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991.
Peacock SJ Limmathurotsakul D Lubell Y Koh GC White LJ Day NP Titball RW 《PLoS neglected tropical diseases》2012,6(1):e1488
Background
Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. Here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates.Methods and Findings
Melioidosis is highly endemic in Thailand and northern Australia, where a biodefense vaccine might be adopted for public health purposes. A cost-effectiveness analysis model was developed, which showed that a vaccine could be a cost-effective intervention in Thailand, particularly if used in high-risk populations such as diabetics. Cost-effectiveness was observed in a model in which only partial immunity was assumed. The review systematically summarized all melioidosis vaccine candidates and studies in animal models that had evaluated their protectiveness. Possible candidates included live attenuated, whole cell killed, sub-unit, plasmid DNA and dendritic cell vaccines. Live attenuated vaccines were not considered favorably because of possible reversion to virulence and hypothetical risk of latent infection, while the other candidates need further development and evaluation. Melioidosis is acquired by skin inoculation, inhalation and ingestion, but routes of animal inoculation in most published studies to date do not reflect all of this. We found a lack of studies using diabetic models, which will be central to any evaluation of a melioidosis vaccine for natural infection since diabetes is the most important risk factor.Conclusion
Vaccines could represent one strand of a public health initiative to reduce the global incidence of melioidosis. 相似文献992.
Park D Spencer JA Koh BI Kobayashi T Fujisaki J Clemens TL Lin CP Kronenberg HM Scadden DT 《Cell Stem Cell》2012,10(3):259-272
Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1(+) stromal cells with "MSC" features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1(+) population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton. 相似文献
993.
JH Sung FA Shah EH Cho SA Gim SJ Jeon KM Kim YM Kim MO Kim PO Koh 《Laboratory animal research》2012,28(2):77-82
Ginkgo biloba extract (EGb 761) exerts a neuroprotective effect against ischemic brain injury through an anti-apoptotic mechanism. Parvalbumin is a calcium buffering protein that plays an important role in modulating intracellular calcium concentration and regulating apoptotic cell death. The aim of this study was to investigate whether EGb 761 affects parvalbumin expression in cerebral ischemic injury. Adult male Sprague-Dawley rats were treated with vehicle or EGb 761 (100 mg/kg) prior to middle cerebral artery occlusion (MCAO) and cerebral cortex tissues were collected 24 h after MCAO. A proteomic approach revealed a reduction in parvalbumin expression in the vehicle-treated animals, whereas EGb 761 pretreatment attenuates the ischemic injury-induced decrease in parvalbumin expression. RT-PCR and Western blot analyses clearly confirmed the fact that EGb 761 prevents the injury-induced decrease in parvalbumin. Moreover, the results of immunohistochemical staining showed that the number of parvalbumin-positive cells was lower in vehicle-treated animals than in sham-operated animals, and EGb 761 averted this decrease. Thus, these results suggest that the maintenance of parvalbumin expression is associated with the neuroprotective function of EGb 761 against neuronal damage induced by ischemia. 相似文献
994.
Radiation therapy has been widely used for treating human cancers. However, cancer cells develop radioresistant phenotypes that decrease the efficacy of radiotherapy. Ionizing radiation (IR) induces the production of reactive oxygen species, which play an important role in apoptotic cell death. Therefore, radiation therapy combined with a sensitizer, which modulates cellular redox status, has the potential to enhance therapeutic efficacy in a variety of human cancers. Here, we investigated the radiosensitizing effects of ursolic acid (UA), a pentacyclic triterpenoid found in rosemary and holy basil. IR-induced apoptosis in cancer cell lines such as DU145, CT26 and B16F10 was significantly enhanced by UA, as reflected by DNA fragmentation, cellular redox status, mitochondrial dysfunction and modulation of apoptotic marker proteins. Additionally, UA combined with IR was also effective for inhibiting tumorigenesis in B16F10 melanoma cells implanted into mice. Taken together, these results suggest that applying UA together with IR may be an effective combination modality for treating cancer. 相似文献
995.
This study examined the cytoprotective mechanisms of a combination of ischemic preconditioning (IPC) and allopurinol against liver injury caused by ischemia/reperfusion (I/R). Allopurinol (50 mg/kg) was intraperitoneally administered 18 and 1 h before sustained ischemia. A rat liver was preconditioned by 10 min of ischemia, followed by 10 min of reperfusion, and then subjected to 90 min of ischemia, followed by 5 h of reperfusion. Rats were pretreated with adenosine deaminase (ADA), 3,7-dimethyl-1-[2-propargyl]-xanthine (DMPX), and N-nitro-l-arginine methyl ester (l-NAME) before IPC. Hepatic nitrite and nitrate and eNOS protein expression levels were increased by the combination of IPC and allopurinol. This increase was attenuated by ADA, DMPX, and l-NAME. I/R induced an increase in alanine aminotransferase activity, whereas it decreased the hepatic glutathione level. A combination of IPC and allopurinol attenuated these changes, which were abolished by ADA, DMPX, and l-NAME. The increase in the liver wet weight-to-dry weight ratio after I/R was attenuated by the combination of IPC and allopurinol. In contrast, hepatic bile flow was decreased after I/R, which was attenuated by the combination of IPC and allopurinol. These changes were restored by l-NAME. I/R induced a decrease in the level of mitochondrial dehydrogenase, whereas it increased mitochondrial swelling. A combination of IPC and allopurinol attenuated these changes, which were restored by ADA, DMPX, and l-NAME. Our findings suggest that a combination of IPC and allopurinol reduces post-ischemic hepatic injury by enhancing NO generation. 相似文献
996.
Won-Young Kim Jae-Young Moon Jin Won Huh Sang-Ho Choi Chae-Man Lim Younsuck Koh Yong Pil Chong Sang-Bum Hong 《PloS one》2016,11(3)
Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03–15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia. 相似文献
997.
998.
Vicari KJ Tallam SS Shatova T Koh KJ Scarlata CJ Humbird D Wolfrum EJ Beckham GT 《Biotechnology for biofuels》2012,5(1):23
ABSTRACT: BACKGROUND: Cost-effective production of lignocellulosic biofuels remains a major financial and technical challenge at the industrial scale. A critical tool in biofuels process development is the techno-economic (TE) model, which calculates biofuel production costs using a process model and an economic model. The process model solves mass and energy balances for each unit, and the economic model estimates capital and operating costs from the process model based on economic assumptions. The process model inputs include experimental data on the feedstock composition and intermediate product yields for each unit. These experimental yield data are calculated from primary measurements. Uncertainty in these primary measurements is propagated to the calculated yields, to the process model, and ultimately to the economic model. Thus, outputs of the TE model have a minimum uncertainty associated with the uncertainty in the primary measurements. RESULTS: We calculate the uncertainty in the Minimum Ethanol Selling Price (MESP) estimate for lignocellulosic ethanol production via a biochemical conversion process: dilute sulfuric acid pretreatment of corn stover followed by enzymatic hydrolysis and co-fermentation of the resulting sugars to ethanol. We perform a sensitivity analysis on the TE model and identify the feedstock composition and conversion yields from three unit operations (xylose from pretreatment, glucose from enzymatic hydrolysis, and ethanol from fermentation) as the most important variables. The uncertainty in the pretreatment xylose yield arises from multiple measurements, whereas the glucose and ethanol yields from enzymatic hydrolysis and fermentation, respectively, are dominated by a single measurement: the fraction of insoluble solids (fIS) in the biomass slurries. CONCLUSIONS: We calculate a $0.15/gal uncertainty in MESP from the TE model due to uncertainties in primary measurements. This result sets a lower bound on the error bars of the TE model predictions. This analysis highlights the primary measurements that merit further development to reduce the uncertainty associated with their use in TE models. While we develop and apply this mathematical framework to a specific biorefinery scenario here, this analysis can be readily adapted to other types of biorefining processes and provides a general framework for propagating uncertainty due to analytical measurements through a TE model. 相似文献
999.
H Tsuchiya T Onishi S Takamoto S Morimoto K Fukuo S Imanaka H Yamamoto S Yukawa E Koh T Sonoda 《Endocrinologia japonica》1985,32(6):851-861
A 52-year-old man with an acromegalic appearance of prolonged duration suffered abdominal colic attacks and hematuria during the middle of the course of the disease. The patient was diagnosed as having urolithiasis caused by increased urinary calcium. The calcium metabolic disorder was not considered to be due to hyperparathyroidism because serum calcium and PTH levels were within the normal range and no abnormality was observed in a parathyroidal scintigraph. The serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels (55.0 and 73.0 pg/ml) were higher than the normal range (27.2-53.8 pg/ml). A selective adenomectomy by the transsphenoidal route (Hardy's method) was performed, resulting in an improvement in the hypercalciuria and urolithiasis, and a decrease in the levels of serum 1,25-(OH)2D (23.0 and 23.0 pg/ml). These findings suggest that GH may promote the activation of vitamin D in the kidney in acromegaly, resulting in an acceleration of calcium absorption in the intestine through the action of activated vitamin D and the induction of increased urinary calcium excretion by the urinary excretion of excessive blood calcium. 相似文献
1000.