Background and purpose: Arsenicals have been used medicinally for decades to treat both infectious disease and cancer. Arsenic trioxide (As 2 O 3 ) is effective for treatment of acute promyelocytic leukaemia (APL), yet the mechanism of action of this drug is still widely debated. Recently, As 2 O 3 was shown to inhibit the activity of the selenoenzyme thioredoxin reductase (TrxR). TrxR has been proposed to be required for selenium metabolism. The effect of inhibitors of TrxR on selenium metabolism has yet to be assessed. This study aims to determine whether chemotherapeutics that target selenocysteine within selenoenzymes may also affect the metabolism of selenium. Experimental approach: A lung cell line, A549, was used to assess the effect of TrxR inhibitors on selenium metabolism, using 75 Se-selenite. The level of mRNA encoding cytosolic TrxR (TrxR1) was determined using real-time reverse transcriptase-PCR. TrxR activity was determined in whole-cell extracts. Key results: Exposure of cells to As 2 O 3 , arsenite or auranofin led to a concentration-dependent reduction of selenium metabolism into selenoproteins. Knockdown of TrxR1, using small inhibitory RNA, did not affect selenium metabolism. Exposure of cells to monomethylarsonic acid, a potent inhibitor of TrxR, did not alter selenium metabolism but did inhibit enzyme activity. Conclusions and implications: As 2 O 3 and auranofin block the metabolism of selenium in A549 cells. Because As 2 O 3 is used to treat APL, our findings may reveal the mechanism of this therapeutic action and lead to further research targeting selenium metabolism to find novel chemotherapeutic agents for the treatment of APL.
These data suggest that CF growth deficiency has prenatal origins. Early nutritional intervention for babies with CF and a low birth weight is warranted to maximize pulmonary potential.
Hepatitis C virus (HCV) has been associated with various lymphoproliferative disorders, and a high prevalence (9%-32%) of chronic HCV infection has been demonstrated among patients with lymphoma. Dual coinfection by HIV and HCV has been demonstrated in approximately 40% of certain populations of HIV-infected individuals. Because of this high prevalence of coinfection by HIV and HCV, the known relations between HCV and lymphoproliferative disorders, and the association of HIV and B cell lymphoma, the potential association between chronic HCV and the development of AIDS-related lymphoma was examined. The prevalence of HCV infection in HIV-infected patients with lymphoma was compared with that in patients with AIDS, diagnosed on the basis of an illness other than lymphoma. Risk factors for HCV infection, overall, were also evaluated. Evidence of HCV infection was ascertained by assessing anti-HCV antibodies, and HCV RNA in serum. The study consisted of 99 homosexual/bisexual men with AIDS-related lymphoma, and 43 other AIDS patients. HCV infection was detected in 11 of 99 (11.1 %) men with lymphoma, and in 5 of 43 (11.6%) other AIDS patients. Further, in patients with AIDS-related lymphoma, no relation was found between HCV infection and lymphoma histology or site. History of use of injected illicit drugs was associated with a significantly elevated risk of HCV infection in the combined group of lymphoma and other AIDS patients. The current study demonstrates no relation between dual infection by HIV and HCV and subsequent increased risk of lymphoma.
We hypothesised that consumption of flavanol-containing apple puree would modulate platelet activity and increase nitric oxide metabolite status, and that high flavanol apple puree would exert a greater effect than low flavanol apple puree. 25 subjects consumed 230 g of apple puree containing 25 and 100mg epicatechin (low and high flavanol apple puree, respectively) and aspirin (75 mg) in random order. Measurements were made at baseline, acutely after treatment (2, 6 and 24 h), and after 14 d of treatment. Low flavanol apple puree significantly attenuated ADP and epinephrine-induced integrin-β3 expression 2 h and 6 h after consumption and ADP and epinephrine-induced P-selectin expression within 2h of consumption. High flavanol apple puree attenuated epinephrine and ADP-induced integrin-β3 expression after 2 and 6h. ADP and epinephrine-induced integrin-β3 expression was significantly attenuated 2, 6 and 24 h after consumption of aspirin, whilst 14 d aspirin consumption attenuated collagen-induced P-selectin expression only. The plasma total nitric oxide metabolite conc. was significantly increased 6h after consumption of both low and high flavanol apple purees. In conclusion, consumption of apple purees containing ⩾25 or 100 mg flavanols transiently attenuated ex vivo integrin-β3 and P-selectin expression and increased plasma nitric oxide metabolite conc. in healthy subjects, but the effect was not enhanced for the high flavanol apple puree.
(-)Deprenyl, a specific monoamine oxidase subtype B inhibitor (MAOI-B), has been reported to be a safe and valuable adjunct to conventional treatment of parkinsonism. A double-blind, clinical comparison of (-)deprenyl with placebo was undertaken in 11 parkinsonian patients; the efficacy of 10 mg daily was studied over 4 weeks. In four cases the clinical score for parkinsonian deficits improved during deprenyl therapy, and in five it deteriorated; there was no change in one patient. Two subjects failed to complete the study. (-)Deprenyl induced euphoria and insomnia. It was concluded that any advantages deriving from the use of (-)deprenyl in parkinsonism are limited, and probably dominated by its elevation of mood. Biochemical analysis failed to reveal any significant increase in platelet or plasma catecholamine concentrations during deprenyl therapy. There was, however, a significant decrease in plasma epinephrine (p < 0.05) and platelet MAO activity (p < 0.005).
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