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Infection in the Hematopoeitic Stem Cell Transplant Recipient with Autoimmune Disease
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Valentina Stosor, Teresa R. Zembower
There are a number of antimetabolite and alkylating agents that are used for the treatment of autoimmune disorders. These include the antimetabolites, azathioprine and methotrexate, and the alkylating agents, cyclophosphamide and chlorambucil.61-64 The primary side effects common to these agents include myelosuppression and gastrointestinal mucositis, both of which can lead to infection, particularly, of bacterial and fungal etiologies. In the case of azathioprine, patients should be screened for thiopurine-S-methyltransferase (TPMT) deficiency (Caucasian prevalence 0.3-11 percent) as patients with low TPMT activity are at high risk for severe and potentially fatal hematopoietic toxicity if treated with conventional doses of this agent.64 Cyclophosphamide is also associated with hemorrhagic cystitis that can mimic urinary tract infections caused by opportunistic viral pathogens.
A male germ cell assay and supporting somatic cells: its application for the detection of phase specificity of genotoxins in vitro
Published in Journal of Toxicology and Environmental Health, Part B, 2020
Khaled Habas, Martin H. Brinkworth, Diana Anderson
Spermatogenic arrest is one of the main causes of male factor infertility. Arrest characterizes a state in which spermatogenesis stops at a specific phase of development of germ cell. The arrest predominantly occurs in the primary spermatocyte stage (Tesarik 2004). 6-Mercaptopurine (6-MP) and 5-bromo-2′-deoxyuridine (BrdU5) are DNA analog drugs widely employed as therapies of acute autoimmune diseases and lymphoblastic leukemia (Jayachandran et al. 2014; Levkoff et al. 2008). 6-MP is metabolized via the enzyme activity of thiopurine methyltransferase (TPMT), and converted through enzymes to form 6-thioguanine nucleotides, resulting in generation of cytotoxicity due to incorporation into DNA during synthesis (Kanemitsu et al. 2009). Male germ cells treated with 6-MP display the greatest response in early meiotic spermatocytes (Generoso, Preston, and Brewen 1975). 6-MP induces chromosomal damage and aberrations in spermatocytes (Mosesso and Palitti 1993). 5BrdU is a thymidine analog that was recognized in the 1950s as a mutagen to target rapidly dividing cancer cells (Djordjevic and Szybalski 1960; Hakala 1959). 5BrdU is incorporated into DNA chains, leading to specific-locus mutations and inhibition of cell proliferation (Littlefield and Gould 1960; Morris 1991). Staub et al. (2000) noted histologically that spermatocytes after injection with 5BrdU exhibited the most label in germ cells. Further, Attia (2012) also reported that 5BrdU labeled spermatocytes and induced a significant increase in DNA damage and apoptosis. Germ cells from adult rodents showed that spermatocytes exerted greatest response to 6-MP and BrdU5 (Habas, Anderson, and Brinkworth 2016; Habas, Brinkworth, and Anderson 2017c).