Using brain microdialysis and LC-MS/MS to detect acetylcholine in rat brain to investigate the effects of ligustrazine. A liquid chromatography-tandem mass spectrometry method has been developed and validated for the determination of acetylcholine in rat brain dialysate sampling by microdialysis. The results indicated that ligustrazine administration by subcutaneous injection significantly increased Ach release in rat medial prefrontal cortex and nucleus accumbens in a dose-related manner. The drug' s effect on Ach release in rat brain could be directly detected by microdialysis combined with HPLC-MS/MS and this method is selective and sensitive.
Acetylcholine ; metabolism ; Animals ; Chromatography, High Pressure Liquid ; Dose-Response Relationship, Drug ; Ligusticum ; chemistry ; Male ; Microdialysis ; Nucleus Accumbens ; metabolism ; Plants, Medicinal ; chemistry ; Prefrontal Cortex ; metabolism ; Pyrazines ; administration & dosage ; isolation & purification ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Objective To explorethe effect of Bailingcapsule on epithelial-mesenchymal transition(EMT) inrats withadenine-in-duced tubulointerstitial fibrosis .Methods Tubulointerstitial fibrosis ani mal models were established and SDrats were dividedinto mo-del group (n=30) ,treatment group (n=30) andcontrol group(n=30) ,randomly .Experi mental rats were harvested at 7 w,12 w,17 wafter onset of experi ment and functional evaluations were performed. Histology ,i mmunohistology were examined to investigateboth histolopathology changes and the expression of bone morphogenic protein-7 (BMP-7) ,transforming growth factor-?1(TGF-?1)and a-smooth muscle actin (?-SMA) in kidneys at three ti me points mentioned above ,respectively .Results Compared with controlgroup ,24 h urinary proteinin model grouplost increasingly and significantly difference appeared at three ti me points relative to controlgroup(P0 .05) rel-ative to control group.There was significant difference at 12 wand 17 w(P

Objective To explore the effect of Bailing capsule on epithelial-mesenchymal transition( EMT) in rats with adenine-in-duced tubulointerstitial fibrosis. Methods Tubulointerstitial fibrosis animal models were established and SD rats were divided into mo-del group ( n = 30), treatment group ( n = 30) and control group( n = 30), randomly. Experimental rats were harvested at 7 w, 12 w,17 w after onset of experiment and functional evaluations were performed. Histology, immunohistology were examined to investigateboth histolopathology changes and the expression of bone morphogenic protein-7 (BMP-7), transforming growth factor-β1 (TGF-β1 )and a-smooth muscle actin (α-SMA) in kidneys at three time points mentioned above, respectively. Results Compared with controlgroup, 24 h urinary protein in model group lost increasingly and significantly difference appeared at three time points relative to controlgroup ( P ＜ 0.01 ). Urinary NAG in model group was markedly higher than that in control group from 7 w after onset (P ＜ 0.01 ) andwas increasingly raised at 12 w and 17 w (P＜0.01). The value of blood BUN and Cr in model group increased at 7 w (P＞0.05) rel-ative to control group. There was significant difference at 12 w and 17.w (P ＜ 0.01 ). Histologically, kidneys in model group, at 7 w,exhibited tubular casts and gently tubular dilation, granuloma in cortex, mononuclear cells infiltration in tubulointerstitial areas, andmild interstitial fibrosis. At 12 w, the degree of tubular injury and tubulointerstitial fibrosis gradually aggravated. Up to 17 w, diffusetubular dilation or atrophy was observed and focal tubules disappear. Diffuse interstitial fibrosis was exhibited. In normal kidneys, im-munohistochemistry suggested that the light expression of BMP-7 was detected in proximal renal tubular epithelial cells and marked ex-pression was identified in distal tubule, collecting duct, and renal tubular epithelial in junction area between cortex and medulla. How-ever, the expression of BMP-7 in kidneys of model group significantly decreased with increasing tubulointerstitial fibrosis and was nega-tive correlation with the expression of TGF-β1(r = -0. 981 P＜0.01) and α-SMA (r= -0.975 P＜0.01). Bailing capsule ad-ministration protected the expression of BMP-7 and reduced TGF-β1 and α-SMA expression before 12 w(P＜ 0.01 ). Conclusions Ourstudy shows an anti-fibrotic reno-protective function of Bailing capsule in rats with tubulointerstitial fibrosis via prevention of epithelial-mesenchymal transition at early stage. However, the beneficial effect lost with increasing tubulointerstitial fibrosis.

Objective:To analyze the clinical characteristics that affect the early outcomes of the elderly patients with transient ischemic attack(TIA) and provide the guidance for the prediction of disease recurrence.Methods:From January 2016 to December 2019, 315 TIA patients over 60 years old based on the time-clinical definition who were admitted to the department of neurology in Beijing Shijitan Hospital were divided into recurrence cerebrovascular events group(RCVEs group) and non-recurrence cerebrovascular events group(non-RCVEs group) according to the recurrence at 1 month after onset. The clinical characteristics of the two groups were compared by Logsitic regression analysis.Results:There were 29 cases in the RCVEs group and 286 cases in the non-RCVEs group. Compared to the non-RCVEs group, patients in RCVEs group were more likely have higher prevalence of hypertension history(14/15, 83/203), moderate or severe intracranial artery stenosis(21/8, 132/154), carotid stenosis(22/7, 107/179), DWI positive, motor symptoms, carotid artery stenting and higher times of TIA episodes(2(2, 3), 2(1, 2)), fasting blood glucose and glycosylated hemoglobin levels(8.86(8.17, 9.56)mmol/L, 5.82(5.27, 6.33)mmol/L). Logistic regression analysis showed that patients in RCVEs group had a DWI positive( B=1.634, OR=5.124, 95% CI: 2.898-9.059, P=0.000) and higher prevalence of moderate to severe stenosis of carotid artery( B=0.572, OR=1.773, 95% CI: 1.050-2.993, P=0.032). Conclusion:DWI positive and moderate to severe carotid stenosis may influence the early poor prognosis in patients with TIA.

From the hospital information system (HIS) of 20 national grade III-A general hospitals, 2 960 cases of herpes zoster as the research object, analyzes the relations between the general information, syndrome of traditional Chinese medicine (TCM), western medicine combined diseases, the relationship between the solar term and the incidence of herpes zoster, and the combined use of Chinese and western medicine. Among the patients with 46-65 year old has the highest percentage of diseased; admission to general outpatient clinic is the most; the most common medical payment is medicare; combined disease such as hypertension, diabetes and coronary heart disease is more common; early treatment effect of herpes zoster is better than the sequelae; summer and autumn solar term patients is hospitalized more, TCM syndrome is damp heat of liver fire; about drugs, western medicine is the most commonly used vitamin B1 and mecobalamin, traditional Chinese medicine is the most frequently used Danhong injection, combination therapy with promoting blood circulation drugs and neurotrophic drugs. Thus, herpes zoster, more common in elderly patients, with no obvious relationship between solar term, should be early diagnosis and early treatment, often with combination of Chinese traditional and western medicine treatment.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Herpes Zoster ; diagnosis ; drug therapy ; epidemiology ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Thiamine ; therapeutic use ; Vitamin B 12 ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo prepare and identify a polyclonal antibody (pAb) against (mouse) cysteinyl leukotriene receptor 1 (CysLT(1)) and to investigate the changes of CysLT(1) receptor expression in BV2 microglial cells after rotenone treatment.

METHODSRabbits were immunized with KLH-coupled CysLT(1) peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by ELISA method, and the specificity of the pAb was tested by antigen blockade. After BV2 cells were treated with rotenone (0.01-1 μmol/L) for 24 h, the expression of CysLT(1) was determined by immunostaining, Western blotting and RT-PCR.

RESULTThe pAb showed a titer of 1/32728, and was not cross-reacted with antigens of CysLT(2) receptor and GPR17. Immunostaining, Western blotting and RT-PCR analysis showed the expression of CysLT(1) receptor in BV2 microglia. Rotenone at 1μmol/L significantly induced an increased expression of CysLT(1) receptor.

CONCLUSIONThe prepared CysLT(1) receptor polyclonal antibody has a high titer and high specificity to meet testing requirements of Western blotting and immunostaining; CysLT(1) is associated with rotenone-induced injury of BV2 microglial cells.

Animals ; Cells, Cultured ; Male ; Mice ; Microglia ; drug effects ; metabolism ; pathology ; Rabbits ; Receptors, Leukotriene ; immunology ; metabolism ; Rotenone ; pharmacology

The aim of this study was to investigate the effect of bortezomib alone and in combination with harringtonine on apoptosis of HL-60 cells. HL-60 cells were treated with bortezomib, harringtonine in different concentrations for 12 - 48 hours. Cell proliferation was analyzed by MTT assay; the apoptosis of HL-60 cells was observed by DNA gel electrophoresis, fluorescence microscopy and flow cytometry. The results showed that 10 - 50 nmol/L bortezomib could effectively inhibit HL-60 cell proliferation, and induced its apoptosis. After treating for 12 hours, 10 nmol/L bortezomib could trigger cells apoptosis. With time prolongation or dose increase, HL-60 cell apoptotic rate significantly increased. Furthermore, co-administration of bortezomib (10 nmol/L) with harringtonine (30 nmol/L) resulted in a higher cell apoptotic rate when compared with that induced by those agents used alone. It is concluded that the bortezomib can induce HL-60 cells apoptosis in a time-and-dose-dependent manner and synergistic effectiveness can be found when bortezomib combined with harringtonine.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; HL-60 Cells ; Harringtonines ; pharmacology ; Humans ; Pyrazines ; pharmacology

OBJECTIVETo investigate the effect of bortezomib alone or combined with harringtonine (HT) or arsenic trioxide (As2O3) on the proliferation capacity and apoptosis of HL-60/ADM cell line and fresh cells from refractory/relapse acute leukemia patients.

METHODSHL-60/ADM cells or refractory/relapse leukemia cells were incubated with bortezomib at different doses alone and in combination with HT or As2O3. The proliferation capacity was observed by MTT assay, cell apoptosis by fluorescence microscopy and flow cytometry. Intracellular concentration of daunorubicin (DNR) was determined by flow cytometry.

RESULTSIn bortezomib-treated HL-60/ADM cells, the proliferation inhibition rate and apoptotic cells increased in a time- and dose-dependent manner. 40 nmol/L bortezomib could maximally inhibit the proliferation of HL-60/ADM cells at 48 hours. 15 micromol/L As2O3 or 752 nmol/L HT combined with different doses of bortezomib could inhibit proliferation and induce apoptosis of HL-60/ADM cells. The As2O3 plus bortezomib or HT plus bortezomib showed a greater anticancer efficacy than either of the drugs alone (P < 0.05, P < 0.01). Bortezomib (10 nmol/L) could markedly enhance the intracellular accumulation of DNR in HL-60/ADM cells (P < 0.05).

CONCLUSIONSBortezomib can inhibit proliferation and induce apoptosis of HL-60/ADM cells and fresh refractory/relapse acute leukemia cells, especially combined with HT or As2O3.

Adolescent ; Adult ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Child ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; HL-60 Cells ; Harringtonines ; pharmacology ; Humans ; Male ; Oxides ; pharmacology ; Pyrazines ; pharmacology ; Young Adult

OBJECTIVETo assess the antitumor efficacy and adverse effects of bortezomib either used alone or in combination with arsenic trioxide for transplanted tumor in nude mice.

METHODSNude mice bearing HL-60 cell xenografts were randomized into 4 groups to receive treatment with normal saline, bortezomib, arsenic trioxide, bortezomib plus arsenic trioxide. The tumor growth inhibition and general condition of the nude mice were observed, and in situ TUNEL assay and immunohistochemistry were performed on the transplanted tumors.

RESULTSBortezomib alone and in combination with arsenic trioxide could both inhibit the growth of the transplanted tumors, prolong the survival of the nude mice, and induce cell apoptosis and growth inhibition of the HL-60 cells in vivo, and the combined administration exhibited even better effects. The administration was well tolerated with causing manifest vital organ damages in the mice.

CONCLUSIONBortezomib in combination with arsenic trioxide has significant antitumor effect in nude mice bearing HL-60 cell xenografts possibly by inducing HL-60 cell apoptosis and growth inhibition without producing no significant adverse effects.

Animals ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Proliferation ; Disease Models, Animal ; HL-60 Cells ; Humans ; Leukemia ; drug therapy ; physiopathology ; Male ; Mice ; Mice, Nude ; Oxides ; pharmacology ; Pyrazines ; pharmacology ; Random Allocation ; Xenograft Model Antitumor Assays

OBJECTIVETo evaluate the feasibility and efficacy of a new MRI imaging method--diffusion weighted imaging (DWI) with short TI version recovery-echo planar imaging (STIR-EPI) sequence in differentiating benign cervical lymph nodes from malignant ones. METHODS Twenty nasopharyngeal carcinoma patients and fourteen volunteers received both conventional MRI and DWI with STIR-EPI. Ability of detecting lymph nodes between conventional MRI and STIR-EPI-DWI was compared, and the difference of apparent diffusion coefficient (ADC) value between metastatic lymph node and normal lymph node was analyzed.

RESULTSDWI was more sensitive in detecting lymph node than conventional MRI. ADC value of metastatic lymph node (0. 766 +/- 0. 119) x 10 (-3) mm(2)/s was significantly lower than that of normal lymph node (0. 975 +/- 0. 179) x 10 - mm2/s (P < 0. 01).

CONCLUSIONAs a new MRI imaging technique in detecting cervical lymph nodes, diffusion weighted imaging ( DWI) with short TI version recovery-echo planar imaging ( STIR-EPI) sequence is more reliable and sensitive than conventional MRI imaging, providing an alternative way to differentiate benign lymph nodes from malignant ones.

Adult ; Aged ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging ; methods ; Echo-Planar Imaging ; methods ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; Neck ; Reproducibility of Results ; Sensitivity and Specificity