Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
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Question: Context: Side effects of mitotane (o,p'-DDD) have suggested estrogenic effects.", "The objective of the study was to explore o,p'-DDD potential estrogenic effect on SHBG and corticosteroid-binding globulin (CBG).", 'Human hepatoma cell lines (HepG2), lacking estrogen receptor (ER)-alpha, and Hep89, stably transfected by ERalpha, were used.', 'The study was conducted at an academic research laboratory and medical center.', 'The study included 10 male patients with recurrent adrenal carcinoma, receiving mitotane (4-6.5 g daily) for more than 6 months.', 'The main outcome measures were SHBG/CBG mRNA levels measured by real-time PCR, culture medium SHBG/CBG concentrations measured by specific immunoassays, and transient transfection experiments with human SHBG proximal promoter reporter constructs.', "Increased serum SHBG and CBG concentrations, which exceeded normal male limits, were observed in most mitotane-treated patients. In the HepG2 cell line, 17beta-estradiol (E2) or o,p'-DDD treatment had no effect on mRNA or SHBG/CBG concentrations. In contrast, in the Hep89 cell line, E2 increased concentrations of SHBG (r = 0.44, P < 0.0001) and CBG (r = 0.585, P < 0.0001) secreted into culture media in a dose-dependent manner. o,p'-DDD significantly increased SHBG (150% vs. control, P < 0.05) and CBG (184% vs. control, P < 0.05) production by Hep89 cells, at a concentration of 2 x 10(-5) m. Transient transfection experiments in Hep89 cells showed that E2 or o,p'-DDD treatment did not increase the transcriptional activity of the minimal proximal promoter of human SHBG gene.
Answer: Mitotane increased SHBG/CBG gene expression and liver production by mechanisms requiring the presence of ERalpha.

Answer: Does mitotane have an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans?


Question: Context: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8\xa0wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention.', 'Volunteers were supplemented daily with 36\xa0mg/kg body weight (BW) of GAA for the first 4\xa0wk of the intervention; afterward GAA dosage was titrated ≤60\xa0mg/kg BW of GAA daily. At baseline, 4, and 8\xa0wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity.', 'Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4\xa0wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P\xa0<\xa00.05). Thalamus creatine levels decreased after 4\xa0wk for 6.5% (P\xa0=\xa00.02), and increased nonsignificantly after 8\xa0wk for 8% (P\xa0=\xa00.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P\xa0<\xa00.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention.
Answer: Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease.

Answer: Does dietary guanidinoacetic acid increase brain creatine levels in healthy men?


Question: Context: Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America.', 'BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10(8.5+/-0.7) in control untreated animals to 10(5.0+/-0.0) in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10(15.5+/-0.5) parasites were quantified from untreated animals, as opposed to 10(5.1+/-0.1) parasites detected in treated mice.
Answer: Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis.

Answer:
Is tamoxifen effective in the treatment of Leishmania amazonensis infections in mice?