ABSTRACT
Multiple sclerosis(MS)is a systemic inflammatory illness of the central nervous system that involves demyelinating lesions in the myelin-rich white matter and pathology in the grey matter.Despite signifi-cant advancements in drug research for MS,the dis-ease's complex pathophysiology makes it difficult to treat the progressive forms of the disease.In this study,we identified a natural flavonoid compound icariin(ICA)as a potent effective agent for MS in ameliorating the deterioration of symptoms including the neurological defi-cit score and the body weight in a murine experimental autoimmune encephalomyelitis(EAE)model.These improvements were associated with decreased demyelin-ation in the corpus callosum and neuron loss in the hippo-campus and cortex confirmed by immunohistochemistry analysis.Meanwhile,it was observed that the activation of microglia in cerebral cortex and hippocampus were inhibited followed by the neuroinflammatory cytokines downregulation such as IL-1β,IL-6 and TNF-α after ICA treatment,which was probably attributable to the sup-pression of microglial NLRP3 inflammasome activation.Additionally,molecular docking also revealed the binding force of ICA to NLRP3 inflammasome protein complexes in vitro.Taken together,our findings have demonstrated that ICA,as pleiotropic agent,prevents EAE-induced MS by improving demyelination and neuron loss,which inter-feres with the neuroinflammation via microglial NLRP3 inflammasome activation.
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AIM: To evaluate the pharmacokinetics and bioequivalence of cetirizine hydrochloride tablets under fasting and fed conditions in Chinese healthy subjects. METHODS: This was a randomized, open-label, double-sequence, two-period, crossover designed study, and healthy subjects enrolled and administrated a single dose of 10 mg test and reference cetirizine hydrochloride tablets in each period under fasting or fed condition. The plasma concentrations of cetirizine were determined by a validated LC-MS/MS method. The pharmacokinetic parameters were calculated with WinNonlin 6.3 and the bioequivalence was evaluated through SAS 9.4 software. RESULTS: In the fasting condition, the major pharmacokinetic parameters of cetirizine of test and reference formulations were as follows, C
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OBJECTIVE： To put forward the suggestions for improving drug management in clinical drug trials in China. METHODS： “Good clinical practice” “Clinical trials drug” “Drugs for clinical trials” “GCP” “Investigational drug products” as search terms， searching CNKI database， Wanfang database， PubMed database and OVID electronic journal full-text database during Jul. 2014-Jul. 2018. The differences of drug management guidelines and management systems （including management model， staffing and budget evaluation） in clinical drugs between China and the United States were summarized. The suggestions were put forward to the shortage of drugs management of clinical trials in China. RESULTS & CONCLUSIONS： A total of 154 literatures were retrieved， including 33 valid literatures. The guidelines for drug management in clinical trials in the United States were relatively perfect， such as the Guidelines for Drug Management in Clinical Trials promulgated by the American Society of Hospital Pharmacists， while China had not yet published such national guidelines. The drug management in clinical trials in the United States had two modes which is the management of part-time pharmacists in hospital pharmacy department and the management of several full-time pharmacists and pharmacy technicians. Pharmacists or pharmaceutical technicians participated in the whole process of management， and a lot of research was carried out on the budget evaluation of clinical trials drug management. Domestic clinical trials drug management included three modes which is full-time pharmacist management， full-time pharmacist and part-time nurse management， part-time pharmacist and part-time nurse management. Pharmacists and nurses jointly participated in the management， but the whole process management had not yet been achieved， and there were few studies on budget evaluation of clinical trials drug management. It is suggested that the management of clinical trials drug in China can improve the management efficiency and level of clinical trials drug by refining the management system of clinical trials drug， standardizing the management mode of clinical trials drug and carrying out management budget evaluation.
ABSTRACT
Objective: To investigate the variation of γδ T cells from healthy human peripheral blood(PB)and neonatus cord blood (CB)in proliferation and subtypes with isopentenyl pyrophosphate(IPP), and to acquire enough γδ T cells possessing distinct characteristics for experimental study.Methods: Mononuclear-cells from peripheral blood and cord blood induced by IPP were stained separately with monoclonal antibodies,which were fluorescein-labeled,and then used for assaying the expressing condition of surfaco molecules,as well as to evaluate the variation of γδ T cells on the percentage, subtypes and pbenotypes by FCM.Results:γδ T cells only account for a small proportion in both PB and CB.However,there was a significant difference in the heterogeneity between peripheral blood and cord blood γδ T cells.Vγ9Vδ2 T cells were dominant in peripheral blood γδ T cells.Most of Vγ9Vδ2 T cells in fresh isolated PBMC were central memory-type(CD27~+ CD45RA~-)and effector memory-type(CD27~-CD45RA~-)with IPP, PB γδ T cells proliferated strongly;The effector memory-typo(CD27~-CD45RA~-)turned into the main subtype in all Vγ9Vδ2 T cells,and HLA-DR and B7 molecules were highly expressed on the populations.But the cord blood γδ T cells showed rather complex subgroup heterogeneity,and Vγ9Vδ2 T cells were almost na(i)ve-type(CD27~+ CD45RA~+); Though γδ T cells were expanded(the percent of γδ T cells was increased),and Vγ9Vδ2 T cells were differentiated towards central memory-type and effector memory-type on day 14 with IPP,most of γδ T celLs still remained in the phase of na(i)ve-type(CD27~+ CD45RA~+).Conclusion:Tbere lies great differences of γδ T cells in quantity and subtypes between healthy person peripheral blood and neonatus cord blood.Peripheral blood γδ T cells can be activated and proliferated with IPP, while cord blood γδ T cells have the potential to deferentiate into director memory-type which can be used for experimental and clinical study with the synergy of corresponding cytokines.The immuno-regulation and effector function will be reported in other papers.