RESUMO
In this paper the effects on the interaction of highly positively charged substitution-inert platinum polynuclear complexes (SI-PPCs) with negatively charged DNA and heparin are examined and compared by theoretical chemistry methods. Electrostatic and hydrogen bonding interactions contribute to the overall effects on the biomolecule. Root Mean Square (RMS) deviation, Solvent Accessible Surface, RMS fluctuation, and interaction analysis all confirm similar effects on both biomolecules, dictated predominantly by the total positive charge and total number of hydrogen bonds formed. Especially, changes in structural parameters suggesting condensation and reduction of available surface area will reduce or prevent normal protein recognition and may thus potentially inhibit biological mechanisms related to apoptosis (DNA) or reduced vascularization viability (HEP). Thermodynamic analyses supported these findings with favourable interaction energies. The comparison of DNA and heparin confirms the general intersectionality between the two biomolecules and confirms the intrinsic dual-nature function of this chemotype. The distinction between the two-limiting mode of actions (HS or DNA-centred) could reflect an intriguing balance between extracellular (GAG) and intracellular (DNA) binding and affinities. The results underline the need to fully understand GAG-small molecule interactions and their contribution to drug pharmacology and related therapeutic modalities. This report contributes to that understanding.
Assuntos
DNA , Simulação de Dinâmica Molecular , Espermidina , Espermina , Espermina/química , DNA/química , DNA/metabolismo , Espermidina/química , Espermidina/metabolismo , Heparina/química , Heparina/metabolismo , Termodinâmica , Ligação de Hidrogênio , Eletricidade EstáticaRESUMO
To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia.Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.
Assuntos
Anticoagulantes , Tratamento Farmacológico da COVID-19 , COVID-19 , Heparina , Humanos , Heparina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Administração por Inalação , Idoso , COVID-19/virologia , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Nebulizadores e Vaporizadores , SARS-CoV-2 , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. CASE PRESENTATION: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. CONCLUSION: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.
Assuntos
Anestésicos , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Masculino , Humanos , Criança , Heparina/uso terapêutico , Fondaparinux , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Anticoagulantes/uso terapêutico , Hirudinas/efeitos adversos , Eosinofilia/induzido quimicamente , Eosinofilia/tratamento farmacológico , Fragmentos de Peptídeos , Proteínas RecombinantesRESUMO
A conductive nanocomposite consisting of heparin-stabilized gold nanoparticles embedded in graphene was prepared and characterized to develop an electrochemical sensor for the determination of esculetin in tea and jam samples. The gold nanoparticles were characterized by spectroscopic and microscopic techniques. The different proportions of graphene in the nanocomposite were evaluated and characterized by electrochemical practices. The heterostructure material on the glassy carbon electrode with esculetin showed π-π stacking interactions with an adsorption-controlled process. The voltammetric profile of esculetin using the proposed nanomaterial presented oxidation and reduction peaks at +0.61 and +0.58 V vs. Ag/AgCl, respectively, facilitating the electron transfer with esculetin through the transfer of two moles of protons and two moles of electrons per mole of esculetin. Using optimized conditions and square wave voltammetry, the calibration curve was obtained with two linear ranges, from 0.1 to 20.5 µmol L-1, with a detection limit of 43.0 nmol L-1. The electrochemical sensor showed satisfactory results for repeatability and stability, although interferences were observed in the presence of high concentrations of ascorbic acid or quercetin. The sensor was successfully applied in the determination of esculetin in samples of mulberry jam, white mulberry leaf tea, and white mulberry powder tea, presenting adequate recovery ranges. This directive provides valuable insights for the development of novel electrochemical sensors using heparin-based conductive nanomaterials with improved sensitivity and sensibility.
Assuntos
Grafite , Nanopartículas Metálicas , Toupeiras , Umbeliferonas , Animais , Grafite/química , Ouro/química , Heparina , Nanopartículas Metálicas/química , CháRESUMO
Ligneous conjunctivitis is a rare chronic form of recurrent membranous inflammation and plasminogen deficiency. Ocular manifestations may be associated with sites other than mucous membranes, such as the oral cavity, internal ear, respiratory, genitals, and kidney. Treatment is extremely difficult because of the lack of topic plasminogen drops, and a high volume is required for systemic supplementation. This report aimed to present two patients with ligneous conjunctivitis treated with membrane excision, topical fresh-frozen plasma, and heparin intra-, and postoperatively. No recurrence was found in the ligneous membrane in the 12-month follow-up. The use of topical fresh-frozen plasma and heparin after membrane excision could be effective to avoid recurrence.
Assuntos
Conjuntivite , Plasminogênio/deficiência , Dermatopatias Genéticas , Humanos , Conjuntivite/tratamento farmacológico , Conjuntivite/cirurgia , Dermatopatias Genéticas/complicações , Dermatopatias Genéticas/terapia , Heparina/uso terapêuticoRESUMO
Cardiovascular disorders, including acute myocardial infarction (AMI), often lead to blood clot formation, impacting blood circulation. Streptokinase, a cost-effective and widely available thrombolytic agent, is crucial in treating thrombosis. This study aimed to produce streptokinase from Streptococcus pyogenes EBL-48 and compare its efficacy with heparin in an animal model. We evaluated the clot-lysing effectiveness of streptokinase produced from Streptococcus pyogenes EBL-48, emphasizing its low cost and ease of production. Streptokinase was produced using pre-optimized fermentation media and purified through ion exchange and gel-filtration chromatography. In vivo analysis involved inducing clots in a trial animal model using ferric chloride, comparing streptokinase with heparin. Ultrasonography assessed the clot-lysing activity of streptokinase. Streptokinase (47 kDa) effectively lysed clots, proving its low cost, easy production, and minimal adverse effects. Ultrasonography confirmed its fibrinolytic efficacy. These findings highlight potential as an affordable and easily produced thrombolytic agent, particularly relevant in resource-limited settings. Streptokinase efficacy and minimal adverse effects make it a promising option for thrombolytic therapy, especially in economically constrained regions. Future studies could optimize production techniques, explore different strains, and conduct clinical trials for human validation. Comparative studies with other thrombolytic agents would enhance understanding of their advantages and limitations.
Assuntos
Fibrinolíticos , Estreptoquinase , Animais , Fermentação , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Heparina , Estreptoquinase/farmacologia , Estreptoquinase/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Loxosceles spp are arthropods found worldwide. Its bite may produce cutaneous loxoscelism (necrotic or edematous) or cutaneous-visceral loxoscelism. Depending on their severity and location, cutaneous forms are managed with local cold application and systemic administration of antihistamines, corticosteroids, antibiotics, polymorphonuclear inhibitors, and analgesics. OBJECTIVE: This study aimed to report a case of cutaneous loxoscelism and to identify the main dermatological manifestations associated with the Loxosceles spp bite. DESIGN AND SETTING: This case report and literature review was conducted in a Mexican university. METHODS: A detailed report on the medical management of a patient with cutaneous loxoscelism treated at the emergency department of a public hospital was published. Scopus, PubMed, Web of Science, and Google Scholar databases were searched to identify articles reporting cutaneous loxoscelism. The following keywords were used during the database search: "loxoscelism" OR "spider bite," OR "loxosceles" OR "loxosceles species" OR "loxosceles venom" OR "loxoscelism case report" AND "cutaneous" OR "dermonecrotic arachnidism." RESULTS: A 62-year-old female patient with cutaneous loxoscelism was treated with systemic dapsone and local heparin spray. Eighteen studies with 22 clinical cases were included in this systematic review. Of the 22 patients, 12 (54.5%) were men. L. rufescens was the predominant spider species. CONCLUSIONS: The administration of dapsone and heparin for the management of cutaneous loxoscelism demonstrated success in this case, with no sequelae observed. In general, the literature review indicated favorable outcomes in patients treated with antimicrobials and corticosteroids, with continuous healing of skin lesions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42023422424 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023422424).
Assuntos
Dapsona , Picada de Aranha , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Dapsona/uso terapêutico , Picada de Aranha/tratamento farmacológico , Hemoglobinas , Heparina , Corticosteroides , RegeneraçãoRESUMO
Metastasis is the leading cause of cancer-related deaths. Despite this relevance, there is no specific therapy targeting metastasis. The interaction of the tumor cell with platelets, forming microemboli is crucial for successful hematogenous dissemination. Heparin disrupts it by a P-selectin-mediated event. However, its clinical use for this purpose is hindered by the requirement of high doses, leading to anticoagulant-related side effects. In this study, we obtained a low-anticoagulant heparin through the fractionation of a pharmaceutical bovine heparin. This derivative was referred to as LA-hep and we investigated its efficacy in inhibiting metastases and explored its capacity of suppressing the interaction between tumor cells and platelets. Our data revealed that LA-hep is as efficient as porcine unfractionated heparin in attenuating lung metastases from melanoma and colon adenocarcinoma cells in an assay with a single intravenous administration. It also prevents platelet arrest shortly after cell injection in wild-type mice and suppresses melanoma-platelets interaction in vitro. Moreover, LA-hep blocks P-selectin's direct binding to tumor cells and platelet aggregation, providing further evidence for the role of P-selectin as a molecular target. Even in P-selectin-depleted mice which developed a reduced number of metastatic foci, both porcine heparin and LA-hep further inhibited metastasis burden. This suggests evidence of an additional mechanism of antimetastatic action. Therefore, our results indicate a dissociation between the heparin anticoagulant and antimetastatic effects. Considering the simple and highly reproducible methodology used to purify LA-hep along with the data presented here, LA-hep emerges as a promising drug for future use in preventing metastasis in cancer patients.
Assuntos
Adenocarcinoma , Neoplasias do Colo , Melanoma , Humanos , Animais , Bovinos , Camundongos , Heparina/farmacologia , Anticoagulantes/farmacologia , Selectina-P/metabolismo , Melanoma/patologia , Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Plaquetas/metabolismo , Preparações Farmacêuticas/metabolismo , Metástase Neoplásica/patologiaRESUMO
Extracorporeal circuits used in renal replacement therapy (RRT) can develop thrombosis, leading to downtimes and reduced therapy efficiency. To prevent this, anticoagulation is used, but the optimal anticoagulant has not yet been identified. Heparin is the most widely used anticoagulant in RRT, but it has limitations, such as unpredictable pharmacokinetics, nonspecific binding to plasma proteins and cells, and the possibility of suboptimal anticoagulation or bleeding complications, specifically in critically ill patients with acute renal failure who are already at high risk of bleeding. Citrate anticoagulation is a better alternative, being considered a standard for continuous renal replacement therapy, since it is associated with a lower risk of bleeding complications and better efficacy, even in patients with acute renal failure or liver disease. The aim of this article is to provide an updated review of the different strategies of anticoagulation in renal replacement therapies that can be implemented in critical scenarios, focusing on the advantages and disadvantages of each one and the beneficial aspects of using citrate over heparin in critical ill patients.
Assuntos
Injúria Renal Aguda , Heparina , Humanos , Heparina/uso terapêutico , Estado Terminal/terapia , Anticoagulantes/efeitos adversos , Terapia de Substituição Renal , Ácido Cítrico/uso terapêutico , Citratos , Injúria Renal Aguda/terapiaRESUMO
Introducción: El síndrome de Paget-Schroetter (SPS) es una trombosis venosa profunda primaria del complejo venoso subclavio-axilar que ocurre después del uso repetitivo y extenuante de los hombros y los brazos. Muestra una incidencia de 1 por 100 000 personas al año. Se informa con mayor frecuencia en atletas jóvenes. Objetivo: Presentar un caso inusual de síndrome de Paget-Schroetter en un individuo joven no deportista. Caso clínico: Varón militar activo de 24 años de edad, sin antecedentes patológicos personales, que ingresó con inflamación del miembro superior izquierdo de 24 horas de evolución. Presentó una trombosis de la vena cefálica izquierda después de un esfuerzo físico de carga y descarga. Tras descartar trastornos secundarios de hipercoagulabilidad se le diagnosticó un SPS. Se le informó de la opción de intervención quirúrgica, pero la rechazó. El diagnóstico fue confirmado con ecografía Doppler y tratado con anticoagulación endovenosa al inicio y luego por vía oral durante 6 meses. Durante el seguimiento no se evidenció trombosis crónica de la vena cefálica izquierda ni formación de intervalo de colaterales vasculares. Conclusiones: El SPS es una condición clínica que necesita un alto índice de sospecha y un diagnóstico oportuno, por tanto, los médicos deben estar atentos a esta rara entidad para su reconocimiento temprano y derivación oportuna a cirugía vascular(AU)
Introduction: Paget-Schroetter syndrome (PSS) is a primary deep vein thrombosis of the subclavian-axillary venous complex that occurs after repetitive and strenuous use of the shoulders and arms. It shows an incidence of 1 per 100,000 people per year. It is reported more frequently in young athletes. Objective: To present an unusual case of Paget-Schroetter syndrome in a young non-athlete individual. Clinical case: 24-year-old active military man with no personal pathological history is presented, who was admitted with inflammation of the left upper limb of 24 hours of evolution. He presented a thrombosis of the left cephalic vein after a physical effort of loading and unloading. After ruling out secondary hypercoagulability disorders, he was diagnosed with SPS. He was informed of the option of surgical intervention, but he declined it. The diagnosis was confirmed with Doppler ultrasound and treated with intravenous anticoagulation at the beginning, and then orally for 6 months. During the follow-up of the patient, there was no evidence of chronic thrombosis of the left cephalic vein or interval formation of vascular collaterals. Conclusions: SPS is a clinical condition that requires a high index of suspicion and prompt diagnosis, therefore, physicians must be attentive to this rare entity for early recognition and timely referral to vascular surgery(AU)
Assuntos
Humanos , Masculino , Adulto , Ultrassonografia Doppler/métodos , Esforço Físico , Trombose Venosa Profunda de Membros Superiores/diagnóstico por imagem , Heparina/administração & dosagem , Militares , Anticoagulantes/uso terapêuticoRESUMO
Objetivo: examinar el efecto de la técnica de tos de mediana intensidad durante la inyección subcutánea de heparina de bajo peso molecular sobre la severidad del dolor y la satisfacción individual en pacientes de cirugía general. Método: estudio prospectivo, cuasi experimental, que incluyó a 100 pacientes a los que se les prescribió una inyección subcutánea de heparina de bajo peso molecular una vez cada 24 horas. Cada paciente recibió dos inyecciones por el mismo investigador utilizando técnica de inyección estándar con técnica de tos de intensidad media y solo técnica de inyección estándar. Resultados: hubo una diferencia estadísticamente significativa entre las puntuaciones medias de los pacientes sobre la intensidad del dolor y los niveles de satisfacción después de las inyecciones administradas por las dos técnicas (p= 0,000). Además, se encontró que el género afectó la severidad del dolor relacionado con la inyección, pero no afectó el nivel de satisfacción individual. Conclusión: se encontró que la técnica de tos de intensidad media reduce la severidad del dolor y aumenta la satisfacción del paciente de cirugía general que reciben inyecciones subcutáneas de heparina de bajo peso molecular. Registro del ensayo: NCT05681338.
Objective: to examine the effect of the medium intensity coughing technique during subcutaneous low molecular weight heparin injection on pain severity and individual satisfaction in general surgery patients. Method: the prospective, quasi-experimental study included 100 patients who had been prescribed a subcutaneous low molecular weight heparin injection once in 24 hours. Each patient received two injections by the same researcher, one using the standard injection technique with medium intensity coughing technique and the other only the standard injection technique. Results: there was a statistically significant difference between patients' mean scores on pain severity and satisfaction levels after injections administered by the two techniques (p= 0.000). Also, it was found that gender affected pain severity relating to the injection but did not affect the level of individual satisfaction. Conclusion: the medium intensity coughing technique was found to reduce pain severity and increase patient satisfaction in general surgery patients receiving subcutaneous low molecular weight heparin injections. Trial registration: NCT05681338.
Objetivo: examinar o efeito da técnica de tosse de média intensidade durante injeção subcutânea de heparina de baixo peso molecular na intensidade da dor e satisfação individual em pacientes submetidos à cirurgia geral. Método: estudo prospetivo, quasi experimental que incluiu 100 pacientes que haviam recebido uma injeção subcutânea de heparina de baixo peso molecular em 24 horas. Cada paciente recebeu duas injeções pelo mesmo pesquisador usando a técnica de injeção padrão com técnica de tosse de média intensidade e apenas técnica de injeção padrão. Resultados: houve diferença estatisticamente significativa entre as pontuações médias dos pacientes quanto à gravidade da dor e níveis de satisfação após as injeções administradas pelas duas técnicas (p = 0,000). Além disso, verificou-se que o sexo do paciente afetou a intensidade da dor relacionada à injeção, mas não afetou o nível de satisfação individual. Conclusão: a técnica de tosse de média intensidade reduz a intensidade da dor e aumenta a satisfação de pacientes submetidos à cirurgia geral recebendo injeções subcutâneas de heparina de baixo peso molecular. Registro do ensaio clínico: NCT05681338.
Assuntos
Humanos , Cirurgia Geral , Medição da Dor , Heparina , Estudos Prospectivos , Satisfação do Paciente , Tosse , AnticoagulantesRESUMO
BACKGROUND: The extracellular matrix (ECM) is a complex tridimensional scaffold that actively participates in physiological and pathological events. The objective of this study was to test whether structural proteins of the ECM and glycosaminoglycans (GAGs) may favor the retention of human apolipoprotein A-I (apoA-I) variants associated with amyloidosis and atherosclerosis. METHODS: Biopolymeric matrices containing collagen type I (Col, a main macromolecular component of the ECM) with or without heparin (Hep, a model of GAGs) were constructed and characterized, and used to compare the binding of apoA-I having the native sequence (Wt) or Arg173Pro, a natural variant inducing cardiac amyloidosis. Protein binding was observed by fluorescence microscopy and unbound proteins quantified by a colorimetric assay. RESULTS: Both, Wt and Arg173Pro bound to the scaffolds containing Col, but the presence of Hep diminished the binding efficiency. Col-Hep matrices retained Arg173Pro more than the Wt. The retained protein was only partially removed from the matrices with saline solutions, indicating that electrostatic interactions may occur but are not the main driving force. Using in addition thermodynamic molecular simulations and size exclusion chromatography approaches, we suggest that the binding of apoA-I variants to the biopolymeric matrices is driven by many low affinity interactions. CONCLUSIONS: Under this scenario Col-Hep scaffolds contribute to the binding of Arg173Pro, as a cooperative platform which could modify the native protein conformation affecting protein folding. GENERAL SIGNIFICANCE: We show that the composition of the ECM is key to the protein retention, and well characterized biosynthetic matrices offer an invaluable in vitro model to mimic the hallmark of pathologies with interstitial infiltration such as cardiac amyloidosis.
Assuntos
Amiloidose , Heparina , Humanos , Amiloidose/metabolismo , Apolipoproteína A-I/genética , Apolipoproteína A-I/química , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Heparina/metabolismoRESUMO
Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P<0.05). Thus, bivalirudin presented a better safety profile than heparin among Chinese STEMI patients undergoing PCI.
Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Heparina/efeitos adversos , Estudos Retrospectivos , Antitrombinas/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , População do Leste Asiático , Resultado do Tratamento , Hirudinas/efeitos adversos , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Fragmentos de Peptídeos/efeitos adversos , Fibrinolíticos , Proteínas Recombinantes/efeitos adversosRESUMO
BACKGROUND: Prolonged hemodialysis (HD) is performed from 6 to 12 h and can last up to 24 h. To prevent system clotting some studies suggest that Regional Citrate Anticoagulation (RCA) use reduces bleeding rates relative to systemic heparin. However, there may be difficulties in the patient's clinical management and completing the prescribed HD with Genius system using RCA. OBJECTIVE: To analyze safety Quality Indicators (IQs) and follow up on prolonged HD with 4% sodium citrate solution in a Genius® hybrid system. METHODS: This is a retrospective cohort conducted in an intensive care unit. RESULTS: 53 random sessions of prolonged HD with 4% sodium citrate solution of critically ill patients with AKI assessed. Evaluated safety indicators were dysnatremia and metabolic alkalosis, observed in 15% and 9.4% of the sessions, respectively. Indicators of effectiveness were system clotting which occurred in 17.3%, and the minimum completion of the prescribed HD time, which was 75.5%. CONCLUSION: The assessment of the indicators showed that the use of RCA with a 4% sodium citrate solution in prolonged HD with the Genius system in critically ill patients with AKI can be performed in a simple, safe, and effective way.
Assuntos
Injúria Renal Aguda , Ácido Cítrico , Humanos , Injúria Renal Aguda/terapia , Anticoagulantes/uso terapêutico , Citratos/uso terapêutico , Ácido Cítrico/uso terapêutico , Estado Terminal/terapia , Heparina/efeitos adversos , Indicadores de Qualidade em Assistência à Saúde , Diálise Renal , Estudos Retrospectivos , Citrato de SódioRESUMO
Objetivo: Discutir o papel das trombofilias na perda gestacional de repetição, com foco em prevalência/associação dessas patologias com perdas de repetição e seu tratamento, por meio de resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publi- cados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando os seguintes descritores: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome" e "treatment". Resultados: A maioria dos estudos relatou forte associação entre os anticorpos antifosfolípides específicos e a síndrome do anticorpo antifosfolípide com perda gestacional de repetição. Mulheres portadoras da mutação do fator V de Leiden, mutação do gene da protrombina e deficiência de proteína S apresentaram alto risco de perda gestacional de repetição em uma grande revisão sistemática. Estudos recentes demonstraram taxas de prevalência das trombofilias hereditárias e da síndrome do anticorpo antifosfolípide, em mulheres com perda gestacional de repetição, semelhantes às da população em geral. Os estudos atuais endossam o uso da heparina associada à aspirina em mulheres com síndrome do anticorpo antifosfolípide, com aumento da taxa de nascidos vivos, mas sem diferença em re- lação às complicações obstétricas. Conclusão: Apesar de novos estudos demons- trarem que a prevalência das trombofilias hereditárias e adquiridas em mulheres com perda gestacional de repetição é semelhante à da população em geral, reco- menda-se a pesquisa rotineira de síndrome do anticorpo antifosfolípide nessas pacientes. O uso de aspirina em baixas doses associada à heparina é a intervenção farmacológica de primeira linha para a prevenção de perda gestacional de repeti- ção em pacientes com síndrome do anticorpo antifosfolípide.
Objective: To discuss the role of thrombophilias in recurrent pregnancy loss, focu- sing on the prevalence/association of these pathologies with recurrent abortion and treatment, through results of clinical trials, systematic reviews and meta-analyses. Methods: This is a non-systematic review of articles published in electronic databa- ses PubMed, Cochrane, SciELO in the last five years, using the following descriptors: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome", and "treatment". Results: Most studies have reported a strong association between specific antiphospholipid antibodies and antiphospho- lipid antibody syndrome with recurrent pregnancy loss. Women carrying the factor V Leiden mutation, prothrombin gene mutation, and protein S deficiency were shown to be at high risk of recurrent pregnancy loss in a large systematic review. Recent studies have shown prevalence rates of hereditary thrombophilias and antiphospholipid antibody syndrome, in women with re- current pregnancy loss, similar to those of the general po- pulation. Current studies endorse the use of heparin plus aspirin in women with antiphospholipid antibody syndrome, with an increase in live birth rate, but with no difference in obstetric complications. Conclusion: Although new studies demonstrate that the prevalence of hereditary and acquired thrombophilias in women with recurrent pregnancy loss is si- milar to that of the general population, routine investigation of antiphospholipid antibody syndrome in these patients is recommended. The use of low-dose aspirin plus heparin is the first-line pharmacological intervention for the prevention of recurrent pregnancy loss in patients with antiphospholipid antibody syndrome.
Assuntos
Humanos , Feminino , Gravidez , Trombofilia/diagnóstico , Aborto , Fator V , Protrombina/genética , Heparina/farmacologia , Aspirina/farmacologia , Deficiência de Proteína S/complicaçõesRESUMO
La determinación de proteínas totales es una técnica de rutina utilizada en la industria biofarmacéutica durante los procesos de purificación de derivados plasmáticos y/o producción de proteínas recombinantes; y la elección del método analítico es un paso crítico para la obtención de resultados confiables. En este trabajo se demostró la interferencia de heparina (Hep), un compuesto comúnmente utilizado como excipiente en la formulación de Concentrados de Factores de la Coagulación (CFC), en la determinación de proteínas por el método de Bradford, cuya interferencia no está descripta como tal en los insertos de los kits comerciales de Bradford ni en la Farmacopea Europea. Esta interferencia fue demostrada tanto en soluciones de Albúmina Sérica Bovina (BSA) fortificadas con Hep, como en muestras de CFC. Para una solución de BSA 40 mg %, la concentración límite de Hep que no interfiere en la determinación de proteínas totales fue de 1,6 UI/ml. Cabe destacar que, si se trabaja a un nivel menor de concentración de proteínas, una proteína diferente o mezclas complejas de proteínas, se debe evaluar el grado de interferencia para cada caso particular, pudiéndose utilizar los valores obtenidos en este trabajo como referencia. Alternativamente, se evaluó la neutralización de la Hep con Polybrene (Poly), previo a la determinación de proteínas por Bradford. En el caso de soluciones de BSA, el efecto interferente se revirtió logrando una correcta cuantificación de proteínas, mientras que en las muestras de CFC, la neutralización con Poly no fue efectiva. Por lo tanto, para considerar el uso de Poly, previo a la aplicación del método de Bradford, debe evaluarse cada caso particular según las características de la muestra proteica en estudio. Si esto no es posible, se recomienda la utilización de un método alternativo, por ejemplo, el colorimétrico que utiliza ácido bicinconínico.
Protein quantification in biological samples is a routine assay used in the biopharmaceutical industry during the purification procedures of plasma-derived products and/or recombinant proteins. Thus, choosing the method for this purpose is a critical step to obtaining reliable results. In this work, it was shown that Heparin (Hep), a compound commonly used as an excipient in the formulation step of Coagulation Factor Concentrates (CFC), interferes in protein quantification by the Bradford assay. This interference was proved both in solutions of Hep-fortified Bovine Serum Albumin (BSA) and in CFC samples. For a 40 mg % BSA solution, the Hep concentration which shows no interference in protein quantification is 1.6 IU/ml. It should be noted that a specific analysis must be carried out if working at a lower protein concentration, with a different protein, or with complex protein solutions, so the values obtained in this work can be used as a reference. Alternatively, Hep neutralization with Polybrene (Poly) was evaluated before protein determination by Bradford. In the case of BSA solutions, the interference was reversed and correct protein quantification was achieved, whereas in the CFC samples, the results were unsatisfactory. Until now, Hep interference in the Bradford assay has not been described in the scientific literature, nor listed in the inserts of the commercial kits for protein quantification by this method. It was concluded that for protein samples containing Hep, the choice of an alternative method, such as the one that uses bicinchoninic acid, is the most convenient option to obtain reliable results
Assuntos
Coagulação Sanguínea , Heparina , Proteínas , Métodos de Análise Laboratorial e de CampoRESUMO
CONTEXT: Heparin, one of the drugs reused in studies with antiviral activity, was chosen to investigate a possible blockade of the SARS-CoV-2 spike protein for viral entry through computational simulations and experimental analysis. Heparin was associated to graphene oxide to increase in the binding affinity in biological system. First, the electronic and chemical interaction between the molecules was analyzed through ab initio simulations. Later, we evaluate the biological compatibility of the nanosystems, in the target of the spike protein, through molecular docking. The results show that graphene oxide interacts with the heparin with an increase in the affinity energy with the spike protein, indicating a possible increment in the antiviral activity. Experimental analysis of synthesis and morphology of the nanostructures were carried out, indicating heparin absorption by graphene oxide, confirming the results of the first principle simulations. Experimental tests were conducted on the structure and surface of the nanomaterial, confirming the heparin aggregation on the synthesis with a size between the GO layers of 7.44 Å, indicating a C-O type bond, and exhibiting a hydrophilic surface characteristic (36.2°). METHODS: Computational simulations of the ab initio with SIESTA code, LDA approximations, and an energy shift of 0.05 eV. Molecular docking simulations were performed in the AutoDock Vina software integrated with the AMDock Tools Software using the AMBER force field. GO, GO@2.5Heparin, and GO@5Heparin were synthesized by Hummers and impregnation methods, respectively, and characterized by X-ray diffraction and surface contact angle.
Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Simulação de Acoplamento Molecular , Glicoproteína da Espícula de Coronavírus/metabolismo , Heparina/metabolismo , SARS-CoV-2/metabolismo , Antivirais/farmacologiaRESUMO
Hypercoagulability, a major complication of metastatic cancers, has usually been treated with heparins from natural sources, or with their synthetic derivatives, which are under intense investigation in clinical oncology. However, the use of heparin has been challenging for patients with risk of severe bleeding. While the systemic administration of heparins, in preclinical models, has shown primarily attenuating effects on metastasis, their direct effect on established solid tumors has generated contradictory outcomes. We investigated the direct antitumoral properties of two sulfated fucans isolated from marine echinoderms, FucSulf1 and FucSulf2, which exhibit anticoagulant activity with mild hemorrhagic potential. Unlike heparin, sulfated fucans significantly inhibited tumor cell proliferation (by ~30-50%), and inhibited tumor migration and invasion in vitro. We found that FucSulf1 and FucSulf2 interacted with fibronectin as efficiently as heparin, leading to loss of prostate cancer and melanoma cell spreading. The sulfated fucans increased the endocytosis of ß1 integrin and neuropilin-1 chains, two cell receptors implicated in fibronectin-dependent adhesion. The treatment of cancer cells with both sulfated fucans, but not with heparin, also triggered intracellular focal adhesion kinase (FAK) degradation, with a consequent overall decrease in activated focal adhesion kinase levels. Finally, only sulfated fucans inhibited the growth of B16-F10 melanoma cells implanted in the dermis of syngeneic C57/BL6 mice. FucSulf1 and FucSulf2 arise from this study as candidates for the design of possible alternatives to long-term treatments of cancer patients with heparins, with the advantage of also controlling local growth and invasion of malignant cells.
Assuntos
Integrina beta1 , Melanoma , Masculino , Animais , Humanos , Camundongos , Proteína-Tirosina Quinases de Adesão Focal , Integrina beta1/metabolismo , Fibronectinas/metabolismo , Neuropilina-1 , Heparina/farmacologia , EndocitoseRESUMO
Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia associated with a highly prothrombotic state due to the development of pathogenic antibodies that recognize human platelet factor 4 (hPF4) complexed with various polyanions. Although nonheparin anticoagulants are the mainstay of care in HIT, subsequent bleeding may develop, and the risk of developing new thromboembolic events remain. We previously described a mouse immunoglobulin G2bκ (IgG2bκ) antibody KKO that mimics the sentinel features of pathogenic HIT antibodies, including binding to the same neoepitope on hPF4-polyanion complexes. KKO, like HIT IgGs, activates platelets through FcγRIIA and induces complement activation. We then questioned whether Fc-modified KKO could be used as a novel therapeutic to prevent or treat HIT. Using the endoglycosidase EndoS, we created deglycosylated KKO (DGKKO). Although DGKKO retained binding to PF4-polyanion complexes, it inhibited FcγRIIA-dependent activation of PF4-treated platelets triggered by unmodified KKO, 5B9 (another HIT-like monoclonal antibody), and IgGs isolated from patients with HIT. DGKKO also decreased complement activation and deposition of C3c on platelets. Unlike the anticoagulant fondaparinux, injection of DGKKO into HIT mice lacking mouse PF4, but transgenic for hPF4 and FcγRIIA, prevented and reversed thrombocytopenia when injected before or after unmodified KKO, 5B9, or HIT IgG. DGKKO also reversed antibody-induced thrombus growth in HIT mice. In contrast, DGKKO was ineffective in preventing thrombosis induced by IgG from patients with the HIT-related anti-PF4 prothrombotic disorder, vaccine-induced immune thrombotic thrombocytopenia. Thus, DGKKO may represent a new class of therapeutics for targeted treatment of patients with HIT.