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Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the adult central nervous system (CNS), however, it causes excitation in the immature CNS neurons. The shift from GABA-induced depolarization to hyperpolarization in postnatal brain is primarily due to progressive decrease in the expression of the Na-K-2Cl symporter 1 (NKCC1) and increased expression of the K-Cl cotransporter 2 (KCC2). Unlike CNS neurons, both immature and mature neurons in the enteric nervous system (ENS) are depolarized by GABA. Molecular mechanisms by which GABA excites ENS neurons are unclear. It is understood, however, that the excitatory action depends on elevated intraneuronal Cl. We aimed to test a hypothesis that high intracellular Cl in ENS neurons is maintained by activity of the NKCCs. We found that NKCC2 immunoreactivity (IR) was expressed in the ENS of the rat colon on postnatal day 1 (P1). The expression level of NKCC2 continuously increased and reached a steady high level on P14 and maintained at that level in adulthood. NKCC1 IR appeared in ENS on P14 and maintained through adulthood. KCC2 IR was not detectable in the ENS in any of the developmental stages. Both NKCC1 IR and NKCC2 IR were co-expressed with GABA receptors in ENS neurons. Exogenous GABA (1 mmol/L) caused membrane depolarization in the ENS neurons. The reversal potential of GABA-induced depolarization was about -16 mV. Blockade of NKCC by bumetanide (50 μmol/L) or furosemide (300 μmol/L) suppressed the depolarizing responses to GABA. Bumetanide (50 μmol/L) shifted the reversal potential of GABA-induced depolarization in the hyperpolarizing direction. Neither the KCC blocker DIOA (20 μmol/L) nor the Cl/HCO exchanger inhibitor DIDS (200 μmol/L) suppressed GABA-evoked depolarization. The results suggest that ENS neurons continuously express NKCC2 since P1 and NKCC1 since P14, which contribute to the accumulation of Cl in ENS neurons and GABA-evoked depolarization in neonate and adult ENS neurons. These results provide the first direct evidence for the contribution of both NKCC2 and NKCC1 to the GABA-mediated depolarization.
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Animals , Rats , Bumetanide , Neurons , Receptors, GABA-A , Symporters , gamma-Aminobutyric AcidABSTRACT
Objective To investigate the effects of Tirofiban on the expression of matrix metalloproteinase(MMP-9)and sCD40L in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI)and to explore the potential mechanism of anti-artherosclerosis and stabilize plaque by Tirofiban.Methods Eighty-six patients with ACS were enrolled and were randomly divided into the control group and the Tirofiban group with different time periods after PCI.The expression of MMP-9 and sCD40L were tested by ELISA at 6 h,12 h,24 h,36 h after PCI.Results After application of Tirofiban 6 h,12 h,24 h,36 h,the expression of MMP-9 decreased from(228.25 ±0.015)ug/L to(53.56 ±0.02)μg/L and the expression of sCD40L decreased from(321.12 ±0.02)ng/L to(123.32 ±0.02)ng/L,compared with the control group,the difference was significant(P ＜ 0.05).Conclusions Tirofiban can inhibite the expression of sCD40L and MMP-9,the inhibition of the expression of MMP-9 may be related to the CD40/CD40L pathway.This effect may be one of the mechanism of reducing atherosclerotic plaque inflammation and preventing plaque rupture by Tirofiban.
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BACKGROUND/AIMS: Functional gastrointestinal disorders are those in which no abnormal metabolic or physical processes, which can account for the symptoms, can be identified. The irritable bowel syndrome (IBS) is a significant functional disorder, which affects 10-20 percent of the population worldwide. Predominant symptoms of IBS are abnormal defecation associated with abdominal pain, both of which may be exacerbated by psychogenic stress. Our study was designed to test a hypothesis that symptoms in a subset of patients with a diagnosis of IBS are associated with an autoimmune degenerative neuropathy in the enteric nervous system. METHODS: Serum was collected from Rome II-IBS patients and controls at the University of North Carolina Functional Gastrointestinal Diseases Center. Assay procedures were immunohistochemical localization of antibody binding to enteric neurons and human protein microarray assay for antigens recognized by antibodies in the sera. RESULTS: Eighty-seven percent of IBS sera and 59% of control sera contained anti-enteric neuronal antibodies. Antibody immunostaining was seen in the nucleus and cytoplasm of neurons in the enteric nervous system. Protein microarray analysis detected antibody reactivity for autoantigens in serum with anti-enteric neuronal antibodies and no reactivity for the same autoantigens in samples not containing anti-enteric neuronal antibodies in our immunostaining assay. Antibodies in sera from IBS patients recognized only 3 antigens out of an 8,000 immunoprotein array. The 3 antigens were: (1) a nondescript ribonucleoprotein (RNP-complex); (2) small nuclear ribonuclear polypeptide A; and (3) Ro-5,200 kDa. CONCLUSIONS: Results of the present study suggest that symptoms in a subset of IBS patients might be a reflection of enteric neuronal damage or loss, caused by circulating anti-enteric autoimmune antibodies.
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Humans , Abdominal Pain , Antibodies , Autoantigens , Cytoplasm , Defecation , Enteric Nervous System , Gastrointestinal Diseases , Irritable Bowel Syndrome , Neurons , North Carolina , Physical Phenomena , Protein Array Analysis , Ribonucleoproteins , RomeABSTRACT
Objective To evaluate the relationship between serum levels of leptin, endothelin and diabetic retinopathy in type 2 diabetes patients. Methods Leptin, endothelia, FBG, PBG, HBA1C, CHOL, TG and other clinical characteristics were tested in 80 type2 diabetes patients and 30 control case. All diabetes patients were divided into three group: non-diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy(PDR) according to the examination results of fundus. Correlations between levels of serum leptin and other parameters were analyzed. Results Plasma level of leptin in the type 2 diabetes with PDR group[(17.41±5.81)μg/L] were higher than that in control, NPDR and NDR group (P＜0.01). Plasma level of ET in the type 2 diabetes with PDR group[(80.68±13.57)mg/L] were higher than that in control, NPDR and NDR group (P＜0.01). The serum leptin levels were positively correlated with BMI(r＝0.468,P＜0.01). Conclusions Serum leptin and endothelin levels were elevated in patient with diabetic retinopathy as diabetic retinopathy aggravated and serum level of leptin and endothelin raised.
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AIM:To establish HPLC fingerprints of Platycodon grandiflorum in different picking times in Henan province.METHODS:HPLC chromatography condition:Hypersil C_(18) column(250 mm×4.6 mm,5 μm);the mobile phase was acetonotrile with 0.05% phosphoric acid and the gradient elution mode was applied in chromatographic separation;The flow rate was 0.5 mL/min;The temperature of column was 30℃;the detective wavelength was set at 210 nm;RESULTS:The overall similarity in samples collected in autumn was higher than that in spring,and autumn was the appropriate for harvest.CONCLUSION:This method is simple and accurate with a good reproducibility.It provids a reliable scientific basis for the quality control of Platycodon grandiflorum.
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@# ObjectiveTo discuss the effect of argon laser on retinal vein obstruction (RVO) . Methods428 eyes of 422 patients with RVO were treated by argon laser.Among them, there were 386 eyes with ischemic RVO,42 eyes with no-ischemic RVO, and 129 eyes with macular vesicular edema(MVE).ResultsThe vision acuity of 207 eyes is improved, and not changed in 138 eyes. The disappearing rate of MVE is 84.45%(82/97). ConclusionUsing argon laser to treat RVO can curb new vascular of retina building, lighten MVE and protect vision function.
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Background and Purpose:Cervical cancer is one of the most common malignant neoplasms among women.The 5-year survival for patients with early stage disease is over 70%.While it is generally accepted that either radical surgery or radiotherapy can achieve cure for the majority of patients with early-stage cervical cancer,there is no standard approach to the patients with bulky disease,whose prognosis remains very poor in spite of the therapeutic advances achieved in recent years.Neoadjuvant chemotherapy has been used as part of the multidisciplinary treatment before either operation or radiation therapy.Although the approach still had many controversies,numerous studies have supported its effectiveness in bulky cervical cancer.The present study was conducted to explore whether neoadjuvant chemotherapy with the combination of vincristine,bleomycin and cisplatin could improve the operability and pathological response rate in Ⅰb_(2)~Ⅱb bulky cervical cancer patients.Methods:A total of fifty-six patients with bulky cervical cancer were histologically diagnosed and staged into Ⅰb_(2)~Ⅱb according to the standards of International Federation of Gynecology and Obstetrics(FIGO) and randomly selected,including 15 cases with Ⅰb_(2),15 with Ⅱa,26 with Ⅱb.They were treated by a regimen of PVB chemotherapy for 2 cycles and followed by operation.The immediate response and adverse effects were analyzed.Results:The overall response rate was 78.6%.The resectability rate for surgery after chemotherapy was 100%.No intolerable toxic and adverse effects were recorded during neoadjuvant chemotherapy.Preoperative neoadjuvant chemotherapy can apparently increase the possibility of resection by operation and enhance the remission rate.The primary tumor sizes were significantly decreased after chemotherapy before surgery(P
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Ambulatory blood pressure monitor (ABPM) was done on 103 hypertensive patients according to clinical stages and left ventricular measure (LVM) was randomly done on a portion of the patients. The results showed that the variability of stage-Ⅱ-group's 24 hour systolic pressure and stage-Ⅲ-group's systolic and diastolic pressures was significantly higher than that of stage-Ⅰ-group (P
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Objective To establish the fingerprint detecting standard for Tanreqing NaCl Injection. Methods Using baicalin as reference substance to calibrate the common peaks by HPLC-ELSD. According to the technical requirements on fingerprint of traditional Chinese medicine injection, their relative retention times and peak area ratios were calculated and the similarity of ten batchs of samples was determined. Results On the basis of systematic methodology, ten batches of injection samples were tested and analyzed so as to establish HPLC fingerprint for the injection. Conclusion The relative retention times and peak area ratios of 16 common peaks on HPLC fingerprint all conform to the requirement. So the established fingerprint can be used as the one of important foundations for quality control of Tanreqing NaCl Injection.
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Objective To evaluate the predictability of ablated depth in photorefractive procedures by Zeiss MEL80 and VISX Star S4 excimer laser.Design Prospective,comparative case series.Participants 168 eyes of 84 people with myopia and cylinder.Main Outcome Measures Corneal thickness and ablated depth.Methods The thickness of cornea by Zeiss MEL80 and VISX Star S4 were measured by anterior segment OCT.The actuality ablated depth and calculated depth were compared.Results There were no significant differences between actuality ablated depth and calculated depth in Zeiss MEL80.And in VISX Star S4,the actuality ablated depth was more than calculated depth.Linear regression of changes in ablated depth on myopia and cylinder yielded the following formulaus:△ablated depth(VISX Star S4)= 2.324 *|myopia|+ 5.270 *|cylinder|-6.772.Conclusions Different excimer laser has different changes between actuality ablated depth and calculated depth.To guarantee the safety of LASIK,Ophthalmologists should know the characteristics of the excimer laser.
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AIM: To establish HPLC-fingerprints and quantitatively determine platycodin-D from Platycodon grandiflorum.METHODS: HPLC analysis was carried out on Hypersil C18 column(250 mm ? 4.6 mm,5 ?m),with a mobile phase of acetonitrile-0.05 mol/L phosphoric acid system,gradient elution,with a flow at 0.5 mL/ min,an ultraviolet detection wavelength was at 210 nm for fingerprint and at 206 nm for platycodin-D,column tem-perature at 30 ℃.RESULTS: Twelve common peaks were identified in chromatograms with reference to platycod-in-D peak from the 18 batches of the samples.CONCLUSION: The method of the HPLC-fingerprint and quantita-tive analysis is rapid,simple and accurate with a good reproducibility and can be used for the quality control of Platycodon grandiflorum.
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AIM:To establish HPLC fingerprints of Platycodon grandiflorum in different picking times in Henan province.METHODS:HPLC chromatography condition:Hypersil C18 column(250 mm?4.6 mm,5 ?m);the mobile phase was acetonotrile with 0.05% phosphoric acid and the gradient elution mode was applied in chromatographic separation;The flow rate was 0.5 mL/min;The temperature of column was 30 ℃;the detective wavelength was set at 210 nm;RESULTS:The overall similarity in samples collected in autumn was higher than that in spring,and autumn was the appropriate for harvest.CONCLUSION:This method is simple and accurate with a good reproducibility.It provids a reliable scientific basis for the quality control of Platycodon grandiflorum.