The protective effect of Dexrazoxane on onco-Cardiology induced by anticancer agents other than anthracyclines / 中国药理学通报

Aim To evaluate the protective effect of Dexrazoxane(Dex)on onco-Cardiology caused by chemotherapeutic drugs other than anthracycline antitumor drugs using zebrafish embryos, including:cisplatin, paclitaxel, vincristine sulfate, 5-fluorouracil and cyclophosphamide. Methods Zebrafish embryos at 24 hpf(hours post-fertilization)were exposed to different concentrations of drugs. The survival rate and the overall animal morphology at 48 hpf, 72 hpf and 96 hpf were observed with a microscope. Heart rate, ventricular contraction fraction, ventricular volume, and cardiac output were measured and calculated by video recordings made with a VCD system. The protective effect of Dex was evaluated using the established model of onco-Cardiology induced by anti-tumor drugs other than anthracyclines. Results In terms of acute toxicity, cisplatin, vincristine sulfate, 5-fluorouracil and cyclophosphamide all significantly reduced the survival rate of zebrafish embryos. The LC50 value was 437.655, 25.538, 65.606 and 19.021 mmol·L-1, respectively. In addition to paclitaxel, the other four anti-tumor drugs all showed significant changes in overall animal morphology and cardiac function indicators. In the study of the protective effect of Dex on four kinds of tumor heart diseases except anthracyclines, only cisplatin had a significant protective effect, which could improve the cardiotoxicity caused by cisplatin. The optimal concentration of Dex was 80 μmol·L-1. Conclusions Zebrafish models of drug toxicity caused by cisplatin, vincristine sulfate, 5-fluorouracil, and cyclophosphamide is established, which proves that Dex only has a protective effect on the toxicity caused by cisplatin.

Oxidative Stress Status and Its Effect on Regulation of Hepcidin in Patients with HbHCS / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the oxidative stress status and its effects on hepcidin in patients with hemoglobin H Constant Spring disease (HbH-CS).</p><p><b>METHODS</b>A total of 35 patients were enrolled in the study, including 15 splenectomized cases and 20 non-splenectomized cases. 20 healthy volunteers were selected as controls. Serum superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) levels, erythropoietin (EPO), serum free transferrin receptor (sFTR), growth differentiation factor 15 (GDF15) as well as the level of hepcidin were detected. Correlation analysis and multiple factor regression analysis were performed to investigate the factors affecting the iron metabolism and erythropoiesis.</p><p><b>RESULTS</b>Compared with healthy control, the SOD and GSH levels in patients with HbHCS decreased, while MDA and GSSG levels increased. The levels of SOD, MDA, GSG and GSSG were not significantly different between the patients with splenectomy and those without splenectomy. Correlation analysis showed that inpatients with HbHCS, EPO, sFTR and GDF15 correlated negatively with SOD level and positively with MDA level. EPO and sFTR levels negatively correlated with Hepcidin.</p><p><b>CONCLUSION</b>Excessive oxidative stress is present in patients with HbHCS, and hepcidin is inhibited by the upregulation of EPO and sFTR, and hence involved in iron overload in patients.</p>

Lower functional connectivity of default mode network in cognitively normal young adults with mutation of APP, presenilins and APOE ε4.

In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) ε4 on the default-mode network (DMN) in cognitively intact young adults (24.1 ± 2.5 years). Both the APP or presenilin-1/2 group and the APOE ε4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE ε4 < APP or presenilin-1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE ε4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE ε4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage.

Abnormal Intrinsic Brain Activity Patterns in Patients with End-Stage Renal Disease Undergoing Peritoneal Dialysis: A Resting-State Functional MR Imaging Study.

PURPOSE: To analyze the spontaneous brain activity patterns in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) by using resting-state functional magnetic resonance (MR) imaging with an amplitude of low-frequency fluctuations (ALFF) algorithm. MATERIALS AND METHODS: This study received institutional review board approval, and all subjects gave informed consent. Forty-four patients with ESRD, 24 of whom were undergoing PD (PD group; eight women; mean age, 34 years ± 8) and 20 who were not undergoing PD or hemodialysis (nondialysis group; six women; mean age, 37 years ± 9) and 24 healthy control subjects (eight women; mean age, 32 years ± 9 years) were included. All subjects underwent neuropsychologic tests, and patients with ESRD underwent laboratory testing. ALFF values were compared among the three groups. The relationship between ALFF values and clinical markers was investigated by using multiple regression analysis. RESULTS: Patients in both the PD and nondialysis groups showed lower ALFF values in default mode network regions than did healthy control subjects (P < .01, false discovery rate corrected). Patients in the PD group showed lower ALFF values than did those in the nondialysis group in the left superior parietal lobe (1.51 ± 0.21 vs 2.01 ± 0.40), left inferior parietal lobe (0.99 ± 0.16 vs 1.13 ± 0.22) and left precuneus (1.45 ± 0.39 vs 1.77 ± 0.41) (P < .01, corrected with simulation software). In patients in the PD group, neuropsychologic test scores correlated with ALFF values of the middle temporal gyrus and the parietal and occipital lobe, serum urea and creatinine levels negatively correlated with ALFF in some default mode network regions, and hemoglobin positively correlated with ALFF in the bilateral precuneus, precentral, and supplementary motor areas (P < .01 corrected). CONCLUSION: Patients with ESRD who were undergoing PD showed more severe spontaneous brain activity abnormalities that correlate with cognitive impairments than did patients who were not undergoing dialysis. Elevated serum urea, creatinine, and lowered hemoglobin levels affect spontaneous brain activity in patients with ESRD.

Diffuse interstitial brain edema in patients with end-stage renal disease undergoing hemodialysis: a tract-based spatial statistics study.

To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P<0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P<0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P>0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes.

Transjugular intrahepatic portosystemic shunt induced short- and long-term cerebral blood flow variations in cirrhotic patients: an arterial spin labeling MRI study.

Short- and long-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on cerebral blood flow (CBF) in patients with cirrhosis are still unclear. The purpose of this longitudinal study was to explore CBF alteration patterns in cirrhotic patients after TIPS. Thirteen cirrhotic patients (7 male, 6 female, mean age 50.0 ± 9.3 years) underwent arterial-spin labeling (ASL) MRI 1-9 days (median 1 days) before TIPS. Follow-up MR examinations were performed about 1 week (median 6 days), 3 months (n = 6), 6-9 months (n = 5) and 12-18 months (n = 5) after TIPS. CBF, ammonia level, Child-Pugh score, number connection test type A (NCT-A) and digit symbol test (DST) scores were converted into relative values by dividing by his/her pre-TIPS values, and then, compared via one-way analysis of variance (ANOVA). Correlations between the pre- and post-TIPS changes of relative CBF (rCBF) and the changes of relative ammonia (rAmmonia), Child-Pugh (rChild-Pugh), and NCT-A/DST (rNCT-A/rDST) scores were calculated by crossing subjects. Compared with the pre-TIPS level, the global rCBF slightly increased by 10.9 % about 1 week later, then rapidly decreased by 14.2 % 3 months later, and flatly decreased by 17.2 % in 6-9 months and 18.0 % in 12-18 months following TIPS. The changes of 3-month rDST score were slightly correlated with 3-month rCBF rather than 1-week rCBF, (P < 0.1, FDR-corrected) No difference was found between the pre- and post-TIPS rAmmonia levels, rChild-Pugh and rNCT-A/rDST scores (Post-hoc P > 0.05). CBF measured at different time points after TIPS insertion showed different patterns, indicating varying longitudinal effects of TIPS on CBF. A sharp decline of rCBF was found in the 1 week to 3 months period after insertion, indicating that high event rate of hepatic encephalopathy might relate with the unadaptable CBF in patients undergoing TIPS insertion.

Changes in cerebral blood flow after transjugular intrahepatic portosystemic shunt can help predict the development of hepatic encephalopathy: an arterial spin labeling MR study.

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) changes after transjugular intrahepatic portosystemic shunt (TIPS) are still unclear. Our aim is to assess the TIPS-induced CBF changes and their potential clinical significance using the arterial spin labeling (ASL) perfusion magnetic resonance imaging. MATERIALS AND METHODS: Nine cirrhotic patients underwent ASL 1-8 days before and 4-7 days after TIPS. CBF was calculated at each voxel and mean CBF values were computed in the whole brain, gray matter and white matter. Changes of CBFs before and after TIPS were compared by paired t-test. RESULTS: Voxel-wise results showed CBF diffusely increased in patients after TIPS, but no region with significant decrease in CBF was found, nor was any significant mean CBF difference detected in the whole brain, gray matter and white matter. Six patients out of nine showed a global CBF increase of 9-39%; one patient presented a global CBF decrease of 6%; another two showed a global CBF decrease of 16% and 31% respectively. Follow-up studies showed that the two patients with greatly decreased global CBF suffered from multiple episodes of overt hepatic encephalopathy (OHE) after TIPS and one died of OHE. CONCLUSIONS: CBF derived from noninvasive ASL MRI could be used as a useful biomarker to predict the development of OHE through consecutively tracking CBF changes in patients with inserted TIPS. Increased CBFs in many cortical regions could be common effects of the TIPS procedure, while decreased global CBF following TIPS might indicate the development of OHE.