{"id":"2e89df7f-f1d3-52ff-888e-1dce931202a4","stable_key":"f8641d02-8413-5bd8-92e9-62ad49286e81:asa-recovery-starts-in-the-marrow","predicate":"limits","statement":"Megakaryocyte thromboxane production was depressed by 70% and that of platelets by 85% at two hours after 20 milligrams per kilogram oral aspirin, full megakaryocyte thromboxane recovery occurred by 72 hours and preceded complete platelet recovery by 24 hours, megakaryocyte synthesis showed substantial recovery by 36 hours while platelet recovery did not begin for 24 hours, and the authors conclude that thromboxane synthesis develops in rat megakaryocytes after approximately 48 hours of cytoplasmic differentiation toward platelet shedding.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"d8cfdf6e-e5d4-5305-921b-8d8b7880afef","mechanism_event_label":"The marrow recovers first and the blood follows, because new platelets have to be built and released.","subject":{"id":"5ed63972-a09f-58b5-9df3-2bba73098850","slug":"megakaryocyte","display_name":"Megakaryocyte","entity_type_key":"cell_type"},"object":{"id":"196e612b-08c7-509f-a4ad-5b98bb0eac69","slug":"platelet-cox-recovery","display_name":"Recovery of platelet cyclooxygenase activity after aspirin","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d8cfdf6e-e5d4-5305-921b-8d8b7880afef","stable_key":"f8641d02-8413-5bd8-92e9-62ad49286e81:asa-recovery-starts-in-the-marrow-event","event_type":"observed_intervention","label":"The marrow recovers first and the blood follows, because new platelets have to be built and released.","description":"Megakaryocyte thromboxane production was depressed by 70% and that of platelets by 85% at two hours after 20 milligrams per kilogram oral aspirin, full megakaryocyte thromboxane recovery occurred by 72 hours and preceded complete platelet recovery by 24 hours, megakaryocyte synthesis showed substantial recovery by 36 hours while platelet recovery did not begin for 24 hours, and the authors conclude that thromboxane synthesis develops in rat megakaryocytes after approximately 48 hours of cytoplasmic differentiation toward platelet shedding.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3cc7ab30-e6f8-51b9-8979-70f0ea692dc8","slug":"platelet","display_name":"Blood platelet","entity_type_key":"cell_type"},"role":"downstream_cell","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3b200ef2-893f-5ca7-93f4-ea657577a760","slug":"thromboxane-b2","display_name":"Thromboxane B2","entity_type_key":"small_molecule"},"role":"measured_product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5ed63972-a09f-58b5-9df3-2bba73098850","slug":"megakaryocyte","display_name":"Megakaryocyte","entity_type_key":"cell_type"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"196e612b-08c7-509f-a4ad-5b98bb0eac69","slug":"platelet-cox-recovery","display_name":"Recovery of platelet cyclooxygenase activity after aspirin","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/aspirin-research/6812167.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"fd3cbdc85225aabdb23690613d2ba4bd49151f144c362d6121721eb45e969389\", \"start_char\": 0, \"end_char\": 1366, \"text_sha256\": \"fd3cbdc85225aabdb23690613d2ba4bd49151f144c362d6121721eb45e969389\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Radioimmunoassay of megakaryocyte and platelet thromboxane B2 recovery in rats after a single oral aspirin dose","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"20 milligrams per kilogram oral aspirin dissolved in dimethyl sulphoxide","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Follows the precursor cell rather than the platelet, which is where the recovery kinetics are actually set. A rat study and the maturation timing is inferred from transit times.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.","comparator":null,"unit":null,"notes":"","entity":{"slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Rat","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The marrow recovers first and the blood follows, because new platelets have to be built and released.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[asa-p6812167] Aspirin inhibits rat megakaryocyte thromboxane synthesis. (1982). https://pubmed.ncbi.nlm.nih.gov/6812167/ DOI: 10.1016/0090-6980(82)90128-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Bone marrow megakaryocytes and platelets","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2e2b375d-8b0a-52c7-a8ee-e3139f691cb9","evidence_kind":"source_excerpt","locator":"Lines 416-427","start_line":416,"end_line":427,"excerpt":"### asa-recovery-starts-in-the-marrow\nMegakaryocyte thromboxane production was depressed by 70% and that of platelets by 85% at two hours after 20 milligrams per kilogram oral aspirin, full megakaryocyte thromboxane recovery occurred by 72 hours and preceded complete platelet recovery by 24 hours, megakaryocyte synthesis showed substantial recovery by 36 hours while platelet recovery did not begin for 24 hours, and the authors conclude that thromboxane synthesis develops in rat megakaryocytes after approximately 48 hours of cytoplasmic differentiation toward platelet shedding.\nCondition category: normal\nnutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.\nplain_language: The marrow recovers first and the blood follows, because new platelets have to be built and released.\norganism: Rat\ntissue_or_cell_type: Bone marrow megakaryocytes and platelets\nexperimental_model: Radioimmunoassay of megakaryocyte and platelet thromboxane B2 recovery in rats after a single oral aspirin dose\nlimitations: Follows the precursor cell rather than the platelet, which is where the recovery kinetics are actually set. A rat study and the maturation timing is inferred from transit times.\nexposure: 20 milligrams per kilogram oral aspirin dissolved in dimethyl sulphoxide\nevidence_span: {\"source_cache\": \"artifacts/aspirin-research/6812167.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"fd3cbdc85225aabdb23690613d2ba4bd49151f144c362d6121721eb45e969389\", \"start_char\": 0, \"end_char\": 1366, \"text_sha256\": \"fd3cbdc85225aabdb23690613d2ba4bd49151f144c362d6121721eb45e969389\"}\n[asa-p6812167] Aspirin inhibits rat megakaryocyte thromboxane synthesis. (1982). https://pubmed.ncbi.nlm.nih.gov/6812167/ DOI: 10.1016/0090-6980(82)90128-9","model_system":"Radioimmunoassay of megakaryocyte and platelet thromboxane B2 recovery in rats after a single oral aspirin dose","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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