This is a prospective randomized placebo-controlled double-blind crossover pilot study determining the effect of dichloroacetate on brain function under clamped hypoglycemia in T1DM.

开始日期2024-10-01

申办/合作机构

Yale University

NCT05120284 / Recruiting临床2期IIT

Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM)

Conduct a multicenter, open label Phase IIA trial of oral DCA in 40 surgical patients with recurrent GBM who have clinically indicated debulking surgery planned. No patients will be recruited at UF. Patients will be genotyped to establish safe dosing regimens and will be randomized to receive DCA (N=20) or no DCA (N=20) for one week prior to surgery. Deidentified blood and tumor tissue obtained at surgery will be assessed at UF for biochemical markers of DCA dynamics.

开始日期2022-07-01

申办/合作机构

University of Florida

NCT02616484 / Active, not recruiting临床3期IIT

Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:

The objective of this research study is to conduct a pivotal phase 3 trial of treatment with the investigational drug dichloroacetate (DCA) in young children with deficiency of the pyruvate dehydrogenase complex (PDC). PDC deficiency (PDCD) is the most common cause of congenital lactic acidosis and is a frequently fatal metabolic disease of childhood for which no proven treatment exists. The investigators predict that DCA represents targeted potential therapy for PDCD because of its ability to increase both the catalytic activity and stability of the enzyme complex. The conclusions of numerous laboratory and clinical investigations are consistent with this postulate and have led to the designation of DCA as an Orphan Product for congenital lactic acidosis by the Food and Drug Administration.
A novel Observer reported outcome (ObsRO) survey that is completed by study participant's parent/caregiver, is the efficacy outcome measure.
Funding Source - FDA OOPD

开始日期2020-07-14

申办/合作机构

University of Florida

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100 项与二氯乙酸相关的转化医学

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100 项与二氯乙酸相关的专利（医药）

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3,197

项与二氯乙酸相关的文献（医药）

2025-01-01·WATER RESEARCH

In-situ activation of persulfate by emplaced magnetite nanoparticles for degradation of 1,2-dichloroethane in porous media

Article

作者: Liu, Guansheng ; Chen, Wei ; Zhong, Hua ; Cui, Peng ; Zheng, Han ; Zhang, Juntao ; Zhou, Lian ; Zhao, Xude

In this study, column experiments were conducted to explore on the method of emplacement of magnetite nanoparticles (MNPs) for in situ activation of persulfate (PS) in sand porous media to degrade 1,2-dichloroethane (DCA), a typical recalcitrant chlorinated compound. Different molar ratios between PS and DCA (0:1, 2:1, 5:1 and 20:1) and mass contents of MNPs in the sand (0 %, 1.9 % and 5.4 %) were tested. In the absence of MNPs, degradation of DCA was negligible for a hydraulic retention time of 7 h. Presence of MNPs at the content of 1.9 % enhanced degradation of DCA and the highest removal efficiency (34.2 %) was observed at the PS-to-DCA molar ratio of 5:1. At the MNPs content of 5.4 %, increase of the PS-to-DCA molar ratio from 2:1 to 20:1 lead to not only increase in DCA removal efficiency but also substantial enhancement in chloride production, indicating that high PS concentration could cause significant degradation of the Cl-containing intermediates. In contrast to MNPs, Fe₃O₄ solids with much larger size (∼1 μm) were much less effective in activating PS for DCA removal even at a significantly higher content in the medium. The transport data could be well fitted by the one-site chemical nonequilibrium model, which showed kinetic DCA sorption to the MNPs as a key process for the transport. In the long-term injection experiment, a stable and significant removal of DCA (∼50 %) was observed for 254 days at the MNP content of 1.9 %. The results of this study show the potential of MNPs as a sustainable PS activator in injection-based in situ chemical oxidation for groundwater remediation.

2024-12-31·Gut microbes

Multi-omics reveals deoxycholic acid modulates bile acid metabolism via the gut microbiota to antagonize carbon tetrachloride-induced chronic liver injury

Article

作者: Chen, Tianbin ; Zeng, Yongjun ; Lin, Caorui ; Zhang, Li ; Ou, Qishui ; Huang, Huanhuan ; Yi, Qiang ; Zeng, Yongbin ; Zheng, Zhiyi ; Fu, Ya ; Liu, Can

Deoxycholic acid (DCA) serves essential functions in both physiological and pathological liver processes; nevertheless, the relationship among DCA, gut microbiota, and metabolism in chronic liver injury remain insufficiently understood. The primary objective of this study is to elucidate the potential of DCA in ameliorating chronic liver injury and evaluate its regulatory effect on gut microbiota and metabolism via a comprehensive multi-omics approach. Our study found that DCA supplementation caused significant changes in the composition of gut microbiota, which were essential for its antagonistic effect against CCl₄-induced chronic liver injury. When gut microbiota was depleted with antibiotics, the observed protective efficacy of DCA against chronic liver injury became noticeably attenuated. Mechanistically, we discovered that DCA regulates the metabolism of bile acids (BAs), including 3-epi DCA, Apo-CA, and its isomers 12-KLCA and 7-KLCA, IHDCA, and DCA, by promoting the growth of A.muciniphila in gut microbiota. This might lead to the inhibition of the IL-17 and TNF inflammatory signaling pathway, thereby effectively countering CCl₄-induced chronic liver injury. This study illustrates that the enrichment of A. muciniphila in the gut microbiota, mediated by DCA, enhances the production of secondary bile acids, thereby mitigating chronic liver injury induced by CCl₄. The underlying mechanism may involve the inhibition of hepatic IL-17 and TNF signaling pathways. These findings propose a promising approach to alleviate chronic liver injury by modulating both the gut microbiota and bile acids metabolism.

2024-12-31·REDOX REPORT

Assessment of renal pathophysiological processes and protective effect of quercetin on contrast-induced acute kidney injury in type 1 diabetic mice using diffusion tensor imaging

Article

作者: Wu, Ziqian ; Ouyang, Siyu ; Li, Yanfei ; Yao, Xiang ; Ren, Ke ; Hu, Jingyi

Purpose: To investigate the renal pathophysiological processes and protective effect of quercetin on contrast-induced acute kidney injury (CI-AKI) in mice with type 1 diabetic mellitus(DM) using diffusion tensor imaging(DTI).Methods: Mice with DM were divided into two groups. In the diabetic + contrast medium(DCA) group, the changes of the mice kidneys were monitored at 1, 24, 48, and 72 h after the injection of iodixanol(4gI/kg). The mice in the diabetic + contrast medium + quercetin(DCA + QE) group were orally given different concentrations of quercetin for seven days before injection of iodixanol. In vitro experiments, renal tubular epithelial (HK-2) cells exposed to high glucose conditions were treated with various quercetin concentrations before treatment with iodixanol(250 mgI/mL).Results: DTI-derived mean diffusivity(MD) and fractional anisotropy(FA) values can be used to evaluate CI-AKI effectively. Quercetin significantly increased the expression of Sirt 1 and reduced oxidative stress by increasing Nrf 2/HO-1/SOD1. The antiapoptotic effect of quercetin on CI-AKI was revealed by decreasing proteins level and by reducing the number of apoptosis-positive cells. In addition, flow cytometry indicated quercetin-mediated inhibition of M1 macrophage polarization in the CI-AKI.Conclusions: DTI will be an effective noninvasive tool in diagnosing CI-AKI. Quercetin attenuates CI-AKI on the basis of DM through anti-oxidative stress, apoptosis, and inflammation.

项与二氯乙酸相关的新闻（医药）

2023-10-03

·Science Daily

A promising treatment on the horizon for cancer-related fatigue

Cancer-related fatigue is a debilitating yet all-too-common condition, which can severely affect quality of life for patients undergoing treatment. For those struggling with CRF, there have been no effective pharmaceutical treatments for the constellation of symptoms that together define the syndrome. Researchers found that a metabolism-targeting drug called dichloroacetate (DCA) helped alleviate CRF in mice, without interfering with cancer treatments. Cancer-related fatigue (CRF) is a debilitating yet all-too-common condition, which can severely affect quality of life for patients undergoing treatment. For those struggling with CRF, there have been no effective pharmaceutical treatments for the constellation of symptoms that together define the syndrome. In a new study led by Yale Cancer Center researchers at Yale School of Medicine, the team found that a metabolism-targeting drug called dichloroacetate (DCA) helped alleviate CRF in mice, without interfering with cancer treatments. The findings are a pathway for future CRF research that may someday lead to a new therapy for patients. The results were published in American Journal of Physiology-Endocrinology and Metabolism on Oct. 2. "This study identifies dichloroacetate, an activator of glucose oxidation, as the first intervention, and particularly the first metabolism-focused intervention, to prevent the whole syndrome of cancer-related fatigue in preclinical models," said senior author Rachel Perry, who is a member of Yale Cancer Center. Researchers used tumor-bearing mouse models to investigate the effectiveness of DCA in treating cancer-related fatigue for patients living with melanoma. The group found that DCA did not affect the rates of tumor growth or compromise the effectiveness of immunotherapy or chemotherapy in two mouse cancer models. DCA also significantly preserved physical function and motivation in mice with late-stage tumors. The data suggests that DCA treatment may have several positive effects, including reducing oxidative stress in muscle tissue of tumor-bearing mice. The researchers said DCA could be a practice-changing approach in the future, when used as an adjuvant therapy to treat cancer-related fatigue. "We hope that this research will provide the bedrock for future clinical trials using dichloroacetate -- an FDA-approved drug for another indication (lactic acidosis) -- to treat the debilitating syndrome of cancer-related fatigue," said Perry, who is also an assistant professor of medicine (endocrinology) and of cellular and molecular physiology at Yale School of Medicine.

2023-03-16

·BioSpace

Saol Therapeutics enhances its IP portfolio for Dichloroacetate (DCA; SL-1009) in Glioblastoma and Rare Pediatric Cancers

By signing an agreement with Medosome Biotec By providing support for clinical trial treatment of GBM at the University of Florida By starting a collaborative research project in rare pediatric cancers with a leading cancer center ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, March 16, 2023 /PRNewswire/ -- Saol Therapeutics ("Saol"), a privately held, clinical-stage pharmaceutical company, announced today the signing of an agreement with Medosome Biotec, LLC to provide Saol the rights to use their patented genotype test for all potential indications where SL-1009 might be used as a therapy. The test is performed to identify potential mutations at GSTZ1 (glutathione S-transferase zeta 1 human enzyme) that categorize individuals as fast or slow metabolizers of DCA (SL-1009). Utilization of the genotype testing enables individual dosing, potentially reducing the incidence of treatment related adverse events. Prior to this agreement Saol only had rights to the patented genotype test for the indication of Pyruvate Dehydrogenase Complex Deficiency (PDCD). "We are pleased to have executed these agreements to support our pursuit of expanded opportunities beyond PDCD" As part of the agreement Saol will aid patient recruitment efforts for the Phase IIA Trial of DCA in Glioblastoma Multiforme (GBM) by providing additional funding and resource support. Glioblastoma is aggressive and the most common type of primary brain cancer in adults. GBM is difficult to treat and there is no known cure. This study, sponsored by the University of Florida and the Food and Drug Administration (FDA) (NCT05120284), is further supported in partnership with Medosome Biotec and Saol. Dr. Peter Stacpoole is Principal Investigator for the PDCD trial and the GBM trial and is Professor of Medicine at University of Florida. Dr. Stacpoole stated, "We are pleased to expand our partnership with Saol Therapeutics. Our partnership has led to over-enrollment of our Phase III study in PDCD (NCT02616484) and we mutually see the broader potential application of DCA as the prototypic inhibitor of Pyruvate Dehydrogenase Kinases (PDKs) that, in turn, inhibit PDC enzymatic activity. We look forward to collaborating with Saol on potential additional indications for DCA. Expansion of our collaboration on the GBM trial will result in the addition of more study sites, allowing for quicker recruitment of patients. We are hopeful that DCA will be an important addition to the treatment of GBM." Saol also recently signed a sponsored research agreement with a leading cancer center to evaluate DCA in rare pediatric solid tumors. The preclinical research will investigate DCA alone and in combination with chemotherapy in several different pediatric tumor models, such as Wilms, Neuroblastoma, Rhabdoid Tumor, Osteosarcoma, Ewing Sarcoma, and Rhabdomyosarcoma. Literature suggests that DCA could be effective in several rare, pediatric, solid tumors. The rationale for the pediatric tumor screening includes the fact that DCA has been widely studied in animals and humans and has a mechanism of action that might override the Warburg effect seen in cancer cells1,2,3,4. Saol is currently studying this medicine in children using a proprietary formulation developed for pediatric use (NCT02616484). "If the pre-clinical assessment provides encouraging data, the work already conducted in pediatric patients may allow us to quickly transition toward clinical investigation", commented Dr. Virinder Nohria, Chairman and Chief Medical Officer at Saol. These agreements, and the additional investments behind them, represent an important next step in the evolution of Saol Therapeutics as an emerging pharmaceutical company. "Now that we have completed enrollment in the PDCD trial we are rapidly transitioning to other important therapeutic areas, and are evaluating the utility of DCA (SL-1009) in adult and pediatric oncology indications with limited treatment options", said Saol CEO David Penake. "We are pleased to have executed these agreements to support our pursuit of expanded opportunities beyond PDCD". Saol expects to have topline data in the PDCD trial in the 3rd quarter of 2023. Should the results of the trial support a subsequent FDA approval, it will be the first and only medicine approved for this rare, pediatric indication. References Aminzadeh S, Vidali S, Sperl W, Kofler B, Feichtinger RG. Energy metabolism in neuroblastoma and Wilms tumor. Transl Pediatr. 2015 Jan;4(1):20-32. doi: 10.3978/j.issn.2224-4336.2015.01.04. Guo JQ, Tang HY, Wang CD, Sang BT, Liu X, Yi FP, Liu GL, Wu XM. Influence of Dichloroacetate on Wilms' Tumor in vitro. Ann Clin Lab Sci. 2022 Jan;52(1):101-108. PMID: 35181623. Kankotia S, Stacpoole PW. Dichloroacetate and cancer: new home for an orphan drug? Biochim Biophys Acta. 2014 Dec;1846(2):617-29. doi: 10.1016/j.bbcan.2014.08.005. Tataranni T, Piccoli C. Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications. Oxid Med Cell Longev. 2019 Nov 14;2019:8201079. doi: 10.1155/2019/8201079. PMID: 31827705. About Dichloroacetate (DCA; SL-1009) DCA, a pan- PDK inhibitor, has the potential to be the 1st approved medication for the mitochondrial disease PDCD and will be available as an oral solution. Gene mutations in the mitochondrial Pyruvate Dehydrogenase Complex (PDC) lead to congenital PDCD. However, PDC is also inhibited by PDKs, that may be over-expressed in PDCD. DCA inhibits PDKs to stimulate residual PDC activity and increase energy (ATP) production by mitochondria. DCA dosing is based on a proprietary genetic test that dichotomizes subjects into "fast" and "slow" drug metabolizers, providing individualized dosing. About Saol Therapeutics Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda. Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases. Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations. For more information, visit . About Medosome Biotec Medosome Biotec, LLC is a privately held, preclinical and early-stage clinical pharmaceutical company with operations in Alachua, FL and Bloomington, IN. The Company focuses on pediatric diseases with an emphasis on developing and offering genetic tests for diagnosing rare diseases and providing personalized dosing of pharmaceutical drugs. For more information, visit Media contact: Brian Nappi, Senior Vice President Strategy, bnappi@saolrx.com

临床2期引进/卖出孤儿药上市批准

2022-10-04

·BioSpace

Saol Therapeutics Announces Enrollment Achievement in Pivotal Phase 3 Trial for Rare Mitochondrial Disease - Pyruvate Dehydrogenase Complex Deficiency (PDCD)

ROSWELL, Ga. and DUBLIN and HAMILTON, Bermuda, Oct. 4, 2022 /PRNewswire/ -- Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, announced today that the pivotal Phase 3 clinical trial evaluating Sodium Dichloroacetate (DCA) for the treatment of a rare, pediatric, ultra-orphan mitochondrial disease, Pyruvate Dehydrogenase Complex Deficiency (PDCD) has achieved its targeted enrollment. Saol is one of the trial collaborators, with topline results anticipated early in the second half of 2023. "I began working on a treatment for PDCD in the 1980s so it is extremely rewarding to finally reach this milestone" "There are many challenges to overcome when enrolling patients in clinical trials for rare diseases", said Saol Therapeutics CEO David Penake. "The hard work of the individual study sites, patient advocacy groups, genetic testing companies, and genetic counseling partners allowed us to exceed our enrollment target of 30 patients. Our team will now prepare for a rapid NDA submission should the treatment prove to be successful." This investigator-initiated, NIH and FDA funded trial, conducted in close partnership with University of Florida, Saol Therapeutics and Medosome Biotec, represents the culmination of years of work for Dr. Peter Stacpoole, Principal Investigator and Professor of Medicine at University of Florida. "I began working on a treatment for PDCD in the 1980s after a family in Connecticut contacted me to see if I could help their child, so it is extremely rewarding to finally reach this milestone", said Stacpoole. Philip E. Yeske, Ph.D., Science & Alliance Officer at United Mitochondrial Disease Foundation, commented "The mitochondrial disease patient community is deeply appreciative of the time, effort, and capital that Saol and its collaborators are investing into this project. An over-enrolled clinical trial is a testament to the desire of the PDCD patient families to play an active role in therapeutic development." Study Design This trial evaluates daily administration of DCA in children with a confirmed pathological mutation in the Pyruvate Dehydrogenase Complex or in a pyruvate dehydrogenase phosphatase gene. The primary efficacy outcome measure is based on a novel Observer Reported Outcome (ObsRO) survey developed specifically for this trial. The study design is a 9-month double-blind crossover comparison between DCA and placebo, during which the ObsRO is completed daily by a parent/caregiver, followed by an open label phase of DCA administration. More information on the clinical trial and participating institutions can be found at Phase 3 PDCD Trial. About DCA (SL-1009) DCA has the potential to be the 1st approved medication for the mitochondrial disease PDCD and will be available as an oral solution. Gene mutations in the mitochondrial Pyruvate Dehydrogenase Complex (PDC) lead to congenital PDCD. However, PDC is also inhibited by pyruvate dehydrogenase kinases (PDK), that may be over-expressed in PDCD. DCA inhibits PDKs to stimulate residual PDC activity and increase energy (ATP) production by mitochondria. DCA dosing is based on a proprietary genetic test that dichotomizes subjects into "fast" and "slow" drug metabolizers, providing individualized dosing. About Pyruvate Dehydrogenase Complex Deficiency (PDCD) PDCD is a mitochondrial disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle and leads to decreased ATP production and energy failure. It affects only a few hundred individuals in the U.S. It is a common cause of congenital lactic acidosis, a life-threatening condition that may occur as early as the neonatal period. Patients may also exhibit extreme tiredness (lethargy), poor feeding, and rapid breathing (tachypnea)and other signs of neurological and neuromuscular dysfunction, such as developmental delay, low muscle tone (hypotonia), abnormal eye movements and seizures. Signs and symptoms usually begin soon after birth but may appear later in childhood. There are currently no FDA-approved therapies for PDCD. About Saol Therapeutics Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda. Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases. Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations. For more information, visit . About Medosome Biotec Medosome Biotec, LLC is a privately held, preclinical and early-stage clinical pharmaceutical company with operations in Alachua, FL. The Company focuses on pediatric diseases with an emphasis on developing and offering genetic tests for diagnosing rare diseases and providing personalized dosing of pharmaceutical drugs. For more information, visit View original content: SOURCE Saol Therapeutics

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100 项与二氯乙酸相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D05857	二氯乙酸	-	DB08809

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
丙酮酸脱氢酶复合物缺乏症	临床3期	美国	Medosome Biotec LLC	2020-07-14
先天性乳酸酸中毒	临床3期	-	University of Florida	1998-10-01
乳酸性酸中毒	临床3期	-	The Valens Co., Inc.	-
乳酸性酸中毒	临床3期	-	Mallinckrodt Plc	-
创伤性脑损伤	临床3期	-	The Valens Co., Inc.	-
创伤性脑损伤	临床3期	-	Mallinckrodt Plc	-
心肌缺血	临床3期	-	Mallinckrodt Plc	-
心肌缺血	临床3期	-	The Valens Co., Inc.	-
多形性胶质母细胞瘤	临床2期	美国	Saol Therapeutics, Inc.	2022-07-01
多形性胶质母细胞瘤	临床2期	美国	University of Florida	2022-07-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01386632 (Pubmed) 人工标引	临床2期	局部晚期头颈部鳞状细胞癌	45	Chemoradiotherapy+dichloroacetate	積襯築範鏇糧範蓋蓋衊(壓積鹽鏇製顧窪願艱願) = However, there were no significant differences in grade 3/4 AE rates. 願製淵夢鏇壓選淵觸齋 (壓繭繭廠鏇繭壓憲憲築 ) 更多	积极	2022-03-21
				Placebo
NCT01386632 (CTgov)	临床2期	晚期头颈癌 \| 头颈部鳞状细胞癌	50	DCA (dichloroacetate) (DCA (Dichloroacetate) Treatment)	鑰廠鑰膚淵齋廠鹽糧淵(遞衊構鹹膚衊觸選獵鏇) = 繭廠膚衊顧鹹製衊積糧鹽蓋顧簾遞蓋獵鑰簾構 (鬱衊淵齋壓襯構築積衊, 餘築積鑰選簾膚鬱醖醖 ~ 憲製繭觸鬱觸糧窪簾構) 更多	-	2017-06-14
				Placebo (Placebo)	鑰廠鑰膚淵齋廠鹽糧淵(遞衊構鹹膚衊觸選獵鏇) = 鑰膚壓壓廠簾願夢築選鹽蓋顧簾遞蓋獵鑰簾構 (鬱衊淵齋壓襯構築積衊, 鏇廠膚膚艱簾鹽壓繭獵 ~ 齋醖繭簾製鹽顧繭繭壓) 更多
NCT01029925 (CTgov)	临床2期	转移性乳腺癌	7	Dichloroacetate (DCA)	築艱淵衊構憲遞齋蓋襯(範壓艱壓範糧願簾鑰構) = 壓壓獵壓遞網夢艱醖蓋獵齋網窪窪壓積艱範積 (醖艱觸範艱夢築選鹹觸, 艱範鑰齋獵鏇觸繭築艱 ~ 窪齋衊淵範鏇獵餘構構) 更多	-	2016-02-12
NCT01386632 (ASCO2015)	临床2期	局部晚期头颈部鳞状细胞癌	50	Dichloroacetate (DCA)	(繭憲夢窪齋範膚顧鏇鹹) = not significantly different (16% DCA vs 4% P; p = 0.35) 淵鹽構艱齋顧觸構夢築 (範獵蓋選襯醖蓋積遞蓋 ) 更多	-	2015-05-20
				Placebo
NCT01029925 (Pubmed \| J Cancer Res Clin Oncol)	临床2期	缺氧 \| 晚期非小细胞肺癌	7	Dichloroacetate	衊製鑰選製構顧壓簾顧(願襯製鬱製廠願顧鏇憲) = two patients had disease progression prior to the first scheduled scans 夢糧齋網艱遞築獵齋遞 (憲築獵觸憲選範選齋積 ) 更多	-	2014-03-01
AACR2012	N/A	乳腺癌	-	Dichloroacetate (DCA)	遞築鏇鬱餘鬱艱網醖壓(憲窪糧鹹網廠膚築鑰夢) = 製範遞艱繭鹽衊範餘廠齋鏇鬱餘齋蓋構構積製 (廠網願願製鬱鏇夢遞醖 )	-	2012-04-15