[ { "key": "DDBCD33E", "version": 16, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/DDBCD33E", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/DDBCD33E", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "DDBCD33E", "version": 16, "itemType": "book", "title": "nothing", "creators": [], "abstractNote": "", "series": "", "seriesNumber": "", "volume": "", "numberOfVolumes": "", "edition": "", "date": "", "publisher": "", "place": "", "originalDate": "", "originalPublisher": "", "originalPlace": "", "format": "", "numPages": "", "ISBN": "", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "ISSN": "", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [], "relations": {}, "dateAdded": "2015-03-06T01:42:35Z", "dateModified": "2015-03-06T01:42:35Z" } }, { "key": "D4MT33TW", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/D4MT33TW", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/D4MT33TW", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Auerbach et al.", "parsedDate": "2010-01", "numChildren": 0 }, "data": { "key": "D4MT33TW", "version": 15, "itemType": "journalArticle", "title": "Toxicity and carcinogenicity studies of methylene blue trihydrate in F344N rats and B6C3F1 mice", "creators": [ { "creatorType": "author", "firstName": "Scott S.", "lastName": "Auerbach" }, { "creatorType": "author", "firstName": "Douglas W.", "lastName": "Bristol" }, { "creatorType": "author", "firstName": "John C.", "lastName": "Peckham" }, { "creatorType": "author", "firstName": "Gregory S.", "lastName": "Travlos" }, { "creatorType": "author", "firstName": "Charles D.", "lastName": "Hébert" }, { "creatorType": "author", "firstName": "Rajendra S.", "lastName": "Chhabra" } ], "abstractNote": "Methylene blue trihydrate has a variety of biomedical and biologically therapeutic applications. Groups of 50 male and 50 female rats and mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 5, 25, or 50 mg/kg bw/day (rats) or 0, 2.5, 12.5, and 25 mg/kg bw/day (mice), 5 days per week for 2 years. In rats survival of all dosed groups was similar to that of the vehicle controls, whereas mice exhibited a dose-dependent increase in survival. Rats receiving 25 and 50 mg/kg bw/day and mice receiving 25 mg/kg bw/day developed mild anemia. The incidences of pancreatic islet cell adenoma and adenoma or carcinoma (combined) were increased in all dosed groups of male rats, but increases were statistically significant in 25 mg/kg bw/day males only and the dose–response was non-linear. There was a corresponding increase in the incidence of pancreatic islet cell hyperplasia but statistically significant only in the 50 mg/kg bw/day male rats. There were no significant increases in neoplastic transformation observed in the mice; however, positive trends were noted for adenoma or carcinoma (combined) of the small intestine and malignant lymphoma.", "publicationTitle": "Food and Chemical Toxicology", "publisher": "", "place": "", "date": "January 2010", "volume": "48", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "169-177", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Food and Chemical Toxicology", "DOI": "10.1016/j.fct.2009.09.034", "citationKey": "", "url": "http://www.sciencedirect.com/science/article/pii/S0278691509004426", "accessDate": "2014-11-24T02:44:21Z", "PMID": "", "PMCID": "", "ISSN": "0278-6915", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "ScienceDirect", "callNumber": "", "rights": "", "extra": "", "tags": [ { "tag": "Carcinogenicity", "type": 1 }, { "tag": "Chronic toxicity", "type": 1 }, { "tag": "Methemoglobin", "type": 1 }, { "tag": "Methylene blue trihydrate", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "FS2IE32N", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/FS2IE32N", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/FS2IE32N", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Cardigan et al.", "parsedDate": "2009-04", "numChildren": 1 }, "data": { "key": "FS2IE32N", "version": 15, "itemType": "journalArticle", "title": "Thrombin generation and clot formation in methylene blue-treated plasma and cryoprecipitate", "creators": [ { "creatorType": "author", "firstName": "Rebecca", "lastName": "Cardigan" }, { "creatorType": "author", "firstName": "Katherine", "lastName": "Philpot" }, { "creatorType": "author", "firstName": "Philip", "lastName": "Cookson" }, { "creatorType": "author", "firstName": "Roger", "lastName": "Luddington" } ], "abstractNote": "BACKGROUND: Methylene blue (MB) treatment of plasma is known to reduce the activity of clotting factors, but its effect on thrombin generation and clot formation is not well documented.\nSTUDY DESIGN AND METHODS: Individual clotting factors and inhibitors and global tests of thrombin generation and clot formation using rotational thrombelastometry (ROTEM) were assessed in a paired study of standard or MB plasma and cryoprecipitate (n = 20 each).\nRESULTS: MB treatment resulted in a 10 percent reduction in endogenous thrombin potential and 30 percent decrease in peak thrombin as well as the expected 20 to 35 percent loss of Factor (F)VIII, fibrinogen, and FXI activity. MB treatment had no effect on the rate of clot formation and increased the clot firmness by 20 percent as assessed by ROTEM. There were minimal further changes in either coagulation factor levels or thrombin generation when thawed plasma was stored for an additional 24 hours. FVIII and fibrinogen content of MB cryoprecipitate was reduced by 30 and 40 percent, respectively, but this was not associated with altered clot time or rate of clot formation by ROTEM and only an 8 percent decrease in clot firmness.\nCONCLUSIONS: It is concluded that MB treatment is associated with a reduction in the thrombin-generating capacity of plasma, but has very little effect on the strength of clot formation as assessed by thrombelastometry. The thrombin-generating capacity of standard and MB plasma is relatively unaltered by subsequent storage of thawed plasma at 4 degrees C for 24 hours.", "publicationTitle": "Transfusion", "publisher": "", "place": "", "date": "Apr 2009", "volume": "49", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "696-703", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Transfusion", "DOI": "10.1111/j.1537-2995.2008.02039.x", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "1537-2995", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 19170989", "tags": [ { "tag": "Algorithms", "type": 1 }, { "tag": "Blood Coagulation", "type": 1 }, { "tag": "Blood Coagulation Tests", "type": 1 }, { "tag": "Blood Preservation", "type": 1 }, { "tag": "Cold Temperature", "type": 1 }, { "tag": "Factor VIII", "type": 1 }, { "tag": "Fibrinogen", "type": 1 }, { "tag": "Hematologic Agents", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Methylene Blue", "type": 1 }, { "tag": "Protein Stability", "type": 1 }, { "tag": "Thrombin", "type": 1 }, { "tag": "blood", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "BQZW6WUZ", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/BQZW6WUZ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/BQZW6WUZ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Wischik et al.", "parsedDate": "2010-11-18", "numChildren": 10 }, "data": { "key": "BQZW6WUZ", "version": 15, "itemType": "patent", "title": "Therapeutic use of diaminophenothiazines", "creators": [ { "creatorType": "inventor", "firstName": "Claude Michel", "lastName": "Wischik" }, { "creatorType": "inventor", "firstName": "Damon Jude", "lastName": "Wischik" }, { "creatorType": "inventor", "firstName": "John Mervyn David", "lastName": "Storey" }, { "creatorType": "inventor", "firstName": "Charles Robert", "lastName": "Harrington" } ], "abstractNote": "The present invention relates generally to methods and materials for use in the treatment or prophylaxis of diseases, for example cognitive disorders, using diaminophenothiazines. In particular it relates to treatments having optimised pharmacokinetic properties, and dosage forms are intended to improve the relative cognitive or CNS benefits of the diaminophenothiazines, for instance compared to haematological effects.", "place": "", "country": "United States", "assignee": "Wis Ta Laboratories Ltd.", "issuingAuthority": "", "patentNumber": "US20100290986 A1", "filingDate": "2008-10-01 Oct 1, 2008", "pages": "", "applicationNumber": "", "priorityNumbers": "", "issueDate": "Nov 18, 2010", "priorityDate": "", "references": "", "legalStatus": "", "DOI": "", "citationKey": "", "url": "http://www.google.com/patents/US20100290986", "accessDate": "2015-03-05T03:08:47Z", "shortTitle": "", "language": "", "rights": "", "extra": "U.S. Classification 424/1.65, 514/224.8, 424/9.6, 424/9.1, 424/9.3; International Classification A61K31/5415, A61P25/16, A61K49/00, A61P25/28, A61P7/06, A61K51/04; Cooperative Classification A61K31/542; European Classification A61K31/542", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "BUWB9DXA", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/BUWB9DXA", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/BUWB9DXA", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Kumar and Atamna", "parsedDate": "2011-03-03", "numChildren": 1 }, "data": { "key": "BUWB9DXA", "version": 15, "itemType": "journalArticle", "title": "Therapeutic Approaches to Delay the Onset of Alzheimer's Disease", "creators": [ { "creatorType": "author", "firstName": "Raj", "lastName": "Kumar" }, { "creatorType": "author", "firstName": "Hani", "lastName": "Atamna" } ], "abstractNote": "The key cytopathologies in the brains of Alzheimer's disease (AD) patients include mitochondrial dysfunction and energy hypometabolism, which are likely caused by the accumulation of small aggregates of amyloid-β (Aβ) peptides. Thus, targeting these two abnormalities of the AD brain may hold promising therapeutic value for delaying the onset of AD. In his paper, we discuss two potential approaches to delay the onset of AD. The first is the use of low dose of diaminophenothiazins (redox active agents) to prevent mitochondrial dysfunction and to attenuate energy hypometabolism. Diaminophenothiazines enhance mitochondrial metabolic activity and heme synthesis, both key factors in intermediary metabolism of the AD brain.The second is to use the naturally occurring osmolytes to prevent the formation of toxic forms of Aβ and prevent oxidative stress. Scientific evidence suggests that both approaches may change course of the basic mechanism of neurodegeneration in AD. Osmolytes are brain metabolites which accumulate in tissues at relatively high concentrations following stress conditions. Osmolytes enhance thermodynamic stability of proteins by stabilizing natively-folded protein conformation, thus preventing aggregation without perturbing other cellular processes. Osmolytes may inhibit the formation of Aβ oligomers in vivo, thus preventing the formation of soluble oligomers. The potential significance of combining diaminophenothiazins and osmolytes to treat AD is discussed.", "publicationTitle": "Journal of Aging Research", "publisher": "", "place": "", "date": "2011-3-3", "volume": "2011", "issue": "", "section": "", "partNumber": "", "partTitle": "", "pages": "", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Aging Res", "DOI": "10.4061/2011/820903", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056246/", "accessDate": "2015-03-05T03:58:00Z", "PMID": "", "PMCID": "", "ISSN": "2090-2204", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: 21423548\nPMCID: PMC3056246", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "5T9UWEXE", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/5T9UWEXE", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/5T9UWEXE", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Petzer et al.", "parsedDate": "2014-02-01", "numChildren": 2 }, "data": { "key": "5T9UWEXE", "version": 15, "itemType": "journalArticle", "title": "The interactions of azure B, a metabolite of methylene blue, with acetylcholinesterase and butyrylcholinesterase", "creators": [ { "creatorType": "author", "firstName": "Anél", "lastName": "Petzer" }, { "creatorType": "author", "firstName": "Brian H.", "lastName": "Harvey" }, { "creatorType": "author", "firstName": "Jacobus P.", "lastName": "Petzer" } ], "abstractNote": "Methylene blue (MB) is reported to possess diverse pharmacological actions and is attracting increasing attention for the treatment of neurodegenerative disorders such as Alzheimer's disease. Among the pharmacological actions of MB, is the significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These activities may, at least in part, underlie MB's beneficial effects in Alzheimer's disease. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl metabolite, is the predominant species. Azure B has been shown to be pharmacologically active and also possesses a variety of biological actions. Azure B therefore may contribute to the pharmacological profile of MB. Based on these considerations, the present study investigates the possibility that azure B may, similar to MB, act as an inhibitor of human AChE and BuChE. The results document that azure B inhibits AChE and BuChE with IC50 values of 0.486μM and 1.99μM, respectively. The results further show that azure B inhibits AChE and BuChE reversibly, and that the modes of inhibition are most likely competitive. Although the AChE and BuChE inhibitory activities of azure B are twofold and fivefold, respectively, less potent than those recorded for MB [IC50(AChE)=0.214μM; IC50(BuChE)=0.389μM] under identical conditions, azure B may be a contributor to MB's in vivo activation of the cholinergic system and beneficial effects in Alzheimer's disease.", "publicationTitle": "Toxicology and Applied Pharmacology", "publisher": "", "place": "", "date": "Feb 1, 2014", "volume": "274", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "488-493", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Toxicol. Appl. Pharmacol.", "DOI": "10.1016/j.taap.2013.10.014", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "1096-0333", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 24161345", "tags": [ { "tag": "Acetylcholinesterase", "type": 1 }, { "tag": "Alzheimer Disease", "type": 1 }, { "tag": "Alzheimer's disease", "type": 1 }, { "tag": "Azure B", "type": 1 }, { "tag": "Azure Stains", "type": 1 }, { "tag": "Butyrylcholinesterase", "type": 1 }, { "tag": "Cholinesterase Inhibitors", "type": 1 }, { "tag": "Enzyme Inhibitors", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Inhibition", "type": 1 }, { "tag": "Inhibitory Concentration 50", "type": 1 }, { "tag": "Linear Models", "type": 1 }, { "tag": "Methylene Blue", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "E5XUNX6R", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/E5XUNX6R", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/E5XUNX6R", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Namdeo Tukaram et al.", "parsedDate": "2010", "numChildren": 1 }, "data": { "key": "E5XUNX6R", "version": 15, "itemType": "journalArticle", "title": "The Effects of Lactose, Microcrystalline Cellulose and Dicalcium Phosphate on Swelling and Erosion of Compressed HPMC Matrix Tablets: Texture Analyzer", "creators": [ { "creatorType": "author", "firstName": "Bendgude", "lastName": "Namdeo Tukaram" }, { "creatorType": "author", "firstName": "Iyer", "lastName": "Vidaya Rajagopalan" }, { "creatorType": "author", "firstName": "Poddar", "lastName": "Sushi Ikumar Shartchandra" } ], "abstractNote": "This paper reviews the use of texture analysis in studying the performance of hydrophilic matrices of highly soluble drugs and different types of excipients (i.e. water-soluble, water-insoluble and swellable, and water insoluble and non-swellable). Tablets were prepared by direct compression, and their swelling and erosion in presence of these different excipients were assessed with the help of volumetric, gravimetric, morphological, and rheological studies. Dissolution test was performed using USP 26 apparatus 2 modified by insertion of a sieve to prevent sticking of the tablets to the bottom of the vessel and allow them to swell 3-dimensionally. Loading 15% of the highly soluble drug in formulations containing 65% lactose showed the most pronounced swelling and erosion and the best sustained drug release, compared to matrices containing microcrystalline cellulose and dicalcium phosphate. The correlation between front movement, mass erosion and solute transport in relation to excipient type on progression of probe displacement and total work was examined throughout texture analysis studies. The formulation containing the soluble excipient lactose showed better swelling and erosion properties compared to formulations containing the swellable and insoluble excipients. In conclusion, it could be said that based on the distinct conventional dosage forms insertion of particular excipients in hydrophilic controlled release tablets containing water soluble drug, the finger print information of drug release profile could be obtained. To study the release profile from hydroxy propyl methyl cellulose K 15M matrices with different types of excpients, diltiazem hydrochloride was used as a model soluble drug.", "publicationTitle": "Iranian Journal of Pharmaceutical Research : IJPR", "publisher": "", "place": "", "date": "2010", "volume": "9", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "349-358", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Iran J Pharm Res", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870058/", "accessDate": "2015-03-05T18:05:47Z", "PMID": "", "PMCID": "", "ISSN": "1735-0328", "archive": "", "archiveLocation": "", "shortTitle": "The Effects of Lactose, Microcrystalline Cellulose and Dicalcium Phosphate on Swelling and Erosion of Compressed HPMC Matrix Tablets", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: 24381599\nPMCID: PMC3870058", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "CH6KEURZ", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/CH6KEURZ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/CH6KEURZ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Sankar et al.", "parsedDate": "2013-10", "numChildren": 1 }, "data": { "key": "CH6KEURZ", "version": 15, "itemType": "journalArticle", "title": "Survival with 98% methemoglobin levels in a school-aged child during the \"festival of colors\"", "creators": [ { "creatorType": "author", "firstName": "Jhuma", "lastName": "Sankar" }, { "creatorType": "author", "firstName": "Shashikant", "lastName": "Devangare" }, { "creatorType": "author", "firstName": "N. K.", "lastName": "Dubey" } ], "abstractNote": "Methemoglobin levels more than 70% have almost always been reported to have been fatal. The case of a 4-year-old boy who survived with methemoglobin levels of 98% is presented here. He was brought to the emergency department with complaints of vomiting, pain abdomen, and altered sensorium following accidental ingestion of paint thinner mixed with \"Holi\" colors. On examination, the child was in altered sensorium, cyanosed with saturations of 55%, who did not respond despite positive pressure ventilation with 100% oxygen. A possibility of toxic methemoglobinemia was considered and confirmed by finding of elevated methemoglobin levels of 98%. The child survived with definitive therapy with methylene blue and aggressive goal-directed approach.", "publicationTitle": "Pediatric Emergency Care", "publisher": "", "place": "", "date": "Oct 2013", "volume": "29", "issue": "10", "section": "", "partNumber": "", "partTitle": "", "pages": "1102-1103", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Pediatr Emerg Care", "DOI": "10.1097/PEC.0b013e3182a60024", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "1535-1815", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 24084608", "tags": [ { "tag": "Accidents", "type": 1 }, { "tag": "Alkanes", "type": 1 }, { "tag": "Antibiotic Prophylaxis", "type": 1 }, { "tag": "Cephalosporins", "type": 1 }, { "tag": "Ceremonial Behavior", "type": 1 }, { "tag": "Child, Preschool", "type": 1 }, { "tag": "Consciousness Disorders", "type": 1 }, { "tag": "Glucose-6-Phosphatase", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Hydrocarbons, Aromatic", "type": 1 }, { "tag": "Hydrocarbons, Halogenated", "type": 1 }, { "tag": "India", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Methemoglobin", "type": 1 }, { "tag": "Methemoglobinemia", "type": 1 }, { "tag": "Methylene Blue", "type": 1 }, { "tag": "Oxygen", "type": 1 }, { "tag": "Paint", "type": 1 }, { "tag": "Pneumonia, Aspiration", "type": 1 }, { "tag": "Solvents", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "AW43XKZP", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/AW43XKZP", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/AW43XKZP", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Ouf et al.", "parsedDate": "2003", "numChildren": 2 }, "data": { "key": "AW43XKZP", "version": 15, "itemType": "journalArticle", "title": "Study of solar photosensitization processes on dermatophytic fungi", "creators": [ { "creatorType": "author", "firstName": "Salama A.", "lastName": "Ouf" }, { "creatorType": "author", "firstName": "Mahmoud H.", "lastName": "Abdel-Kader" }, { "creatorType": "author", "firstName": "Hisham A.", "lastName": "Shokeir" }, { "creatorType": "author", "firstName": "Amira A.", "lastName": "El-Adly" } ], "abstractNote": "The antifungal activity of solar simulator was evaluated in presence of haematoporphyrin derivative (HPD), methylene blue (MB) and toluidine blue O (TBO) as photosensitizers. Seven dermatophytes were used as test fungi. The solar simulator at fluence rate 400 W/m2 for 30 minutes induced marked inhibition for spore germination of the photosensitized fungi. The rate of inhibition varied according to the fungal species and concentration of the photosensitizer. There was an increase in percentage inhibition of spore germination as the concentration of HPD or MB increased. Complete inhibition for spore germination of Trichophyton. verrucosum, T. mentagrophytes, and Miccrosporum canis was induced when these species were pretreated with 10(-3) M of HPD or MB before irradiation. Epidermophyton floccosum, T. rubrum, M. gypseum and T. violaceum were less sensitive to irradiation when pretreated with HPD or MB. On contrary, the maximum reduction in percentage spore germination was induced at the lowest concentration (10(-7) M) of TBO. The tested dermatophytes were mostly capable of producing different enzymes (keratinase, phosphatases, amylase, lipase). The separate application of radiation or photosensitizer was ineffective or exerted slight inhibition on enzyme production. However, the activity of the enzymes was drastically inhibited when the fungi were irradiated after their treatment with photosensitizer. T. verrucosum and T. mentagrophytes were the most sensitive. In a trail to apply a control measure against dermatomycosis using solar simulator radiation, the results revealed that the radiation was successful in curing the MB-photosensitized guinea pigs, artificially infected with T. verrucosum, T. mentagrophytes or M. canis. The percentage of recovery reached 100% in some treatments.", "publicationTitle": "Acta Microbiologica Polonica", "publisher": "", "place": "", "date": "2003", "volume": "52", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "65-79", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Acta Microbiol. Pol.", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0137-1320", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 12916729", "tags": [ { "tag": "Amylases", "type": 1 }, { "tag": "Animals", "type": 1 }, { "tag": "Arthrodermataceae", "type": 1 }, { "tag": "Dermatomycoses", "type": 1 }, { "tag": "Erythrocyte Count", "type": 1 }, { "tag": "Guinea Pigs", "type": 1 }, { "tag": "Hematoporphyrin Derivative", "type": 1 }, { "tag": "Hemoglobins", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Leukocyte Count", "type": 1 }, { "tag": "Lipase", "type": 1 }, { "tag": "Methylene Blue", "type": 1 }, { "tag": "Peptide Hydrolases", "type": 1 }, { "tag": "Phosphoric Monoester Hydrolases", "type": 1 }, { "tag": "Photosensitizing Agents", "type": 1 }, { "tag": "Spores, Fungal", "type": 1 }, { "tag": "Sunlight", "type": 1 }, { "tag": "Tolonium Chloride", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "QX4IF2QI", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/QX4IF2QI", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/QX4IF2QI", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Rojas et al.", "parsedDate": "2009-10-20", "numChildren": 0 }, "data": { "key": "QX4IF2QI", "version": 15, "itemType": "journalArticle", "title": "Striatal neuroprotection with methylene blue", "creators": [ { "creatorType": "author", "firstName": "J. C.", "lastName": "Rojas" }, { "creatorType": "author", "firstName": "N.", "lastName": "Simola" }, { "creatorType": "author", "firstName": "B. A.", "lastName": "Kermath" }, { "creatorType": "author", "firstName": "J. R.", "lastName": "Kane" }, { "creatorType": "author", "firstName": "T.", "lastName": "Schallert" }, { "creatorType": "author", "firstName": "F.", "lastName": "Gonzalez-Lima" } ], "abstractNote": "Recent literature indicates that low-dose Methylene Blue (MB), an autoxidizable dye with powerful antioxidant and metabolic enhancing properties, might prevent neurotoxin-induced neural damage and associated functional deficits. This study evaluated whether local MB may counteract the anatomical and functional effects of the intrastriatal infusion of the neurotoxin rotenone (Rot) in the rat. To this end, stereological analyses of striatal lesion volumes were performed and changes in oxidative energy metabolism in the striatum and related motor regions were mapped using cytochrome oxidase histochemistry. The influence of MB on striatal levels of oxidative stress induced by Rot was determined, and behavioral tests were used to investigate the effect of unilateral MB coadministration on motor asymmetry. Rot induced large anatomical lesions resembling “metabolic strokes,” whose size was greatly reduced in MB-treated rats. Moreover, MB prevented the decrease in cytochrome oxidase activity and the perilesional increase in oxidative stress associated with Rot infusion in the striatum. MB also prevented the indirect effects of the Rot-induced lesion on cytochrome oxidase activity in related motor regions, such as the striatal regions rostral and caudal to the lesion, the substantia nigra compacta and reticulata, and the pedunculopontine nucleus. At a network level, MB maintained a global strengthening of functional connectivity in basal ganglia–thalamocortical motor circuits, as opposed to the functional decoupling observed in Rot-alone subjects. Finally, MB partially prevented the behavioral sensorimotor asymmetries elicited by Rot. These results are consistent with protective effects of MB against neurotoxic damage in the brain parenchyma. This study provides the first demonstration of the anatomical, metabolic and behavioral neuroprotective effects of MB in the striatum in vivo, and supports the notion that MB could be a valuable intervention against neural damage associated with oxidative stress and energy hypometabolism.", "publicationTitle": "Neuroscience", "publisher": "", "place": "", "date": "October 20, 2009", "volume": "163", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "877-889", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Neuroscience", "DOI": "10.1016/j.neuroscience.2009.07.012", "citationKey": "", "url": "http://www.sciencedirect.com/science/article/pii/S0306452209011373", "accessDate": "2014-11-24T01:19:18Z", "PMID": "", "PMCID": "", "ISSN": "0306-4522", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "ScienceDirect", "callNumber": "", "rights": "", "extra": "", "tags": [ { "tag": "Cytochrome oxidase", "type": 1 }, { "tag": "Methylthioninium chloride", "type": 1 }, { "tag": "Parkinson Disease", "type": 1 }, { "tag": "Rotenone", "type": 1 }, { "tag": "mitochondria", "type": 1 }, { "tag": "stroke", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "T5F2494T", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/T5F2494T", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/T5F2494T", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "D'sa et al.", "parsedDate": "2014-08-12", "numChildren": 0 }, "data": { "key": "T5F2494T", "version": 15, "itemType": "journalArticle", "title": "Severe methemoglobinemia due to ingestion of toxicants", "creators": [ { "creatorType": "author", "firstName": "S. R.", "lastName": "D'sa" }, { "creatorType": "author", "firstName": "P.", "lastName": "Victor" }, { "creatorType": "author", "firstName": "M.", "lastName": "Jagannati" }, { "creatorType": "author", "firstName": "T. I.", "lastName": "Sudarsan" }, { "creatorType": "author", "firstName": "R. a. B.", "lastName": "Carey" }, { "creatorType": "author", "firstName": "J. V.", "lastName": "Peter" } ], "abstractNote": "Abstract Background. Toxin-induced methemoglobinemia is seen in poisoning with oxidizing agents. We report the clinical features and outcome of patients admitted with severe methemoglobinemia due to intentional ingestion of toxicants. Methods. In this observational case series, patients admitted with toxin-induced methemoglobinemia between September 2011 and January 2014 were identified from the institutional poisoning database. Clinical profile and outcome of patients with methemoglobin concentration greater than or equal to 49% is reported. Results. Of the 824 patients admitted with poisoning, 5 patients with methemoglobin concentration greater than or equal to 49% were included. The implicated compounds were nitrobenzene, benzoylphenylurea, flubendamide and RishabTM. One patient refused to name the compound. All patients were managed in the intensive care unit. Altered sensorium [Glasgow coma scale (GCS) < 10] was common (80%); 2 patients presented with a GCS greater than 4. All patients manifested cyanosis, low oxygen saturation and chocolate-brown-colored blood despite supplemental oxygen therapy. The median methemoglobin concentration was 64.7% (range 49.8–91.6%); 2 patients had methemoglobin concentration greater than 70%. One patient needed inotropes. Four patients required mechanical ventilation for 4–14 days. All patients were treated with methylene blue; 4 received more than one dose. Three patients also received intravenous ascorbic acid 500 mg, once daily, for 3 days. Following treatment, there was evidence of haemolysis in all patients; 2 required blood transfusion. All patients survived. Conclusion. Patients with severe toxin-induced methemoglobinemia present with altered sensorium and cyanosis and may require ventilatory support and inotropes. Though methemoglobin concentrations greater than 70% are considered fatal, aggressive management with methylene blue and supportive therapy can lead to survival.", "publicationTitle": "Clinical Toxicology", "publisher": "", "place": "", "date": "August 12, 2014", "volume": "52", "issue": "8", "section": "", "partNumber": "", "partTitle": "", "pages": "897-900", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Clinical Toxicology", "DOI": "10.3109/15563650.2014.947377", "citationKey": "", "url": "http://informahealthcare.com.www2.lib.ku.edu/doi/abs/10.3109/15563650.2014.947377", "accessDate": "2014-11-08T18:25:12Z", "PMID": "", "PMCID": "", "ISSN": "1556-3650", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "informahealthcare.com.www2.lib.ku.edu (Atypon)", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "G8Z9SNGR", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/G8Z9SNGR", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/G8Z9SNGR", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Poteet et al.", "parsedDate": "2013-03-29", "numChildren": 0 }, "data": { "key": "G8Z9SNGR", "version": 15, "itemType": "journalArticle", "title": "Reversing the Warburg Effect as a Treatment for Glioblastoma", "creators": [ { "creatorType": "author", "firstName": "E.", "lastName": "Poteet" }, { "creatorType": "author", "firstName": "G. R.", "lastName": "Choudhury" }, { "creatorType": "author", "firstName": "A.", "lastName": "Winters" }, { "creatorType": "author", "firstName": "W.", "lastName": "Li" }, { "creatorType": "author", "firstName": "M.-G.", "lastName": "Ryou" }, { "creatorType": "author", "firstName": "R.", "lastName": "Liu" }, { "creatorType": "author", "firstName": "L.", "lastName": "Tang" }, { "creatorType": "author", "firstName": "A.", "lastName": "Ghorpade" }, { "creatorType": "author", "firstName": "Y.", "lastName": "Wen" }, { "creatorType": "author", "firstName": "F.", "lastName": "Yuan" }, { "creatorType": "author", "firstName": "S. T.", "lastName": "Keir" }, { "creatorType": "author", "firstName": "H.", "lastName": "Yan" }, { "creatorType": "author", "firstName": "D. D.", "lastName": "Bigner" }, { "creatorType": "author", "firstName": "J. W.", "lastName": "Simpkins" }, { "creatorType": "author", "firstName": "S.-H.", "lastName": "Yang" } ], "abstractNote": "", "publicationTitle": "Journal of Biological Chemistry", "publisher": "", "place": "", "date": "2013-03-29", "volume": "288", "issue": "13", "section": "", "partNumber": "", "partTitle": "", "pages": "9153-9164", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1074/jbc.M112.440354", "citationKey": "", "url": "http://www.jbc.org/cgi/doi/10.1074/jbc.M112.440354", "accessDate": "2014-11-08T18:36:46Z", "PMID": "", "PMCID": "", "ISSN": "0021-9258, 1083-351X", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "en", "libraryCatalog": "CrossRef", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "X6ZR98JA", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/X6ZR98JA", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/X6ZR98JA", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Lamb et al.", "parsedDate": "2001-09-15", "numChildren": 0 }, "data": { "key": "X6ZR98JA", "version": 15, "itemType": "journalArticle", "title": "Retinyl Palmitate and the Blue-Light-Induced Phototoxicity of Human Ocular Lipofuscin", "creators": [ { "creatorType": "author", "firstName": "Laura E.", "lastName": "Lamb" }, { "creatorType": "author", "firstName": "Mariusz", "lastName": "Zareba" }, { "creatorType": "author", "firstName": "Sotirios N.", "lastName": "Plakoudas" }, { "creatorType": "author", "firstName": "Tadeusz", "lastName": "Sarna" }, { "creatorType": "author", "firstName": "John D.", "lastName": "Simon" } ], "abstractNote": "Lipofuscin accumulation in the retinal pigment epithelium is associated with the onset of age-related macular degeneration. Lipofuscin is phototoxic and affects cellular function through the photochemical generation of reactive oxygen intermediates. Mass spectral analysis of solvent extracts of human retinal lipofuscin granules reveals the presence of retinyl palmitate, the substrate for the enzymatic regeneration of 11-cis-retinal. Retinyl palmitate has an appreciable binding constant for phosphatidylcholine liposomes, and based on the glycophospholipids present in lipofuscin, retinal palmitate likely accumulates within the lipid content of the granule. Photochemical oxidation of retinal palmitate generates anhydroretinol, an intracellular signaling retinoid in the signal transduction cascade from the plasma membrane that causes apoptosis by generating reactive oxygen intermediates. These data are used to propose a model for the phototoxicity of lipofuscin.", "publicationTitle": "Archives of Biochemistry and Biophysics", "publisher": "", "place": "", "date": "September 15, 2001", "volume": "393", "issue": "2", "section": "", "partNumber": "", "partTitle": "", "pages": "316-320", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Archives of Biochemistry and Biophysics", "DOI": "10.1006/abbi.2001.2492", "citationKey": "", "url": "http://www.sciencedirect.com/science/article/pii/S0003986101924920", "accessDate": "2014-11-24T01:13:45Z", "PMID": "", "PMCID": "", "ISSN": "0003-9861", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "ScienceDirect", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "7I9M42PV", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/7I9M42PV", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/7I9M42PV", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Dirnagl et al.", "parsedDate": "2009-04", "numChildren": 1 }, "data": { "key": "7I9M42PV", "version": 15, "itemType": "journalArticle", "title": "Preconditioning and tolerance against cerebral ischaemia", "creators": [ { "creatorType": "author", "firstName": "Ulrich", "lastName": "Dirnagl" }, { "creatorType": "author", "firstName": "Kyra", "lastName": "Becker" }, { "creatorType": "author", "firstName": "Andreas", "lastName": "Meisel" } ], "abstractNote": "Neuroprotection and brain repair in patients after acute brain damage are still major unfulfilled medical needs. Pharmacological treatments are either ineffective or confounded by adverse effects. Consequently, endogenous mechanisms by which the brain protects itself against noxious stimuli and recovers from damage are being studied. Research on preconditioning, also known as induced tolerance, over the past decade has resulted in various promising strategies for the treatment of patients with acute brain injury. Several of these strategies are being tested in randomised clinical trials. Additionally, research into preconditioning has led to the idea of prophylactically inducing protection in patients such as those undergoing brain surgery and those with transient ischaemic attack or subarachnoid haemorrhage who are at high risk of brain injury in the near future. In this Review, we focus on the clinical issues relating to preconditioning and tolerance in the brain; specifically, we discuss the clinical situations that might benefit from such procedures. We also discuss whether preconditioning and tolerance occur naturally in the brain and assess the most promising candidate strategies that are being investigated.", "publicationTitle": "Lancet neurology", "publisher": "", "place": "", "date": "2009-4", "volume": "8", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "398-412", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Lancet Neurol", "DOI": "10.1016/S1474-4422(09)70054-7", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668955/", "accessDate": "2014-11-24T02:41:14Z", "PMID": "", "PMCID": "", "ISSN": "1474-4422", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: 19296922\nPMCID: PMC2668955", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "WRJSHKVK", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/WRJSHKVK", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/WRJSHKVK", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Kapitola et al.", "parsedDate": "1997", "numChildren": 1 }, "data": { "key": "WRJSHKVK", "version": 15, "itemType": "journalArticle", "title": "Possible participation of EDRF-NO in the hormonal regulation of bone blood flow in rats", "creators": [ { "creatorType": "author", "firstName": "J.", "lastName": "Kapitola" }, { "creatorType": "author", "firstName": "V.", "lastName": "Schreiber" }, { "creatorType": "author", "firstName": "J.", "lastName": "Andrle" }, { "creatorType": "author", "firstName": "T.", "lastName": "Haas" }, { "creatorType": "author", "firstName": "J.", "lastName": "Kubícková" } ], "abstractNote": "An increase in bone blood flow (BBF) was observed in rats after castration whereas a decrease in BBF occurred after oestradiol or testosterone. The possible participation of prostaglandins in these changes was demonstrated. The present results show that the endothelium-derived relaxing factor, i. e. nitric oxide (EDRF-NO), might play a role in these hormonal actions on BBF. Until now, almost nothing is known about the possible action of NO on bone circulation. Methylene blue (MB) as a substance blocking EDRF-NO was administered to sham-operated or oophorectomized (OOX) female rats. We determined local blood flow (85Sr-microsphere uptake), cardiac output, blood pressure, heart rate, density of the tibia and ash weight, as well as 24-h incorporation of 45Ca and 3H-proline into the tibia. The administration of MB (0.5% in the food for 4 weeks) significantly lowered both 85Sr-microsphere uptake and blood flow values in the tibia and distal femur of sham-operated and OOX rats. MB lowered cardiac output and blood pressure to the same extent, indicating no change in the vascular resistance. After the administration of MB (0.1% in the food), 85Sr-microsphere uptake decreased significantly in the tibia of OOX females while no significant change was found in soft tissues. Bone density and ash weight were significantly lower in OOX rats and in sham-operated rats after MB treatment. Finally, the 24-h incorporation of both 45Ca and 3H-proline decreased significantly in OOX females after MB administration (0.04% in the food). It can be concluded that 1) MB lowers BBF, suggesting the participation of EDRF-NO in BBF regulation, 2) MB does not influence or may even suppress cardiac output and blood pressure in high dosage, 3) MB lowers 24-hour incorporation of 45Ca and 3H-proline into the tibia of OOX rats, which is in agreement with the circulatory effect, 4) MB lowers bone density and ash weight of the tibia in non-castrated female rats. The effects of MB observed in our experiments partially differ from those of arginine-derived blocking agents. This requires further elucidation.", "publicationTitle": "Physiological Research / Academia Scientiarum Bohemoslovaca", "publisher": "", "place": "", "date": "1997", "volume": "46", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "15-20", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Physiol Res", "DOI": "", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0862-8408", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 9728516", "tags": [ { "tag": "Animals", "type": 1 }, { "tag": "Bone and Bones", "type": 1 }, { "tag": "Estradiol", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Femur", "type": 1 }, { "tag": "Hemorheology", "type": 1 }, { "tag": "Hormones", "type": 1 }, { "tag": "Indicators and Reagents", "type": 1 }, { "tag": "Methylene Blue", "type": 1 }, { "tag": "Nitric Oxide", "type": 1 }, { "tag": "Ovariectomy", "type": 1 }, { "tag": "Proline", "type": 1 }, { "tag": "Rats", "type": 1 }, { "tag": "Rats, Wistar", "type": 1 }, { "tag": "Testosterone", "type": 1 }, { "tag": "Tibia", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "2QXGCT4F", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/2QXGCT4F", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/2QXGCT4F", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "McDonagh et al.", "parsedDate": "2013", "numChildren": 0 }, "data": { "key": "2QXGCT4F", "version": 15, "itemType": "journalArticle", "title": "PharmGKB summary: methylene blue pathway", "creators": [ { "creatorType": "author", "firstName": "Ellen M.", "lastName": "McDonagh" }, { "creatorType": "author", "firstName": "José M.", "lastName": "Bautista" }, { "creatorType": "author", "firstName": "Ilan", "lastName": "Youngster" }, { "creatorType": "author", "firstName": "Russ B.", "lastName": "Altman" }, { "creatorType": "author", "firstName": "Teri E.", "lastName": "Klein" } ], "abstractNote": "", "publicationTitle": "Pharmacogenetics and Genomics", "publisher": "", "place": "", "date": "09/2013", "volume": "23", "issue": "9", "section": "", "partNumber": "", "partTitle": "", "pages": "498-508", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "", "DOI": "10.1097/FPC.0b013e32836498f4", "citationKey": "", "url": "http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=01213011-201309000-00007", "accessDate": "2014-11-08T18:55:03Z", "PMID": "", "PMCID": "", "ISSN": "1744-6872", "archive": "", "archiveLocation": "", "shortTitle": "PharmGKB summary", "language": "en", "libraryCatalog": "CrossRef", "callNumber": "", "rights": "", "extra": "", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "FFQV3CQR", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/FFQV3CQR", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/FFQV3CQR", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Disanto and Wagner", "parsedDate": "1972-07-01", "numChildren": 1 }, "data": { "key": "FFQV3CQR", "version": 15, "itemType": "journalArticle", "title": "Pharmacokinetics of highly ionized drugs II: Methylene blue—absorption, metabolism, and excretion in man and dog after oral administration", "creators": [ { "creatorType": "author", "firstName": "Anthony R.", "lastName": "Disanto" }, { "creatorType": "author", "firstName": "John G.", "lastName": "Wagner" } ], "abstractNote": "Methylene blue was administered orally to seven normal human subjects at a dose of 10 mg. in capsule form. Total urinary recovery ranged from 53 to 97% of the dose, with an average of 74%. Of the material recovered, an average of 78% was excreted as Ieucomethylene blue (stabilized in some salt, complex, or combination form) and the remainder as methylene blue. Some excretion rate-time plots of both methylene blue and leucomethylene blue showed evidence of a circadian rhythm. In a male dog and a female dog, administered 15 mg./kg. methylene blue orally, no drug was detected in blood. The female dog was catheterized and urine was collected for 10 hr. postdosing; recovery was 2.4% of the dose. The female dog was also administered a 10-mg. dose of methylene blue orally, and urine was collected by catheter over 14 hr. Recovery was 3.8% of the dose. It was concluded that methylene blue is well absorbed in man and poorly absorbed in the dog after oral administration.", "publicationTitle": "Journal of Pharmaceutical Sciences", "publisher": "", "place": "", "date": "July 1, 1972", "volume": "61", "issue": "7", "section": "", "partNumber": "", "partTitle": "", "pages": "1086-1090", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J. Pharm. Sci.", "DOI": "10.1002/jps.2600610710", "citationKey": "", "url": "http://onlinelibrary.wiley.com/doi/10.1002/jps.2600610710/abstract", "accessDate": "2014-11-24T01:46:21Z", "PMID": "", "PMCID": "", "ISSN": "1520-6017", "archive": "", "archiveLocation": "", "shortTitle": "Pharmacokinetics of highly ionized drugs II", "language": "en", "libraryCatalog": "Wiley Online Library", "callNumber": "", "rights": "Copyright © 1972 Wiley-Liss, Inc., A Wiley Company", "extra": "", "tags": [ { "tag": "Absorption, species dependent—methylene blue after oral administration, man, dog", "type": 1 }, { "tag": "Methylene blue—species-dependent absorption, metabolism, and excretion after oral administration, man, dog", "type": 1 }, { "tag": "Pharmacokinetics of highly ionized drugs—species-dependent absorption, metabolism, and excretion of methylene blue, man, dog", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "K4JRTBWH", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/K4JRTBWH", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/K4JRTBWH", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Poteet et al.", "parsedDate": "2012-10-31", "numChildren": 1 }, "data": { "key": "K4JRTBWH", "version": 15, "itemType": "journalArticle", "title": "Neuroprotective Actions of Methylene Blue and Its Derivatives", "creators": [ { "creatorType": "author", "firstName": "Ethan", "lastName": "Poteet" }, { "creatorType": "author", "firstName": "Ali", "lastName": "Winters" }, { "creatorType": "author", "firstName": "Liang-Jun", "lastName": "Yan" }, { "creatorType": "author", "firstName": "Kyle", "lastName": "Shufelt" }, { "creatorType": "author", "firstName": "Kayla N.", "lastName": "Green" }, { "creatorType": "author", "firstName": "James W.", "lastName": "Simpkins" }, { "creatorType": "author", "firstName": "Yi", "lastName": "Wen" }, { "creatorType": "author", "firstName": "Shao-Hua", "lastName": "Yang" } ], "abstractNote": "Methylene blue (MB), the first lead chemical structure of phenothiazine and other derivatives, is commonly used in diagnostic procedures and as a treatment for methemoglobinemia. We have previously demonstrated that MB could function as an alternative mitochondrial electron transfer carrier, enhance cellular oxygen consumption, and provide protection in vitro and in rodent models of Parkinson’s disease and stroke. In the present study, we investigated the structure-activity relationships of MB in vitro using MB and six structurally related compounds. MB reduces mitochondrial superoxide production via alternative electron transfer that bypasses mitochondrial complexes I-III. MB mitigates reactive free radical production and provides neuroprotection in HT-22 cells against glutamate, IAA and rotenone toxicity. Distinctly, MB provides no protection against direct oxidative stress induced by glucose oxidase. Substitution of a side chain at MB’s 10-nitrogen rendered a 1000-fold reduction of the protective potency against glutamate neurototoxicity. Compounds without side chains at positions 3 and 7, chlorophenothiazine and phenothiazine, have distinct redox potentials compared to MB and are incapable of enhancing mitochondrial electron transfer, while obtaining direct antioxidant actions against glutamate, IAA, and rotenone insults. Chlorophenothiazine exhibited direct antioxidant actions in mitochondria lysate assay compared to MB, which required reduction by NADH and mitochondria. MB increased complex IV expression and activity, while 2-chlorphenothiazine had no effect. Our study indicated that MB could attenuate superoxide production by functioning as an alternative mitochondrial electron transfer carrier and as a regenerable anti-oxidant in mitochondria.", "publicationTitle": "PLoS ONE", "publisher": "", "place": "", "date": "2012-10-31", "volume": "7", "issue": "10", "section": "", "partNumber": "", "partTitle": "", "pages": "", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "PLoS One", "DOI": "10.1371/journal.pone.0048279", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485214/", "accessDate": "2015-03-05T03:57:07Z", "PMID": "", "PMCID": "", "ISSN": "1932-6203", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: 23118969\nPMCID: PMC3485214", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "NH4PVXPM", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/NH4PVXPM", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/NH4PVXPM", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Rojas and Gonzalez-Lima", "parsedDate": "2013-08-15", "numChildren": 1 }, "data": { "key": "NH4PVXPM", "version": 15, "itemType": "journalArticle", "title": "Neurological and psychological applications of transcranial lasers and LEDs", "creators": [ { "creatorType": "author", "firstName": "Julio C.", "lastName": "Rojas" }, { "creatorType": "author", "firstName": "F.", "lastName": "Gonzalez-Lima" } ], "abstractNote": "Transcranial brain stimulation with low-level light/laser therapy (LLLT) is the use of directional low-power and high-fluency monochromatic or quasimonochromatic light from lasers or LEDs in the red-to-near-infrared wavelengths to modulate a neurobiological function or induce a neurotherapeutic effect in a nondestructive and non-thermal manner. The mechanism of action of LLLT is based on photon energy absorption by cytochrome oxidase, the terminal enzyme in the mitochondrial respiratory chain. Cytochrome oxidase has a key role in neuronal physiology, as it serves as an interface between oxidative energy metabolism and cell survival signaling pathways. Cytochrome oxidase is an ideal target for cognitive enhancement, as its expression reflects the changes in metabolic capacity underlying higher-order brain functions. This review provides an update on new findings on the neurotherapeutic applications of LLLT. The photochemical mechanisms supporting its cognitive-enhancing and brain-stimulatory effects in animal models and humans are discussed. LLLT is a potential non-invasive treatment for cognitive impairment and other deficits associated with chronic neurological conditions, such as large vessel and lacunar hypoperfusion or neurodegeneration. Brain photobiomodulation with LLLT is paralleled by pharmacological effects of low-dose USP methylene blue, a non-photic electron donor with the ability to stimulate cytochrome oxidase activity, redox and free radical processes. Both interventions provide neuroprotection and cognitive enhancement by facilitating mitochondrial respiration, with hormetic dose–response effects and brain region activational specificity. This evidence supports enhancement of mitochondrial respiratory function as a generalizable therapeutic principle relevant to highly adaptable systems that are exquisitely sensitive to energy availability such as the nervous system.", "publicationTitle": "Biochemical Pharmacology", "publisher": "", "place": "", "date": "August 15, 2013", "volume": "86", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "447-457", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Biochemical Pharmacology", "DOI": "10.1016/j.bcp.2013.06.012", "citationKey": "", "url": "http://www.sciencedirect.com/science/article/pii/S0006295213003833", "accessDate": "2014-12-16T20:11:52Z", "PMID": "", "PMCID": "", "ISSN": "0006-2952", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "ScienceDirect", "callNumber": "", "rights": "", "extra": "", "tags": [ { "tag": "Cytochrome oxidase", "type": 1 }, { "tag": "Low-level light therapy", "type": 1 }, { "tag": "Methylene Blue", "type": 1 }, { "tag": "Neuroprotection", "type": 1 }, { "tag": "Photobiomodulation", "type": 1 }, { "tag": "cognitive enhancement", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "HZAW8Q66", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/HZAW8Q66", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/HZAW8Q66", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "HZAW8Q66", "version": 15, "itemType": "webpage", "title": "MPrize@home volunteers? - Methuselah Foundation Forums", "creators": [], "abstractNote": "", "websiteTitle": "", "websiteType": "", "date": "", "publisher": "", "place": "", "DOI": "", "citationKey": "", "url": "http://www.mfoundation.org/forums/showthread.php?t=1368", "accessDate": "2014-11-24T02:16:04Z", "shortTitle": "", "language": "", "rights": "", "extra": "", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "8VWFTATP", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/8VWFTATP", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/8VWFTATP", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "8VWFTATP", "version": 15, "itemType": "webpage", "title": "MPrize@home - Project Ideas", "creators": [], "abstractNote": "MPrize@home - posted in Project Ideas : See how many we are on these forums; what if we could share the lab work... at home? The idea of MPrize@home is to share mouse life extension tests, which is currently one of the most relevant and lacking thing to do for life extension.Alone, it can not be done at home: such tests usually involve many mice (eg 80) and very well defined conditions.But if we distribute the work, discussions, polls and tests showed in this thread suggest that it should...", "websiteTitle": "LONGECITY", "websiteType": "", "date": "", "publisher": "", "place": "", "DOI": "", "citationKey": "", "url": "http://www.longecity.org/forum/topic/30474-mprizehome/", "accessDate": "2014-11-24T02:04:18Z", "shortTitle": "", "language": "", "rights": "", "extra": "", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "H3MS6CGU", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/H3MS6CGU", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/H3MS6CGU", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Gonzalez-Lima et al.", "parsedDate": "2014-04-15", "numChildren": 5 }, "data": { "key": "H3MS6CGU", "version": 15, "itemType": "journalArticle", "title": "Mitochondrial respiration as a target for neuroprotection and cognitive enhancement", "creators": [ { "creatorType": "author", "firstName": "F.", "lastName": "Gonzalez-Lima" }, { "creatorType": "author", "firstName": "Bryan R.", "lastName": "Barksdale" }, { "creatorType": "author", "firstName": "Julio C.", "lastName": "Rojas" } ], "abstractNote": "This paper focuses on brain mitochondrial respiration as a therapeutic target for neuroprotection and cognitive enhancement. We propose that improving brain mitochondrial respiration is an important future direction in research and treatment of Alzheimer's disease (AD) and other conditions associated with cognitive impairment and neurodegeneration. The central thesis is that supporting and improving brain mitochondrial respiration constitutes a promising neurotherapeutic principle, with potential applications in AD as well as in a wide variety of neuropsychological conditions. We propose three different interventional approaches to improve brain mitochondrial respiration based on (a) pharmacology, (b) photobiomodulation and (c) nutrition interventions, and provide detailed examples for each type of intervention. First, low-dose USP methylene blue is described as a pharmacological intervention that can successfully increase mitochondrial respiration and result in memory enhancement and neuroprotection. Second, transcranial low-level light/laser therapy with near-infrared light is used to illustrate a photobiomodulation intervention with similar neurometabolic mechanisms of action as low-dose methylene blue. Finally, a nutrition intervention to improve mitochondrial respiration is proposed by increasing ketone bodies in the diet. The evidence discussed for each intervention supports a fundamental neurotherapeutic strategy based on improving oxidative energy metabolism while at the same time reducing the pro-oxidant tendencies of the nervous system. Targeting brain mitochondrial respiration with these three types of interventions is proposed as part of a holistic neurotherapeutic approach to improve brain energy metabolism and antioxidant defenses. This strategy represents a promising new bioenergetics direction for treatment of AD and other neuropsychological disorders featuring cognitive impairment and neurodegeneration.", "publicationTitle": "Biochemical Pharmacology", "publisher": "", "place": "", "date": "Apr 15, 2014", "volume": "88", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "584-593", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Biochem. Pharmacol.", "DOI": "10.1016/j.bcp.2013.11.010", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "1873-2968", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 24316434", "tags": [ { "tag": "Alzheimer Disease", "type": 1 }, { "tag": "Alzheimer's disease", "type": 1 }, { "tag": "Brain energy metabolism", "type": 1 }, { "tag": "Cognition", "type": 1 }, { "tag": "Dose-Response Relationship, Drug", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Ketogenesis", "type": 1 }, { "tag": "Ketone Bodies", "type": 1 }, { "tag": "Laser Therapy", "type": 1 }, { "tag": "Low-level light/laser therapy", "type": 1 }, { "tag": "Methylene Blue", "type": 1 }, { "tag": "Mild Cognitive Impairment", "type": 1 }, { "tag": "mitochondria", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "72T3K4T5", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/72T3K4T5", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/72T3K4T5", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "creatorSummary": "Thoorens et al.", "parsedDate": "2014-10-01", "numChildren": 0 }, "data": { "key": "72T3K4T5", "version": 15, "itemType": "journalArticle", "title": "Microcrystalline cellulose, a direct compression binder in a quality by design environment—A review", "creators": [ { "creatorType": "author", "firstName": "Gregory", "lastName": "Thoorens" }, { "creatorType": "author", "firstName": "Fabrice", "lastName": "Krier" }, { "creatorType": "author", "firstName": "Bruno", "lastName": "Leclercq" }, { "creatorType": "author", "firstName": "Brian", "lastName": "Carlin" }, { "creatorType": "author", "firstName": "Brigitte", "lastName": "Evrard" } ], "abstractNote": "The ICH quality vision introduced the concept of quality by design (QbD), which requires a greater understanding of the raw material attributes, of process parameters, of their variability and their interactions. Microcrystalline cellulose (MCC) is one of the most important tableting excipients thanks to its outstanding dry binding properties, enabling the manufacture of tablets by direct compression (DC). DC remains the most economical technique to produce large batches of tablets, however its efficacy is directly impacted by the raw material attributes. Therefore excipients’ variability and their impact on drug product performance need to be thoroughly understood. To help with this process, this review article gathers prior knowledge on MCC, focuses on its use in DC and lists some of its potential critical material attributes (CMAs).", "publicationTitle": "International Journal of Pharmaceutics", "publisher": "", "place": "", "date": "October 1, 2014", "volume": "473", "issue": "1–2", "section": "", "partNumber": "", "partTitle": "", "pages": "64-72", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "International Journal of Pharmaceutics", "DOI": "10.1016/j.ijpharm.2014.06.055", "citationKey": "", "url": "http://www.sciencedirect.com/science/article/pii/S0378517314004840", "accessDate": "2015-03-05T18:34:00Z", "PMID": "", "PMCID": "", "ISSN": "0378-5173", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "ScienceDirect", "callNumber": "", "rights": "", "extra": "", "tags": [ { "tag": "Binder", "type": 1 }, { "tag": "Critical material attributes", "type": 1 }, { "tag": "Direct compression", "type": 1 }, { "tag": "Microcrystalline cellulose", "type": 1 }, { "tag": "Quality by design", "type": 1 }, { "tag": "Tablets", "type": 1 } ], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "GCQ75267", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/GCQ75267", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/GCQ75267", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "parsedDate": "2015-02-12", "numChildren": 0 }, "data": { "key": "GCQ75267", "version": 15, "itemType": "encyclopediaArticle", "title": "Microcrystalline cellulose", "creators": [], "abstractNote": "Microcrystalline cellulose is a term for refined wood pulp and is used as a texturizer, an anti-caking agent, a fat substitute, an emulsifier, an extender, and a bulking agent in food production. The most common form is used in vitamin supplements or tablets. It is also used in plaque assays for counting viruses, as an alternative to carboxymethylcellulose.\nIn many ways, cellulose makes the ideal excipient. A naturally occurring polymer, it is composed of glucose units connected by a 1-4 beta glycosidic bond. These linear cellulose chains are bundled together as microfibril spiralled together in the walls of plant cell. Each microfibril exhibits a high degree of three-dimensional internal bonding resulting in a crystalline structure that is insoluble in water and resistant to reagents. There are, however, relatively weak segments of the microfibril with weaker internal bonding. These are called amorphous regions; some argue that they are more accurately called dislocations, because of the single-phase structure of microfibrils. The crystalline region is isolated to produce microcrystalline cellulose.\nApproved within the European Union as a thickener, stabilizer or emulsifiers microcrystalline cellulose was granted the E number E460(ii) with basic cellulose given the number E460 (i)", "encyclopediaTitle": "Wikipedia, the free encyclopedia", "series": "", "seriesNumber": "", "volume": "", "numberOfVolumes": "", "edition": "", "date": "2015-02-12T02:34:32Z", "publisher": "", "place": "", "pages": "", "ISBN": "", "DOI": "", "citationKey": "", "url": "http://en.wikipedia.org/w/index.php?title=Microcrystalline_cellulose&oldid=646741281", "accessDate": "2015-03-02T20:03:50Z", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "en", "libraryCatalog": "Wikipedia", "callNumber": "", "rights": "Creative Commons Attribution-ShareAlike License", "extra": "Page Version ID: 646741281", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } }, { "key": "JNVHW7XQ", "version": 15, "library": { "type": "group", "id": 262524, "name": "BrainEnhancements", "links": { "alternate": { "href": "https://www.zotero.org/groups/brainenhancements", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/262524/items/JNVHW7XQ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/brainenhancements/items/JNVHW7XQ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 1687986, "username": "mirage662", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/mirage662", "type": "text/html" } } }, "numChildren": 4 }, "data": { "key": "JNVHW7XQ", "version": 15, "itemType": "webpage", "title": "Methylene Blue trihydrate | C16H24ClN3O3S - PubChem", "creators": [], "abstractNote": "", "websiteTitle": "", "websiteType": "", "date": "", "publisher": "", "place": "", "DOI": "", "citationKey": "", "url": "http://pubchem.ncbi.nlm.nih.gov/compound/Methylene_Blue_trihydrate#section=Melting-Point", "accessDate": "2014-12-31T03:07:13Z", "shortTitle": "", "language": "", "rights": "", "extra": "", "tags": [], "collections": [ "VVM4E5XJ" ], "relations": {}, "dateAdded": "2015-03-05T22:49:07Z", "dateModified": "2015-03-05T22:49:07Z" } } ]