ABSTRACT
Parkinson's disease (PD) is a common neurodegenerative disorder associated with aging.Recent studies in animal models of PD and analyses of brain specimen from PD patients revealed an increase in the level and activity of the non-receptor tyrosine kinase Abelson (c-Abl) in dopaminergic neurons with phosphorylation of protein substrates,such as a-synuclein and the E3 ubiquitin ligase, Parkin.Most significantly inhibition of c-Abl kinase activity by small molecular compounds used in the clinic to treat human leukemia has shown promising neuroprotective effects in cell and animal models of PD.This has raised hope that similar beneficial outcome may also be observed in the treatment of PD patients by using c-Abl inhibitors.Here we highlight the background for the current optimism, reviewing c-Abl and its relationship to pathophysiological pathways prevailing in PD, as well as discussing issues related to the pharmacology and safety of current c-Abl inhibitors.Clearly more rigorously controlled and well-designed trials are needed before the c-Abl inhibitors can be used in the neuroclinic to possibly benefit an increasing number of PD patients.
ABSTRACT
Objective To study the apllication value of cerebraspinal fluid minimal residual leukemia cells(MRLCs) combined with lactate dehydrogenase(LDH) detection in early diagnosis of central nervous system leukemia(CNSL) to provide a laboratory basis for clinical diagnosis and evaluation of disease progression and therapeutic effect.Methods Thirty inpatiernts without blood disease and central nervous system(CNS) organic diseases,and normal CSF routine and detected biochemical indexes were selected as the control group and 96 cases of acute leukemia (AL) diagnosed by bone marrow puncture FAB morphology and flow cytometry typing served as the disease group.Flow cytometry was used to detect the MRLCs in CSF,the activity of LDH in CSF was detected by the rate method,and the detection results were performed the comparative analysis.Results Among 96 cases of AL,30 patients with CNSL had 13 cases of positive MRLCs in CSF,the positive rate was 43.33%,among 66 cases of non-MRLCs,MRLCs was not detected detected.Among 96 cases of AL,CSF LDH level in 30 cases of CNSL was (30.54±10.29)U/L,which was significantly higher (16.16±7.12)U/L in the patients without CNSL,the difference between the two groups was statistically significant (P<0.05).Conclusion The detection of MRLCs and LDH in CSF of AL can be used as a laboratory diagnostic index for early diagnosis of CNSL,and MRLCs combined with LDH detection can improve the positive diagnosis rate of CNSL.
ABSTRACT
Objective To study the apoptosis of human leukemia K562 cells induced by snake venom of Agkistrodon Halys Pallas in Zhejiang Province.Methods IC_ 50 value and cytotoxity of K562 cell were detected by MTT method.Apoptotic cells were dyed by Hoechest 33258.Sub-G1 peak and cell cycle were detected by FCM.Protein expression of Bcl-2 gene was detected by FCM and western-blot method.Results The snake venom of Agkistrodon Halys Pallas in Zhejiang Province inhibited the growth of K562 cells,which appeared dose-dependent.The snake venom induced apoptosis of K562 cells.Meanwhile,protein expression of Bcl-2 was down-regulated.Conclusion Snake venom of Agkistrodon Halys Pallas in Zhejiang could induce apoptosis of human leukemia K562 cells.The mechanism may be related to down-regulation of Bcl-2 gene expression.