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  1 / 3256 MEDLINE  
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[PMID]:28470638
[Au] Autor:Pape A; Ippolito A; Warszawska J; Raimann F; Zacharowski K
[Ti] Título:[Management of Massive Intraoperative Blood Loss Using a Case Study].
[Ti] Título:Management des massiven intraoperativen Blutverlusts anhand eines Fallbeispiels..
[So] Source:Anasthesiol Intensivmed Notfallmed Schmerzther;52(4):288-296, 2017 Apr.
[Is] ISSN:1439-1074
[Cp] País de publicação:Germany
[La] Idioma:ger
[Ab] Resumo:Massive intraoperative bleeding is a major and potentially life-threatening complication during surgical procedures. The lethal triade of hemorrhagic shock with metabolic acidosis, hypothermia and coagulopathy enhances bleeding tendency. Avoiding this vitious circle requires a well-structured and standardized procedure. Primary goals include the maintenance of adequate tissue oxygenation, restauration of proper coagulatory function, normothermia and homeostasis of acid-base and electrolyte balance. In the present article, these therapeutic goals and their pathophysiological background are illustrated with a clinical case example.
[Mh] Termos MeSH primário: Perda Sanguínea Cirúrgica/prevenção & controle
Substitutos Sanguíneos/administração & dosagem
Transfusão de Sangue/métodos
Monitorização Intraoperatória/métodos
[Mh] Termos MeSH secundário: Transfusão de Sangue Autóloga
Estudos de Casos e Controles
Seres Humanos
Masculino
Meia-Idade
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Blood Substitutes)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1055/s-0042-102821


  2 / 3256 MEDLINE  
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[PMID]:29287072
[Au] Autor:Baughman T; Peterson C; Ortega C; Preston SR; Paton C; Williams J; Guy A; Omodei G; Johnson B; Williams H; O'Neill SL; Ritchie SA; Dobson SL; Madan D
[Ad] Endereço:Intellectual Ventures Laboratory and Global Good, Bellevue, Washington, United States of America.
[Ti] Título:A highly stable blood meal alternative for rearing Aedes and Anopheles mosquitoes.
[So] Source:PLoS Negl Trop Dis;11(12):e0006142, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We investigated alternatives to whole blood for blood feeding of mosquitoes with a focus on improved stability and compatibility with mass rearing programs. In contrast to whole blood, an artificial blood diet of ATP-supplemented plasma was effective in maintaining mosquito populations and was compatible with storage for extended periods refrigerated, frozen, and as a lyophilized powder. The plasma ATP diet supported rearing of both Anopheles and Aedes mosquitoes. It was also effective in rearing Wolbachia-infected Aedes mosquitoes, suggesting compatibility with vector control efforts.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/farmacologia
Aedes/fisiologia
Anopheles/fisiologia
Insetos Vetores/fisiologia
Plasma/química
Wolbachia/fisiologia
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/sangue
Aedes/efeitos dos fármacos
Aedes/microbiologia
Animais
Anopheles/efeitos dos fármacos
Anopheles/microbiologia
Substitutos Sanguíneos/química
Dieta
Suplementos Nutricionais
Feminino
Insetos Vetores/efeitos dos fármacos
Insetos Vetores/microbiologia
Masculino
Óvulo
Controle Biológico de Vetores
Reprodução/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Substitutes); 8L70Q75FXE (Adenosine Triphosphate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006142


  3 / 3256 MEDLINE  
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[PMID]:28778289
[Au] Autor:Tolich DJ; McCoy K
[Ad] Endereço:Blood Management, Cleveland Clinic Health System, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Electronic address: detoli@ccf.org.
[Ti] Título:Alternative to Blood Replacement in the Critically Ill.
[So] Source:Crit Care Nurs Clin North Am;29(3):291-304, 2017 Sep.
[Is] ISSN:1558-3481
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This article reviews treatments and strategies that can be used to reduce, or as adjuncts to, blood transfusion to manage blood volumes in patients who are critically ill. Areas addressed include iatrogenic anemia, fluid management, pharmaceutical agents, hemostatic agents, hemoglobin-based oxygen carriers, and management of patients for whom blood is not an option.
[Mh] Termos MeSH primário: Anemia/terapia
Substitutos Sanguíneos/uso terapêutico
Transfusão de Sangue
Estado Terminal/terapia
[Mh] Termos MeSH secundário: Anemia/etiologia
Seres Humanos
Unidades de Terapia Intensiva
Equilíbrio Hidroeletrolítico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Blood Substitutes)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:N
[Da] Data de entrada para processamento:170806
[St] Status:MEDLINE


  4 / 3256 MEDLINE  
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[PMID]:28704250
[Au] Autor:MacKay EJ; Stubna MD; Holena DN; Reilly PM; Seamon MJ; Smith BP; Kaplan LJ; Cannon JW
[Ad] Endereço:From the *Department Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; †Mountain Track Apps, Philadelphia, Pennsylvania; ‡Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; §Department of Surgery, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; and ‖Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
[Ti] Título:Abnormal Calcium Levels During Trauma Resuscitation Are Associated With Increased Mortality, Increased Blood Product Use, and Greater Hospital Resource Consumption: A Pilot Investigation.
[So] Source:Anesth Analg;125(3):895-901, 2017 Sep.
[Is] ISSN:1526-7598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Admission hypocalcemia predicts both massive transfusion and mortality in severely injured patients. However, the effect of calcium derangements during resuscitation remains unexplored. We hypothesize that any hypocalcemia or hypercalcemia (either primary or from overcorrection) in the first 24 hours after severe injury is associated with increased mortality. METHODS: All patients at our institution with massive transfusion protocol activation from January 2013 through December 2014 were identified. Patients transferred from another hospital, those not transfused, those with no ionized calcium (Ca) measured, and those who expired in the trauma bay were excluded. Hypocalcemia and hypercalcemia were defined as any level outside the normal range of Ca at our institution (1-1.25 mmol/L). Receiver operator curve analysis was also used to further examine significant thresholds for both hypocalcemia and hypercalcemia. Hospital mortality was compared between groups. Secondary outcomes included advanced cardiovascular life support, damage control surgery, ventilator days, and intensive care unit days. RESULTS: The massive transfusion protocol was activated for 77 patients of whom 36 were excluded leaving 41 for analysis. Hypocalcemia occurred in 35 (85%) patients and hypercalcemia occurred in 9 (22%). Mortality was no different in hypocalcemia versus no hypocalcemia (29% vs 0%; P = .13) but was greater in hypercalcemia versus no hypercalcemia (78% vs 9%; P < .01). Receiver operator curve analysis identified inflection points in mortality outside a Ca range of 0.84 to 1.30 mmol/L. Using these extreme values, 15 (37%) had hypocalcemia with a 60% mortality (vs 4%; P < .01) and 9 (22%) had hypercalcemia with a 78% mortality (vs 9%; P < .01). Patients with extreme hypocalcemia and hypercalcemia also received more red blood cells, plasma, platelets, and calcium repletion. CONCLUSIONS: Hypocalcemia and hypercalcemia occur commonly during the initial resuscitation of severely injured patients. Mild hypocalcemia may be tolerable, but more extreme hypocalcemia and any hypercalcemia should be avoided. Further assessment to define best practice for calcium management during resuscitation is warranted.
[Mh] Termos MeSH primário: Substitutos Sanguíneos/administração & dosagem
Recursos em Saúde/utilização
Mortalidade Hospitalar
Hipercalcemia/sangue
Hipocalcemia/sangue
Ressuscitação/mortalidade
[Mh] Termos MeSH secundário: Adulto
Cálcio/sangue
Feminino
Recursos em Saúde/tendências
Mortalidade Hospitalar/tendências
Seres Humanos
Hipercalcemia/diagnóstico
Hipocalcemia/diagnóstico
Masculino
Meia-Idade
Mortalidade/tendências
Projetos Piloto
Ressuscitação/tendências
Ferimentos e Lesões/sangue
Ferimentos e Lesões/diagnóstico
Ferimentos e Lesões/terapia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Substitutes); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE
[do] DOI:10.1213/ANE.0000000000002312


  5 / 3256 MEDLINE  
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[PMID]:28622333
[Au] Autor:Kohno M; Ikeda T; Hashimoto R; Izumi Y; Watanabe M; Horinouchi H; Sakai H; Kobayashi K; Iwazaki M
[Ad] Endereço:Division of General Thoracic Surgery, Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
[Ti] Título:Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model.
[So] Source:PLoS One;12(6):e0178724, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs. METHODS: Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer's solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups. RESULTS: In the HbV/rHSA and mRBC/rHSA groups, all mice survived ≥7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs. CONCLUSIONS: The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.
[Mh] Termos MeSH primário: Transfusão de Componentes Sanguíneos/métodos
Substitutos Sanguíneos/farmacologia
Hemoglobinas/farmacocinética
Pneumonectomia
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Substitutes); 0 (Hemoglobins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178724


  6 / 3256 MEDLINE  
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[PMID]:28601310
[Au] Autor:Morton AP; Moore EE; Moore HB; Gonzalez E; Chapman MP; Peltz E; Banerjee A; Silliman C
[Ad] Endereço:Department of Surgery-Trauma Research Center, University of Colorado, Denver, Colorado. Electronic address: alexander.morton@ucdenver.edu.
[Ti] Título:Hemoglobin-based oxygen carriers promote systemic hyperfibrinolysis that is both dependent and independent of plasmin.
[So] Source:J Surg Res;213:166-170, 2017 Jun 01.
[Is] ISSN:1095-8673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hyperfibrinolysis plays an integral role in the genesis of trauma-induced coagulopathy. Recent data demonstrate that red blood cell lysis promotes fibrinolysis; however, the mechanism is unclear. Hemoglobin-based oxygen carriers (HBOCs) have been developed for resuscitation and have been associated with coagulopathy. We hypothesize that replacement of whole blood (WB) using an HBOC results in a coagulopathy because of the presence of free hemoglobin. MATERIALS AND METHODS: WB was sampled from healthy donors (n = 6). The clotting profile of each citrated sample was evaluated using native thromboelastography. Serial titrations were performed using both HBOC (PolyHeme) and normal saline (NS; 5%, 25%, and 50%) and evaluated both with and without a 75-ng/mL tissue plasminogen activator (tPA) challenge. Tranexamic acid (TXA) was added to inhibit plasmin-dependent fibrinolysis. Fibrinolysis was measured and recorded as lysis at 30 min (LY30), the percentage of clot LY30 after maximal clot strength. Dilution of WB with NS or HBOC was correlated using LY30 via Spearman rho coefficients. Groups were also compared using a Friedman test and post hoc analysis with a Bonferroni adjustment. RESULTS: tPA-provoked fibrinolysis was enhanced by both HBOC (median LY30 at 5%, 25%, and 50% titrations: 11%, 21%, and 44%, respectively; Spearman = 0.94; P < 0.001) and NS (11%, 28%, and 58%, respectively; Spearman = 0.790; P < 0.001). However, HBOC also enhanced fibrinolysis without the addition of tPA (1%, 4%, 5%; Spearman = 0.735; P = 0.001) and NS did not (1%, 2%, 1%; r = 0.300; P = 0.186. Moreover, addition of TXA did not alter or inhibit this fibrinolysis (WB versus 50% HBOC: 1.8% versus 5.7%, P = 0.04). There was no significant difference in fibrinolysis of HBOC with or without TXA (50% HBOC versus 50% HBOC + TXA: 5.6% versus 5.7%, P = 0.92). In addition, the increased fibrinolysis seen with NS was reversed when TXA was present (WB versus 50% NS: 1.8% versus 1.7%, P = 1.0). CONCLUSIONS: HBOCs enhance fibrinolysis both with and without addition of tPA; moreover, this mechanism is independent of plasmin as the phenomenon persists in the presence of TXA. Our findings indicate the hemoglobin molecule or its components stimulate fibrinolysis by both tPA-dependent and innate mechanisms.
[Mh] Termos MeSH primário: Substitutos Sanguíneos/efeitos adversos
Fibrinolisina/metabolismo
Fibrinólise/efeitos dos fármacos
Hemoglobinas/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Biomarcadores/metabolismo
Fibrinólise/fisiologia
Voluntários Saudáveis
Seres Humanos
Masculino
Tromboelastografia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Substitutes); 0 (Hemoglobins); 0 (PolyHeme); EC 3.4.21.7 (Fibrinolysin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170612
[St] Status:MEDLINE


  7 / 3256 MEDLINE  
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[PMID]:28520579
[Au] Autor:Laing RW; Bhogal RH; Wallace L; Boteon Y; Neil DAH; Smith A; Stephenson BTF; Schlegel A; Hübscher SG; Mirza DF; Afford SC; Mergental H
[Ad] Endereço:1 Liver Unit, Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 2 National Institute for Health Research, Birmingham Liver Biomedical Research Unit and Centre for Liver Research, Institute of Immunology and Immunotherapy, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, United Kingdom.
[Ti] Título:The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion.
[So] Source:Transplantation;101(11):2746-2756, 2017 Nov.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Normothermic machine perfusion of the liver (NMP-L) is a novel technique that preserves liver grafts under near-physiological conditions while maintaining their normal metabolic activity. This process requires an adequate oxygen supply, typically delivered by packed red blood cells (RBC). We present the first experience using an acellular hemoglobin-based oxygen carrier (HBOC) Hemopure in a human model of NMP-L. METHODS: Five discarded high-risk human livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC-perfused livers. Perfusion parameters, oxygen extraction, metabolic activity, and histological features were compared during 6 hours of NMP-L. The cytotoxicity of Hemopure was also tested on human hepatic primary cell line cultures using an in vitro model of ischemia reperfusion injury. RESULTS: The vascular flow parameters and the perfusate lactate clearance were similar in both groups. The HBOC-perfused livers extracted more oxygen than those perfused with RBCs (O2 extraction ratio 13.75 vs 9.43 % ×10 per gram of tissue, P = 0.001). In vitro exposure to Hemopure did not alter intracellular levels of reactive oxygen species, and there was no increase in apoptosis or necrosis observed in any of the tested cell lines. Histological findings were comparable between groups. There was no evidence of histological damage caused by Hemopure. CONCLUSIONS: Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP-L perfusion fluid.
[Mh] Termos MeSH primário: Substitutos Sanguíneos/farmacologia
Hemoglobinas/farmacologia
Fígado/efeitos dos fármacos
Preservação de Órgãos/métodos
Perfusão/métodos
Traumatismo por Reperfusão/prevenção & controle
[Mh] Termos MeSH secundário: Adulto
Idoso
Apoptose
Substitutos Sanguíneos/toxicidade
Células Cultivadas
Metabolismo Energético/efeitos dos fármacos
Feminino
Hemoglobinas/toxicidade
Hepatectomia
Seres Humanos
Fígado/metabolismo
Fígado/patologia
Fígado/cirurgia
Masculino
Meia-Idade
Necrose
Preservação de Órgãos/efeitos adversos
Consumo de Oxigênio/efeitos dos fármacos
Perfusão/efeitos adversos
Espécies Reativas de Oxigênio/metabolismo
Traumatismo por Reperfusão/etiologia
Traumatismo por Reperfusão/metabolismo
Traumatismo por Reperfusão/patologia
Fatores de Tempo
Sobrevivência de Tecidos/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Substitutes); 0 (HBOC 201); 0 (Hemoglobins); 0 (Reactive Oxygen Species)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001821


  8 / 3256 MEDLINE  
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[PMID]:28397408
[Au] Autor:Kawaguchi AT; Yamano M; Haida M; Ohba H; Kakiuchi T; Tsukada H
[Ad] Endereço:Tokai University School of Medicine, Kanagawa.
[Ti] Título:Effect of Oxygen Affinity of Liposome-Encapsulated Hemoglobin on Cerebral Ischemia and Reperfusion as Detected by Positron Emission Tomography in Nonhuman Primates.
[So] Source:Artif Organs;41(4):336-345, 2017 Apr.
[Is] ISSN:1525-1594
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We tested a hypothesis that liposome-encapsulated hemoglobin (LEH) with high oxygen (O ) affinity (h-LEH, P O = 10 mm Hg) may work better than LEH with low O affinity (l-LEH, P O = 40 mm Hg) in cerebral ischemia and reperfusion injury using positron emission tomography (PET) in primates undergoing middle cerebral artery (MCA) occlusion and reperfusion. Cerebral blood flow (CBF), O extract fraction (OEF), and cerebral metabolic rate of O (CMRO ) were successively determined by PET before ischemia, at 2 h of ischemia, immediately after reperfusion, and 3 h after reperfusion. Five minutes after MCA occlusion, 10 mL/kg of h-LEH (n = 6) was intravenously infused and compared with the results from previous data of monkeys treated with l-LEH (n = 6), empty liposome (n = 4), or saline (n = 8) as control. After the series of PET studies, the integrated area of cerebral infarction was determined histologically in 12 coronal brain slices. There was no significant difference in CBF, OEF, or CMRO up to 2 h of ischemia. A high CBF with a low OEF tended to be suppressed after reperfusion in LEH-treated monkeys. Three hours after reperfusion, the area of mild CMRO reduction (down to -30%) decreased (P < 0.05) and the area of mild CMRO increase (up to 30%) expanded in LEH-treated monkeys (P < 0.05) regardless of O affinity with no difference in the area of moderate-to-severe reduction (<-30%) or increase (<+30%) in CMRO compared to animals treated with empty liposome or saline. Distribution of CMRO reduction and histological damages showed that LEH mainly protected the cerebral cortex rather than basal ganglia where neuronal dendritic processes were severely lost. There was little difference between the animals treated with l-LEH or h-LEH both at 10 mL/kg or between treatment with empty liposome or saline. In conclusion, LEH was effective regardless of O affinity in preserving CMRO and in reducing the area of histological damage in the cerebral cortex, but not in basal ganglia, shortly after occlusion/reperfusion of MCA in monkey.
[Mh] Termos MeSH primário: Substitutos Sanguíneos/uso terapêutico
Encéfalo/metabolismo
Infarto Cerebral/tratamento farmacológico
Circulação Cerebrovascular/efeitos dos fármacos
Hemoglobinas/uso terapêutico
Traumatismo por Reperfusão/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Substitutos Sanguíneos/administração & dosagem
Substitutos Sanguíneos/química
Encéfalo/patologia
Infarto Cerebral/diagnóstico por imagem
Infarto Cerebral/metabolismo
Infarto Cerebral/patologia
Modelos Animais de Doenças
Hemoglobinas/administração & dosagem
Hemoglobinas/química
Seres Humanos
Lipossomos
Macaca fascicularis
Oxigênio/química
Oxigênio/metabolismo
Tomografia por Emissão de Pósitrons
Reperfusão
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Substitutes); 0 (Hemoglobins); 0 (Liposomes); S88TT14065 (Oxygen)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170412
[St] Status:MEDLINE
[do] DOI:10.1111/aor.12905


  9 / 3256 MEDLINE  
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[PMID]:28397407
[Au] Autor:Abuchowski A
[Ad] Endereço:Prolong Pharmaceuticals, South Plainfield, NJ, USA.
[Ti] Título:SANGUINATE (PEGylated Carboxyhemoglobin Bovine): Mechanism of Action and Clinical Update.
[So] Source:Artif Organs;41(4):346-350, 2017 Apr.
[Is] ISSN:1525-1594
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Historically, blood substitutes were under development that would provide oxygen carrying capacity as well as fluid replacement for both trauma and surgical indications. Their development was halted by the inability of the products to deliver therapeutic amounts of oxygen targeted to hypoxic tissue as well as from the inherent toxicity of the molecules. This led to the concept of an oxygen therapeutic that would be targeted for indications caused by anemia/ischemia/hypoxia but would not exhibit the toxicity that plagued earlier products. The complex pathophysiology of diseases such as sickle cell and hemorrhagic stroke not only has hypoxia as a pivotal event but also includes inflammation and vasoconstriction that perpetuate the oxygen deprivation. There is a need for an effective therapeutic that addresses the multiple events of inflammation and oxygen deprivation. SANGUINATE acts as a dual mode carbon monoxide (CO) and oxygen delivery therapeutic. SANGUINATE is designed not only to treat hypoxia but also to act on concurrent pathologies such as inflammation and reperfusion injury. This expands the potential therapeutic utility of SANGUINATE beyond anemia into indications such as early brain injury and delayed kidney graft function, where inflammation plays a pivotal pathological role as well as in indications such as sickle cell disease where the inflammation and hypoxia contribute to the development of comorbidities such as vaso-occlusive crisis. Clinical trials in multiple indications are underway.
[Mh] Termos MeSH primário: Substitutos Sanguíneos/farmacologia
Monóxido de Carbono/metabolismo
Carboxihemoglobina/farmacologia
Hipóxia/tratamento farmacológico
Oxigênio/metabolismo
Vasoconstrição/efeitos dos fármacos
[Mh] Termos MeSH secundário: Anemia/tratamento farmacológico
Anemia Falciforme/tratamento farmacológico
Animais
Substitutos Sanguíneos/administração & dosagem
Substitutos Sanguíneos/química
Substitutos Sanguíneos/uso terapêutico
Isquemia Encefálica/tratamento farmacológico
Carboxihemoglobina/administração & dosagem
Carboxihemoglobina/química
Carboxihemoglobina/uso terapêutico
Bovinos
Função Retardada do Enxerto/tratamento farmacológico
Seres Humanos
Polietilenoglicóis/química
Traumatismo por Reperfusão/tratamento farmacológico
Acidente Vascular Cerebral/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Substitutes); 30IQX730WE (Polyethylene Glycols); 7U1EE4V452 (Carbon Monoxide); 9061-29-4 (Carboxyhemoglobin); S88TT14065 (Oxygen)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170412
[St] Status:MEDLINE
[do] DOI:10.1111/aor.12934


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[PMID]:28326562
[Au] Autor:Fukui T; Kawaguchi AT; Takekoshi S; Miyasaka M; Sumiyoshi H; Tanaka R
[Ad] Endereço:Department of Plastic Surgery, Tokai University School of Medicine, Kanagawa.
[Ti] Título:Liposome-Encapsulated Hemoglobin Accelerates Skin Wound Healing in Diabetic dB/dB Mice.
[So] Source:Artif Organs;41(4):319-326, 2017 Apr.
[Is] ISSN:1525-1594
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Since liposome-encapsulated hemoglobin with high O affinity (h-LEH, P O  = 10 mm Hg) has been reported to accelerate skin wound healing in normal mice, it was tested in dB/dB mice with retarded wound healing, as seen in human diabetics. Two full-thickness dorsal wounds 6 mm in diameter encompassed by silicone stents were created in dB/dB mice. Two days later (day 2), the animals were randomly assigned to receive intravenous h-LEH (2 mL/kg, n = 7) or saline (2 mL/kg, n = 7). The same treatment was repeated 4 days after wounding (day 4), and the size of the skin lesions was analyzed by photography, surface perfusion was detected by Laser-Doppler imager, and plasma cytokines and chemokines were determined on days 0, 2, 4, and 7, when all animals were euthanized for morphological studies. The size of the ulcer compared to the skin defect or silicone stent became significantly reduced on days 4 and 7 in mice treated with h-LEH (47 ± 8% of original size), similar to the level in wild-type mice, compared to saline-treated dB/dB mice (68 ± 18%, P < 0.01). Mice treated with h-LEH had significantly attenuated inflammatory cytokines, increased surface perfusion, and increased Ki67 expression on day 7 in accordance with the ulcer size reduction, while there was no significant difference in chemokines, histological granulation, epithelial thickness, and granulocyte infiltration detected by immunohistochemical staining in the ulcer between the treatment groups. The results suggest that h-LEH (2 mL/kg) early after wounding may accelerate skin wound healing in dB/dB mice to levels equivalent to wild-type mice probably via mechanism(s) involving reduced hypoxia, increased surface perfusion, suppressed inflammation, accelerated in situ cell proliferation and protein synthesis.
[Mh] Termos MeSH primário: Substitutos Sanguíneos/farmacologia
Diabetes Mellitus Tipo 2/fisiopatologia
Hemoglobinas/farmacologia
Fenômenos Fisiológicos da Pele/efeitos dos fármacos
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Aerobiose/efeitos dos fármacos
Animais
Substitutos Sanguíneos/administração & dosagem
Modelos Animais de Doenças
Hemoglobinas/administração & dosagem
Seres Humanos
Hipóxia/tratamento farmacológico
Subunidade alfa do Fator 1 Induzível por Hipóxia
Lipossomos
Masculino
Camundongos
Microcirculação/efeitos dos fármacos
Distribuição Aleatória
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Substitutes); 0 (Hemoglobins); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Liposomes)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1111/aor.12864



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