To determine the incidence and clinical relevance of active human herpesvirus 6 (HHV-6) infection, 92 consecutive unselected recipients of autologous or allogeneic stem cell grafts were investigated in a prospective longitudinal study. Active infection was assessed by the presence of viral deoxyribonucleic acid (DNA) in 846 peripheral blood mononuclear cell specimens and 115 plasma specimens, by means of a specially developed polymerase chain reaction designed to avoid detection of latent genome. The incidence of HHV-6 infection observed was 42.5%, irrespective of the type or source of graft, and infection was significantly associated with partial (P=.002) or total myelosuppression (P=.01) and fever (P<. 000001). Infusion of bone marrow as the source of graft, reactivation occurring before platelet or neutrophil engraftment, and presence of HHV-6 DNA in plasma were identified as risk factors for symptomatic HHV-6 infection (P<.002).
Taken together, the results suggest that PM2.5 exposure destroys BTB integrity through excessive ROS-mediated autophagy. Our finding could contribute to a better understanding of PM2.5-induced male reproductive toxicity.
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor widely used in China that is harmful to the male reproductive system. Many studies have shown that DEHP causes testicular toxicity through oxidative stress, but the specific mechanism is unknown. Because the Notch pathway is a key mechanism for regulating cell growth and proliferation, we investigated whether Notch is involved in DEHP-induced testicular toxicity and whether vitamins E and C could rescue testicular impairment in Sprague-Dawley (SD) rats. Compared with the control group, we found that DEHP exposure induced testicular toxicity through oxidative stress injury, and it decreased the testosterone level (P < .01) and upregulated nuclear factor-erythroid 2 related factor (Nrf2) expression (P < .01). Therefore, because oxidative stress might be the initiating factor of DEHP-induced testicular toxicity, treatment with the antioxidant vitamins E and C activated the Notch1 signaling pathway in the testis and in Leydig cells. Treatment with vitamins E and C normalized the oxidative stress state after DEHP exposure and restored testicular development to be similar to the control group. In summary, antioxidant vitamins E and C may be used to treat DEHP-induced testicular toxicity.
This study attempts to evaluate the outcome of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) in patients with severe paediatric systemic lupus erythematosus (SLE). Five patients (n = 2 females, n = 3 males) with severe or refractory paediatric SLE received autologous peripheral blood CD34+ cell transplants between July 2005 and February 2009. The patients ranged in age from 6 to 14 years, and the course of disease extended over a period from 5 to 90 months. All of the patients received conventional therapy for 3 to 87 months. After their discharge from the hospital, the patients continued to maintain their regular follow-up visits and basic quality of life. The patients exhibited decreased immune function after the auto-PBHSCT. The CD4+ and CD19+ cells were significantly reduced. Viremia occurred in four patients 2 months after the transplantation. All of the patients went into clinical remission in 3-6 months. The severity of encephalopathy, nephritis and organ damage declined in varying degrees. The disease recurred in patient 2 at 9 months and in patient 4 at 12 months after the transplantation. Because the disease was relatively mild, we were able to administer small doses of glucocorticoids that were sufficient to control the course of the disease. Macrophage activation syndrome occurred in patient 3 at 18 months after the transplantation. At the end of the follow-up period, three of the five patients were completely off their medications. Another two patients sustained small doses of glucocorticoids. The developmental levels of these patients were comparable to those of normal children at the end of the follow-up. The quality of life improved significantly. The auto-PBHSCT is effective for severe and refractory paediatric SLE. The incidence of lethal infection and other adverse reactions is low. Long-term remission can be achieved. A milder form of the disease may have recurred after the transplantation.
Di-(2-ethylhexyl) phthalate (DEHP), is known to impair testicular functions and reproduction. However, its effects on immature testis Blood-testis barrier (BTB) and the underlying mechanisms remain obscure. We constructed a rat model to investigate the roles of autophagy in BTB toxicity induced by DEHP. Sprague–Dawley rats were developmentally exposed to 0, 250 and 500 mg/kg DEHP via intragastric administration from postnatal day (PND) 1 to PND 35. Testicular morphology, expressions of BTB junction proteins and autophagy related proteins were detected. In addition, expressions of oxidative stress markers were also analyzed. Our results demonstrated that developmental DEHP exposure induced decreasing organ coefficients of immature testes and severe testicular damage in histomorphology. The expressions of junctional proteins were down-regulated significantly after DEHP treatment. Intriguingly, DEHP simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation. Moreover, the expressions of HO-1 and SOD levels remarkably decreased after DEHP exposure. Vitamins E and C could alleviate the DEHP-induced oxidative stress, reverse the autophagy defect and restore the BTB impairment. Taken together, DEHP exposure destroys immature testis blood-testis barrier (BTB) integrity through excessive ROS-mediated autophagy.
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