1.Long term toxicity of vinorelbine tartrate on immune and hematopoietic systems in rats
Tianxian PEI ; Hingjing WANG ; Hinying TENG ; Chuanmin GUO ; Guangshen GAO ; Dong YANG ; Xucong GAO ; Xiuping SHEN ; Zongpeng ZHANG
Chinese Journal of Pharmacology and Toxicology 2014;(4):562-568
OBJECTlVE To study the Iong term toxicity of vinoreIbine tartrate(NVB)on rat immune and hematopoietic systems pathoIogicaIIy. METHODS SD Rats were randomIy divided into 4 groups:normaI controI group and NVB 5.0,10.0,and 20.0 mg·m-2 groups,each group containing 6 maIe and femaIe rats. The rats in NBV groups were administered different concentrations of NVB by intravenous drip on the 1st and 8th days,21 da cycIe,for 4 cycIes. On the 14th day after the Iast administration, white bIood ceIIs(WBC),neutrophiI(Neut),Iymphocytes(Lym),red bIood ceIIs(RBC)and reticuIo-cyte‰(RET‰)were detected by ADVIA2120 hematoIogy anaIyzer. Thymus,sternum marrow,spIeen and mesenteric Iymph nodes were observed by histopathoIogicaI examination. The thymus and spIeen were preciseIy weighed to obtain the reIative organ coefficients. Bone marrow smears were made for counting and cIassification. RESULTS Compared with normaI controI group,WBC,Neut,Lym,RBC and RET% of peripheraI bIood of NVB 5,10 and 20 mg·m-2 groups were decreased(P﹤0.05,P﹤0.01). The Neut vaIue of maIe rats was(2.35±0.56)×109·L-1 in normaI controI group,but was reduced to (1.66±0.44),(0.67±0.22)and(0.20±0.02)×109·L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The Neut vaIue of femaIe rats was(1.26± 0.27)× 109 L-1 in normaI controI group,but was reduced to(1.14±0.56),(0.47±0.13)and(0.21±0.08)×109 L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The resuIts of counting and cIassification of bone marrow smears showed that the myeIoid ceII ratio decreased(P﹤0.05,P﹤0.01). The myeIoid ceII ratio of maIe rats was(42.7±6.1)% in normaI controI group,but was reduced to(28.8±5.3)%,(22.0±3.2)% and(18.9±3.9)% in NVB 5,10 and 20 mg·m-2 groups. The myeIoid ceII ratio of femaIe rats in normaI controI group was(35.4±3.0)%, but was reduced to(31.2±4.7)%,(22.9±6.7)% and(20.8±4.2)% in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient was reduced(P﹤0.05,P﹤0.01). The thymus coefficient of maIe rats in normaI controI group was 0.36±0.04,but was reduced to 0.31±0.06,0.18±0.03 and 0.08±0.01 in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient of femaIe rats in normaI controI group was 0.29±0.06,but was reduced to 0.25±0.06,0.19±0.06 and 0.07±0.01 in NVB 5,10 and 20 mg·m-2 groups. Histopatho-IogicaI examination showed that thymus was atrophiedand bone marrow was suppressed. SpIeen com-pensatory extrameduIIary hematopoietic ceIIs were increased in NVB 5.0,10.0 and 20.0 mg·m-2 groups (maIe and femaIe)to different degrees,but the mesenteric Iymph nodes of NVB groups showed no sig-nificant pathoIogicaI changes. CONCLUSlON NVB has immune and hematopoietic toxicity on SD rats, as is showed by thymic atrophy and bone marrow suppression.
2.Study of hippocampal subregion in patients with temporal lobe epilepsy by neurite orientation dispersion and density imaging
Wenrui YANG ; Xucong WANG ; Jian LI ; Mengnan YAN ; Jinqin LI ; Yanling ZHANG ; Bing CHEN
Journal of Practical Radiology 2024;40(9):1403-1407
Objective To explore the hippocampal(HC)microstructural changes in patients with unilateral temporal lobe epilepsy(TLE)by neurite orientation dispersion and density imaging(NODDI).Methods The NODDI indexes of the whole HC and HC subregions of temporal lobe epilepsy with hippocampal sclerosis(TLE-HS)patients,non-HS patients and healthy controls(control group)were calculated.The differences of NODDI indexes among and within the three groups were compared,and the correlation between the difference indexes and the clinical characteristics of the patients was analyzed.Results A total of 47 patients with TLE(27 cases of TLE-HS,20 cases of non-HS)and 22 cases of healthy controls were enrolled.In the TLE-HS group,the free-water isotropic vol-ume fraction(fiso)values of the HC and granular cell layer of dentate gyrus(GC-DG)subregions of the affected side were signifi-cantly higher than those of the contralateral side;the orientation dispersion index(ODI)values of the CA1 and CA4 subregions were significantly lower than those of the contralateral side;and the neurite density index(NDI)values of the HC,CA1,CA2-3,CA4 and GC-DG subregions of the affected side decreased significantly.There was no significant difference between the affected side and the contralateral side in the non-HS group.The fiso values of the HC and GC-DG subregions of the affected side in the TLE-HS group were significantly higher than those in the control group,the ODI values of the HC CA1 subregions of the affected side in the TLE-HS group were significantly lower than those in the control group and the non-HS group,the NDI values of the HC and subiculum(Sub),CA1,CA4 and GC-DG subregions of the affected side in the TLE-HS group were significantly lower than those in the con-trol group,and the NDI values of the HC and CA1,CA4 and GC-DG subregions of the affected side in the non-HS group were significantly lower than those in the control group.In the TLE-HS group,the NDI value of the HC CA4 subregion of the affected side was negatively correlated with the disease course,but there was no clear correlation between other subregion variables and disease course,onset frequency and duration of single onset.Conclusion NODDI technique has the ability to detect the microstructural changes of HC in patients with TLE,among which NDI is more likely to highlight neuronal damage and fiber reorganization in patients with TLE.
3.Automatic segmentation technique combined with neurite orientation dispersion and density imaging for observing volume and microstructure changes of hippocampal subregion in patients with hippocampal sclerosis medial temporal lobe epilepsy
Wenrui YANG ; Xucong WANG ; Jian LI ; Mengnan YAN ; Jinqin LI ; Yanling ZHANG ; Bing CHEN
Chinese Journal of Medical Imaging Technology 2024;40(6):838-842
Objective To explore the value of automatic segmentation technique combined with neurite dispersion and density imaging(NODDI)for displaying volume and microstructure changes of hippocampal subregion in patients with hippocampal sclerosis medial temporal lobe epilepsy(mTLE-HS).Methods MRI data of 33 patients with left mTLE-HS(mTLE-HS group)and 35 healthy adults(control group)were retrospectively analyzed.The hippocampal subregions were automatically segmented using FreeSurfer software,the volume of cornu Ammonis(CA)1,CA2-3,CA4,granulose cell-dentate gyrus(GC-DG)and subiculum were measured,then the NODDI parameters of each subregion were obtained through post-processing.The intra-and inter-groups hippocampal subregion volumes and NODDI parameters were compared,and the correlations of parameters being significantly different with the onset age and disease courses were analyzed.Results The volume of hippocampal subregions in mTLE-HS group were all lower than those in control group(all P<0.05).In mTLE-HS group,the neurite density index(NDI)of left CA1 and CA4 subregions were both lower,while the free-water isotropic volume fraction(fiso)of the left CA1 subregion was higher than those of the right side(all P<0.05).The orientation dispersion index(ODI)of left CA1,CA2-3 and CA4 subregions,as well as NDI of left CA1,CA4 and GC-DG subregions in mTLE-HS group were all lower than those in control group(all P<0.05),while fiso of left CA1,GC-DG and subiculum subregions in mTLE-HS group were all higher than those in control group(all P<0.05).The volume of left hippocampal subregions in patients with mTLE-HS were all moderately positively correlated with the onset age(r=0.540-0.667,all P<0.001)but weakly negatively correlated with disease courses(r=-0.492--0.386,all P<0.05).NDI of left CA4 and GC-DG subregions in patients with mTLE-HS were both weakly negatively correlated with disease courses(r=-0.418,-0.388,both P<0.05).Conclusion Automatic segmentation technique combined with NODDI could be used to display the volume and microstructure changes of mTLE-HS.NDI might be a biomarker of mTLE-HS being sensitive to progressive neuronal damage.