Efeitos adversos do uso de ciclosporina em pacientes com dermatite atópica grave / Adverse effects of using cyclosporine in patients with severe atopic dermatitis

Introdução: A dermatite atópica (DA) é uma doença inflamatória da pele, multifatorial, crônica e recorrente, caracterizada por lesões eczematosas e prurido intenso. Nos casos graves refratários aos tratamentos tópicos, tem se utilizado imunossupressão sistêmica para o controle da doença, sendo a ciclosporina considerada por muitos como terapia de escolha. Este estudo visa avaliar a incidência e gravidade dos eventos adversos relacionados ao uso de ciclosporina em pacientes com DA grave. Métodos: Estudo retrospectivo observacional com análise de prontuários de pacientes com dermatite atópica grave em uso de ciclosporina atendidos em hospital terciário no período de 3 anos. Resultados: Avaliados 80 pacientes com dermatite atópica grave usando ciclosporina, com média de idade de 25,5 anos e 41 do sexo feminino (51,3%). Foram relatados eventos adversos em 25 pacientes. O tempo médio de uso de ciclosporina no grupo com eventos adversos foi de 29,3 meses. Os eventos de maior gravidade foram alteração da função renal e hipertensão, sendo mais observados nos casos de doença mais refratária, quando o uso de ciclosporina foi muito prolongado, superior a 60 meses. As reações evidenciadas foram: hipertensão arterial 40%, alteração renal 20%, náuseas/vômitos 16%, cefaleia 12%, herpes de repetição 12% e outros 4%. Os eventos adversos normalizaram após suspensão da ciclosporina. Conclusão: Pacientes com dermatite atópica grave que usaram ciclosporina por tempo prolongado tiveram maior frequência de eventos adversos potencialmente graves. Todos os efeitos adversos normalizaram após a suspensão de medicação.

Rationale: Atopic dermatitis (AD) is an inflammatory, multifactorial, chronic, recurrent skin disease characterized by eczematous lesions and intense itching. In severe cases refractory to topical treatments, systemic immunosuppression has been used to control the disease, and cyclosporine is largely considered firstline therapy. This study aims to assess the incidence and severity of adverse events related to the use of cyclosporine in patients with severe AD. Methods: This retrospective observational study analyzed medical records of patients with severe atopic dermatitis using cyclosporine treated at a tertiary hospital over a 3-year period. Results: Eighty patients with severe atopic dermatitis using cyclosporine were evaluated. Their mean age was 25.5 years, and 41 (51.3%) were female. Adverse events were reported in 25 patients. The mean duration of cyclosporine treatment in the group with adverse events was 29.3 months. The most serious events were changes in renal function and hypertension, which were most often observed in cases of more refractory disease, when the use of cyclosporine was very prolonged (over 60 months). The adverse reactions were hypertension (40%), renal changes (20%), nausea/vomiting (16%), headache (12%), recurrent herpes (12%) and others (4%). Adverse events were under control after cyclosporine was discontinued. Conclusion: Patients with severe atopic dermatitis who used cyclosporine for a long time had a higher frequency of potentially serious adverse events. All adverse effects were under control after discontinuation of medication.

Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology

Abstract: Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.

Eficácia da ciclosporina no controle da dermatite atópica em cães / Efficacy of cyclosporine in the control of atopic dermatitis in dogs

A dermatite atópica é uma dermatopatia inflamatória, pruriginosa, crônica, de origem genética, resultante da perda da função de barreira física da pele e da hiperreatividade à alérgenos ambientais, trofoalérgenos, alérgenos microbianos e a irritantes primários. Este estudo avaliou a eficácia da ciclosporina no controle do prurido e das lesões associadas à dermatite atópica em cães. Selecionaram-se 24 cães com diagnóstico de dermatite atópica baseados nos critérios de Favrot et al. (2010), os quais foram divididos em dois grupos de 12 cães, onde o Grupo 1, recebeu ciclosporina (5mg/kg/vo/24h), e o Grupo 2, foi tratado com prednisona (0,5mg/kg/vo/24h) em doses decrescentes, ambos por 60 dias. Os animais foram continuamente avaliados, e seus escores sintomato-lesionais, baseados na escala de CADESI-03, estabelecidos nos dias 0, 30 e 60. Em adição, os escores de prurido de cada animal, baseado nos critérios de Rybnicek, foram semanalmente avaliados, do dia 0 ao 63. Todos os dados coletados foram analisados pelo teste não paramétrico de Kruskal-Wallis, seguido do teste de Dunn´s e para as análises entre os grupos foi utilizado o teste t, considerado o nível de significância mínimo de 5%. A ciclosporina teve uma eficácia similar, no controle lesional, ao grupo que recebeu prednisona no dia (+30) (p<0,05) e no dia (+60) (p<0,001) do tratamento, em relação ao dia zero. Uma diferença significativa do escore do prurido foi observada nos dias +28, +35, +42, +49, +56 e +63 (p<0,001), e no dia +21 (p<0,01) em relação ao momento inicial do tratamento, porém sua eficácia foi inferior ao Grupo 2, a partir do 42º dia de avaliação, mantendo-se esta diferença nos dias +49, +56 e +63 (p>0,05). Apesar da ciclosporina ter sido menos eficaz no controle do prurido, este se manteve em níveis aceitáveis, e seu uso contínuo não foi associado a efeitos colaterais relevantes.(AU)

Atopic dermatitis is an itchy, chronic inflammatory skin disease of genetic origin, resulting from loss of the physical barrier function of the skin and hyper-reactivity to environmental allergens, trofoallergens, microbial allergens and to primary irritants. The efficacy of cyclosporine in the control of pruritus and lesions associated with atopic dermatitis in dogs was evaluated. Twenty-four dogs with atopic dermatitis were selected, based on Favrot et al.'s criteria (2010). They were divided into two groups of 12 dogs, where Group 1 received cyclosporine (5mg/kg/vo/24h), and Group 2 was treated with prednisone (0.5mg/kg/vo/24h) in decreasing doses, both for 60 days. The animals were continuously evaluated, and theirits lesional symptomatology scores were based on a Cadesi-03 scale, set on days 0, 30 and 60. Pruritus scores of each dog, based on Rybnicek´s criteria, were weekly evaluated, from day 0 to day 63. All collected data were analyzed by the nonparametric Kruskal-Wallis´ test, followed by Dunn's test, and for the analysis between the groups, considered the minimum significance level of 5%, t-test was used. Cyclosporin had similar efficacy in lesional control in the group which received prednisone on day (+30) (p<0.05) and on the day (+60) (p<0.001) of treatment, compared with day zero. A significant difference of the itching score was observed on days +28, +35, +42, +49, +56 and +63 (p<0.001), and on day +21 (p<0.01) when compared to initial treatment. However, its efficacy was lower than Group 2, from 42 days of evaluation on, keeping such difference on days +49, +56 and +63 (p>0.05). Although cyclosporin have been less effective in controlling itching, it remained at acceptable levels, and its continued use was not associated with significant side effects.(AU)

Multicenter questionnaires on the current management of atopic dermatitis in Korea

PURPOSE: The effective management of atopic dermatitis (AD) adjusted to individual clinical courses and demands can be challenging to both patients and physicians. Understanding of actual situations, experienced and perceived by patients with AD and their caregivers, is essential to improve clinical outcomes and satisfaction in real practice. METHODS: This multicenter survey was conducted in patients with AD or their caregivers from 9 centers with questionnaires on diagnosis and management of AD. RESULTS: A total of 324 patients and caregivers participated in the study. Most of the AD cases were initially diagnosed by physicians (80.6%), followed by self-diagnosis. Patients and caregivers thought that allergic substances, such as house dust mites, food, and pollutants, are responsible for AD development; moisturization, environmental control, and improvement of the body constitution are important for AD management. Allergy tests were performed in 194 patients (59.9%), but allergen avoidance strategy was instructed in only 81 subjects (41.8%). Major topical medications were steroids (81.8%) and topical immunomodulators (34.3%), while systemic medications were steroids (42.6%), antihistamines (36.4%), and cyclosporins (2.8%). One hundred eighty-one subjects (55.9%) had received complementary alternative medicine, including Oriental medicine. Many subjects desired to receive individualized management, use of specialized institutions for AD as well as evidence-based, effective, sustainable treatment. CONCLUSION: Our findings suggest that there may still be an unmet need for patients with AD in real practice. Personalized, evidencebased, and multidisciplinary approaches, including patient education, should be implemented for good outcomes.

Trasplantes renales en niños y adolescentes en el hospital Dr. Gustavo Fricke de Viña del Mar: recuento histórico y resultados según grupo de edad / History of kidney transplants performed in children and teenagers in Hospital Doctor. Gustavo Fricke, Viña del Mar: a detailed narration of each kidney transplant

Historia de los trasplantes renales efectuados en niños y adolescentes en el Hospital Dr. Gustavo Fricke de Viña del Mar: Una narración pormenorizada de cada trasplante. En este artículo se narra la historia de los trasplantes renales pediátricos efectuados en el hospital Dr. Gustavo Fricke entre 1984 y 2000. Durante el período se efectuaron 19 trasplantes en niños y adolescentes. De ellos, 42 por ciento se efectuó en niños menores de 15 años y 58 por ciento en adolescentes entre 15 y 18 años. El tiempo que permanecieron en diálisis crónica fue de 26 y 13 meses, respectivamente. Los niños recibieron un riñón más frecuentemente desde un donante fallecido (75 por ciento) y los adolescentes de un donante vivo (91 por ciento). El esquema inmunosupresor más utilizado fue la combinación de azatioprina, ciclosporina y corticoides. Los niños presentaron con mayor frecuencia un rechazo agudo y la necesidad de una reintervención quirúrgica en el postoperatorio que los adolescentes. A la fecha de corte de esta historia, transcurridos 30 años del primer trasplante pediátrico, 43 por ciento de los injertos renales efectuados en niños y 36 por ciento en adolescentes está funcionando, con un rango de duración entre 16 y 20 años...

History of kidney transplants performed in children and teenagers in Hospital Dr. Gustavo Fricke, Viña del Mar, Chile: A detailed narration of each kidney transplant This article told the history of pediatric renal transplants performed in Hospital Dr. Gustavo Fricke between 1984 and 2000. During this period 19 kidney transplants were performed in children and adolescents. Of these, 42 percent were performed in children under 15 years (range: 3-14) and 58 percent in adolescents (15-18 years). The time that patients remain in chronicdialysis was 26 months and 13 months, respectively. Children received a kidney more frequently from a deceased donor(75 percent) and adolescents from a living donor (91 percent). The immunosuppressive regimen most often used was the combination of azathioprine, cyclosporine and corticosteroids. Children had more often acute rejection in the postoperative period and the need of a reoperation. After 30 years of the first pediatric transplant, 43 percent of the renal grafts performed in children and 36 percent in adolescents are functioning, with a length between 16 and 20 years...

Cyclophilin A as a New Therapeutic Target for Hepatitis C Virus-induced Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.

Avaliação clínica do crescimento gengival induzido por Ciclosporina-A ou Tacrolimus em indivíduos transplantados renais na ausência de bloqueadores de canais de cálcio: estudo prospectivo de 12 meses / Clinical evaluation of the gingival overgrowth induced by Ciclosporine-A or Tacrolimus in kidney transplant recipients in the absence of calcium channel blockers: a 12-month prospective study

O crescimento gengival é um efeito colateral comum nos indivíduos que recebem transplante de órgão e estão sob terapia imunossupressora. O objetivo deste estudo foi avaliar prospectivamente a ocorrência e severidade do crescimento gengival induzido pelo tacrolimus ou ciclosporina-A, na ausência de bloqueadores de canais de cálcio em indivíduos transplantados renais. Participaram do estudo 64 indivíduos que passaram por cirurgia de transplante e receberam ciclosporina (n=33) ou tacrolimus (n=31) como droga imunossupressora principal. Eles foram avaliados em 5 momentos: pré-transplante, 1, 3, 6 e 12 meses após transplante. Em todas as avaliações foram coletados dados demográficos e parâmetros clínicos periodontais (distância da margem gengival à junção cemento-esmalte, profundidade clínica de sondagem, nível clínico de inserção, índice de placa, sangramento à sondagem, e crescimento gengival). O valor médio de crescimento gengival no grupo ciclosporina foi maior que no grupo tacrolimus após 1 (p=0,04), 3 (p=0,001), 6 (p=0,007) e 12 meses (p=0,001). O crescimento gengival clinicamente significante foi observado em 30,3% (10 sujeitos) no grupo ciclosporina e 12,9% (4 sujeitos) no grupo tacrolimus após o período de 12 meses. Porém, essa diferença não foi estatisticamente significante (p=0,56). Concluímos que apesar de não ter sido encontrada diferença significante na ocorrência de crescimento gengival clinicamente significante, a severidade no grupo ciclosporina foi maior que no grupo tacrolimus após 12 meses de terapia imunossupressora.

Gingival overgrowth (GO) is a common side effect in recipients of organ transplants that are under immunosuppressive therapy. The aim of this study was to assess prospectively the occurrence and severity of gingival overgrowth induced by tacrolimus (Tcr) or ciclosporin A (CiA), in the absence of calcium channel blockers, in renal transplant patients. Sixty-four individuals undergoing transplantation received as the main immunosuppressant CiA (n=33) or Tcr (n=31). They were assessed at five time intervals: pre-transplant, 1, 3, 6, and 12 months after transplant. Demographic data and periodontal clinical parameters (cement-enamel junction to the gingival margin, probing depth, clinical attachment level, plaque index, bleeding on probing, and GO) were measured at all time intervals. The mean GO scores in CiA group were higher than Tcr group after 1 (p=0.04), 3 (p=0.001), 6 (p=0.007) and 12 months (p=0.001). A clinically significant GO was observed in 30.3% (10 subjects) in CiA group, and 12.9% (4 subjects) in Tcr group after 12 months. However, this difference was not significant (p=0.56). Although there was no significant difference in the occurrence of clinically significant GO, the severity in CiA group was higher than in Tcr group after 12 months of immunosuppressive therapy.

Advances in ulcerative colitis therapy / 대한내과학회지

Ulcerative colitis is an idiopathic inflammatory bowel disease characterized by colonic mucosal inflammation and chronic relapsing episodes. The initial therapeutic approach depends on both the extent of colonic involvement and the severity of the disease process at presentation. The mainstay of ulcerative colitis therapy is the administration of 5-aminosalicylic acid (5-ASA) or steroid. Additional medical therapy or colectomy should be considered if the patient remains symptomatic despite conventional therapy, regardless of the extent of colonic involvement. Cyclosporins are effective as a short-term rescue therapy for steroid-refractory ulcerative colitis. Recently, new 5-ASA and steroid formulations with altered delivery, dosing regimens, and less frequent administration have been introduced and demonstrated to be efficacious in active mild to moderate colitis. Infliximab is given to try to avoid the need for colectomy and has proven efficacious in ulcerative colitis. This review outlines the standard therapy for ulcerative colitis and discusses new insights into the recent trend focusing on new therapies, including biological agents and leukocytapheresis.

Effect of P-glycoprotein on the absorption of buagafuran in rat intestinal lumen / 药学学报

To study the effect of P-glycoprotein (P-gp) on the absorption of buagafuran in ileum, the concentration of buagafuran in Caco-2 cells, rat averted intestinal sacs and recirculating perfusion were determined by UV-HPLC method. Verapamil and cyclospirin A (CsA) were used as P-gp inhibitors. The results showed that the transportation of buagafuran across Caco-2 monolayer showed vectorial manner. The permeation of buagafuran from apical (A) to basolateral (B) side was 11% and 24.8% from B to A side. Verapamil and CsA were found to increase the transport of buagafuran by 1.4 and 1.35 fold from A to B side and decrease by 71% and 75% from B to A side, respectively, compared with control. The uptake of buagafuran in Caco-2 cell was also enhanced by P-gp inhibitors, especially in low concentration of buagafuran. Ninety percent of buagafuran was absorbed after 90 min perfusion. Verapamil and CsA were found to improve the absorption of buagafuran at all time points, especially at 30 min (12.4% and 21.5%, respectively). During the incubation, only 14% of buagafuran left in rat averted intestinal sacs, while buagafuran levels were increased in both intestine homogenate and sacs by adding verapamil and CsA. The results indicated that buagafuran was one of the P-gp substrates based on the present study. The absorption of buagafuran can be blocked by P-gp, resulting in the enhancement of buagafuran metabolism in intestine. The poor bioavailability of buagafuran may be partially due to the effect of P-gp on its absorption and transportation in intestinal lumen.

Opções terapêuticas na Asma grave / Therapeutic options for severe asthma

Estima-se que 10 dos asmáticos sofram de asma persistente grave. Estes doentes apresentam controle insatisfatório da sua asma, com sintomas persistentes graves e maior risco de exacerbações, hospitalizações e morte e geralmente com marcada deterioração da qualidade de vida. A terapêutica baseia-se na avaliação do grau de gravidade e otimização da terapêutica com minimização de efeitos secundários. Os doentes mantêm controle inadequado dos sintomas e apesar de administradas altas doses de corticosteróides inalados e agonistas p2 de longa duração, freqüentemente necessitam de medicação adicional com teofilina de libertação lenta, anti-Ieucotrienos e/ou corticosteróides oral. Nos doentes com asma córtico-dependente ou córtico-resistente outras opções terapêuticas devem ser equacionadas como os fármacos poupadores de corticosteróides: ciclosporina, metotrexato, imunoglobulina endovenosa e sais de ouro. O omalizumabe, anticorpo monoclonal anti-IgE, foi recentemente incluído dentro das alternativas terapêuticas disponíveis. Para se conseguir um controle mais eficaz desta doença complexa é fundamental a caracterização futura dos diferentes fenótipos desta síndrome

Avaliação pós-transplante de ovários íntegros e fatiados sem anastomose vascular / Endocrinological, morphological and gestational assessment of intact and sliced ovarian orthotopic reimplantation or transplantation without vascular pedicle

OBJETIVO: Avaliar a fertilização, bem como aspectos endócrinos e histológicos do ovário após seu reimplante ou transplante ortotópico, sem anastomose vascular. MÉTODOS: Foram utilizadas 56 coelhas da raça Nova Zelândia Branca e Califórnia distribuídas em: Grupo 1 (n=8) - controle, apenas laparotomia e laparorrafia; Grupo 2A (n=8) - reimplante ortotópico de ovários íntegros; Grupo 2B (n=8) - reimplante ortotópico de ovários fatiados; Grupo 2C (n=8) - reimplantes ovarianos de um lado, íntegros, e, do outro lado, fatiados; Grupo Grupo 3A (n=8) - transplante ortotópico de ovários íntegros; Grupo 3B (n=8) - transplante ortotópico de ovários fatiados; Grupo 3C (n=8) - transplantes ovarianos de um lado, íntegros, e, do outro lado, fatiados. A partir do terceiro mês pós-operatório, cada coelha foi colocada para cópula. Dosou-se o estradiol, a progesterona, o FSH e o LH no nono mês pós-operatório. Estudou as morfologias macro e microscópicas dos ovários, tubas e útero, de todas os animais. Os números de gestações e de filhotes foram avaliados por meio do teste Qui-quadrado e as dosagens hormonais foram comparadas pelo one-way Anova, seguido pelo teste de Tukey-Kramer. RESULTADOS: No Grupo 1, sete (87,5 por cento) coelhas engravidaram entre o segundo e terceiro meses após início da cópula. No Grupo 2, as gestações ocorreram entre o quinto e o oitavo meses pós-operatórios e, no Grupo 3, entre o quarto e o oitavo meses pós-operatórios. A porcentagem de gravidez observada foi de 37,5 por cento no Grupo 2A, 50 por cento no Grupo 2B e 2C, 37,5 por cento no Grupo 3A, 50 por cento no Grupo 3B e 62,5 por cento no Grupo 3C. Os níveis hormonais e o estudo morfofuncional dos ovários, tubas e úteros não apresentaram alterações. CONCLUSÃO: O reimplante ou transplante ovariano homógeno ortotópico sem pedículo vascular é eficaz para a manutenção de níveis normais de hormônios ovarianos e permitiu a fertilização natural.

OBJETIVE: To assess the natural pregnancy and to determine the morphofunctional aspects of ovaries of rabbits submitted to bilateral oophorectomy and orthotopic allogeneic or autologous intact and sliced ovarian transplantation without a vascular pedicle. METHODS: Fifty-six female New Zealand White and California rabbits were studied. The ovaries were removed and orthotopically transplanted or replaced without vascular anastomoses: Group 1 (n = 8), only laparotomy and laparorrhaphy were performed; Group 2A (n = 8) intact ovaries were reimplanted on both sides; Group 2B (n = 8) both ovaries were sliced and orthotopically reimplanted; Group 2C (n = 8), an intact ovary was reimplanted on one side and a sliced ovary on the other side; Group 3A (n = 8) intact ovaries were transplanted on both sides, Group 3B (n = 8) both ovaries were sliced and orthotopically transplanted, Group 3C (n = 8), an intact ovary was transplanted on one side and a sliced ovary on the other side. Three months later, the females were paired with males for copulation. Estradiol, progesterone, follicle stimulating hormone and luteinizing hormone levels were assessed. The morphological aspect of the ovaries was studied and the number of pregnancies and litters were also determined.Tthe number of successful pregnancies and the number of litters was compared between the groups by the chi-square test. One-way ANOVA and the Tukey-Kramer tests compared the hormonal dosages. The significance was of p < 0.05. RESULTS: Pregnancies occurred in seven (87.5 percent) rabbits of Group 1, in 37.5 percent in Groups 2A and 3A, in 50 percent of groups 2B, 2C and 3B, and in 62.5 percent of group 3C. Hormone levels and histology confirmed the vitality of all ovaries. CONCLUSION: Intact or sliced orthotopic allogeneic and autologous ovarian transplantation without a vascular pedicle is viable in rabbits, and preserves their fertility and hormonal functions.

Monitorização terapêutica de ciclosporina em um grupo de pacientes transplantados reanis / Blood monitoring of cyclosporine in renal transplant patiens

A ciclosporina é um dos imunossupressores mais utilizados em transplantes. neste trabalho foram avaliados resultados das dosagens sangíneas de ciclosporina de pacientes transplantados renais atendidos pelo Laboratório de Toxicologia da Universidade Estadual de Maringá (UEM) em 2001. A monitorização compreendru dosagens em C0 (concentração anterior à ingestão da próxima dose) e C3 (concentração três horas após a ingestão do medicamento), por imunofluorescência polarizada. Infromações sobre sexo, idade, data de transplante e medicamentos utilizados, foram obtidas. 82% dos pacientes tinham entre 25-59 anos, com predominância do sexo masculino (68%). Cicliosporina-Neoral®, azatioprina e prednisona constituiu o esquema terapêutico mais utilizado (72%). em C0, 83,6% dos resultados apresentaram-se dentro, enquanto que em C3,62,4% mostraram-se acima da faixa terapêutica recomendada (100 a 400 ng/ml). Não houve relação entre C0 ou C3 e tempo de transplante ou tratamento imunossupressor. A monitorização terapêutica é fundamental para minimizar efeitos tóxicos ou mesmo a rejeição do rrgão transplantado...

O efeito da ciclosporina-A na osseointegração / The influence of cyclosporin-A on osseointegration

Agentes imunossupressores provocam alterações severas no metabolismo ósseo mineral podendo resultar em osteopenia. Tais alterações podem ser prejudiciais no processo e manutenção da osseointegração. Este estudo teve o objetivo de avaliar a influência da administração de ciclosporina-A (CSA) na osseointegração de implantes de titânio, através da avaliação: durante a cicatrização óssea ao redor de implantes dentais (Estudo I); da densidade óssea ao redor implantes dentais (Estudo II); da retenção do implante após a cicatrização óssea de implantes dentais (Estudo III) e radiográfica da qualidade óssea ao redor de implantes dentais já osseointegrados (Estudo IV). Os resultados permitiram concluir que a administração de CSA durante a cicatrização óssea resulta em diminuição da osseointegração e da densidade óssea ao redor do implante dental. Ainda, a administração de CSA após o período de cicatrização óssea ao redor do implante reduz a sua retenção mecânica ao tecido ósseo e promove a diminuição da qualidade e da densidade óssea radiográfica ao redor do implante dental.

Anemia aplástica adquirida del adulto. Su tratamiento a propósito de dos casos / Acquired aplastic anemia of the adult: the treatment of two cases

Severe aplastic anemia has an elevated mortality if treatment is unsatisfactory. Immunosuppression is the treatment of choice in adults, comparable with allogeneic bone marrow transplant in children. We report two adult patients (both males, aged 59 and 67 years old) who were treated successfully with lymphoglobulin and cyclosporine. The initial response started within 3 months of treatment and was almost complete after 2 years, when cyclosporine was stopped. After three years, both patients have almost normal blood counts, with minor sequels: avascular necrosis of both femoral heads due to the use steroids, that recovered spontaneously in 1 patient and reduced vision due to thrombocytopenic retinal hemorrhages, in the other (Rev Méd Chile 2003; 131: 1439-43).

Trasplante de células hematopoyéticas de sangre periférica utilizando quimioterapia inmunosupresora sin destrucción de la médula ósea: "minitrasplante" / Peripheral blood hematopoietic cell transplant using immunosuppressive chemotherapy without bone marrow destruction: minitransplant

Using a nonmyeloablative, immunosuppressive, fludarabine (FLU)-base conditioning regimen, we have performed allogeneic peripheral blood stem cell transplants in 17 patients (six with chronic granulocytic leukemia, four with acute myelogenous leukemia, five with acute lymphoblastic leukemia, one with myelodysplasia and one, with thalassemia major). Conditioning regimen consisted of FLU/busulfan/cyclophosphamide or FLU melphalan. To avoid graft vs. host disease (GVHD), cyclosporine and methotrexate were used. Median granulocyte recovery time to 0.5 x 10(9) was 11 days, whereas median platelet recovery time to 20 x 10(9) was 12 days. Seven patients did not need red blood cell transfusions and four did not need platelet transfusions. In thirteen individuals (76), the procedure could be completed fully on an outpatient basis. Follow-up times range between 1 and 14 months. Five of 17 patients developed acute GVHD whereas 4/10 developed chronic GVHD. The 14-month survival (SV) is 70 and median SV is not reached. Five patients (29) have died, three due to relapse of the disease and two due to GVHD. The transplant-related mortality was 5.8. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and may represent another approach in management of patients requiring allogeneic stem cell transplant.

Reversal of multidrug-resistance in human leukemia cell line K562/A02 by a cyclosporin D analogue PSC 833 / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy of PSC 833 on multidrug resistance (MDR) reversal and its mechanism.</p><p><b>METHODS</b>Human erythroleukemic cell line K562 and its doxorubicin-resistant counterpart K562/A02 were used in the study. Cytotoxicity was assessed by MTT assay, P-gp expression by direct immunofluorescence and mdr1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) with beta-actin as internal control. Intracellular DNR retention was measured with flow cytometry.</p><p><b>RESULTS</b>K562/A02 cells displayed high levels of mdr1 mRNA and P-glycoprotein and reduced DNR retention compared to their parental K562 cells. 1 micromol/L of PSC 833 had no effect on the levels of mdr1 mRNA and P-gp expression in K562/A02 cells (P > 0.05). PSC 833 conferred a dose-dependent increase on chemosensitivity of K562/A02 to DNR, and its effect was at least 3-fold more potent than that of CsA or Ver. PSC 833 could increase DNR retention in K562/A02 cells. A 100.9% restoration of intracellular DNR retention of the level of K562 cells was gained by PSC 833 at 1.0 micromol/L in K562/A02 cells, whereas only a 86.9% restoration of DNR retention was obtained by CsA at 10 micromol/L in the K562/A02 cells. No effect on DNR sensitivity and retention was found in K562 cells (P > 0.05).</p><p><b>CONCLUSION</b>PSC 833 is at least 3 approximately 10 fold more potent than CsA or Ver with respect to MDR reversing activity, and it may function by inhibiting the function of P-gp and not reducing the levels of mdr1 mRNA and P-gp directly.</p>