The action of subconjunctival cyclophosphamide in rabbits / Ação da ciclofosfamida subconjuntival em coelhos

ABSTRACT Objective: To observe clinically, in rabbits, the side effects of topical injection of subconjunctival cyclophosphamide, studying its role as an antifibrotic drug. Methods: Prospective study in 20 albino rabbits of New Zealand race. All rabbits were treated with cyclophosphamide, 10mg/ml in a volume of 0.3 ml, in the left eye through subconjunctival injection. They were evaluated for 1, 7, 30, and 60 days after the procedure. All the animals were examined for the detection of ocular reactions such as necrosis, hyperemia, chemosis, secretion, opacity, and iritis. Other side effects as changes in the behavior, in the feed, and the water consumption were also evaluated. Results: It was observed that from the 20 rabbits studied, three rabbits (15%) showed side effects only at the 24 hours analysis. One rabbit (5%) presented hyperemia, one rabbit (5%) had hyperemia associated with iritis, and one rabbit (5%) presented hyperemia associated with secretion. These reactions were not observed at 1, 7, 30, and 60 days. Conclusion: Cyclophosphamide subconjunctival injection induces minor side effects on the conjunctiva of rabbits such as hyperemia, associated with iritis and secretion.

RESUMO Objetivo: Observar clinicamente os efeitos colaterais de injeção subconjuntival de ciclofosfamida, pensando em sua ação como um agente antifibrótico. Métodos: Estudo prospectivo realizado com 20 coelhos albinos da raça Nova Zelândia. Todos os coelhos foram submetidos a 0,3 ml de injeção subconjuntival de ciclofosfamida 10mg/ml no olho esquerdo e foram avaliados de acordo com os efeitos locais no primeiro dia após a injeção, 7, 30 e 60 dias. Foram examinados para detecção de reações oculares como necrose, hiperemia, quemose, secreção, opacidade corneana, irite além de alterações comportamentais e variação no consumo de água e alimentação. Resultados: Dos 20 coelhos estudados, apenas 3 apresentaram reações oculares e somente na leitura de 24 horas. Um coelho (5%) apresentou hiperemia, 1 coelho (5%) apresentou hiperemia associada a presença de irite e 1 coelho (5%) apresentou hiperemia associada a presença de secreção. As reações não foram mais observadas durante os exames de 7, 30 e 60 dias. Conclusão: A ciclofosfamida subconjuntival causou poucos efeitos colaterais na conjuntiva dos coelhos. Os únicos efeitos encontrados foram hiperemia, irite e secreção.

Estudo comparativo da inibição da proliferação de fibroblastos in vitro na conjuntiva utilizando mitomicina C e ciclofosfamida / Comparative study of inhibition of fibroblasts proliferation in vitro in the conjunctiva using mitomycin and ciclophosphamide

RESUMO Objetivo: Avaliar a inibição da proliferação de fibroblastos in vitro das conjuntivas obtidas através de exérese de pterígios de pacientes utilizando mitomicina C (MMC) e ciclofosfamida (CF). Métodos: Os pterígios foram retirados de 7 pacientes e submetidos a cultivo celular. Após o cultivo, 3 fragmentos de dimensões iguais deste material foram colhidos de áreas adjacentes do pterígio removido de cada paciente. Eles foram randomicamente selecionados de tal forma que: um fragmento de cada paciente foi exposto: ao meio de cultura (grupo controle), a MMC e a CF por igual período de tempo nas concentrações de 0,4 mg/ml e 10 mg/ml respectivamente. Após este período realizou-se a contagem celular de fibroblastos destes 3 grupos. Cada grupo continha 7 fragmentos. Resultados: Com a utilização da MMC tivemos uma taxa de 95% da inibição da proliferação dos fibroblastos, enquanto com a CF 100%. Conclusões: Ambas as drogas apresentaram elevada taxa da inibição da proliferação de fibroblastos, porém a CF apresentou inibição maior que a MMC.

Abstract Objective: To evaluate the inhibition of fibroblast proliferation in vitro of conjunctiva obtained by excision of pterygium from patients using mitomycin (MMC) and cyclophosphamide (CF). Methods: Pterygiums were removed from 7 patients and subjected to cell culture. After cell cultivation, 3 fragments of equal dimensions of these tissues were collected from adjacent areas of each patient removed pterygium. They were randomly selected in such a way that one fragment of each patient was exposed to: the culture medium (group control), to MMC and to CF for an equal period of time at concentrations of 0,4 mg/dl and 10 mg/dl respectively. After this period, the fibroblast cell count of these groups were performed. Each group had seven fragments. Results: With the use of MMC we had a 95% rate of inhibition of fibroblast proliferation, while with CF 100%. Conclusion: Both drugs showed a high rate of inhibition of fibroblast proliferation, but CF showed greater inhibition than MMC.

Is rituximab effective for systemic sclerosis? A systematic review and meta-analysis

Abstract Background: Systemic sclerosis (SSc) Is a clinically complex and challenging disease, that leads to skin fibrosis. Its most frequent complication is interstitial lung disease (ILD), which leads to a worse prognosis. In this situation, cyclophosphamide is considered the gold standard for its treatment, despite the controversies regarding its efficacy and toxicity. However, studies using rituximab (RTX) have shown that this drug may be a promising therapeutic option. Objectives: This paper objective was to analyze the scientific evidence on the RTX effects on SSc. Methods: A systematic review (SR) was performed including clinical trials (CTs) on the use of RTX in SSc, published up to May 2020. The studies were identified through systematic searches in bibliographic databases using a predefined search strategy. The following databases were used: PUBMED, SCOPUS, SCIELO, LILACS, SCIENCE DIRECT, WEB OF SCIENCE, COCHRANE, WHOLIS, PAHO and EMBASE. Also, a manual search was performed. The methodological quality of the studies was determined using Jadad scale, Risk of Bias Tool (RoB 2.0) and Risk of Bias in Non-Randomized Studies - of Interventions tool (ROBINS-I). A meta-analysis of the randomized CTs was performed, using Review Manager. Results: Ten CTs were included in this SR. Of these, three were randomized and seven were non-randomized. Five showed a statistically significant improvement in forced vital capacity (FVC) at some time during follow-up. Regarding the skin, eight studies showed statistically significant improvements according toa the modified Rodnan skin score. The meta-analysis found positive effects of RTX in SSc, with a statistical significance for lung disease. Conclusion: Rituximab is a promising strategy for the SSc-associated ILD and cutaneous fibrosis treatment. PROSPERO registration number: CRD42019132018.(AU)

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis with nephrotic-range proteinuria in children: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CTX) in the treatment of children with Henoch-Schönlein purpura nephritis (HSPN) and nephrotic-range proteinuria.@*METHODS@#A prospective clinical trial was conducted in 68 pediatric patients who were admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics and who were diagnosed with HSPN and nephrotic-range proteinuria from August 2016 to November 2019. The patients were randomly divided into two groups:MMF treatment (@*RESULTS@#At months 3, 6, and 12 of treatment, there was no significant difference in the complete remission rate and the response rate between the MMF treament and CTX treatment groups (@*CONCLUSIONS@#MMF and CTX have similar efficacy and safety in the treatment of HSPN children with nephrotic-range proteinuria.

Esclerosis sistémica y neoplasias, a propósito de un estudio en la provincia de Holguín / Systemic Sclerosis and neoplastic purpose of a study at Holguin province

La esclerosis sistémica (ES) es una enfermedad de causa desconocida, que se caracteriza por una producción exagerada de moléculas que componen la matriz extracelular. La disminución en la producción de óxido nítrico por las células endoteliales de la microvasculatura parece desempeñar un papel central en la patogenia de la enfermedad. Los resultados alcanzados en un estudio de serie de casos de un universo de 44 pacientes y muestra de 31, con baja incidencia de las causas neoplásicas en la muerte y como reacciones secundarias a tratamiento inmunosupresor con ciclofosfamida, según la conducta terapéutica aplicada, fue el motivo para la presentación de este trabajo, que reflejó la posible relación entre la esclerosis sistémica y las neoplasias. Se concluyó que la relación entre autoinmunidad y cáncer puede ser el resultado de un origen etiológico común (genético, hormonal, metabólico o factores ambientales) o un mecanismo de síndrome paraneoplásico. La enfermedad es terreno de riesgo para la ocurrencia de neoplasias, así como las neoplasias pueden inducir ES(AU)

The systemic sclerosis (SS) is a disease of unknown cause, that the fact that they fix the extra-cell womb characterizes itself for a production exaggerated of molecules. The decrease in the production of nitric oxide for the microvasculature's endothelial cells seems to play a central role in the pathogenesis of the disease. The results attained in 44 patients' study of series of cases of universe and inmunosupresor with cyclophosphamide according to therapeutic applied conduct shows of 31, with low incidence of the causes neoplastic in the death like secondary reactions and to treatment you went from motivation for the presentation of this work, that you reflected the possible relation between the systemic sclerosis and the neoplastic. It was concluded that the relation between auto-immunity and cancer can stem from an etiological common origin (genetic, hormonal, metabolic or environmental factors) or a mechanism of syndrome paraneoplastic. The disease is earthly of risk for neoplastic funny remark, the same way that the neoplastic can induce SS(AU)

Cistitis hemorrágica por infección viral en receptores de trasplante hematopoyético haploidéntico: reporte de dos casos / Hemorrhagic cystitis due to viral infection in patients who received hematopoietic haploidentical transplantation: two case reports

Introducción: Las infecciones por virus o la reactivación de virus en estado latente son frecuentes durante el estado de inmunosupresión que sigue al trasplante de progenitores hematopoyéticos, y constituyen una causa importante de complicaciones, como la cistitis hemorrágica, que se caracteriza por disuria, polaquiuria, dolor abdominal y hematuria. La aparición precoz se asocia a la administración de citostáticos como la ciclofosfamida, y el comienzo tardío a la primoinfección o reactivación de virus como citomegalovirus, los adenovirus o los poliomavirus como el BK y el JC. Objetivo: Describir las características clínicas, la evolución y el manejo de la cistitis hemorrágica postrasplante. Casos clínicos: Se presentan dos pacientes con leucemia mieloide aguda que desarrollaron cistitis hemorrágica asociada a infección viral por virus BK y citomegalovirus después del trasplante haploidéntico con ciclofosfamida postrasplante. La cistitis hemorrágica de causa viral después del trasplante hematopoyético en estos pacientes estuvo asociada a una severa inmunosupresión, por lo que constituyó una complicación potencialmente letal. Los dos pacientes presentaron cistitis hemorrágica grado IV y fallecieron a pesar del tratamiento. Conclusiones: El trasplante haploidéntico con la administración de ciclofosfamida postrasplante incrementa la posibilidad de donantes de progenitores hematopoyéticos para los pacientes sin un hermano HLA idéntico pero el mayor nivel de inmunosupresión podría aumentar la incidencia de cistitis hemorrágica de causa viral(AU)

Introduction: Viral infections or latent-virus reactivation are frequent during the immunosuppressed cincition that follows hematopoietic stem-cell transplantation, and an important cause of complications, such as hemorrhagic cystitis, characterized by dysuria, urinary frequency, abdominal pain, and hematuria. The early appearance is associated with the administration of cytostatic drugs such as cyclophosphamide, and the late onset is associated with primary infection or reactivation of viruses such as cytomegalovirus, adenoviruses, or polyomaviruses such as BK and JC. Objective: To describe the clinical characteristics, evolution and management of post-transplant hemorrhagic cystitis. Clinical cases: The cases are presented of two patients with acute myeloid leukemia who developed hemorrhagic cystitis associated with viral infection by BK virus and cytomegalovirus after haploidentical transplantation with post-transplant cyclophosphamide. Viral hemorrhagic cystitis after hematopoietic transplantation in these patients was associated with severe immunosuppression, making it a potentially lethal complication. Both patients presented grade IV hemorrhagic cystitis and died despite treatment. Conclusions: Haploidentical transplantation with the of post-transplant cyclophosphamide administration increases the possibility for donors of hematopoietic progenitor cells to patients without an identical HLA match, but the higher level of immunosuppression could increase the incidence of viral hemorrhagic cystitis(AU)

Evaluation of immunomodulatory effects of lomefloxacin in mice

Lomefloxacin is a flouroquinolone antibiotic that is quite efficacious against many gram negative and gram positive pathogens. Lomefloxacin evince antibacterial effects by modifying DNA gyrase in gram negative pathogens and topoisomerase IV in gram positive pathogens. This study is designed to assess the immunomodulatory effects of lomefloxacin in male albino mice. Three doses of lomefloxacin 12.5 mg/kg, 25 mg/kg and 50 mg/kg were used and delayed type hypersensitivity assay, cyclophosphamide induced neutropenic assay, carbon clearance assay, heamagglutination assay and mice lethality test were performed to evaluate the effects of lomefloxacin on immune system of mice. DTH assay has depicted the significant immunosuppressant potential of lomefloxacin at 25 mg/kg and 50 mg/kg dose. Total leukocyte count have exhibited highly significant reduction (P<0.001) in leukocyte count after cyclophosphamide administration. Differential leukocyte count has shown significant (P<0.01) reduction in lymphocyte count, whereas, highly significant (P<0.001) increase in monocyte count and significant (P<0.05) increase neutrophil count has been observed. In carbon clearance assay, highly significant (P<0.01) increase in phagocytic index has been noted at 12.5 mg/kg and 25 mg/kg doses. Humoral immune system responses are suppressed in dose dependent manner by both heamagglutination assay (P<0.001) and mice lethality assay (P<0.001). Results clearly depict that lomefloxacin possess quite significant immunomodulatory potential

5-fluorouracil and cyclophosphamide modify functional activity in submandibular gland of rats / El 5-fluorouracilo y la ciclofosfamida modifican la actividad funcional en la glándula submandibular de las ratas

Objective: Chemotherapy treatment against cancer produce systemic toxicities, among which are those related to important structures of the stomatognathic system and its functional activity. 5 Fluorouracil (5-FU) and cyclophosphamide (Cf) are drugs widely used in solid tumors and in bone marrow transplantation, respectively. The objective of this work was to evaluate the toxicity of these drugs regarding functional activity of the submandibular glands, by measuring the percentage of glycogen consumption in two experimental models. Material and Methods: 84 male Wistar rats aged three months were used, housed in individual cages, with controlled temperature and lighting and ad libitum diet. They were divided into four experimental groups: 1) Control (C); 2) Treated with 5-FU+leucovorin (LV) at 20 and 10mg/Kg of body weight respectively for five consecutive days; 3) treated with Cf i.p. at 50mg/Kg of body weight for two consecutive days; and 4) rats with paired feeding (PF): for five and two days respectively, the amount administered resulted from the average of the ingested food of groups 2 and 3. Both submandibular glands were excised. The submandibular glycogen concentration was analyzed at initial time (t0) and after 60 minutes of mechanical stimulation (t60). Results: the average variation changed significantly between time 0 and 60 in the groups C and PF. (p-value=0.0001), the 5-FU + LV treatment group had an average concentration higher at t0 than groups C and PF, without significant consumption at T60. While group Cf showed a lower average concentration at time 0 with respect to groups C and PF, without significant consumption at T60. Conclusion: 5-FU+LV and Cf affect the metabolism of carbohydrates, decreasing the use of glycogen as a metabolic substrate. In the present experimental model, the toxicity of these drugs affected the functional activity of the submandibular gland.

Objetivo: el tratamiento de quimioterapia contra el cáncer produce toxicidades sistémicas, entre las que se encuentran las relacionadas con estructuras importantes del sistema estomatognático y su actividad funcional. El 5-fluorouracilo (5-FU) y la ciclofosfamida (Cf ) son fármacos ampliamente utilizados en tumores sólidos y en trasplantes de médula ósea, respectivamente. El objetivo de este trabajo fue evaluar la toxicidad de estos fármacos con respecto a la actividad funcional de las glándulas submandibulares, midiendo el porcentaje de consumo de glucógeno en dos modelos experimentales. Material y Métodos: se utilizaron 84 ratas Wistar machos de tres meses de edad, alojadas en jaulas individuales, con temperatura e iluminación controladas y dieta ad libitum. Se dividieron en cuatro grupos experimentales: 1) Control (C); 2) Tratados con 5-FU+leucovorina (LV) a 20 y 10mg/Kg de peso corporal, respectivamente, durante cinco días consecutivos; 3) tratados con Cf i.p. a 50mg/Kg de peso corporal durante dos días consecutivos; y 4) ratas con alimentación por parejas (PF): durante cinco y dos días respectivamente, la cantidad administrada resultó del promedio de los alimentos ingeridos de los grupos 2 y 3. Ambas glándulas submandibulares fueron extirpadas. La concentración de glucógeno submandibular se analizó en el momento inicial (t0) y después de 60 minutos de estimulación mecánica (t60). Resultados: la variación promedio cambió significativamente entre el tiempo 0 y 60 en los grupos C y PF. (p=0,0001), el grupo de tratamiento 5-FU+LV tuvo una concentración promedio más alta en t0 que los grupos C y PF, sin un consumo significativo en T60. Mientras que el grupo Cf mostró una concentración promedio más baja en el tiempo 0 con respecto a los grupos C y PF, sin un consumo significativo en T60. Conclusión: 5-FU + LV y Cf afectan el metabolismo de los carbohidratos, disminuyendo el uso de glucógeno como sustrato metabólico. En el presente modelo experimental, la toxicidad de estos medicamentos afectó la actividad funcional de la glándula submandibular.

Cardiotoxicidade nas Terapias Neoadjuvante e Adjuvante do Câncer de Mama / Cardiotoxicity in Adjuvant and Neoadjuvant Therapy for Breast Cancer / Cardiotoxicidad en Terapias de Cáncer de Mama Neoadyuvante y Adyuvante

Introdução: O câncer de mama é o mais comum entre as mulheres em todo o mundo, representando quase 25% de todos os casos de câncer. Alguns fármacos possuem características peculiares relacionadas à cardiotoxicidade. Objetivo: Analisar a incidência, as características clínicas e os fatores de risco associados à ocorrência de cardiotoxicidade em pacientes submetidas ao protocolo doxorrubicina e ciclofosfamida seguido ou não de taxanos e naquelas que realizaram o mesmo protocolo associado ao trastuzumabe. Método: Trata-se de um estudo de coorte realizado em um hospital público do Rio de Janeiro. Foram incluídas 153 pacientes que iniciaram tratamento entre os meses de setembro e novembro de 2012. A cardiotoxicidade foi definida com base nos critérios do Cardiac Review and Evaluation Committee e da Sociedade Brasileira de Cardiologia. Foi calculado o risco relativo (RR), utilizando-se um intervalo de confiança (IC) de 95%. Resultados: A incidência de cardiotoxicidade foi de 17%. Observou-se queda da fração de ejeção do ventrículo esquerdo em 31,3% e 52,2% das pacientes nos grupos human epidermal growth factor receptor-type 2 (HER-2) negativo e positivo, respectivamente. Foram identificados três casos de insuficiência cardíaca, sendo dois em pacientes HER-2 positivas. As pacientes que utilizaram trastuzumabe apresentaram maior risco de desenvolver cardiotoxicidade (RR=3,53; IC 95%: 1,84-6,79) em comparação com as mulheres do grupo HER-2 negativo. Conclusão:Foi possível verificar a ocorrência de casos de cardiotoxicidade em ambos os grupos com maior incidência para o grupo HER-2 positivo.

Introduction: Breast cancer is the most common among women worldwide, accounting for almost 25% of all cancer cases. Some drugs have a peculiar characteristic related to cardiotoxicity. Objective: Analyze the incidence, clinical characteristics and risk factors associated with cardiotoxicity in patients undergoing protocol doxorubicin and cyclophosphamide followed or not by taxanes and in those who underwent the same protocol associated with trastuzumab. Method: Cohort study conducted in a public hospital in Rio de Janeiro. 153 patients were included between September and November 2012. Cardiotoxicity was defined based on the criteria of the Cardiac Review and Evaluation Committee and the Brazilian Society of Cardiology. The relative risk (RR) was calculated using a 95% confidence interval (CI). Results: The incidence of cardiotoxicity was 17%. Left ventricular ejection fraction decreased in 31.3% and 52.2% of the patients in the negative and positive human epidermal growth factor receptor-type 2 (HER-2) groups, respectively. Three cases of heart failure were identified, two in HER-2 positive patients. Patients using trastuzumab had a higher risk of developing cardiotoxicity (RR=3.53; CI 95%: 1.84-6.79) compared to women in the HER-2 negative group. Conclusion: It was possible to verify the occurrence of cases of cardiotoxicity in both groups with higher incidence for the HER-2 positive group.

Introducción: El cáncer de mama es el más común entre las mujeres en todo el mundo, y representa casi el 25% de todos los casos de cáncer. Algunos medicamentos tienen característica peculiar relacionada con la cardiotoxicidad. Objetivo: Analizar la incidencia, las características clínicas y los factores de riesgo asociados con la cardiotoxicidad en pacientes sometidos al protocolo doxorrubicina y ciclofosfamida seguidos o no por taxanos y en aquellos que se sometieron al mismo protocolo asociado con trastuzumab. Método: Este es un estudio de cohorte realizado en un hospital público en Río de Janeiro. Se incluyeron 153 pacientes que comenzaron el tratamiento entre septiembre y noviembre de 2012. La cardiotoxicidad se definió según los criterios del Comité de Revisión y Evaluación Cardíaca y la Sociedad Brasileña de Cardiología. El riesgo relativo (RR) se calculó utilizando un intervalo de confianza (IC) del 95%. Resultados: La incidencia de cardiotoxicidad fue del 17%. La fracción de eyección del ventrículo izquierdo disminuyó en el 31,3% y el 52,2% de los pacientes en los grupos human epidermal growth factor receptor-type 2 (HER-2) negativo y positivo, respectivamente. Se identificaron tres casos de insuficiencia cardíaca, dos en pacientes con HER-2 positivo. Los pacientes que usaban trastuzumab tenían un mayor riesgo de desarrollar cardiotoxicidad (RR=3,53; IC 95%: 1,84-6,79) en comparación con las mujeres en el grupo negativo HER-2. Conclusión: Fue posible verificar la aparición de casos de cardiotoxicidad en ambos grupos con mayor incidencia para el grupo HER-2 positivo.

First phytochemical and biological study of the ethanolic extract from leaves of Capirona decorticans (Rubiaceae) / Primeiro estudo fitoquímico e biológico do extrato etanólico de folhas de Capirona decorticans (Rubiaceae)

Capirona decorticans (Rubiaceae) is popularly used to treat warts, wounds, mycoses and scabies, and is also a component of the Ayahuasca tea. Despite its popular use, the phytochemical and pharmacological research on this species is limited. Therefore, this work quantified phenolic compounds in the ethanolic extract (EE) and hydromethanolic fraction (FM) (406, 293 mgEAG g-1, respectively) from leaves of C. decorticans. We identified flavonoids by LC-MS/MS-MMR-ESI (apigenin, rutin, luteolin, miricetin, quercetin, quercetin-3--D-glucoside, quercetrin), and evaluated oxidative stress and mutagenic/antimutagenic effect of EE and FM through an in vivo experiment using Swiss mice and cyclophosphamide (CP) as an inducer of DNA damage and oxidative stress. Mice were pretreated for 15 consecutive days with EE or FM (250 mg kg-1) and then intraperitoneally injected with CP (25 mg kg-1). Carbonylated proteins, ascorbic acid, catalase and thiobarbituric acid-reactive substances were measured in hepatic and renal tissues. The mutagenic/antimutagenic effect was evaluated through the Micronucleus Test. Protein carbonylation in the liver of animals exposed to CP was reduced by FM. There was no significant effect on other markers of oxidative stress. The groups treated with the extracts showed a significant percentage reduction (EE = 96% and FM = 71%) in the frequency of micronucleated polychromatic erythrocytes induced by CP. EE showed mutagenicity when used alone. The EE and FM of C. decorticans leaves showed antioxidant potential equivalent to that observed in other species, did not cause oxidative stress, nor toxicity, and had a protective and antimutagenic effect, although the EE showed signs of mutagenicity.

Capirona decorticans (Rubiaceae) é popularmente usada para tratar verrugas, feridas, micoses e sarna, e como um componente do chá de Ayahuasca. Apesar do uso popular, são limitadas as pesquisas fitoquímicas e farmacológicas sobre a espécie. Portanto, este estudo quantificou compostos fenólicos no extrato etanólico (EE) e na fração hidrometanólica (FM) (406 e 293 mgEAG g-1, respectivamente) de folhas de C. decorticans. Identificamos flavonoides por LC-MS / MS-MMR-ESI (apigenina, rutina, luteolina, miricetina, quercetina, quercetina-3--D-glicosídeo, quercetrina), e avaliamos o estresse oxidativo e o efeito mutagênico/antimutagênico de EE e FM em um experimento in vivo utilizando camundongos Swiss e ciclofosfamida (CP) como um indutor de danos no DNA e estresse oxidativo. Os camundongos foram pré-tratados por 15 dias consecutivos com EE ou FM (250 mg kg-1) e injetados intraperitonealmente com CP (25 mg kg-1). Proteínas carboniladas, ácido ascórbico, catalase e substâncias reativas ao ácido tiobarbitúrico foram dosadas em tecidos hepáticos e renais. O efeito mutagênico/antimutagênico foi avaliado através do Teste de Micronúcleo. Houve carbonilação protéica no fígado de animais expostos à CP, que foi reduzida pela FM. Não houve efeito significativo sobre outros marcadores de estresse oxidativo. Os grupos tratados com os extratos apresentaram uma redução percentual significativa (EE = 96% e FM = 71%) na frequência de eritrócitos policromáticos micronucleados induzidos pela PC. O EE também apresentou mutagenicidade quando utilizado isoladamente. O EE e FM das folhas de C. decorticans apresentaram potencial antioxidante equivalente ao observado em outras espécies, não causaram estresse oxidativo, nem toxicidade, e tiveram efeito protetor e antimutagênico, embora a EE tenha apresentado mutagenicidade.

Arterial Stiffness Use for Early Monitoring of Cardiovascular Adverse Events due to Anthracycline Chemotherapy in Breast Cancer Patients. A Pilot Study / Uso da Rigidez Arterial para Monitoramento Precoce de Eventos Adversos Cardiovasculares por Antracíclicos em Pacientes com Câncer de Mama. Um Estudo Piloto

Abstract Background: Chemotherapy with doxorubicin and cyclophosphamide, although efficient for treating breast cancer, is associated with cardiovascular complications. Recent studies seek to identify methods that can early detect cardiological and vascular changes as a strategy to decrease the incidence of cardiovascular comorbidities. Objective: To evaluate the role of arterial stiffness measurement in the monitoring of doxorubicin and cyclophosphamide-induced cardiotoxicity in breast cancer patients. Methods: Prospective longitudinal study in 24 breast cancer patients undergoing treatment with doxorubicin and cyclophosphamide. Patients underwent an indirect evaluation of arterial stiffness through non-invasive measurement of hemodynamic parameters such as pulse wave velocity with the Mobil-O-Graph® 24H PWA device at three different times of the chemotherapy treatment (pre-chemotherapy, after the first and the fourth cycle). The left ventricular ejection fraction was also evaluated by Doppler echocardiography (pre-chemotherapy and after the fourth chemotherapy cycle). Data were considered significant when p ≤ 0.05. Results: Patients had a mean age of 52.33 ± 8.85 years and body mass index of 31 ± 5.87 kg/m2. There was no significant difference between the hemodynamic parameters evaluated by the oscillometric method or in the left ventricular ejection fraction in the different evaluated periods. Conclusion: Evaluations of arterial stiffness by oscillometry and measurement of left ventricular ejection fraction by Doppler echocardiography showed equivalence in the values found, suggesting that the evaluation method of arterial stiffness studied could be used as a marker for cardiovascular adverse events associated with doxorrubicin-based chemotherapy drugs.

Resumo Fundamento: O tratamento quimioterápico com doxorrubicina e ciclofosfamida, apesar de eficiente no combate ao câncer de mama, está associado a complicações cardiovasculares. Trabalhos recentes identificam métodos que possam detectar alterações cardiológicas e vasculares precocemente, visando a uma estratégia para diminuição na incidência de comorbidades cardiovasculares. Objetivo: Avaliar o papel da medida da rigidez arterial no acompanhamento da ocorrência de eventos adversos cardiovasculares induzidos por doxorrubicina e ciclofosfamida em pacientes com câncer de mama. Métodos: Estudo longitudinal prospectivo realizado com 24 pacientes com câncer de mama em tratamento com doxorrubicina e ciclofosfamida. As pacientes foram submetidas à avaliação indireta da rigidez arterial, por mensuração não invasiva de parâmetros hemodinâmicos, como a velocidade de onda de pulso, pelo equipamento Mobil-O-Graph® 24H PWA em três diferentes momentos do tratamento quimioterápico (pré-quimioterapia, após o primeiro e após o quarto ciclos). Foi avaliada também a fração de ejeção do ventrículo esquerdo pelo ecoDopplercardiograma (pré-quimioterapia e após o quarto ciclo quimioterápico). Os valores de p ≤ 0,05 foram considerados significativos. Resultados: As pacientes apresentaram média de idade de 52,33 ± 8,85 anos e índice de massa corporal de 31 ± 5,87 kg/m2. Não houve diferença significativa entre os parâmetros hemodinâmicos avaliados pelo método oscilométrico ou na fração de ejeção do ventrículo esquerdo, nos diferentes períodos avaliados. Conclusão: As avaliações de rigidez arterial por oscilometria e medida da fração de ejeção do ventrículo esquerdo por ecoDopplercardiograma mostraram equivalência nos valores encontrados, sugerindo que o método de avaliação da rigidez arterial estudado possa ser utilizado como mais um marcador para eventos adversos cardiovasculares associados aos medicamentos quimioterápicos baseados em doxorrubicina.

The therapeutic effects of curcumin and capsaicin against cyclophosphamide side effects on the uterus in rats

Abstract Purpose: To evaluate the impact of systemic cyclophosphamide treatment on the rat uterus and investigate the potential therapeutic effects of natural antioxidant preparations curcumin and capsaicin against cyclophosphamide side effects. Methods: A 40 healthy adult female Wistar albino rats were used in this study. Rats were randomly divided into four groups to determine the effects of curcumin and capsaicin against Cyclophosphamide side effects on the uterus (n=10 in each group); Group 1 was the control group (sham-operated), Group 2 was the cyclophosphamide group, Group 3 was the cyclophosphamide + curcumin (100mg/kg) group, and Group 4 was the cyclophosphamide + capsaicin (0.5 mg/kg) group. Results: Increased tissue oxidative stress and histological damage in the rat uterus were demonstrated due to the treatment of systemic cyclophosphamide chemotherapy alone. The level of tissue oxidant and antioxidant markers and histopathological changes were improved by the treatment of curcumin and capsaicin. Conclusion: Cytotoxic effects of natural alkylating chemotherapeutic agents like cyclophosphamide on the uterus can be prevented by curcumin and capsaicin.

Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review / Rotina de administração de ciclofosfamida em doenças autoimunes reumáticas: uma revisão

Abstract Cyclophosphamide is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy, administration of cyclophosphamide, and post-chemotherapy, taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare - but serious - side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

Resumo A ciclofosfamida (CFM) é um agente alquilante vastamente usado para o tratamento de neoplasias malignas e pode ser usado no tratamento de diversas doenças reumatológicas. O erro de administração de medicamentos pode levar à diminuição da eficácia ou ao aumento da toxicidade medicamentosa. Diversos erros ocorrem na administração de medicamentos injetáveis. O trabalho objetivou a estruturação de uma rotina do uso de ciclofosfamida, bem como a criação de um documento de orientações farmacoterapêuticas para o paciente. A rotina foi esquematizada em três fases, a pré-quimioterapia (pré-QT), a administração da ciclofosfamida e a pós-quimioterapia (pós-QT), que levaram em consideração os medicamentos que devem ser administrados antes e depois da ciclofosfamida para prevenção aos efeitos adversos, incluindo náusea e cistite hemorrágica. As reações adversas podem alterar os exames laboratoriais e a rotina incluiu manejo clínico para alteração clínica dos leucócitos, das plaquetas, dos neutrófilos e do sódio incluindo o ajuste de dose de ciclofosfamida em caso de insuficiência renal. A ciclofosfamida é responsável por outras reações adversas raras, mas sérias, como hepatotoxicidade, hiponatremia severa e falência cardíaca. Outras reações adversas incluem perda de cabelo, amenorreia e menopausa. A rotina foi composta também por orientações ao paciente pós-QT. A compatibilidade dos medicamentos injetáveis com o veículo foi descrita, bem como o tempo de estabilidade e o tempo de infusão. A rotina visou ao uso racional da ciclofosfamida e prevenir os efeitos adversos e os episódios de recidiva, os quais podem onerar o sistema de saúde.

Antral Follicles Count and Anti-Müllerian Hormone Levels after Gonadotoxic Chemotherapy in Patients with Breast Cancer: Cohort Study / Contagem de folículos antrais e níveis de hormônio anti-Mülleriano após quimioterapia gonadotóxica em pacientes com câncer de mama: estudo de coorte

Abstract Aim To assess ovarian reserve (OVR) by means of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and antral follicle count (AFC) measurement in eumenorrheic women with breast cancer, exposed to gonadotoxic chemotherapy. Method Fifty-two women (35.3 ± 3.8 years old) with breast cancer and undergoing cyclophosphamide-containing chemotherapy were enrolled. The assessment was performed before chemotherapy (T1) and after 2 (T2) and 6 months (T3). Results Six months after chemotherapy, the prevalence of regular cycles was 60%. Anti-Müllerian hormone decreased down to undetectable levels at T2 and T3 (T1: 2.53 [1.00–5.31]; T2 < 0.08; T3: < 0.08 [< 0.08–1.07] ng/mL), (p< 0.0001). Antral follicle count was 11 [8.0–13.5] follicles at T1 and lower at T2 (5.50 [3.75–8.0] and T3 (5.0 [2.5–7.0]) (p< 0.0001). In patients who remained with regular cycles during chemotherapy or resumed normal menses, FSH and estradiol levels remained unchanged. Conclusion Anti-Müllerian hormone and AFC are useful as markers of OVR decline in women exposed to chemotherapy. Follicle-stimulating hormone is only adequate in women who become amenorrheic.

Resumo Objetivo Avaliar a reserva ovariana (OVR) através da contagem de folículos antrais (AFC), dosagem sérica de hormônio folículo estimulante (FSH) e hormônio anti-Mülleriano (AMH) em mulheres com câncer de mama submetidas a quimioterapia gonadotóxica. Método Foram incluídas na pesquisa 52 mulheres (35,3 ± 3,8 anos) com câncer de mama, em tratamento com quimioterapia com ciclofosfamida. As dosagens e medidas foram realizadas antes do início da quimioterapia (T1) e após 2 (T2) e 6 meses (T3). Resultados Seis meses após quimioterapia, a prevalência de ciclos regulares foi de 60%. O AMH sérico diminuiu a níveis indetectáveis em T2 e T3 (T1: 2,53 [1,00–5,31] ]; T2 < 0,08; T3: < 0,08 [< 0,08–1,07] ng/mL) (p< 0,0001). A contagem de folículos antrais foi de 11 [8,0–13,5] folículos em T1, e ainda menor em T2 (5,50 [3,75–8,0] e T3 (5,0 [2,5–7,0]), (p< 0,0001). Em pacientes que mantiveram ciclos regulares durante a quimioterapia ou retomaram a menstruação normalmente, os níveis de FSH e estradiol permaneceram inalterados. Conclusão O AMH e a AFC são marcadores úteis do declínio da OVR em mulheres expostas à quimioterapia. O FSH só é adequado em mulheres que se tornam amenorreicas.

Atrial Function in Patients with Breast Cancer After Treatment with Anthracyclines / Função Atrial em Pacientes com Câncer de Mama Após tratamento com Antraciclinas

Abstract Background: Atrial electromechanical delay (EMD) is used to predict atrial fibrillation, measured by echocardiography. Objectives: The aim of this study was to assess atrial EMD and mechanical function after anthracycline-containing chemotherapy. Methods: Fifty-three patients with breast cancer (48 ± 8 years old) who received 240 mg/m2of Adriamycin, 2400 mg/m2 of cyclophosphamide, and 960 mg/m2 of paclitaxel were included in this retrospective study, as were 42 healthy subjects (47 ± 9 years old). Echocardiographic measurements were performed 11 ± 7 months (median 9 months) after treatment with anthracyclines. Results: Left intra-atrial EMD (11.4 ± 6.0 vs. 8.1 ± 4.9, p=0.008) and inter-atrial EMD (19.7 ± 7.4 vs. 14.7 ± 6.5, p=0.001) were prolonged; LA passive emptying volume and fraction were decreased (p=0.0001 and p=0.0001); LA active emptying volume and fraction were increased (p=0.0001 and p=0.0001); Mitral A velocity (0.8 ± 0.2 vs. 0.6 ± 0.2, p=0.0001) and mitral E-wave deceleration time (201.2 ± 35.6 vs. 163.7 ± 21.8, p=0.0001) were increased; Mitral E/A ratio (1.0 ± 0.3 vs. 1.3 ± 0.3, p=0.0001) and mitral Em (0.09 ± 0.03 vs. 0.11 ± 0.03, p=0.001) were decreased; Mitral Am (0.11 ± 0.02 vs. 0.09 ± 0.02, p=0.0001) and mitral E/Em ratio (8.8 ± 3.2 vs. 7.6 ± 2.6, p=0.017) were increased in the patients. Conclusions: In patients with breast cancer after anthracycline therapy: Left intra-atrial, inter-atrial electromechanical intervals were prolonged. Diastolic function was impaired. Impaired left ventricular relaxation and left atrial electrical conduction could be contributing to the development of atrial arrhythmias.

Resumo Fundamento: Atraso eletromecânico atrial (AEA) é utilizado para prever fibrilação atrial, medido pela ecocardiografia. Objetivos: O propósito deste estudo era verificar o AEA e a função mecânica após quimioterapia com antraciclinas. Métodos: Cinquenta e três pacientes com câncer de mama (48 ± 8 anos) que receberam 240 mg/m2 de adriamicina, 2400 mg/m2 de ciclofosfamida, e 960 mg/m2 de paclitaxel foram incluídas neste estudo retrospectivo, além de 42 indivíduos saudáveis (47 ± 9 anos). Medidas ecocardiográficas foram realizadas por aproximadamente 11 ± 7 meses (média de 9 meses) após tratamento com antraciclinas. Resultados: AEA esquerdo intra-atrial (11,4 ± 6,0 vs. 8,1 ± 4,9, p=0,008) e AEA interarterial (19,7 ± 7,4 vs. 14,7 ± 6,5, p=0,001) foram prolongados; Volume de esvaziamento passivo e fracionamento de AE diminuíram (p=0,0001 e p=0,0001); Volume de esvaziamento ativo e fracionamento de AE (p=0,0001 e p=0,0001); Tempo de aceleração mitral A (0,8 ± 0,2 vs. 0,6 ± 0,2, p=0,0001) e de desaceleração de onda-E mitral (201,2 ± 35,6 vs. 163,7 ± 21,8, p=0,0001) aumentarão; Razão mitral E/A (1,0 ± 0,3 vs. 1,3 ± 0,3, p=0,0001) e mitral Em (0,09 ± 0,03 vs. 0,11 ± 0,03, p=0,001) diminuíram; Razão mitral Am (0,11 ± 0,02 vs. 0,09 ± 0,02, p=0,0001) e mitral E/Em (8,8 ± 3,2 vs. 7,6 ± 2,6, p=0,017) aumentaram nos pacientes. Conclusões: Em pacientes com câncer de mama após terapia com antraciclina: intervalos eletromecânicos intra-atriais esquerdos, intra-atriais foram prolongados. A função diastólica foi prejudicada. O relaxamento ventricular esquerdo foi prejudicado, e a condução elétrica atrial esquerda pode estar contribuindo para o desenvolvimento de arritmias atriais.

Ethyl pyruvate ameliorates the damage induced by cyclophosphamide on adult mice testes

Background: Cyclophosphamide [CP] is a chemotherapy drug which causes deleterious effects on testicular tissue and increases free radicals in the body. The aim of this study is to investigate the protective effects of ethyl pyruvate [EP] on testicular improvement in CP treated animals

Materials and Methods: In this experimental study, 15 male mice [6-8 weeks] were divided into 3 groups. The control group received normal saline [0.1 ml/day] intraperito-neal [IP], CP group received CP [15 mg/kg/week, IP], and the CP+EP group received EP [40 mg/kg/day, IP] plus CP. After 35 days, we assessed serum total antioxidant capacity [TAC] along with histomorphometric and histochemical analyses of the testicles

Results: The mean thickness of the germinal epithelium, diameter of seminiferous tubules, and the number of Leydig cells in the CP+EP group were higher than those of the CP group [P<0.05]. The number of the mast cells in the CP+EP group significantly reduced compared with the CP group [P<0.05]. Alkaline phosphatase [ALP], periodic acid-schiff [PAS] positive reactions and lipid granules in cytoplasm of the Leydig cells in the CP group increased compared with the other groups [P<0.05]. TAC in the CP group significantly reduced compared with the other groups [P<0.05]

Conclusion: This study showed the ability of EP to reduce the destructive side effects of CP in the adult mice reproductive system

Função ovariana em mulheres lúpicas submetidas ao uso de ciclofosfamida em dois grandes centros de atendimento reumatológico de Curitiba, Estado do Paraná / Ovarian function in systemic lupus erythematosus patients undergoing the use of cyclophosphamide in two major rheumatologic care centers in Curitiba, Paraná State

OBJETIVO: Avaliar a resposta ovariana após uso de ciclofosfamida (CFM) em pacientes com lúpus eritematoso sistêmico (LES) e correlacionar os achados de tempo de doença e idade no período de utilização de CFM e dose cumulativa com alterações no ciclo menstrual e/ou evolução para insuficiência ovariana (IO). MÉTODOS: Foi um estudo transversal, retrospectivo, com 50 pacientes com diagnóstico de LES e que fizeram tratamento com CFM com seguimento clínico de, pelo menos, 1 ano. Foram incluídas pacientes com idade entre 12 e 40 anos e que apresentavam ciclos menstruais regulares prévios ao tratamento. Foram excluídas pacientes que descontinuaram o seguimento, ou este foi menor do que um ano, além daquelas que apresentaram irregularidade/ausência menstrual antes do uso do fármaco. Todas as mulheres estudadas foram submetidas à entrevista e à aplicação de questionário. Neste foram abordadas questões relevantes de padrão de ciclo menstrual antes e posterior à terapia, assim como períodos gestacionais e método contraceptivo. Foi questionado se as pacientes foram orientadas sobre os efeitos colaterais e as consequências da CFM. Para análise estatística, foram utilizados os testes t de Student, Mann-Whitney, do χ2 e o não paramétrico de Kolmogorov-Smirnov. RESULTADOS: A média de idade das pacientes incluídas no do estudo foi de 30,8 anos, e a média de idade no momento do uso de CFM, de 25,3 anos. Após a CFM, 24% das pacientes não menstruaram mais, 28% voltaram a ter ciclos regulares e 48% delas permaneceram com ciclos irregulares. Verificou-se que as pacientes que evoluíram com falência ovariana tinham maior tempo de doença (12,3 anos) do que aquelas que não evoluíram (8,9 anos). Treze pacientes tiveram gestação após a CFM, em todas ocorreu de forma espontânea; no entanto, 66% evoluíram com abortamento. A média de idade das pacientes que fizeram uso de CFM e evoluíram com falência ovariana foi de 28,1 anos. A amenorreia ocorreu em 50% das pacientes ...

PURPOSE: To evaluate the ovarian response after cyclophosphamide use (CPM) in patients with systemic lupus erythematosus (SLE) and to correlate the age and cumulative dose findings with changes in menstrual cycle and/or progression to ovarian failure (OF). METHODS: This was a cross-sectional, retrospective study of 50 patients with a diagnosis of SLE who used CFM with a clinical follow-up of at least 1 year. Included were patients aged 12-40 years, who had undergone chemotherapy for SLE control and who had regular menstrual cycles before the beginning of CPM treatment. Patients who discontinued follow-up, who were followed up for less than one year or who had irregular/absent menses before the beginning of CPM treatment were excluded. All women studied were submitted to an interview and a questionnaire containing questions about the pattern of the menstrual cycle before and after therapy, and about the gestational periods and contraception. We asked if the patients had been instructed about the side effects and consequences of CFM. Statistical analysis was performed using the Student t-test and the Mann Whitney, χ2 and nonparametric Kolmogorov-Smirnov tests. RESULTS: The mean age of the patients included in the study was 30.8 years and the mean age at the time of use of CPM was 25.3 years. After CFM, 24% of patients stopped menstruating, 28% returned to regular cycles and 48% continued to have irregular cycles. It was found that the patients who developed OF had longer disease duration (12.3 years) than those who did not develop it (8.9 years). Thirteen patients became spontaneously pregnant after CFM; however, 66% progressed to abortion. The mean age of the patients who used CFM and developed OF was 28.1 years. Amenorrhea occurred in 50% of those aged 31-40 years, in 22.2% of those aged 21-30 years and in 7.7% of those aged 12-20 years. Our study showed no statistical correlation between cumulative dose and OF, although cumulative ...

Single Nodular Opacity of Granulomatous Pneumocystis Jirovecii Pneumonia in an Asymptomatic Lymphoma Patient

The radiologic findings of a single nodule from Pneumocystis jirovecii pneumonia (PJP) have been rarely reported. We described a case of granulomatous PJP manifesting as a solitary pulmonary nodule with a halo sign in a 69-year-old woman with diffuse large B cell lymphoma during chemotherapy. The radiologic appearance of the patient suggested an infectious lesion such as angioinvasive pulmonary aspergillosis or lymphoma involvement of the lung; however, clinical manifestations were not compatible with the diseases. The nodule was confirmed as granulomatous PJP by video-assisted thoracoscopic surgery biopsy.

Hemofilia adquirida A: relato de caso / Acquired hemophilia A: case report

Hemofilia adquirida A (HAA) é uma doença rara ? incidênciade 1/1.000.000 ao ano -, com maior prevalência em pessoas de65 a 85 anos. A doença caracteriza-se pela presença de autoanticorposcontra fator VIII (FVIII), o que induz a inibição daligação entre este com fator de Von Willebrand e consequenteinativação de sua função anticoagulante. O objetivo deste trabalhofoi apresentar um caso de Hemofilia adquirida A e destacar anecessidade do médico generalista para o reconhecimento destadoença, visto que sua alta taxa de mortalidade - aproximadamentemais de 20% - a torna um importante diagnóstico diferencialde coagulopatias graves. Paciente do sexo masculino, 59anos, com quadro de dor no ombro esquerdo e evolução parahematomas em diversas partes do corpo. Confirmado o diagnósticode hemofilia adquirida A, iniciou-se o tratamento suportivoe de supressão de inibidor de fator VIII, entretanto, houve novossangramentos. Após terapêutica com ciclofosfamida, foi obtidaa supressão das recorrências dos casos hemorrágicos. Devido aposterior desenvolvimento de anemia, o quimioterápico foi suspenso.Um mês após a retirada do fármaco, o paciente segue semreincidência do quadro. O diagnóstico de hemofilia adquirida Aé evidente caso haja o conhecimento prévio dos achados semiológicose sua rotina de investigação laboratorial, mas frequentementeé atrasado devido à falta de familiaridade com a doençapelos médicos generalistas, fator que interfere diretamente nocurso da Hemofilia adquirida A, pois o diagnóstico precoce éum fator determinante para a redução da taxa de mortalidade.(AU)

Acquired hemophilia A (AHA) is a rare disease ? incidence of1/1.000.000 per year - with a higher prevalence in the elderly.The condition is characterized by the presence of autoantibodiesagainst factor VIII, which induces inhibition of its binding tovon Willebrand factor and consequent inactivation of theiranticoagulant function. The objective of this paper was topresent a case of Acquired hemophilia A and emphasize theneed of primary care physicians to recognize this disease, animportant differential diagnosis of severe coagulopathy, withhigh mortality rate. A fifty-nine years old male patient, withleft shoulder pain and development of hematomas in severalareas of the body. The diagnosis of Acquired hemophilia Awas confirmed and supportive treatment and suppression offactor VIII inhibitor was initiated. However, there was furtherbleeding. After therapy with cyclophosphamide, suppressionof recurrent bleeding cases was obtained. Due to furtherdevelopment of anemia, chemotherapy was discontinued.One month after withdrawal of treatment the patient remainswithout recurrence. The diagnosis of Acquired hemophilia Acan be easier done if there is prior knowledge of the clinicalfindings and interpretation of laboratory investigation. Delayeddiagnosis due to lack of familiarity with the disease by generaldoctors directly interferes in the course of Acquired hemophiliaA, because the early diagnosis is a key factor in reducing themortality rate.(AU)