Aim To investigate the effect of Aesculus hippocastanum seed extract(AH) on concanavalin A (ConA)-induced acute liver injury in mice,and to ex-plore whether the mechanism was related to the inhibi-tory effect of AH on oxidative stress and c-Jun N-termi-nal kinase (JNK). Methods ConA(20 mg·kg-1) was administered via tail vein injecting to induce he-patic damage in mice. The groups of AH were given at 12.5,25,50 mg·kg-1by oral gavage separately for 20 days. The serum levels of AST,ALT,TP,and Alb were determined by automatic biochemical analyzer and the A/G ratio was calculated. TNF-α and IFN-γ levels were assayed by ELISA. The liver tissue was attained by HE and the histopathological changes were calculat-ed. The MDA, SOD, GSH contents of liver tissues were assayed by related kits. The activity of caspase-3 was detected by spectrophotometry. The expressions of cytochrome C and Bax, Bcl-2, p-JNK and p-Akt were detected by Western blot. Results The serum levels of ALT, AST, IFN-γ and TNF-α in AH groups were significantly lower than those in ConA-injured group, while the levels of TP,Alb and A/G were significantly higher. The SOD and GSH levels of liver tissues signif-icantly increased and MDA level decreased; liver his-topathological changes were consistent with those of the serological indicators, and AH treatment significantly reduced the pathological damage induced by ConA. In AH group,the expression of cytochrome C,caspase-3, Bax/Bcl-2 ratio and p-JNK markedly decreased, while the expression of p-Akt protein increased compared with ConA model group. Conclusion AH could sig-nificantly protect the ConA-induced acute liver injury in mice via inhibition of ROS and JNK pathway.

OBJECTIVETo study Xionggui nasal sprays and its evaluation in release in vitro and absorption in vivo.

METHODEstablishing the best prescription of Xionggui nasal sprays through orthogonal design methods, The in vitro release action of Xionggui nasal sprays was studied using dynamic dialyse method. The in vivo rat nasal recirculation methods were used to study the rule of Xionggui nasal sprays absorption.

RESULTThe optimum prescription was: Pemulen TR-1 0.35%, EDTA 0.2%, PEG400 1%, xanthan gum 0.2%; trolamine: right amount(adjust pH). Its release in vitro and absorption in vivo meet to Higuchi distribution.

CONCLUSIONThe preparation method of Xionggui nasal sprays was appropriate. The release of drug and its uptake was well correlated.

Absorption ; Administration, Intranasal ; Aerosols ; Angelica sinensis ; chemistry ; Animals ; Drug Carriers ; Drug Combinations ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Edetic Acid ; Emulsions ; Ethanolamines ; Female ; Ligusticum ; chemistry ; Male ; Nasal Mucosa ; metabolism ; Plants, Medicinal ; chemistry ; Polyethylene Glycols ; Polysaccharides, Bacterial ; Rats ; Rats, Sprague-Dawley

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Objective To investigate the expression of interleukin-17 (IL-17) in peripheral blood mononuclear cells (PBMC) of patients with multiple myeloma and analyse it's clinical significance.Methods Thirty patients with multiple myeloma in the Department of Hematopathy,the Third Affiliated Hospital of Xinxiang Medical University from January 2016 to January 2017 were selected as observation group;and thirty healthy donors whose gender and age machted with patients in the observation group were selected as control group.Peripheral blood mononuclear cells were obtained from subjects in observation group and control group by using the method of density gradient centrifugation.The content of IL-17 in supernatant of PBMC culture solution of subjects in the two groups was detected by enzyme linked immunosorbent assay and the expression of IL-17 mRNA in PBMC was detected by quantitative real-time polymerase chain reaction;the cellular morphology of PBMC of subjects in control group was observed by scanning electron microscope after co-culturing with the serum of patients in observation group.Results The content of IL-17 in supernatant of PBMC culture solution of subjects in the observation group and control group was (30.79 ± 4.96),(10.10 ± 4.15) ng · L-1 respectively;the content of IL-17 in supernatant of PBMC culture solution of subjects in the observation group was significantly higher than that in the control group (t =3.412,P ＜ 0.05).The expression of IL-17 mRNA in PBMC in the observation group and control group was 4.28 ± 1.34 and 2.45 ±0.95 respectively;the expression of IL-17 mRNA in PBMC in the observation was significantly higher than that in the control group (t =2.796,P ＜0.05).After co-culturing of PBMC of subjects in the control group with the serum of patients in the observation group,the morphology of PBMC changed obviously,and membrane desquamate,membrane disintegration,even membranolysis were observed in some cells with the prolongation of co-culture time.Conclusion The over-expression of IL-17 in PBMC of patients with multiple myeloma may play a certain role in the occurrence and development of this disease.

OBJECTIVETo study the preparation of solid lipid nanoparticles loaded with Xionggui powder-supercritical carbon dioxide fluid extraction and their evaluation in vitro release.

METHODTo prepare solid lipid nanoparticles (SLN) loaded with Xionggui powder-supercritical carbon dioxide fluid extraction (XG-CO2-SFE) using a hot dispersion- ultrasonic technique, establishing the best prescription of XG-CO2-SFE-SLN through orthogonal design methods using entrapment efficiency of nanoparticles as index, and investigating their physicochemical characterizations. The invro release action of SLN was studied in different dissolution mediums using dynamic dialyse method.

RESULTThe best prescription was: phospholipid: F-68: stearie acid glyceride = 5: 2 : 1, the entrapment efficiency of nanoparticles was 96.3%, and the results revealed the nanoparticles were sphere like with the mean size of 245.8 nm, the mean Zeta potential was -33.5 mV. The in vitro release meet to Weibull distribution in physiological brine and to single-index model in pH 7.4 phosphate liquid (40% EtOH).

CONCLUSIONThe preparation method of the XG-CO2-SFE-SLN was appropriate, and the XG-CO2-SFE-SLN was released completely.

Angelica sinensis ; chemistry ; Chromatography, Supercritical Fluid ; Delayed-Action Preparations ; Drug Carriers ; Drug Combinations ; Drug Compounding ; methods ; Drug Delivery Systems ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; Ligusticum ; chemistry ; Nanostructures ; Particle Size ; Phospholipids ; Poloxamer ; Solubility

Objective The choice of surgical approaches for salvage surgery based on the location and invasion of recurrent and residual lesions of nasopharyngeal carcinoma (NPC),surgical results,complications,and survival were assessed.Methods Thirty-seven cases with recurrent and residual lesions of NPC underwent salvage surgery between March 1991 and January 2005 were analysed retrospectively.Of 37 patients,23 were men and 14 women,with a median age of 46.5 years (26 -57 years) ;4 were at stage Ⅰ,10 at stage Ⅱ,14 at stage Ⅲ,and 9 at stage Ⅳ; 5 cases were with cervical metastasis,including 3 cases of N1 and 2 cases N2.All recurrent and residual lesions of NPC were determined by biopsy.On the location and invasion of recurrent and residual lesions of NPC,8 cases underwent endoscopic resection of lesions,12 cases of the palate nasopharyngectomy,5 cases of maxillary swing,4 cases of maxillary swing plus preronal approach,2 cases of lateral rhinotomy plus coronalflap approach,and 6 cases transfacial plus nasal pyramid swing approach.Five cases with cervical metastasis received neck dissection in addition to the operations for recurrent and residual lesions of NPC. Postoperatively 31 cases received radiotherapy with dosage of 60 Gy,among them 15 cases with concurrent chemoradiation therapy,and 6 cases with clear surgical margin did not received radiotherapy or chemotherapy. The cases were followed up for 12 - 72 months,with a median of 45 months.Results Total resection for the recurrent and residual lesions of NPC acounted for 91.8% (34/37) and subtotal resection for 8.2% (3/37). The accidence of perioperative complications was 24.3% (9/37). The 3- and 5-year overall disease-free survival rates (DFSR) were 62.1% and 43.3%,respectively. The 3- and 5-year overall survival rates (OSR) were 72.9% and 51.3%,respectively.The 5 year DFSR of cases at stage Ⅰ - Ⅳ were 100%,40%,28% and 11% (χ2 =10.0,P ＜0.01＝,respectively.The 5 year OSR were 100%,70%,35% and 28% (χ2 = 11.5,P ＜0.01),respectively.Conclusions Salvage surgery is a justified treatment for the recurren and residual lesions of NPC,by which some patients with recurren and residual lesions of NPC can be salvaged.