Treatment of Chronic Venous Ulcers With Heterologous Fibrin Sealant: A Phase I/II Clinical Trial.

Background: Heterologous fibrin sealant (HFS) consists of a fibrinogen-rich cryoprecipitate extracted from Bubalus bubalis buffalo blood and a thrombin-like enzyme purified from Crotalus durissus terrificus snake venom. This study evaluated the safety and immunogenicity of HFS, estimated the best dose, and assessed its preliminary efficacy in the treatment of chronic venous ulcers (CVU). Methods: A phase I/II non-randomized, single-arm clinical trial was performed on 31 participants, accounting for a total of 69 active CVUs. All ulcers were treated with HFS, essential fatty acid, and Unna boot for 12 weeks. The outcomes assessed were: (1) primary safety, immunogenicity analyses, and confirmation of the lowest safe dose; (2) secondary promising efficacy by analyzing the healing process. Immunogenicity was evaluated using the serum-neutralizing (IgM and IgG) and non-neutralizing (IgA and IgE) antibody techniques against the product. The immuno-detection of IgE class antibodies was assessed using dot-blot assay before and at the end of treatment. Positive samples on dot-blot assays were subsequently analyzed by western blotting to verify the results. Results: No severe systemic adverse events related to the use of HFS were observed. Local adverse events potentially related to treatment include ulcer pain (52%), peri-ulcer maceration (16%), peri-ulcer pruritus (12%), critical colonization (8%), peri-ulcer eczema (4%), the opening of new ulcers (4%), and increased ulcerated area 4%). Neutralizing and non-neutralizing antibodies did not show significant deviations at any of the evaluated time points. Blot assays showed that all patients presented negative immunological reactions, either before or after treatment, with the thrombin-like enzyme component. In addition, two participants showed a positive immunological reaction to the cryoprecipitate component, while another two were positive before and during treatment. Regarding the secondary outcomes of preliminary efficacy, a total healing and significant reduction of the area was observed in 47.5 and 22%, respectively. A qualitative improvement was observed in the wound beds of unhealed ulcers. Conclusions: The investigational HFS bioproduct proved to be safe and non-immunogenic with a good preliminary efficacy for the treatment of CVU, according to the protocol and doses proposed. A multicentric phase III clinical trial will be necessary to verify these findings.

Heterologous fibrin sealant derived from snake venom: from bench to bedside - an overview.

Hemostatic and adhesive agents date back to World War II, when homologous fibrin sealant came onto scene. Considering that infectious diseases can be transmitted via human blood, a new heterologous fibrin sealant was standardized in the 1990s. Its components were a serine protease (a thrombin-like enzyme) extracted from the venom of Crotalus durissus terrificus snakes and a fibrinogen-rich cryoprecipitate extracted from the blood of Bubalus bubalis buffaloes. This new bioproduct has been used as a coagulant, sealant, adhesive and recently as a candidate scaffold for mesenchymal stem cells and bone and cartilage repair. This review discusses the composition of a new heterologous fibrin sealant, and cites published articles related to its preclinical applications aiming at repairing nervous system traumas and regenerating bone marrow. Finally, we present an innovative safety trial I/II that found the product to be a safe and clinically promising candidate for treating chronic venous ulcers. A multicenter clinical trial, phase II/III, with a larger number of participants will be performed to prove the efficacy of an innovative biopharmaceutical product derived from animal venom.

Heterologous fibrin sealant derived from snake venom: from bench to bedside an overview

Abstract Hemostatic and adhesive agents date back to World War II, when homologous fibrin sealant came onto scene. Considering that infectious diseases can be transmitted via human blood, a new heterologous fibrin sealant was standardized in the 1990s. Its components were a serine protease (a thrombin-like enzyme) extracted from the venom of Crotalus durissus terrificus snakes and a fibrinogen-rich cryoprecipitate extracted from the blood of Bubalus bubalis buffaloes. This new bioproduct has been used as a coagulant, sealant, adhesive and recently as a candidate scaffold for mesenchymal stem cells and bone and cartilage repair. This review discusses the composition of a new heterologous fibrin sealant, and cites published articles related to its preclinical applications aiming at repairing nervous system traumas and regenerating bone marrow. Finally, we present an innovative safety trial I/II that found the product to be a safe and clinically promising candidate for treating chronic venous ulcers. A multicenter clinical trial, phase II/III, with a larger number of participants will be performed to prove the efficacy of an innovative biopharmaceutical product derived from animal venom.

Heterologous fibrin sealant derived from snake venom: from bench to bedside - an overview

Hemostatic and adhesive agents date back to World War II, when homologous fibrin sealant came onto scene. Considering that infectious diseases can be transmitted via human blood, a new heterologous fibrin sealant was standardized in the 1990s. Its components were a serine protease (a thrombin-like enzyme) extracted from the venom of Crotalus durissus terrificus snakes and a fibrinogen-rich cryoprecipitate extracted from the blood of Bubalus bubalis buffaloes. This new bioproduct has been used as a coagulant, sealant, adhesive and recently as a candidate scaffold for mesenchymal stem cells and bone and cartilage repair. This review discusses the composition of a new heterologous fibrin sealant, and cites published articles related to its preclinical applications aiming at repairing nervous system traumas and regenerating bone marrow. Finally, we present an innovative safety trial I/II that found the product to be a safe and clinically promising candidate for treating chronic venous ulcers. A multicenter clinical trial, phase II/III, with a larger number of participants will be performed to prove the efficacy of an innovative biopharmaceutical product derived from animal venom.(AU)

Quality of life index in autoimmune bullous dermatosis patients.

BACKGROUND: Autoimmune bullous dermatoses are complex diseases triggered by autoantibodies action against epidermal antigens or the dermoepidermal junction. Blisters and vesicles that evolve with erosion areas characterize them. Although rare, they present high morbidity, affecting the quality of life of patients. OBJECTIVES: To assess the magnitude of autoimmune bullous dermatoses on life quality of patients treated in a public university service in countryside of Brazil. METHODS: This cross-sectional study was based on an inquiry with autoimmune bullous dermatoses patients assisted at outpatient university referral service. Elements related to quality of life were evaluated by the Dermatology Life Quality Index, as well as clinical and demographic data. RESULTS: The study evaluated 43 patients with pemphigus foliaceus, 32 with pemphigus vulgaris, 6 with bullous pemphigoid and 3 with dermatitis herpetiformis. The average age was 48 ± 16 years and 34 (40%) were female. The median score (p25-p75) of the Dermatology Life Quality Index was 16 (9-19), classified as "severe impairment" of life quality, in which the greater impact was related to symptoms and feelings, daily and leisure activities. CONCLUSIONS: Autoimmune bullous dermatoses inflict severe impairment of quality of life for patients followed by a public outpatient clinic in the countryside of Brazil.

Quality of life index in autoimmune bullous dermatosis patients

BACKGROUND: Autoimmune bullous dermatoses are complex diseases triggered by autoantibodies action against epidermal antigens or the dermoepidermal junction. Blisters and vesicles that evolve with erosion areas characterize them. Although rare, they present high morbidity, affecting the quality of life of patients. OBJECTIVES: To assess the magnitude of autoimmune bullous dermatoses on life quality of patients treated in a public university service in countryside of Brazil. METHODS: This cross-sectional study was based on an inquiry with autoimmune bullous dermatoses patients assisted at outpatient university referral service. Elements related to quality of life were evaluated by the Dermatology Life Quality Index, as well as clinical and demographic data. RESULTS: The study evaluated 43 patients with pemphigus foliaceus, 32 with pemphigus vulgaris, 6 with bullous pemphigoid and 3 with dermatitis herpetiformis. The average age was 48 ± 16 years and 34 (40%) were female. The median score (p25-p75) of the Dermatology Life Quality Index was 16 (9-19), classified as "severe impairment" of life quality, in which the greater impact was related to symptoms and feelings, daily and leisure activities. CONCLUSIONS: Autoimmune bullous dermatoses inflict severe impairment of quality of life for patients followed by a public outpatient clinic in the countryside of Brazil. .

Low-level laser therapy on the treatment of oral and cutaneous pemphigus vulgaris: case report.

Pemphigus vulgaris is a chronic autoimmune mucocutaneous disease that initially is manifested by painful intraoral erosions and ulcers which spread to other mucosa and the skin, generally more than 5 months after oral lesion manifestation. The treatment consists of prednisone alone or in combination with an immunosuppressive agent, and the clinical response is perceived within 2 to 4 weeks. Low-level laser therapy has been effective in accelerating the healing of injured tissue, thus inducing cell proliferation and increasing ATP, nucleic acid, and collagen synthesis. We reported two cases of pemphigus vulgaris that received systemic treatment associated with low-level laser therapy for oral and cutaneous lesions. We observed prompt analgesic effect in oral lesions and accelerated healing of oral and cutaneous wounds. Therefore, the present report suggests LLLT as a noninvasive technique that should be considered as an adjuvant therapy in oral and skin disorders in patients with PV.

Africanized honeybee stings: how to treat them / Picadas de abelhas africanizadas: como tratá-las?

INTRODUCTION: In 1956, Africanized honeybees (AHB) migrated from Brazil to other regions of the Western Hemisphere, including South, Central, and North America, except for Canada. Despite being productive, they are highly aggressive and cause fatal accidents. This study aimed to evaluate patients at the Clinical Hospital of Botucatu Medical School (HC-FMB) and to propose treatment guidelines. METHODS: From 2005 to 2006, the clinical and laboratorial aspects of 11 patients (7 male and 4 female) and the anatomopathological aspects of one patient who had died in 2003 were analyzed. RESULTS: The age of the surviving patients varied from 5 to 87 years, with a mean of 42.5 years. The majority of accidents occurred in the afternoon, and the number of stings ranged from 20 to 500. The principal signs and symptoms were pain and local inflammatory signs, nausea, tachycardia, and vomiting. Biochemical findings presented increased levels of creatine phosphokinase, lactate dehydrogenase, and aspartate/alanine aminotransferase. An 11-year-old male patient died upon entering the attic of a two-storey building where he was attacked by a swarm, receiving more than 1,000 stings. He was sent to HC-FMB where he was treated, but he died 24h later. Observed at the autopsy were erythematous-purpuric skin lesions besides necrosis at the sting locations, rhabdomyolysis, focal myocardial necrosis, tubular hydropic degeneration and focal tubular acute necrosis of the kidneys, myoglobinuria, and centrolobular necrosis in the liver. CONCLUSIONS: Accidents caused by multiple AHB stings always constitute a medical emergency. As there is no specific antivenom, we have developed guidelines, including first aid, drugs, and the proper removal of stingers.

INTRODUÇÃO: As abelhas africanizadas (AHBs) migraram do Brasil em 1956 para todo o continente Americano. Apesar de produtivas, são agressivas causando acidentes fatais. O objetivo foi avaliar pacientes atendidos no Hospital das Clínicas da Faculdade de Medicina de Botucatu (HC-FMB) e propor um roteiro de tratamento. MÉTODOS: Entre 2005 e 2006, foram analisados os aspectos clínicos e laboratoriais de 11 pacientes e anatomopatológicos de um que foi a óbito em 2003. RESULTADOS: A idade dos pacientes variou entre 5 e 87 com média de 42,5 anos. Sete eram do sexo masculino e quatro do feminino. O número de picadas variou entre 20 e 500. Nove deles receberam mais de 50 picadas. Os principais sinais e sintomas foram dor local, náuseas, taquicardia e vômitos. Os exames hematológicos mostraram leucocitose, neutrofilia, anemia e desvio à esquerda escalonado. Os exames bioquímicos revelaram níveis elevados de creatinofosfoquinase, desidrogenase lática e aspartato/alanina aminotransferase. O paciente que foi a óbito 24h após o atendimento tinha 11 anos, era do sexo masculino e foi atacado ao adentrar um edifício de dois andares recebendo mais de 1.000 picadas. O exame anatomopatológico mostrou lesões eritemato-purpúricas, além de necrose nos locais das picadas. Apresentou também rabdomiólise, necroses focais do miocárdio, degeneração hidrópica acompanhada de necrose tubular renal aguda, mioglobinúria e necrose centrolobular no fígado. CONCLUSÕES: Os pacientes acometidos por múltiplas picadas necessitam de tratamento imediato e por não dispormos de um soro específico desenvolvemos um roteiro que inclui os primeiros socorros, as drogas a serem empregadas e a retirada dos ferrões corretamente.

Africanized honeybee stings: how to treat them.

INTRODUCTION: In 1956, Africanized honeybees (AHB) migrated from Brazil to other regions of the Western Hemisphere, including South, Central, and North America, except for Canada. Despite being productive, they are highly aggressive and cause fatal accidents. This study aimed to evaluate patients at the Clinical Hospital of Botucatu Medical School (HC-FMB) and to propose treatment guidelines. METHODS: From 2005 to 2006, the clinical and laboratorial aspects of 11 patients (7 male and 4 female) and the anatomopathological aspects of one patient who had died in 2003 were analyzed. RESULTS: The age of the surviving patients varied from 5 to 87 years, with a mean of 42.5 years. The majority of accidents occurred in the afternoon, and the number of stings ranged from 20 to 500. The principal signs and symptoms were pain and local inflammatory signs, nausea, tachycardia, and vomiting. Biochemical findings presented increased levels of creatine phosphokinase, lactate dehydrogenase, and aspartate/alanine aminotransferase. An 11-year-old male patient died upon entering the attic of a two-story building where he was attacked by a swarm, receiving more than 1,000 stings. He was sent to HC-FMB where he was treated, but he died 24h later. Observed at the autopsy were erythematous-purpuric skin lesions besides necrosis at the sting locations, rhabdomyolysis, focal myocardial necrosis, tubular hydropic degeneration and focal tubular acute necrosis of the kidneys, myoglobinuria, and centrolobular necrosis in the liver. CONCLUSIONS: Accidents caused by multiple AHB stings always constitute a medical emergency. As there is no specific antivenom, we have developed guidelines, including first aid, drugs, and the proper removal of stingers.

Pênfigo foliáceo no Hospital das Clínicas da Faculdade de Medicina de Botucatu, SP / Pemphigus foliaceus in University Hospital of the School of Medicine of Botucatu, SP

FUNDAMENTOS - O pênfigo foliáceo é doença bolhosa, auto-imune, com características endêmicas no Brasil e em outros países da América do Sul. OBJETIVOS - Correlacionar os dados clínicos e epidemiológicos observados e os referidos na literatura. MÉTODO - Realizado estudo restrospectivo sobre portadores de pênfigo foliáceo atendidos no Hospital das Clínicas da Faculdade de Medicina de Botucatu, SP, no período de junho/76 a julho/93, com análise das variáveis idade, sexo, cor, procedência, profissäo, época de adoecimento. RESULTADOS - Nesse período, foram atendidos 63 doentes, em média 3,7 casos/ano; a faixa etária mais freqüentemente atingida foi a dos vinte aos sessenta anos, sendo a maioria dos doentes (77,8 porcento) de raça branca, e o sexo feminino foi pouco mais afetado do que o masculino. A maioria dos doentes do sexo masculino relatou atividades na lavoura, e a das mulheres, atividades domésticas. Quanto à procedência, foi bem variada, sem detecçäo de áreas de endemia, a maior parte proveniente da zona rural; houve tendência a adoecerem mais no veräo e outono. Verificou-se ocorrência de casos semelhantes em familiares consangüíneos e vizinhos. CONCLUSAO - Os dados observados no presente trabalho concordam com os da literatura

Metabolismo protéico no pênfigo foliáceo endêmico: avaliaçäo estática e cinética (15N-glicina) em doentes em jejum ou alimentados, na presença ou näo de corticoterapia sistêmica / Protein metabolism in patients with pemphigus foliaceus. Static and kinetic (15N-Gly) studies in fasted and fed states with or without glucocorticoid therapy

Com o objetivo de verificar as conseqüências do pênfigo foliáceo e do tratamento com corticosteróides sobre o estado nutricional e metabolismo protéico dos seus portadores, foram avaliados oito doentes, com média de idade de 37 ñ 19,9 anos, a maioria do sexo feminino (n=6) e de cor branca (n=6), sendo quatro com a forma localizada da doença e quatro com a forma disseminada da mesma, sem comprometimento importante da filtraçäo glomerular e da funçäo hepática. Durante o período de estudo de onze dias, todos os doentes foram submetidos ao protocolo dietético, composto de jejum (DO), seguido de dez dias com dieta oral regional completa, oferecendo 1,8g de proteína e 46 kcal/kg/dia, na ausência (D1) e na presença (D1+C) de 40 a 60 mg/dia de prednisona. Foram realizadas avaliaçöes clínicas, hematimétrica (hematócrito, hemoglobina, velocidade de hemossedimentaçäo, leucócitos e linfócitos totais), dietética (ingestäo alimentar), antropométrica (peso, altura, circunferência de membros e pregas cutâneas), de proteínas (albumina, transferrina, transtiretina, proteína ligadora do retinol e ceruloplasmina) e de aminoácidos (N-amínico, triptofano e tirosina) plasmáticos e cinética da 15N-glicina (dose única, via oral usando o 15N-NH3 urinário em nove horas como produto final), em D0, no último dia de D1 e D1+C. Metade dos doentes apresentaram algum grau de desnutriçäo protéico-energética, 75 por cento deles portadores da forma generalizada da doença. Houve associaçäo entre os doentes clinicamente mais graves, com os piores níveis de desnutriçäo protéico-energética. O comprometimento hematimétrico com leucocitose, VHS elevado e hematócrito e hemoglobina diminuídos, foi mais prevalente que a desnutriçäo protéico-energética e o mau estado clínico. Os indicadores antropométricos mostraram, em idênticas proporçöes, déficit de massa magra, de adiposidade, eutrofia e sobre-peso-obesidade. As proteínas plasmáticas indicaram déficit protéico visceral nos doentes com desnutriçäo protéico energética grave a moderada e atividade inflamatória em um doente eutrófico. As alteraçöes dos indicadores estáticos e dinâmicos do metabolismo protéico global, nas situaçöes de jejum e alimentado, sugerem estado de hipercatabolismo nos doentes. A corticoterapia mostrou-se ineficaz no período de sete dias, na normalizaçäo clínica, hematimétrica e nutricional dos doentes...

Avaliaçäo tardia da funçäo renal em doentes com paracoccidioidomicose tratados com anfotericina B por meio da determinaçäo do ritmo de filtraçäo glomerular com EDTA Cr51 / Late survery of the renal function in patients presenting paracoccidioidomycosis treated with amphoytericin B, by means of determination of the glomerular filtration rate using EDTA Cr51

A avaliaçäo tardia da funçäo renal foi realizada em 18 indivíduos que receberam anfotericina B no tratamento da paracoccidioidomicose pela detereminaçäo do ritmo de filtraçäo glomerular (RFG) pela técnica da análise comportamental simplificada, com uso de EDTA CR51 pela determinaçäo da meia vida biológica do EDTA Cr51 e dosagens de uréia e creatinina séricas. Dos indivíduos estudados 17 eram do sexo masculino e um do feminino, com idades variando entre 22 e 76 anos, sendo que 10 receberam 2g de anfotericina B e oito receberam 4g. Näo houve diferença significativa entre os dois grupos com relaçäo à idade, dose em mg/Kg de peso/dia, tempo de término do tratamento, valores de uréia, creatinina, ritmo de filtraçäo glomerular e meia vida biológica do EDTA Cr51. Analisando-se os dados em conjunto, notamos que a média dos valores de ritmo de filtraçäo glomerular foi menor que a normalidade e a média dos valores de meia vida biológica do EDTA Cr51 maior que o normal