice had increased IL-6 and TNF-α secretion compared with wild-type mice. A therapeutic intervention with A2BR blockade was studied by using a plasma biomarker to direct therapy to those mice predicted to die. Pharmacological blockade of A2BR even 32 h after the onset of sepsis increased survival by 65% in those mice predicted to die. Thus, even the late treatment with an A2BR antagonist significantly improved survival of mice (ICR/CD-1) that were otherwise determined to die according to plasma IL-6 levels. Our findings of enhanced bacterial clearance and host survival suggest that antagonism of A2BRs offers a therapeutic target to improve macrophage function in a late treatment protocol that improves sepsis survival. PMID:21242513

  4. Rapid growth in the early marine period improves the marine survival of Chinook salmon (Oncorhynchus tshawytscha) in Puget Sound, Washington

    USGS Publications Warehouse

    Duffy, Elisabeth J.; Beauchamp, David A.

    2011-01-01

    We examined the effect of early marine entry timing and body size on the marine (smolt-to-adult) survival of Puget Sound Chinook salmon (Oncorhynchus tshawytscha). We used data from coded wire tag release groups of hatchery Chinook salmon to test whether hatchery release date, release size, and size in offshore waters in July and September influenced marine survival. Marine survival was most strongly related to the average body size in July, with larger sizes associated with higher survivals. This relationship was consistent over multiple years (1997–2002), suggesting that mortality after July is strongly size-dependent. Release size and date only slightly improved this relationship, whereas size in September showed little relationship to marine survival. Specifically, fish that experienced the highest marine survivals were released before 25 May and were larger than 17 g (or 120 mm fork length) by July. Our findings highlight the importance of local conditions in Puget Sound (Washington, USA) during the spring and summer, and suggest that declines in marine survival since the 1980s may have been caused by reductions in the quality of feeding and growing conditions during early marine life.

  5. Rapid growth in the early marine period improves the marine survival of Chinook salmon (Oncorhynchus tshawytscha) in Puget Sound, Washington

    USGS Publications Warehouse

    Duffy, E.J.; Beauchamp, D.A.

    2011-01-01

    We examined the effect of early marine entry timing and body size on the marine (smolt-to-adult) survival of Puget Sound Chinook salmon (Oncorhynchus tshawytscha). We used data from coded wire tag release groups of hatchery Chinook salmon to test whether hatchery release date, release size, and size in offshore waters in July and September influenced marine survival. Marine survival was most strongly related to the average body size in July, with larger sizes associated with higher survivals. This relationship was consistent over multiple years (1997-2002), suggesting that mortality after July is strongly size-dependent. Release size and date only slightly improved this relationship, whereas size in September showed little relationship to marine survival. Specifically, fish that experienced the highest marine survivals were released before 25 May and were larger than 17 g (or 120 mm fork length) by July. Our findings highlight the importance of local conditions in Puget Sound (Washington, USA) during the spring and summer, and suggest that declines in marine survival since the 1980s may have been caused by reductions in the quality of feeding and growing conditions during early marine life.

  6. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    PubMed Central

    Lotem, Michal; Merims, Sharon; Frank, Stephen; Hamburger, Tamar; Nissan, Aviram; Kadouri, Luna; Cohen, Jonathan; Straussman, Ravid; Eisenberg, Galit; Frankenburg, Shoshana; Carmon, Einat; Alaiyan, Bilal; Shneibaum, Shlomo; Ozge Ayyildiz, Zeynep; Isbilen, Murat; Mert Senses, Kerem; Ron, Ilan; Steinberg, Hanna; Smith, Yoav; Shiloni, Eitan; Gure, Ali Osmay; Peretz, Tamar

    2016-01-01

    Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. PMID:27294163

  7. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  8. Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer Normalization, Not Destruction

    PubMed Central

    Whatcott, Clifford J.; Hanl, Haiyong; Von Hoff, Daniel D.

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. The microenvironment of pancreatic cancer could be one of the “perfect storms” that support the growth of a cancer. Indeed, pancreatic cancer may be the poster child of a problem with the microenvironment. In this article, we review the rationale and attempts to date on modifying or targeting structural proteins in the microenvironment including hyaluronan (HA) (in primary and metastases), collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed, working in this area has produced a regimen that improves survival for patients with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in initial clinical trials, PEGylated hyaluronidase appears promising. We also review a new approach that is different than targeting/destroying the microenvironment and that is orchestrating, reengineering, reprogramming, or normalizing the microenvironment (including normalizing structural proteins, normalizing an immunologically tumor-friendly environment to a less friendly environment, reversing epithelial-to-mesenchymal transition, and so on). We believe this will be most effectively done by agents that have global effects on transcription. There is initial evidence that this can be done by agents such as vitamin D derivatives and other new agents. There is no doubt these opportunities can now be tried in the clinic with hopefully beneficial effects. PMID:26222082

  9. A PPARγ AGONIST ENHANCES BACTERIAL CLEARANCE THROUGH NEUTROPHIL EXTRACELLULAR TRAP FORMATION AND IMPROVES SURVIVAL IN SEPSIS.

    PubMed

    Araújo, Cláudia V; Campbell, Clarissa; Gonçalves-de-Albuquerque, Cassiano F; Molinaro, Raphael; Cody, Mark J; Yost, Christian C; Bozza, Patricia T; Zimmerman, Guy A; Weyrich, Andrew S; Castro-Faria-Neto, Hugo C; Silva, Adriana R

    2016-04-01

    Dysregulation of the inflammatory response against infection contributes to mortality in sepsis. Inflammation provides critical host defense, but it can cause tissue damage, multiple organ failure, and death. Because the nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) exhibits therapeutic potential, we characterized the role of PPARγ in sepsis. We analyzed severity of clinical signs, survival rates, cytokine production, leukocyte influx, and bacterial clearance in a cecal ligation and puncture (CLP) model of sepsis in Swiss mice. The PPARγ agonist rosiglitazone treatment improved clinical status and mortality, while increasing IL-10 production and decreasing TNF-α and IL-6 levels, and peritoneal neutrophil accumulation 24 h after CLP. We noted increased bacterial killing in rosiglitazone treated mice, correlated with increased generation of reactive oxygen species. Polymorphonuclear leukocytes (PMN) incubated with LPS or Escherichia coli and rosiglitazone increased peritoneal neutrophil extracellular trap (NET)-mediated bacterial killing, an effect reversed by the PPARγ antagonist (GW 9662) treatment. Rosiglitazone also enhanced the release of histones by PMN, a surrogate marker of NET formation, effect abolished by GW 9662. Rosiglitazone modulated the inflammatory response and increased bacterial clearance through PPARγ activation and NET formation, combining immunomodulatory and host-dependent anti-bacterial effects and, therefore, warrants further study as a potential therapeutic agent in sepsis. PMID:26618986

  10. Perioperative treatment options in resectable pancreatic cancer - how to improve long-term survival

    PubMed Central

    Sinn, Marianne; Bahra, Marcus; Denecke, Timm; Travis, Sue; Pelzer, Uwe; Riess, Hanno

    2016-01-01

    Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas (PDAC) - since the approval of gemcitabine in 1997 - more effective cytotoxic substances (nab-paclitaxel) and combinations (FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging (stroma depletion, immunotherapy, anti-inflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of “borderline resectability”. Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future. PMID:26989460

  11. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    PubMed Central

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  12. Biotechnology in the pulp and paper industry; A review

    SciTech Connect

    Trotter, P.C. )

    1990-05-01

    This paper reviews biotechnology in the pulp and paper industry. As to biopulping and biobleaching, little effort is being devoted to improving strength properties of pulps. However, positive results have been reported in improving tensile properties by treating mechanical pulps with white-rot organisms and in enzymatic beating of chemical pulps with hemicellulase enzymes. Papermaking is another seemingly overlooked area, although biological systems and processes have been used in the past and ought to be important still. On the other hand, waste treatment has been a stronghold of biotechnology within the industry for years. New possibilities may emerge via biotechnology for removing color and AOX from bleach plant effluents. New research on the use of white-rot organisms and soil bacteria to detoxify chlorinated organics in soils and groundwater may yield technologies that the industry can apply.

  13. Tuftsin-derived T-peptide prevents cellular immunosuppression and improves survival rate in septic mice

    PubMed Central

    Gao, Yu-Lei; Chai, Yan-Fen; Dong, Ning; Han, Su; Zhu, Xiao-Mei; Zhang, Qing-Hong; Yao, Yong-Ming

    2015-01-01

    The primary mechanisms of sepsis induced cellular immunesuppression involve immune dysfunction of T lymphocytes and negative immunoregulation of regulatory T cells (Tregs). It has been found that tuftsin is an immune modulating peptide derived from IgG in spleen. T-peptide is one of tuftsin analogs. Herein, we examined the effect of T-peptide on cell-mediated immunity in the presence of lipopolysaccharide (LPS) and the survival rate in septic mice. T-peptide regulated the proliferative ability of CD4+CD25− T cells in dual responses. Meanwhile, 10 and 100 μg/ml T-peptides were able to enhance the apoptotic rate of CD4+CD25− T cells compared with 1 μg/ml T-peptide, but markedly lowered interleukin (IL)-2 levels. When CD4+CD25+ Tregs were treated with T-peptide for 24 hours, and co-cultured with normal CD4+CD25− T cells, the suppressive ability of CD4+CD25+ Tregs on CD4+CD25− T cells was significantly lowered, along with decreased expression in forkhead/winged helix transcription factor p-3 (Foxp-3) as well as cytotoxic T lymphocyte-associated antigen (CTLA)-4, and secretion of transforming growth factor (TGF)-β. Moreover, T-peptide has the ability to improve outcome of septic mice in a dose- and time- dependent manner, and associated with improvement in the microenvironment of cellular immunosuppression in septic mice. PMID:26577833

  14. Medium Osmolarity and Pericellular Matrix Development Improves Chondrocyte Survival When Photoencapsulated in Poly(Ethylene Glycol) Hydrogels at Low Densities

    PubMed Central

    Villanueva, Idalis; Bishop, Nikki L.

    2009-01-01

    The ability to encapsulate cells over a range of cell densities is important toward mimicking cell densities of native tissues and rationally designing strategies where cell source and/or cell numbers are clinically limited. Our preliminary findings demonstrate that survival of freshly isolated adult bovine chondrocytes dramatically decreases when photoencapsulated in poly(ethylene glycol) hydrogels at low densities (4 million cells/mL). During enzymatic digestion of cartilage, chondrocytes undergo a harsh change in their microenvironment. We hypothesize that the absence of exogenous antioxidants, the hyposmotic environment, and the loss of a protective pericellular matrix (PCM) increase chondrocytes' susceptibility to free radical damage during photoencapsulation. Incorporation of antioxidants and serum into the encapsulation medium improved cell survival twofold compared to phosphate-buffered saline. Increasing medium osmolarity from 330 to 400 mOsm (physiological) improved cell survival by 40% and resulted in ∼2-fold increase in adenosine triphosphate (ATP) production 24 h postencapsulation. However, cell survival was only temporary. Allowing cells to reproduce some PCM before photoencapsulation in 400 mOsm medium resulted in superior cell survival during and postencapsulation for up to 15 days. In summary, the combination of antioxidants, physiological osmolarity, and the development of some PCM result in an improved robustness against free radical damage during photoencapsulation. PMID:19331581

  15. Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience

    PubMed Central

    Tan, Daryl; Horning, Sandra J.; Hoppe, Richard T.; Levy, Ronald; Rosenberg, Saul A.; Sigal, Bronislava M.; Warnke, Roger A.; Natkunam, Yasodha; Han, Summer S.; Yuen, Alan; Plevritis, Sylvia K.

    2013-01-01

    Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1 to 2 FL treated at Stanford University from 1960-2003 were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n = 180); era 2, anthracycline (1976-1986, n = 426); era 3, aggressive chemotherapy/purine analogs (1987-1996, n = 471); and era 4, rituximab (1997-2003, n = 257). Clinical characteristics, patterns of care, and survival were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at the time of diagnosis. The median OS was 13.6 years. Age, gender, and stage did not differ across the eras. Although primary treatment varied, event-free survival after the first treatment did not differ between eras (P = .17). Median OS improved from 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (P < .001), with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement. PMID:23777769

  16. Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy.

    PubMed

    Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

    2013-10-15

    Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n = 8; 0.5, 0.3, 0.1 μg g(-1)) or D with vitamins C and E (DCE; n = 8; 200 and 100 mg kg(-1), respectively) on postnatal days 1-3 (P1-3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n = 8). A fourth group received vitamins alone (CCE; n = 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μM), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (cardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min(-1)) or afterload (cardiac output: -5.3 ± 2.0 vs.1.4 ± 1.2 ml min(-1)); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes cardiac

  17. 21 CFR 872.1720 - Pulp tester.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DENTAL DEVICES Diagnostic Devices § 872.1720 Pulp tester. (a) Identification. A pulp tester is an AC or... current transmitted by an electrode to stimulate the nerve tissue in the dental pulp. (b)...

  18. 21 CFR 872.1720 - Pulp tester.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DENTAL DEVICES Diagnostic Devices § 872.1720 Pulp tester. (a) Identification. A pulp tester is an AC or... current transmitted by an electrode to stimulate the nerve tissue in the dental pulp. (b)...

  19. 21 CFR 872.1720 - Pulp tester.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DENTAL DEVICES Diagnostic Devices § 872.1720 Pulp tester. (a) Identification. A pulp tester is an AC or... current transmitted by an electrode to stimulate the nerve tissue in the dental pulp. (b)...

  20. Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain.

    PubMed

    Srivastava, Amit K; Bulte, Camille A; Shats, Irina; Walczak, Piotr; Bulte, Jeff W M

    2016-01-01

    Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebrally transplanted, either alone, or together with syngeneic MSCs in immunocompetent BALB/c mice (n=20) or immunodeficient Rag2(-/-) mice as survival control (n=8). No immunosuppressive drug was given to any animal. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that co-transplantation of MSCs significantly improved (p<0.05) engrafted GRP survival. No significant change in signal intensities was observed in immunodeficient Rag2(-/-) mice, with transplanted cells surviving in both the GRP only and the GRP+MSC group. In contrast, on day 21 post-transplantation, we observed a 94.2% decrease in BLI signal intensity in immunocompetent mice transplanted with GRPs alone versus 68.1% in immunocompetent mice co-transplanted with MSCs and GRPs (p<0.05). Immunohistochemical analysis demonstrated a lower number of infiltrating CD45, CD11b(+) and CD8(+) cells, reduced astrogliosis, and a higher number of FoxP3(+) cells at the site of transplantation for the immunocompetent mice receiving MSCs. The present study demonstrates that co-transplantation of MSCs can be used to create a microenvironment that is more conducive to the survival of allogeneic GRPs. PMID:26515691

  1. The Evaluation of More Lymph Nodes in Colon Cancer Is Associated with Improved Survival in Patients of All Ages

    PubMed Central

    2016-01-01

    Background Improvement in survival of patients with colon cancer is reduced in elderly patients compared to younger patients. The aim of this study was to investigate whether the removal of ≥ 12 lymph nodes can explain differences in survival rates between elderly and younger patients diagnosed with colon cancer. Methods In a population-based cohort study, all patients (N = 41,074) diagnosed with colon cancer stage I to III from 2003 through 2010 from the Netherlands Cancer Registry were included. Age groups were defined as < 66, 66–75 and > 75 years of age. Main outcome measures were overall and relative survival, the latter as a proxy for disease specific survival. Results Over an eight years time period there was a 41.2% increase in patients with ≥ 12 lymph nodes removed, whereas the percentage of patients with the presence of lymph node metastases remained stable (35.7% to 37.5%). After adjustment for patient and tumour characteristics and adjuvant chemotherapy, it was found that for patients in which ≥ 12 lymph nodes were removed compared to patients with < 12 lymph nodes removed, there was a statistically significant higher overall survival (< 66: HR: 0.858 (95% CI, 0.789–0.933); 66–75: HR: 0.763 (95% CI, 0.714–0.814); > 75: HR: 0.734 (95% CI, 0.700–0.771)) and relative survival (< 66: RER: 0.783 (95% CI, 0.708–0.865); 66–75: RER: 0.672 (95% CI, 0.611–0.739); > 75: RER: 0.621 (95% CI, 0.567–0.681)) in all three age groups. Conclusions The removal of ≥ 12 lymph nodes is associated with an improvement in both overall and relative survival in all patients. This association was stronger in the elderly patient. The biology of this association needs further clarification. PMID:27196666

  2. C-myb Regulates Autophagy for Pulp Vitality in Glucose Oxidative Stress.

    PubMed

    Lee, Y H; Kim, H S; Kim, J S; Yu, M K; Cho, S D; Jeon, J G; Yi, H K

    2016-04-01

    Diabetes mellitus is closely related to oral-complicated diseases by oxidative stress. This study investigates whether cellular myeloblastosis (c-myb) could protect human dental pulp cells against glucose oxidative stress and regulate autophagy activity for pulp vitality. Diabetes mellitus was induced by streptozotocin in Sprague-Dawley rats, and their pulp tissue in teeth was analyzed in terms of pulp cavity and molecules by hematoxylin and eosin and immunohistochemistry staining. Human dental pulp cells were serially subcultured and treated with glucose oxidase in the presence of elevated glucose to generate glucose oxidative stress. The replication-deficient adenovirus c-myb and small interfering RNA c-myb were introduced for c-myb expression. The pulp tissue from the diabetic rats was structurally different from normal tissue in terms of narrow pulp capacity, reduced c-myb, and dentinogenesis molecules. Glucose oxidase treatment decreased c-myb and dentinogenesis molecules (bone morphogenetic protein 2 and 7, dentin matrix protein 1, and dentin sialophosphoprotein) in human dental pulp cells. However, overexpression of c-myb by adenovirus c-myb increased dentinogenesis, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B-light chain 3, and Beclin-1), and cell survival via p-AMPK/AKT signaling even with glucose oxidative stress. In contrast, the lack of c-myb decreased the above molecules and cell survival by downregulating p-AMPK/AKT signaling. The results indicate that diabetes leads to irreversible damage to dental pulp, which is related to downexpression of autophagy via the p-AMPK/AKT pathway by decline of c-myb. The findings of this study provide a new insight that c-myb could ameliorate autophagy activity and that it is applicable for monitoring complicated diseases of dental pulp. The involvement of c-myb in pulp pathology could serve a therapeutic target in oral-complicated diseases. PMID:26661713

  3. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    SciTech Connect

    Barker, Christopher A.; Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A.

    2013-07-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  4. Oocyte pre-IVM with caffeine improves bovine embryo survival after vitrification.

    PubMed

    Bernal-Ulloa, Sandra Milena; Lucas-Hahn, Andrea; Herrmann, Doris; Hadeler, Klaus-Gerd; Aldag, Patrick; Baulain, Ulrich; Niemann, Heiner

    2016-09-15

    Cryopreservation of in vitro produced bovine embryos is associated with significantly reduced survival rates, mainly due to insufficient quality of the embryos. Caffeine supplementation during IVM has been used to delay meiotic resumption and concomitantly also increased embryo quality. Here, we investigated the influence of pre-IVM with caffeine on oocyte maturation, intraoocyte cAMP concentration, developmental competence after IVF, and blastocyst cryotolerance. Oocytes were obtained by slicing of ovaries and were submitted to either 2 hours culture before IVM with or without caffeine (0, 1, 5, 10, 20, 30 mM), or standard IVM (no pre-IVM). Oocytes were in vitro matured and fertilized and zygotes were cultured under standard in vitro conditions until Day 8. Expanded blastocysts derived from either standard control or the 10-mM caffeine treatments were submitted to vitrification. Caffeine delayed meiotic resumption after 9-hour IVM in a concentration-dependent manner. The cAMP levels were similar before and after IVM. Matured oocytes, cleavage, and blastocyst rates were reduced in the 30-mM caffeine concentration and were similar among the other treatment groups. Number and proportion of inner cell mass and trophectoderm cells in blastocysts did not differ among treatments. Forty-eight hours after thawing, hatching rates were higher in the 10-mM caffeine group (73.8%) compared with the standard control (59.7%). Reexpansion rates and total number of cells after 48 hours were similar in both treatments. The ratio of live/total cells was higher in the caffeine treatment. These results suggest that caffeine supplementation before IVM delayed meiotic resumption and improved blastocyst quality shown in higher cryotolerance. PMID:27180328

  5. Improving the survivability of Nb-encapsulated Ga targets for the production of 68Ge

    NASA Astrophysics Data System (ADS)

    Bach, H. T.; Claytor, T. N.; Hunter, J. F.; Olivas, E. R.; Kelsey, C. T., IV; Engle, J. W.; Connors, M. A.; Nortier, F. M.; Runde, W. H.; Moddrell, C.; Lenz, J. W.; John, K. D.

    2013-03-01

    At the Los Alamos Neutron Science Center (LANSCE) Isotope Production Facility (IPF), radioisotopes are produced for medical, scientific, and industrial applications by irradiating various targets with a 100 MeV, 230 μA proton beam. The medical isotope germanium-68 is produced by irradiating Nb capsules containing molten Ga target material. During irradiation, the Nb is subjected to intense radiation damage, corrosive attack by Ga, and mechanical and thermally-induced stresses for an extended period. Maintaining the structural integrity of the Nb target capsules during irradiation is crucial to contain the molten Ga target and the radioisotope product. In the present work, we focus on potential material related factors and assess the effect of the Nb stock material on target durability. We do so by comparing post-irradiation target mortality information to data collected during pre-irradiation ultrasound testing and X-ray imaging. We also explore possible failure mechanisms by using MCNP6 simulations and ANSYS codes to predict the induced atom displacement levels, hydrogen gas built-up, temperature distribution, and mechanical stresses. Our analysis, performed entirely in the context of an aggressive production program that allows for only limited diagnostic interference, suggests that using Nb stock with reasonably large and uniform grains is the most important factor in reducing early target failure at integrated beam current values <18 mAh and random failure at the face of the rear window at <60 mAh. We discuss possible failure mechanisms of failed targets that were fabricated using the same stock material and grain structure and then irradiated to integrated beam current values of up to 60 mAh and more. Based on these observations, we have enacted new specifications for Nb stock material quality, target design, and limits on integrated beam current. These changes have resulted in improved Nb capsule survivability.

  6. Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

    PubMed Central

    Heist, Rebecca S.; Duda, Dan G.; Sahani, Dushyant V.; Ancukiewicz, Marek; Fidias, Panos; Sequist, Lecia V.; Temel, Jennifer S.; Shaw, Alice T.; Pennell, Nathan A.; Neal, Joel W.; Gandhi, Leena; Lynch, Thomas J.; Engelman, Jeffrey A.; Jain, Rakesh K.

    2015-01-01

    Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non–small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment—while reducing blood flow, volume, and permeability in the overall population—may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy. PMID:25605928

  7. Effect of shortening kraft pulping integrated with extended oxygen delignification on biorefinery process performance of eucalyptus.

    PubMed

    Li, Jing; Zhang, Chunyun; Hu, Huichao; Chai, Xin-Sheng

    2016-02-01

    The aim of this work was to study the impact of shortening kraft pulping (KP) process integrated with extended oxygen delignification (OD) on the biorefinery process performance of eucalyptus. Data showed that using kraft pulps with high kappa number could improve the delignification efficiency of OD, reduce hexenuronic acid formation in kraft pulps. Pulp viscosity for a target kappa number of ∼10 was comparable to that obtained from conventional KP and OD process. The energy and alkali consumption in the integrated biorefinery process could be optimized when using a KP pulp with kappa number of ∼27. The process could minimize the overall methanol formation, but greater amounts of carbonate and oxalate were formed. The information from this study will be helpful to the future implementation of short-time KP integrated with extended OD process in actual pulp mill applications for biorefinery, aiming at further improvement in the biorefinery effectiveness of hardwood. PMID:26706725

  8. Binding and desulfurization characteristics of pulp black liquor in biocoalbriquettes.

    PubMed

    Kim, Heejoon; Lu, Guoqing; Li, Tianji; Sadakata, Masayoshi

    2002-04-01

    To control pollutant emissions from coal combustion in some developing countries, biocoalbriquette, an artificially produced solid fuel, was developed. Both the breaking strength and production costs of the biocoalbriquette have become essentially the most important factors in popularizing it in these countries. To increase the breaking strength and decrease the production costs, it is proposed in this study to use pulp black liquor, a byproduct from the pulp production industry, as a binder. The influences of pulp black liquor on the briquetting and combustion characteristics were investigated. Furthermore, the desulfurization characteristics of pulp black liquor were also evaluated through combustion experiments. The study results show that the briquetting pressure has a limited effect on the breaking strength. An increase in the briquetting pressure yields greater breaking strength of up to the 50 MPa. Above 50 MPa, the breaking strength changes very little with the briquetting pressure. The use of pulp black liquor has had a greater effect on increasing the breaking strength than on changing the briquetting pressure and also on improving the combustion characteristics of the biocoalbriquette. On the other hand, pulp black liquor has some desulfurization capabilities. When used as a binder, it not only increases the breaking strength and decreases the necessary briquetting pressure, but it also improves some characteristics of the combustion and reduces the pollutants emission. PMID:11999073

  9. Surgical Intervention Improves Survival for Metastatic Non-Small Cell Lung Cancer Patients

    PubMed Central

    Shen, Hong; Cao, Ying; Li, Xiaofen; Tan, Yinuo; Chen, Jiaqi; Yang, Ziru; Kong, Yiyao; Yuan, Ying

    2016-01-01

    Abstract Surgical intervention for stage IV non-small cell lung cancer (NSCLC) is still controversial. This study sought to evaluate the clinical effects of surgical intervention on survival in patients with stage IV NSCLCs and to identify the cohort benefitting the most from surgery. A retrospective study from the Surveillance, Epidemiology, and End Results database was performed to compare the survival of stage IV NSCLC patients who had undergone surgery with those who did not undergo surgery. Overall survival (OS) was evaluated using the Kaplan–Meier method and the log-rank test. The Cox proportional hazards model was used for multivariate analysis. The total number of eligible patients was 43,538, including 16.8% in the M1a stage and 83.2% in the M1b stage. The percentages of patients with no surgery (NONE), only metastatic tumor resection (MTR), only primary tumor resection (PTR), and both primary and metastatic tumor resection (PMTR) were 89.0%, 6.7%, 3.5%, and 0.8%, respectively; the corresponding 5-year survival rates were 2.0%, 4.0%, 13.0%, and 20.0%, respectively (P < 0.001); and the corresponding OS rates were 11.1 months, 14.7 months, 29.4 months, and 34.9 months, respectively (P < 0.001). Notably, the pairwise comparisons of 5-year survival rate and OS among the subgroups were all statistically significant. The multivariate analysis showed that surgical intervention was correlated with longer survival in patients with stage IV NSCLC. The stratified analysis showed significant differences in the OS on strata of the M1a stage and strata of the M1b stage. In the M1a stage, patients with PTR had significantly better OS than those with NONE (P < 0.001) or MTR (P < 0.001) but showed no significant differences compared with those with PMTR (P = 0.174); patients with MTR did not have prolonged survival compared with patients with NONE (P = 0.185), and they also did not have prolonged survival compared with patients with PMTR (P

  10. Improvement in Overall Survival from Extremity Soft Tissue Sarcoma over Twenty Years

    PubMed Central

    Jacobs, Andrew J.; Michels, Ryan; Stein, Joanna; Levin, Adam S.

    2015-01-01

    Several patient demographic factors, including marital status, have been demonstrated to have prognostic significance for survival in extremity soft tissue sarcoma (ESTS). A study population of 12,546 adult patients diagnosed with ESTS from 1991 to 2010 was identified from the SEER database, a large population-based registry, in order to determine whether overall survival had changed over this recent 20-year period. The study population was divided into three groups by year of diagnosis: 1991–1996, 1997–2003, and 2004–2010. We used the Kaplan-Meier method and Cox proportional hazards regression to assess survival differences between different demographic groups and prognostic clinical characteristics. Over the course of time, the 5-year overall survival rates have increased from 28% in the earliest time period to 62% in the latest (P < 0.0001). On multivariate analysis, the mortality rate progressively declined from the 1991–1996 group (HR: 3.02, CI: 2.78–3.29) to the 1997–2003 group (HR: 2.21, CI: 2.06–2.37), with the 2004–2010 group having the best overall survival, despite increases in the proportion of patients with tumors greater than 5 cm in size (P < 0.0001), and those presenting with metastasis (P < 0.0001). PMID:25821397

  11. Is Pulp Inflammation a Prerequisite for Pulp Healing and Regeneration?

    PubMed Central

    Goldberg, Michel; Njeh, Akram; Uzunoglu, Emel

    2015-01-01

    The importance of inflammation has been underestimated in pulpal healing, and in the past, it has been considered only as an undesirable effect. Associated with moderate inflammation, necrosis includes pyroptosis, apoptosis, and nemosis. There are now evidences that inflammation is a prerequisite for pulp healing, with series of events ahead of regeneration. Immunocompetent cells are recruited in the apical part. They slide along the root and migrate toward the crown. Due to the high alkalinity of the capping agent, pulp cells display mild inflammation, proliferate, and increase in number and size and initiate mineralization. Pulp fibroblasts become odontoblast-like cells producing type I collagen, alkaline phosphatase, and SPARC/osteonectin. Molecules of the SIBLING family, matrix metalloproteinases, and vascular and nerve mediators are also implicated in the formation of a reparative dentinal bridge, osteo/orthodentin closing the pulp exposure. Beneath a calciotraumatic line, a thin layer identified as reactionary dentin underlines the periphery of the pulp chamber. Inflammatory and/or noninflammatory processes contribute to produce a reparative dentinal bridge closing the pulp exposure, with minute canaliculi and large tunnel defects. Depending on the form and severity of the inflammatory and noninflammatory processes, and according to the capping agent, pulp reactions are induced specifically. PMID:26538825

  12. Delayed implantation of nigral grafts improves survival of dopamine neurones and rate of functional recovery.

    PubMed

    Sinclair, S R; Fawcett, J W; Dunnett, S B

    1999-04-26

    In order to test the hypothesis that poor survival of dopaminergic neurones in nigral transplants may be due, at least in part, to acute toxic changes in the host striatum within the first hour after injury, we experimentally evaluated the consequences of imposing a brief delay (20 min, 1 or 3 h) between positioning the injection cannula and extruding the graft tissue. A delay of as little as 1 h resulted in a three-fold increase in survival of dopamine neurones in the grafts and a more rapid abolition of amphetamine-induced rotational asymmetry in the host animals. These results suggest that acute but rapidly resolving changes in the host striatal environment induced by the implantation procedure itself can have a significantly deleterious effect on the survival of embryonic nigral grafts. PMID:10363936

  13. Thieves or mutualists? Pulp feeders enhance endozoochore local recruitment.

    PubMed

    Fedriani, José M; Zywiec, Magdalena; Delibes, Miguel

    2012-03-01

    The persistence of mutualisms despite the strong incidence of exploiters could be explained if exploiters deny one or more services (i.e., cheat) while eventually supplying some subtler but critical services. Pulp feeders usually ingest fruit reward without dispersing seeds and thus are considered to be mainly cheaters or thieves of seed-disperser mutualisms. By consuming the fruit pulp, however, they could release seeds from pulp inhibitory effect, enhancing germination and, potentially, subsequent seedling emergence, growth, survival, and thus local recruitment. We evaluated such a largely neglected hypothesis by considering the interaction between Pyrus bourgaeana and its pulp feeders. We experimentally showed that pericarp removal had a consistent strong positive effect on seed performance (e.g., lower rotting and higher germination percentages) and seedling fate (greater emergence, growth, and survival to two years old). Interestingly, these relatively large positive effects of depulpation on plant fitness persisted for a surprisingly long time. Though seedlings experienced higher mortality under fruiting conspecifics, the benefits of depulpation were not overridden by high propagule mortality beneath fruiting trees or in adverse microhabitats after two years of monitoring. Specifically, the cumulative probability of establishment for depulped seeds was 4-25 times higher than for seeds in whole ripe fruits. Thus, under some circumstances, pulp feeders can provide essential services to endozoochorous plants. Our study contributes to clarifying the apparent paradox of plant-frugivore mutualisms that persist in the face of exploitation by pulp feeders. Because "thieves" and "mutualists" refer to the extremes of a complex continuum, and because organisms displaying concurrent cheating and honest behaviors during different host stages are likely prevalent, the persistent language of mutualists vs. thieves, cheaters, or exploiters might be misleading. PMID:22624212

  14. Chronic Inflammation and Angiogenic Signaling Axis Impairs Differentiation of Dental-Pulp Stem Cells

    PubMed Central

    Boyle, Michael; Chun, Crystal; Strojny, Chelsee; Narayanan, Raghuvaran; Bartholomew, Amelia; Sundivakkam, Premanand; Alapati, Satish

    2014-01-01

    Dental-pulp tissue is often exposed to inflammatory injury. Sequested growth factors or angiogenic signaling proteins that are released following inflammatory injury play a pivotal role in the formation of reparative dentin. While limited or moderate angiogenesis may be helpful for dental pulp maintenance, the induction of significant level of angiogenesis is probably highly detrimental. Hitherto, several studies have addressed the effects of proinflammatory stimuli on the survival and differentiation of dental-pulp stem cells (DPSC), in vitro. However, the mechanisms communal to the inflammatory and angiogenic signaling involved in DPSC survival and differentiation remain unknown. Our studies observed that short-term exposure to TNF-α (6 and 12 hours [hrs]) induced apoptosis with an upregulation of VEGF expression and NF-κB signaling. However, long-term (chronic) exposure (14 days) to TNF-α resulted in an increased proliferation with a concomitant shortening of the telomere length. Interestingly, DPSC pretreated with Nemo binding domain (NBD) peptide (a cell permeable NF-κB inhibitor) significantly ameliorated TNF-α- and/or VEGF-induced proliferation and the shortening of telomere length. NBD peptide pretreatment significantly improved TNF-α-induced downregulation of proteins essential for differentiation, such as bone morphogenic proteins (BMP)-1 & 2, BMP receptor isoforms-1&2, trasnforming growth factor (TGF), osteoactivin and osteocalcin. Additionally, inhibition of NF-κB signaling markedly increased the mineralization potential, a process abrogated by chronic exposure to TNF-α. Thus, our studies demonstrated that chronic inflammation mediates telomere shortening via NF-κB signaling in human DPSC. Resultant chromosomal instability leads to an emergence of increased proliferation of DPSC, while negatively regulating the differentiation of DPSC, in vitro. PMID:25427002

  15. Patterns of Improved Survival in Patients With Multiple Myeloma in the Twenty-First Century: A Population-Based Study

    PubMed Central

    Turesson, Ingemar; Velez, Ramon; Kristinsson, Sigurdur Y.; Landgren, Ola

    2010-01-01

    Purpose Randomized multiple myeloma (MM) studies show improved response rates and better progression-free survival for newer therapies. However, a less pronounced effect has been found for overall survival (OS). Using population-based data including detailed treatment information for individual patients, we assessed survival patterns for all patients diagnosed with MM in Malmö, Sweden from 1950 to 2005. Patients and Methods We identified 773 patients with MM (48% males). On the basis of the age limit used for treatment with high-dose melphalan with autologous stem-cell support (HDM-ASCT; ≤ 65 years old) in Sweden, we constructed Kaplan-Meier curves and used the Breslow generalized Wilcoxon test to evaluate OS patterns (diagnosed in six calendar periods) for patients 65 years old or younger and patients older than 65 years. Results Including all age groups, patients diagnosed from 1960 to 1969 had a better survival than patients diagnosed from 1950 to 1959. In subsequent 10-year calendar periods, median OS increased from 24.3 to 56.3 months (P = .036) in patients ≤ 65 years old. In contrast, OS did not improve among patients older than age 65 years (21.2 to 26.7 months, P = .7). Conclusion With the establishment of HDM-ASCT as the standard therapy for younger patients with MM, OS has improved significantly for this age group in the general MM population. With novel therapies being commonly used at disease progression, presumably it becomes increasingly difficult to confirm survival differences between defined induction, consolidation, and maintenance therapies in the future. Consequently, in the era of novel MM therapies, population-based studies will serve as a necessary complement to randomized trials. PMID:20038719

  16. Standardized Electrolyte Supplementation and Fluid Management Improves Survival During Amphotericin Therapy for Cryptococcal Meningitis in Resource-Limited Settings

    PubMed Central

    Bahr, Nathan C.; Rolfes, Melissa A.; Musubire, Abdu; Nabeta, Henry; Williams, Darlisha A.; Rhein, Joshua; Kambugu, Andrew; Meya, David B.; Boulware, David R.

    2014-01-01

    Background  Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa. Methods  Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001–2002, and universal in 2006–2012. In 2001–2009, serum potassium (K+) was monitored on days 1, 7, and 14 of treatment with replacement (K+, Mg2+) per clinician discretion. In 2011–2012, K+ was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K+, Mg2+) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies. Results  With limited intravenous fluids, the 14-day survival was 49% in 2001–2002. With universal intravenous fluids, the 30-day survival improved to 62% in 2006–2010 (P = .003). In 2011–2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006–2010 cohort). The cumulative incidence of severe hypokalemia (<2.5 mEq/L) decreased from 38% in 2010 to 8.5% in 2011–2012 with universal supplementation (P < .001). Conclusions  Improved survival was seen in a resource-limited setting with proactive fluid and electrolyte management (K+, Mg2+), as part of comprehensive amphotericin-based cryptococcal therapy

  17. The superoxide dismutase (SOD)-mimic manganese-deferoxamine (Mn-DFO) improves survival following hemorrhagic and endotoxic shock

    SciTech Connect

    de Garavilla, L.; Chermak, T.; Valentine, H.L.; Hanson, R.C. )

    1990-02-26

    The novel, low-molecular weight, organo-metallic complex Mn-DFO functions in vitro as an SOD-mimic effectively dismutating the superoxide radical. Oxygen-derived free radicals appear to be involved in the pathology of both endotoxic (ENDO) and hemorrhagic (HEM) shock whereby treatment with SOD is associated with improvements in survival. Therefore, the following models were utilized to evaluate the in vivo activity of Mn-DFO. Male rats (350-450g) were anesthetized with ketamine (100mg/kg, ip) and subjected to HEM hypotension by withdrawing approximately 40% of the animals' blood volume over a 10 minute period. MABP was maintained constant at 40mmHg for 60 minutes, followed by complete autoreinfusion. Survival was reduced to 20% in the control group at 24 hour post-reinfusion. A single post-shock dose of Mn-DFO (10mg/kg, iv) more than doubled the survival rate for up to 24 hour post-reinfusion as compared to control. Female mice (CFmal and-1, 20-25g) were challenged with 500ug of ENDO and 0.8ug of actinomycin/animal and dosed 1 hour pre and post with Mn-DFO (30mg/kg/dose, iv). Survival improved from 60% in the control group to 100% in the Mn-DFO group at 18 hours post ENDO challenge. Using a multiple dosing regimen, Mn-DFO significantly improved survival for up to 48 hours post-ENDO. Thus, unlike other SOD-mimics, Mn-DFO appears to exhibit in vivo activity.

  18. Survival of Salmonella enterica serotype Tennessee during simulated gastric passage is improved by low water activity and high fat content.

    PubMed

    Aviles, Bryan; Klotz, Courtney; Smith, Twyla; Williams, Robert; Ponder, Monica

    2013-02-01

    The low water activity (a(w) 0.3) of peanut butter prohibits the growth of Salmonella in a product; however, illnesses are reported from peanut butter contaminated with very small doses, suggesting the food matrix itself influences the infectious dose of Salmonella, potentially by improving Salmonella's survival in the gastrointestinal tract. The purpose of our study was to quantify the survival of a peanut butter outbreak-associated strain of Salmonella enterica serotype Tennessee when inoculated into peanut butters with different fat contents and a(w) (high fat, high a(w); high fat, low a(w); low fat, high a(w); low fat, low a(w)) and then challenged with a simulated gastrointestinal system. Exposures to increased fat content and decreased a(w) both were associated with a protective effect on the survival of Salmonella Tennessee in the simulated gastric fluid compared with control cells. After a simulated intestinal phase, the populations of Salmonella Tennessee in the control and low-fat formulations were not significantly different; however, a 2-log CFU/g increase occurred in high-fat formulations. This study demonstrates that cross-protection from low-a(w) stress and the presence of high fat results in improved survival in the low pH of the stomach. The potential for interaction of food matrix and stress adaptations could influence the virulence of Salmonella and should be considered for risk analysis. PMID:23433384

  19. Quinic acid could be a potential rejuvenating natural compound by improving survival of Caenorhabditis elegans under deleterious conditions.

    PubMed

    Zhang, Longze; Zhang, Junjing; Zhao, Baolu; Zhao-Wilson, Xi

    2012-12-01

    Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which is found to be active in enhancing DNA repair and immunity in model systems and able to generate neuroprotective effects in neurons. However, QA's role in improving survival is not well studied. Here we report that QA can provide protection in Caenorhabidits elegans and improve worm survival under stress. Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2) survived 17.8% and 29.7% longer, respectively, than the control worms. Our data suggest that under heat stress, QA can upregulate the expression of the small heat shock protein hsp-16.2 gene, which could help the worms survive a longer time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2 (gk249)] life span by 15.7% under normal culture conditions. However, under normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated the expression of daf-16 and sod-3 in a DAF-16-dependent manner, and downregulated the level of reactive oxygen species (ROS), suggesting that under normal conditions QA acts in different pathways. As a natural product, QA demonstrates great potential as a rejuvenating compound. PMID:22950425

  20. Salvage Treatment Improved Survival of Patients With Relapsed Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

    SciTech Connect

    Zhang Xinxing; Xie Conghua; Xu Yong; Deng Di; Zhao Yanhai; Zou Bingwen; Zhou Lin; Li Mei; Wang Jin; Liu Weiping; Huang Meijuan

    2009-07-01

    Purpose: To evaluate the clinical outcome of salvage treatment for patients with relapsed natural killer (NK)/T-cell lymphoma, nasal type. Methods and Materials: Forty-four patients who had achieved complete response during initial treatment and experienced histologically proven relapse were reviewed. Twenty-nine of them received salvage treatment with radiotherapy (RT) alone (n = 7), chemotherapy (CT) alone (n = 10), or both RT and CT (n = 12); the other 15 patients received best supportive care alone. Results: The estimated 5-year overall survival (OS) rate for patients with or without salvage treatment was 37.8% vs. 0 (p < 0.0001), respectively. Salvage CT did not improve survival of relapsed Stage IE and IIE patients. Among relapsed Stage IIIE and IVE patients who received salvage treatment, RT developed significantly better survival when compared with that of non-RT (1-year OS, 62.5% vs. 0, p = 0.006). Relapsed Ann Arbor stage and receiving salvage treatment were found to be significant factors influencing OS at both univariate and multivariate levels. Conclusions: Salvage treatment improved survival in patients with relapsed NK/T-cell lymphoma, nasal type. Salvage RT may play an important role in salvage treatment of relapsed extranodal NK/T-cell lymphoma.

  1. Quinic Acid Could Be a Potential Rejuvenating Natural Compound by Improving Survival of Caenorhabditis elegans under Deleterious Conditions

    PubMed Central

    Zhang, Longze; Zhang, Junjing

    2012-01-01

    Abstract Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which is found to be active in enhancing DNA repair and immunity in model systems and able to generate neuroprotective effects in neurons. However, QA's role in improving survival is not well studied. Here we report that QA can provide protection in Caenorhabidits elegans and improve worm survival under stress. Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2) survived 17.8% and 29.7% longer, respectively, than the control worms. Our data suggest that under heat stress, QA can upregulate the expression of the small heat shock protein hsp-16.2 gene, which could help the worms survive a longer time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2 (gk249)] life span by 15.7% under normal culture conditions. However, under normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated the expression of daf-16 and sod-3 in a DAF-16–dependent manner, and downregulated the level of reactive oxygen species (ROS), suggesting that under normal conditions QA acts in different pathways. As a natural product, QA demonstrates great potential as a rejuvenating compound. PMID:22950425

  2. 21 CFR 872.1720 - Pulp tester.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DENTAL DEVICES Diagnostic Devices § 872.1720 Pulp tester. (a) Identification. A pulp tester is an AC or... current transmitted by an electrode to stimulate the nerve tissue in the dental pulp. (b) Classification... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pulp tester. 872.1720 Section 872.1720 Food...

  3. Low thyroid hormone levels improve survival in murine model for ocular melanoma

    PubMed Central

    Fabian, Ido Didi; Rosner, Mordechai; Fabian, Ina; Vishnevskia-Dai, Vicktoria; Zloto, Ofira; Maman, Elena Shinderman; Cohen, Keren; Ellis, Martin; Lin, Hung-Yun; Hercbergs, Aleck; Davis, Paul J.; Ashur-Fabian, Osnat

    2015-01-01

    Uveal melanoma is highly metastatic, prognosis is poor and there are no effective treatments to extend survival. Accumulating evidence suggests that thyroid hormones have a mitogenic effect via binding to αvβ3 integrin. We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin. In two independent experiments oral propylthiouracil (PTU) was used to induce hypothyroidism (n=9), thyroxine to induce hyperthyroidism (n=11) and mice given plain water served as control (n=8). At day 21, the subretinal space was inoculated with 102 B16F10 cells. In non-inoculated mice (n=6 of each group) serum free T4 (FT4) levels were measured and additional non-inoculated mice (3 given PTU and 4 given thyroxine or water) served as internal control to demonstrate the impact of the dissolved substance. The PTU-inoculated mice showed clinical evidence of intraocular tumor growth significantly later than the thyroxine mice (P=0.003) and survival time was significantly longer (P<0.001). FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group. Our findings suggest that hyperthyroidism shortens survival, whereas relative hypothyroidism may have a protective role in metastatic ocular melanoma. PMID:25868390

  4. Coronary Artery Bypass Graft Surgery Using the Radial Artery as a Secondary Conduit Improves Patient Survival

    PubMed Central

    Lin, John; Cheng, Wen; Czer, Lawrence S.; De Robertis, Michele A.; Mirocha, James; Ruzza, Andrea; Kass, Robert M.; Khoynezhad, Ali; Ramzy, Danny; Esmailian, Fardad; Trento, Alfredo

    2013-01-01

    Background The clinical benefits of the left internal thoracic artery–to–left anterior descending coronary artery graft are well established in coronary artery bypass graft surgery (CABG). However, limited data are available regarding the long‐term outcome of the radial artery (RA) as a secondary conduit over the established standard of the saphenous venous graft. Methods and Results We compared the 12‐year survival outcome in a set of propensity‐matched CABG patients who received either the RA or the saphenous vein as a secondary conduit. A multivariable logistic regression that included 18 baseline characteristics was used to define the propensity of receiving an RA graft. The propensity model resulted in 260 matched pairs who underwent first‐time isolated CABG from 1996 to 2001 with similar preoperative characteristics (C statistic=0.86). The cumulative 12‐year survival estimated by use of the Kaplan–Meier method was higher for the RA graft patients (hazard ratio 0.76; P=0.03). This survival advantage was especially significant in diabetics (P=0.005), in women (P=0.02), and in the elderly (P=0.04.) The protective effect appeared beginning at year 5 post surgical intervention. Conclusion The RA as a secondary conduit provided superior long‐term survival after CABG, especially in diabetic patients, women, and the elderly. This effect was most pronounced >5 years after surgery. PMID:23969224

  5. Improved survival after palliative resection of unsuspected stage IV pancreatic ductal adenocarcinoma

    PubMed Central

    Kim, Younghwan; Kim, Song Cheol; Song, Ki Byoung; Kim, Jayoun; Kang, Dae Ryong; Lee, Jae Hoon; Park, Kwang-Min; Lee, Young-Joo

    2016-01-01

    Background Palliative resection of stage IV pancreatic ductal adenocarcinoma (PDAC) has not shown its benefit until now. In our retrospective review, we compared the results of palliative resection to non-resection. Methods Between 2000 and 2009, metastasis of PDAC was confirmed in the operating room in 150 patients. 35 underwent palliative resection (resection group; R) and 115 did bypass or biopsy. 35 patients (biopsy or bypass group: NR) in the 115 patients were matched with the patients undergoing resection for tumor size and the metastasis of peritoneal seeding. Demographic, clinical, operative data and survival were analyzed. Results There was no significant difference of major complication (Clavien–Dindo classification 3–5) between two groups. There was no 30-day mortality in either group. More patients in R received postoperative chemotherapy (82.9% vs. 57.1%; P = 0.019). Multivariate analysis showed resection and postoperative chemotherapy as independent factor related to survival (hazard ratio, 0.44; 95% CI, 0.25–0.76; P = 0.003). Patients in R showed better survival rates compared to those in NR (P < 0.001). Conclusion Our study suggests resection for stage IV PDAC can be associated with increased survival. In patients of stage IV PDAC, palliative resection with chemotherapy could have some benefit in selected patients. PMID:27037201

  6. Improving fat graft survival through preconditioning of the recipient site with microneedling.

    PubMed

    Sezgin, Billur; Ozmen, Selahattin; Bulam, Hakan; Omeroglu, Suna; Yuksel, Seher; Cayci, Banu; Peker, Tuncay

    2014-05-01

    Although fat grafts are considered the ideal soft-tissue fillers, the main concern dealing with this technique is not being able to predict long-term graft survival due to high absorption rates. The purpose of this study was to investigate the angiogenic effects of preconditioning the recipient area with micro-needling and to determine its overall impact on fat graft survival. The study consisted of a sham, control and study group. The source of fat was the Wistar albino rat inguinal fat pad while the recipient area was a dorsal subcutaneous pouch. The dorsal area was preconditioned with standard technique micro-needling 1-week prior to fat graft transfer in the study group while the control group did not undergo micro-needling. At the end of 15 weeks, morphological, biochemical, histological and immunohistochemical evaluation was carried out. Fat grafts in the study group had better integrity and a higher level of vascularity compared to the control group. Volume analysis demonstrated higher graft survival in the study group in comparison to the control group. Histomorphometric and immunohistochemical evaluation showed better graft integrity and uniform adipocytes, less fibrosis, less vacuolisation and inflammation and better vascularisation in the study group. Although higher triglyceride concentrations were measured for the study group, the difference between the two groups was statistically insignificant. In conclusion, fat grafting performed in an area preconditioned with micro-needling results in higher graft volume, better integrity and vascularisation and an overall higher graft survival rate. PMID:24529693

  7. ENDOSCOPIC ULTRASONOGRAPHY IN ESOPHAGEAL CANCER LEADS TO IMPROVED SURVIVAL RATES: RESULTS FROM A POPULATION-BASED STUDY

    PubMed Central

    Wani, Sachin; Das, Ananya; Rastogi, Amit; Drahos, Jennifer; Ricker, Winifred; Parsons, Ruth; Bansal, Ajay; Yen, Roy; Hosford, Lindsay; Jankowski, Meghan; Sharma, Prateek; Cook, Michael B.

    2015-01-01

    Background and Aims The advantages of endoscopic ultrasound (EUS) and computed tomography-positron emission tomography (CT-PET) in relation to survival in esophageal cancer (EC) patients are unclear. This study aimed to assess the effect of EUS, CT-PET and its combination on overall survival relative to cases not receiving these procedures. Methods Patients aged ≥ 66 years diagnosed with EC were identified in the Surveillance, Epidemiology, and End Results-Medicare linked database. Cases were split into four analytic groups: EUS only (n=318), CT-PET only (853), EUS+CT-PET (189) and “no EUS or CT-PET” (2,439). Survival times were estimated by Kaplan-Meier method and compared by using log-rank test for each group versus the “no EUS or CT-PET” group. Multivariable Cox proportional hazards models were used to compare 1, 3 and 5-year survival rates. Results Kaplan-Meier analyses showed that patients undergoing EUS, CT-PET and EUS+CT-PET had improved survival for all stages, all compared with “no EUS or CT-PET”, with the exception of stage 0 disease. Receipt of EUS increased the likelihood of receiving endoscopic therapies, esophagectomy and chemoradiation. Multivariable Cox proportional hazards models showed that receipt of EUS was a significant predictor for improved 1-year (HR 0.49, 95% CI 0.39–0.59, p<0.0001), 3-year (HR 0.57, 95% CI 0.48–0.66, p<0.0001) and 5-year (HR 0.59, 95% CI 0.50–0.68) survival. Similar results were noted when results were stratified based on histology, as well as for CT-PET and EUS+CT-PET groups. Conclusions Receipt of either EUS or CT-PET alone in EC patients is associated with improved 1, 3 and 5-year survival. Future studies should identify barriers to dissemination of these staging modalities. PMID:25236485

  8. Biotechnological potential of coffee pulp and coffee husk for bioprocesses.

    PubMed

    Pandey; Soccol; Nigam; Brand; Mohan; Roussos

    2000-10-01

    Advances in industrial biotechnology offer potential opportunities for economic utilization of agro-industrial residues such as coffee pulp and coffee husk. Coffee pulp or husk is a fibrous mucilagenous material (sub-product) obtained during the processing of coffee cherries by wet or dry process, respectively. Coffee pulp/husk contains some amount of caffeine and tannins, which makes it toxic in nature, resulting the disposal problem. However, it is rich in organic nature, which makes it an ideal substrate for microbial processes for the production of value-added products. Several solutions and alternative uses of the coffee pulp and husk have been attempted. These include as fertilizers, livestock feed, compost, etc. However, these applications utilize only a fraction of available quantity and are not technically very efficient. Attempts have been made to detoxify it for improved application as feed, and to produce several products such as enzymes, organic acids, flavour and aroma compounds, and mushrooms, etc. from coffee pulp/husk. Solid state fermentation has been mostly employed for bioconversion processes. Factorial design experiments offer useful information for the process optimization. This paper reviews the developments on processes and products developed for the value-addition of coffee pulp/husk through the biotechnological means. PMID:10959086

  9. POZONE technology to bleach pulp

    SciTech Connect

    Wang, H.; Shi, Y.; Le, L.; Wang, S.M.; Wei, J.; Chang, S.G.

    1997-09-01

    Currently, there has been a move in the pulp and paper industry to reduce or eliminate chlorine-based bleaching due to environmental concerns. The POZONE process, a chemical means of ozone production, has been used to bleach wood pulp. The brightness, Kappa number, and viscosity of wood pulp subjected to POZONE treatment have been determined. Brightness increases of up to 44 points and Kappa number decreases of as much as 22 points have been achieved. Promise for effective industrial application has been demonstrated.

  10. Preoperative statin use is not associated with improvement in survival after glioblastoma surgery.

    PubMed

    Bhavsar, S; Hagan, K; Arunkumar, R; Potylchansky, Y; Grasu, R; Dang, A; Carlson, R; Cowels, C; Arnold, B; Rahlfs, T F; Lipski, I; Walsh, C; Nguyen, A T; Feng, L; Cata, J P

    2016-09-01

    Cohort studies have suggested that the use of statins is associated with decreased risk of glioma formation and mortality. Here, a cohort of patients with glioblastoma multiforme (GBM) was analyzed to further investigate associations between preoperative use of statins and recurrence, and progression free and overall survival. Patients who had surgery for GBM (N=284) were followed up for a median of 18.1months. Seventy-eight patients were taking statins preoperatively while the rest were not. Cox proportional hazards models adjusted for several covariates of interest were applied before and after propensity score matching. Compared with statin users, those not taking the lipid-lowering drugs had similar progression free survival before (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26; p=0.68) and after propensity score matching (HR 0.95, 95% CI 0.67-1.35; p=0.68). Mortality was similar between both groups of patients before (HR 0.94, 95% CI 0.70-1.22; p= 0.73) and after propensity score matching (HR 1.13, 95% CI 0.78-1.64; p=0.49). Age and dexamethasone use were independent prognostic factors of survival. Contrary to previously published evidence, this study could not find an association between preoperative statin use and longer survival in GBM patients. Due to the small number of patients and retrospective nature of the study, further work is needed to understand the role of perioperative statins in GBM patients. PMID:27396375

  11. Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome.

    PubMed

    Fuentes-Julián, Sherezade; Arnalich-Montiel, Francisco; Jaumandreu, Laia; Leal, Marina; Casado, Alfonso; García-Tuñon, Ignacio; Hernández-Jiménez, Enrique; López-Collazo, Eduardo; De Miguel, Maria P

    2015-01-01

    The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC) into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical practice. PMID

  12. Adipose-Derived Mesenchymal Stem Cell Administration Does Not Improve Corneal Graft Survival Outcome

    PubMed Central

    Fuentes-Julián, Sherezade; Arnalich-Montiel, Francisco; Jaumandreu, Laia; Leal, Marina; Casado, Alfonso; García-Tuñon, Ignacio; Hernández-Jiménez, Enrique; López-Collazo, Eduardo; De Miguel, Maria P.

    2015-01-01

    The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC) into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical practice. PMID

  13. VEGF and FGF2 Improve Revascularization, Survival, and Oocyte Quality of Cryopreserved, Subcutaneously-Transplanted Mouse Ovarian Tissues

    PubMed Central

    Li, Sheng-Hsiang; Hwu, Yuh-Ming; Lu, Chung-Hao; Chang, Hsiao-Ho; Hsieh, Cheng-En; Lee, Robert Kuo-Kuang

    2016-01-01

    This study was conducted to investigate the effect of the vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. Autologous subcutaneous transplantation of vitrified-thawed mouse ovarian tissues treated with (experimental group) or without (control group) VEGF and FGF2 was performed. After transplantation to the inguinal region for two or three weeks, graft survival, angiogenesis, follicle development, and oocyte quality were examined after gonadotropin administration. VEGF coupled with FGF2 (VEGF/FGF2) promoted revascularization and significantly increased the survival rate of subcutaneously-transplanted cryopreserved ovarian tissues compared with untreated controls. The two growth factors did not show long-term effects on the ovarian grafts. In contrast to the untreated ovarian grafts, active folliculogenesis was revealed as the number of follicles at various stages and of mature oocytes in antral follicles after gonadotropin administration were remarkably higher in the VEGF/FGF2-treated groups. Although the fertilization rate was similar between the VEGF/FGF2 and control groups, the oocyte quality was much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio of blastocyst development. Introducing angiogenic factors, such as VEGF and FGF2, may be a promising strategy to improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. PMID:27483256

  14. Percutaneous Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock Is Associated with Improved Short- and Long-Term Survival.

    PubMed

    Hryniewicz, Katarzyna; Sandoval, Yader; Samara, Michael; Bennett, Mosi; Cabuay, Barry; Chavez, Ivan J; Seatter, Susan; Eckman, Peter; Zimbwa, Peter; Dunn, Aaron; Sun, Benjamin

    2016-01-01

    Mortality due to refractory cardiogenic shock (RCS) exceeds 50%. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for RCS. The aim of our study was to evaluate outcomes of patients with RCS treated with percutaneous VA-ECMO (pVA-ECMO). Retrospective review of patients supported with VA-ECMO at our institution in 2012-2013. Clinical characteristics, bleeding, vascular complications, and outcomes including survival were assessed. A total of 37 patients were supported with VA-ECMO for RCS. The majority of VA-ECMO (76%) was placed in the catheterization laboratory. Nearly half (49%) of the patients presented with acute myocardial infarction. Seven patients (19%) underwent insertion of pVA-ECMO in the setting of cardiopulmonary resuscitation with mechanical chest compression device. Median duration of support was 5 days. Index hospitalization, 30-day, and 1-year survival were 65%, 65%, and 57%, respectively. Survival rate for discharged patients was 87.5% with a median follow-up of 450 days. Refractory cardiogenic shock supported with pVA-ECMO is associated with an improved survival in patients with a traditionally poor prognosis. PMID:27045967

  15. VEGF and FGF2 Improve Revascularization, Survival, and Oocyte Quality of Cryopreserved, Subcutaneously-Transplanted Mouse Ovarian Tissues.

    PubMed

    Li, Sheng-Hsiang; Hwu, Yuh-Ming; Lu, Chung-Hao; Chang, Hsiao-Ho; Hsieh, Cheng-En; Lee, Robert Kuo-Kuang

    2016-01-01

    This study was conducted to investigate the effect of the vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. Autologous subcutaneous transplantation of vitrified-thawed mouse ovarian tissues treated with (experimental group) or without (control group) VEGF and FGF2 was performed. After transplantation to the inguinal region for two or three weeks, graft survival, angiogenesis, follicle development, and oocyte quality were examined after gonadotropin administration. VEGF coupled with FGF2 (VEGF/FGF2) promoted revascularization and significantly increased the survival rate of subcutaneously-transplanted cryopreserved ovarian tissues compared with untreated controls. The two growth factors did not show long-term effects on the ovarian grafts. In contrast to the untreated ovarian grafts, active folliculogenesis was revealed as the number of follicles at various stages and of mature oocytes in antral follicles after gonadotropin administration were remarkably higher in the VEGF/FGF2-treated groups. Although the fertilization rate was similar between the VEGF/FGF2 and control groups, the oocyte quality was much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio of blastocyst development. Introducing angiogenic factors, such as VEGF and FGF2, may be a promising strategy to improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. PMID:27483256

  16. Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry.

    PubMed

    Adam, R; Karam, V; Delvart, V; Trunečka, P; Samuel, D; Bechstein, W O; Němec, P; Tisone, G; Klempnauer, J; Rossi, M; Rummo, O O; Dokmak, S; Krawczyk, M; Pratschke, J; Kollmar, O; Boudjema, K; Colledan, M; Ericzon, B G; Mantion, G; Baccarani, U; Neuhaus, P; Paul, A; Bachellier, P; Zamboni, F; Hanvesakul, R; Muiesan, P

    2015-05-01

    This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data. PMID:25703527

  17. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    PubMed Central

    Wang, Xiaojie; Hao, Jianqiang; Leung, Gigi; Breitkopf, Trisia; Wang, Eddy; Kwong, Nicole; Akhoundsadegh, Noushin; Warnock, Garth L.; Shapiro, Jerry; McElwee, Kevin J.

    2015-01-01

    Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation. PMID:26000314

  18. Managing hospitals in turbulent times: do organizational changes improve hospital survival?

    PubMed Central

    Lee, S Y; Alexander, J A

    1999-01-01

    OBJECTIVE: To examine (1) the degree to which organizational changes affected hospital survival; (2) whether core and peripheral organizational changes affected hospital survival differently; and (3) how simultaneous organizational changes affected hospital survival. DATA SOURCES: AHA Hospital Surveys, the Area Resource File, and the AHA Hospital Guides, Part B: Multihospital Systems. STUDY DESIGN: The study employed a longitudinal panel design. We followed changes in all community hospitals in the continental United States from 1981 through 1994. The dependent variable, hospital closure, was examined as a function of multiple changes in a hospital's core and peripheral structures as well as the hospital's organizational and environmental characteristics. Cox regression models were used to test the expectations that core changes increased closure risk while peripheral changes decreased such risk, and that simultaneous core and peripheral changes would lead to higher risk of closure. PRINCIPAL FINDINGS: Results indicated more peripheral than core changes in community hospitals. Overall, findings contradicted our expectations. Change in specialty, a core change, was beneficial for hospitals, because it reduced closure risk. The two most frequent peripheral changes, downsizing and leadership change, were positively associated with closure. Simultaneous organizational changes displayed a similar pattern: multiple core changes reduced closure risk, while multiple peripheral changes increased the risk. These patterns held regardless of the level of uncertainty in hospital environments. CONCLUSIONS: Organizational changes are not all beneficial for hospitals, suggesting that hospital leaders should be both cautious and selective in their efforts to turn their hospitals around. PMID:10536977

  19. Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma

    PubMed Central

    Seidensticker, Ricarda; Seidensticker, Max; Doegen, Kathleen; Mohnike, Konrad; Schütte, Kerstin; Stübs, Patrick; Kettner, Erika; Pech, Maciej; Amthauer, Holger; Ricke, Jens

    2016-01-01

    Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies. Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy). Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence. Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions (“toolbox”) rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID: DRKS00006237. PMID:26966431

  20. Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma.

    PubMed

    Seidensticker, Ricarda; Seidensticker, Max; Doegen, Kathleen; Mohnike, Konrad; Schütte, Kerstin; Stübs, Patrick; Kettner, Erika; Pech, Maciej; Amthauer, Holger; Ricke, Jens

    2016-01-01

    Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies. Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy). Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence. Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions ("toolbox") rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID: DRKS00006237. PMID:26966431

  1. Canola straw chemimechanical pulping for pulp and paper production.

    PubMed

    Hosseinpour, Reza; Fatehi, Pedram; Latibari, Ahmad Jahan; Ni, Yonghao; Javad Sepiddehdam, S

    2010-06-01

    Non-wood is one of the most important raw materials for pulp and paper production in several countries due to its abundance and cost-effectiveness. However, the pulping and papermaking characteristics of canola straw have rarely been investigated. The objective of this work was to determine the potential application of canola straw in the chemimechanical pulping (CMP) process. At first, the chemical composition and characteristics of canola straw were assessed and compared with those of other non-woods. Then, the CMP pulping of canola straw was conducted using different dosages of sodium sulfite and sodium hydroxide. The results showed that, by applying a mild chemical pretreatment, i.e., 4-12% (wt.) NaOH and 8-12% (wt.) Na(2)SO(3), in the CMP pulping of canola straw, the pulp brightness reached almost 40%ISO, and the strength properties were comparable to those of bagasse CMP and of wheat straw CMP. The impact of post-refining on the properties of canola straw CMP was also discussed in this work. PMID:20144862

  2. Improvements in breast cancer survival between 1995 and 2012 in Denmark: The importance of earlier diagnosis and adjuvant treatment.

    PubMed

    Jensen, Maj-Britt; Ejlertsen, Bent; Mouridsen, Henning T; Christiansen, Peer

    2016-06-01

    Background Breast cancer mortality has declined from 1995 through 2012 which may be attributed to earlier diagnosis, changes in lifestyle risk factors, and improved treatments. To a large extent the relative contribution of these modalities are unknown. Mammography screening was introduced late in Denmark; in 1995 around 20% of the Danish female population aged 50-69 was covered by population-based screening, and this was in 2008 extended to the entire population. Breast conserving surgery gradually replaced mastectomy, and sentinel node biopsy was introduced. In the same period adjuvant treatment was extended considerable. Methods A population-based study of 68 842 breast cancer patients registered in the clinical database of the Danish Breast Cancer Cooperative Group in 1995-2012. Comprehensive data on prognostic factors, comorbidity and treatment together with complete follow-up for survival were used to evaluate improvements in mortality and standardized mortality rate in successive time periods. Results The results from this study demonstrated a significant improvement in prognosis in successive time periods covering 1995-2012. Apart from patients with a high Charlson Comorbidity Index (CCI) improvements were seen in all subgroups of patients. Prognostic factors were more favorable in the latest time period accordingly to the introduction of nationwide screening. In the study period adjuvant treatment was extended considerable. Conclusion The impact of screening was by nature of limited magnitude. The modified treatment strategies implemented by the use of nationwide guidelines seemed to have a major impact on the substantial survival improvements. PMID:26797010

  3. A novel pharmacological strategy by PTEN inhibition for improving metabolic resuscitation and survival after mouse cardiac arrest

    PubMed Central

    Li, Jing; Wang, Huashan; Zhong, Qiang; Zhu, Xiangdong; Chen, Sy-Jou; Qian, Yuanyu; Costakis, Jim; Bunney, Gabrielle; Beiser, David G.; Leff, Alan R.; Lewandowski, E. Douglas; ÓDonnell, J. Michael

    2015-01-01

    Sudden cardiac arrest (SCA) is a leading cause of death in the United States. Despite return of spontaneous circulation, patients die due to post-SCA syndrome that includes myocardial dysfunction, brain injury, impaired metabolism, and inflammation. No medications improve SCA survival. Our prior work suggests that optimal Akt activation is critical for cooling protection and SCA recovery. Here, we investigate a small inhibitor of PTEN, an Akt-related phosphatase present in heart and brain, as a potential therapy in improving cardiac and neurological recovery after SCA. Anesthetized adult female wild-type C57BL/6 mice were randomized to pretreatment of VO-OHpic (VO) 30 min before SCA or vehicle control. Mice underwent 8 min of KCl-induced asystolic arrest followed by CPR. Resuscitated animals were hemodynamically monitored for 2 h and observed for 72 h. Outcomes included heart pressure-volume loops, energetics (phosphocreatine and ATP from 31P NMR), protein phosphorylation of Akt, GSK3β, pyruvate dehydrogenase (PDH) and phospholamban, circulating inflammatory cytokines, plasma lactate, and glucose as measures of systemic metabolic recovery. VO reduced deterioration of left ventricular maximum pressure, maximum rate of change in the left ventricular pressure, and Petco2 and improved 72 h neurological intact survival (50% vs. 10%; P < 0.05). It reduced plasma lactate, glucose, IL-1β, and Pre-B cell colony enhancing factor, while increasing IL-10. VO increased phosphorylation of Akt and GSK3β in both heart and brain, and cardiac phospholamban phosphorylation while reducing p-PDH. Moreover, VO improved cardiac bioenergetic recovery. We concluded that pharmacologic PTEN inhibition enhances Akt activation, improving metabolic, cardiovascular, and neurologic recovery with increased survival after SCA. PTEN inhibitors may be a novel pharmacologic strategy for treating SCA. PMID:25795713

  4. A novel pharmacological strategy by PTEN inhibition for improving metabolic resuscitation and survival after mouse cardiac arrest.

    PubMed

    Li, Jing; Wang, Huashan; Zhong, Qiang; Zhu, Xiangdong; Chen, Sy-Jou; Qian, Yuanyu; Costakis, Jim; Bunney, Gabrielle; Beiser, David G; Leff, Alan R; Lewandowski, E Douglas; ÓDonnell, J Michael; Vanden Hoek, Terry L

    2015-06-01

    Sudden cardiac arrest (SCA) is a leading cause of death in the United States. Despite return of spontaneous circulation, patients die due to post-SCA syndrome that includes myocardial dysfunction, brain injury, impaired metabolism, and inflammation. No medications improve SCA survival. Our prior work suggests that optimal Akt activation is critical for cooling protection and SCA recovery. Here, we investigate a small inhibitor of PTEN, an Akt-related phosphatase present in heart and brain, as a potential therapy in improving cardiac and neurological recovery after SCA. Anesthetized adult female wild-type C57BL/6 mice were randomized to pretreatment of VO-OHpic (VO) 30 min before SCA or vehicle control. Mice underwent 8 min of KCl-induced asystolic arrest followed by CPR. Resuscitated animals were hemodynamically monitored for 2 h and observed for 72 h. Outcomes included heart pressure-volume loops, energetics (phosphocreatine and ATP from (31)P NMR), protein phosphorylation of Akt, GSK3β, pyruvate dehydrogenase (PDH) and phospholamban, circulating inflammatory cytokines, plasma lactate, and glucose as measures of systemic metabolic recovery. VO reduced deterioration of left ventricular maximum pressure, maximum rate of change in the left ventricular pressure, and Petco2 and improved 72 h neurological intact survival (50% vs. 10%; P < 0.05). It reduced plasma lactate, glucose, IL-1β, and Pre-B cell colony enhancing factor, while increasing IL-10. VO increased phosphorylation of Akt and GSK3β in both heart and brain, and cardiac phospholamban phosphorylation while reducing p-PDH. Moreover, VO improved cardiac bioenergetic recovery. We concluded that pharmacologic PTEN inhibition enhances Akt activation, improving metabolic, cardiovascular, and neurologic recovery with increased survival after SCA. PTEN inhibitors may be a novel pharmacologic strategy for treating SCA. PMID:25795713

  5. Improved five year survival after combined radiotherapy-chemotherapy for Stage I-II non-Hodgkin's lymphoma

    SciTech Connect

    Monfardini, S.; Banfi, A.; Bonadonna, G.; Rilke, F.; Milani, F.; Valagussa, P.; Lattuada, A.

    1980-02-01

    In order to improve the prognosis of patients with localized non-Hodgkin's lymphomas (NHL) who are treated with radiotherapy (RT), a prospective controlled study utilizing a combined modality approach was carried out in patients with pathologic Stage I-II NHL. After treatment with regional RT, patients in complete remission were randomized to receive either no further therapy or 6 cycles of cyclophosphamide, vincristine and prednisolone (CVP). At 5 years from completion of irradiation, the relapse-free survival was 46.3% after RT and 72.1% after RT plus CVP (P=0.005). The corresponding findings for the overall survival calculated from the beginning of irradiation were 55.8 and 82.8% respectively (P=0.03). The favorable effects of adjuvant chemotherapy on relapse-free survival were statistically significant only in the subgroup with diffuse histology. In patients who relapsed after RT alone, the salvage therapy failed to induce a high incidence of second durable remission. Adjuvant chemotherapy is indicated to improve the curve rate in pathologic stage I-II NHL with diffuse histology when regional RT is utilized.

  6. Elevated PDGFRB gene copy number gain is prognostic for improved survival outcomes in resected malignant pleural mesothelioma.

    PubMed

    Tsao, Anne S; Harun, Nusrat; Fujimoto, Junya; Devito, Vikki; Lee, J Jack; Kuhn, Elisabetta; Mehran, Reza; Rice, David; Moran, Cesar; Hong, Waun Ki; Shen, Li; Suraokar, Milind; Wistuba, Ignacio

    2014-06-01

    PDGF/PDGFR pathway has been implicated in malignant pleural mesothelioma (MPM) carcinogenesis, and evidence suggests autocrine mechanisms of proliferation. We sought to evaluate the incidence of PDGFRB gene copy number gain (CNG) by fluorescence in situ hybridization and PDGFR pathway protein expression by immunohistochemistry (IHC) and correlate it to patient clinical outcome. Eighty-eight archived tumor blocks from resected MPM with full clinical information were used to perform IHC biomarkers (PDGFRα, PDGFRβ, p-PDGFRβ) and fluorescence in situ hybridization analysis of PDGFRB gene CNG. Spearman rank correlation, Wilcoxon rank-sum test, Kruskal-Wallis test, BLiP plots, and Kaplan-Meier method were used to analyze the biomarkers and correlation to clinical outcome. Several correlations between the IHC biomarkers were seen; however, none correlated to clinically relevant patient demographics or histology. In the CNG analysis, PDGFRB gene CNG in >10% of tumor cells had lower cytoplasmic p-PDGFRβ (P=.029), while PDGFRB gene CNG in >40% of tumor cells had a higher cytoplasmic PDGFRβ (P=.04). PDGFRB gene CNG status did not associate with patient demographics or tumor characteristics. PDGFR pathway IHC biomarkers did not associate with survival outcomes. However, patients with PDGFRB CNG >40% of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72], P=.0096) and improved overall survival (HR 0.32 [95% CI 0.11-0.89], P=.029). PDGFRB CNG >40% of MPM tumor cells is a potential prognostic biomarker for surgery and may identify a unique population of mesothelioma patients. Future validation of this biomarker in prospective trials is needed. From a retrospective review of archived tissue specimens from patients with resected malignant pleural mesothelioma tumors, we show that patients with PDGFRB CNG >40% of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72], P=.0096) and improved overall survival (HR 0.32 [95% CI 0

  7. Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life.

    PubMed

    Bower, H; Andersson, T M-L; Björkholm, M; Dickman, P W; Lambert, P C; Derolf, Å R

    2016-01-01

    We evaluated temporal trends in survival of Swedish acute myeloid leukemia (AML) patients diagnosed between 1973 and 2011 using relative survival ratios (RSRs) and a measure called the loss in expectation of life (LEL). RSRs increased most for patients <60 years at diagnosis during the first calendar periods, but between 1997-2005 and 2006-2011 the most pronounced increase was for those aged 61-70 years at diagnosis; RSR changed from 0.16 (95% confidence interval (CI): 0.13-0.19) to 0.28 (95% CI: 0.23-0.33), respectively. The LEL for males aged 35 years at diagnosis was 41.0 (95% CI: 40.1-41.8) years in 1975 and 19.5 (95% CI: 16.4-22.5) years in 2011. For males aged 65 years, the corresponding figures were 13.8 (95% CI: 13.7-14.0) and 12.0 (95% CI: 11.3-12.8). Conditional LEL estimates suggested that patients who survive 5 years postdiagnosis have shorter remaining lifespan than the general population. The proportion of expected life lost (PELL) suggested that male 65-year-old patients lost 75% of their life expectancy in 2005 and 66% if they were diagnosed in 2011. Survival continued to increase to 2011, with larger improvements in those aged 61-70 years at diagnosis. The LEL and PELL are intuitive measures that may be useful in communicating survival statistics to patients, clinicians and health-care providers. PMID:26849011

  8. Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life

    PubMed Central

    Bower, H; Andersson, T M-L; Björkholm, M; Dickman, P W; Lambert, P C; Derolf, Å R

    2016-01-01

    We evaluated temporal trends in survival of Swedish acute myeloid leukemia (AML) patients diagnosed between 1973 and 2011 using relative survival ratios (RSRs) and a measure called the loss in expectation of life (LEL). RSRs increased most for patients <60 years at diagnosis during the first calendar periods, but between 1997–2005 and 2006–2011 the most pronounced increase was for those aged 61–70 years at diagnosis; RSR changed from 0.16 (95% confidence interval (CI): 0.13–0.19) to 0.28 (95% CI: 0.23–0.33), respectively. The LEL for males aged 35 years at diagnosis was 41.0 (95% CI: 40.1–41.8) years in 1975 and 19.5 (95% CI: 16.4–22.5) years in 2011. For males aged 65 years, the corresponding figures were 13.8 (95% CI: 13.7–14.0) and 12.0 (95% CI: 11.3–12.8). Conditional LEL estimates suggested that patients who survive 5 years postdiagnosis have shorter remaining lifespan than the general population. The proportion of expected life lost (PELL) suggested that male 65-year-old patients lost 75% of their life expectancy in 2005 and 66% if they were diagnosed in 2011. Survival continued to increase to 2011, with larger improvements in those aged 61–70 years at diagnosis. The LEL and PELL are intuitive measures that may be useful in communicating survival statistics to patients, clinicians and health-care providers. PMID:26849011

  9. Therapeutic Cancer Vaccines in Prostate Cancer: The Paradox of Improved Survival Without Changes in Time to Progression

    PubMed Central

    Madan, Ravi A.; Fojo, Tito; Dahut, William L.

    2010-01-01

    Therapeutic cancer vaccines represent a new class of agents in the treatment of cancer. Sipuleucel-T is an antigen-presenting cell–based vaccine that recently demonstrated a significant 4.8-month improvement in overall survival in advanced prostate cancer patients and was well tolerated. The findings of that study have been met with skepticism, primarily because the agent did not change initial disease progression and yet led to longer survival. Although the commonly accepted treatment paradigm suggests that treatments should initially decrease tumor volume, perhaps vaccines work differently. Vaccines may induce delayed responses not seen in the first few months of therapy or they may initiate a dynamic immune response that ultimately slows the tumor growth rate, resulting in longer survival. Subsequent therapies may also combine with the induced immune response, resulting in a combination that is more effective than conventional treatments alone. Also, other treatments may alter tumor-associated antigen expression, enhancing the immune response. Future trials are currently planned to investigate these hypotheses; however, the results of the sipuleucel-T vaccine in prostate cancer should not be dismissed. Results with another vaccine in prostate cancer are similar, perhaps suggesting a class effect. In a broader context, clinicians may need to reconsider how they measure success. Several agents have been approved that produce superior disease progression results, but do not affect overall survival. Given the toxicity and costs of cancer therapies, perhaps studies should put more weight on long-term survival endpoints than on short-term endpoints that may be less consequential. PMID:20798195

  10. Intraocular lymphoma in Korea: the Consortium for Improving Survival of Lymphoma (CISL) study

    PubMed Central

    Lee, Seul; Kim, Moon Jin; Kim, Jin Seok; Kim, Seok Jin; Kwon, Yoon Hyung; Chung, In Young; Kang, Jung Hun; Yang, Deok-Hwan; Kang, Hye Jin; Yoon, Dok Hyun; Kim, Won Seog; Kim, Hyo-Jin

    2015-01-01

    Background Intraocular lymphoma (IOL) is a rare malignant lymphoma that most closely resembles a diffuse large B-cell lymphoma, and it is a subtype of primary central nervous system lymphoma (PCNSL). IOL is located inside the eye in the retina, uvea, and/or optic nerve. We retrospectively analyzed IOL patient data to identify treatment patterns and survival rates in Korea. Methods Cytological confirmation for a diagnosis of IOL was performed for all patients. The clinical data collected from medical records included Ann Arbor stage, International Prognostic Index, performance status, date of diagnosis, treatment modality and response, date of relapse, and date of last follow-up. Results Twenty patients who were diagnosed with IOL, between December 2007 and June 2014 at multiple centers in Korea, were included in the analysis. Four patients were diagnosed with IOL alone, not involving the CNS. Two patients with isolated IOL later developed PCNSL. Nine patients developed CNS lesions before the onset of ocular lymphoma. Five patients had simultaneous onset in the eye and CNS. Twelve patients were treated by intravitreal injection of methotrexate for IOL. The median progression-free survival (PFS) for patients was 19.7 months (95% CI, 8.7-30.7 mo). The estimated 3-year overall survival (OS) for all patients was 75.1%. Conclusion Treatment for IOL patients included radiotherapy and intraocular chemotherapy. IOL patients showed favorable PFS and OS. These patients would require long-term follow-up to identify relapse and adverse effects of radiotherapy or intraocular chemotherapy. PMID:26770952

  11. Autophagy in SDF-1α-mediated DPSC migration and pulp regeneration.

    PubMed

    Yang, Jing-Wen; Zhang, Yu-Feng; Wan, Chun-Yan; Sun, Zhe-Yi; Nie, Shuai; Jian, Shu-Juan; Zhang, Lu; Song, Guang-Tai; Chen, Zhi

    2015-03-01

    Critical morphological requirements for pulp regeneration are tissues replete with vascularisation, neuron formation, and dentin deposition. Autophagy was recently shown to be related to angiogenesis, neural differentiation, and osteogenesis. The present study aimed to investigate the involvement of autophagy in stromal cell-derived factor-1α (SDF-1α)-mediated dental pulp stem cell (DPSC) migration and pulp regeneration, and identify its presence during pulp revascularisation of pulpectomised dog teeth with complete apical closure. In vitro studies showed that SDF-1α enhanced DPSCs migration and optimised focal adhesion formation and stress fibre assembly, which were accompanied by autophagy. Moreover, autophagy inhibitors significantly suppressed, whereas autophagy activator substantially augmented SDF-1α-stimulated DPSCs migration. Furthermore, after ectopic transplantation of tooth fragment/silk fibroin scaffold with DPSCs into nude mice, pulp-like tissues with vascularity, well-organised fibrous matrix formation, and new dentin deposition along the dentinal wall were generated in SDF-1α-loaded samples accompanied by autophagy. More importantly, in a pulp revascularisation model in situ, SDF-1α-loaded silk fibroin scaffolds improved the de novo ingrowth of pulp-like tissues in pulpectomised mature dog teeth, which correlated with the punctuated LC3 and Atg5 expressions, indicating autophagy. Our findings provide novel insights into the pulp regeneration mechanism, and SDF-1α shows promise for future clinical application in pulp revascularisation. PMID:25617122

  12. Vaccination of free-living juvenile wild rabbits (Oryctolagus cuniculus) against myxomatosis improved their survival.

    PubMed

    Guitton, Jean-Sébastien; Devillard, Sébastien; Guénézan, Michel; Fouchet, David; Pontier, Dominique; Marchandeau, Stéphane

    2008-04-17

    For several decades, the populations of the European wild rabbit (Oryctolagus cuniculus) have declined, which is partly due to myxomatosis. Vaccination against this disease is expected to contribute to restoration of rabbit populations but the actual impact of myxomatosis is not well known and vaccination might have some negative effects. We analyzed the capture-mark-recapture data obtained in a 4-year field experiment (1991-1994) in a park near Paris, France wherein 300 out of 565 seronegative juvenile rabbits were vaccinated at first capture against myxomatosis with the nontransmissible Dervaximyxo SG33 vaccine. After accounting for weight at first capture, age-class (juvenile/adult), "trap-happiness" and season (spring/autumn) of the capture event, vaccinated rabbits had 1.8-fold greater odds of surviving than the unvaccinated rabbits. The average summer survival risk for vaccinated juveniles was 0.63 (+/-0.08 S.E.) whereas it was 0.48 (+/-0.08 S.E.) for unvaccinated juvenile rabbits. PMID:18045714

  13. Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

    PubMed Central

    Grumbles, Robert M.; Liu, Yang; Thomas, Christie M.; Wood, Patrick M.

    2013-01-01

    Abstract Few options exist for treatment of pervasive motoneuron death after spinal cord injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis. Local transplantation of embryonic motoneurons into an axotomized peripheral nerve is a promising approach to arrest the atrophy of denervated muscles; however, muscle reinnervation is limited by poor motoneuron survival. The aim of the present study was to test whether acute electrical stimulation of transplanted embryonic neurons promotes motoneuron survival, axon growth, and muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to mimic the widespread denervation seen after disease or injury. Acutely dissociated rat embryonic ventral spinal cord cells were transplanted into the distal tibial nerve stump as a neuron source for muscle reinnervation. Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h. Other groups were used to control for the cell transplantation and stimulation. When neurons were stimulated acutely, there were significantly more neurons, including cholinergic neurons, 10 weeks after transplantation. This led to enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and more medial and lateral gastrocnemius muscles were functionally connected to the transplant. Reinnervation reduced muscle atrophy significantly. These data support the concept that electrical stimulation rescues transplanted motoneurons and facilitates muscle reinnervation. PMID:23544978

  14. Ripping Improves Tree Survival and Growth on Unused Reclaimed Mined Lands

    NASA Astrophysics Data System (ADS)

    Fields-Johnson, Christopher W.; Burger, James A.; Evans, Daniel M.; Zipper, Carl E.

    2014-06-01

    There is renewed interest in re-establishing trees on 0.6 million ha of mining-disturbed lands in the Appalachian mountains of Eastern United States. Many coal-mined lands reclaimed to meet requirements of US federal law have thick herbaceous vegetation and compacted soils which impede tree establishment. Mitigation practices were applied on three mine sites and evaluated for success in enabling planted trees to become established. Eastern white pine ( Pinus strobus), hybrid poplar ( Populus deltoids × Populus trichocarpa), and mixed Appalachian hardwoods were established using weed control only and weed control with subsoil ripping. Trees were measured in October of 2008 after 5 years of growth. Subsoil ripping increased mixed hardwood survival from 43 to 71 %, hybrid poplar biomass index from 1.51 to 8.97 Mg ha-1, and Eastern white pine biomass index from 0.10 to 0.32 Mg ha-1. When restoring trees to unused mined sites, subsoil ripping can aid survival and growth to an extent that will result in a valuable forest.

  15. AG490 improves the survival of human myoblasts in vitro and in vivo.

    PubMed

    Gérard, Catherine; Dufour, Christine; Goudenege, Sébastien; Skuk, Daniel; Tremblay, Jacques P

    2012-01-01

    Cell therapies consist in transplanting healthy cells into a disabled tissue with the goal to repopulate it and restore its function at least partially. In muscular diseases, most of the time, myoblasts are chosen for their expansion capacity in culture. Nevertheless, cell transplantation has limitations, among them, death of the transplanted cells, during the days following the graft. One possibility to counteract this problem is to enhance the proliferation of the transplanted myoblasts before their fusion with the existing muscle fibers. AG490 is a specific inhibitor of janus tyrosine kinase 2 (JAK2). The hypothesis is to block myoblast differentiation with AG490, thus permitting their proliferation. The inhibition of myoblast fusion by AG490 was confirmed in this study by gene expression and with a myosin heavy chain staining (MyHC). Moreover, cell survival was estimated by flow cytometry. AG490 was found to protect myoblasts in vitro from apoptosis induced by H(2)O(2) or by preventing attachment of cells to their substrate. Finally, in an in vivo model of muscle regeneration, when AG490 was coinjected with the myoblasts their survival was increased by 45% at 5 days after their transplantation. PMID:22963730

  16. Ripping improves tree survival and growth on unused reclaimed mined lands.

    PubMed

    Fields-Johnson, Christopher W; Burger, James A; Evans, Daniel M; Zipper, Carl E

    2014-06-01

    There is renewed interest in re-establishing trees on 0.6 million ha of mining-disturbed lands in the Appalachian mountains of Eastern United States. Many coal-mined lands reclaimed to meet requirements of US federal law have thick herbaceous vegetation and compacted soils which impede tree establishment. Mitigation practices were applied on three mine sites and evaluated for success in enabling planted trees to become established. Eastern white pine (Pinus strobus), hybrid poplar (Populus deltoids × Populus trichocarpa), and mixed Appalachian hardwoods were established using weed control only and weed control with subsoil ripping. Trees were measured in October of 2008 after 5 years of growth. Subsoil ripping increased mixed hardwood survival from 43 to 71%, hybrid poplar biomass index from 1.51 to 8.97 Mg ha(-1), and Eastern white pine biomass index from 0.10 to 0.32 Mg ha(-1). When restoring trees to unused mined sites, subsoil ripping can aid survival and growth to an extent that will result in a valuable forest. PMID:24668411

  17. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Komaki, Ritsuko; Allen, Pamela K.; Wei, Xiong; Blumenschein, George R.; Tang, Ximing; Lee, J. Jack; Welsh, James W.; Wistuba, Ignacio I.; Liu, Diane D.; Hong, Waun Ki

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant

  18. Strength loss in kraft pulping

    NASA Astrophysics Data System (ADS)

    Iribarne, Jose

    Unbleached kraft pulps from two U.S. mills were 21% and 26% weaker than comparable laboratory pulps from the same chip sources, when assessed as the tear index at a tensile index of 70 kN.m/kg. The phenomena involved were clarified by characterizing the differences between the mill and laboratory pulps in terms of fundamental fiber properties. All of the strength loss could be explained by a reduction in intrinsic fiber strength of 9% to 11%, as estimated from wet zero-span tensile tests and fiber length distributions. Most of the effects of different fiber shape and length were isolated by PFI mill refining and decrilling, respectively. The higher fiber coarseness of mill pulps was a factor in their maximum density and bond strength, but changes in these variables were analogous to those of laboratory pups due to similar swelling. Specific bond strength, determined from a wet pressing experiment, was similar in mill and laboratory pulps. Neither carbohydrate composition nor crystalline structure, assessed through x-ray diffraction analysis, were significant factors in the observed fiber strength differences. The mill pulps were not more heterogeneous than the laboratory pulps, within the resolution of a fractionation experiment. The number of weak points in each pulp was assessed through analysis of the amount of fiber cutting during PFI mill refining and treatments with potassium superoxide or cellulase. The results suggested that the chemistry of kraft pulping preferentially weaken short, slender fibers, while mechanical stresses during the hot discharge of batch digesters mainly affect long, thick fibers. The greater number of weak points in the long-fiber fractions of mill pulps is probably associated with their lower wet zero-span tensile indices. Automated optical detection of major singularities with a prototype instrument suggested that only the weak points induced by mechanical stress could be detected by local variations in birefringence. In contrast

  19. Cold stress improves the ability of Lactobacillus plantarum L67 to survive freezing.

    PubMed

    Song, Sooyeon; Bae, Dong-Won; Lim, Kwangsei; Griffiths, Mansel W; Oh, Sejong

    2014-11-17

    The stress resistance of bacteria is affected by the physiological status of the bacterial cell and environmental factors such as pH, salts and temperature. In this study, we report on the stress response of Lactobacillus plantarum L67 after four consecutive freeze-thaw cycles. The cold stress response of the cold-shock protein genes (cspC, cspL and cspP) and ATPase activities were then evaluated. The cold stress was adjusted to 5 °C when the bacteria were growing at the mid-exponential phase. A comparative proteomic analysis was performed with two-dimensional gel electrophoresis (2D SDS-PAGE) and a matrix assisted laser desorption/ionization-mass spectrometer. Only 56% of the L. plantarum L67 cells without prior exposure to cold stress survived after four consecutive freeze-thaw cycles. However, 78% of the L. plantarum L67 cells that were treated with cold stress at 5 °C for 6 h survived after freeze-thaw conditions. After applying cold stress to the culture for 6h, the cells were then stored for 60 days at 5 °C, 25 °C and 35 °C separately. The cold-stressed culture of L. plantarum L67 showed an 8% higher viability than the control culture. After applying cold stress for 6h, the transcript levels of two genes (cspP and cspL) were up-regulated 1.4 (cspP) and 1.2 (cspL) times compared to the control. However, cspC was not up-regulated. A proteomic analysis showed that the proteins increased after a reduction of the incubation temperature to 5 °C. The importance of the expression of 13 other relevant proteins was also determined through the study. The exposure of L. plantarum cells to low temperatures aids their ability to survive through subsequent freeze-thaw processes and lyophilization. PMID:25261832

  20. Community-based interventions to improve neonatal survival in low-resource settings.

    PubMed

    McKenzie, L; Ellis, M

    2011-01-01

    As child mortality declines globally, neonatal mortality (death in the 1st month of life) has become an increasingly important cause of under-5 deaths. Emerging evidence showing the effectiveness of low-cost community-based interventions proves that expensive hospital interventions are not needed to make progress with newborn survival in low-income countries where the vast majority of deaths occur. This paper discusses the use of two approaches to community-based interventions: home visits by community health workers and participatory women's groups. Both are shown to reduce neonatal mortality but they might also have synergy when combined. Although further research is needed to explore contextual factors which might amplify or limit the degree of effect achievable, these interventions look very promising as a low-cost and sustainable approach towards Millennium Development Goal 4. PMID:21781412

  1. Non-tumour bone marrow lymphocytes correlate with improved overall survival in childhood acute lymphoblastic leukaemia.

    PubMed

    Edwin, Claire; Dean, Joanne; Bonnett, Laura; Phillips, Kate; Keenan, Russell

    2016-10-01

    Composition of tumour immune cell infiltrates correlates with response to treatment and overall survival (OS) in several cancer settings. We retrospectively examined immune cells present in diagnostic bone marrow aspirates from paediatric patients with B-cell acute lymphoblastic leukaemia. Our analysis identified a sub-group (∼30% of patients) with >2.37% CD20 and >6.05% CD7 expression, which had 100% OS, and a sub-group (∼30% of patients) with ≤2.37% CD20 and ≤6.05% CD7 expression at increased risk of treatment failure (66.7% OS, P < 0.05). Immune cell infiltrate at diagnosis may predict treatment response and could provide a means to enhance immediate treatment risk stratification. PMID:27348401

  2. Overexpression of protein kinase C ɛ improves retention and survival of transplanted mesenchymal stem cells in rat acute myocardial infarction

    PubMed Central

    He, H; Zhao, Z-H; Han, F-S; Liu, X-H; Wang, R; Zeng, Y-J

    2016-01-01

    We assessed the effects of protein kinase C ɛ (PKCɛ) for improving stem cell therapy for acute myocardial infarction (AMI). Primary mesenchymal stem cells (MSCs) were harvested from rat bone marrow. PKCɛ-overexpressed MSCs and control MSCs were transplanted into infarct border zones in a rat AMI model. MSCs and PKCɛ distribution and expression of principal proteins involved in PKCɛ signaling through the stromal cell-derived factor 1 (SDF-1)/CXC chemokine receptor type 4 (CXCR4) axis and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway were analyzed by immunofluorescence and western blot 1 day after transplantation. Echocardiographic measurements and histologic studies were performed at 4 weeks after transplantation, and MSC survival, expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β (TGFβ), cardiac troponin I (cTnI), von Willebrand factor (vWF), smooth muscle actin (SMA) and factor VIII and apoptosis in infarct border zones were assessed. Rat heart muscles retained more MSCs and SDF-1, CXCR4, PI3K and phosphorylated AKT increased with PKCɛ overexpression 1 day after transplantation. MSC survival and VEGF, bFGF, TGFβ, cTnI, vWF, SMA and factor VIII expression increased in animals with PKCɛ-overexpressed MSCs at 4 weeks after transplantation and cardiac dysfunction and remodeling improved. Infarct size and apoptosis decreased as well. Inhibitory actions of CXCR4 or PI3K partly attenuated the effects of PKCɛ. Activation of PKCɛ may improve retention, survival and differentiation of transplanted MSCs in myocardia. Augmentation of PKCɛ expression may enhance the therapeutic effects of stem cell therapy for AMI. PMID:26775707

  3. Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis

    PubMed Central

    2013-01-01

    Introduction Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. Methods Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. Results Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. Conclusions These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory

  4. Gliptin and GLP-1 analog treatment improves survival and vascular inflammation/dysfunction in animals with lipopolysaccharide-induced endotoxemia.

    PubMed

    Steven, Sebastian; Hausding, Michael; Kröller-Schön, Swenja; Mader, Michael; Mikhed, Yuliya; Stamm, Paul; Zinßius, Elena; Pfeffer, Amanda; Welschof, Philipp; Agdauletova, Saule; Sudowe, Stephan; Li, Huige; Oelze, Matthias; Schulz, Eberhard; Klein, Thomas; Münzel, Thomas; Daiber, Andreas

    2015-03-01

    Dipeptidyl peptidase (DPP)-4 inhibitors are used to treat hyperglycemia by increasing the incretin glucagon-like peptide-1 (GLP-1). Previous studies showed anti-inflammatory and antiatherosclerotic effects of DPP-4 inhibitors. Here, we compared the effects of linagliptin versus sitagliptin and liraglutide on survival and vascular function in animal models of endotoxic shock by prophylactic therapy and treatment after lipopolysaccharide (LPS) injection. Gliptins were administered either orally or subcutaneously: linagliptin (5 mg/kg/day), sitagliptin (50 mg/kg/day) or liraglutide (200 µg/kg/day). Endotoxic shock was induced by LPS injection (mice 17.5-20 mg/kg i.p., rats 10 mg/kg/day). Linagliptin and liraglutide treatment or DPP-4 knockout improved the survival of endotoxemic mice, while sitagliptin was ineffective. Linagliptin, liraglutide and sitagliptin ameliorated LPS-induced hypotension and vascular dysfunction in endotoxemic rats, suppressed inflammatory parameters such as whole blood nitrosyl-iron hemoglobin (leukocyte-inducible nitric oxide synthase activity) or aortic mRNA expression of markers of inflammation as well as whole blood and aortic reactive oxygen species formation. Hemostasis (tail bleeding time, activated partial thromboplastin time) was impaired in endotoxemic rats and recovered under cotreatment with linagliptin and liraglutide. Finally, the beneficial effects of linagliptin on vascular function and inflammatory parameters in endotoxemic mice were impaired in AMP-activated kinase (alpha1) knockout mice. The improved survival of endotoxemic animals and other data shown here may warrant further clinical evaluation of these drugs in patients with septic shock beyond the potential improvement of inflammatory complications in diabetic individuals with special emphasis on the role of AMP-activated kinase (alpha1) in the DPP-4/GLP-1 cascade. PMID:25600227

  5. Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma

    PubMed Central

    Chen, Yu-Kuei; Tung, Chun-Wei; Lee, Jui-Ying; Hung, Yi-Chun; Lee, Chien-Hung; Chou, Shah-Hwa; Lin, Hung-Shun; Wu, Ming-Tsang; Wu, I-Chen

    2016-01-01

    This study aimed to identify noninvasive protein markers capable of detecting the presence and prognosis of esophageal squamous-cell carcinoma (ESCC). Analyzing microarray expression data collected from 17-pair ESCC specimens, we identified one protein, matrix metalloproteinase-1 (MMP1), as a possibly useful marker. Plasma MMP1 was then measured by enzyme-linked immunosorbent assay (ELISA) in 210 ESCC patients and 197 healthy controls. ESCC patients had higher mean levels of MMP1 than controls (8.7 ± 7.5 vs. 6.7 ± 4.9 ng/mL, p < 0.0001). Using the highest quartile level (9.67 ng/mL) as cut-off, we found a 9.0-fold risk of ESCC in those with higher plasma MMP1 after adjusting for covariates (95% confidence interval = 2.2, 36.0). Heavy smokers and heavy drinkers with higher plasma MMP1 had 61.4- and 31.0 times the risk, respectively, than non-users with lower MMP1. In the survival analysis, compared to those with MMP1 ≤ 9.67 ng/mL, ESCC patients with MMP1 > 9.67 ng/mL had a 48% increase in the risk of ESCC death (adjusted hazard ratio = 1.48; 95% CI = 1.04–2.10). In conclusion, plasma MMP1 may serve as a noninvasive marker of detecting the presence and predicting the survival of ESCC. PMID:27436512

  6. Improving survival by exploiting tumor dependence on stabilized mutant p53 for treatment

    PubMed Central

    Alexandrova, EM; Yallowitz, AR; Li, D; Xu, S; Schulz, R; Proia, DA; Lozano, G; Dobbelstein, M; Moll, UM

    2015-01-01

    SUMMARY Missense mutations in p53 generate aberrant proteins with abrogated tumor suppressor functions that can also acquire oncogenic gain-of-functions (GOF) that promote malignant progression, invasion, metastasis and chemoresistance1–5. Mutant p53 (mutp53) proteins undergo massive constitutive stabilization specifically in tumors, which is the key requisite for GOF6–8. Although currently 11 million patients worldwide live with tumors expressing highly stabilized mutp53, it is unknown whether mutp53 is a therapeutic target in vivo. Here we use a novel mutp53 mouse model expressing an inactivatible R248Q hotspot mutation (floxQ) to show that tumors depend on sustained mutp53 expression. Upon Tamoxifen-induced mutp53 ablation, allo-transplanted and autochthonous tumors curb their growth, thus extending animal survival by 37%, and advanced tumors undergo apoptosis and tumor regression or stagnation. The HSP90/HDAC6 chaperone machinery, which is significantly upregulated in cancer compared to normal tissues, is a major determinant of mutp53 stabilization9–12. We show that long-term HSP90 inhibition significantly extends the survival of mutp53 Q/−2 and H/H (R172H allele3) mice by 59% and 48%, respectively, but not their respective p53−/− littermates. This mutp53-dependent drug effect occurs in H/H mice treated with 17DMAG+SAHA and in H/H and Q/− mice treated with the potent Hsp90 inhibitor ganetespib. Notably, drug activity correlates with induction of mutp53 degradation, tumor apoptosis and prevention of T-lymphomagenesis. These proof-of-principle data identify mutp53 as an actionable cancer-specific drug target. PMID:26009011

  7. Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1).

    PubMed

    Wideman, Rhonda D; Yu, Irene L Y; Webber, Travis D; Verchere, C Bruce; Johnson, James D; Cheung, Anthony T; Kieffer, Timothy J

    2006-09-01

    Glucagon-like peptide 1 (GLP-1) is a hormone that has received significant attention as a therapy for diabetes because of its ability to stimulate insulin biosynthesis and release and to promote growth and survival of insulin-producing beta cells. While GLP-1 is produced from the proglucagon precursor by means of prohormone convertase (PC) 1/3 activity in enteroendocrine L cells, the same precursor is differentially processed by PC2 in pancreatic islet alpha cells to release glucagon, leaving GLP-1 trapped within a larger fragment with no known function. We hypothesized that we could induce GLP-1 production directly within pancreatic islets by means of delivery of PC1/3 and, further, that this intervention would improve the viability and function of islets. Here, we show that adenovirus-mediated expression of PC1/3 in alpha cells increases islet GLP-1 secretion, resulting in improved glucose-stimulated insulin secretion and enhanced survival in response to cytokine treatment. PC1/3 expression in alpha cells also improved performance after islet transplantation in a mouse model of type 1 diabetes, possibly by enhancing nuclear Pdx1 and insulin content of islet beta cells. These results demonstrate a unique strategy for liberating GLP-1 from directly within the target organ and highlight the potential for up-regulating islet GLP-1 production as a means of treating diabetes. PMID:16938896

  8. Does aggressive surgical resection improve survival in advanced stage 3 and 4 neuroblastoma? A systematic review and meta-analysis.

    PubMed

    Mullassery, Dhanya; Farrelly, Paul; Losty, Paul D

    2014-11-01

    The role of surgery in the management of advanced staged neuroblastoma (NBL) is controversial. A systematic review and meta-analysis is reported to address robust evidence for curative "gross total tumor resection" (GTR) in Stage 3 and Stage 4 neuroblastoma. Studies were identified using Medline, Embase, and Cochrane databases using pre-specified search terms. Primary outcomes were 5-year overall (OS) and disease-free survival (DFS) after GTR and subtotal resection (STR) in Stage 3 or 4 NBL. Data were analyzed using Review Manager. The Mantel-Haenszel method and a random effects model was utilized to calculate odds ratios (95% CI). Fifteen studies (five Stage 3 and 13 Stage 4) met full inclusion criteria. The pooled odds ratio for 5 year OS in Stage 3 following GTR compared to STR was 2.4 (95% CI 1.19-4.85). In Stage 4 disease, the pooled odds ratio for 5 year overall survival (OS) following GTR compared to STR was 1.65 (95% CI 0.96-1.91); a pooled odds ratio for 5 year DFS following GTR compared to STR was 1.55 (95% CI 1.12-2.14). A clear survival benefit is shown for GTR over STR in Stage 3 NBL only. Though some advantage can be demonstrated for GTR as defined by DFS in Stage 4 NBL GTR did not significantly improve OS in Stage 4 disease. PMID:25247398

  9. Colony-Stimulating Factor 2 (CSF-2) Improves Development and Posttransfer Survival of Bovine Embryos Produced in Vitro

    PubMed Central

    Loureiro, Bárbara; Bonilla, Luciano; Block, Jeremy; Fear, Justin M.; Bonilla, Aline Q. S.; Hansen, Peter J.

    2009-01-01

    In this study, we tested the role of colony-stimulating factor 2 (CSF2) as one of the regulatory molecules that mediate maternal effects on embryonic development during the preimplantation period. Our objective was to verify effects of CSF2 on blastocyst yield, determine posttransfer survival, and evaluate properties of the blastocyst formed after CSF2 treatment. In vitro, CSF2 increased the percentage of oocytes that became morulae and blastocysts. Blastocysts that were treated with CSF2 tended to have a greater number of inner cell mass cells and had a higher ratio of inner cell mass to trophectoderm cells. There was no effect of CSF2 on the incidence of apoptosis. Treatment with CSF2 from d 5 to 7 after insemination increased embryonic survival as indicated by improved pregnancy rate at d 30–35 of gestation. Moreover, treatment with CSF2 from either d 1–7 or 5–7 after insemination reduced pregnancy loss after d 30–35. Results indicate that treatment with CSF2 can affect embryonic development and enhance embryo competence for posttransfer survival. The fact that treatment with CSF2 during such a narrow window of development altered embryonic function much later in pregnancy suggests that CSF2 may exert epigenetic effects on the developing embryo that result in persistent changes in function during the embryonic and fetal periods of development. PMID:19797121

  10. Dihydroxyselenolane (DHS) supplementation improves survival following whole-body irradiation (WBI) by suppressing tissue-specific inflammatory responses.

    PubMed

    Kunwar, Amit; Verma, Prachi; Bhilwade, H N; Iwaoka, Michio; Priyadarsini, K Indira

    2016-09-01

    Dihydroxyselenolane (DHS), a simple water-soluble organoselenium compound, was evaluated for radioprotection in BALB/c mice after whole-body irradiation (WBI) (8Gy (60)Co, 1Gy/min), by monitoring 30-d post-irradiation survival and biochemical/histological changes in radiosensitive organs. Intraperitoneal administration of DHS at 2mg/kg for five consecutive days before irradiation and three times per week during the post-irradiation period showed maximum benefit (40% improvement in 30 d post-irradiation survival). DHS treatment, despite inducing expression of glutathione peroxidases (GPx1, GPx2, and GPx4) in spleen and intestine, did not protect against radiation-induced acute (10-day) haematopoietic and gastrointestinal toxicities. DHS treatment significantly reduced radiation-induced DNA damage in peripheral leukocytes and inflammatory responses in intestine, lung, and circulation. The anti-inflammatory effect of DHS was associated with reductions in lipid peroxidation, expression of pro-inflammatory genes such as Icam-1, Ccl-2, and iNos-2, and subsequent infiltration of inflammatory cells. Irradiated mice treated with DHS survived until day 30 post-irradiation and showed restoration of spleen cellularity and intestinal villi, but had moderately increased systemic and tissue-specific inflammatory responses. Another organoselenium compound, selenomethionine, evaluated in parallel with DHS at the same dose and treatment schedule, showed comparable radioprotective effects. The mechanism of radioprotection by DHS is mainly via suppression of inflammatory responses. PMID:27542713

  11. SOD Mimetic Improves the Function, Growth and Survival of Small Size Liver Grafts after Transplantation in Rats

    PubMed Central

    Cui, Yi-Yao; Qian, Jian-Ming; Yao, Ai-Hua; Ma, Zhen-Yu; Qian, Xiao-Feng; Zha, Xiao-Min; Zhao, Yi; Ding, Qiang; Zhao, Jia; Wang, Shui; Wu, Jian

    2012-01-01

    BACKGROUND Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and an increased mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted. AIMS The present study aims to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase (SOD) mimetic, MnTBAP, on graft function, growth and survival in the recipient rats. METHODS Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP). RESULTS Serum ALT levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of TNF-α and IL-1β and DNA binding activity of NF-κB in the grafts were increased significantly in SSGLT recipients compared to sham-operated controls. Both phosphorylated p38 MAPK and nuclear c-jun were increased in SSGLT. All these changes were strikingly reversed by the administration of MnTBAP, with an increase in serum SOD activity. Moreover, in situ bromo-deoxyuridine incorporation demonstrated that graft regeneration in SSGLT+MnTBAP group was much profound than in the SSGLT group. Finally, the survival of recipients with MnTBAP treatments was significantly improved. CONCLUSIONS Enhanced oxidant stress with activation of the p38-c-Jun-NF-κB signaling pathway contributes to SFS-associated graft failure, retarded graft growth and poor survival. MnTBAP effectively reversed the pathologic changes in SFS-associated graft failure. PMID:22955229

  12. Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2008-12-01

    Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of

  13. Exendin-4 improved rat cortical neuron survival under oxygen/glucose deprivation through PKA pathway.

    PubMed

    Wang, M-D; Huang, Y; Zhang, G-P; Mao, L; Xia, Y-P; Mei, Y-W; Hu, B

    2012-12-13

    Previous studies demonstrated that exendin-4 (Ex-4) may possess neurotrophic and neuroprotective functions in ischemia insults, but its mechanism remained unknown. Here, by using real-time PCR and ELISA, we identified the distribution of active GLP-1Rs in the rat primary cortical neurons. After establishment of an in vitro ischemia model by oxygen/glucose deprivation (OGD), neurons were treated with various dosages of Ex-4. The MTT assay showed that the relative survival rate increased with the dosage of Ex-4 ranging from 0.2 to 0.8 μg/ml (P<0.001, vs. OGD group). The apoptosis rate was reduced from (49.47±2.70)% to (14.61±0.81)% after Ex-4 treatment (0.4 μg/ml) 12h after OGD (P<0.001). Moreover, immunofluorescence staining indicated that Ex-4 increased glucose-regulated proteins 78 (GRP78) and reduced C/EBP-homologous protein (CHOP). Western blot analysis demonstrated that, after neurons were treated with Ex-4, GRP78 was up-regulated over time (P<0.01, vs. OGD group), while CHOP levels rose to a peak 8h after OGD and then decreased (P<0.05, vs. OGD group). This effect was changed by both the protein kinase A (PKA) inhibitor H89 (P<0.01, P<0.05, respectively, vs. Ex-4 group) and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (P<0.01, P<0.01, respectively, vs. Ex-4 group) but not by the mitogen-activated protein kinase (MAPK) inhibitor U0126. Our study also revealed that, compared with the Ex-4 group, inhibition of the PKA signaling pathway significantly decreased the survival rate of neurons, down-regulated the expression of B-cell lymphoma 2 (Bcl-2) and up-regulated the Bax expression 3h after ODG (P<0.05, P<0.01, respectively), while neither PI3K nor MAPK inhibition exerted such effects. Furthermore, Western blotting exhibited that PKA expression was elevated in the presence or absence of OGD insults (P<0.05). This study indicated that Ex-4 protected neurons against OGD by modulating the unfolded protein response (UPR) through the PKA pathway and

  14. Dissolving pulp from jute stick.

    PubMed

    Matin, Mhafuza; Rahaman, M Mostafizur; Nayeem, Jannatun; Sarkar, Mamon; Jahan, M Sarwar

    2015-01-22

    Jute stick is woody portion of jute plant, which remain as leftover after extracting bast fibre. Presently, it is being used for fencing in the rural area. In this investigation, biorefinery concept was initiated in producing dissolving pulp from jute stick by pre-hydrolysis kraft process. At 170°C for 1h of pre-hydrolysis, 70% of hemicelluloses was dissolved with negligible loss of α-cellulose. At this condition, 75% of dissolved sugars in the pre-hydrolysis liquor were in the oligomeric form. The pre-hydrolysed jute stick was subsequently pulped by kraft process with the variation of active alkali. The pulp yield was 36.2% with kappa number 18.5 at the conditions of 16% active alkali for 2h of cooking at 170°C. Final pulp was produced with 92% α-cellulose and 89% brightness after D0EpD1EpD1 bleaching. The produced dissolving pulp can be used in rayon production. PMID:25439866

  15. Immunomodulatory and Antimicrobial Activity of Babassu Mesocarp Improves the Survival in Lethal Sepsis

    PubMed Central

    Prado, Dayanna S.; Barcellos, Priscila S.; Gonçalves, Azizedite G.

    2016-01-01

    Attalea speciosa syn Orbignya phalerata Mart. (babassu) has been used in the treatment of inflammatory and infectious diseases. Aim of the study. To investigate the antimicrobial and immunological activity of babassu mesocarp extract (EE). Material and Methods. The in vitro antimicrobial activity was evaluated by disk diffusion assay and by determination of the minimum inhibitory concentration (MIC) to Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). The flavonoids and phenolic acids content were determined by chromatography. The in vivo assays were performed in Swiss mice submitted to sepsis by cecal ligation and puncture (CLP). The mice received EE subcutaneously (125 or 250 mg/Kg), 6 hours after the CLP. The number of lymphoid cells was quantified and the cytokines production was determined by ELISA after 12 h. Results. EE was effective as antimicrobial to E. faecalis, S. aureus, and MRSA. EE is rich in phenolic acids, a class of compounds with antimicrobial and immunological activity. An increased survival can be observed in those groups, possibly due to a significant inhibition of TNF-α and IL-6. Conclusions. The EE showed specific antimicrobial activity in vitro and an important antiseptic effect in vivo possibly due to the antimicrobial and immunomodulatory activity.

  16. An anti-apoptotic peptide improves survival in lethal total body irradiation

    SciTech Connect

    McDunn, Jonathan E.; Muenzer, Jared T.; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C.; Davis, Christopher G.; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S.

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 {mu}M) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  17. An anti-apoptotic peptide improves survival in lethal total body irradiation

    PubMed Central

    McDunn, Jonathan E.; Muenzer, Jared T.; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C.; Davis, Christopher G.; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S.

    2009-01-01

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5–10 μM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation. PMID:19303399

  18. Dietary plant phenolic improves survival of bacterial infection in Manduca sexta caterpillars.

    PubMed

    Del Campo, Marta L; Halitschke, Rayko; Short, Sarah M; Lazzaro, Brian P; Kessler, André

    2013-03-01

    Plant phenolics are generally thought to play significant roles in plant defense against herbivores and pathogens. Many plant taxa, including Solanaceae, are rich in phenolic compounds and some insect herbivores have been shown to acquire phenolics from their hosts to use them as protection against their natural enemies. Here we demonstrate that larvae of an insect specialist on Solanaceae, the tobacco hornworm, Manduca sexta L. (Lepidoptera: Sphingidae), acquire the plant phenolic chlorogenic acid (CA), and other caffeic acid derivatives as they feed on one of their hosts, Nicotiana attenuata L. (Solanaceae), and on artificial diet supplemented with CA. We test the hypothesis that larvae fed on CA-supplemented diet would have better resistance against bacterial infection than larvae fed on a standard CA-free diet by injecting bacteria into the hemocoel of fourth instars. Larvae fed CA-supplemented diet show significantly higher survival of infection with Enterococcus faecalis (Andrewes & Horder) Schleifer & Kilpper-Bälz, but not of infection with the more virulent Pseudomonas aeruginosa (Schroeter) Migula. Larvae fed on CA-supplemented diet possess a constitutively higher number of circulating hemocytes than larvae fed on the standard diet, but we found no other evidence of increased immune system activity, nor were larvae fed on CA-supplemented diet better able to suppress bacterial proliferation early in the infection. Thus, our data suggest an additional defensive function of CA to the direct toxic inhibition of pathogen proliferation in the gut. PMID:23420018

  19. Inhibitory killer cell immunoglobulin-like receptor (iKIR) mismatches improve survival after T-cell-repleted haploidentical transplantation.

    PubMed

    Bastos-Oreiro, Mariana; Anguita, Javier; Martínez-Laperche, Carolina; Fernández, Lucía; Buces, Elena; Navarro, Almudena; Pascual, Cristina; Pérez-Corral, Ana; Balsalobre, Pascual; Muñoz, Cristina; Kwon, Mi; Serrano, David; Perez-Martinez, Antonio; Buño, Ismael; Gayoso, Jorge; Díez-Martín, José Luís

    2016-05-01

    Alloreactivity triggered by interaction between killer cell immunoglobulin-like receptors (KIRs) and natural killer (NK) cells plays a role in the graft-versus-tumor effect after hematopoietic stem cell transplantation (SCT). Our aim in this study was to evaluate this role in the setting of T-cell-repleted haploidentical SCT with postinfusion high-dose cyclophosphamide (PT-Cy). We included 33 patients. Among patient-donor pairs with at least 1 inhibitory KIR (iKIR) gene mismatch, event-free survival (EFS) and cumulative incidence of relapse 1 year after transplant were significantly better (85% vs. 37% [P = 0.008] and 18% vs. 46% [P = 0.041], respectively). A subanalysis in 12 patients with Hodgkin's lymphoma (HL) showed an improvement in EFS 1 year after transplant in those patients with KIR ligand mismatch (100% vs. 25%, P = 0.012), although overall survival (OS) was not affected (85% vs. 80%, P = 0.2). Eight of 12 patient-donors pairs presented iKIR mismatches. Of note, this outcome was better in the small subgroup, both for EFS (100% vs. 25%, P = 0.012) and for OS (100% vs. 37%, P = 0.004). Our data suggest that in the setting of T-cell-repleted haploidentical SCT with PT-Cy, iKIR mismatch is associated with improved survival, with particularly good results for both iKIR and KIR ligand mismatches in patients with HL. PMID:26133015

  20. Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma.

    PubMed

    Jackson, Matthew W; Rusthoven, Chad G; Jones, Bernard L; Kamdar, Manali; Rabinovitch, Rachel

    2016-05-01

    Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared. Am. J. Hematol. 91:476-480, 2016. © 2016 Wiley Periodicals, Inc. PMID:26852276

  1. Soluble Guanylate Cyclase Stimulation Prevents Fibrotic Tissue Remodeling and Improves Survival in Salt-Sensitive Dahl Rats

    PubMed Central

    Geschka, Sandra; Kretschmer, Axel; Sharkovska, Yuliya; Evgenov, Oleg V.; Lawrenz, Bettina; Hucke, Andreas; Hocher, Berthold; Stasch, Johannes-Peter

    2011-01-01

    Background A direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO) and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension. Methods and Results Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d) for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1. Conclusions Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions. PMID:21789188

  2. Reduced BDNF attenuates inflammation and angiogenesis to improve survival and cardiac function following myocardial infarction in mice

    PubMed Central

    Ma, Yonggang; Ramirez, Trevi A.; Zhang, Jianhua; Dai, Qiuxia; Hensler, Julie G.; Lopez, Elizabeth F.; Ghasemi, Omid; Jin, Yu-Fang; Lindsey, Merry L.

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) increases in failing hearts, but BDNF roles in cardiac remodeling following myocardial infarction (MI) are unclear. Male BDNF+/+ [wild-type (WT)] and BDNF+/− heterozygous (HET) mice at 6–9 mo of age were subjected to MI and evaluated at days 1, 3, 5, 7, or 28 post-MI. At day 28 post-MI, 76% of HET versus 40% of WT survived, whereas fractional shortening improved and neovascularization levels were reduced in the HET (all, P < 0.05). At day 1, post-MI, matrix metalloproteinase-9, and myeloperoxidase (MPO) increased in WT, but not in HET. Concomitantly, monocyte chemotactic protein-1 and -5 levels increased and vascular endothelial growth factor (VEGF)-A decreased in HET. Neutrophil infiltration peaked at days 1–3 in WT mice, and this increase was blunted in HET. To determine if MPO administration could rescue the HET phenotype, MPO was injected at 3 h post-MI. MPO restored VEGF-A levels without altering matrix metalloproteinase-9 or neutrophil content. In conclusion, reduced BDNF levels modulated the early inflammatory and neovascularization responses, leading to improved survival and reduced cardiac remodeling at day 28 post-MI. Thus reduced BDNF attenuates early inflammation following MI by modulating MPO and angiogenic response through VEGF-A. PMID:24142413

  3. Des-acyl-ghrelin (DAG) normalizes hyperlactacidemia and improves survival in a lethal rat model of burn trauma.

    PubMed

    Sheriff, Sulaiman; Kadeer, Nijiati; Friend, Lou Ann; James, J Howard; Alexander, J Wesley; Balasubramaniam, Ambikaipakan

    2014-10-01

    Critical illness, including burn injury, results in elevated plasma lactate levels. Dysregulation of PI3K/Akt signaling has been shown to play a predominant role in the inactivation of skeletal muscle PDC and, hence, in hyperlactacidemia in rat models of sepsis and endotoxemia. This observation, and our previous finding that DAG can reverse burn-induced skeletal muscle proteolysis through the activation of PI3K/Akt pathway, led us to hypothesize that DAG may also attenuate hyperlactacidemia in burn injury. Our investigations revealed that burn injury significantly elevated both skeletal muscle lactate production and plasma lactate levels. Moreover, this was accompanied in skeletal muscle by a 5-7 fold increase in mRNA expression of pyruvate dehydrogenase kinases (PDK) 2 and 4, and a ∼30% reduction in PDC activity. DAG treatment of burn rats completely normalized not only the mRNA expression of the PDKs and PDC activity, but also hyperlactacidemia within 24h of burn injury. DAG also normalized epinephrine-induced lactate production by isolated skeletal muscles from normal rats. Moreover, DAG also improved survival in a lethal rat model of burn trauma. These findings with DAG may have clinical implications because chances of survival for critically ill patients are greatly improved if plasma lactate levels are normalized within 24h of injury. PMID:25063053

  4. Deacetylation-mediated interaction of SIRT1-HMGB1 improves survival in a mouse model of endotoxemia

    PubMed Central

    Hwang, Jung Seok; Choi, Hyuk Soo; Ham, Sun Ah; Yoo, Taesik; Lee, Won Jin; Paek, Kyung Shin; Seo, Han Geuk

    2015-01-01

    Inflammatory signal-mediated release of high-mobility group box 1 (HMGB1) is a damage-associated molecular pattern or alarmin. The inflammatory functions of HMGB1 have been extensively investigated; however, less is known about the mechanisms controlling HMGB1 release. We show that SIRT1, the human homolog of the Saccharomyces cerevisiae protein silent information regulator 2, which is involved in cellular senescence and possibly the response to inflammation, forms a stable complex with HMGB1 in murine macrophage RAW264.7 cells. SIRT1 directly interacted with HMGB1 via its N-terminal lysine residues (28–30), and thereby inhibited HMGB1 release to improve survival in an experimental model of sepsis. By contrast, inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor-α promoted HMGB1 release by provoking its dissociation from SIRT1 dependent on acetylation, thereby increasing the association between HMGB1 and chromosome region maintenance 1, leading to HMGB1 translocation. In vivo infection with wild-type SIRT1 and HMGB1K282930R, a hypo-acetylation mutant, improved survival (85.7%) during endotoxemia more than infection with wild-type SIRT1 and HMGB1-expressing adenovirus, indicating that the acetylation-dependent interaction between HMGB1 and SIRT1 is critical for LPS-induced lethality. Taken together, we propose that SIRT1 forms an anti-inflammatory complex with HMGB1, allowing cells to bypass the response to inflammation. PMID:26522327

  5. Diabetes and cardiovascular disease: Changing the focus from glycemic control to improving the long-term survival

    PubMed Central

    Wang, Cecilia C. Low; Reusch, Jane EB

    2012-01-01

    Diabetes is the fifth leading cause of death worldwide and contributes to leading causes of death, cancer and cardiovascular disease including coronary heart disease, stroke, peripheral vascular disease and other vascular disease. While glycemic management remains a cornerstone of diabetes care, the co-management of hypertension, atherosclerosis, cardiovascular risk reduction and prevention of long-term consequences associated with diabetes are now well recognized as essential to improve long-term survival. Clinical trial evidence substantiates the importance of glycemic control, LDL-cholesterol lowering therapy, blood-pressure lowering, control of albuminuria, and comprehensive approaches targeting multiple risk factors to reduce cardiovascular risk. This article presents a review of the role of diabetes in pathogenesis of atherosclerosis and cardiac dysfunction, recent evidence regarding degree of glycemic control and mortality, and available evidence for a multi-faceted approach to improve long-term outcomes for patients. PMID:23062569

  6. Free Pulp Transfer for Fingertip Reconstruction—The Algorithm for Complicated Allen Fingertip Defect

    PubMed Central

    Spyropoulou, Georgia-Alexandra; Shih, Hsiang-Shun

    2015-01-01

    Abstract Background: We present a review of all the cases of free toe pulp transfer and an algorithm for application of free pulp transfer in complicated Allen fingertip defect. Methods: Seventeen patients underwent free toe pulp transfer for fingertip reconstruction by the senior author. Twelve cases were Allen type II with oblique pulp defect, 4 were Allen type III, and 1 patient had 2 fingertip injuries classified both as type IV. According to the algorithm presented, for the type III defects where the germinal matrix is still preserved, we use free pulp transfer and nail bed graft to preserve the nail growth instead of toe to hand transfer. For the type IV injuries with multiple defects, a combination of web flap from both big toe and second toe is possible for 1-stage reconstruction. Results: All pulp flaps survived completely. Static 2-point discrimination ranged from 6 to 15 mm (mean: 10.5 mm). No patient presented dysesthesia, hyperesthesia, pain at rest, or cold intolerance. The donor site did not present any nuisances apart from partial skin graft loss in 3 cases. Conclusions: We tried to classify and modify the defects’ reconstruction according to Allen classification. Free toe pulp transfer is a “like with like” reconstruction that provides sensate, glabrous skin with good color and texture match for fingertip trauma, and minimal donor site morbidity compared with traditional toe to hand transfer. PMID:26894009

  7. [Utilization of organic resources in paper pulp waste liquid].

    PubMed

    Lin, Qiaojia; Liu, Jinghong; Yang, Guidi; Huang, Biao

    2005-04-01

    In this paper, one hundred percent of condensed sulfate paper pulp waste liquid was used as the raw material of adhesive, and the activation of its lignin as well as the improving effects of phenol formaldehyde resin and polyfunctional aqueous polymer isocyanate (PAPI) were studied. The results showed that adding formaldehyde to the waste liquid could increase the reactivity of contained lignin, and adding 30% phenol formaldehyde resin or 20% PAPI could make the waste liquid in place of pure phenol formaldehyde resin for producing class I plywood. Furthermore, the cost could be reduced by 55.5% and 49.0%, respectively, in comparing with pure phenol formaldehyde resin. This approach fully used the organic resources in paper pulp waste liquid, reduced environment pollution at the same time, and had unexceptionable economic, social and ecological benefits. The feasibility of preparing adhesives from paper pulp waste liquid was also analyzed by infrared spectrum. PMID:16011170

  8. Doxycycline Attenuates Protein Aggregation in Cardiomyocytes and Improves Survival of a Mouse Model of Cardiac Proteinopathy

    PubMed Central

    Zheng, Hanqiao; Tang, Mingxin; Zheng, Qingwen; Kumarapeli, Asangi R. K.; Horak, Kathleen M.; Tian, Zongwen; Wang, Xuejun

    2010-01-01

    Objective The goal of this preclinical study was to assess the therapeutic efficacy of doxycycline (Doxy) for desmin-related cardiomyopathy (DRC) and to elucidate the potential mechanisms involved. Background DRC, exemplifying cardiac proteinopathy, is characterized by intrasarcoplasmic protein aggregation and cardiac insufficiency. No effective treatment for DRC is presently available. Doxy was shown to attenuate aberrant intranuclear aggregation and toxicity of misfolded proteins in non-cardiac cells and animal models of other proteinopathies. Methods Mice and cultured neonatal rat cardiomyocytes with transgenic (TG) expression of a human DRC-linked missense mutant αB-crystallin (CryABR120G) were used for testing the effect of Doxy. Doxy was administered via drinking water (6 mg/ml) initiated at 8 or 16 weeks of age. Results Doxy treatment initiated at 16 weeks of age significantly delayed the premature death of CryABR120G TG mice, with a median lifespan of 30.4 weeks (placebo group 25 weeks, p<0.01). In another cohort of CryABR120G TG mice, Doxy treatment initiated at 8 weeks of age significantly attenuated cardiac hypertrophy in one month. Further investigation revealed that Doxy significantly reduced the abundance of CryAB-positive microscopic aggregates, detergent-resistant CryAB oligomers, and total ubiquitinated proteins in CryABR120G TG hearts. In cell culture, Doxy treatment dose-dependently suppressed the formation of both microscopic protein aggregates and detergent-resistant soluble CryABR120G oligomers, and reversed the upregulation of p62 protein induced by adenovirus-mediated CryABR120G expression. Conclusions Doxy suppresses CryABR120G induced aberrant protein aggregation in cardiomyocytes and prolongs CryABR120G based DRC mouse survival. PMID:20947000

  9. Improved red blood cell survival after cardiac operations with administration of urea during cardiopulmonary bypass

    SciTech Connect

    Roberts, D.; Bake, B.; William-Olsson, G.

    1985-01-01

    The plasma hemoglobin and red blood cell survival (half-life of /sup 51/Cr) was studied in 48 patients undergoing single valve replacement or coronary artery bypass graft. Urea or placebo was administered during cardiopulmonary bypass in a prospective, randomized, double-blind manner to test the potential effect on mechanical hemolysis. The mean plasma hemoglobin level at the end of extracorporeal circulation was significantly lower in the urea-treated groups (coronary artery bypass 342 mg/L; valve replacement 364 mg/L) than in the control groups (coronary artery bypass 635 mg/L, valve replacement 518 mg/L. The half-life of /sup 51/Cr was significantly longer in the urea-treated patients (coronary artery bypass 18 days; valve replacement 16 days) than in the control groups (coronary artery bypass 12.4 days; valve replacement 12.7 days) but still below the normal reference value (29 +/- 4 days). The plasma hemoglobin returned to near normal values (50 mg/L) the day after operation (day 1) and remained low with no differences between control and urea-treated groups. The total blood hemoglobin was followed for 2 weeks after operation and showed significantly less anemia in the urea-treated group. The lowest mean blood hemoglobin level was noted between days 5 and 9-114 (coronary artery bypass) and 107 (valve replacement) gm/L in the urea-treated patients compared to 92.3 gm/L in the control subjects. The reduction in the severity of the anemia led to less transfusion in the urea-treated patients (approximately 0.5 unit/patient) than in the control subjects (approximately 1 unit/patient) between days 3 and 14.

  10. Improved survival of gastric cancer with tumour Epstein–Barr virus positivity: an international pooled analysis

    PubMed Central

    Camargo, M Constanza; Kim, Woo-Ho; Chiaravalli, Anna Maria; Kim, Kyoung-Mee; Corvalan, Alejandro H; Matsuo, Keitaro; Yu, Jun; Sung, Joseph J Y; Herrera-Goepfert, Roberto; Meneses-Gonzalez, Fernando; Kijima, Yuko; Natsugoe, Shoji; Liao, Linda M; Lissowska, Jolanta; Kim, Sung; Hu, Nan; Gonzalez, Carlos A; Yatabe, Yashushi; Koriyama, Chihaya; Hewitt, Stephen M; Akiba, Suminori; Gulley, Margaret L; Taylor, Philip R; Rabkin, Charles S

    2015-01-01

    Background and objective About 9% of gastric carcinomas have Epstein–Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors. Methods We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58 years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% non-cardia) and year of diagnosis. Variations by study and continent were assessed using study-specific HRs for EBV positivity. Results During median 3.0 years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4). Conclusions Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association. PMID:23580779

  11. Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock.

    PubMed Central

    Wu, C C; Chen, S J; Szabó, C; Thiemermann, C; Vane, J R

    1995-01-01

    1. We have investigated the effects of aminoguanidine, a relatively selective inhibitor of the cytokine-inducible isoform of nitric oxide synthase (iNOS), on the delayed circulatory failure, vascular hyporeactivity to vasoconstrictor agents, and iNOS activity in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide; LPS). In addition, we have evaluated the effect of aminoguanidine on the 24 h survival rate in a murine model of endotoxaemia. 2. Male Wistar rats were anaesthetized and instrumented for the measurement of mean arterial blood pressure (MAP) and heart rate (HR). Injection of LPS (10 mg kg-1, i.v.) resulted in a fall in MAP from 115 +/- 4 mmHg (time 0, control) to 79 +/- 9 mmHg at 180 min (P < 0.05, n = 10). The pressor effect of noradrenaline (NA, 1 microgram kg-1, i.v.) was also significantly reduced at 60, 120 and 180 min after LPS injection. In contrast, animals pretreated with aminoguanidine (15 mg kg-1, i.v., 20 min prior to LPS injection) maintained a significantly higher MAP (at 180 min, 102 +/- 3 mmHg, n = 10, P < 0.05) when compared to rats given only LPS (LPS-rats). Cumulative administration of aminoguanidine (15 mg kg-1 and 45 mg kg-1) given 180 min after LPS caused a dose-related increase in MAP and reversed the hypotension. Aminoguanidine also significantly alleviated the reduction of the pressor response to NA: indeed, at 180 min, the pressor response returned to normal in aminoguanidine pretreated LPS-rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7541282

  12. Aggressive surgical resection does not improve survival in operable esophageal squamous cell carcinoma with N2-3 status

    PubMed Central

    Zheng, Yu-Zhen; Zhao, Wei; Hu, Yi; Ding-Lin, Xiao-Xiao; Wen, Jing; Yang, Hong; Liu, Qian-Wen; Luo, Kong-Jia; Huang, Qing-Yuan; Chen, Jun-Ying; Fu, Jian-Hua

    2015-01-01

    metastasis, and aggressive surgical resection does not improve survival in patients with N2-3 status. PMID:26229406

  13. Percutaneous Intraductal Radiofrequency Ablation Combined with Biliary Stent Placement for Nonresectable Malignant Biliary Obstruction Improves Stent Patency but not Survival

    PubMed Central

    Wang, Jianfeng; Zhao, Lizhen; Zhou, Chuanguo; Gao, Kun; Huang, Qiang; Wei, Baojie; Gao, Jun

    2016-01-01

    biliary obstruction is safe and feasible and effectively increases stent patency time. However, it does not improve patient survival. PMID:27082582

  14. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    SciTech Connect

    Elshaikh, Mohamed A.; Vance, Sean; Suri, Jaipreet S.; Mahan, Meredith; Munkarah, Adnan

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  15. Composition, texture and methane potential of cellulosic residues from Lewis acids organosolv pulping of wheat straw.

    PubMed

    Constant, Sandra; Barakat, Abdellatif; Robitzer, Mike; Di Renzo, Francesco; Dumas, Claire; Quignard, Françoise

    2016-09-01

    Cellulosic pulps have been successfully isolated from wheat straw through a Lewis acids organosolv treatment. The use of Lewis acids with different hardness produced pulps with different delignification degrees. The cellulosic residue was characterised by chemical composition, X-ray diffraction, FT-IR spectroscopy, N2 physisorption, scanning electron microscopy and potential for anaerobic digestibility. Surface area and pore volume increased with the hardness of the Lewis acid, in correspondence with the decrease of the amount of lignin and hemicellulose in the pulp. The non linearity of the correlation between porosity and composition suggests that an agglomeration of cellulose fibrils occurs in the early stages of pulping. All organosolv pulps presented a significantly higher methane potential than the parent straw. A methane evolution of 295Ncm(3)/g OM was reached by a moderate improvement of the accessibility of the native straw. PMID:27295251

  16. Application of thermophilic enzymes and water jet system to cassava pulp.

    PubMed

    Chaikaew, Siriporn; Maeno, Yuka; Visessanguan, Wonnop; Ogura, Kota; Sugino, Gaku; Lee, Seung-Hwan; Ishikawa, Kazuhiko

    2012-12-01

    Co-production of fermentable sugars and nanofibrillated cellulose from cassava pulp was achieved by the combination of thermophilic enzymes (endoglucanase, β-glucosidase, and α-amylase) and a new atomization system (Star Burst System; SBS), which employs opposing water jets. The SBS represents a key technology for providing cellulose nanofibers and improving the enzymatic saccharification of cassava pulp. Depending on the enzymes used, the production of glucose from cassava pulp treated with the SBS was 1.2- to 2.5-fold higher than that from pulp not treated with the SBS. Nanofibrillated cellulose with the gel-like property in suspension was produced (yield was over 90%) by α-amylase treatment, which completely released trapped starch granules from the fibrous cell wall structure of cassava pulp pretreated with the SBS. The SBS provides an environmentally low-impact pretreatment system for processing biomass material into value-added products. PMID:23073093

  17. High-alkali low-temperature polysulfide pulping (HALT) of Scots pine.

    PubMed

    Paananen, Markus; Sixta, Herbert

    2015-10-01

    High-alkali low-temperature polysulfide pulping (HALT) was effectively utilised to prevent major polysaccharide losses while maintaining the delignification rate. A yield increase of 6.7 wt% on wood was observed for a HALT pulp compared to a conventionally produced kappa number 60 pulp with comparable viscosity. Approximately 70% of the yield increase was attributed to improved galactoglucomannan preservation and 30% to cellulose. A two-stage oxygen delignification sequence with inter-stage peroxymonosulphuric acid treatment was used to ensure delignification to a bleachable grade. In a comparison to conventional pulp, HALT pulp effectively maintained its yield advantage. Diafiltration trials indicate that purified black liquor can be directly recycled, as large lignin fractions and basically all dissolved polysaccharides were separated from the alkali-rich BL. PMID:26119050

  18. Simultaneous production of bio-ethanol and bleached pulp from red algae.

    PubMed

    Yoon, Min Ho; Lee, Yoon Woo; Lee, Chun Han; Seo, Yung Bum

    2012-12-01

    The red algae, Gelidium corneum, was used to produce bleached pulp for papermaking and ethanol. Aqueous extracts obtained at 100-140 °C were subjected to saccharification, purification, fermentation, and distillation to produce ethanol. The solid remnants were bleached with chlorine dioxide and peroxide to make pulp. In the extraction process, sulfuric acid and sodium thiosulfate were added to increase the extract yield and to improve de-polymerization of the extracts, as well as to generate high-quality pulp. An extraction process incorporating 5% sodium thiosulfate by dry weight of the algae provided optimal production conditions for the production of both strong pulp and a high ethanol yield. These results suggest that it might be possible to utilize algae instead of trees and starch for pulp and ethanol production, respectively. PMID:23073109

  19. Sufficient virus-neutralizing antibody in the central nerve system improves the survival of rabid rats

    PubMed Central

    2012-01-01

    Background Rabies is known to be lethal in human. Treatment with passive immunity for the rabies is effective only when the patients have not shown the central nerve system (CNS) signs. The blood–brain barrier (BBB) is a complex functional barrier that may compromise the therapeutic development in neurological diseases. The goal of this study is to determine the change of BBB integrity and to assess the therapeutic possibility of enhancing BBB permeability combined with passive immunity in the late stage of rabies virus infection. Methods The integrity of BBB permeability in rats was measured by quantitative ELISA for total IgG and albumin levels in the cerebrospinal fluid (CSF) and by exogenously applying Evans blue as a tracer. Western blotting of occludin and ZO-1, two tight junction proteins, was used to assess the molecular change of BBB structure. The breakdown of BBB with hypertonic arabinose, recombinant tumor necrosis factor-alpha (rTNF-γ), and focused ultrasound (FUS) were used to compare the extent of BBB disruption with rabies virus infection. Specific humoral immunity was analyzed by immunofluorescent assay and rapid fluorescent focus inhibition test. Virus-neutralizing monoclonal antibody (mAb) 8-10E was administered to rats with hypertonic breakdown of BBB as a passive immunotherapy to prevent the death from rabies. Results The BBB permeability was altered on day 7 post-infection. Increased BBB permeability induced by rabies virus infection was observed primarily in the cerebellum and spinal cord. Occludin was significantly decreased in both the cerebral cortex and cerebellum. The rabies virus-specific antibody was not strongly elicited even in the presence of clinical signs. Disruption of BBB had no direct association with the lethal outcome of rabies. Passive immunotherapy with virus-neutralizing mAb 8-10E with the hypertonic breakdown of BBB prolonged the survival of rabies virus-infected rats. Conclusions We demonstrated that the BBB

  20. Tumor eosinophil infiltration and improved survival of colorectal cancer patients: Iowa Women's Health Study.

    PubMed

    Prizment, Anna E; Vierkant, Robert A; Smyrk, Thomas C; Tillmans, Lori S; Lee, James J; Sriramarao, P; Nelson, Heather H; Lynch, Charles F; Thibodeau, Stephen N; Church, Timothy R; Cerhan, James R; Anderson, Kristin E; Limburg, Paul J

    2016-05-01

    The role of the innate immune response in colorectal cancer is understudied. We examined the survival of colorectal cancer patients in relation to eosinophils, innate immune cells, infiltrating the tumor. Tissue microarrays were constructed from paraffin-embedded tumor tissues collected between 1986 and 2002 from 441 post-menopausal women diagnosed with colorectal cancer in the Iowa Women's Health Study. Tissue microarrays were stained with an eosinophil peroxidase antibody. Eosinophils in epithelial and stromal tissues within the tumor (called epithelial and stromal eosinophils, hereafter) were counted and scored into three and four categories, respectively. In addition, the degree of eosinophil degranulation (across epithelial and stromal tissues combined) was quantified and similarly categorized. We used Cox regression to estimate the hazard ratios and 95% confidence interval for all-cause and colorectal cancer death during 5-year follow-up after diagnosis and during follow-up through 2011 ('total follow-up'). The hazard ratios associated with eosinophil scores were adjusted for age of diagnosis, SEER (Surveillance, Epidemiology, and End Results) stage, tumor grade, body mass, and smoking history. High tumor stromal eosinophil score was inversely correlated with age and stage, and was associated with a decreased risk for all-cause and colorectal cancer death: hazard ratios (95% confidence intervals) were 0.61 (0.36-1.02; P-trend=0.02) and 0.48 (0.24-0.93; P-trend=0.01), respectively, during the 5-year follow-up for the highest vs lowest category. The inverse associations also existed for total follow-up for all-cause and colorectal cancer death for the highest vs lowest stromal eosinophil score: hazard ratios (95% confidence intervals) were 0.72 (0.48-1.08; P-trend=0.04) and 0.61 (0.34-1.12; P-trend=0.04), respectively. Further adjustment for treatment, comorbidities, additional lifestyle factors, tumor location, or molecular markers did not markedly change the

  1. Assessing Community Based Improved Maternal Neonatal Child Survival (IMNCS) Program in Rural Bangladesh

    PubMed Central

    Mistry, Sabuj Kanti; Chowdhury, Tridib Roy; Ishaque, Tanveen; Shah, Rasheduzzaman

    2015-01-01

    Objectives A community based approach before, during and after child birth has been proven effective address the burden of maternal, neonatal and child morbidity and mortality in the low and middle income countries. We aimed to examine the overall change in maternal and newborn health outcomes due the “Improved Maternal Newborn and Child Survival” (IMNCS) project, which was implemented by BRAC in rural communities of Bangladesh. Methods The intervention was implemented in four districts for duration of 5-years, while two districts served as comparison areas. The intervention was delivered by community health workers who were trained on essential maternal, neonatal and child health care services. A baseline survey was conducted in 2008 among 7, 200 women with pregnancy outcome in last year or having a currently alive child of 12–59 months. A follow-up survey was administered in 2012–13 among 4, 800 women of similar characteristics in the same villages. Findings We observed significant improvements in maternal and essential newborn care in intervention areas over time, especially in health care seeking behaviors. The proportion of births taking place at home declined in the intervention districts from 84.3% at baseline to 71.2% at end line (P<0.001). Proportion of deliveries with skilled attendant was higher in intervention districts (28%) compared to comparison districts (27.4%). The number of deliveries was almost doubled at public sector facility comparing with baseline (P<0.001). Significant improvement was also observed in healthy cord care practice, delayed bathing of the new-born and reduction of infant mortality in intervention districts compared to that of comparison districts. Conclusions This study demonstrates that community-based efforts offer encouraging evidence and value for combining maternal, neonatal and child health care package. This approach might be considered at larger scale in similar settings with limited resources. PMID:26340672

  2. Survive On Call - A QI Project to Improve Access to Hospital Clinical Guidelines.

    PubMed

    Penders, Robert; Mallet, Mark

    2016-01-01

    Accessing clinical guidelines and telephone numbers can be time consuming for junior doctors, particularly during a busy on-call shift. Smartphones allow instant access to this information, without leaving a patient's bedside. This overcomes the relative paucity of fixed desktop computers available in most clinical areas. In this project, a trainee doctor developed a clinical smartphone app to improve the access of clinical and hospital-specific information. A representative sample of ten junior doctors were recruited to quantify the amount of time spent accessing guidelines using desktop computers, versus the App. The average time to access a common guideline (Hypokalaemia management) with the App was 12.4 seconds (95% CI 2.3), versus 76.8 seconds (95% CI 30.6) using a computer. A difference of 64.4 seconds (p < 0.001). The average time to access an Amiodarone prescribing guideline with the App was 25.9 seconds (95% CI 12.9), versus 142.0 seconds (95% CI 44.8) using a computer. A difference of 116.1 seconds (p < 0.001). User feedback was collected after each stage of release within the hospital. Following final release, users rated how much time they felt it saved them. 96.1% of respondents felt it either saved them time a 'few times a week' (53.85%) or 'significantly saved time every day' (42.31%). The project has significantly improved staff satisfaction with how easily they can access clinical guidelines and telephone numbers. They clearly feel it has improved their working efficiency. This has been supported by quantitative measures of actual time saved using the App. The ability to access such information in as little time as possible may be even more pertinent where decision-making is time-critical - for example in Anaesthesia and Emergency Medicine. Further study into these specialties is warranted to determine whether mobile information can impact upon patient safety and clinical outcomes. PMID:27239310

  3. Improved Vascular Survival and Growth in the Mouse Model of Hindlimb Ischemia by a Remote Signaling Mechanism

    PubMed Central

    Takeda, Kotaro; Duan, Li-Juan; Takeda, Hiromi; Fong, Guo-Hua

    2015-01-01

    Deficiencies in prolyl hydroxylase domain proteins (PHDs) may lead to the accumulation of hypoxia-inducible factor-α proteins, the latter of which activate local angiogenic responses by paracrine mechanisms. Here, we investigate whether a keratinocyte-specific PHD deficiency may promote vascular survival and growth in a distantly located ischemic tissue by a remote signaling mechanism. We generated mice that carry a keratinocyte-specific Phd2 knockout (kPhd2KO) and performed femoral artery ligation. Relative to wild-type controls, kPhd2KO mice displayed improved vascular survival and arteriogenesis in ischemic hind limbs, leading to the accelerated recovery of hindlimb perfusion and superior muscle regeneration. Similar protective effects were also seen in type 1 and type 2 diabetic mice. Molecularly, both abundance of hypoxia-inducible factor-1α protein and expression of vascular endothelial growth factor-A were increased in epidermal tissues of kPhd2KO mice, accompanied by increased plasma concentration of vascular endothelial growth factor-A. Contrary to kPhd2KO mice, which are PHD2 deficient in all skin tissues, localized kPhd2KO in hindlimb skin tissues did not have similar effects, excluding paracrine signaling as a major mechanism. Confirming the existence of remote effects, hepatocyte-specific Phd2 knockout also protected hind limbs from ischemia injury. These data indicate that vascular survival and growth in ischemia-injured tissue may be stimulated by suppressing PHD2 in a remotely located tissue and may provide highly effective angiogenesis therapies without the need for directly accessing target tissues. PMID:24440788

  4. Radiotherapy and Sorafenib in the Management of Patients with Hepatocellular Carcinoma Have Led to Improved Survival: A Single Center Experience

    PubMed Central

    Moore, Assaf; Cohen-Naftaly, Michal; Benjaminov, Ofer; Braun, Marius; Issachar, Assaf; Mor, Eitan; Tovar, Anna; Sarfaty, Michal; Gordon, Noa; Stemmer, Salomon M.

    2016-01-01

    Background & Aims: Hepatocellular Carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer mortality worldwide. We aimed to assess the effect of novel treatment options on the survival of HCC patients. Methods: This retrospective study included all HCC patients diagnosed between 2000 and 2013 referred to the Davidoff center and treated by a multidisciplinary team. Results: The analysis included 321 patients (median age, 64 years; 74.8% males; 74.1% viral carriers; 76.0% cirrhosis; 56.7% diagnosis at an early stage). The estimated hazard ratio by multivariate analysis for the effect of the period of diagnosis (2007-2013 vs. 2000-2006) on survival was 0.72 (95% CI: 0.54-0.96; p=0.027). There was no difference in the distribution by CP score, by BCLC stage at diagnosis or in the proportion of patients undergoing surgical procedures (liver transplantation or resection). In the later time frame, there was a significant decrease in the proportion of patients undergoing percutaneous treatments (14.6% vs.4.2%, p=0.004) and embolization (46.9% vs.24.6%, p=0.001), and a significant increase in radiotherapy (1.5% vs. 8.4%, p=0.009) and treatment with sorafenib (6% vs. 18.3%, p=0.002). Conclusion: Technological/pharmaceutical innovations have led to advancement in HCC treatment. Since there was no significant difference in the proportion of patients undergoing surgical procedures during the evaluated timeframe, the improved survival may stem from better management of advanced stage patients by a multidisciplinary team. PMID:27313777

  5. Extracellular Administration of BCL2 Protein Reduces Apoptosis and Improves Survival in a Murine Model of Sepsis

    PubMed Central

    Iwata, Akiko; de Claro, R. Angelo; Morgan-Stevenson, Vicki L.; Tupper, Joan C.; Schwartz, Barbara R.; Liu, Li; Zhu, Xiaodong; Jordan, Katherine C.; Winn, Robert K.; Harlan, John M.

    2011-01-01

    Background Severe sepsis and septic shock are major causes of morbidity and mortality worldwide. In experimental sepsis there is prominent apoptosis of various cell types, and genetic manipulation of death and survival pathways has been shown to modulate organ injury and survival. Methodology/Principal Findings We investigated the effect of extracellular administration of two anti-apoptotic members of the BCL2 (B-cell lymphoma 2) family of intracellular regulators of cell death in a murine model of sepsis induced by cecal ligation and puncture (CLP). We show that intraperitoneal injection of picomole range doses of recombinant human (rh) BCL2 or rhBCL2A1 protein markedly improved survival as assessed by surrogate markers of death. Treatment with rhBCL2 or rhBCL2A1 protein significantly reduced the number of apoptotic cells in the intestine and heart following CLP, and this was accompanied by increased expression of endogenous mouse BCL2 protein. Further, mice treated with rhBCL2A1 protein showed an increase in the total number of neutrophils in the peritoneum following CLP with reduced neutrophil apoptosis. Finally, although neither BCL2 nor BCL2A1 are a direct TLR2 ligand, TLR2-null mice were not protected by rhBCL2A1 protein, indicating that TLR2 signaling was required for the protective activity of extracellularly adminsitered BCL2A1 protein in vivo. Conclusions/Significance Treatment with rhBCL2A1 or rhBCL2 protein protects mice from sepsis by reducing apoptosis in multiple target tissues, demonstrating an unexpected, potent activity of extracellularly administered BCL2 BH4-domain proteins. PMID:21390214

  6. Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract

    PubMed Central

    Watson, Debbie; Sleator, Roy D; Hill, Colin; Gahan, Cormac GM

    2008-01-01

    Background The majority of commensal gastrointestinal bacteria used as probiotics are highly adapted to the specialised environment of the large bowel. However, unlike pathogenic bacteria; they are often inadequately equipped to endure the physicochemical stresses of gastrointestinal (GI) delivery in the host. Herein we outline a patho-biotechnology strategy to improve gastric delivery and host adaptation of a probiotic strain Bifidobacterium breve UCC2003 and the generally regarded as safe (GRAS) organism Lactococcus lactis NZ9000. Results In vitro bile tolerance of both strains was significantly enhanced (P < 0.001), following heterologous expression of the Listeria monocytogenes bile resistance mechanism BilE. Strains harbouring bilE were also recovered at significantly higher levels (P < 0.001), than control strains from the faeces and intestines of mice (n = 5), following oral inoculation. Furthermore, a B. breve strain expressing bilE demonstrated increased efficacy relative to the wild-type strain in reducing oral L. monocytogenes infection in mice. Conclusion Collectively the data indicates that bile tolerance can be enhanced in Bifidobacterium and Lactococcus species through rational genetic manipulation and that this can significantly improve delivery to and colonisation of the GI tract. PMID:18844989

  7. Survive On Call - A QI Project to Improve Access to Hospital Clinical Guidelines

    PubMed Central

    Penders, Robert; Mallet, Mark

    2016-01-01

    Accessing clinical guidelines and telephone numbers can be time consuming for junior doctors, particularly during a busy on-call shift. Smartphones allow instant access to this information, without leaving a patient's bedside. This overcomes the relative paucity of fixed desktop computers available in most clinical areas. In this project, a trainee doctor developed a clinical smartphone app to improve the access of clinical and hospital-specific information. A representative sample of ten junior doctors were recruited to quantify the amount of time spent accessing guidelines using desktop computers, versus the App. The average time to access a common guideline (Hypokalaemia management) with the App was 12.4 seconds (95% CI 2.3), versus 76.8 seconds (95% CI 30.6) using a computer. A difference of 64.4 seconds (p < 0.001). The average time to access an Amiodarone prescribing guideline with the App was 25.9 seconds (95% CI 12.9), versus 142.0 seconds (95% CI 44.8) using a computer. A difference of 116.1 seconds (p < 0.001). User feedback was collected after each stage of release within the hospital. Following final release, users rated how much time they felt it saved them. 96.1% of respondents felt it either saved them time a ‘few times a week’ (53.85%) or ‘significantly saved time every day’ (42.31%). The project has significantly improved staff satisfaction with how easily they can access clinical guidelines and telephone numbers. They clearly feel it has improved their working efficiency. This has been supported by quantitative measures of actual time saved using the App. The ability to access such information in as little time as possible may be even more pertinent where decision-making is time-critical - for example in Anaesthesia and Emergency Medicine. Further study into these specialties is warranted to determine whether mobile information can impact upon patient safety and clinical outcomes. PMID:27239310

  8. Preliminary analysis of the state of the art of robotics and precision engineering and evaluation of potential for improved energy utilization in the pulp, paper, and related energy-consuming processes. Final report

    SciTech Connect

    1982-01-01

    This study was undertaken to conduct a preliminary analysis of the state of the art of two technologies, robotics and precision engineering, and to evaluate their potential for improved energy utilization in the pulp, paper, and related energy consuming processes. Activity in the robotics field is growing rapidly, most activity being related to the development of smart robots rather than to systems. There is a broad base of support, both in industry and the universities, for upgrading robot machine capabilities. A large part of that support is associated with visualization and tactile sensors which facilitate assembly, placement, inspection, and tracking. Progress in this area is relatively rapid and development times are short for specifically engineered applications. The critical path in the development of robotic systems lies in the generation of reliable sensor signals. Robotic systems require a broad spectrum of sensors from which hierarchical logic systems can draw decision making information. This requirement resulted in the establishment of a program at the National Bureau of Standards which is attempting to develop a spectrum of sensor capabilities. Such sensors are applicable to robotic system automatic process control in a variety of energy-intensive industries. Precision engineering is defined as the generation or manufacture of components wherein geometry, dimension, and surface finish are controlled to within several hundred Angstroms in single point turning operations. Investigation into the state of the art of precision engineering in the United States finds that this capability exists in several national laboratories and is intended to be used exclusively for the development of weapons. There is an attempt at the present time by Lawrence Livermore Laboratory to expand its capability into industry. Several corporations are now beginning to develop equipment to support the precision engineering field.

  9. Interferon alpha 2b as maintenance therapy in low grade malignant lymphoma improves duration of remission and survival.

    PubMed

    Aviles, A; Duque, G; Talavera, A; Guzman, R

    1996-02-01

    We assessed the efficacy and toxicity of interferon alpha 2b (IFN) as maintenance therapy in patients with low grade malignant lymphoma. Between March 1986 and December 1989, 98 patients with low-grade malignant lymphoma in complete remission after conventional chemotherapy were randomly assigned to received IFN, 5.0 MU three times a week for one year, as maintenance therapy (n = 48), or to receive no treatment (control group, n = 50). In March 1994, the median duration of response had not yet been reached in the patients treated with IFN compared to 46 months in the control group. At 9-years 62% of the patients in the IFN arm remain in first complete remission compared to only 25% in the control group (p <.001). In addition, the median duration of survival has not yet been reached in either the IFN arm compared to 74 months in the control group (p <.001). Quality of life was excellent in both groups and severe side effects secondary to IFN treatment were not observed. All patients completed the planned dose of IFN. We conclude that IFN as maintenance therapy in low-grade malignant lymphoma is an excellent therapeutic option because it improves the duration of remission and survival without producing severe side effects or reducing the quality of life. PMID:8833409

  10. Deinked pulp manufacturers make a midwest market

    SciTech Connect

    White, K.M. ); Meade, K.

    1993-09-01

    Deinked pulp manufacturers, a burgeoning trend in recycling, are opening up the market for office waste paper in the Midwest. Great Lakes Pulp and Fibre, Inc., (Menominee, Michigan), a new paper group formed by industry veterans, is planning a major deinked pulp mill in Michigan's Upper Peninsula that will recycle large amounts of office waste paper. The mill will have the capacity to process nearly 275,000 tons per year (tpy)-673 tpd-of mixed office paper into 182,000 tpd of sheet-dried, deinked pulp. That pulp would be sold to nearby fine paper manufacturers that want to have recycled content without adding their own deinking.

  11. Improved Survival in Patients With Stage III-IV Head and Neck Cancer Treated With Radiotherapy as Primary Local Treatment Modality

    SciTech Connect

    Rusthoven, Kyle E.; Raben, David; Chen Changhu

    2008-10-01

    Purpose: To evaluate the overall and cause-specific survival in patients with Stage III-IVb head and neck squamous cell carcinoma treated with radiotherapy (RT) as the primary local treatment modality. Methods and Materials: The survival of patients with American Joint Committee on Cancer Stage III-IVb head and neck squamous cell carcinoma treated with primary RT was queried using the Surveillance, Epidemiology and End Results database. The effect of the year of treatment on overall and cause-specific survival was analyzed as a categorical and continuous variable. The patterns of care for these patients were also evaluated. Results: Between 1988 and 2004, 6,759 patients were identified. Survival was significantly improved in patients treated more recently. When analyzed as a continuous variable, each year was associated with a 3% and 4.1% reduction in the relative risk of overall and cause-specific mortality, respectively (p < 0.0001). Patients treated after 1998 had a 7.6% and 6.1% absolute improvement in overall and cause-specific survival, respectively, compared with patients treated before 1998 (overall survival, hazard ratio, 0.81; cause-specific survival, hazard ratio, 0.77; p < 0.0001). This benefit in survival was limited to tumors of the oral cavity, oropharynx, and hypopharynx. The use of RT increased among patients treated more recently. This shift in patterns of care was most pronounced for tumors of the larynx and hypopharynx. Conclusions: The overall and cause-specific survival of patients with Stage III-IVb head and neck squamous cell carcinoma treated with primary RT has improved with time. The improvement is consistent with that observed in a large meta-analysis of randomized patients treated with concurrent chemoradiotherapy.

  12. Alkaline pulping of some eucalypts from Sudan.

    PubMed

    Khristova, P; Kordsachia, O; Patt, R; Dafaalla, S

    2006-03-01

    Four eucalypts (Eucalyptus camaldulensis, Eucalyptus microtheca, Eucalyptus tereticornis and Eucalyptus citriodora) grown in Sudan were examined for their suitability for pulping and papermaking with different alkaline methods. Their physical, morphological and chemical characteristics are reported. The pulping trials with E. citriodora and E. tereticornis were carried out using the kraft-AQ, soda-AQ, modified AS/AQ (ASA), ASAM and kraft methods. For the other two species, only the ASAM and the kraft process were applied. ASAM pulping gave the best results in terms of yield, degree of delignification, mechanical and optical pulp properties. The best pulps, obtained in kraft and ASAM cooking of E. citriodora, were bleached to 88% ISO brightness in a totally chlorine free bleaching sequence (OQ1O/PQ2P). The bleached pulps, especially the ASAM pulp, showed good papermaking properties and would be suitable for manufacture of writing and printing grades of paper. PMID:15935655

  13. Effects of dental trauma on the pulp.

    PubMed

    Love, R M

    1997-05-01

    Infection of the root canal system following dental trauma induces pulp and periapical disease and prevents healing of previously healthy pulp. A clinical goal in treating trauma is the maintenance of pulp vitality, and clinicians should be aware of factors that influence pulp healing. The learning objective of this article is to review the factors and techniques that influence pulp vitality and examine the influence pulp has on the healing of adjacent tissues. The potential routes for bacterial infection of the root canal system are discussed, with the clinical crown as the primary portal of entry. Uncomplicated and complicated crown fractures, as well as the crown-root and root fractures, are reviewed. Complications in pulp healing include canal obliteration, disturbed root development, apexogenesis, apexification, and the various forms of resorption. PMID:9550069

  14. Miglustat improves purkinje cell survival and alters microglial phenotype in feline Niemann-Pick disease type C.

    PubMed

    Stein, Veronika M; Crooks, Alexandra; Ding, Wenge; Prociuk, Maria; O'Donnell, Patricia; Bryan, Caroline; Sikora, Tracey; Dingemanse, Jasper; Vanier, Marie T; Walkley, Steven U; Vite, Charles H

    2012-05-01

    Niemann-Pick disease type C (NPC disease) is an incurable cellular lipid-trafficking disorder characterized by neurodegeneration and intralysosomal accumulation of cholesterol and glycosphingolipids. Treatment with miglustat, a small imino sugar that reversibly inhibits glucosylceramide synthase, which is necessary for glycosphingolipid synthesis, has been shown to benefit patients with NPC disease. The mechanism(s) and extent of brain cellular changes underlying this benefit are not understood. To investigate the basis of the efficacy of miglustat, cats with disease homologous to the juvenile-onset form of human NPC disease received daily miglustat orally beginning at 3 weeks of age. The plasma half-life of miglustat was 6.6 ± 1.1 hours, with a tmax, Cmax, and area under the plasma concentration-time curve of 1.7 ± 0.6 hours, 20.3 ± 4.6 μg/mL, and 104.1 ± 16.6 μg hours/mL, respectively. Miglustat delayed the onset of neurological signs and increased the lifespan of treated cats and was associated with decreased GM2 ganglioside accumulation in the cerebellum and improved Purkinje cell survival. Ex vivo examination of microglia from the brains of treated cats revealed normalization of CD1c and class II major histocompatibility complex expression, as well as generation of reactive oxygen species. Together, these results suggest that prolonged Purkinje cell survival, reduced glycosphingolipid accumulation, and/or the modulation of microglial immunophenotype and function contribute to miglustat-induced neurological improvement in treated cats. PMID:22487861

  15. Miglustat Improves Purkinje Cell Survival and Alters Microglial Phenotype in Feline Niemann-Pick Disease Type C

    PubMed Central

    Stein, Veronika M.; Crooks, Alexandra; Ding, Wenge; Prociuk, Maria; O’Donnell, Patricia; Bryan, Caroline; Sikora, Tracey; Dingemanse, Jasper; Vanier, Marie T.; Walkley, Steven U.; Vite, Charles H.

    2012-01-01

    Niemann-Pick disease type C (NPC disease) is an incurable cellular lipid trafficking disorder characterized by neurodegeneration and intralysosomal accumulation of cholesterol and glycosphingolipids. Treatment with miglustat, a small imino sugar that reversibly inhibits glucosylceramide synthase, which is necessary for glycosphingolipid synthesis, has been shown to benefit patients with NPC disease. The mechanism(s) and extent of brain cellular changes underlying this benefit are not understood. To investigate the basis of the efficacy of miglustat, cats with disease homologous to the juvenile-onset form of human NPC disease received daily miglustat orally beginning at 3 weeks of age. The plasma half-life of miglustat was 6.6 ± 1.1 hours, with a tmax, Cmax, and area under the plasma concentration-time curve of 1.7 ± 0.6 hours, 20.3 ± 4.6 μg/ml, and 104.1 ± 16.6 μg hours/ml, respectively. Miglustat delayed the onset of neurological signs and increased the lifespan of treated cats, and was associated with decreased GM2 ganglioside accumulation in the cerebellum and improved Purkinje cell survival. Ex vivo examination of microglia from the brains of treated cats revealed normalization of CD1c and class II major histocompatibility complex expression, as well as generation of reactive oxygen species. Together, these results suggest that prolonged Purkinje cell survival, reduced glycosphingolipid accumulation, and/or the modulation of microglial immunophenotype and function contribute to miglustat-induced neurological improvement in treated cats. PMID:22487861

  16. Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation.

    PubMed

    Bachanova, Veronika; Weisdorf, Daniel J; Wang, Tao; Marsh, Steven G E; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R; Ladner, Martha; Guethlein, Lisbeth A; Parham, Peter; Miller, Jeffrey S; Cooley, Sarah A

    2016-09-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. PMID:27220262

  17. Improving survival and preventing recurrence of diffuse large B-cell lymphoma in younger patients: current strategies and future directions

    PubMed Central

    Karlin, Lionel; Coiffier, Bertrand

    2013-01-01

    Prognosis of diffuse large B-cell lymphoma (DLBCL) has considerably improved during the last decade, mainly due to the addition of rituximab to chemotherapy. However, a significant proportion of patients still experience primary refractory disease or short-term relapses, conferring poor survival. Thus, achieving first-line complete remission is of major importance, especially in young and fit patients. Current strategies are based on the age-adapted International Prognostic Index, which separates patients into three prognostic subgroups (low-risk, intermediate-risk, and high-risk). However, it is based only on clinical variables, and we have learned from daily practice that there remains a marked heterogeneity within each subgroup. Recently, biological prognostic factors have emerged, and should now be part of initial evaluation to guide treatment. Among those, so-called double-hit DLBCL with deregulation of both MYC and BCL2 genes usually follows a particularly aggressive course and should be treated more intensively. But for many other patients, the indication of high-dose therapy rather than immunochemotherapy alone remains controversial. In these cases, the interest of an early 18F fluoro-2-deoxy-d-glucose positron emission tomography evaluation-based strategy is now being assessed in ongoing clinical trials. Moreover, other strategies to improve response and survival consist in adding novel agents to standard chemotherapy. In this field, newly developed anti-CD20 monoclonal antibodies and immunomodulatory drugs could be of particular interest during induction therapy to optimize the quality of response, but also in maintenance treatment, in order to decrease the risk of relapse. Only well-conducted clinical trials will be able to resolve all these issues. Therefore, physicians should be encouraged, as far as possible, to propose them to their patients. PMID:23579927

  18. Epidermal growth factor improves survival and prevents intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia

    PubMed Central

    Dominguez, Jessica A.; Vithayathil, Paul J.; Khailova, Ludmila; Lawrance, Christopher P.; Samocha, Alexandr J.; Jung, Enjae; Leathersich, Ann M.; Dunne, W. Michael; Coopersmith, Craig M.

    2011-01-01

    Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either Pseudomonas aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 hours after the onset of pneumonia. Systemic EGF decreased seven-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 hours after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines, kidney and liver function were unaffected by EGF therapy although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments were done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF mice) which were compared to WT mice subjected to pneumonia. IFABP-EGF mice had improved survival compared to WT mice following pneumonia (50% vs. 28% respectively, p<0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine. PMID:21701422

  19. Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia.

    PubMed

    Dominguez, Jessica A; Vithayathil, Paul J; Khailova, Ludmila; Lawrance, Christopher P; Samocha, Alexandr J; Jung, Enjae; Leathersich, Ann M; Dunne, W Michael; Coopersmith, Craig M

    2011-10-01

    Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine. PMID:21701422

  20. Effect of organosolv and soda pulping processes on the metals content of non-woody pulps.

    PubMed

    González, M; Cantón, L; Rodríguez, A; Labidi, J

    2008-09-01

    In this work the effect of different pulping processes (ethyleneglycol, diethyleneglycol, ethanolamine and soda) of tow abounded raw materials (empty fruit bunches - EFB and rice straw) on the ash, silicates and metals (Fe, Zn, Cu, Pb, Mn, Ni and Cd) content of the obtained pulps have been studied. Results showed that pulps obtained by diethyleneglycol pulping process presented lower metals content (756 microg/g and 501 microg/g for EFB and rice straw pulp, respectively) than soda pulps (984 microg/g and 889 microg/g). Ethanolamine pulps presented values of holocellulose (74% and 77% for EFB and rice straw pulp, respectively), alpha-cellulose (74% and 69%), kappa number (18.7 and 18.5) and viscosity (612 and 90 6ml/g) similar to those of soda pulp, and lower lignin contents (11% and 12%). PMID:18226892

  1. Pulp reaction to vital bleaching.

    PubMed

    Fugaro, Jessica O; Nordahl, Inger; Fugaro, Orlando J; Matis, Bruce A; Mjör, Ivar A

    2004-01-01

    This study evaluated the histological changes in dental pulp after nightguard vital bleaching with 10% carbamide peroxide gel. Fifteen patients between 12 and 26 years of age with caries-free first premolars scheduled for orthodontic extraction were treated with 10% Opalescence (Ultradent Products, Inc). Tooth #5 had four days of bleaching, tooth #12 was treated for two weeks, tooth #21 was bleached for two weeks followed by two weeks without treatment and tooth #28, serving as the control, was without treatment. All teeth were extracted at the same time. Immediately after extraction, 4 mm of the most apical portion of the root was sectioned off and each specimen was placed in a vial containing 10% neutral buffered formalin. The samples were prepared for histological evaluation at the Scandinavian Institute of Dental Materials (NIOM) and microscopically examined independently at both NIOM and Indiana University School of Dentistry (IUSD). Pulp reactions were semi-quantitatively graded as none, slight, moderate and severe. Slight pulpal changes were detected in 16 of the 45 bleached teeth. Neither moderate nor severe reactions were observed. The findings indicate that the slight histological changes sometimes observed after bleaching tend to resolve within two weeks post-treatment. Statistical differences existed only between the untreated control and the four-day (p=0.0109) and two-week (p=0.0045) treatment groups. The findings from this study demonstrated that nightguard vital bleaching procedures using 10% carbamide peroxide might cause initial mild, localized pulp reactions. However, the minor histological changes observed did not affect the overall health of the pulp tissue and were reversible within two weeks post-treatment. Therefore, two weeks of treatment with 10% carbamide peroxide used for nightguard vital bleaching is considered safe for dental pulp. PMID:15279473

  2. Unexpected Ecological Resilience in Bornean Orangutans and Implications for Pulp and Paper Plantation Management

    PubMed Central

    Meijaard, Erik; Albar, Guillaume; Nardiyono; Rayadin, Yaya; Ancrenaz, Marc; Spehar, Stephanie

    2010-01-01

    Ecological studies of orangutans have almost exclusively focused on populations living in primary or selectively logged rainforest. The response of orangutans to severe habitat degradation remains therefore poorly understood. Most experts assume that viable populations cannot survive outside undisturbed or slightly disturbed forests. This is a concern because nearly 75% of all orangutans live outside protected areas, where degradation of natural forests is likely to occur, or where these are replaced by planted forests. To improve our understanding of orangutan survival in highly altered forest habitats, we conducted population density surveys in two pulp and paper plantation concessions in East Kalimantan, Indonesia. These plantations consist of areas planted with fast-growing exotics intermixed with stands of highly degraded forests and scrublands. Our rapid surveys indicate unexpectedly high orangutan densities in plantation landscapes dominated by Acacia spp., although it remains unclear whether such landscapes can maintain long-term viable populations. These findings indicate the need to better understand how plantation-dominated landscapes can potentially be incorporated into orangutan conservation planning. Although we emphasize that plantations have less value for overall biodiversity conservation than natural forests, they could potentially boost the chances of orangutan survival. Our findings are based on a relatively short study and various methodological issues need to be addressed, but they suggest that orangutans may be more ecologically flexible than previously thought. PMID:20877646

  3. Treatment of recycled kraft pulps with Trichoderma reesei hemicellulases and cellulases.

    PubMed

    Oksanen, T; Pere, J; Paavilainen, L; Buchert, J; Viikari, L

    2000-02-28

    Effects of recycling ECF-bleached softwood kraft pulp on pulp properties were evaluated in the laboratory. The tensile strength, fiber flexibility and WRV lost during drying of the pulp were recovered by refining between the cycles which, however, resulted in deteriorated drainage properties. The recycled pulps were treated with purified Trichoderma reesei cellulases and hemicellulases and the changes in fiber properties due to enzymatic treatments were characterized. The endoglucanases (EG I and EG II) significantly improved pulp drainage already at low dosage levels, and EG II was found to be more effective at a given level of carbohydrate solubilization. Combining hemicellulases with the endoglucanase treatments increased the positive effects of the endoglucanases on pulp drainage. However, as a result of the endoglucanase treatments a slight loss in strength was observed. Combining mannanase with endoglucanase treatments appeared to increase this negative effect, whereas the impact of xylanase was not significant. Although the drainage properties of the pulps could be improved by selected enzymes, the water retention capacity of the dried hornified fibers could not be recovered by any of the enzymes tested. PMID:10702909

  4. Improved Survival for Children and Adolescents With Acute Lymphoblastic Leukemia Between 1990 and 2005: A Report From the Children's Oncology Group

    PubMed Central

    Hunger, Stephen P.; Lu, Xiaomin; Devidas, Meenakshi; Camitta, Bruce M.; Gaynon, Paul S.; Winick, Naomi J.; Reaman, Gregory H.; Carroll, William L.

    2012-01-01

    Purpose To examine population-based improvements in survival and the impact of clinical covariates on outcome among children and adolescents with acute lymphoblastic leukemia (ALL) enrolled onto Children's Oncology Group (COG) clinical trials between 1990 and 2005. Patients and Methods In total, 21,626 persons age 0 to 22 years were enrolled onto COG ALL clinical trials from 1990 to 2005, representing 55.8% of ALL cases estimated to occur among US persons younger than age 20 years during this period. This period was divided into three eras (1990-1994, 1995-1999, and 2000-2005) that included similar patient numbers to examine changes in 5- and 10-year survival over time and the relationship of those changes in survival to clinical covariates, with additional analyses of cause of death. Results Five-year survival rates increased from 83.7% in 1990-1994 to 90.4% in 2000-2005 (P < .001). Survival improved significantly in all subgroups (except for infants age ≤ 1 year), including males and females; those age 1 to 9 years, 10+ years, or 15+ years; in whites, blacks, and other races; in Hispanics, non-Hispanics, and patients of unknown ethnicity; in those with B-cell or T-cell immunophenotype; and in those with National Cancer Institute (NCI) standard- or high-risk clinical features. Survival rates for infants changed little, but death following relapse/disease progression decreased and death related to toxicity increased. Conclusion This study documents ongoing survival improvements for children and adolescents with ALL. Thirty-six percent of deaths occurred among children with NCI standard-risk features emphasizing that efforts to further improve survival must be directed at both high-risk subsets and at those children predicted to have an excellent chance for cure. PMID:22412151

  5. Does Thermosensitive Liposomal Vinorelbine Improve End-Point Survival after Percutaneous Radiofrequency Ablation of Liver Tumors in a Mouse Model?

    PubMed

    Wang, Song; Mei, Xing-Guo; Goldberg, S Nahum; Ahmed, Muneeb; Lee, Jung-Chieh; Gong, Wei; Han, Hai-Bo; Yan, Kun; Yang, Wei

    2016-06-01

    -12-mm) tumors. No significant difference in end-point survival was noted in the treatment arms with large or small tumors. Conclusion Thermo-Vin can effectively increase tumor destruction and improve animal survival. End-point survival is most affected in animals with medium-sized tumors, suggesting that combination therapy should be tailored to tumor size and the expected volume of ablation of the device used. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:26785043

  6. Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis

    PubMed Central

    Sindac, Janice; Yestrepsky, Bryan D.; Barraza, Scott J.; Bolduc, Kyle L.; Blakely, Pennelope K.; Keep, Richard F.; Irani, David N.; Miller, David J.; Larsen, Scott D.

    2012-01-01

    Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoxicity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analog 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses. PMID:22428985

  7. Neonatal transfer of membrane-bound stem cell factor improves survival and heart function in aged mice after myocardial ischemia.

    PubMed

    Sun, Zhuo; Lee, Chyan-Jang; Mejia-Guerrero, Salvador; Zhang, Yuemei; Higuchi, Koji; Li, Ren-Ke; Medin, Jeffrey A

    2012-12-01

    Stem cell mobilization to injured tissue contributes to neovascularization, resulting in regeneration after myocardial infarction (MI). We previously showed that direct cardiac injection of a recombinant lentivirus (LV) that engineers expression of membrane-bound stem cell factor (mSCF) improves outcomes immediately after MI. In this study, we evaluated the effect of neonatal LV/mSCF transduction on MI outcomes in aged mice. We constructed a recombinant LV harboring an α-myosin heavy chain promoter that drives mSCF expression and injected it into the temporal vein of neonatal mice. One year later, sustained expression of mSCF in the adult mouse hearts was detected by genomic and quantitative RT-PCR and immunohistochemistry. To evaluate the contribution of neonatal LV/mSCF delivery to recovery from MI, we induced an MI in adult LV/mSCF-transduced, LV only-transduced, and nontransduced control mice. Strikingly, LV/mSCF transduction reduced infarct scar size, enhanced angiogenesis, improved ventricular function, and significantly increased survival of the mice. Regional overexpression of CD11b, a marker of monocytes and proangiogenic cells, was observed on monocytes isolated from the infarcted hearts of LV/mSCF-transduced mice. Our data suggest a model of neonatal gene delivery that leads to sustained mSCF expression during adulthood to aid recovery from MI and prevent heart failure. PMID:22998370

  8. Epoetin alfa improves survival after chemoradiation for Stage III esophageal cancer: Final results of a prospective observational study

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Tribius, Silke; Yekebas, Emre F.; Bahrehmand, Roia; Wildfang, Ingeborg; Kilic, Ergin; Muellerleile, Ulrich; Gross, Eberhard; Schild, Steven E.; Alberti, Winfried

    2006-06-01

    Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

  9. Improving survival and storage stability of bacteria recalcitrant to freeze-drying: a coordinated study by European culture collections.

    PubMed

    Peiren, Jindrich; Buyse, Joke; De Vos, Paul; Lang, Elke; Clermont, Dominique; Hamon, Sylviane; Bégaud, Evelyne; Bizet, Chantal; Pascual, Javier; Ruvira, María A; Macián, M Carmen; Arahal, David R

    2015-04-01

    The objective of this study is to improve the viability after freeze-drying and during storage of delicate or recalcitrant strains safeguarded at biological resource centers. To achieve this objective, a joint experimental strategy was established among the different involved partner collections of the EMbaRC project ( www.embarc.eu ). Five bacterial strains considered as recalcitrant to freeze-drying were subjected to a standardized freeze-drying protocol and to seven agreed protocol variants. Viability of these strains was determined before and after freeze-drying (within 1 week, after 6 and 12 months, and after accelerated storage) for each of the protocols. Furthermore, strains were exchanged between partners to perform experiments with different freeze-dryer-dependent parameters. Of all tested variables, choice of the lyoprotectant had the biggest impact on viability after freeze-drying and during storage. For nearly all tested strains, skim milk as lyoprotectant resulted in lowest viability after freeze-drying and storage. On the other hand, best freeze-drying and storage conditions were strain and device dependent. For Aeromonas salmonicida CECT 894(T), best survival was obtained when horse serum supplemented with trehalose was used as lyoprotectant, while Aliivibrio fischeri LMG 4414(T) should be freeze-dried in skim milk supplemented with marine broth in a 1:1 ratio. Freeze-drying Campylobacter fetus CIP 53.96(T) using skim milk supplemented with trehalose as lyoprotectant resulted in best recovery. Xanthomonas fragariae DSM 3587(T) expressed high viability after freeze-drying and storage for all tested lyoprotectants and could not be considered as recalcitrant. In contrary, Flavobacterium columnare LMG 10406(T) did not survive the freeze-drying process under all tested conditions. PMID:25773973

  10. Improving survival and growth of planted Austrocedrus chilensis seedlings in disturbed patagonian forests of Argentina by managing understory vegetation.

    PubMed

    Pafundi, Leticia; Urretavizcaya, M Florencia; Defossé, Guillermo E

    2014-12-01

    This study was aimed at determining, under field conditions, early interactions between planted cypress seedlings and their associated shrubs in a mesic area of Andean Patagonia and, in a nursery, the effects of increasing light availability on cypress performance when soil water was not a limiting factor. The field experiment was performed in a former cypress-coihue mixed forest (42°02'S, 71°33'W), which was replaced in the 1970s by a plantation of radiata pine. In 2005, 800 cypress seedlings were planted under maqui shrubs in a clear-cut area of the pine stand. In 2007, two treatments were set: no-competition treatment ([NCT] i.e., the surrounding aboveground biomass was removed) and competition treatment ([CT] i.e., without disturbance). The nursery experiment (42°55'S, 71°21'W) consisted of two groups: "shade" (grown under shade cloth) and "sun" (grown at full sun) cypress seedlings. After one growing season, seedling survival and stem growth (in height and diameter) were determined at both sites. Furthermore, the growth rate of leaves, stems, and roots was determined in the nursery. In the field experiment, height growth and survival in NCT were significantly greater than in CT, and a competition process occurred between cypress and surrounding shrubs. In the nursery, sun plants grew more in diameter and increased root weight more than shade plants. Results also showed that in mesic areas of Patagonia, decreasing competition and increasing light levels produced stouter seedlings better adapted to support harsh environmental conditions. Therefore, the removal of protecting shrubs could be a good management practice to improve seedling establishment. PMID:25216990

  11. Adjusting for treatment switching in the METRIC study shows further improved overall survival with trametinib compared with chemotherapy.

    PubMed

    Latimer, Nicholas R; Bell, Helen; Abrams, Keith R; Amonkar, Mayur M; Casey, Michelle

    2016-05-01

    Trametinib, a selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK1) and MEK2, significantly improves progression-free survival compared with chemotherapy in patients with BRAF V600E/K mutation-positive advanced or metastatic melanoma (MM). However, the pivotal clinical trial permitted randomized chemotherapy control group patients to switch to trametinib after disease progression, which confounded estimates of the overall survival (OS) advantage of trametinib. Our purpose was to estimate the switching-adjusted treatment effect of trametinib for OS and assess the suitability of each adjustment method in the primary efficacy population. Of the patients randomized to chemotherapy, 67.4% switched to trametinib. We applied the rank-preserving structural failure time model, inverse probability of censoring weights, and a two-stage accelerated failure time model to obtain estimates of the relative treatment effect adjusted for switching. The intent-to-treat (ITT) analysis estimated a 28% reduction in the hazard of death with trametinib treatment (hazard ratio [HR], 0.72; 95% CI, 0.52-0.98) for patients in the primary efficacy population (data cut May 20, 2013). Adjustment analyses deemed plausible provided OS HR point estimates ranging from 0.48 to 0.53. Similar reductions in the HR were estimated for the first-line metastatic subgroup. Treatment with trametinib, compared with chemotherapy, significantly reduced the risk of death and risk of disease progression in patients with BRAF V600E/K mutation-positive advanced melanoma or MM. Adjusting for switching resulted in lower HRs than those obtained from standard ITT analyses. However, CI are wide and results are sensitive to the assumptions associated with each adjustment method. PMID:27172483

  12. Improving Survival and Growth of Planted Austrocedrus chilensis Seedlings in Disturbed Patagonian Forests of Argentina by Managing Understory Vegetation

    NASA Astrophysics Data System (ADS)

    Pafundi, Leticia; Urretavizcaya, M. Florencia; Defossé, Guillermo E.

    2014-12-01

    This study was aimed at determining, under field conditions, early interactions between planted cypress seedlings and their associated shrubs in a mesic area of Andean Patagonia and, in a nursery, the effects of increasing light availability on cypress performance when soil water was not a limiting factor. The field experiment was performed in a former cypress-coihue mixed forest (42°02'S, 71°33'W), which was replaced in the 1970s by a plantation of radiata pine. In 2005, 800 cypress seedlings were planted under maqui shrubs in a clear-cut area of the pine stand. In 2007, two treatments were set: no-competition treatment ([NCT] i.e., the surrounding aboveground biomass was removed) and competition treatment ([CT] i.e., without disturbance). The nursery experiment (42°55'S, 71°21'W) consisted of two groups: "shade" (grown under shade cloth) and "sun" (grown at full sun) cypress seedlings. After one growing season, seedling survival and stem growth (in height and diameter) were determined at both sites. Furthermore, the growth rate of leaves, stems, and roots was determined in the nursery. In the field experiment, height growth and survival in NCT were significantly greater than in CT, and a competition process occurred between cypress and surrounding shrubs. In the nursery, sun plants grew more in diameter and increased root weight more than shade plants. Results also showed that in mesic areas of Patagonia, decreasing competition and increasing light levels produced stouter seedlings better adapted to support harsh environmental conditions. Therefore, the removal of protecting shrubs could be a good management practice to improve seedling establishment.

  13. Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle

    PubMed Central

    Suhara, Tomohiro; Hishiki, Takako; Kasahara, Masataka; Hayakawa, Noriyo; Oyaizu, Tomoko; Nakanishi, Tsuyoshi; Kubo, Akiko; Morisaki, Hiroshi; Kaelin, William G.; Suematsu, Makoto; Minamishima, Yoji Andrew

    2015-01-01

    Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyperlacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori cycle, a lactate–glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo 13C-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from 13C-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients. PMID:26324945

  14. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    PubMed Central

    Clarke†, Jennifer L.; Ennis†, Michele M.; Yung, W. K. Alfred; Chang, Susan M.; Wen, Patrick Y.; Cloughesy, Timothy F.; DeAngelis, Lisa M.; Robins, H. Ian; Lieberman, Frank S.; Fine, Howard A.; Abrey, Lauren; Gilbert, Mark R.; Mehta, Minesh; Kuhn, John G.; Aldape, Kenneth D.; Lamborn, Kathleen R.; Prados, Michael D.

    2011-01-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998–2005, 105 of whom had surgery (excluding biopsies) during the study or ≤30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005–2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment. PMID:21813511

  15. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    PubMed

    Clarke, Jennifer L; Ennis, Michele M; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; Deangelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Lamborn, Kathleen R; Prados, Michael D

    2011-10-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998-2005, 105 of whom had surgery (excluding biopsies) during the study or ≤ 30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005-2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment. PMID:21813511

  16. Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

    SciTech Connect

    Adachi, Naoki; Kubota, Yoshitaka; Kosaka, Kentarou; Akita, Shinsuke; Sasahara, Yoshitarou; Kira, Tomoe; Kuroda, Masayuki; Mitsukawa, Nobuyuki; Bujo, Hideaki; Satoh, Kaneshige

    2015-08-07

    Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDR may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings.

  17. [Functional morphology of pulp tissue].

    PubMed

    Heine, H; Schaeg, G; Türk, R

    1989-01-01

    As compared with mesenchyme no genuine defense cells are developed in the tissue of the dental pulp and the nervous tissue. This is a further hint for the common development from ectoderm. The three dimensional meshwork of pulpa fibroblasts ("mesectoderm") is structured by elongated cell processes connected with each other by a variety of special cell junctions ("electronic cell coupling"). Metabolites from the microcirculation and neuropeptides from vegetative axons influence the activity of fibroblasts synthetizing groundsubstance. The meshwork of the groundsubstance has exclusion effects concerning molecules with a distinct molecular weight and charge. Thus a primitive defense system is established. With this the role of a newly described cell type of the dental pulp, the "lymphocytic pericyte" is discussed. Because of the poor capacity of the pulpa tissue for immunological reactions pathologically disorders may easily become chronically spreading their antigenic components throughout the body. PMID:2800671

  18. Intrathecal enzyme replacement therapy improves motor function and survival in a preclinical mouse model of infantile neuronal ceroid lipofuscinosis.

    PubMed

    Lu, Jui-Yun; Nelvagal, Hemanth R; Wang, Lingling; Birnbaum, Shari G; Cooper, Jonathan D; Hofmann, Sandra L

    2015-01-01

    The neuronal ceroid lipofuscinoses (NCLs) are a group of related hereditary lysosomal storage disorders characterized by progressive loss of neurons in the central nervous system resulting in dementia, loss of motor skills, seizures and blindness. A characteristic intralysosomal accumulation of autofluorescent storage material occurs in the brain and other tissues. Three major forms and nearly a dozen minor forms of NCL are recognized. Infantile-onset NCL (CLN1 disease) is caused by severe deficiency in a soluble lysosomal enzyme, palmitoyl-protein thioesterase-1 (PPT1) and no therapy beyond supportive care is available. Homozygous Ppt1 knockout mice reproduce the known features of the disease, developing signs of motor dysfunction at 5 months of age and death around 8 months. Direct delivery of lysosomal enzymes to the cerebrospinal fluid is an approach that has gained traction in small and large animal models of several other neuropathic lysosomal storage diseases, and has advanced to clinical trials. In the current study, Ppt1 knockout mice were treated with purified recombinant human PPT1 enzyme delivered to the lumbar intrathecal space on each of three consecutive days at 6 weeks of age. Untreated PPT1 knockout mice and wild-type mice served as additional controls. Four enzyme concentration levels (0, 2.6, 5.3 and 10.6 mg/ml of specific activity 20 U/mg) were administered in a volume of 80 μl infused over 8 min. Each group consisted of 16-20 mice. The treatment was well tolerated. Disease-specific survival was 233, 267, 272, and 284days for each of the four treatment groups, respectively, and the effect of treatment was highly significant (p<0.0001). The timing of motor deterioration was also delayed. Neuropathology was improved as evidenced by decreased autofluorescent storage material in the spinal cord and a decrease in CD68 staining in the cortex and spinal cord. The improvements in motor function and survival are similar to results reported for

  19. Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia.

    PubMed

    Krug, U; Berdel, W E; Gale, R P; Haferlach, C; Schnittger, S; Müller-Tidow, C; Braess, J; Spiekermann, K; Staib, P; Beelen, D; Serve, H; Schliemann, C; Stelljes, M; Balleisen, L; Maschmeyer, G; Grüneisen, A; Eimermacher, H; Giagounidis, A; Rasche, H; Hehlmann, R; Lengfelder, E; Thiel, E; Reichle, A; Aul, C; Ludwig, W-D; Kern, W; Haferlach, T; Köpcke, W; Görlich, D; Sauerland, M C; Heinecke, A; Wörmann, B J; Hiddemann, W; Büchner, T

    2016-06-01

    We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects ⩾60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts ⩾5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P=0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P=0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P=0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes. PMID:26859081

  20. Palliative photodynamic therapy for biliary tract carcinoma may improve survival and has a similar outcome to attempted curative surgery with positive resection margins

    NASA Astrophysics Data System (ADS)

    Pereira, Stephen P.; Matull, W. Rudiger; Dhar, Dipok K.; Ayaru, Laskshmana; Sandanayake, Neomal S.; Chapman, Michael H.

    2009-06-01

    There is a need for better management strategies to improve survival and quality of life in patients with biliary tract cancer (BTC). We compared treatment outcomes in 321 patients (median age 65 years, range 29-102; F:M; 1:1) with a final diagnosis of BTC (cholangiocarcinoma n=237, gallbladder cancer n=84) seen in a tertiary referral cancer centre between 1998-2007. Of 89 (28%) patients who underwent surgical intervention with curative intent, 38% had R0 resections and had the most favourable outcome, with a 3 year survival of 57%. Even though PDT patients had more advanced clinical T-stages, their survival was similar to those treated with attempted curative surgery which resulted in R1/2 resections (median survival 12 vs. 13 months, ns). In a subgroup of 36 patients with locally advanced BTC treated with PDT as part of a prospective phase II study, the median survival was 12 (range 2-51) months, compared with 5 months in matched historical controls treated with stenting alone (p < 0.0001). In this large UK series, long-term survival with BTC was only achieved in surgical patients with R0 resection margins. Palliative PDT resulted in similar survival to those with curatively intended R1/R2 resections.

  1. Pulp blood flow assessment in human teeth by laser Doppler flowmetry

    NASA Astrophysics Data System (ADS)

    Pettersson, Hans; Oberg, P. Ake

    1991-05-01

    A laser Doppler instrument has been designed for blood flow measurements in the human pulp. By using infrared laser light from a laser diode the penetration into the tooth is considerably improved in comparison with earlier He-Ne measurements. A hand-held, pen-shaped probe facilitates the clinical use of the instrument. Restricted blood flow conditions in trauma patients, as well as the heart-rate synchronous pulsating nature of pulp blood in normal subjects, have been investigated.

  2. Reversible Disassembly of the Actin Cytoskeleton Improves the Survival Rate and Developmental Competence of Cryopreserved Mouse Oocytes

    PubMed Central

    Hosu, Basarab G.; Mullen, Steven F.; Critser, John K.; Forgacs, Gabor

    2008-01-01

    Effective cryopreservation of oocytes is critically needed in many areas of human reproductive medicine and basic science, such as stem cell research. Currently, oocyte cryopreservation has a low success rate. The goal of this study was to understand the mechanisms associated with oocyte cryopreservation through biophysical means using a mouse model. Specifically, we experimentally investigated the biomechanical properties of the ooplasm prior and after cryopreservation as well as the consequences of reversible dismantling of the F-actin network in mouse oocytes prior to freezing. The study was complemented with the evaluation of post-thaw developmental competence of oocytes after in vitro fertilization. Our results show that the freezing-thawing process markedly alters the physiological viscoelastic properties of the actin cytoskeleton. The reversible depolymerization of the F-actin network prior to freezing preserves normal ooplasm viscoelastic properties, results in high post-thaw survival and significantly improves developmental competence. These findings provide new information on the biophysical characteristics of mammalian oocytes, identify a pathophysiological mechanism underlying cryodamage and suggest a novel cryopreservation method. PMID:18665248

  3. Transgenic mouse milk expressing human bile salt-stimulated lipase improves the survival and growth status of premature mice.

    PubMed

    Wang, Yuanyuan; Sheng, Zheya; Wang, Yuhang; Li, Qinghe; Gao, Yu; Wang, Yuhui; Dai, Yunping; Liu, George; Zhao, Yaofeng; Li, Ning

    2015-03-01

    The lactating human mammary gland and the pancreas both produce bile salt-stimulated lipase (BSSL), a lipolytic enzyme acting on a wide range of substrates, including triglyceride, cholesterol esters, and fat-soluble vitamins esters. Breast milk BSSL has a particularly important role in the digestion of milk fat by newborn infants. We report the generation of transgenic mice that harbored a human BSSL gene controlled by a mammary gland-specific promoter. BSSL levels in transgenic mouse milk were raised to 376.8 μg/ml, corresponding to an activity of 9.15 U/ml. Premature wild-type neonates nursed by transgenic dams exhibited significantly higher survival rate than did the control neonates nursed by wild dams (95 vs. 83.3 % and, P < 0.05). They also showed 43.8 % greater body weight gain and 33.3 % lesser fecal crude fat levels than did the controls. This study provides significant evidence that increased levels of BSSL in milk may reduce mortality and improve the growth and fat absorption in premature mice during neonatal development. PMID:25385005

  4. Resveratrol Ameliorates Motor Neuron Degeneration and Improves Survival in SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Song, Lin; Zhang, Xiaojie; Li, Jia; Le, Weidong

    2014-01-01

    Resveratrol has recently been used as a supplemental treatment for several neurological and nonneurological diseases. It is not known whether resveratrol has neuroprotective effect on amyotrophic lateral sclerosis (ALS). To assess the effect of resveratrol on the disease, we tested this agent on an ALS model of SOD1G93A transgenic mouse. Rotarod measurement was performed to measure the motor function of the ALS mice. Nissl staining and SMI-32 immunofluorescent staining were used to determine motor neurons survival in the spinal cord of the ALS mice. Hematoxylin-eosin (H&E), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) staining were applied to pathologically analyze the skeletal muscles of the ALS mice. We found that resveratrol treatment significantly delayed the disease onset and prolonged the lifespan of the ALS mice. Furthermore, resveratrol treatment attenuated motor neuron loss, relieved muscle atrophy, and improved mitochondrial function of muscle fibers in the ALS mice. In addition, we demonstrated that resveratrol exerted these neuroprotective effects mainly through increasing the expression of Sirt1, consequently suppressing oxidative stress and downregulating p53 and its related apoptotic pathway. Collectively, our findings suggest that resveratrol might provide a promising therapeutic intervention for ALS. PMID:25057490

  5. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes.

    PubMed

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-02-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system. PMID:26768767

  6. Low-concentration methylene blue maintains energy production and strongly improves survival of Leigh syndrome French Canadian skin fibroblasts.

    PubMed

    Legault, Jean; Larouche, Pierre-Luc; Côté, Isabelle; Bouchard, Line; Pichette, André; Robinson, Brian H; Morin, Charles

    2011-01-01

    Leigh syndrome French Canadian (LSFC) is a recessive disease caused by mutations in the LRPPRC gene (leucine-rich pentatricopeptide repeat containing protein). These mutations induce a cytochrome c oxidase (COX) deficiency resulting in episodes of acute acidotic crisis that will often lead to death. There is no effective treatment. Methylene blue (MB) is a redox dye that increases COX content and activity in vitro and in vivo suggesting that MB could prevent and treat LSFC. In this study, the protective effect of low-concentration MB was tested on two LSFC cell lines, including LSFC-F1, homozygous for the mutation A354V, and LSFC-F2 a compound heterozygous for the mutations A354V and C12775STOP. MB effect on metabolic activity was assessed on both LSFC cells in stable and acidotic conditions. For LSFC-F1, results showed that metabolic activity drastically decline after 96 hours in both conditions but not LSFC-F2 and normal cells. MB completely prevents the decrease of metabolic activity in LSFC-F1. Intracellular ATP content was also measured in both culture media. After 96 hours in acidotic medium, ATP content was almost completely depleted for both LSFC cells. Interestingly, MB completely restores ATP content in LSFC-F1 and LSFC-F2 cells. Finally, MB strongly improves the survival of both LSFC cells. PMID:22202226

  7. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes

    PubMed Central

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-01-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system. PMID:26768767

  8. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die based upon high IL-6 levels

    PubMed Central

    Vyas, Dinesh; Javadi, Pardis; DiPasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-01-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 hours following cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 hours after the septic insult. The first aim of this study was to see if earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die based upon high IL-6 levels. Mice (n=184) were subjected to CLP, had IL-6 levels drawn six hours later and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning six or twelve hours post-operatively. Overall one-week survival improved from 25.5% to 35.9% with earlier administration of antibiotics (p<0.05). In mice with IL-6 levels >14,000 pg/ml, 25% survived if imipenem was started at 6 hours, while none survived if antibiotics were started later (p<0.05). Based upon these results, we examined whether targeted antibody therapy could improve survival in mice with elevated IL-6 levels. A different cohort of mice (n=54) had their blood drawn six hours after CLP and then were randomized to receive either monoclonal anti-IL-6 IgG or irrelevant rat IgG. Anti-IL-6 antibody failed to improve either overall survival or outcome in mice with IL-6 levels >14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. PMID:15947070

  9. Xylanase and laccase based enzymatic kraft pulp bleaching reduces adsorbable organic halogen (AOX) in bleach effluents: a pilot scale study.

    PubMed

    Sharma, Abha; Thakur, Vasanta Vadde; Shrivastava, Anita; Jain, Rakesh Kumar; Mathur, Rajeev Mohan; Gupta, Rishi; Kuhad, Ramesh Chander

    2014-10-01

    In present study, xylanase and laccase were produced in a cost-effective manner up to 10 kg substrate level and evaluated in elemental chlorine free bleaching of Eucalyptus kraft pulp. Compared to the pulp pre-bleached with xylanase (15%) or laccase (25%) individually, the ClO2 savings were higher with sequential treatment of xylanase followed by laccase (35%) at laboratory scale. The sequential enzyme treatment when applied at pilot scale (50 kg pulp), resulted in improved pulp properties (50% reduced post color number, 15.71% increased tear index) and reduced AOX levels (34%) in bleach effluents. The decreased AOX level in effluents will help to meet AOX discharge limits, while improved pulp properties will be value addition to the paper. PMID:25036336

  10. TIGER -- A technology to improve the delivery capability of nuclear bombs and the survivability of the delivery aircraft

    SciTech Connect

    1980-12-31

    The TIGER (Terminal guided and Extended-Range) Program was initiated in 1972 to study improved delivery capabilities for stockpiled tactical nuclear bombs. The Southeast Asia conflict fostered the development of air-delivered standoff conventional weapons utilizing terminal guidance systems. SNL initiated the TIGER program to determine if current nuclear bombs could be provided with a similarly accurate standoff capabilities. These conventional weapon delivery techniques, while allowing highly accurate attack, generally require entering the target area at high altitude to establish line of sight to the target. In parallel with the TIGER program, system studies analyzed this concept and showed marked improvement in aircraft and weapon survivability with moderate standoff (10--20 km) if low level deliveries (60 m) could be accomplished. As a result of this work, the TIGER program was redirected in early 1974 to demonstrate a standoff bomb with good accuracy (90 m CEP) when delivered from low flying aircraft. This program redirection resulted in the selection of an inertial guidance system to replace the earlier terminal guidance systems. This program was called the Extended-Range Bomb (ERB). In May 1974, a joint Air Force/DOE study identified the desirability of having a single tactical weapon which could be employed against either fixed, preselected targets, or mobile battlefield targets. Studies conducted on the ERB system showed that the inertially guided weapon could fly not only the standoff mission but also a return-to-target mission against the mobile battlefield targets whose locations are not known accurately enough to use a standoff delivery. The ERB program evolved from these initial investigations into an exploratory program to develop the hardware and demonstrate the technology required to fly standoff and return-to-target trajectories. The application of this technology in the form of field retrofit kits to the B61 bomb is called TIGER II.

  11. Enhancing fermentable sugar yield from cassava pulp for bioethanol production: microwave-coupled enzymatic hydrolysis approach.

    PubMed

    Sudha, A; Sivakumar, V; Sangeetha, V; Devi, K S Priyenka

    2015-08-01

    Cassava pulp, a potential biological feedstock for ethanol production has been subjected to microwave-assisted alkali pretreatment and microwave-coupled enzymatic hydrolysis. Microwave pretreatment may be a good alternative as it can reduce the pretreatment time and improve the enzymatic activity during hydrolysis. Liquid to solid ratio for the pretreatment of cassava pulp was found to be 20:1. Cassava pulp was pretreated at various NaOH concentration, microwave temperature and gave maximum yield of reducing sugar with 1.5% NaOH at 90 °C in 30 min than conventional alkali pretreatment after enzymatic hydrolysis. The subsequent enzymatic saccharification of pretreated cassava pulp using α amylase dosage of 400 IU at microwave temperature of 90 °C resulted in highest reducing sugar yield of 723 mg/g pulp. Microwave-assisted alkali pretreatment improved the enzymatic saccharification of cassava pulp by increasing its accessibility to hydrolytic enzymes. Microwave-assisted alkali pretreatment and microwave-coupled enzymatic hydrolysis are found to be efficient for improving the yield of reducing sugar. PMID:25832789

  12. Adjunctive use of the non-ionic surfactant Poloxamer 188 improves fetal dopaminergic cell survival and reinnervation in a neural transplantation strategy for Parkinson's disease.

    PubMed

    Quinn, M; Mukhida, K; Sadi, D; Hong, M; Mendez, I

    2008-01-01

    Although neural transplantation of fetal dopaminergic cells is a promising therapy for Parkinson's disease, poor transplanted cell survival limits its efficacy. In the present study it was hypothesized that the use of Poloxamer 188 (P188), a non-ionic surfactant, during cell preparation and transplantation may protect cells from associated mechanical injury and thus improve transplanted cell survival in a rat model of Parkinson's disease. Fetal rat dopaminergic tissue was dissociated in media with or without P188 and then cultured for 1 week or transplanted into the striatum of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway. Fetal dopaminergic cell survival and reinnervation of the host brain were examined using tyrosine hydroxylase immunohistochemistry and stereological quantification. The number of surviving tyrosine hydroxylase-immunoreactive cells in vitro and in vivo was significantly increased by 2.2-fold by incubating fetal dopaminergic cells with P188 during tissue dissociation. Furthermore, the striatal reinnervation in parkinsonian rats that received intrastriatal transplants of P188-exposed dopaminergic cells was significantly enhanced (1.8-fold increase) compared with rats that received non-P188-treated cells. In conclusion, P188 protects fetal dopaminergic cells from mechanical injury by increasing cell survival and enhances dopaminergic fibre outgrowth into the transplanted striatum. Use of P188 may thus be an important adjunct to improve the clinical efficacy of neural transplantation for Parkinson's disease. PMID:18093176

  13. Electron-beam stimulation of the reactivity of cellulose pulps for production of derivatives

    NASA Astrophysics Data System (ADS)

    Iller, Edward; Kukiełka, Aleksandra; Stupińska, Halina; Mikołajczyk, Włodzimierz

    2002-03-01

    New alternative technologies for manufacture of cellulose fibers are currently under development. The effect of electron beam irradiation on various types of cellulose pulps have been studied in order to improve the reactivity of raw material for production of cellulose derivatives. Three different types of textile pulps, Alicell (Canada), Borregaard (Norwegian), Ketchikan (USA) and Kraft softwood as well as Kraft hardwood pulps, have been irradiated with 10 MeV electron beam from LAE 13/g linear accelerator with dose 10, 15, 20, 25 and 50 kGy. Electron paramagnetic resonance spectroscopy (ESR) and gel permeation chromatography (GPC) were applied for determination of structural changes in irradiated pulps. Such parameters as viscosity, average degree of polymerization and α-cellulose contents were determinated by means of analytical methods. Results of there investigations are presented and discussed.

  14. Biological modification of loblolly pine chips with Ceriporiopsis subvermispora prior to kraft pulping

    NASA Astrophysics Data System (ADS)

    Villalba, Laura L.

    The ability of the white-rot fungus Ceriporiopsis subvermispora to selectively degrade lignin in loblolly pine chips and the effect on kraft pulps was investigated. The effect of fungal treatment was assessed by comparing changes in untreated wood chips with chips incubated for two and four weeks. The kraft pulping step included two different cooking times and two levels of chemical dosage as the variables, 16 and 22% for the effective alkali and 60 and 90 min at 170°C. The other cooking variables were kept constant for all the experiments and were: sulfidity, 22%; liquor/wood ratio 4:1; time to Tmax 90 min.; Tmax 170°C. Scanning electron microscopy (SEM) revealed that the colonization introduced significant chemical and physical changes. Pore size distribution analyses revealed a statistically significant increase in the average pore size as fungal treatment progressed. Significant reduction in the extractives content (23%) was found in the first 2 weeks, after which the reduction leveled off. Lignin losses reached 2% in the first 2 weeks of incubation, followed by an 11% loss after 4 weeks of treatment. Lignin phenolic hydroxyl groups increased 14% after 4 weeks of incubation. Fungal treatment caused 4 and 6% carbohydrate loss in 2 and 4 weeks-treated chips, respectively. The selectivity of the fungal treatment was emphasized in the subsequent kraft pulping. The best response regarding improved delignification was found in kraft pulps processed at the mildest pulping conditions without affecting pulp viscosity. Benefits of fungal treatment regarding freeness of kraft pulps were evidenced after 4 weeks of incubation with a maximum of 35% freeness reduction in kraft pulps refined at 12,000 rev in a PFI mill. Strength properties of kraft pulps of fungal treated chips were superior to those of the control. This method involves chemical and physical modification of wood chips using fungi. The approach improved chip impregnation, which in turn, led to more uniform

  15. Cold temperature improves mobility and survival in Drosophila models of autosomal-dominant hereditary spastic paraplegia (AD-HSP)

    PubMed Central

    Baxter, Sally L.; Allard, Denise E.; Crowl, Christopher; Sherwood, Nina Tang

    2014-01-01

    Autosomal-dominant hereditary spastic paraplegia (AD-HSP) is a crippling neurodegenerative disease for which effective treatment or cure remains unknown. Victims experience progressive mobility loss due to degeneration of the longest axons in the spinal cord. Over half of AD-HSP cases arise from loss-of-function mutations in spastin, which encodes a microtubule-severing AAA ATPase. In Drosophila models of AD-HSP, larvae lacking Spastin exhibit abnormal motor neuron morphology and function, and most die as pupae. Adult survivors display impaired mobility, reminiscent of the human disease. Here, we show that rearing pupae or adults at reduced temperature (18°C), compared with the standard temperature of 24°C, improves the survival and mobility of adult spastin mutants but leaves wild-type flies unaffected. Flies expressing human spastin with pathogenic mutations are similarly rescued. Additionally, larval cooling partially rescues the larval synaptic phenotype. Cooling thus alleviates known spastin phenotypes for each developmental stage at which it is administered and, notably, is effective even in mature adults. We find further that cold treatment rescues larval synaptic defects in flies with mutations in Flower (a protein with no known relation to Spastin) and mobility defects in flies lacking Kat60-L1, another microtubule-severing protein enriched in the CNS. Together, these data support the hypothesis that the beneficial effects of cold extend beyond specific alleviation of Spastin dysfunction, to at least a subset of cellular and behavioral neuronal defects. Mild hypothermia, a common neuroprotective technique in clinical treatment of acute anoxia, might thus hold additional promise as a therapeutic approach for AD-HSP and, potentially, for other neurodegenerative diseases. PMID:24906373

  16. Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats

    PubMed Central

    Yang, Weng-Lang; Ma, Gaifeng; Zhou, Mian; Aziz, Monowar; Yen, Hao-Ting; Marvropoulos, Spyros A; Ojamaa, Kaie; Wang, Ping

    2016-01-01

    Sepsis is a major healthcare concern, especially in the elderly population. The use of an animal model closely resembling clinical conditions in this population may provide a better prediction in translating bench studies to the bedside. Ghrelin inhibits sympathetic nerve activity and inflammation in young septic animals; however, aged animals become hyporesponsive to ghrelin. In this study, we evaluated the efficacy of combined human ghrelin and growth hormone (GH) for sepsis treatment in the elderly utilizing a clinically relevant animal model of sepsis. Male Fischer 344 rats 22 to 24 months old were subjected to cecal ligation and puncture (CLP). Human ghrelin plus GH or vehicle (normal saline) was administered subcutaneously at 5 h after CLP. At 20 h after CLP, blood and tissue samples were collected for various analyses. Combined treatment attenuated serum levels of lactate, lactate dehydrogenase, creatinine, blood urea nitrogen, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in aged septic rats. The integrity of the microscopic structure in the lungs, liver and kidneys was well preserved after treatment. Expression of IL-6, TNF-α, macrophage inflammatory protein-2 and keratinocyte-derived chemokine as well as myeloperoxidase activity and caspase-3 activation were significantly reduced in the lungs and liver of treated rats. Moreover, treated rats showed an improvement in cardiovascular function and increased expression of ghrelin receptor and c-fos in the brainstem. Finally, the 10-d survival of aged septic rats was increased from 29% to 64% after combined treatment and was associated with less body weight loss. Our findings warrant the development of combined human ghrelin and GH for sepsis treatment in the geriatric population. PMID:26835699

  17. Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein.

    PubMed

    Guitart, Kathrin; Loers, Gabriele; Buck, Friedrich; Bork, Ute; Schachner, Melitta; Kleene, Ralf

    2016-06-01

    Prion protein (PrP) protects neural cells against oxidative stress, hypoxia, ischemia, and hypoglycemia. In the present study we confirm that cultured PrP-deficient neurons are more sensitive to oxidative stress than wild-type neurons and present the novel findings that wild-type, but not PrP-deficient astrocytes protect wild-type cerebellar neurons against oxidative stress and that exosomes released from stressed wild-type, but not from stressed PrP-deficient astrocytes reduce neuronal cell death induced by oxidative stress. We show that neuroprotection by exosomes of stressed astrocytes depends on exosomal PrP but not on neuronal PrP and that astrocyte-derived exosomal PrP enters into neurons, suggesting neuronal uptake of astrocyte-derived exosomes. Upon exposure of wild-type astrocytes to hypoxic or ischemic conditions PrP levels in exosomes were increased. By mass spectrometry and Western blot analysis, we detected increased levels of 37/67 kDa laminin receptor, apolipoprotein E and the ribosomal proteins S3 and P0, and decreased levels of clusterin/apolipoprotein J in exosomes from wild-type astrocytes exposed to oxygen/glucose deprivation relative to exosomes from astrocytes maintained under normoxic conditions. The levels of these proteins were not altered in exosomes from stressed PrP-deficient astrocytes relative to unstressed PrP-deficient astrocytes. These results indicate that PrP in astrocytes is a sensor for oxidative stress and mediates beneficial cellular responses, e.g. release of exosomes carrying PrP and other molecules, resulting in improved survival of neurons under hypoxic and ischemic conditions. GLIA 2016;64:896-910. PMID:26992135

  18. Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival.

    PubMed

    Powe, Desmond G; Voss, Melanie J; Zänker, Kurt S; Habashy, Hany O; Green, Andrew R; Ellis, Ian O; Entschladen, Frank

    2010-11-01

    Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a non-hypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. Kaplan-Meier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary. PMID:21317458

  19. Human Dental Pulp Stem Cells and Gingival Fibroblasts Seeded into Silk Fibroin Scaffolds Have the Same Ability in Attracting Vessels

    PubMed Central

    Woloszyk, Anna; Buschmann, Johanna; Waschkies, Conny; Stadlinger, Bernd; Mitsiadis, Thimios A.

    2016-01-01

    Neovascularization is one of the most important processes during tissue repair and regeneration. Current healing approaches based on the use of biomaterials combined with stem cells in critical-size bone defects fail due to the insufficient implant vascularization and integration into the host tissues. Therefore, here we studied the attraction, ingrowth, and distribution of blood vessels from the chicken embryo chorioallantoic membrane into implanted silk fibroin scaffolds seeded with either human dental pulp stem cells or human gingival fibroblasts. Perfusion capacity was evaluated by non-invasive in vivo Magnetic Resonance Imaging while the number and density of blood vessels were measured by histomorphometry. Our results demonstrate that human dental pulp stem cells and gingival fibroblasts possess equal abilities in attracting vessels within silk fibroin scaffolds. Additionally, the prolonged in vitro pre-incubation period of these two cell populations favors the homogeneous distribution of vessels within silk fibroin scaffolds, which further improves implant survival and guarantees successful healing and regeneration. PMID:27148078

  20. 21 CFR 186.1673 - Pulp.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Pulp. 186.1673 Section 186.1673 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 186.1673 Pulp....

  1. Pulp and Paper Industry Effluent Management.

    ERIC Educational Resources Information Center

    Gove, George W.

    1978-01-01

    Presents a literature review of wastes from pulp and paper industry, covering publications of 1976-77. This review focuses on: (1) receiving water, toxicity, and effluent characterization; (2) pulping liquor disposal and recovery; and (3) physicochemical and biological treatment. A list of 238 references is also presented. (HM)

  2. Changes are in Store for Pulping Technology

    ERIC Educational Resources Information Center

    Environmental Science and Technology, 1975

    1975-01-01

    The pulp and paper industry are being forced by economic considerations and air pollution regulations to consider alternatives to the use of sulfur systems, be they kraft, acid or neutral sulfite. To meet environmental requirements and combat erosion of profits, modernized non-sulfur pulping methods will increasingly appear on the scene. (BT)

  3. 21 CFR 186.1673 - Pulp.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Pulp. 186.1673 Section 186.1673 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 186.1673 Pulp....

  4. DIETARY SUPPLEMENTATION WITH BLUEBERRY EXTRACTS IMPROVES THE SURVIVAL AND FUNCTION OF GRAFTED EMBRYONIC DOPAMINE NEURONS IN RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transplantation of embryonic dopamine (DA) neurons into the striatum is a viable treatment for Parkinson's disease (PD). However, transplanted cells survive poorly. This study provides evidence that dietary supplementation with blueberry extract (BBE) provides an efficacious, easily administered a...

  5. Breeding Strategy To Generate Robust Yeast Starter Cultures for Cocoa Pulp Fermentations

    PubMed Central

    Meersman, Esther; Steensels, Jan; Paulus, Tinneke; Struyf, Nore; Saels, Veerle; Mathawan, Melissa; Koffi, Jean; Vrancken, Gino

    2015-01-01

    Cocoa pulp fermentation is a spontaneous process during which the natural microbiota present at cocoa farms is allowed to ferment the pulp surrounding cocoa beans. Because such spontaneous fermentations are inconsistent and contribute to product variability, there is growing interest in a microbial starter culture that could be used to inoculate cocoa pulp fermentations. Previous studies have revealed that many different fungi are recovered from different batches of spontaneous cocoa pulp fermentations, whereas the variation in the prokaryotic microbiome is much more limited. In this study, therefore, we aimed to develop a suitable yeast starter culture that is able to outcompete wild contaminants and consistently produce high-quality chocolate. Starting from specifically selected Saccharomyces cerevisiae strains, we developed robust hybrids with characteristics that allow them to efficiently ferment cocoa pulp, including improved temperature tolerance and fermentation capacity. We conducted several laboratory and field trials to show that these new hybrids often outperform their parental strains and are able to dominate spontaneous pilot scale fermentations, which results in much more consistent microbial profiles. Moreover, analysis of the resulting chocolate showed that some of the cocoa batches that were fermented with specific starter cultures yielded superior chocolate. Taken together, these results describe the development of robust yeast starter cultures for cocoa pulp fermentations that can contribute to improving the consistency and quality of commercial chocolate production. PMID:26150457

  6. Breeding Strategy To Generate Robust Yeast Starter Cultures for Cocoa Pulp Fermentations.

    PubMed

    Meersman, Esther; Steensels, Jan; Paulus, Tinneke; Struyf, Nore; Saels, Veerle; Mathawan, Melissa; Koffi, Jean; Vrancken, Gino; Verstrepen, Kevin J

    2015-09-01

    Cocoa pulp fermentation is a spontaneous process during which the natural microbiota present at cocoa farms is allowed to ferment the pulp surrounding cocoa beans. Because such spontaneous fermentations are inconsistent and contribute to product variability, there is growing interest in a microbial starter culture that could be used to inoculate cocoa pulp fermentations. Previous studies have revealed that many different fungi are recovered from different batches of spontaneous cocoa pulp fermentations, whereas the variation in the prokaryotic microbiome is much more limited. In this study, therefore, we aimed to develop a suitable yeast starter culture that is able to outcompete wild contaminants and consistently produce high-quality chocolate. Starting from specifically selected Saccharomyces cerevisiae strains, we developed robust hybrids with characteristics that allow them to efficiently ferment cocoa pulp, including improved temperature tolerance and fermentation capacity. We conducted several laboratory and field trials to show that these new hybrids often outperform their parental strains and are able to dominate spontaneous pilot scale fermentations, which results in much more consistent microbial profiles. Moreover, analysis of the resulting chocolate showed that some of the cocoa batches that were fermented with specific starter cultures yielded superior chocolate. Taken together, these results describe the development of robust yeast starter cultures for cocoa pulp fermentations that can contribute to improving the consistency and quality of commercial chocolate production. PMID:26150457

  7. Cortical representation area of human dental pulp.

    PubMed

    Kubo, K; Shibukawa, Y; Shintani, M; Suzuki, T; Ichinohe, T; Kaneko, Y

    2008-04-01

    To elucidate the dental pulp-representing area in the human primary somatosensory cortex and the presence of A-beta fibers in dental pulp, we recorded somatosensory-evoked magnetic fields from the cortex in seven healthy persons using magnetoencephalography. Following non-painful electrical stimulation of the right maxillary first premolar dental pulp, short latency (27 ms) cortical responses on the magnetic waveforms were observed. However, no response was seen when stimulation was applied to pulpless teeth, such as devitalized teeth. The current source generating the early component of the magnetic fields was located anterior-inferiorly compared with the locations for the hand area in the primary somatosensory cortex. These results demonstrate the dental pulp representation area in the primary somatosensory cortex, and that it receives input from intradental A-beta neurons, providing a detailed organizational map of the orofacial area, by adding dental pulp to the classic "sensory homunculus". PMID:18362319

  8. Comparative study of the efficiency of synthetic and natural mediators in laccase-assisted bleaching of eucalyptus kraft pulp.

    PubMed

    Moldes, D; Díaz, M; Tzanov, T; Vidal, T

    2008-11-01

    The natural phenolic compounds syringaldehyde and vanillin were compared to the synthetic mediators 1-hydroxybenzotriazole, violuric acid and promazine in terms of boosting efficiency in a laccase-assisted biobleaching of eucalyptus kraft pulp. Violuric acid and 1-hydroxybenzotriazole revealed to be the most effective mediators of the bioprocess. Nevertheless, laccase-syringaldehyde system also improved the final pulp properties (28% delignification and 63.5% ISO brightness) compared to the process without mediator (23% and 61.5% respectively), in addition to insignificant denaturation effect over laccase. The efficiency of the biobleaching process was further related to changes in non-conventionally used optical and chromatic parameters of pulp, such as (L*), chroma (C*) and dye removal index (DRI) showing good correlation. Adverse coupling reactions of the natural phenolic mediators on pulp lignin were predicted by electrochemical studies, demonstrating the complexity of the laccase-mediator reaction on pulp. PMID:18499450

  9. Pretreatment with xylanase and its significance in hemicellulose removal from mixed hardwood kraft pulp as a process step for viscose.

    PubMed

    Kaur, Prabhjot; Bhardwaj, Nishi K; Sharma, Jitender

    2016-07-10

    The upturn of viscose fiber market has triggered an augmented dissolving pulp usage over the last decade. Dissolving pulp is feasible to obtain from kraft pulp after two essential steps including hemicellulose removal and subsequent pulp activation. Prerequisite of conversion being hemicellulose reduction can be gently done by using xylanase treatment prior to alkali extraction. Herein, the significance of xylanase treatment and the optimum xylanase dose required in conjunction with subsequent alkali extraction was investigated. An increase in xylanase dose prior to alkali extraction had no significant effect on pentosans while the Fock reactivity and viscosity both improved at the dose of 50AXU/g. Also, alkali extraction without xylanase pretreatment resulted in decreased Fock reactivity, alpha cellulose, brightness and viscosity of paper grade pulp. A moderate dose of xylanase prior to alkali extraction can thus be used to facilitate the hemicellulose removal while simultaneously protecting the native structure of cellulose. PMID:27106156

  10. Dynamic hydrostatic pressure promotes differentiation of human dental pulp stem cells.

    PubMed

    Yu, V; Damek-Poprawa, M; Nicoll, S B; Akintoye, S O

    2009-09-01

    The masticatory apparatus absorbs high occlusal forces, but uncontrolled parafunctional or orthodontic forces damage periodontal ligament (PDL), cause pulpal calcification, pulp necrosis and tooth loss. Morphology and functional differentiation of connective tissue cells can be controlled by mechanical stimuli but effects of uncontrolled forces on intra-pulpal homeostasis and ability of dental pulp stem cells (DPSCs) to withstand direct external forces are unclear. Using dynamic hydrostatic pressure (HSP), we tested the hypothesis that direct HSP disrupts DPSC survival and odontogenic differentiation. DPSCs from four teenage patients were subjected to HSP followed by assessment of cell adhesion, survival and recovery capacity based on odontogenic differentiation, mineralization and responsiveness to bone morphogenetic protein-2 (BMP-2). HSP down-regulated DPSC adhesion and survival but promoted differentiation by increasing mineralization, in vivo hard tissue regeneration and BMP-2 responsiveness despite reduced cell numbers. HSP-treated DPSCs displayed enhanced odontogenic differentiation, an indication of favorable recovery from HSP-induced cellular stress. PMID:19555657

  11. Dynamic Hydrostatic Pressure Promotes Differentiation of Human Dental Pulp Stem Cells

    PubMed Central

    Yu, V; Damek-Poprawa, M.; Nicoll, S. B.; Akintoye, S.O.

    2009-01-01

    The masticatory apparatus absorbs high occlusal forces, but uncontrolled parafunctional or orthodontic forces damage periodontal ligament (PDL), cause pulpal calcification, pulp necrosis and tooth loss. Morphology and functional differentiation of connective tissue cells can be controlled by mechanical stimuli but effects of uncontrolled forces on intra-pulpal homeostasis and ability of dental pulp stem cells (DPSCs) to withstand direct external forces are unclear. Using dynamic hydrostatic pressure (HSP), we tested the hypothesis that direct HSP disrupts DPSC survival and odontogenic differentiation. DPSCs from four teenage patients were subjected to HSP followed by assessment of cell adhesion, survival and recovery capacity based on odontogenic differentiation, mineralization and responsiveness to bone morphogenetic protein-2 (BMP-2). HSP down-regulated DPSC adhesion and survival but promoted differentiation by increasing mineralization, in vivo hard tissue regeneration and BMP-2 responsiveness despite reduced cell numbers. HSP-treated DPSCs displayed enhanced odontogenic differentiation, an indication of favorable recovery from HSP-induced cellular stress. PMID:19555657

  12. Overview of the government/industry workshop on opportunities for new materials in pulp and paper processing

    SciTech Connect

    Young, J.K.; Fowler, R.A.

    1994-05-01

    This report presents a synopsis of the presentations made at the two-day workshop conducted in Portland, Oregon, on August 12 and 13, 1993, for the Advanced Industrial Concepts division (AICD) of the US Department of Energy (DOE) Office of Industrial Technologies (OIT) and DOE national laboratory representatives from the pulp and paper industry. The information from the presentations is supplemented by additional statistics, as appropriate. The workshop objectives were (1) to develop a strategy and framework for collaboration between the pulp and paper industries and DOE`s national laboratories, (2) to identify major challenges to pulp and paper industry modernization, and (3) to identify research objectives for DOE national laboratories to improve materials and process technology in pulp and paper mills. Prior to the workshop, participants had the opportunity to tour paper mills and gain familiarity with pulp and paper processing methods. During the workshop, research needs for materials and processing that were identified at earlier AICD workshops were reviewed. Major problems of the pulp and paper industry were addressed, and ways in which DOE national laboratories are interacting with other industries to foster innovation and solve problems were presented. As a result of this and other workshops, a Pulp Paper Mill of the future strategy is being developed to address challenges identified in these proceedings. Continued efforts are expected by AICD to match candidate materials and processes from DOE national laboratories with the technology needs of pulp and paper mills.

  13. Adjuvant chemotherapy is not associated with improved survival for all high-risk factors in stage II colon cancer.

    PubMed

    Verhoeff, S R; van Erning, F N; Lemmens, V E P P; de Wilt, J H W; Pruijt, J F M

    2016-07-01

    Adjuvant chemotherapy can be considered in high-risk stage II colon cancer comprising pT4, poor/undifferentiated grade, vascular invasion, emergency surgery and/or <10 evaluated lymph nodes (LNs). Adjuvant chemotherapy administration and its effect on survival was evaluated for each known risk factor. All patients with high-risk stage II colon cancer who underwent resection and were diagnosed in the Netherlands between 2008 and 2012 were included. After stratification by risk factor(s) (vascular invasion could not be included), Cox regression was used to discriminate the independent association of adjuvant chemotherapy with the probability of death. Relative survival was used to estimate disease-specific survival. A total of 4,940 of 10,935 patients with stage II colon cancer were identified as high risk, of whom 790 (16%) patients received adjuvant chemotherapy. Patients with a pT4 received adjuvant chemotherapy more often (37%). Probability of death in pT4 patients receiving chemotherapy was lower compared to non-recipients (3-year overall survival 91% vs. 73%, HR 0.43, 95% CI 0.28-0.66). The relative excess risk (RER) of dying was also lower for pT4 patients receiving chemotherapy compared to non-recipients (3-year relative survival 94% vs. 85%, RER 0.36, 95% CI 0.17-0.74). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between receipt of adjuvant chemotherapy and survival was observed. In high-risk stage II colon cancer, adjuvant chemotherapy was associated with higher survival in pT4 only. To prevent unnecessary chemotherapy-induced toxicity, further refinement of patient subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated. PMID:26914273

  14. Improved graft-versus-host disease-free, relapse-free survival associated with bone marrow as the stem cell source in adults

    PubMed Central

    Mehta, Rohtesh S.; de Latour, Regis Peffault; DeFor, Todd E; Robin, Marie; Lazaryan, Aleksandr; Xhaard, Aliénor; Bejanyan, Nelli; de Fontbrune, Flore Sicre; Arora, Mukta; Brunstein, Claudio G.; Blazar, Bruce R.; Weisdorf, Daniel J.; MacMillan, Margaret L.; Socie, Gerard; Holtan, Shernan G.

    2016-01-01

    We previously reported that bone marrow grafts from matched sibling donors resulted in best graft-versus-host disease-free, relapse-free survival at 1-year post allogeneic hematopoietic cell transplantation. However, pediatric patients comprised the majority of bone marrow graft recipients in that study. To better define this outcome in adults and pediatric patients at 1- and 2-years post- allogeneic hematopoietic cell transplantation, we pooled data from the University of Minnesota and the Hôpital Saint-Louis in Paris, France (n=1901). Graft-versus-host disease-free, relapse-free survival was defined as the absence of grade III–IV acute graft-versus-host disease, chronic graft-versus-host disease (requiring systemic therapy or extensive stage), relapse and death. In adults, bone marrow from matched sibling donors (n=123) had best graft-versus-host disease-free, relapse-free survival at 1- and 2-years, compared with peripheral blood stem cell from matched sibling donors (n=540) or other graft/donor types. In multivariate analysis, peripheral blood stem cells from matched sibling donors resulted in a 50% increased risk of events contributing to graft-versus-host disease-free, relapse-free survival at 1- and 2-years than bone marrow from matched sibling donors. With limited numbers of peripheral blood stem cell grafts in pediatric patients (n=12), graft-versus-host disease-free, relapse-free survival did not differ between bone marrow and peripheral blood stem cell graft from any donor. While not all patients have a matched sibling donor, graft-versus-host disease-free, relapse-free survival may be improved by the preferential use of bone marrow for adults with malignant diseases. Alternatively, novel graft-versus-host disease prophylaxis regimens are needed to substantially impact graft-versus-host disease-free, relapse-free survival with the use of peripheral blood stem cell. PMID:27036159

  15. Utilization of geothermal energy in a pulp and paper mill

    SciTech Connect

    Hotson, G.W.

    1997-01-01

    The Tasman Pulp and Paper Company Ltd.`s Mill at Kawerau, New Zealand, has been utilizing geothermal energy for more than 30 years. The mill produces approximately 200,000 tonnes of kraft pulp and 400,000 tonnes of newsprint per annum. Geothermal energy produces 26% of the process steam requirements and 6% of the mill`s electrical load. The management of the mill`s energy sources is complex and ever changing, which has resulted in unique control strategies being developed over the years to improve efficiencies in the operation of the plant. Complete utilization of the geothermal resource has been the aim of the company and has led to pioneering plant and process developments.

  16. Improved Survival of Mice After Total Body Irradiation with 10 MV Photon, 2400 MU/min SRS Beam

    PubMed Central

    KALASH, RONNY; BERHANE, HEBIST; YANG, YONG; EPPERLY, MICHAEL W.; WANG, HONG; DIXON, TRACY; RHIEU, BYUNG; GREENBERGER, JOEL S.; HUQ, MOHAMMED SAIFUL

    2014-01-01

    Background/Aim We evaluated the radiobiological effects of stereotactic radiosurgery (SRS) photon beams on survival of C57BL/6NTac mice following total body irradiation. Materials and Methods Survival of Lewis lung carcinoma (3LL) cells was tested after irradiation using 6 MV: 300 MU/min or 1400 MU/min; or 10 MV: 300 MU/min or 2400 MU/min. Survival of C57BL/6NTac mice after a dose which is lethal to 50% of the mice in 30 days (LD50/30) (9.25 Gy) total body irradiation (TBI) and 21 Gy to orthotopic 3LL tumors was tested. We quantitated levels of organ-specific gene transcripts by Real Time Polymerase Chain Reaction (RT-PCR). Results While 3LL cell survival and inhibition of orthotopic tumor growth was uniform, 10 MV photons at 2400 MU/min TBI led to significantly greater survival (p=0.0218), with higher levels of intestinal (Sod2), (Gpx1), (Nrf2), and (NFκB) RNA transcripts. Conclusion Clinical 10 MV-2400 cGy/min SRS beams led to unexpected protection of mice on TBI and increased radioprotective gene transcripts. PMID:24425830

  17. Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

    PubMed Central

    Kiang, Juliann G.; Zhai, Min; Liao, Pei-Jyun; Elliott, Thomas B.; Gorbunov, Nikolai V.

    2014-01-01

    Exposure to ionizing radiation alone (RI) or combined with traumatic tissue injury (CI) is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W CI) or burns (R-B CI) experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide) therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit. PMID:25374650

  18. Modification in the properties of paper by using cellulase-free xylanase produced from alkalophilic Cellulosimicrobium cellulans CKMX1 in biobleaching of wheat straw pulp.

    PubMed

    Walia, Abhishek; Mehta, Preeti; Guleria, Shiwani; Shirkot, Chand Karan

    2015-09-01

    Alkalophilic Cellulosimicrobium cellulans CKMX1 isolated from mushroom compost is an actinomycete that produces industrially important and environmentally safer thermostable cellulase-free xylanase, which is used in the pulp and paper industry as an alternative to the use of toxic chlorinated compounds. Strain CKMX1 was previously characterized by metabolic fingerprinting, whole-cell fatty acids methyl ester analysis, and 16S rDNA and was found to be C. cellulans CKMX1. Crude enzyme (1027.65 U/g DBP) produced by C. cellulans CKMX1, having pH and temperature optima of 8.0 and 60 °C, respectively, in solid state fermentation of apple pomace, was used in the production of bleached wheat straw pulp. Pretreatment with xylanase at a dose of 5 U/g after pulping decreased pulp kappa points by 1.4 as compared with the control. Prebleaching with a xylanase dose of 5 U/g pulp reduced the chlorine charge by 12.5%, increased the final brightness points by approximately 1.42% ISO, and improved the pulp strength properties. Xylanase could be substituted for alkali extraction in C-Ep-D sequence and used for treating chemically bleached pulp, resulting in bleached pulp with higher strength properties. Modification of bleached pulp with 5 U of enzyme/g increased pulp whiteness and breaking length by 1.03% and 60 m, respectively; decreased tear factor of pulp by 7.29%; increased bulk weight by 3.99%, as compared with the original pulp. Reducing sugars and UV-absorbing lignin-derived compound values were considerably higher in xylanase-treated samples. Cellulosimicrobium cellulans CKMX1 has a potential application in the pulp and paper industries. PMID:26220821

  19. Steam system opportunity assessment for the pulp and paper, chemical manufacturing, and petroleum refining industries: Main report

    SciTech Connect

    None, None

    2002-10-01

    This report assesses steam generation and use in the pulp and paper, chemical, and petroleum refining industries, and estimates the potential for energy savings from implementation of steam system performance and efficiency improvements.

  20. Attenuated mild colonic inflammation and improved survival from severe DSS-colitis of transgenic Cu/Zn-SOD mice.

    PubMed

    Kruidenier, Laurens; van Meeteren, Marieke E; Kuiper, Ineke; Jaarsma, Dick; Lamers, Cornelis B H W; Zijlstra, Freek J; Verspaget, Hein W

    2003-03-15

    Mucosal tissue damage in chronic inflammatory bowel disease (IBD) is partly caused by an enduring exposure to excessive amounts of reactive oxygen metabolites (ROM). To protect themselves from the toxic effects of ROM, most intestinal cell types constitutively express the highly specific, key ROM-neutralizing cytosolic enzyme Cu/Zn-superoxide dismutase (SOD). Under inflammatory conditions, however, its protein and activity levels have consistently been reported as being decreased. To elucidate a direct functional relationship between intracellular Cu/Zn-SOD expression and intestinal inflammation, we investigated the effects of transgenic human Cu/Zn-SOD overexpression in acute and chronic murine dextran sodium sulfate (DSS)-induced colitis. When subjected to a mild form of acute colitis, the Cu/Zn-SOD overexpressing mice showed a significantly lower colonic activity of neutrophilic myeloperoxidase (MPO) than their nontransgenic littermates. This difference was particularly evident in the male animals. In contrast, a severe acute colitis did not lead to any differences in MPO activity between both groups. Yet, when the animals were subsequently allowed to recover, MPO levels were again significantly lower in the transgenes, suggesting an involvement of Cu/Zn-SOD in, particularly, the clearance of neutrophils. Specific, immunohistochemical identification of neutrophils confirmed the validity of the MPO activity measurements. In addition, transgenic animals showed a remarkable survival benefit from severe DSS colitis over their nontransgenic littermates, particularly during or shortly after the acute inflammatory phase. During the chronic inflammatory phase, which was not characterized by massive neutrophil infiltration, no effects of Cu/Zn-SOD overexpression were noted. Paradoxically, overexpression of Cu/Zn-SOD did not obviously improve the colitis-related (oxidative) injury or symptoms at any stage of the experiment. Surprisingly, however, we did observe a

  1. Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

    PubMed

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-04-01

    The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease.Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan.A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995-2003 vs 2004-2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival.Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%-16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol.By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  2. Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients

    PubMed Central

    Keskin, Metin; Bayraktar, Adem; Sivirikoz, Emre; Yegen, Gülcin; Karip, Bora; Saglam, Esra; Bulut, Mehmet Türker; Balik, Emre

    2016-01-01

    Abstract The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors. Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann–Whitney U test and the Mantel–Cox log-rank sum test. A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P < 0.001). Advanced T-stage (P < 0.001), lymph node invasion (P = 0.001) and incomplete mesorectum (P = 0.007) were encountered significantly more often in patients with positive CRM status. Logistic regression analysis revealed that APR (P < 0.001) and open resection (P = 0.046) were independent predictors of positive CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively). This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates. PMID:26844498

  3. Effects of N-Acetylcysteine on Cytokines in Non-Acetaminophen Acute Liver Failure: Potential Mechanism of Improvement in Transplant-Free Survival

    PubMed Central

    Stravitz, R. Todd; Sanyal, Arun J.; Reisch, Joan; Bajaj, Jasmohan S.; Mirshahi, Faridoddin; Cheng, Jianfeng; Lee, William M.

    2016-01-01

    Background N-Acetylcysteine (NAC) improves transplant-free survival in patients with non-acetaminophen acute liver failure (ALF) when administered in early stages of hepatic encephalopathy. The mechanisms of this benefit are unknown. Aim To determine whether NAC improves transplant-free survival in ALF by ameliorating the surge of pro-inflammatory cytokines. Methods Serum samples were obtained from 78 participants of the randomized, ALF Study Group NAC Trial with grade 1 or 2 hepatic encephalopathy on randomization. Concentrations of ten cytokines, chosen to represent a wide array of inflammatory responses, were determined by multiplex ELISA. Results In univariate analysis, predictors of transplant-free survival included NAC administration (P=0.012), admission bilirubin (P=0.003), INR (P=0.0002), grade 1 vs. grade 2 encephalopathy (P=0.006) and lower admission interleukin (IL)-17 concentrations (P=0.011). IL-17 levels were higher in patients with grade 2 vs. 1 encephalopathy on randomization (P=0.007) and in those who progressed to grade 3 or 4 encephalopathy over the following 7 days (P≤0.01). Stepwise multivariate logistic regression analysis identified only NAC administration and lower IL-17 concentrations as independent predictors of transplant-free survival. In patients with detectable IL-17 concentrations on admission, 78% of those who received NAC vs. 44% of those who received placebo had undetectable levels by day 3-5 (P=0.042), and the mean decrease in IL-17 concentrations between admission and late samples was significantly greater in patients who received NAC vs. placebo (P=0.045). Conclusions NAC may improve transplant-free survival in patients with non-acetaminophen ALF by ameliorating the production of IL-17, which is associated with progression of hepatic encephalopathy and poor outcome. PMID:23782487

  4. Microencapsulation of Lactobacillus rhamnosus GG by Transglutaminase Cross-Linked Soy Protein Isolate to Improve Survival in Simulated Gastrointestinal Conditions and Yoghurt.

    PubMed

    Li, Chun; Wang, Chun-Ling; Sun, Yu; Li, Ai-Li; Liu, Fei; Meng, Xiang-Chen

    2016-07-01

    Microencapsulation is an effective way to improve the survival of probiotics in simulated gastrointestinal (GI) conditions and yoghurt. In this study, microencapsulation of Lactobacillus rhamnosus GG (LGG) was prepared by first cross-linking of soy protein isolate (SPI) using transglutaminase (TGase), followed by embedding the bacteria in cross-linked SPI, and then freeze-drying. The survival of microencapsulated LGG was evaluated in simulated GI conditions and yoghurt. The results showed that a high microencapsulation yield of 67.4% was obtained. The diameter of the microencapsulated LGG was in the range of 52.83 to 275.16 μm. Water activity did not differ between free and microencapsulated LGG after freeze-drying. The survival of microencapsulated LGG under simulated gastric juice (pH 2.5 and 3.6), intestinal juice (0.3% and 2% bile salt) and storage at 4 °C were significantly higher than that of free cells. The survival of LGG in TGase cross-linked SPI microcapsules was also improved to 14.5 ± 0.5% during storage in yoghurt. The microencapsulation of probiotics by TGase-treated SPI can be a suitable alternative to polysaccharide gelation technologies. PMID:27228279

  5. Kraft Pulp Bleaching and Delignification by Dikaryons and Monokaryons of Trametes versicolor

    PubMed Central

    Addleman, Katherine; Archibald, Frederick

    1993-01-01

    The ability of 10 dikaryotic and 20 monokaryotic strains of Trametes (Coriolus) versicolor to bleach and delignify hardwood and softwood kraft pulps was assessed. A dikaryon (52P) and two of its mating-compatible monokaryons (52J and 52D) derived via protoplasting were compared. All three regularly bleached hardwood kraft pulp more than 20 brightness points (International Standards Organization) in 5 days and softwood kraft pulp the same amount in 12 days. Delignification (kappa number reduction) by the dikaryon and the monokaryons was similar, but the growth of the monokaryons was slower. Insoluble dark pigments were commonly found in the mycelium, medium, and pulp of the dikaryon only. Laccase and manganese peroxidase (MnP) but not lignin peroxidase activities were secreted during bleaching by all three strains. Their laccase and MnP isozyme patterns were compared on native gels. No segregation of isozyme bands between the monokaryons was found. Hardwood kraft pulp appeared to adsorb several laccase isozyme bands. One MnP isozyme (pI, 3.2) was secreted in the presence of pulp by all three strains, but a second (pI, 4.9) was produced only by 52P. A lower level of soluble MnP activity in one monokaryon (52D) was associated with reduced bleaching ability and a lower level of methanol production. Since monokaryon 52J bleached pulp better than its parent dikaryon 52P, especially per unit of biomass, this genetically simpler monokaryon will be the preferred subject for further genetic manipulation and improvement of fungal pulp biological bleaching. Images PMID:16348851

  6. Extraction optimization and nanoencapsulation of jujube pulp and seed for enhancing antioxidant activity.

    PubMed

    Han, Hye Jung; Lee, Ji-Soo; Park, Sun-Ah; Ahn, Jun-Bae; Lee, Hyeon Gyu

    2015-06-01

    The aim of this study was to optimize extraction conditions for jujube pulp and seed in order to obtain maximum active ingredient yield and antioxidant activity, as well as to prepare chitosan nanoparticles loaded with jujube pulp and seed extracts for enhancing stability. The extraction conditions, i.e. temperature, time, and ethanol concentration, were optimized at the following respective values: 61.2 °C, 38 h, and 60.4% for pulp, and 58 °C, 34 h, and 59.2% for seed. The jujube nanoparticle size significantly increased with a higher chitosan/sodium tripolyphosphate ratio and extract concentration. Entrapment efficiency was greater than 80% regardless of preparation conditions. The stabilities of jujube pulp and seed extract in terms of total phenolic content and antioxidant activity were effectively enhanced by nanoencapsulation. In conclusion, jujube pulp and seed extracts prepared using optimal conditions could be useful as a natural functional food ingredient with antioxidant activity, and nanoencapsulation can be used to improve the stability of jujube extract. Therefore, these results could be used to promote the utilization of not only jujube pulp but also seed, by product. PMID:25911157

  7. Effect of depth beating on the fiber properties and enzymatic saccharification efficiency of softwood kraft pulp.

    PubMed

    Gao, Wenhua; Xiang, Zhouyang; Chen, Kefu; Yang, Rendang; Yang, Fei

    2015-01-01

    Commercial bleached softwood kraft pulp was mechanically fibrillated by a PFI-mill with beating revolution from 5000 to 30,000 r. The extent of fibrillating on the pulp was evaluated by beating degree, fiber morphological properties (fiber length, width, coarseness and curls index), water retention value (WRV) and physical properties of paper made from the pulp. Depth beating process significantly affected the pulp fibrillations as showed by the decreased fiber length and width as well as the SEM analysis, but the effects were limited after beating revolution of 15,000. Depth beating process also improved the total internal pore and inter-fibril surface areas as shown by the increased WRV values. Substrate enzymatic digestibility (SED) of beaten pulp at 5000 revolutions could reach 95% at cellulase loading of 15 FPU/g of glucan. After the enzymatic hydrolysis, the size of the pulp residues was reduced to micro-scale, and a relative uniform size distribution of the residues appeared at 10,000 r beating revolution. PMID:25965499

  8. The microbial challenge to pulp regeneration.

    PubMed

    Fouad, A F

    2011-07-01

    Pulp regeneration is considered in cases where the dental pulp has been destroyed because of microbial irritation. Diverse oral and food-borne micro-organisms are able to invade the pulp space, form biofilm on canal walls, and infiltrate dentinal tubules. Prior to pulp regeneration procedures, the pulp space and dentinal walls need to be sufficiently disinfected to allow for and promote regeneration. The necessary level of disinfection is likely higher than that accepted for traditional endodontic therapy, because in traditional techniques the mere lowering of bacterial loads and prevention of bacterial access to periapical tissues is conducive to healing. Moreover, several of the non-specific antimicrobials used in traditional endodontic therapy may cause significant changes in remaining dentin that interfere with its inherent potential to mediate regeneration. Non-specific antimicrobials also suppress all microbial taxa, which may allow residual virulent micro-organisms to preferentially repopulate the pulp space. Therefore, it is important for endodontic pathogens to be studied by molecular methods that allow for a broad depth of coverage. It is then essential to determine the most effective protocols to disinfect the pulp space, with minimal disruption of remaining dentin. These protocols include the topical use of effective antibiotics, including newer agents that have demonstrated efficacy against endodontic pathogens. PMID:21677080

  9. A Review on Vital Pulp Therapy in Primary Teeth

    PubMed Central

    Parisay, Iman; Ghoddusi, Jamileh; Forghani, Maryam

    2015-01-01

    Maintaining deciduous teeth in function until their natural exfoliation is absolutely necessary. Vital pulp therapy (VPT) is a way of saving deciduous teeth. The most important factors in success of VPT are the early diagnosis of pulp and periradicular status, preservation of the pulp vitality and proper vascularization of the pulp. Development of new biomaterials with suitable biocompatibility and seal has changed the attitudes towards preserving the reversible pulp in cariously exposed teeth. Before exposure and irreversible involvement of the pulp, indirect pulp capping (IPC) is the treatment of choice, but after the spread of inflammation within the pulp chamber and establishment of irreversible pulpitis, removal of inflamed pulp tissue is recommended. In this review, new concepts in preservation of the healthy pulp tissue in deciduous teeth and induction of the reparative dentin formation with new biomaterials instead of devitalization and the consequent destruction of vital tissues are discussed. PMID:25598803

  10. A review on vital pulp therapy in primary teeth.

    PubMed

    Parisay, Iman; Ghoddusi, Jamileh; Forghani, Maryam

    2015-01-01

    Maintaining deciduous teeth in function until their natural exfoliation is absolutely necessary. Vital pulp therapy (VPT) is a way of saving deciduous teeth. The most important factors in success of VPT are the early diagnosis of pulp and periradicular status, preservation of the pulp vitality and proper vascularization of the pulp. Development of new biomaterials with suitable biocompatibility and seal has changed the attitudes towards preserving the reversible pulp in cariously exposed teeth. Before exposure and irreversible involvement of the pulp, indirect pulp capping (IPC) is the treatment of choice, but after the spread of inflammation within the pulp chamber and establishment of irreversible pulpitis, removal of inflamed pulp tissue is recommended. In this review, new concepts in preservation of the healthy pulp tissue in deciduous teeth and induction of the reparative dentin formation with new biomaterials instead of devitalization and the consequent destruction of vital tissues are discussed. PMID:25598803

  11. Vital Pulp Therapy—Current Progress of Dental Pulp Regeneration and Revascularization

    PubMed Central

    Zhang, Weibo; Yelick, Pamela C.

    2010-01-01

    Pulp vitality is extremely important for the tooth viability, since it provides nutrition and acts as biosensor to detect pathogenic stimuli. In the dental clinic, most dental pulp infections are irreversible due to its anatomical position and organization. It is difficult for the body to eliminate the infection, which subsequently persists and worsens. The widely used strategy currently in the clinic is to partly or fully remove the contaminated pulp tissue, and fill and seal the void space with synthetic material. Over time, the pulpless tooth, now lacking proper blood supply and nervous system, becomes more vulnerable to injury. Recently, potential for successful pulp regeneration and revascularization therapies is increasing due to accumulated knowledge of stem cells, especially dental pulp stem cells. This paper will review current progress and feasible strategies for dental pulp regeneration and revascularization. PMID:20454445

  12. CYP2B6rs2279343 Is Associated with Improved Survival of Pediatric Rhabdomyosarcoma Treated with Cyclophosphamide

    PubMed Central

    A. Abdelrahim, Mohamed E.; Elnadi, Enas; Hesham, Reem M.; Yassin, Dina

    2016-01-01

    Background Rhabdomyosarcoma (RMS) is a small round blue cell malignant tumor, representing 7% of childhood malignancies, and over 50% of all soft tissue sarcomas. Cyclophosphamide (CPA) is a prodrug and is the mainstay of RMS treatment. CYP2B6 is a highly polymorphic drug metabolizing enzyme involved in CPA bioactivation. The influence of CYP2B6 single nucleotide polymorphisms (SNPs) on the survival of RMS is still unknown. Methods We genotyped CYP2B6SNPs rs2279343, rs3745274, and rs3211371 by restriction fragment polymorphism (RFLP) after PCR amplification in a cohort of 73 pediatric RMS patients treated with CPA-based first line treatment. We then analyzed the association between those genotypes and survival outcome of RMS. Results The frequencies of CYP2B6 rs2279343, rs3745274, and rs3211371 were 63%, 45.2%, and 5.5%, respectively. There was no association between rs3745274, rs3211371 genotypes and survival outcomes of RMS. However, the carriers of at least one mutant allele CYP2B6rs2279343 had significantly longer event-free survival (p-value = 0.03). Conclusion Our results demonstrated that CYP2B6 rs2279343 may predict EFS in RMS patients and warrants future studies to clarify the pharmacogenetics of CPA in pediatrics. If validated, integration of genetic factors with clinical and molecular characteristics could be used for a composite algorithm to better stratify risk prior to treatment. PMID:27388155

  13. RhG-CSF improves radiation-induced myelosuppression and survival in the canine exposed to fission neutron irradiation.

    PubMed

    Yu, Zu-Yin; Li, Ming; Han, A-Ru-Na; Xing, Shuang; Ou, Hong-Ling; Xiong, Guo-Lin; Xie, Ling; Zhao, Yan-Fang; Xiao, He; Shan, Ya-Jun; Zhao, Zhen-Hu; Liu, Xiao-Lan; Cong, Yu-Wen; Luo, Qing-Liang

    2011-01-01

    Fission-neutron radiation damage is hard to treat due to its critical injuries to hematopoietic and gastrointestinal systems, and so far few data are available on the therapeutic measures for neutron-radiation syndrome. This study was designed to test the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in dogs which had received 2.3 Gy mixed fission-neutron-γ irradiation with a high ratio of neutrons (~90%). Following irradiation, rhG-CSF treatment induced 100% survival versus 60% in controls. Only two of five rhG-CSF-treated dogs experienced leukopenia (white blood cells [WBC] count < 1.0 × 10(9)/L) and neutropenia (neutrophil [ANC] count < 0.5 × 10(9)/L), whereas all irradiated controls displayed a profound period of leukopenia and neutropenia. Furthermore, administration of rhG-CSF significantly delayed the onset of leukopenia and reduced the duration of leucopenia as compared with controls. In addition, individual dogs in the rhG-CSF-treated group exhibited evident differences in rhG-CSF responsiveness after neutron-irradiation. Finally, histopathological evaluation of the surviving dogs revealed that the incidence and severity of bone marrow, thymus and spleen damage decreased in rhG-CSF-treated dogs as compared with surviving controls. Thus, these results demonstrated that rhG-CSF administration enhanced recovery of myelopoiesis and survival after neutron-irradiation. PMID:21785235

  14. A Diagnostic Aid To Pulp Production

    NASA Astrophysics Data System (ADS)

    Kowalski, Allan; Lebensold, Julian M.

    1989-03-01

    Pitch deposits in the production of pulp from wood are a very significant problem in the pulp and paper industry. Conservative estimates place the annual cost at around $30 million a year. At the present time problems in this domain are handled by human experts, whose time might otherwise be available for research. Development of an expert system in this area would be expected to have several beneficial effects. Quantitatively, it will decrease down time, thus allowing for greater production, and qualitatively it will decrease the occurrence of contamination in the final pulp.

  15. Review of the clinical research conducted by the Consortium for Improving Survival of Lymphoma of the Korean Society of Hematology Lymphoma Working Party

    PubMed Central

    Kim, Won Seog; Kim, Jin Seok; Park, Byeong-Bae

    2013-01-01

    The Consortium for Improving Survival of Lymphoma (CISL) in Korean Society of Hematology Lymphoma Working Party had first meeting in February, 2006 with 10 institutions and 12 members. Now CISL comprised of 64 centers. CISL has concentrated research activity on lymphomas which are relatively frequent in Korea and has tried to give favors for the Korean lymphoma patients. CISL has conducted more than 30 retrospective studies to evaluate Korean peculiar lymphoma subtypes. More than 30 prospective trials have been being performed for diffuse large B-cell lymphoma, marginal zone lymphoma, extra-nodal NK/T-cell lymphoma, and so on. The first prospective trial for advanced marginal zone lymphoma has led to use Rituximab containing chemotherapy with the re-imbursement of health insurance in Korea. The multi-center trials of the CISL with new therapeutic modalities will improve further the survival of lymphoma patients not only quantitatively but also qualitatively. PMID:24086936

  16. Recent Advances in Pulp Capping Materials: An Overview

    PubMed Central

    Qureshi, Asma; E., Soujanya; Nandakumar; Pratapkumar; Sambashivarao

    2014-01-01

    Emphasis has shifted from the “doomed” organ concept of an exposed pulp to one of hope and recovery. The era of vital-pulp therapy has been greatly enhanced with the introduction of various pulp capping materials. The aim of this article is to summarize and discuss about the various and newer pulp capping materials used for protection of the dentin-pulp complex. PMID:24596805

  17. [Comparison of sorting of fluorescently and magnetically labelled dental pulp stem cells].

    PubMed

    Kerényi, Farkas; Tarapcsák, Szabolcs; Hrubi, Edit; Baráthne, Szabó Ágnes; Hegedüs, Viktória; Balogh, Sára; Bágyi, Kinga; Varga, Gábor; Hegedüs, Csaba

    2016-03-01

    Stem cells are present in many tissues, such as dental pulp. Stem cells can be easily isolated from dental pulp because third molars are often removed from patients. Stem cells could be separated from the tissue derived heterogeneous cell population. There are two main methods to separate a cell type from the other ones: the fluorescence activated cell sorting (FACS) and the magnetic activated cell sorting (MACS). The aim of this study was to compare these methods' effect on cell surviving and population growth after sorting on dental pulp cells. The anti-STRO-1 antibody was used as primary antibody to specifically label stem cells. Two secondary antibodies were used: magnetic or fluorescent labelled. We sorted the cells by MACS or by FACS or by combination of both (MACS-FACS). Our results show that the effectivity of MACS and FACS sorting are comparable while of MACS-FACS was significantly higher (MACS 79.53 ± 5.78%, FACS 88.27 ± 3.70%, MACS-FACS 98.43 ± 0.67%). The cell surviving and the post-sorting population growth, on the contrary, are very different. The cell population is growing on first week after MACS but after FACS did not. Moreover, after MACS-FACS, on first week the cell number of population decreased. Taken together, our results suggest to use MACS instead of FACS, at least in case of sorting dental pulp stem cells with anti-STRO-1 antibody. PMID:27188159

  18. Females increase reproductive investment in response to helper-mediated improvements in allo-feeding, nest survival, nestling provisioning and post-fledging survival in the Karoo scrub-robin Cercotrichas coryphaeus

    USGS Publications Warehouse

    Lloyd, P.; Andrew, Taylor W.; Du Plessis, M.A.; Martin, T.E.

    2009-01-01

    In many cooperatively-breeding species, the presence of one or more helpers improves the reproductive performance of the breeding pair receiving help. Helper contributions can take many different forms, including allo-feeding, offspring provisioning, and offspring guarding or defence. Yet, most studies have focussed on single forms of helper contribution, particularly offspring provisioning, and few have evaluated the relative importance of a broader range of helper contributions to group reproductive performance. We examined helper contributions to multiple components of breeding performance in the Karoo scrub-robin Cercotrichas coryphaeus, a facultative cooperative breeder. We also tested a prediction of increased female investment in reproduction when helpers improve conditions for rearing young. Helpers assisted the breeding male in allo-feeding the incubating female, increasing allo-feeding rates. Greater allo-feeding correlated with greater female nest attentiveness during incubation. Nest predation was substantially lower among pairs breeding with a helper, resulting in a 74% increase in the probability of nest survival. Helper contributions to offspring provisioning increased nestling feeding rates, resulting in a reduced incidence of nestling starvation and increased nestling mass. Nestling mass had a strong, positive effect on post-fledging survival. Controlling for female age and habitat effects, annual production of fledged young was 130% greater among pairs breeding with a helper, and was influenced most strongly by helper correlates with nest survival, despite important helper effects on offspring provisioning. Females breeding with a helper increased clutch size, supporting the prediction of increased female investment in reproduction in response to helper benefits. ?? 2009 J. Avian Biol.

  19. Role of antiviral therapy in reducing recurrence and improving survival in hepatitis B virus-associated hepatocellular carcinoma following curative resection (Review)

    PubMed Central

    ZUO, CHAOHUI; XIA, MAN; WU, QUNFENG; ZHU, HAIZHEN; LIU, JINGSHI; LIU, CHEN

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality worldwide, with the majority of cases associated with persistent hepatitis B virus (HBV) or hepatitis C virus infection. In particular, chronic HBV infection is a predominant risk factor for the development of HCC in Asian and African populations. Hepatic resection, liver transplantion and radiofrequency ablation are increasingly used for the curative treatment of HCC, however, the survival rate of HCC patients who have undergone curative resection remains unsatisfactory due to the high recurrence rate. HCC is a complex disease that is typically resistant to the most commonly used types of chemotherapy and radiotherapy; therefore, the development of novel treatment strategies is required to improve the survival rate of this disease. A high viral load of HBV DNA is the most important correctable risk factor for HCC recurrence, for example nucleos(t)ide analogs improve the outcome following curative resection of HBV-associated HCC, and interferon-α exhibits antitumor activity against various types of cancer via direct inhibitory effects on tumor cells, anti-angiogenesis, enhanced immunogenicity of tumors, immunomodulatory effects and liver dysfunction. In the present review, antiviral treatment for HBV-associated HCC is described as a strategy to reduce recurrence and improve survival. PMID:25624883

  20. Radiation therapy for favorable histology Wilms tumor: Prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

    SciTech Connect

    Breslow, Norman E. . E-mail: norm@u.washington.edu; Beckwith, J. Bruce; Haase, Gerald M.; Kalapurakal, John A.; Ritchey, Michael L.; Shamberger, Robert C.; Thomas, Patrick; D'Angio, Giulio J.; Green, Daniel M.

    2006-05-01

    Purpose: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Methods and Materials: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Results: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Conclusions: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes.

  1. Antiangiogenic agents significantly improve survival in tumor-bearing mice by increasing tolerance to chemotherapy-induced toxicity

    PubMed Central

    Zhang, Danfang; Hedlund, Eva-Maria E.; Lim, Sharon; Chen, Fang; Zhang, Yin; Sun, Baocun; Cao, Yihai

    2011-01-01

    Chemotherapy-induced broad toxicities are the leading cause of the drug-induced mortality in cancer patients. Antiangiogenic drugs (ADs) in combination with chemotherapy are widely used as front-line therapy for the treatment of various human cancers. However, the beneficial mechanisms underlying combination therapy are poorly understood. Here we show that, in several murine tumor models, administration of sunitinib markedly reduced chemotherapy-induced bone marrow toxicity. Intriguingly, in a sequential treatment regimen, delivery of ADs followed by chemotherapy demonstrated superior survival benefits compared with simultaneous administration of two drugs. In murine tumor models, we show that VEGF increased chemotoxicity by synergistically suppressing bone marrow hematopoiesis with cytostatic drugs. These findings shed light on molecular mechanisms by which ADs in combination with chemotherapy produce survival benefits in cancer patients and provide conceptual information guiding future designs of clinical trials, current practice, and optimization of ADs for the treatment of cancer. PMID:21367692

  2. Indirect pulp therapy and stepwise excavation.

    PubMed

    Bjørndal, Lars

    2008-01-01

    Various treatment concepts have been suggested to solve the deep carious lesion dilemma. Recent systematic reviews are presented. Their conclusions are based on very few studies, and the main message is that optimal randomized clinical studies are lacking. Observational studies on indirect pulp treatment and stepwise excavation demonstrate that these treatments avoid pulp exposures, but it cannot be said which approach is best. A less invasive modified stepwise excavation approach is described, focusing on changing on active lesion into on arrested lesion even without performing an excavation close to the pulp. In Denmark and Sweden a randomized clinical multi-center trial is currently taking place, the Caries and Pulp (CAP) trial. This trial is investigating the effects of stepwise excavation over 2 visits versus 1 complete excavation of deep caries in permanent teeth. Guidelines for treatment are presented. PMID:18615988

  3. Indirect pulp therapy and stepwise excavation.

    PubMed

    Bjørndal, Lars

    2008-07-01

    Various treatment concepts have been suggested to solve the deep carious lesion dilemma. Recent systematic reviews are presented. Their conclusions are based on very few studies, and the main message is that optimal randomized clinical studies are lacking. Observational studies on indirect pulp treatment and stepwise excavation demonstrate that these treatments avoid pulp exposures, but it cannot be said which approach is best. A less invasive modified stepwise excavation approach is described, focusing on changing an active lesion into an arrested lesion even without performing an excavation close to the pulp. In Denmark and Sweden a randomized clinical multi-center trial is currently taking place, the Caries and Pulp (CAP) trial. This trial is investigating the effects of stepwise excavation over 2 visits versus 1 complete excavation of deep caries in permanent teeth. Guidelines for treatment are presented. PMID:18565369

  4. ADVANCED FILTRATION OF PULP MILL WASTES

    EPA Science Inventory

    Laboratory and pilot plants studies of reverse osmosis (hyperfiltration) and ultrafiltration of pulp mill wastes were performed by International Paper Company and Oak Ridge National Laboratory (subcontractor). Decker filtrates were treated with dynamically formed reverse osmosis ...

  5. Improved Acid Stress Survival of Lactococcus lactis Expressing the Histidine Decarboxylation Pathway of Streptococcus thermophilus CHCC1524*

    PubMed Central

    Trip, Hein; Mulder, Niels L.; Lolkema, Juke S.

    2012-01-01

    Degradative amino acid decarboxylation pathways in bacteria generate secondary metabolic energy and provide resistance against acid stress. The histidine decarboxylation pathway of Streptococcus thermophilus CHCC1524 was functionally expressed in the heterologous host Lactococcus lactis NZ9000, and the benefits of the newly acquired pathway for the host were analyzed. During growth in M17 medium in the pH range of 5–6.5, a small positive effect was observed on the biomass yield in batch culture, whereas no growth rate enhancement was evident. In contrast, a strong benefit for the engineered L. lactis strain was observed in acid stress survival. In the presence of histidine, the pathway enabled cells to survive at pH values as low as 3 for at least 2 h, conditions under which the host cells were rapidly dying. The flux through the histidine decarboxylation pathway in cells grown at physiological pH was under strict control of the electrochemical proton gradient (pmf) across the membrane. Ionophores that dissipated the membrane potential (ΔΨ) and/or the pH gradient (ΔpH) strongly increased the flux, whereas the presence of glucose almost completely inhibited the flux. Control of the pmf over the flux was exerted by both ΔΨ and ΔpH and was distributed over the transporter HdcP and the decarboxylase HdcA. The control allowed for a synergistic effect between the histidine decarboxylation and glycolytic pathways in acid stress survival. In a narrow pH range around 2.5 the synergism resulted in a 10-fold higher survival rate. PMID:22351775

  6. The use of Emeraid Exotic Carnivore Diet improves postsurgical recovery and survival of long-tailed ducks

    USGS Publications Warehouse

    Olsen, Glenn H.; Ford, Scott; Perry, Matthew C.; Wells-Berlin, Alicia M.

    2010-01-01

    Gavage feeding is a commonly used technique in wildlife rehabilitation. While implanting satellite transmitters in long-tailed ducks (Clangula hyemalis), a need for extra postsurgical nutritional support was identified. A new product, Emeraid Exotic Carnivore Diet, has proven effective in maintaining and even increasing the birds' body weights while in captivity. This has resulted in a 54-g increase in weight at release and better survival postrelease. Tips for mixing and using the new diet are included.

  7. Improved acid stress survival of Lactococcus lactis expressing the histidine decarboxylation pathway of Streptococcus thermophilus CHCC1524.

    PubMed

    Trip, Hein; Mulder, Niels L; Lolkema, Juke S

    2012-03-30

    Degradative amino acid decarboxylation pathways in bacteria generate secondary metabolic energy and provide resistance against acid stress. The histidine decarboxylation pathway of Streptococcus thermophilus CHCC1524 was functionally expressed in the heterologous host Lactococcus lactis NZ9000, and the benefits of the newly acquired pathway for the host were analyzed. During growth in M17 medium in the pH range of 5-6.5, a small positive effect was observed on the biomass yield in batch culture, whereas no growth rate enhancement was evident. In contrast, a strong benefit for the engineered L. lactis strain was observed in acid stress survival. In the presence of histidine, the pathway enabled cells to survive at pH values as low as 3 for at least 2 h, conditions under which the host cells were rapidly dying. The flux through the histidine decarboxylation pathway in cells grown at physiological pH was under strict control of the electrochemical proton gradient (pmf) across the membrane. Ionophores that dissipated the membrane potential (ΔΨ) and/or the pH gradient (ΔpH) strongly increased the flux, whereas the presence of glucose almost completely inhibited the flux. Control of the pmf over the flux was exerted by both ΔΨ and ΔpH and was distributed over the transporter HdcP and the decarboxylase HdcA. The control allowed for a synergistic effect between the histidine decarboxylation and glycolytic pathways in acid stress survival. In a narrow pH range around 2.5 the synergism resulted in a 10-fold higher survival rate. PMID:22351775

  8. Neoadjuvant Chemotherapy with FOLFOX4 Regimen to Treat Advanced Gastric Cancer Improves Survival without Increasing Adverse Events: A Retrospective Cohort Study from a Chinese Center

    PubMed Central

    Zhu, Rui-Juan; Yang, Gui-Fang; Li, Yan

    2014-01-01

    Background/Aim. To evaluate the clinical efficacy of FOLFOX4 (5-fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for advanced gastric cancer (AGC). Patients and Methods. Fifty-eight AGC patients were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and 35 in the adjuvant group. R0 resection, survival, and adverse events were compared. Results. The two groups were well-matched, with no significant differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes dissection (16 (0–49) versus 13 (3–40)) between the two groups (P > 0.05). The number of lymph node metastases in the neoadjuvant group (3 (0–14)) was significantly fewer than that in the adjuvant group (6 (0–27)) (P = 0.04). The neoadjuvant group had significantly better median overall survival (29.0 versus 22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant group (P = 0.013). The positive expression rate of Ki-67 in the neoadjuvant group (40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; P = 0.015). Conclusion. The FOLFOX4 neoadjuvant chemotherapy could improve survival without increasing adverse events in patients with AGC. PMID:25136668

  9. Linking Reproduction and Survival Can Improve Model Estimates of Vital Rates Derived from Limited Time-Series Counts of Pinnipeds and Other Species

    PubMed Central

    Battaile, Brian C.; Trites, Andrew W.

    2013-01-01

    We propose a method to model the physiological link between somatic survival and reproductive output that reduces the number of parameters that need to be estimated by models designed to determine combinations of birth and death rates that produce historic counts of animal populations. We applied our Reproduction and Somatic Survival Linked (RSSL) method to the population counts of three species of North Pacific pinnipeds (harbor seals, Phoca vitulina richardii (Gray, 1864); northern fur seals, Callorhinus ursinus (L., 1758); and Steller sea lions, Eumetopias jubatus (Schreber, 1776))—and found our model outperformed traditional models when fitting vital rates to common types of limited datasets, such as those from counts of pups and adults. However, our model did not perform as well when these basic counts of animals were augmented with additional observations of ratios of juveniles to total non-pups. In this case, the failure of the ratios to improve model performance may indicate that the relationship between survival and reproduction is redefined or disassociated as populations change over time or that the ratio of juveniles to total non-pups is not a meaningful index of vital rates. Overall, our RSSL models show advantages to linking survival and reproduction within models to estimate the vital rates of pinnipeds and other species that have limited time-series of counts. PMID:24324541

  10. Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: Final results of BSG 98 prospective trial

    PubMed Central

    Frappaz, Didier; Schell, Matthias; Thiesse, Philippe; Marec-Bérard, Perrine; Mottolese, Carmine; Perol, David; Bergeron, Christophe; Philip, Thierry; Ricci, Anne Claire; Galand-Desme, Sophie; Szathmari, Alexandru; Carrie, Christian

    2008-01-01

    Radiation therapy remains the only treatment that provides clinical benefit to children with diffuse brainstem tumors. Their median survival, however, rarely exceeds 9 months. The authors report a prospective trial of front-line chemotherapy aimed at delaying radiation until time of clinical progression. The aim was to investigate the possibility that radiotherapy would maintain its activity in children whose disease progressed after chemotherapy. Twenty-three patients took part in this protocol, the BSG 98 protocol, which consisted of frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules. Each cycle included three courses delivered monthly; the first course was 1,3-bis(2-chloroethyl)-1-nitrosourea– cisplatin, and the second and third were high-dose methotrexate. Three patients underwent one cycle; 5 patients each, two and three cycles; and 10 patients, four cycles. Twenty of the 23 patients eventually received local radiation therapy. A historical cohort of 14 patients who received at least local radiation therapy served as controls. Four patients experienced severe iatrogenic infections, and 11 patients required platelet transfusions. Median survival increased significantly in patients participating in the protocol compared to that in the historical controls (17 months, 95% confidence interval [CI], 10–23 months, vs. 9 months, 95% CI, 8–10 months; p = 0.022), though hospitalization was prolonged (57 vs. 25 days, p = 0.001). Although frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules significantly increases overall median survival, its cost from infection and hospitalization deserves honest discussion with the children and their parents. PMID:18577561

  11. Postoperative dendritic cell vaccine plus activated T-cell transfer improves the survival of patients with invasive hepatocellular carcinoma

    PubMed Central

    Shimizu, Koichi; Kotera, Yoshihito; Aruga, Atsushi; Takeshita, Nobuhiro; Katagiri, Satoshi; Ariizumi, Shun-ichi; Takahashi, Yutaka; Yoshitoshi, Kenji; Takasaki, Ken; Yamamoto, Masakazu

    2014-01-01

    The recurrence rate after surgery in patients with hepatocellular carcinoma (HCC) is very high, while prognosis is quite poor. However, there is no standard treatment to prevent recurrence of HCC after a curative operation. In this study, we investigated the clinical utilization of an autologous tumor lysate-pulsed dendritic cell vaccine plus ex vivo activated T cell transfer (ATVAC) in an adjuvant setting for postoperative HCC as a non-randomized controlled trial. Ninety-four patients with invasive HCC received informed consent information regarding the study, and 42 opted to have the ATVAC after surgery. Their recurrence-free survival (RFS) and overall survival (OS) were measured after 5 years and compared with those of 52 patients who selected to have the curative operation alone. The median RFS and OS were 24.5 months and 97.7 months in the patients receiving adjuvant ATVAC and 12.6 months and 41.0 months in the group receiving surgery alone (P = 0.011 and 0.029). In the treated group, patients with positive delayed-type hypersensitivity (DTH) had a better prognosis (RFS P = 0.019, OS P = 0.025). No adverse events of grade 3 or more were observed. A postoperative dendritic cell vaccine plus activated T cell transfer would be a feasible and effective treatment for preventing recurrence in HCC patients and achieving long-term survival especially in DTH positive patients. PMID:24419174

  12. The native ant, Tapinoma melanocephalum, improves the survival of an invasive mealybug, Phenacoccus solenopsis, by defending it from parasitoids.

    PubMed

    Feng, Dong-Dong; Michaud, J P; Li, Pan; Zhou, Zhong-Shi; Xu, Zai-Fu

    2015-01-01

    Mutualistic ants can protect their partners from natural enemies in nature. Aenasius bambawalei is an important parasitoid of the the invasive mealybug Phenacoccus solenopsis. We hypothesized that mutualism between native ants and mealybugs would favor survival of mealybugs. To test this, we examined effects of tending by the native mutualistic ant Tapinoma melanocephalum on growth of P. solenopsis colonies on Chinese hibiscus, Hibiscus rosa-sinensis, in a field setting. Ant workers with access to honeydew of mealybugs lived much longer than those provisioned only with water in the laboratory, and number of ant workers foraging increased significantly with growth of mealybug colonies in the field. In later observations, there were significant differences in densities of mealybugs between ant-tended and -excluded treatments. Survival rate of mealybugs experiencing parasitoid attack was significantly higher on ant-tended plants than on ant-excluded plants. When the parasitoid was excluded, there was no difference in survival rate of mealybugs between ant-tended and -excluded plants. In most cases, ants directly attacked the parasitoid, causing the parasitoid to take evasive action. We conclude that native ants such as T. melanocephalum have the potential to facilitate invasion and spread of P. solenopsis in China by providing them with protection from parasitoids. PMID:26503138

  13. The native ant, Tapinoma melanocephalum, improves the survival of an invasive mealybug, Phenacoccus solenopsis, by defending it from parasitoids

    PubMed Central

    Feng, Dong-Dong; Michaud, J.P.; Li, Pan; Zhou, Zhong-Shi; Xu, Zai-Fu

    2015-01-01

    Mutualistic ants can protect their partners from natural enemies in nature. Aenasius bambawalei is an important parasitoid of the the invasive mealybug Phenacoccus solenopsis. We hypothesized that mutualism between native ants and mealybugs would favor survival of mealybugs. To test this, we examined effects of tending by the native mutualistic ant Tapinoma melanocephalum on growth of P. solenopsis colonies on Chinese hibiscus, Hibiscus rosa-sinensis, in a field setting. Ant workers with access to honeydew of mealybugs lived much longer than those provisioned only with water in the laboratory, and number of ant workers foraging increased significantly with growth of mealybug colonies in the field. In later observations, there were significant differences in densities of mealybugs between ant-tended and -excluded treatments. Survival rate of mealybugs experiencing parasitoid attack was significantly higher on ant-tended plants than on ant-excluded plants. When the parasitoid was excluded, there was no difference in survival rate of mealybugs between ant-tended and -excluded plants. In most cases, ants directly attacked the parasitoid, causing the parasitoid to take evasive action. We conclude that native ants such as T. melanocephalum have the potential to facilitate invasion and spread of P. solenopsis in China by providing them with protection from parasitoids. PMID:26503138

  14. Mesenchymal stromal (stem) cells suppress pro-inflammatory cytokine production but fail to improve survival in experimental staphylococcal toxic shock syndrome

    PubMed Central

    2014-01-01

    Background Toxic shock syndrome (TSS) is caused by an overwhelming host-mediated response to bacterial superantigens produced mainly by Staphylococcus aureus and Streptococcus pyogenes. TSS is characterized by aberrant activation of T cells and excessive release of pro-inflammatory cytokines ultimately resulting in capillary leak, septic shock, multiple organ dysfunction and high mortality rates. No therapeutic or vaccine has been approved by the U.S. Food and Drug Administration for TSS, and novel therapeutic strategies to improve clinical outcome are needed. Mesenchymal stromal (stem) cells (MSCs) are stromal cells capable of self-renewal and differentiation. Moreover, MSCs have immunomodulatory properties, including profound effects on activities of T cells and macrophages in specific contexts. Based on the critical role of host-derived immune mediators in TSS, we hypothesized that MSCs could modulate the host-derived proinflammatory response triggered by Staphylococcal enterotoxin B (SEB) and improve survival in experimental TSS. Methods Effects of MSCs on proinflammatory cytokines in peripheral blood were measured in wild-type C57BL/6 mice injected with 50 μg of SEB. Effects of MSCs on survival were monitored in fatal experimental TSS induced by consecutive doses of D-galactosamine (10 mg) and SEB (10 μg) in HLA-DR4 transgenic mice. Results Despite significantly decreasing serum levels of IL-2, IL-6 and TNF induced by SEB in wild-type mice, human MSCs failed to improve survival in experimental TSS in HLA-DR4 transgenic mice. Similarly, a previously described downstream mediator of human MSCs, TNF-stimulated gene 6 (TSG-6), did not significantly improve survival in experimental TSS. Furthermore, murine MSCs, whether unstimulated or pre-treated with IFNγ, failed to improve survival in experimental TSS. Conclusions Our results suggest that the immunomodulatory effects of MSCs are insufficient to rescue mice from experimental TSS, and that mediators other than

  15. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer

    PubMed Central

    Russell, Samantha; Duquette, Mark; Liu, Joyce; Drapkin, Ronny; Lawler, Jack; Petrik, Jim

    2015-01-01

    Most women are diagnosed with epithelial ovarian cancer (EOC) at advanced stage, where therapies have limited effectiveness and the long-term survival rate is low. We evaluated the effects of combined antiangiogenic and chemotherapy treatments on advanced stage EOC. Treatment of EOC cells with a recombinant version of the thrombospondin-1 type I repeats (3TSR) induced more apoptotic cell death (36.5 ± 9.6%) in vitro compared to untreated controls (4.1 ± 1.4). In vivo, tumors were induced in an orthotopic, syngeneic mouse model of advanced stage EOC. Mice were treated with 3TSR (4 mg/kg per day) alone or in combination with chemotherapy drugs delivered with maximum tolerated dose or metronomic scheduling. Pretreatment with 3TSR induced tumor regression, normalized tumor vasculature, and improved uptake of chemotherapy drugs. Combination 3TSR and metronomic chemotherapy induced the greatest tumor regression (6.2-fold reduction in size compared to PBS-treated controls) and highest survival when treatment was initiated at advanced stage. 3TSR binding to its receptor, CD36 (cluster of differentiation 36), increased binding of CD36 and SHP-1, which significantly inhibited phosphorylation of the VEGF receptor. In this study, we describe a novel treatment approach and mechanism of action with 3TSR and chemotherapy that induces regression of advanced stage EOC and significantly improves survival.—Russell, S., Duquette, M., Liu, J., Drapkin, R., Lawler, J., Petrik, J. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer. PMID:25395453

  16. Postmastectomy Radiotherapy Improves Disease-Free Survival of High Risk of Locoregional Recurrence Breast Cancer Patients with T1-2 and 1 to 3 Positive Nodes

    PubMed Central

    Li, Fang-Yan; Lin, Qin; Lin, Huan-Xin; Sun, Jia-Yuan

    2015-01-01

    Objectives The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node. Methods We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients). Results The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0–1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients. Conclusions PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes. PMID:25781605

  17. Integrating black liquor gasification with pulping - Process simulation, economics and potential benefits

    NASA Astrophysics Data System (ADS)

    Lindstrom, Erik Vilhelm Mathias

    Gasification of black liquor could drastically increase the flexibility and improve the profit potential of a mature industry. The completed work was focused on research around the economics and benefits of its implementation, utilizing laboratory pulping experiments and process simulation. The separation of sodium and sulfur achieved through gasification of recovered black liquor, can be utilized in processes like modified continuous cooking, split sulfidity and green liquor pretreatment pulping, and polysulfide-anthraquinone pulping, to improve pulp yield and properties. Laboratory pulping protocols have been developed for these modified pulping technologies and different process options evaluated. The process simulation work around BLG has led to the development of a WinGEMS module for the low temperature MTCI steam reforming process, and case studies comparing a simulated conventional kraft process to different process options built around the implementation of a BLG unit operation into the kraft recovery cycle. Pulp yield increases of 1-3% points with improved product quality, and the potential for capital and operating cost savings relative to the conventional kraft process have been demonstrated. Process simulation work has shown that the net variable operating cost for a pulping process using BLGCC is highly dependent on the cost of lime kiln fuel and the selling price of green power to the grid. Under the assumptions taken in the performed case study, the BLGCC process combined with split sulfidity or PSAQ pulping operations had net variable operating cost 2-4% greater than the kraft reference. The influence of the sales price of power to the grid is the most significant cost factor. If a sales price increase to 6 ¢/KWh for green power could be achieved, cost savings of about $40/ODtP could be realized in all investigated BLG processes. Other alternatives to improve the process economics around BLG would be to modify or eliminate the lime kiln unit

  18. High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning

    PubMed Central

    Reshef, Ran; Huffman, Austin P.; Gao, Amy; Luskin, Marlise R.; Frey, Noelle V.; Gill, Saar I.; Hexner, Elizabeth O.; Kambayashi, Taku; Loren, Alison W.; Luger, Selina M.; Mangan, James K.; Nasta, Sunita D.; Richman, Lee P.; Sell, Mary; Stadtmauer, Edward A.; Vonderheide, Robert H.; Mick, Rosemarie; Porter, David L.

    2015-01-01

    Purpose To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. Patients and Methods We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. Results Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 108 CD8 cells per kilogram optimally segregated patients receiving CD8hi and CD8lo grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8hi graft, whereas approximately half of younger donors provided CD8hi grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8lo doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8hi doses (P = .03), but not for recipients of younger unrelated donor CD8lo grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. Conclusion Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT. PMID:26056179

  19. Daily home gardening improved survival for older people with mobility limitations: an 11-year follow-up study in Taiwan

    PubMed Central

    Lêng, Chhian Hūi; Wang, Jung-Der

    2016-01-01

    Aims To test the hypothesis that gardening is beneficial for survival after taking time-dependent comorbidities, mobility, and depression into account in a longitudinal middle-aged (50–64 years) and older (≥65 years) cohort in Taiwan. Methods The cohort contained 5,058 nationally sampled adults ≥50 years old from the Taiwan Longitudinal Study on Aging (1996–2007). Gardening was defined as growing flowers, gardening, or cultivating potted plants for pleasure with five different frequencies. We calculated hazard ratios for the mortality risks of gardening and adjusted the analysis for socioeconomic status, health behaviors and conditions, depression, mobility limitations, and comorbidities. Survival models also examined time-dependent effects and risks in each stratum contingent upon baseline mobility and depression. Sensitivity analyses used imputation methods for missing values. Results Daily home gardening was associated with a high survival rate (hazard ratio: 0.82; 95% confidence interval: 0.71–0.94). The benefits were robust for those with mobility limitations, but without depression at baseline (hazard ratio: 0.64, 95% confidence interval: 0.48–0.87) when adjusted for time-dependent comorbidities, mobility limitations, and depression. Chronic or relapsed depression weakened the protection of gardening. For those without mobility limitations and not depressed at baseline, gardening had no effect. Sensitivity analyses using different imputation methods yielded similar results and corroborated the hypothesis. Conclusion Daily gardening for pleasure was associated with reduced mortality for Taiwanese >50 years old with mobility limitations but without depression. PMID:27486315

  20. Vector control improves survival of three species of prairie dogs (Cynomys) in areas considered enzootic for plague

    USGS Publications Warehouse

    Biggins, Dean E.; Godbey, Jerry L.; Gage, Kenneth L.; Carter, Leon G.; Montenieri, John A.

    2010-01-01

    Plague causes periodic epizootics that decimate populations of prairie dogs (PDs) (Cynomys), but the means by which the causative bacterium (Yersinia pestis) persists between epizootics are poorly understood. Plague epizootics in PDs might arise as the result of introductions of Y. pestis from sources outside PD colonies. However, it remains possible that plague persists in PDs during interepizootic periods and is transmitted at low rates among highly susceptible individuals within and between their colonies. If this is true, application of vector control to reduce flea numbers might reduce mortality among PDs. To test whether vector control enhances PD survival in the absence of obvious plague epizootics, we reduced the numbers of fleas (vectors for Y. pestis) 96–98% (1 month posttreatment) on 15 areas involving three species of PDs (Cynomys leucurus, Cynomys parvidens in Utah, and Cynomys ludovicianus in Montana) during 2000–2004 using deltamethrin dust delivered into burrows as a pulicide. Even during years without epizootic plague, PD survival rates at dusted sites were 31–45% higher for adults and 2–34% higher for juveniles compared to survival rates at nondusted sites. Y. pestis was cultured from 49 of the 851 flea pools tested (6882 total fleas) and antibodies against Y. pestis were identified in serum samples from 40 of 2631 PDs. Although other explanations are possible, including transmission of other potentially fatal pathogens by fleas, ticks, or other ectoparasites, our results suggest that plague might be maintained indefinitely in PD populations in the absence of free epizootics and widespread mortality among these animals. If PDs and their fleas support enzootic cycles of plague transmission, there would be important implications for the conservation of these animals and other species.

  1. Improved ischemic island skin flap survival with continuous intraarterial infusion of adenosine triphosphate--magnesium chloride and superoxide dismutase: a rat model.

    PubMed

    Zimmerman, T J; Sasaki, G H; Khattab, S

    1987-03-01

    Neurovascular island skin flaps are still hampered by occasional necrosis of their most distal aspect. Cells subjected to prolonged hypoxic conditions become intracellularly depleted of needed metabolic substrates and eventually die. Once hypoxic conditions are improved, ischemic tissue suffers further injury from the rapid accumulation of oxygen free radicals. This study showed 53% survival of a standard random flap constructed on the inferior epigastric neurovascular bundle of a rat. Random flap survival increased to 65% after intraarterial infusion of adenosine triphosphate--magnesium chloride (ATP-MgCl2); to 75% after superoxide dismutase infusion; and to 98% after combined ATP-MgCl2 and superoxide dismutase infusion. Neither substrate appeared to act by increasing blood flow to the ischemic tissue. PMID:3296921

  2. Dietary organic selenium improves growth, survival and resistance to Vibrio mimicus in cultured marron, Cherax cainii (Austin, 2002).

    PubMed

    Nugroho, Rudy Agung; Fotedar, Ravi

    2013-07-01

    To determine the effects of dietary organic selenium (OS) supplementation on the growth performance and immune competence of marron, Cherax cainii (Austin, 2002), a group of marron were fed 0.2 g kg(-1) of Sel-Plex(®) supplemented basal diet and then compared with another group (control) of marron fed basal diet without any supplementation. After 90 days of feeding, final weight, average weekly gains (AWG), relative gain rate (RGR), specific growth rate (SGR), survival, total and differential haemocyte counts (THC and DHC), were compared between the two groups. Surviving marron from each group were then divided into three sub-groups (three tanks per sub-group with seven marron per tank); (1) first sub-group was injected with 20 μL of 3.24 × 10(6) cfu Vibrio mimicus; (2) the second sub-group was injected with 20 μL normal saline and (3) the third sub-group was not subjected to injection and became the control group. THC, DHC, neutral red retention time (NRRT) and Vibrio ranks of post-injected marron were evaluated for 96 h, at every 24-h interval. The results showed that after 90 days of feeding, final weight, AWG, RGR, SGR, survival, THC, proportion of hyaline cells of OS-fed marron were significantly higher (P < 0.05) than the control group, whereas proportion of granular and semigranular cells were not affected by dietary OS. After challenging with V. mimicus, survival rate of marron without dietary OS significantly decreased (P < 0.05) as compared to the control group of marron. THC of marron in all sub-groups were significantly reduced (P < 0.05) after the challenge. However, THC and granular cells of sub-groups fed OS were higher than other sub-groups. Vibrio ranks and NRRT of marron fed OS were significantly lower and slower, respectively, than marron fed without OS. These findings demonstrated the benefits of OS inclusion in the marron diet in terms of growth, health and disease resistance. PMID:23603239

  3. Urethane dimethacrylate induces cytotoxicity and regulates cyclooxygenase-2, hemeoxygenase and carboxylesterase expression in human dental pulp cells.

    PubMed

    Chang, Hsiao-Hua; Chang, Mei-Chi; Wang, Hsin-Hui; Huang, Guay-Fen; Lee, Yuan-Ling; Wang, Yin-Lin; Chan, Chiu-Po; Yeung, Sin-Yuet; Tseng, Shuei-Kuen; Jeng, Jiiang-Huei

    2014-02-01

    The toxic effect of urethane dimethacrylate (UDMA), a major dental resin monomer, on human dental pulp is not fully clear. In this study, we investigated the influence of UDMA on the cytotoxicity, cell cycle distribution, apoptosis and related gene expression of dental pulp cells. The role of reactive oxygen species, hemeoxygenase-1 (HO-1) and carboxylesterase (CES) in UDMA cytotoxicity, was evaluated. UDMA induced morphological changes of pulp cells and decreased cell viability by 29-49% at concentrations of 0.1-0.35 mM. UDMA induced G0/G1, G2/M cell cycle arrest and apoptosis. The expression of cdc2, cyclinB1 and cdc25C was inhibited by UDMA. Moreover, UDMA stimulated COX-2, HO-1 and CES2 mRNA expression of pulp cells. The cytotoxicity of UDMA was attenuated by N-acetyl-l-cysteine, catalase and esterase, but was enhanced by Zn-protoporphyrin (HO-1 inhibitor), BNPP (CES inhibitor) and loperamide (CES2 inhibitor). Exposure of UDMA may potentially induce the inflammation and toxicity of dental pulp. These findings are important for understanding the clinical response of human pulp to resin monomers after operative restoration and pulp capping, and also provide clues for improvement of dental materials. PMID:24140606

  4. Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor.

    PubMed

    Glasner, Ariella; Avraham, Roi; Rosenne, Ella; Benish, Marganit; Zmora, Oded; Shemer, Shaily; Meiboom, Hadas; Ben-Eliyahu, Shamgar

    2010-03-01

    Clinical practice does not consider perioperative paracrine and neuroendocrine stress responses as risk factors for cancer recurrence, although recent animal studies provided supportive evidence. Suggested mechanisms include the effects of stress-hormones on tumor cells and on host physiology. In this study, in mice undergoing primary tumor excision, we tested the survival-enhancing potential of perioperative blockade of catecholamines and prostaglandins, and studied potential mediating mechanisms. C57BL/6J mice were inoculated intrafootpad with syngeneic B16F10.9-melanoma or Lewis lung carcinoma, and the paw was amputated when a developing tumor exceeded 100 microl. The clinically used beta-adrenergic antagonist propranolol, and/or the cyclooxygenase-2 inhibitor etodolac, were administered once before amputation, and recurrence-free survival was monitored. In different studies, NK cytotoxicity, leukocytes' molecular functional markers, and vascular endothelial growth factor secretion by tumor cells were studied in the context of surgery and drug treatments. The findings indicated that the combination of propranolol and etodolac, but neither drug alone, significantly and markedly improved survival rates in both tumor models, and was as effective as established immunostimulatory agents (IL-12 and polyinosinic-polycytiylic acid). Surgery markedly reduced NK cytotoxicity and NK cell expression of Fas ligand and CD11a, reduced all circulating lymphocyte-subtype concentrations, and increased corticosterone levels. Propranolol and etodolac administration counteracted these perturbations. B16 and 3LL secreted vascular endothelial growth factor in vitro, but secretion was not affected by catecholamine agonists, prostaglandins, corticosterone, propranolol, or etodolac. Overall, propranolol and etodolac administration, which could be applied perioperatively in most cancer patients with minimal risk and low cost, has counteracted several immunologic and endocrinologic

  5. Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage.

    PubMed

    Baylis, James R; St John, Alexander E; Wang, Xu; Lim, Esther B; Statz, Matthew L; Chien, Diana; Simonson, Eric; Stern, Susan A; Liggins, Richard T; White, Nathan J; Kastrup, Christian J

    2016-09-01

    Hemorrhage is the leading cause of preventable death in trauma, and hemorrhage from noncompressible junctional anatomic sites is particularly difficult to control. The current standard is QuikClot Combat Gauze packing, which requires 3 min of compression. We have created a novel dressing with calcium carbonate microparticles that can disperse and self-propel upstream against flowing blood. We loaded these microparticles with thrombin and tranexamic acid and tested their efficacy in a swine arterial bleeding model without wound compression. Anesthetized immature female swine received 5 mm femoral arteriotomies to induce severe junctional hemorrhage. Wounds were packed with kaolin-based QuikClot Combat Gauze (KG), propelled thrombin-microparticles with protonated tranexamic acid (PTG), or a non-propelling formulation of the same thrombin-microparticles with non-protonated tranexamic acid (NPTG). Wounds were not compressed after packing. Each animal then received one 15 mL/kg bolus of hydroxyethyl starch solution followed by Lactated Ringer as needed for hypotension (maximum: 100 mL/kg) for up to 3 h. Survival was improved with PTG (3-h survival: 8/8, 100%) compared with KG (3/8, 37.5%) and NPTG (2/8, 25%) (P <0.01). PTG animals maintained lower serum lactate and higher hemoglobin concentrations than NPTG (P <0.05) suggesting PTG decreased severity of subsequent hemorrhagic shock. However, total blood loss, Lactated Ringer infusion volumes, and mean arterial pressures of surviving animals were not different between groups (P >0.05). Thus, in this swine model of junctional arterial hemorrhage, gauze with self-propelled, prothrombotic microparticles improved survival and 2 indicators of hemorrhagic shock when applied without compression, suggesting this capability may enable better treatment of non-compressible junctional wounds. PMID:27206277

  6. Vitamin D treatment improves survival and infant lung structure after intra-amniotic endotoxin exposure in rats: potential role for the prevention of bronchopulmonary dysplasia.

    PubMed

    Mandell, Erica; Seedorf, Gregory; Gien, Jason; Abman, Steven H

    2014-03-01

    Vitamin D (vit D) has anti-inflammatory properties and modulates lung growth, but whether vit D can prevent lung injury after exposure to antenatal inflammation is unknown. We hypothesized that early and sustained vit D treatment could improve survival and preserve lung growth in an experimental model of bronchopulmonary dysplasia induced by antenatal exposure to endotoxin (ETX). Fetal rats (E20) were exposed to ETX (10 μg), ETX + Vit D (1 ng/ml), or saline (control) via intra-amniotic (IA) injections and delivered 2 days later. Newborn pups exposed to IA ETX received daily intraperitoneal injections of vit D (1 ng/g) or saline for 14 days. Vit D treatment improved oxygen saturations (78 vs. 87%; P < 0.001) and postnatal survival (84% vs. 57%; P < 0.001) after exposure to IA ETX compared with IA ETX alone. Postnatal vit D treatment improved alveolar and vascular growth at 14 days by 45% and 25%, respectively (P < 0.05). Vit D increased fetal sheep pulmonary artery endothelial cell (PAEC) growth and tube formation by 64% and 44%, respectively (P < 0.001), and prevented ETX-induced reductions of PAEC growth and tube formation. Vit D directly increased fetal alveolar type II cell (ATIIC) growth by 26% (P < 0.001) and enhanced ATIIC growth in the presence of ETX-induced growth suppression by 73% (P < 0.001). We conclude that antenatal vit D therapy improved oxygenation and survival in newborn rat pups and enhanced late lung structure after exposure to IA ETX in vivo, which may partly be due to direct effects on vascular and alveolar growth. PMID:24414254

  7. Potential of hot water extraction of birch wood to produce high-purity dissolving pulp after alkaline pulping.

    PubMed

    Borrega, Marc; Tolonen, Lasse K; Bardot, Fanny; Testova, Lidia; Sixta, Herbert

    2013-05-01

    The potential of hot water extraction of birch wood to produce highly purified dissolving pulp in a subsequent soda-anthraquinone pulping process was evaluated. After intermediate extraction intensities, pulps with low xylan content (3-5%) and high cellulose yield were successfully produced. Increasing extraction intensity further decreased the xylan content in pulp. However, below a xylan content of 3%, the cellulose yield dramatically decreased. This is believed to be due to cleavage of glycosidic bonds in cellulose during severe hot water extractions, followed by peeling reactions during alkaline pulping. Addition of sodium borohydride as well as increased anthraquinone concentration in the pulping liquor increased the cellulose yield, but had no clear effects on pulp purity and viscosity. The low intrinsic viscosity of pulps produced after severe extraction intensities and soda-anthraquinone pulping corresponded to the viscosity at the leveling-off degree of polymerization, suggesting that nearly all amorphous cellulose had been degraded. PMID:23260272

  8. Tityus serrulatus scorpion venom improves survival and lung inflammation in lethal sepsis induced by CLP in mice.

    PubMed

    Maciel, Márcia C G; Fialho, Eder M S; Guerra, Rosane N M; Borges, Valéria M; Kwasniewski, Fábio H; Nascimento, Flávia R F

    2014-10-01

    Tityus serrulatus venom (Tsv) modifies the behavior of immune cells and induces the production of inflammatory and anti-inflammatory cytokines; such action may interfere with physiological or pathological states. Because sepsis is characterized as an inflammatory disorder, the aim of present study was to investigate the effect of a non-lethal dose of Tsv in mice submitted to a polymicrobial infection by cecal ligation and puncture (CLP) model. The parameters evaluated were survival index, cellularity on lymphoid organs, peritoneal cavity and brochoalveolar space, production of IL-10, IL-12, IL-6, TNF-α, IFN-γ and MCP-1, pulmonary inflammation and oxidative burst. The results demonstrated that in sharp contrast to CLP group in which sepsis was lethal in a 24 h period all mice pretreated with Tsv survived even 60 h after CLP. Lung inflammation, another hallmark of CLP group, was also dramatically down regulated in Tsv/CLP group. Despite pretreatment with Tsv did not reduce the inflammatory serum cytokines when compared to CLP group; there was an increase in IL-10. In conclusion, subcutaneous Tsv administration 6 h before CLP was able to control the harmful effects of sepsis (lethality and lung inflammation). We suggest that both systemic IL-10 and oxidative burst are involved in this effect. PMID:24976596

  9. IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

    PubMed Central

    Murdocca, Michela; Malgieri, Arianna; Luchetti, Andrea; Saieva, Luciano; Dobrowolny, Gabriella; de Leonibus, Elvira; Filareto, Antonio; Quitadamo, Maria Chiara; Novelli, Giuseppe; Musarò, Antonio; Sangiuolo, Federica

    2012-01-01

    Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA is caused by low levels of survival motor neuron (SMN) protein that induce selective loss of α-motor neurons (MNs) in the spinal cord, resulting in progressive muscle atrophy and consequent respiratory failure. To date, no effective treatment is available to counteract the course of the disease. Among the different therapeutic strategies with potential clinical applications, the evaluation of trophic and/or protective agents able to antagonize MNs degeneration represents an attractive opportunity to develop valid therapies. Here we investigated the effects of IPLEX (recombinant human insulinlike growth factor 1 [rhIGF-1] complexed with recombinant human IGF-1 binding protein 3 [rhIGFBP-3]) on a severe mouse model of SMA. Interestingly, molecular and biochemical analyses of IGF-1 carried out in SMA mice before drug administration revealed marked reductions of IGF-1 circulating levels and hepatic mRNA expression. In this study, we found that perinatal administration of IPLEX, even if does not influence survival and body weight of mice, results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice. Additionally, we show that phenotypic changes observed are not SMN-dependent, since no significant SMN modification was addressed in treated mice. Collectively, our data indicate IPLEX as a good therapeutic candidate to hinder the progression of the neurodegenerative process in SMA. PMID:22669476

  10. Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high-fat diet.

    PubMed

    Leontieva, Olga V; Paszkiewicz, Geraldine M; Blagosklonny, Mikhail V

    2014-08-01

    Recent discoveries have revealed the key role of mTOR (target of rapamycin) in aging. Furthermore, rapamycin extends lifespan in mice, especially in female mice. Here, we treated obese male mice on high-fat diet with rapamycin given intermittently: either weekly (once a week) or alternating bi-weekly (three injections every other week). While only marginally reducing obesity, intermittent administration of rapamycin significantly extended lifespan. Significance was achieved for weekly treated group and for the three rapamycin-received groups combined. In weekly treatment group, 100% mice were alive by the age of 2 years, whereas 60% of mice died in untreated group by this age. The effect of weekly treatment on survival was highly significant and cannot be fully explained by partial reduction in obesity. Alternating bi-weekly treatments seem to be less effective than weekly treatment, although effects of additional factors (see ) may not be excluded. After one year of treatment, all survived mice were sacrificed 8 days after the last administration of rapamycin to avoid its direct interference with parameters examined. Fasting levels of cardiac and hepatic p-S6, a marker of mTORC1 activity, were lower in weekly treatment group compared with control mice. In contrast, levels of p-Akt (S473), glucose, triglycerides and insulin were unchanged, whereas leptin and IGF-1 tended to be lower. Thus, weekly treatment with rapamycin may slow down aging in obese male mice on high-fat diet. PMID:24655348

  11. Cross-platform comparison of independent datasets identifies an immune signature associated with improved survival in metastatic melanoma

    PubMed Central

    Lardone, Ricardo D.; Plaisier, Seema B.; Navarrete, Marian S.; Shamonki, Jaime M.; Jalas, John R.

    2016-01-01

    Platform and study differences in prognostic signatures from metastatic melanoma (MM) gene expression reports often hinder consensus arrival. We performed survival/outcome-based pairwise comparisons of three independent MM gene expression profiles using the threshold-free algorithm rank-rank hypergeometric overlap analysis (RRHO). We found statistically significant overlap for genes overexpressed in favorable outcome (FO) groups, but no overlap for poor outcome (PO) groups. This “favorable outcome signature” (FOS) of 228 genes coinciding on all three overlapping gene lists showed immune function predominated in FO MM. Surprisingly, specific cell signature-enrichment analysis showed B cell-associated genes enriched in FO MM, along with T cell-associated genes. Higher levels of B and T cells (p<0.05) and their relative proximity (p<0.05) were detected in FO-to-PO tumor comparisons from an independent MM patients cohort. Finally, expression of FOS in two independent Stage III MM tumor datasets correctly predicted clinical outcome in 12/14 and 44/70 patients using a weighted gene voting classifier (area under the curve values 0.96 and 0.75, respectively). This RRHO-based, cross-study analysis emphasizes the RRHO approach power, confirms T cells relevance for prolonged MM survival, supports a favorable role for B cells in anti-melanoma immunity, and suggests B cells potential as means of intervention in melanoma treatment. PMID:26883106

  12. [Study on dioxin emission for typical non-wood pulp making in China].

    PubMed

    Wang, Zhi-Fang; Ding, Qiong; Wang, Kai-Xiang; Wu, Chang-Min; Qu, Yun-Huan; Zhao, Xiao-Dong

    2012-02-01

    Based on the requirement of National Implementation Plan for the Stockholm Convention on Persistent Organic Pollutants (NIP), six industries including pulp and paper industry have been set as the priority key sectors to implement the best available technology and best environmental practice (BAT/BEP) within a specific time for UPOPs reduction. Non-wood pulping has always played important role in virgin pulp production in China, its elemental chlorinated bleaching process has been confirmed as main source of Dioxin emission for the sector. As the signature party of Stockholm Convention and long time existing country of non-wood pulping, identification of Dioxin emission situation is significant importance to China to committee the obligation of Stockholm Convention. The Dioxin concentrations in outflow water of bamboo, straw, reed, and bagasse pulping processes (chlorination alkaline extraction hypochlorite, CEH) are 41.8 pg x L(-1), 72.7 pg x L(-1), 7.46 pg x L(-1), and 19.7 pg x L(-1) respectively, which are all around the national waste water discharge standard (30 pg x L(-1)). But relevant data will easily exceed national standard while the limitation of unit water consumption for pulp making is decreased. So the application of best available techniques/best environmental practices (BAT/BEP) is very necessary to improve relevant mills up to the above standard, and proceed the sector meeting the national and international requirements for Dioxin emission. At the same time, the text calculates emission factors on bamboo, straw, reed and bagasse pulp making process through whole process monitoring, which will provide meaningful reference for increasing relevant factors in UNEP Toolkit. PMID:22509599

  13. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice

    PubMed Central

    2011-01-01

    Background Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. Methods We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n = 15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Results Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a

  14. Improved Survival and Reduced Phenotypic Severity Following AAV9/MECP2 Gene Transfer to Neonatal and Juvenile Male Mecp2 Knockout Mice

    PubMed Central

    Gadalla, Kamal KE; Bailey, Mark ES; Spike, Rosemary C; Ross, Paul D; Woodard, Kenton T; Kalburgi, Sahana Nagabhushan; Bachaboina, Lavanya; Deng, Jie V; West, Anne E; Samulski, R Jude; Gray, Steven J; Cobb, Stuart R

    2013-01-01

    Typical Rett syndrome (RTT) is a pediatric disorder caused by loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. The demonstrated reversibility of RTT-like phenotypes in mice suggests that MECP2 gene replacement is a potential therapeutic option in patients. We report improvements in survival and phenotypic severity in Mecp2-null male mice after neonatal intracranial delivery of a single-stranded (ss) AAV9/chicken β-actin (CBA)-MECP2 vector. Median survival was 16.6 weeks for MECP2-treated versus 9.3 weeks for green fluorescent protein (GFP)-treated mice. ssAAV9/CBA-MECP2–treated mice also showed significant improvement in the phenotype severity score, in locomotor function, and in exploratory activity, as well as a normalization of neuronal nuclear volume in transduced cells. Wild-type (WT) mice receiving neonatal injections of the same ssAAV9/CBA-MECP2 vector did not show any significant deficits, suggesting a tolerance for modest MeCP2 overexpression. To test a MECP2 gene replacement approach in a manner more relevant for human translation, a self-complementary (sc) adeno-associated virus (AAV) vector designed to drive MeCP2 expression from a fragment of the Mecp2 promoter was injected intravenously (IV) into juvenile (4–5 weeks old) Mecp2-null mice. While the brain transduction efficiency in juvenile mice was low (~2–4% of neurons), modest improvements in survival were still observed. These results support the concept of MECP2 gene therapy for RTT. PMID:23011033

  15. Reducing Endoglin Activity Limits Calcineurin and TRPC‐6 Expression and Improves Survival in a Mouse Model of Right Ventricular Pressure Overload

    PubMed Central

    Kapur, Navin K.; Qiao, Xiaoying; Paruchuri, Vikram; Mackey, Emily E.; Daly, Gerard H.; Ughreja, Keshan; Morine, Kevin J.; Levine, Jonathan; Aronovitz, Mark J.; Hill, Nicholas S.; Jaffe, Iris Z.; Letarte, Michelle; Karas, Richard H.

    2014-01-01

    Background Right ventricular (RV) failure is a major cause of mortality worldwide and is often a consequence of RV pressure overload (RVPO). Endoglin is a coreceptor for the profibrogenic cytokine, transforming growth factor beta 1 (TGF‐β1). TGF‐β1 signaling by the canonical transient receptor protein channel 6 (TRPC‐6) was recently reported to stimulate calcineurin‐mediated myofibroblast transformation, a critical component of cardiac fibrosis. We hypothesized that reduced activity of the TGF‐β1 coreceptor, endoglin, limits RV calcineurin expression and improves survival in RVPO. Methods and Results We first demonstrate that endoglin is required for TGF‐β1‐mediated calcineurin/TRPC‐6 expression and up‐regulation of alpha‐smooth muscle antigen (α‐SMA), a marker of myofibroblast transformation, in human RV fibroblasts. Using endoglin haploinsufficient mice (Eng+/−) we show that reduced endoglin activity preserves RV function, limits RV fibrosis, and attenuates activation of the calcineurin/TRPC‐6/α‐SMA pathway in a model of angio‐obliterative pulmonary hypertension. Next, using Eng+/− mice or a neutralizing antibody (Ab) against endoglin (N‐Eng) in wild‐type mice, we show that reduced endoglin activity improves survival and attenuates RV fibrosis in models of RVPO induced by pulmonary artery constriction. To explore the utility of targeting endoglin, we observed a reversal of RV fibrosis and calcineurin levels in wild‐type mice treated with a N‐Eng Ab, compared to an immunoglobulin G control. Conclusion These data establish endoglin as a regulator of TGF‐β1 signaling by calcineurin and TRPC‐6 in the RV and identify it as a potential therapeutic target to limit RV fibrosis and improve survival in RVPO, a common cause of death in cardiac and pulmonary disease. PMID:25015075

  16. Intensity-modulated radiotherapy following null-margin resection is associated with improved survival in the treatment of intrahepatic cholangiocarcinoma

    PubMed Central

    Jia, Angela Y.; Wu, Jian-Xiong; Zhao, Yu-Ting; Li, Ye-Xiong; Wang, Zhi; Rong, Wei-Qi; Wang, Li-Ming; Jin, Jing; Wang, Shu-Lian; Song, Yong-Wen; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Wang, Wen-Qing; Liu, Xin-Fan; Yu, Zi-Hao

    2015-01-01

    Background The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature. Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection. Methods Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study. Null-margin resection was performed on all patients; 14 patients were further treated with IMRT. The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy). The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively. Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049). Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081). IMRT was well-tolerated. Acute toxicity included one case of Grade 3 leukopenia; late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy. Conclusions The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC. Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels. PMID:25830032

  17. Improved neonatal survival after participatory learning and action with women’s groups: a prospective study in rural eastern India

    PubMed Central

    Roy, Swati Sarbani; Mahapatra, Rajendra; Rath, Shibanand; Bajpai, Aparna; Singh, Vijay; Rath, Suchitra; Nair, Nirmala; Tripathy, Prasanta; Gope, Raj Kumar; Sinha, Rajesh; Costello, Anthony; Pagel, Christina

    2013-01-01

    Abstract Objective To determine whether a women’s group intervention involving participatory learning and action has a sustainable and replicable effect on neonatal survival in rural, eastern India. Methods From 2004 to 2011, births and neonatal deaths in 36 geographical clusters in Jharkhand and Odisha were monitored. Between 2005 and 2008, these clusters were part of a randomized controlled trial of how women’s group meetings involving participatory learning and action influence maternal and neonatal health. Between 2008 and 2011, groups in the original intervention clusters (zone 1) continued to meet to discuss post-neonatal issues and new groups in the original control clusters (zone 2) met to discuss neonatal health. Logistic regression was used to examine neonatal mortality rates after 2008 in the two zones. Findings Data on 41 191 births were analysed. In zone 1, the intervention’s effect was sustained: the cluster-mean neonatal mortality rate was 34.2 per 1000 live births (95% confidence interval, CI: 28.3–40.0) between 2008 and 2011, compared with 41.3 per 1000 live births (95% CI: 35.4–47.1) between 2005 and 2008. The effect of the intervention was replicated in zone 2: the cluster-mean neonatal mortality rate decreased from 61.8 to 40.5 per 1000 live births between two periods: 2006–2008 and 2009–2011 (odds ratio: 0.69, 95% CI: 0.57–0.83). Hygiene during delivery, thermal care of the neonate and exclusive breastfeeding were important factors. Conclusion The effect of participatory women’s groups on neonatal survival in rural India, where neonatal mortality is high, was sustainable and replicable. PMID:24052679

  18. JAB1 accelerates odontogenic differentiation of dental pulp stem cells.

    PubMed

    Lian, Min; Zhang, Ye; Shen, Qijie; Xing, Jing; Lu, Xiaohui; Huang, Dan; Cao, Peipei; Shen, Shuling; Zheng, Ke; Zhang, Jinlong; Chen, Jie; Wang, Yi; Feng, Guijuan; Feng, Xingmei

    2016-06-01

    Jun activation domain-binding protein 1 (JAB1) is a multifunctional protein that participates in the control of cell proliferation and the stability of multiple proteins. JAB1 regulates several key proteins, and thereby produces varied effects on cell cycle progression, genome stability and cell survival. Some studies have shown that the loss of JAB1 in osteochondral progenitor cells severely impairs embryonic limb development in mice. However, the biological significance of JAB1 activity in the odontogenic differentiation of dental pulp stem cells (DPSCs) remains unclear. This study aimed to determine the role of JAB1, a key player in tooth development, in reparative dentin formation, especially odontogenic differentiation. We found that increased expression of JAB1 promoted odontogenic differentiation of DPSCs via Wnt/β-catenin signaling. The role of JAB1 in the odontogenic differentiation of DPSCs was further confirmed by knocking down JAB1. Our findings provide novel insights on odontogenic differentiation of DPSCs. PMID:26989054

  19. Microencapsulation in genipin cross-linked gelatine-maltodextrin improves survival of Bifidobacterium adolescentis during exposure to in vitro gastrointestinal conditions.

    PubMed

    Borza, Antonela D; Annan, Nana T; Moreau, Debra L; Allan-Wojtas, Paula M; Ghanem, Amyl; Rousseau, Dérick; Paulson, Allan T; Hansen, Lisbeth Truelstrup

    2010-01-01

    To improve survival during exposure to adverse conditions, probiotic Bifidobacterium adolescentis 15703T cells were encapsulated in novel mono-core and multi-core phase-separated gelatine-maltodextrin (GMD) microspheres where the gelatine (G) phase was cross-linked with genipin (GP). Microscopy showed that encapsulated cells were exclusively associated with maltodextrin (MD) core(s). Small (average diameter 37 microm) and large (70 microm) GMD and G microspheres were produced by modulating factors (e.g. mixing speed, surfactant, GP and G concentrations) affecting the size, structural stability and phase-separation. In vitro sequential gastro-intestinal (GI) juice challenge experiments revealed increased survival of cells encapsulated in GMD ( approximately 10(6-7) cfu mL(-1)) and G (approximately 10(5) cfu mL(-1)) microspheres as compared to free cells (approximately 10(4) cfu mL(-1)). In GMD microspheres, the bacteria derive energy from MD to survive during exposure to acid and bile salts. In conclusion, the novel food grade GMD microencapsulation formulation was shown to protect probiotic bifidobacteria from adverse conditions. PMID:19860547

  20. Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study

    PubMed Central

    Wu, San-Gang; Xie, Wei-Hao; Zhang, Zhao-Qiang; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; Yong Bao; He, Zhen-Yu

    2016-01-01

    This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC. PMID:27323696

  1. Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study.

    PubMed

    Wu, San-Gang; Xie, Wei-Hao; Zhang, Zhao-Qiang; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; Yong Bao; He, Zhen-Yu

    2016-01-01

    This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC. PMID:27323696

  2. Improved survival with the addition of radiotherapy to androgen deprivation: questions answered and a review of current controversies in radiotherapy for non-metastatic prostate cancer.

    PubMed

    Amini, Arya; Kavanagh, Brian D; Rusthoven, Chad G

    2016-01-01

    The contemporary standard of care for locally advanced high-risk prostate cancer includes a combination of dose-escalated radiotherapy (RT) plus androgen-deprivation therapy (ADT). However, 20 years ago, at the inception of the National Cancer Institute of Canada (NCIC) led study (NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110), the survival impact of prostate RT for high-risk disease was uncertain. Recently, Mason, Warde and colleagues presented the final results of this NCIC/MRC study (PMID: 25691677) randomizing 1,205 high-risk prostate cancer patients to ADT + RT vs. ADT alone. These updated results confirm substantial improvements with the addition of RT to ADT for the endpoints of overall survival (OS), disease-free survival (DFS), and biochemical recurrence. Close examination of subtleties of this trial's design highlight some of the most salient controversies in the field of prostate RT, including the risk-stratified roles of ADT, optimal ADT duration, and RT field design in the dose-escalated and intensity-modulated radiotherapy (IMRT) era. PMID:26855950

  3. Effects of Acellular Amniotic Membrane Matrix and Bone Marrow-Derived Mesenchymal Stem Cells in Improving Random Skin Flap Survival in Rats

    PubMed Central

    Chehelcheraghi, Farzaneh; Eimani, Hossein; Homayoonsadraie, Seyed; Torkaman, Giti; Amini, Abdollah; Alavi Majd, Hamid; Shemshadi, Hashem

    2016-01-01

    Background The necrotic skin flap represents a great challenge in plastic and reconstructive surgery. In this study, we evaluated the effect of bioscaffolds, acellular amniotic membranes (AAMs), and bone marrow-derived mesenchymal stem cells (BM-MSCs) on random skin flap (RSF) survival in rats by applying a cell-free extracellular matrix scaffold as a supportive component for the growth and proliferation of BM-MSCs on RSFs. AAM matrix scaffolds were created by incubating AMs in ethylenediaminetetraacetic acid 0.05% at 37°C, and cell scrapers were used. Objectives The aim of the present study was to assess the effect of AAM as a scaffold in TE, and combined with transplanted BM-MSCs, on the survival of RSFs and on the biomechanical parameters of the incision-wound flap margins 7 days after flap elevation. Materials and Methods BM-MSCs and AAMs were transplanted into subcutaneous tissue in the flap area. On the 7th postoperative day, the surviving flap areas were measured using digital imaging software, and the flap tissue was collected for evaluation. Forty rats were randomly divided into four groups of 10 each: group 1 received an AAM injection; group 2 underwent BM-MSC transplantation; group 3 received both AAM injection + BM-MSC transplantation; and group 4 was the control group, receiving only saline. Results The survival area in the AAM/BM-MSC group was significantly higher than in the control group (18.49 ± 1.58 versus 7.51 ± 2.42, P < 0.05). The biomechanical assessment showed no significant differences between the experimental groups and the control group (P > 0.05), and there was no correlation with flap survival. Conclusions Our findings showed that the treatment of flaps with BM-MSC and AAM transplantations significantly promoted flap survival compared to a control group. The viability of the flap was improved by combining BM-MSCs with AAM matrix scaffolds. PMID:27621924

  4. Improvement of Survi