Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation / 中国结合医学杂志

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Synergistic Effects of Arsenic Trioxide and Radiation: Triggering the Intrinsic Pathway of Apoptosis

Background: Arsenic trioxide [ATO] has been reported as an effective anti-cancer and a US Food and Drug Administration [FDA] approved drug for treatment of some cancers. The aim of this study was to determine the underlying apoptosis molecular and cellular mechanisms of ATO in the presence or absence of ionizing radiation [IR] in vitro in the glioblastoma multiforme [GBM] cell line, U87MG

Methods: Cells were treated by different concentrations of ATO either in presence or absence of IR. Viability and apoptosis pathway of both treated and control groups were evaluated using MTT assay and the expression analysis of Box, Bcl-2, and caspase-3 genes, respectively. All treatments were performed on 100-ujm diameter spheroids

Results: Results showed a significant reduction in the survival of the cells in all treated groups. As expected, cell survival was much less in combination treatment than treatment with only ATO. Moreover, combination therapy made Box and caspase-3 up-regulated and Bcl-2 down-regulated

Conclusion: ATO and radiation had a synergistic apoptotic effect on GBM cells by up-regulation of caspase-3 and alteration of the Bax-Bcl-2 balance; therefore, ATO may act as a potential anti-cancer agent against GBM cells through triggering the mitochondria! pathway of apoptosis

Kidney Transplantation in a Patient with End Stage Renal Disease after Complete Remission of Acute Promyelocytic Leukemia

In general, a 2-yr disease-free duration is recommended before kidney transplantation (KT) in end-stage renal disease (ESRD) patients who also have acute leukemia. However, the optimal disease-free interval has not been specified for all subtypes of acute leukemia. Among these subtypes, acute promyelocytic leukemia (APL) shows a favorable prognosis and low relapse rate compared to other types of leukemia. We here report KT after complete remission (CR) of APL in an ESRD patient. Irreversible kidney injury developed in a 23-yr-old man with APL. First, we induced CR and subsequently performed KT 7 months after the achievement of CR. The patient's clinical course after KT was favorable, without allograft rejection or relapse of APL up to1 yr after KT. On the basis of our clinical experience, it is suggested that a long wait may not be necessary before KT in patients with ESRD and APL.

Acute promyelocytic leukemia: An experience from a tertiary care centre in north India.

Background: There are very limited data reported about acute promyelocytic leukemia (APL) from developing countries. We reviewed the clinical course and treatment outcome of APL patients treated at our center. Materials and Methods: Between January 1997 and December 2007, 33 patients with APL received induction therapy using ATRA + daunorubicin (n = 26), As = 26), As2O3 (n = 4) or daunorubicin + cytosar ( n = 3). Results: Median age was 30 years with a male to female ratio of 1.68. Twenty seven patients (82%) achieved CR. Complications during induction therapy were febrile neutropenia (33%), ATRA syndrome (30%), bleeding (58%), and diarrhea in (6%) patients. During induction and follow up, 8 (24.24%) patients died, 6 (18.18%) during induction, 1 (3%) during maintenance, and 1 (3%) after relapse. Median OS is 128 months while median EFS is 61 months. Four patients relapsed at a median time of 61 months. At the time of censoring, 25 patients were alive at a median follow up of 13 months (range 0.6 -127 months); 21 in CR1, 3 in CR2, 1 in CR3. Comparisons among the risk groups (CR and relapse rate and survival statistics) were not statistically significant. Conclusions: APL is a highly curable malignancy. Our results confirm the findings of the published literature from larger cooperative studies from the West. We may further improve outcome with quicker diagnosis and more efficient supportive care system.

Historia del tratamiento de la Sífilis / The history of Syphilis´ treatment

El nombre sífilis proviene del griego siph: cerdo y philus: amor. Recuerda al personaje de una obra, llamado Syphilo, que fue castigado por los dioses a sufrir una terrible enfermedad. Se analizan los datos sobre la sífilis en la antigüedad (que difieren según su fuente). Su mención en la Edad Media, su controversial origen, la ayuda de los paleopatólogos para encontrarlo. Luego de la Revolución Francesa y el inicio de la Edad Contemporánea, el porcentaje de enfermos fue creciendo y se acentuó la segregación de los mismos por la sociedad. Desde el año 1500 hasta principios del siglo XX el tratamiento de la sífilis dependía del mercurio. Tenía una gran variedad de formas de aplicación. La vía tópica: el ungüento gris, en calomelano o tabletas, en inyecciones, en fricciones y fumigaciones en donde el mercurio se introducía en el cuerpo por lo pulmones. Se adjudicó a la madera del guayaco pretendidas características curativas, que no poseía. Los ioduros se utilizaron para el terciarismo. Ehrlich en 1907, patentó el compuesto 606 o Salvarsan y en 1910, el Neo-Salvarsan o Arsfenamina (compuesto 914). Por estos descubrimientos recibió el Premio Nobel. En 1887, Julios Wagner Jauregg sugirió que la fiebre terapéuticamente inducida era útil en el tratamiento de enfermos psicóticos. En 1912 publicó sus satisfactorios resultados al tratar la paresias con una combinación de mercurio-iodo y tuberculina de Koch. En 1917 ingresó a su servicio un enfermo de malaria, con cuya sangre escarificaron la piel palúdica de tres paréticos, en lugar de darle inmediatamente quinina. Por ello fue galardona con el Premio Nobel. Se utilizó luego el bismuto, a partir de 1922, pero posteriormente fue sustituido por las sulfamidas, de aplicación dificultosa. El avance terapéutico más importante ocurrió en 1943, año en que se comenzó a utilizar la penicilina por Mahoney y colaboradores. Luego se confirmó la eficacia de la tetraciclina para los alérgicos a la penicilina. Últimamente se confirmó la eficacia de la azitromicina en dosis de 500mg cada día, durante los 10 días o el régimen de 500mg en días alternos.

The name Syphilis comes from greek language: Siph: Pig and Philus: Love, meaning, in honor of the Sheppard of a story where the Character, Named Syphilo, is punished by the gods to suffer a terrible disease. Data about Syphilis was analized in ancient times (which differ according to the source). Its mention in the middle age, its controversial origin, the help provided from paleopathologists to find it. When the French revolution and the beginning of the contemporary age began, the percentage of sick people grew. The segregation of these is proved by the society. From the year 1500 to the beginnings of the XX century, the treatment of Syphilis depended on mercury. There were a great variety of application methods: topical: the grey ointment, in «calomelanos or tabs¼, in injections, in frictions and fumigations where the mercury was introduced in the body by the lungs. Guayacos wood was named with curative features which it did not posses. The iodides were used for tertiary syphilis. In 1907, Ehrlich formulates the 606 compound or Salvarsan and in 1910 the Neo-Salvarsan or Arsfenamina or compound 914.Due to these discoveries he received the nobel prize. In 1887, Julius Wagner of Jauregg suggested that: the inducted therapeutic fiber was useful in the treatment of the psychosis. In 1912 he published his satisfactory results in treating the paresis with a combination of mercury and iodides and tuberculin of Koch. In 1917 he treated a patient who had malaria and instead of giving him immediately quinine, he made a scarification with his paludic blood the skin of 3 paretic patients. Because of this he was awarded with the nobel prize. Since 1922 bismuth was used, but then it was substituted by the sulphamidas of difficult application. The most important therapeutical advance happened in 1943, year in which penicillin was put in use by Mahoney and col. Later it was confirmed the efficiency of the tetracycline for the penicillin-allergic patients. Lately it has been confirmed the efficiency of the azithromizine in 500 mg dosis each day during 10 days or the regimen of 500 mg in alternate days.

Early relapse after non myeloablative allogeneic stem cell transplantation in a patient with acute promyelocytic leukemia in complete molecular remission.

We described a 41-year-old patient with acute promyelocytic leukemia (APL) who experienced two successive relapses: one after all-trans retinoic acid (ATRA) treatment and chemotherapy, and another after ATRA treatment and chemotherapy, followed by autologous peripheral blood stem cell transplantation. A third complete remission (CR) was achieved with arsenic trioxide (As2O3) therapy. Mini-transplantation was performed as consolidation therapy. While the patient was in molecular remission at the beginning of conditioning regimen, a new relapse arose after transplantation at time of cell recovery. This raises a potential relationship between relapse and the severe immunosuppression induced by mini-transplantation. To our knowledge, this is the first description of a mini-allograft in an APL patient achieving molecular remission after As2O3 therapy.

Eosinofilia pulmonar tropical filariotica e o seu diagnostico diferencial / Tropical pulmonary eosinophilia its differential diagnosis

Os autores fazem uma ampla revisao sobre a eosinofilia pulmonar tropical (EPT) de origem filarial e o seu diagnostico diferencial com relacao a outras sindromes afins. Abordaram os aspectos epidemiologicos, clinicos, diagnosticos, terapeuticos e fisiopatogenicos, enfatizando os novos avancos ocorridos no conhecimento da doenca filarial e sua repercussao para um melhor entendimento da EPT. Tambem destacaram a ocorrencia de uma forma denominada EPT-LIKE, causada por helmintos intestinais, de dificil diagnostico diferencial com relacao a EPT e que pode ocorrer tambem em areas nao endemicas de filariose. No final do artigo, os autores sugerem um roteiro para a interpretacao dos dados epidemiologicos, clinicos, laboratoriais, radiologicos (e ultra-sonograficos) e terapeuticos na orientacao para a suspeicao diagnostica do paciente portador de EPT...