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Disruption of pulmonary endothelial permeability and associated barrier integrity increase the severity of acute respiratory distress syndrome (ARDS). This study investigated the potential ability of the human immunodeficiency virus-1 (HIV-1) integrase inhibitor raltegravir to protect against acute lung injury (ALI) and the underlying mechanisms. Accordingly, the impact of raltegravir treatment on an in vitro lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cell (HPMEC) model of ALI and an in vivo LPS-induced two-hit ALI rat model was examined. In the rat model system, raltegravir treatment alleviated ALI-associated histopathological changes, reduced microvascular permeability, decreased Evans blue dye extravasation, suppressed the expression of inflammatory proteins including HMGB1, TLR4, p-NF-κB, NLRP3, and MPO, and promoted the upregulation of protective proteins including claudin 18.1, VE-cadherin, and aquaporin 5 as measured via western blotting. Immunohistochemical staining further confirmed the ability of raltegravir treatment to reverse LPS-induced pulmonary changes in NLRP3, claudin 18.1, and aquaporin 5 expression. Furthermore, in vitro analyses of HPMECs reaffirmed the ability of raltegravir to attenuate LPS-induced declines in VE-cadherin and claudin 18.1 expression while simultaneously inhibiting NLRP3 activation and reducing the expression of HMGB1, TLR4, and NF-kB, thus decreasing overall vascular permeability. Overall, our findings suggested that raltegravir may represent a viable approach to treating experimental ALI that functions by maintaining pulmonary microvascular integrity.
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Objective: To explore the predictive effect of microvascular permeability surface (PS) on spontaneous hemorrhagic transformation (HT) in acute ischemic stroke patients. Methods: A retrospective analysis was performed on 43 patients with acute ischemic stroke who underwent CT perfusion imaging (CTPI). Neither arterial thrombolysis nor intravenous thrombolysis was carried out in these patients. The patients were divided into HT group (n=20) and control group (n=23) according to whether HT occurred within 2 weeks after the onset of stroke detected with CT or MRI. Mann-whitney U test was used to compare the differences of CTPI parameters, including PS, cerebral blood volume (CBV) and cerebral blood flow (CBF) between the affected and contralateral areas in HT group, and CTPI parameters of the affected area were also compared between HT and control groups. ROC curve was used to analyze the efficiency of PS value to predict HT. Results: In HT group, PS (Z=-5.410, P<0.001) and CBV (Z=-3.517, P<0.001) of the affected area were higher than those of contralateral area, while CBF (Z=-2.245, P=0.024) of the affected area was lower than that of contralateral area. PS (Z=-5.065, P<0.001) and CBV (Z=-3.458, P=0.001) of the affected area in HT group were higher than those in control group, while there was no statistical difference of CBF (Z=-1.729, P=0.084) of the affected area between HT and control group. ROC analysis showed that the AUC was 0.952 for predicting HT in acute ischemic stroke patients with the threshold of PS as 0.032 4 ml/(100 ml•min). The sensitivity, specificity and accuracy was 90.00%, 82.60% and 86.05%, respectively. Conclusion: PS value can be used to predict HT in patients with acute ischemic stroke, therefore being helpful to appropriate treatments in clinic.
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Objective TostudythevalueofquantitativeparametersofDCE-MRIandthreedimensionalarterialspinlabeling(3D-ASL) inpreoperativegliomagrading.Methods 70patientsdiagnosedpathologicallywithinitialgliomawereassessedretrospectively,including 32caseswithlow-gradeglioma(LGG)and38caseswithhigh-gradeglioma(HGG).Allpatientsunderwentconventional,enhanced, DCEand3D-ASL MRIat3.0Tbeforesurgery.TheparametricvaluesofDCEsuchasvolumetransferconstant(Ktrans),extravascular extracellularspacevolumefraction(Ve),therateconstant(Kep),fractionalplasmavolume(Vp),cerebralbloodflow (CBF)andcerebral bloodvolume(CBV)wereobtainedbycorrespondingpost-processingsoftware.ThecerebralbloodflowofASL (ASL-CBF)wasalso obtained.Ttestoftwoindependentsampleswasusedtoanalyzewhetherthemaximumandaveragevaluesofeachparameterwere statisticallydifferentbetweenLGGand HGG.Thediagnosticaccuracyofdifferenttechniqueforgliomagradingwasdeterminedby ROCcurveanalysis.Results ThemaximumvaluesofDCE-Ktrans,Ve,rCBVandmaximumvalueofASL-rCBFwerestatisticallydifferent betweentheHGGandLGG (P＜0.05).AlltheparametricaveragevalueswerestatisticallydifferentbetweentheHGGandLGG (P＜0.05).ThemaximumandaveragevaluesofKtranshadarelativelyhighestdiagnosticefficiencyinallparameters,withtheAUCwere0.986 and0.971,theoptimumthresholdwere0.264and0.068,thesensitivitywere93.3%and94.1%,andthespecificitywere100%and 100%,respectively.ThemaximumvaluesofVe,rCBV,ASL-rCBFandtheaveragevaluesofallparametershadarelativelyhigher diagnosticefficiency.Conclusion ThemaximumvaluesofKtrans,VeandrCBFofDCE,themaximumvalueofASL-rCBFandtheaverage valueofeachparameterwereusefultodistinguishbetweenLGGand HGG.ThemaximumandaveragevaluesofKtransarethebest parametersforidentifyingHGGandLGG.
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There is endothelial hyperpermeability in sepsis,trauma,ischaemia-reperfusion injury,acute respiratory distress syndrome and thrombosis,while an important mechanism underlying this process is increased paracellular leakage of plasma fluid and protein because of cytoskeleton contration under the role of histamine, thrombin,vascular endothelial growth factor and activated neutrophil. Structural changes initiate with agonist-re-ceptor binding,followed by activation of intracellular signalling molecules,then phosphorylate alter the hyperme-ability of cell-cell adhesion. Targeting key signalling molecules that mediate endothelial-junction-cytoskeleton dissociation demonstrates a therapeutic potential to improve vascular barrier function during inflammatory injury.
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Objective: To clarify that protection of Tongxinluo against myocardial ischemia/reperfusion injury relates to enhancing endothelial barrier in diabetic rats. Methods: A total of 32 Zucker diabetic rats were randomized into 4 groups:Sham group, Model group, Insulin group and Tongxinluo group, n=8 in each group. In addition, there was a Control group containing 8 non-diabetic Zucker rats. Myocardial ischemia/reperfusion injury model was established by a 45-min ischemia and 3-h reperfusion protocol. The size of infarction was detected by pathological staining, the microvascular permeability was examined by Miles assay to obtain the lfuorescein isothiocyanate concentration in myocardial tissue, the Triton X-100 soluble and insoluble VE-cadherin was measured by membrane protein extraction and western blot analysis. Results:The size of infarction in Model group was obviously higher than that in Control group (55.2 ± 1.4)%vs (36.2± 1.3)%,P0.05. Both insulin group and Tongxinluo group got lower lfuorescein isothiocyanate concentration (all P Conclusion: Protection of Tongxinluo against myocardial ischemia/reperfusion injury in diabetic rats is as effective as insulin, but the effect is independent of reducing blood glucose and may be related to enhancing endothelial barrier.
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ObjectiveTo investigate whether the T1-weighted dynamic contrast-enhanced perfusion magnetic resonance imaging (DCEPMRI) technique can help to delineate the clinical target volume of brain glioma patients.MethodsThe DCE T1-weighted images from 28 glioma patients were collected after GdDTPA was injected.After the acquired images were processed and analyzed using modified Tofts-Kermode'two compartment analysis model and de-convolution method,the value and its pseudo mapping of quantitative parameter Ktrans related to microvascular permeability were obtained.The tumor size in the largest diameter slice measured both in routine enhanced MRI and Ktrans mapping of T1-weighted DCEPMRI were compared.ResultsThe vascular permeability and tumor infiltration was lower in low grade glioma,the difference of the tumor size between T1-weighted DCEPMRI and routine enhanced MRI reached 0.2％ -0.3％ there was significant difference of tumor size between T1 -weighted DCEPMRI and routine enhanced MRI ( grade Ⅰ and Ⅱ grade with 2.93 cm2∶2.46 cm2(t=6.90,P=0.000) and 4.18 cm2∶3.21 cm2(t=10.22,P=0.000) ).While in high grade glioma,the vascular permeability and the tumor infiltration were higher,the difference of the tumor size between T1-weighted DCEPMRI and routine enhanced MRI reached 25％ - 26％( the size of grade Ⅲ and Ⅳ were 6.46 cm2 vs 5.48 cm2 ( t =10.83,P =0.000) and 8.26 cm2 vs 6.52 cm2(t =18.53,P =0.000) ).ConclusionsThe pseudo mapping of quantitative parameter Ktrans related to microvascular permeability acquired by T1-weighted DCEPMRI reflect the infiltrating circumscription in glioma,T1-weighted DCEPMRI can provide more information in delineation the clinical target volume,and it can be used as a new method for tumor volume evaluation.
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Objective To investigate the effects of hydroxyethyl starch(HES 130/0.4)on leukocyte activation,mast cell degranulation and vascular permeability in rat mesentery during the early phase of endotoxemia.Methods Thirty-six male Wistar rats weishing 200-250 g were randomly divided into 3 groups(n=12 each):Ⅰ normal control group received only normal saline(NS);Ⅱ LPS group and Ⅲ HES group received LPS 2 mg/kg iv followed by iv HES infusion at 16 ml·kg-1·h-1 for 60 min(HES group)or equal volume of NS(LPS group).The animals were anesthetized with intramuscular 20% urethane 1 ml/100 g.The abdomen was opened and the mesentery of small intestine was pulled out and placed on transparent observation plate at constant temperature and moisture and examined under microscope for microcirculatory changes.Leukocytes rolling along,adhering to and emigrating from mesenteric venules,mast cell degranulation and FTTC-albumin effux from venules were examined before(baseline)and during the 90 min after LPS administration.The expression of CD11b and CD18 on the leukocytes was determined using flow cylometry.Results The number of leukocytes rolling along,adhering to and emigrating from venules and degranulated mast cells were signitlcanfly increased in LPS group as compared with control group.These LPS-induced changes were significantly inhibited in HES group.The albumin effiux Was enhanced and CD11b/CD18 expression upregulated in both LPS and HES groups.Conclusion Hydroxyethyl starch(130/0.4)can ameliorate the increased vascular permeability and microcirculatory disturbance in rat mesentery during the early phase of endotoxemia.
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Objective To evaluate the protective effect on the pulmonary micmvascolar permeability and thereby to ameliorate the lungs injury attributed to cardiopuimonary bypass(CPB).Method Twenty-four adult hybrid health dogs were randomly divided into three groups(8 in each group):group C(normal saline given after CPB),group N1(NAC given intravenously just before CPB)and group N2(NAC given just after CPB).The changes of respiratory index(RI)and malondialdehyde(MDA)content in lung tissue were observed.Samples were taken three times,before CPB(T0),30 min after CPB surned off(T1)and 60 min after CPB sumed off(T2).The leucocyte count and slbumin content in bronchoalveolar lavage fluid(BAlF),the pulmonary micmvascular permeability index(PMPI),and the histological changes of lung under light microscope and electromicroscope in 3 groups were examined.Results No significant differences were found in the levels of Ri and MDA content of lung tissue between groups before CPB.However,they gradually reduced after CPB(P<0.05)in the three groups,but they still were significantly lower in group N1 and group N2 compared with those in group C at,T1 and T2(P<0.05)and those in group N1 were significantly lowere than those in group N2 at T1 and T2(P<0.05).MDA gradually increased after CPB in three groups(P<0.05),but it was still significantly lower in group N1 and group N2 than that in group C at T1 and T2(P<0.05).The leucocyte count and albumin content in BALF were significantly lower in group N1 and group N2 in comparison with those in group C(P<0.05)and they were significantly lower in group N1 compared with those in group N2(P<0.05).The PMPI were significantly lower in group N1 and sroup N2 compared with those in group C(P<0.05)and they were significantly lower in group N1 compared with those in group N2(P<0.05).By using electromicroscope,the apparent inflammatory change of lung with endothelium cellular swelling,inter-endothelial cells spaces widened,and the indistinctness,deformation or decurtation of microfilarnent were observed.And the dissolution of laminated body,swollen mitochondria and plasmolysis were found in alveolar epithelial cell Ⅱ in group C.However,these changes were markedly alleviated in group N2 and group N1.Conclusions The results clearly demonstrate that NAC could protectie effect on the CPB injured lung and reduce the pulmonary microvascalar permeability,and the protetive effect is better in group N1 than that in group N2.
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Objective To study the role of P38 mitogen-activated protein kinase(P38 MAPK) activation in high level glucose-induced microvascular hyperpermeability.Methods Rats were induced to diabetis by intraperitoneal injection of streptozotocin(STZ).The rats were divided into 5 groups,including normal,diabetes,control,MKK6b(A) and MKK6b(E) groups.The permeability coefficient to albumin(Pa) was measured in venules of in vivo mesenterium using a fluorescence ratio technique;Morphological changes of microvascular endothelial cell were monitored by observing fluorescence of F-actin stained with rhodamine-phalloidin.Results The permeability of diabetic rats was obviously increased.The activation of P38 MAPK by MKK6b(E) could increase microvascular permeability in normal rats,and the inhibition of P38 MAPK by MKK6b(A) could inhibit hyperpermeability of diabetic rats.Conclusion The activation of P38 MAPK induced by hyperglycemia may play a role in diabetic microvascular hyperpermeability.
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Re-expansion pulmonary edema (RPE) is a rare complication associated with the treatment of collapsed lung caused by pneumothorax, atelectasis, pleural effusion in which a large amount of air or effusion fluid is evacuated. In general RPE is resulted from more than 3 days of lung collapse and application of high negative intrapleural pressure. However, it is reported that RPE could be developed despite the collapse period is short and negative pressure suction is not performed. It also has been known that the rate of reexpansion is more important than amount of evacuated air, or collapse period in the development of RPE. Seventeen-year-old female was undergone suture hemostasis for liver laceration, in which RPE was occurred after closed thoracostomy for pleural effusion on postoperative-27 day. We present a case report with review of related articles.