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Objective:To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSC) on the apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR) model rats and on the regulation of p38 mitogen-activated protein kinase (p38MAPK) pathway.Methods:Forty-five SPF male 8-week old SD rats were selected.The DR rat model was established by intraperitoneal injection of streptozotocin (STZ) combined with a high-sugar and high-fat diet.The fasting blood glucose (FBG) and body weight of the rats were measured every week during the high-sugar and high-fat diet, and fundus angiography was used to observe the circulation and leakage of retinal blood vessels.Forty rats with successful modeling were randomly divided into model group and hUC-MSC injection group according to the random number table method, with 20 rats in each group.Another 20 normal rats fed routinely were served as control group, and intraperitoneally injected with the same amount of citric acid buffer.The hUC-MSC injection group was injected intravitreously with hUC-MSC, and the control group and model group were injected intravitreously with the same amount of phosphate buffer saline (PBS). Fluoro gold (FG) retrograde tracer labeling RGCs was used to observe the number of survived RGCs.Hematoxylin-eosin staining was used to observe the pathological changes of retina.TUNEL method was used to observe the apoptosis of RGCs.Western blot was used to detect B cell lymphoma /leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), p38MAPK and phosphorylated (p-) p38MAPK protein expression in retinal tissues.The use and care of the rats complied with the ARVO statement.The study protocol was approved by an Animal Ethics Committee of Zhengzhou central Hospital Affiliated to Zhengzhou University (NO.2980316).Results:The FBG of control rats was maintained at a normal level, and the body weight gradually increased over time, and was gradually decreased as the course of disease prolonged.The retinal blood vessels ran normally without fluorescein leakage in the control group.In the modeling group, the FBG was maintained at a high level, and the body weight increased slowly and gradually decreased with the prolongation of the disease course since the second week after modeling.The distal retinal vessels were found twisted with large area of capillary fluorescein leakage in the modeling group.The density of RGCs in the control group, model group and hUC-MSC injection group were (2 136.10±215.17), (849.40±167.82), (1 549.20±183.26) cells/mm 2, with significant overall differences ( F=115.218, P<0.01). The density of RGCs in the model group and the hUC-MSC injection group were significantly lower than that of the control group, and the density of RGCs in the hUC-MSC injection group was significantly higher than that of the model group, and the differences were statistically significant (all at P<0.05). The retina in the control group was with clear structure, distinct layers, and a large number of complete RGCs.The number of RGCs in the model group was significantly reduced with nuclear pyknosis, thinned and atrophied RGC layer.The retinal structure was relatively complete, and there were more RGCs in the hUC-MSC injection group than the model group.The apoptosis rates of RGCs in the control group, model group and hUC-MSC injection group were (2.16±1.11)%, (43.47±2.26)%, (20.75±2.18)%, with significant overall difference ( F=445.159, P<0.01). The apoptosis rates of RGCs in the model group and hUC-MSC injection group were significantly higher than that of the control group, and the apoptosis rate of RGCs in the hUC-MSC injection group was lower than that of the model group, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in the relative expression levels of Bax, Bcl-2 and p-p38MAPK proteins in the retina tissues among the three groups ( F=30.982, 12.526, 73.158, all at P<0.01). The relative expression of Bax and p-p38MAPK protein were significantly higher, and the relative expression of Bcl-2 protein was significantly lower in the hUC-MSC injection group and the hUC-MSC injection group than those of the control group, and the differences were statistically significant (all at P<0.05). The relative expression of Bax and p-p38MAPK protein was significantly lower, and the relative expression of Bcl-2 protein was significantly higher in the hUC-MSC injection group than those in the model group, and the differences were statistically significant (all at P<0.05). There was no significant difference in the relative expression of p38MAPK protein among the three groups ( F=1.182, P=0.322). Conclusions:Intravitreal injection of hUC-MSC can inhibit the apoptosis of RGCs in DR model rats and protect the retinal structure of rats, which may play an anti-apoptotic effect by inhibiting the p38MAPK signaling pathway.
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This article was aimed to study the inhibitory effect of ginseng polysaccharide injection on tumor growth a-mong ICR mice after inoculation of S180 cells, and its immune mechanism as well as its synergic effect in reducing toxicity of cytoxan (CTX). The experiment was carried out in ICR mice after inoculation of S180 cells. The mice were randomly divided into the model group, the control group, the CTX group, and the drug combination group. After 10 days of medication, the inhibition of tumor growth, WBC, thymus index and spleen index were measured in mice dur-ing the experiment. The immunodepressed mice model was induced by CTX. Effects of ginseng polysaccharide injec-tion on serum hemolysin and monomuclear macrophage phagocytosis were evaluated. The results showed that the com-bination of ginseng polysaccharide injection and CTX can significantly increase the tumor inhibiting rate. It can also reduce the side effect and toxicity of CTX, which may improve the immunosuppression induced by CTX. It was con-cluded that ginseng polysaccharide injection can increase the therapeutic effects and reduce the toxicity of CTX.
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OBJECTIVE Toexplorethefeasibilityofpreparingamigrainemodelusingratdura materofsuperiorsagittalsinusinfollowingelectricalstimulation.METHODS MaleSDratswereexposed to 1 h electrical stimulation after brain electrode implantation,at 3 V,6 Hz,and a pulse of 0.25 ms.At 0, 1 5,30 min,and 1 h,orbital blood and brain tissue were taken.The content of calcitonin gene-related peptide (CGRP),substance P and prostaglandin E2 (PGE2 )in the plas ma and brain tissue was detec-tedbyradioimmunoassay.RESULTS ThebraintissuecontentofCGRP,substancePandPGE2in the sham group and normal group was not significantly different.CGRP,substance P and PGE2 in brain tissue of model group were 3.41 ±0.93,1 .80 ±0.64,3.41 ±0.93 and (1 .80 ±0.64)ng·g -1 respec-tively,significantly different from sham group(P<0.05).At different time points,the content of CGRP, substance P and PGE2 in plasma orbital venous plexus showed no significant difference between sham groupandmodelgroup.CONCLUSION ThereleaseofCGRP,PGE2andsubstancePinbraintissue is significantly different fro m that of plas ma after electrical sti mulation.The results suggest that a model of migraine can be constructed by electrical stimulation.
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Objective To investigate the outcomes of arthroscopic treatment of anterior cruciate ligament tibial eminence avul-sion fractures by using loop ligature fixation .Methods 26 patients with anterior cruciate ligament tibial eminence avulsion frac-tures .All the patients were fellowed up at least one year .Results The X-ray indicated that all the avulsion fractures of tibial anteri-or eminence were healed after 6 months of the operation .The mean Lysholm score improved from (50 .8 ± 6 .5) preoperatively to (92 .7 ± 4 .3)postoperatively(t=36 .7 ,P<0 .05) .The mean IKDC 2000 subject score improved from (55 .6 ± 7 .4)preoperatively to (90 .7 ± 4 .2) postoperatively(t=22 .5 ,P<0 .05) .Conclusion Arthroscopic treatment of anterior cruciate ligament tibial eminence avulsion fractures by using loop ligature fixation could provide satisfying reduction ,stable fixation and well healing of the avulsed fragment .This arthroscopic suture fixation method is a minimally invasive ,simple and effective treatment for patients with tibial eminence fracture .
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<p><b>OBJECTIVE</b>To study the pharmacokinetics and bioavailability of ginkgolides sustained-release tablet and conventional tablet in Beagle dogs.</p><p><b>METHOD</b>The concentrations of ginkgolides in plasma were determined by LC-MS. The main pharmacokinetic parameters of ginkgolides sustained-release tablet and conventional tablet in vivo were obtained using Pharmacokinetic software DAS 2.0.</p><p><b>RESULT</b>The C(max) of grinkgolide A in ginkgolide sustained-release tablet and conventional tablet were 443.51, 1 039.30 microg x L(-1), respecitvely. t(max) were 2.92, 1.08 h, respectively. AUC(0-12h) were 1 808.21, 2 041.37 h x microg(-1) x L(-1), respectively. MRT were 5.18, 3.18 h, respectively. The relative bioavailability of ginkgolides A was 88.58%. The C(max) of ginkgolide B in ginkgolide sustained-release tablet and conventional tablet were 407.13, 547.38 microg x L(-1), respectively. t(max) were 2.92, 1.08 h, respectively. AUC(01-12 h) were 1 987.31, 1 748.04 h x microg(-1) x L(-1), respectively. MRT were 6.05, 4.98 h, respectively. The relative bioavailability of ginkgolides B was 113.69%.</p><p><b>CONCLUSION</b>The ginkgolides sustained-release tablets have good sustained release characteristics and are bioequivalent to the reference formulation.</p>
Subject(s)
Animals , Dogs , Male , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Methods , Delayed-Action Preparations , Pharmacokinetics , Ginkgolides , Pharmacokinetics , Lactones , Mass Spectrometry , Methods , Quality Control , Tablets , Pharmacokinetics , Therapeutic EquivalencyABSTRACT
<p><b>OBJECTIVE</b>To investigate pharmacokinetic parameters of peoniflorin, albiflorin and amygdaloside after administration of Guizhi Fuling capsule in beagle dogs.</p><p><b>METHOD</b>Plasma was collected from forelimb vein of Beagle dogs after oral administration of Guizhi Fuling capsule. HPLC-MS/MS method was used to determine the concentrations of constituents in plasma. The pharmacokinetic parameters were analyzed by program DAS 2.0.</p><p><b>RESULT</b>The limit of quantitation of peoniflorin, albiflorin and amygdaloside were 0.25, 2.64, 0.04 microg x L(-1), respectively. After administrated with different doses, half-life of peoniflorin in dogs were 4.33, 3.62 h, albiflorin were 6.16, 5.91 h, amygdaloside were 2.43, 1.32 h. The AUC(0-t) of all components were related to dose.</p><p><b>CONCLUSION</b>The pharmacokinetic course of peoniflorin, albiflorin and amygdaloside can be described by two-compartment model, and these components have high expose.</p>
Subject(s)
Animals , Dogs , Male , Administration, Oral , Amygdalin , Blood , Area Under Curve , Benzoates , Blood , Bridged-Ring Compounds , Blood , Capsules , Pharmacokinetics , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Pharmacokinetics , Glucosides , Blood , Half-Life , Monoterpenes , Tandem Mass Spectrometry , MethodsABSTRACT
The presence of hyl gene in 364 PFGE clones of Enterococcus faecium was detected by colony hybridization under conditions of high stringency. The isogenic hyl-deficient mutant (* hyl) was constructed with suicide pTX4577 and screened by allelic replacement. Moreover, an in vitro study was made on the effect of hyl gene detection on the growth ability of hylgene detection on the mutant, and an in vivo study was made on the decrease of virulence in the mouse peritonitis model. The results showed, in the clinical isolates, the positive percentage of hyl gene was 32.8%, which was significantly higher than that (5.3%) in the non-clinical isolates. The * hyl was selected by kanamycin and identified by PCR, pulsed field gel electrophoresis (PFGE) and Southern blot. The experimental evidence indicated that the growth ability of * hyl was remarkably reduced in comparison with that of the wild-type strain. The percentage survival of mice in TX2466 groups was 0, while that of * hyl groups was 50% at the same inoculum in mouse peritonitis. The differences were significant. These data suggest that hyl gene in specific E. faecium strains may be enriched in determinants that make them more likely to cause clinical infections. Being important in the pathogenesis, hyl gene is probably a major virulence factor of Enterococcus faecium.
Subject(s)
Animals , Male , Mice , Enterococcus faecium , Genetics , Virulence , Genes, Bacterial , Gram-Positive Bacterial Infections , Microbiology , Hyaluronoglucosaminidase , Genetics , Mice, Inbred ICR , Mutation , Peritonitis , Microbiology , Virulence , Virulence Factors , Genetics , MetabolismABSTRACT
Objective To evaluate the clinical application value of multi-slice helical CT volumetric (VH) scanning in lumber spine. Methods One thousand of patients with back and leg pain who underwent CT examinations were selected as subjects. We simulated the traditional protocol of single-slice(SS) discrete scanning for L3/4, L4/5, and LS/S1 intervertebral discs. The VH scanning mode was performed with 120 kV, 210 mAs,pitch of 1.5 and coverage of 97. 5 mm. The simulated SS scanning mode was performed with 120 kV, 240 mAs and coverage of 45.0 mm. The diagnostic outcomes and the radiation doses were compared between the two scanning modes. Two groups doctors observed ten terms, including the osseous spinal stenosis,narrowed intervertebral space and so on in two scanning modes respectively. Then consistency analysis of the data was carried out. Results The VH scanning mode showed far more features than the SS mode. The detection rates of the VH mode in the osseous spinal stenosis, narrowed intervertebral space,herniated nucleus pulposus, narrowed lateral recess, vertebral lesion, hypertrophy of L5 transverse process,abnormal direction of facet, facet degeneration, lumbar spondyloschisis, and paraspinal soft tissue were 11.8% (n =118), 38. 5% (n =385), 9. 3% (n =93), 46. 8% (n =468), 31.4% (n =314), 5.7% (n =57), 25.4% (n = 254), 49. 7% (n = 497), 9.9% (n = 99), and 0. 6% (n = 6) respectively, while the detection rates of the SS mode in ten terms were 5.6% (n = 56), 0, 0. 6% (n = 6), 27. 9% (n = 279),22.4% (n =224), 1.2% (n = 12), 16.7% (n = 167), 37.2% (n =372), 0.5% (n =5), and 0.2%(n = 2) respectively. The difference between the two groups had statistically significance (average P <0.05), except the paraspinal soft tissue abnormal (P > 0.05). The detection rates of the VH mode were higher than the SS mode in the osseous spinal stenosis, narrowed intervertebral space, herniated nucleus pulposus, lumbar spondyloschisis, being 6.2% (n = 62) , 38. 5% (n = 385) , 8.7% (n = 87), and 9.4%(n =94), respectively. In addition, VH mode only partially showed the articular facets, narrowed lateral recess, hypertrophy of L.5 transverse process, and paraspinal soft tissue. We could not acquire the imaging slices paralleling to intervertebral discs in SS mode in 467 patients (46.7%) with lumbosacral angle greater than 35°. The radiation dose of VH mode (164.9 mGy/em) was slightly higher than SS mode (147.0 mGy/cm) Conclusion MSCT VH scanning mode can significantly improve the diagnostic rate of lumbar spine diseases compared with SS mode, and was not restricted by the lumbosacral angle with slightly increasing radiation dosage.
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Objective: To determine the potency of QN-2013, a derivative of quinoxaline 1,4-N-oxide, as a hypoxia-selective cytotoxin or a radiosensitizer. Methods: In vitro cytotoxicity and radiosensitization, as well as in vivo antitumor activity were determined by colony formation and tumor growth delay respectively. The changes in the cell cycle, DNA damage and repair of damaged DNA were assayed by FCM and “comet” assay, separately. Results: ICN250 and ICair50 of QN-2013 for HeLa-S3 cells were 0.08 and 1.7 mmol*L－1 respectively, namely, HCR=21. This suggested that QN-2013 was a fairly hypoxic cytotoxin, but inferior to SR-4233. QN-2013 had an evident radiosensitization either in vitro or in vivo. It was noted, however, that the value of in vitro SERs increased exponentially with increasing concentration of the drug, but the in situ antitumor activity seemed to be independent of doses of the drug. The systemic toxicity of QN-2013 was superior to an LD50 of 265 mg*kg－1 compared with 80 mg*kg－1 for SR-4233. In hypoxic condition QN-2013 induced S retension effect and G2M block in HeLa-S3 cells, caused DNA double strand break, and inhibited the repair of radiation-induced DNA damages. All of these reactivenesses might be involved in the action mechanism of QN-2013. Conclusion: QN-2013 is a fair hypoxia-selective cytotoxin, and has shown improved antitumor activity in vivo in combination with radiation. In general, These results suggest that the series of quinoxaline di-N-oxide derivatives hold out bright prospect for the development of novel bioreductive antitumor drugs.
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Objective To observe the protective effects of the extracts of Rhizoma Zingiberis and Pericarpium Citri Reticulatae on myocardial ischemia reduced by isoproterenol(ISO) in rats,and to explore their optimal ratio.Methods Acute myocardial ischemia rat model was established by continuously subcutaneous injection of large-dose.Then the content of the serum creatine kinase(CK) within 24 hours in rats were detected,and the optiaml ratio of Rhizoma Zingiberis and Pericarpium Citri Reticulatae was optimized by uniform design.Results Compared with the control group,the content of CK in the model group was significantly increased(P
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Objective To observe the analgesic action and anti-inflammation effect of borneol. Methods The analgesic action and anti-inflammation effect of borneol were observed by mouse hot-plate test,mouse acetic-acid-induced twisting test,mouse abdominal cavity capillary permeability increase test induced by acetic acid,and rat pedal swelling test induced by carrageenin. Results Borneol reduced the pedal swelling of rats,ED50=0.3242 g?kg-1,increased pain threshold in mice ED50=0.3870 g?kg-1,inhibited twisting response of mice obviously,ED50=0.5813 g?kg-1. In the same dose,the analgesic action of borneol was stronger than the anti-inflammatory effect. Conclusion Borneol has certain analgesic action and anti-inflammation effect.