Objective: Polygoni Multiflori Radix (PM) is a traditional herbal medicine with repeated reports of liver injury events in recent years. We wondered whether the classical processing method, namely, nine-time steaming and sun drying (NSSD), had toxicity-attenuating effects on PM and the relationships between toxicity and times of processing, as well as with the alteration trends of its compounds. Materials and Methods: The chemical fingerprints of different PM extracts were developed using ultra-high-performance liquid chromatography. The spectrum-toxicity correlation between the chemical fingerprints and hepatocellular toxicity was analyzed with multiple correlation analysis. Results: The results suggested that the hepatotoxicity of NSSD processing products markedly decreased with the repeated steaming and sun drying, which was obviously superior to the product processed by the modern method. Comprehensive analysis revealed that the contents of cis-stilbene glycoside and emodin-8-O-β-D-glucoside related to liver injury susceptibility were reduced with the times of NSSD processing, which was consistent with the decreased trend of hepatocellular toxicity. After the five times of NSSD, the contents of them as well as the hepatotoxicity of PM were steady. Moreover, we found that the contents of catechin and physcion declined rapidly after the one time of NSSD and then remained stable until the nine times of NSSD. Based on the fact, they could be utilized to indicate whether PM products were processed by steaming and sun drying. Conclusions: This paper confirmed that the NSSD had a good influence on the toxicity attenuating to PM and found four compounds which could apply for the quality control of PM. 相似文献
BackgroundImproved survivorship in patients with breast cancer means many are currently living with the late effects of radiotherapy, particularly fibrosis. Personalized treatment is not currently considered for patients with breast cancer. Radiation-induced lymphocyte apoptosis (RILA), a predictive assay, could offer a novel approach in predicting patients at a higher risk of developing this late toxicity and therefore improving informed decision-making.Materials and MethodsA systematic search of PubMed and Embase was performed and eight clinical trials were identified that investigate RILA as a predictor of late breast fibrosis after radiotherapy.ResultsMedian RILA scores were lower in patients who experienced ≥ grade 2 fibrosis than in patients who experienced ≥ grade 1. A clear inverse relationship between RILA scores and late toxicity was reported in the literature; however, there were several other confounding factors involved in the development of fibrosis. CD8 lymphocytes were reported to have superior sensitivity and specificity over CD4 lymphocytes.ConclusionRILA was reported to be an effective biomarker in predicting fibrosis in breast cancer but other factors also need to be considered before clinical implementation. 相似文献
Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.
Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.
Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk. 相似文献
BackgroundMidostaurin, a multikinase inhibitor, is approved for treatment of FLT3-mutant acute myeloid leukemia (AML). A phase I study established that midostaurin 75 mg orally twice daily for 14 days with standard dose azacitidine was safe and tolerable in elderly patients with AML. Herein, we report the phase II expansion cohort of previously untreated elderly or unfit patients with AML.Patients and MethodsPrimary objectives were to further describe the toxicity profile and determine the response rate in untreated patients with AML. Patients received midostaurin 75 mg orally twice daily on days 8 to 21 in combination with intravenous azacitidine at 75 mg/m2 on days 1 to 7. Plasma inhibitory activity assay for FLT3 was performed pretreatment and on day 8 and day 15 of each cycle.ResultsTwenty-six patients (median age, 74 years; range, 59-85 years) with FLT3 wild-type AML were accrued. Patients received a median of 2 cycles of therapy (range, 1-10 cycles). Seven (29%) of 24 evaluable patients achieved a clinical response (4 complete response; 1 complete response with incomplete count recovery; and 2 partial response). The median overall survival was 244 days (95% confidence interval, 203-467 days). Hematologic, infectious, and gastrointestinal toxicities were comparable to similar studies. Peripheral blood FLT3 wild-type phosphorylation declined to 8% to 55% of pretreatment by day 15 of cycle 1 (7 patients) and declined with subsequent cycles (< 10% baseline) in 2 patients who were analyzed after cycle 3.ConclusionMultiple cycles of azacitidine and midostaurin were not well-tolerated, but persistent inhibition of FLT3 wild-type phosphorylation suggest intermittent dosing of midostaurin should be considered in future low-intensity regimens for FLT3-mutant AML. 相似文献