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OBJECTIVE@#To explore the therapeutic mechanism of tanshinone IIA in the treatment of pulmonary arterial hypertension (PAH) in rats.@*METHODS@#A total of 100 male SD rats were randomized into 5 groups (n=20), and except for those in the control group with saline injection, all the rats were injected with monocrotaline (MCT) on the back of the neck to establish models of pulmonary hypertension. Two weeks after the injection, the rat models received intraperitoneal injections of tanshinone IIA (10 mg/kg), phosphatidylinositol 3 kinase (PI3K) inhibitor (1 mg/kg), both tanshinone IIA and PI3K inhibitor, or saline (model group) on a daily basis. After 2 weeks of treatment, HE staining and α-SMA immunofluorescence staining were used to evaluate the morphology of the pulmonary vessels of the rats. The phosphorylation levels of PI3K, protein kinase B (PKB/Akt) and endothelial nitric oxide synthase (eNOS) in the lung tissue were determined with Western blotting; the levels of eNOS and NO were measured using enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#The results of HE staining and α-SMA immunofluorescence staining showed that tanshinone IIA effectively inhibited MCT-induced pulmonary artery intimamedia thickening and muscularization of the pulmonary arterioles (P < 0.01). The results of Western blotting showed that treatment with tanshinone IIA significantly increased the phosphorylation levels of PI3K, Akt and eNOS proteins in the lung tissue of PAH rats; ELISA results showed that the levels of eNOS and NO were significantly decreased in the rat models after tanshinone IIA treatment (P < 0.01).@*CONCLUSION@#Treatment with tanshinone IIA can improve MCT-induced pulmonary hypertension in rats through the PI3K/Akt-eNOS signaling pathway.
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Animales , Masculino , Ratas , Abietanos , Hipertensión Pulmonar/tratamiento farmacológico , Monocrotalina/toxicidad , Óxido Nítrico Sintasa de Tipo III/uso terapéutico , Fosfatidilinositol 3-Quinasa/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Arteria Pulmonar , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Lung cancer, a malignancy with high incidence rate and mortality rate, is a major threat to human life and health. At present, the common methods for the treatment of lung cancer include surgical resection, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, but these methods generally have the problems of severe toxic/side effect and high treatment cost. Traditional Chinese medicine(TCM) has a history of more than 2 000 years of application in China and has its unique advantages in the treatment of tumors. Modern pharmacological experiments have found that TCM can inhibit tumor growth, prolong patients' survival, and improve clinical symptoms and patients' quality of life by inducing tumor cell apoptosis, inhibiting tumor angiogenesis, and reducing tumor cell drug resistance. Apoptosis is a process of spontaneous programmed cell death, which is closely related to the occurrence and development of the tumor. Studies have shown that many Chinese medicines can inhibit the development of lung cancer by inducing apoptosis. This study searched, analyzed, and summarized the available papers on the mechanism of TCM in the treatment of lung cancer by inducing apoptosis. It is found that Chinese medicine induces lung cancer cell apoptosis mainly by regulating apoptosis-related factors and apoptosis-related signaling pathways [inhibitor of apoptosis proteins (IAPs), B cell lymphoma-2 (Bcl-2), p53 protein, the second mitochondria-derived activator of caspase (SMAC)/direct IAP-binding protein with low isoelectric point (DIABLO), extrinsic apoptotic pathway, endogenous mitochondrial pathway, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In addition, the Wnt/β-catenin/survivin signaling pathway and the Notch signaling pathway also play an important role in inducing apoptosis.
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This study aimed to prepare evodiamine-glycyrrhizic acid(EVO-GL) micelles to enhance the anti-hepatic fibrosis activity of evodiamine. Firstly, EVO-GL micelles were prepared with use of thin film dispersion method. With particle size, encapsulation efficiency, loading capacity of micelles and the solubility of evodiamine as the indexes, the effect of different factors on micelles was observed to screen the optimal preparation methods and process. Then the pharmaceutical properties and the therapeutic effects of EVO-GL micelles prepared by optimal process were evaluated on CCl_4-induced hepatic fibrosis. The results showed that the micelles prepared by the thin film dispersion method had an even size, with an average particle size of(130.80±12.40)nm, Zeta potential of(-41.61±3.12) mV, encapsulation efficiency of 91.23%±1.22%, drug loading of 8.42%±0.71%, high storage stability at 4 ℃ in 3 months, and slow in vitro release. Experimental results in the treatment of CCl_4-induced hepatic fibrosis in rats showed that EVO-GL micelles had a synergistic anti-hepatic fibrosis effect, which significantly reduced the liver function index of hepatic fibrosis rats. In conclusion, the EVO-GL micelles prepared with glycyrrhizic acid as a carrier would have a potential application prospect for the treatment of hepatic fibrosis.
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Animales , Ratas , Portadores de Fármacos , Ácido Glicirrínico , Cirrosis Hepática , Micelas , Tamaño de la Partícula , Quinazolinas , SolubilidadRESUMEN
<p><b>OBJECTIVE</b>To investigate the selective inhibitory effect of glycyrrhetinic acid on 4 hepatocellular carcinoma (HCC) cells with different proliferation rates and explore the underlying mechanisms.</p><p><b>METHODS</b>MTT method was used to detect the proliferation rates of 4 HCC cell lines, namely SMMC-7721, SK-HEP1, HEPG2 and HEP3B. Following treatment of the cells with glycyrrhetinic acid (5, 10, 20, 30, 40, and 60 µmol/L), the cell viability was analyzed using MTT assay and the expressions of total ERK protein, p-ERK protein and topoisomerase IIα were detected using Western blotting.</p><p><b>RESULTS</b>Among the 4 cell lines, SMMC-7721 had the lowest and SK-HEP1 had the highest proliferation rate. Treatment with glycyrrhetinic acid for 48 h dose-dependently inhibited the proliferation of all the 4 cell lines in vitro and produced the strongest inhibitory effect in SMMC-7721 cells with the IC of 28.04 µmol/L. The proliferation rate of the cells was positively correlated with the expression levels of p-ERK and topoisomerase IIα, which were the lowest in SMMC-7721 cells and the highest in SK-HEP1 cells. Treatment with 50 µmol/L glycyrrhetinic acid significantly down-regulated the expressions of p-ERK and topoisomerase IIα in the 4 HCC cell lines (P<0.05), while 25 µmol/L glycyrrhetinic acid significantly reduced the expression of topoisomerase IIα and p-ERK in SMMC-7721, HEPG2 and HEP3B cells (P<0.05) but not in SK-HEP1 cells.</p><p><b>CONCLUSION</b>Glycyrrhetinic acid can inhibit the proliferation of different HCC cells particularly in cells with a low proliferation rate. The inhibitory effect of glycyrrhetinic acid might be mediated by reducing the expressions of topoisomerase IIα and inhibiting the ERK pathway.</p>
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In this study, the total alkaloids of Huangteng were given to the rats by the methods of intragastric administration and tail vein. After the concentration changes of palmatine and jatrorrhizine in the plasma of rats were determined by RP-HPLC, pharmacokinetic parameters and oral bioavailability were calculated by 3P97 software. After the rats were pre-treated with total alkaloid 60 mg•kg⁻¹ by the methods of intragastric administration and tail vein, the main pharmacokinetic parameters were determined as follows: in the intragastric administration group, the Cmax of palmatine and jatrorrhizine were (0.91±0.06), (0.70±0.08) mg•L⁻¹; tmax of palmatine and jatrorrhizine were (35.24±0.83), (47.76±1.24) min; t1/2 of palmatine and jatrorrhizine were (187.03±1.53), (105.64±16.99) min, AUC of palmatine and jatrorrhizine were (280.30±18.69), (144.36±1.06) mg•min•L⁻¹; in the intravenous injection group, the t1/2 of palmatine and jatrorrhizine were (172.18±12.38), (147.26±1.82) min; AUC of palmatine and jatrorrhizine were (2 553.14±214.91), (328.83±10.81) mg•min•L⁻¹. The oral bioavailability of palmatine was 10.98% and jatrorrhizine was 43.90%.
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In this study, a central venous catheter (CVC)-associated infection model was established in rats to investigate and evaluate the effect of biofilms on the virulence of the pathogens. Twenty-four adult SD rats were randomly divided into biofilm positive (BF+) and biofilm negative (BF-) groups to be challenged with strains of S.epidermidis. Serum levels of inflammatory cytokines were measured and the infection rate and counts of bacteria cells were studied. Compared to rats of BF- group, the serum level of TNF and IL-6 significantly increased in rats of BF+ group (P < 0.01) and the level of IL-10 and IFN-γ significantly decreased (P < 0.01), striking the balance of pro-inflammatory/anti-inflammatory cytokines. The infection rate and bacterial counts in tissues and blood of rats of BF + group were significantly higher than those of rats of BF- group (P < 0.05).Inflammatory cell infiltration in vital organs (heart, lung, liver and kidneys) was more significant in rats of BF+ group than that of rats of BF- group. CVC-associated infection model can be successfully reproduced in rats by injecting 5 × 10(6) CFU of S.epidermidis. Biofilm formation can significantly enhance the virulence of the bacteria, leading to uncontrolled infection. The serum level of inflammatory cytokines, infection rate and the extent of inflammatory cell infiltration are important markers for evaluating the virulence of biofilm.
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Biopelículas/crecimiento & desarrollo , Infecciones Relacionadas con Catéteres/etiología , Catéteres Venosos Centrales/efectos adversos , Modelos Animales de Enfermedad , Infecciones Estafilocócicas/etiología , Staphylococcus epidermidis/fisiología , Animales , Infecciones Relacionadas con Catéteres/sangre , Catéteres Venosos Centrales/microbiología , Citocinas/sangre , Masculino , Especificidad de Órganos , Ratas , Infecciones Estafilocócicas/sangre , Staphylococcus epidermidis/patogenicidad , VirulenciaRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of L-Arginine (L-Arg) on pulmonary surfactant (PS) expression and alveolar macrophage (AM) in rats with pulmonary injury induced by lipopolysaccharide (LPS).</p><p><b>METHODS</b>Model of acute lung injury (ALI) was made by injection (iv) with LPS 5 mg/kg in rats. Fourty-eight male SD rats were randomly divided into 3 groups(n = 16): control, model (LPS) and L-Arg groups. L-Arg (500 mg/kg ip ,L-Arg group) or saline (control and LPS group) was administrated at 3 h or 6 h after LPS injection respectively for 3 h. The expression of surfactant protein A (SP-A) mRNA in the lung tissue was detected by ISH. The total protein (TP) in the bronchoalveolar lavage fluid (BALF) was detected. Rat AM were isolated from the bronchial alveolar lavage fluid of SD rats and harvested by selective plating technique. LPS and L-Arg were added to the culture medium. The concentration of nitric oxide (NO),the activity of lactate dehydrogenase (LDH), the contents of tumor necrosis factor alpha (TNF-alpha) and interleukin- 6 (IL-6) in the culture supernatants were respectively measured.</p><p><b>RESULTS</b>Compared with the control group, the expression of SP-A mRNA was significantly decreased, the TP concentration was significantly increased in LPS group. Compared with LPS group at the same time points, treatment with L-Arg at 3 h after LPS, the expression of SP-A mRNA in lung tissue was increased markedly, whereas TP concentration was decreased significantly. In cultured rat AM, LDH activity, NO, TNF-alpha and IL-6 contents in culture medium were significantly increased in LPS group to compared with those of control group. LDH activity, TNF-alpha and IL-6 contents were decreased in L-Arg group compared with those of LPS group.</p><p><b>CONCLUSION</b>L-Arg can protect the lung against LPS-induced pulmonary injury by up-regulating the expression of PS and inhibiting inflammatory transmitters from AM.</p>
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Animales , Masculino , Ratas , Lesión Pulmonar Aguda , Quimioterapia , Metabolismo , Arginina , Farmacología , Usos Terapéuticos , Lipopolisacáridos , Macrófagos Alveolares , Metabolismo , Surfactantes Pulmonares , Metabolismo , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>To develop a method for detecting the topical concentration of hydrocortisone (HC) in the subcutaneous adipose of rats using microdialysis sampling technique and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).</p><p><b>METHODS</b>Topical samples were collected by applying the probe into the subcutaneous adipose of rats, with alcohol (5%)-ringers solution as the perfusion solution. A LC-MS/MS method was established for detecting the HC concentration in the dialysates.</p><p><b>RESULTS</b>The protonated precursor to produce ion transitions monitored for HC was m/z 363.2→121.1. The calibration curve was linear over the range of 0.5-1000 ng/ml, with the intra- and inter-day precision and accuracy within ∓15%, and no significant matrix effect was noted. The in vivo recovery of the probe was about 59%.</p><p><b>CONCLUSION</b>A selective and sensitive method has been successfully established for the on-line HC detection in the subcutaneous adipose of rats.</p>
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Animales , Masculino , Ratas , Administración Cutánea , Cromatografía Liquida , Métodos , Hidrocortisona , Farmacocinética , Microdiálisis , Métodos , Ratas Wistar , Grasa Subcutánea , Química , Metabolismo , Espectrometría de Masas en Tándem , MétodosRESUMEN
<p><b>OBJECTIVE</b>To study the effect of podophyllotoxin nanostructured lipid carriers (POD-NLC) on immortalized human cervical epithelial cells (H8) infected with HPV in vitro.</p><p><b>METHODS</b>POD-NLC was prepared by emulsion evaporation method and characterized using transmission electron microscopy, Zetasizer analyzer and high-performance liquid chromatography (HPLC). H8 cells were treated with different concentrations (0.0001-1 µg/ml) of POD-NLC, free POD, or blank nanostructured lipid carriers (NLC), and the cell proliferation was assessed using MTT assay to evaluate the cytotoxic effects. The changes of cell morphology were observed using fluorescence microscopy, and the cell cycle changes and cell apoptosis were analyzed using flow cytometry.</p><p><b>RESULTS</b>POD-NLC showed a spherical or elliptical shape with good stability in vitro. The average particle size of POD-NLC was 85.6∓10.25 nm, with a Zeta potential of 26.2∓4.1 mV and entrapment efficiency of POD of (88.56∓3.1)%. POD-NLC caused a significant inhibition of H8 cell proliferation in a concentration- and time-dependent manner. At an equivalent concentration, POD-NLC produced a stronger inhibitory effect on cell proliferation than POD. The inhibition rate of H8 cells after a 48-h exposure to POD-NLC and POD reached 95.8% and 65.6%, respectively, and at the highest concentration of 1 µg/ml, the IC(50) of POD-NLC and POD was 0.015 µg/ml and 0.13 µg/ml, respectively. Blank NLC did not obviously affect the proliferation of H8 cells. POD-NLC and POD both caused obvious increases in G(2)/M phase cell percentages and induced typical apoptotic changes of the cells, and their effects were comparable (P>0.05).</p><p><b>CONCLUSION</b>Compared with POD, POD-NLC has more potent effect in inhibiting H8 cell proliferation and inducing cell apoptosis, suggesting its potential in the treatment of cervical HPV infection.</p>
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Femenino , Humanos , Apoptosis , Ciclo Celular , Proliferación Celular , Cuello del Útero , Biología Celular , Portadores de Fármacos , Farmacología , Células Epiteliales , Infecciones por VIH , Patología , Lípidos , Nanoestructuras , Tamaño de la Partícula , Podofilotoxina , FarmacologíaRESUMEN
To examine the histological changes of diabetic rats' skin and the effects on the percutaneous absorption of hydrocortisone (HC, a glucocorticoid), male Wistar rats were randomly divided into five groups: control group, diabetes one-week group (W1), two-week group (W2), three-week group (W3), and four-week group (W4), while each group contained 6 rats. Diabetes mellitus (DM) rat model was prepared with the method of streptozocin (STZ, 40 mg x kg(-1)) intraperitoneal injection. Abdominal skin was cut to carry out an in-vitro penetration experiment on an improved Franz diffusion cells, and phosphate buffer (PBS, pH 7.4) was used as receptor solution. The solution was analyzed with HPLC, and then the penetrating rate can be calculated. Meanwhile, rats' abdominal skins of different DM periods were HE stained and made into tissue slices to find if any histological changes occurred. The penetrating rate of control, W1, W2, W3, and W4 groups were 2.39 +/- 1.25, 3.22 +/- 1.72, 3.02 +/- 1.89, 3.63 +/- 2.02 and 5.00 +/- 3.36 microg x h(-1) x cm(-2), respectively. There was significant difference between the control and the W4 group (P < 0.05), but no significant differences were found between any other two groups (P > 0.05). The tissue slices showed that compared to the normal rats' skin, little change was observed in one-week DM rats' skin, but the skin of one-month DM rats' skin was observed thinner, and it became much thinner than that of rats with two-month diabetes, especially the epidermis. After making a rat into diabetic, the rats' skin goes through a pathological change, and this change is closely interrelated with the increase of the permeation of HC. Therefore, it is necessary to adjust the dose while some drug was applied on the skin in case of diabetes mellitus.
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Animales , Masculino , Ratas , Diabetes Mellitus Experimental , Metabolismo , Patología , Hidrocortisona , Farmacocinética , Distribución Aleatoria , Ratas Wistar , Piel , Patología , Absorción CutáneaRESUMEN
To investigate the modulation on the P-glycoprotein in the jejunum by combined use of Glycyrrhiza inflata and Kansui with ussing chamber and rt-pcr, Rhodamine 123 (R123), a P-gp substrate and fluorescein sodium (CF), a model drug of non-P-gp substrate transported by a passive diffusion were taken as investigational drugs. Because these two drugs can be easily assayed and widely used in various research fields. The permeability of R123 or CF via Wistar rat jejunum membranes was evaluated by in vitro ussing chamber after oral administration of four different decoctions of Glycyrrhiza inflata and Kansui for 1 week. And the concentration of R123 or CF was determined by the fluorospectrophotometry in the receiving solution. Meanwhile the expression of mdr1a in P-glycoprotein was detected by real-time fluorescent quantitative PCR. After oral administration of combined decoction of the single drug, the absorptive directed permeability of R123 increased significantly (P < 0.01). On the other hand, Kansui and combine decoction of the two drugs also decrease the permeability of secretory directed transport (P < 0.05). No action of Glycyrrhiza inflata was found on the secretory transport of R123 [Papp = (2.56 +/- 0.38) x 10(-5), cm x s(-1)] across the jejunum tissues, while Papp of control group was found [Papp = (2.35 +/- 0.27) x 10(-5), cm x s(-1)]. After oral administration of Kansui decoction for 1 week and 2 weeks, the levels of mdr1a expression in Wistar rats were lower than that of the control group, but there were no significant difference in the results. Meanwhile, Glycyrrhiza inflata had no effect on transport of CF across the jejunum tissues, though the other three groups could decrease the permeability of CF, as compared with control group. Kansui may slightly inhibit P-glycoprotein function in the intestinal membrane. For another, some compositions in Kansui inhibit P-glycoprotein function, and some others strengthen the tight junction between cells in the intestinal membrane to decrease permeability of CF. As the inhibitory action to P-glycoprotein was enhanced by combination of Glycyrrhiza inflata and Kansui, based on the results, it may be one of the mechanisms of creating toxicity once co-administration of Glycyrrhiza inflata and Kansui.
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Animales , Masculino , Ratas , Subfamilia B de Transportador de Casetes de Unión a ATP , Genética , Metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Farmacocinética , Administración Oral , Transporte Biológico , Permeabilidad de la Membrana Celular , Medicamentos Herbarios Chinos , Farmacología , Euphorbia , Química , Fluoresceína , Farmacocinética , Glycyrrhiza , Química , Absorción Intestinal , Mucosa Intestinal , Metabolismo , Yeyuno , Metabolismo , Plantas Medicinales , Química , ARN Mensajero , Metabolismo , Distribución Aleatoria , Ratas Wistar , Rodamina 123 , FarmacocinéticaRESUMEN
<p><b>OBJECTIVE</b>To evaluate the effect of different preparation methods on the encapsulation efficiency (EE) and drug loading (DL) of paclitaxel-loaded polybutylcyanoacrylate nanoparticles (PTX-PBCA-NPs) and optimize the preparation of PTX-PBCA-NPs.</p><p><b>METHODS</b>With DL and EE as the major indexes, the qualities of PTX-PBCA-NPs produced by the interfacial polymerization and emulsion polymerization method were compared. The optimized prescription was obtained by orthogonal design.</p><p><b>RESULTS</b>The ranges of EE of PTX-PBCA-NPs with the two methods were both 94.39%-99.23%. The highest DL with interfacial polymerization was (1.07-/+0.03)%, as compared to (0.86-/+0.01)% with emulsion polymerization. The optimized preparation conditions resulted in the mean size of PTX-PBCA-NPs of 235.6 nm, DL of 0.80%, and EE of 95.71%.</p><p><b>CONCLUSION</b>The EE of PTX-PBCA-NPs prepared by the above two methods is consistent with the requirement of the Pharmacopoeia of China, and PTX-PBCA-NPs containing higher DL can be obtained via interfacial polymerization.</p>
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Preparaciones de Acción Retardada , Portadores de Fármacos , Química , Sistemas de Liberación de Medicamentos , Enbucrilato , Química , Nanopartículas , Química , Paclitaxel , PolimerizacionRESUMEN
<p><b>OBJECTIVE</b>To compare the therapeutic effects of minocycline, metronidazole and iodine glycerin on periodontitis.</p><p><b>METHODS</b>A total of 123 patients were randomly divided into 3 groups to receive the 3 topical remedies administered into the periodontal pockets. The total response rate of the 3 treatments was calculated, and the changes in GI, PL I, PD and BO P were observed.</p><p><b>RESULTS</b>All the clinical indices of the 3 groups showed obvious improvements after the treatments compared with the baseline levels. The clinical indices of minocycline group and metronidazole group showed significant greater improvements than those of iodine glycerin group. The total response rate in minocycline group and metronidazole group was higher than that of iodine glycerin group.</p><p><b>CONCLUSIONS</b>Minocycline and metronidazole as topical remedies can be effective auxiliary treatments of periodontitis.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Administración Tópica , Antibacterianos , Usos Terapéuticos , Yodo , Usos Terapéuticos , Metronidazol , Usos Terapéuticos , Minociclina , Usos Terapéuticos , Bolsa Periodontal , Periodontitis , QuimioterapiaRESUMEN
<p><b>OBJECTIVE</b>To prepare lidocaine nanoemulsion and investigate its transdermal delivery ability in vitro.</p><p><b>METHODS</b>The optimal Km (surfactant/cosurfactant) value and the component proportion were determined by pseudoternary phase diagrams combined with Origin software analysis. The diameter and distribution range were detected by Zeta particle size analysis instrument, and the morphology of the nanoemulsion was observed by electron microscope. The permeation flux of lidocaine was determined in vitro using the modified Franz diffusion cell combined with HPLC, and the cumulative transdermal absorption amount and the apparent skin transdermal velocity were compared among nanoemulsion, gel and tincture containing 5% lidocaine. The permeation mode of lidocaine nanoemulsion was analyzed.</p><p><b>RESULTS</b>The average drop size of lidocaine nanoemulsion was 29.8-/+14.4 nm, and 98% of the drop sizes ranged from 15.1 to 45.5 nm and 2% from 77.9 to 261.3 nm. The nanoemulsion drop showed a spherical morphology in a polydisperse system. The Kp value of the nanoemulsion (3.07-/+0.74 cm/h) was significantly higher than that of gel (1.27-/+0.35 cm/h) and tincture (0.97-/+0.18 cm/h), and the permeation rate of the nanoemulsion was 69.82-/+7.48 microg x cm(-2) x h(-1), which fitted the the Zero-order release dynamic procedure.</p><p><b>CONCLUSIONS</b>The component proportion of lidocaine nanoemulsion can be conveniently obtained through pseudoternary phase diagrams and Origin software analysis, and the drop size, distribution, morphology and system type can be determined by Malvern Zetasizer combined with electron microscopy. The results also indicate that the nanoemulsion system with high permeation rate may provide a new promising means for local anesthesia.</p>
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Animales , Masculino , Ratas , Administración Cutánea , Anestésicos Locales , Metabolismo , Emulsiones , Lidocaína , Metabolismo , Nanopartículas , Tamaño de la Partícula , Permeabilidad , Ratas Wistar , Absorción CutáneaRESUMEN
<p><b>OBJECTIVE</b>To develop and validate a sensitive method for quantitative analysis of podophyllotoxin in blood and dermal microdialysis samples of rats based on liquid chromatography-tandem mass spectrometry (UFLC-MS-MS).</p><p><b>METHODS</b>The microdialysis samples were prepared by liquid-liquid extraction using ethyl acetate with etoposide as the internal standard (IS). Podophyllotoxin was separated with an Agilent ZORBAX XDB-C18 column (2.1 mmx50 mm, 3.5 microm). The mobile phase consisted of acetonitrile: 10 mmol/L ammonium acetate (40:60, V/V) at a flow rate of 0.3 ml/min and the analysis was performed at the ambient temperature. The UFLC-MS/MS system was operated in the mode of multiple reaction monitoring using the electrospray ionization technique in positive mode.</p><p><b>RESULTS</b>Podophyllotoxin and etoposide responses were optimized at the transitions m/z 432.7-->397.3 and 589.5-->229.5, respectively. Calibration curves were linear over the range 2.0-1000 ng/ml. The lowest limits of quantification and detection values were 2.0 ng/ml and 0.7 ng/ml, respectively. The inter- and intra-day precision and accuracy were both less than 15%.</p><p><b>CONCLUSION</b>This selective and sensitive method can be used to quantity podophyllotoxin in the blood and dermal microdialysates of rats.</p>
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Animales , Ratas , Cromatografía Liquida , Métodos , Microdiálisis , Métodos , Podofilotoxina , Sangre , Farmacocinética , Sensibilidad y Especificidad , Piel , Metabolismo , Espectrometría de Masas en Tándem , MétodosRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of imatinib on rat C6 glioma cell apoptosis and cell cycle.</p><p><b>METHODS</b>MTT assay was used to determine the OD value of C6 glioma cells following treatment with imatinib at different concentrations (0.156, 10 and 15 micromo/L) for 24, 48 and 72 h. The cell apoptosis was assayed by Hochest/PI staining and the cell cycle changes were analyzed by flow cytometry.</p><p><b>RESULTS</b>Imatinib treatment resulted in increased number of apoptotic cells in a time- and dose-dependent manner. A 72-h treatment of the cells with imatinib at 10 and 15 micromo/L caused increased cell percentage in G(0)/G(1) phase to (68.53-/+0.83)% and (70.41-/+0.62)%, (P<0.01), decreased the percentage of G(2) phase cells to (14.48-/+0.12)% and (13.84-/+2.86)% (P<0.01), and decreased the percentage of S phase cells to (16.98-/+0.72)% and (15.78-/+2.28)%, respectively (P<0.01).</p><p><b>CONCLUSION</b>Imatinib can induce apoptosis and affect the distribution of the cell cycle of C6 cells in vitro.</p>
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Animales , Ratas , Antineoplásicos , Farmacología , Apoptosis , Benzamidas , Ciclo Celular , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Glioma , Patología , Mesilato de Imatinib , Piperazinas , Farmacología , Pirimidinas , FarmacologíaRESUMEN
Objective To analyze the effect of minimally invasive puncture combined with continuous lumbar subarachnoid drainage in the treatment of thalamic expanding hematoma. Methods Seventy-eight patients with thalamic expanding hematoma admitted in our department from 2004 to 2008 underwent minimally invasive puncture combined with continuous lumbar subarachnoid drainage according to the size of intracranial hematoma and the involvement of the cerebral ventricles. Results Of the 78 cases, death occurred in 10 cases, with a mortality rate of 12.8%. The other 68 (87.2%) patients exhibited postoperative recovery of different degrees. Follow-up of the 68 patients for over 6 months after the operation showed that 30 patients had grade 1 Activity of Daily Living (ADL) with independence in daily living, 25 had grade 2 ADL (partially independent in daily living), 19 had grade 3 ADL (capable of assisted walking), 3 had grade 4 ADL (bedridden but conscious), and one patient had grade 5 ADL (in persistent vegetative state). Conclusion This combined treatment with individualized operations reduces the surgical trauma to the minimum and lowers the cost for effective elimination of the hematoma. This procedure also effectively lowers the intracranial pressures and promotes the neurological recovery of the patients with thalamic expanding hematoma.
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<p><b>OBJECTIVE</b>To investigate the effect of liquorice in functional modulation of intestinal P-glycoprotein (P-gp) in rats.</p><p><b>METHODS</b>An in vitro diffusion chamber system (Ussing chamber) was used to examine the direct effect of liquorice decoction on rhodamine 123 (a subtrate of P-gp) transport and evaluate the permeability of rhodamine 123 or fluorescein sodium through rat jejunum membranes after oral administration of liquorice decoction.</p><p><b>RESULTS</b>Direct application of liquorice decoction did not obviously affect rhodamine 123 transport across the intestinal mucosa. Oral administration of liquorice decoction (10 g/kg, twice daily for a week) significantly increased the absorption of rhodamine 123 and also enhanced rhodamine 123 secretion across the jejunum mucosa. Liquorice had no obvious effect on the transport of CF across the jejunum mucosa.</p><p><b>CONCLUSION</b>Liquorice may slightly inhibit P-gp function in the intestinal mucosa to increase the intestinal absorption of rhodamine 123.</p>
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Animales , Masculino , Ratas , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Metabolismo , Glycyrrhiza , Absorción Intestinal , Mucosa Intestinal , Metabolismo , Intestinos , Metabolismo , Extractos Vegetales , Farmacología , Ratas Sprague-Dawley , Rodamina 123 , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To summarize the experiences in the treatment of distal radius fracture by locking pi-shaped plate internal fixation.</p><p><b>METHODS</b>All the 32 cases (left 11, right 21) of unstable fractures of distal radius treated by locking pi plate fixation. Among them, 11 were male and 21 female with an average age of 36 years (range, from 23 to 67 years). There were 16 cases of type B, 9 type C1 and 7 type C2 according to AO classification. Autogeneic bone grafting was applied in 27 patients. All the 32 cases were followed up. The range of motion of the wrist joint and radiographic parameters including palmar inclination, radial length and ulnar variance were evaluated.</p><p><b>RESULTS</b>All the patients were followed up for 19 to 28 months postoperatively (mean 25 months). Anatomical reduction was achieved in all the cases. Delayed union or non-union was not observed. According to rating scale of Gartland-Werley, 25 cases got excellent results and 7 good. No complications such as loss of reduction, tendon rupture occurred.</p><p><b>CONCLUSION</b>Locking pi-shaped plate fixation is a reliable and effective method in the treatment of unstable fracture of distal radius.</p>
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placas Óseas , Fijación Interna de Fracturas , Métodos , Fracturas del Radio , Cirugía GeneralRESUMEN
<p><b>OBJECTIVE</b>To evaluate the anti-proliferative and apoptosis-inducing effect of podophyllotoxin solid lipid nanoparticles (PDP-SLN) in human cervical carcinoma cells in vitro.</p><p><b>METHODS</b>Hela cells were treated with PDP and PDP-SLN at different concentrations (0.0005-5 micromol/L), and the proliferation of the cells was assessed using MTT assay and the apoptotic index was determined by flow cytometry.</p><p><b>RESULTS</b>Both PDP and PDP-SLN showed obvious inhibitory effect on the cell proliferation in a dose- and time-dependent manner. At the same concentration, PDP-SLN produced stronger inhibitory effect on the cells than PDP, with IC50 24, 48, and 72 h after the cell exposure to PDP-SLN and PDP of 4.10, 0.65, 0.20 micromol/L and 9.2, 4.0, 1.3 micromol/L, respectively. Both PDP and PDP-SLN significantly induced the apoptosis of the Hela cell, and the apoptosis rates of the cells incubated in the presence of 0.5 micromol/L PDP-SLN reached 90.8% at 24 h and 94.2% at 72 h, significantly higher than the rate of cells incubated with PDP (64.1% at 24 h and 68.4% at 72 h, P<0.01).</p><p><b>CONCLUSION</b>PDP-SLN can effectively suppress the proliferation and induce apoptosis of Hela cells in vitro.</p>