Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection / 亚洲男科学杂志(英文版)

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg-1) on day 36 or a dose of 40 mg kg-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.

Investigaçäo de neuropatia periférica durante o período recente do transplante de medula óssea / Peripheral neuropathy investigation in the early stage of bone marrow transplantation

Investigamos prospectivamente a incidência de neuropatia periférica em 43 pacientes através do estudo da velocidade de conduçao nervosa e do teste de limiar de sensibilidade vibratória (palestesiômetro) realizados antes e após o transplante de medula óssea. Nesse período as principais drogas utilizadas para o condicionamento e imunossupressao foram o bussulfan, ciclofosfamida, ciclosporina A, methotrexate e corticoesteróides. Foram estudadas as velocidades de conduçao nervosa nos nervos mediano motor, fibular, tibial, mediano sensitivo e sural. Obtivemos alteraçoes estatisticamente significativas na duraçao do potencial composto proximal do nervo mediano motor, na amplitude distal do nervo tibial posterior e na amplitude proximal do nervo sural. As diferenças observadas nao se correlacionaram com alteraçoes clínicas, e nao foram suficientes para o diagnóstico de neuropatia periférica. Acreditamos que o esquema terapêutico utilizado nao provoca toxicidade neurológica periférica no período recente do transplante de medula óssea.

Cataract caused by myleran toxicity

A case of cataract related to Busulfan [Myleran] was studied with light and electron microscopy. Clinical evaluation revealed bilateral posterior subcapsular cartaracts. Histological abnormalities included the presence of numerous abnormal dense bodies and Morgagnian globules in the anterior subcapsular region with marked cellular destruction and accumulation of granular debris posteriorly. Electron microscopy revealed that abnormal dense inclusions resembled myelinoid bodies. Acid phosphatase activity was localized in the epithelium and was hardly visible in the area of cellular necrosis. It is felt that the myleran - induced disturbance of polar lipid catabolism was responsible for cataract formation this case