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1.
Chinese Medical Journal ; (24): 839-844, 2018.
Article in English | WPRIM | ID: wpr-687031

ABSTRACT

<p><b>Objective</b>Hydrogen sulfide (HS), a gaseous signal molecule, plays a crucial role in many pathophysiologic processes in the cardiovascular system. Autophagy has been shown to participate in the occurrence of many cardiac diseases. Increasing evidences indicated that HS regulates myocardial structure and function in association with the altered autophagy and plays a "switcher" role in the autophagy of myocardial diseases. The aim of this review was to summarize these insights and provide the experimental evidence that HS targets cardiomyocyte autophagy to regulate cardiovascular function.</p><p><b>Data Sources</b>This review was based on data in articles published in the PubMed databases up to October 30, 2017, with the following keywords: "hydrogen sulfide," "autophagy," and "cardiovascular diseases."</p><p><b>Study Selection</b>Original articles and critical reviews on HS and autophagy were selected for this review.</p><p><b>Results</b>When autophagy plays an adaptive role in the pathogenesis of diseases, HS restores autophagy; otherwise, when autophagy plays a detrimental role, HS downregulates autophagy to exert a cardioprotective function. For example, HS has beneficial effects by regulating autophagy in myocardial ischemia/reperfusion and plays a protective role by inhibiting autophagy during the operation of cardioplegia and cardiopulmonary bypass. HS postpones cardiac aging associated with the upregulation of autophagy but improves the left ventricular function of smoking rats by lowering autophagy.</p><p><b>Conclusions</b>HS exerts cardiovascular protection by regulating autophagy. Cardiovascular autophagy would likely become a potential target of HS therapy for cardiovascular diseases.</p>


Subject(s)
Animals , Autophagy , Cardiovascular Diseases , Cardiovascular System , Cell Biology , Humans , Hydrogen Sulfide , Therapeutic Uses , Myocytes, Cardiac , Cell Biology
2.
Chinese Medical Journal ; (24): 2226-2232, 2016.
Article in English | WPRIM | ID: wpr-307437

ABSTRACT

<p><b>BACKGROUND</b>Clarifying the mechanisms underlying vascular smooth muscle cell (VSMC) proliferation is important for the prevention and treatment of vascular remodeling and the reverse of hyperplastic lesions. Previous research has shown that the gaseous signaling molecule sulfur dioxide (SO2) inhibits VSMC proliferation, but the mechanism for the inhibition of the angiotensin II (AngII)-induced VSMC proliferation by SO2has not been fully elucidated. This study was designed to investigate if SO2inhibited VSMC proliferation in mice with hypertension induced by AngII.</p><p><b>METHODS</b>Thirty-six male C57 mice were randomly divided into control, AngII, and AngII + SO2groups. Mice in AngII group and AngII + SO2group received a capsule-type AngII pump implanted under the skin of the back at a slow-release dose of 1000 ng·kg-1·min-1. In addition, mice in AngII + SO2received intraperitoneal injections of SO2donor. Arterial blood pressure of tail artery was determined. The thickness of the aorta was measured by elastic fiber staining, and proliferating cell nuclear antigen (PCNA) and phosphorylated-extracellular signal-regulated kinase (P-ERK) were detected in aortic tissues. The concentration of SO2 in serum and aortic tissue homogenate supernatant was measured using high-performance liquid chromatography with fluorescence determination. In the in vitro study, VSMC of A7R5 cell lines was divided into six groups: control, AngII, AngII + SO2, PD98059 (an inhibitor of ERK phosphorylation), AngII + PD98059, and AngII + SO2 + PD98059. Expression of PCNA, ERK, and P-ERK was determined by Western blotting.</p><p><b>RESULTS</b>In animal experiment, compared with the control group, AngII markedly increased blood pressure (P < 0.01) and thickened the aortic wall in mice (P < 0.05) with an increase in the expression of PCNA (P < 0.05). SO2, however, reduced the systemic hypertension and the wall thickness induced by AngII (P < 0.05). It inhibited the increased expression of PCNA and P-ERK induced by AngII (P < 0.05). In cell experiment, PD98059, an ERK phosphorylation inhibitor, blocked the inhibitory effect of SO2on VSMC proliferation (P < 0.05).</p><p><b>CONCLUSIONS</b>ERK signaling is involved in the mechanisms by which SO2inhibits VSMC proliferation in AngII-induced hypertensive mice via ERK signaling.</p>


Subject(s)
Angiotensin II , Pharmacology , Animals , Cell Proliferation , Extracellular Signal-Regulated MAP Kinases , Metabolism , Hypertension , Drug Therapy , Male , Mice , Muscle, Smooth, Vascular , Cell Biology , Signal Transduction , Sulfur Dioxide , Therapeutic Uses
3.
Article in Chinese | WPRIM | ID: wpr-297364

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the relationship between Chinese medical constitutions and chemotherapy-induced leucopenia (CIL) of primary breast cancer patients.</p><p><b>METHODS</b>Totally 306 breast cancer patients undergoing adjunctive chemotherapy for the 1st time, and effective 291 breast cancer patients were recruited in this study.Nine Basic Constitutional Scale was used before first chemotherapy. Chinese medical constitutions were classified and quantitatively scored. The highest grading for any item of adverse reactions in each case during the whole chemotherapy course was recorded after chemotherapy. Data were statistically analyzed using SPSS16.0.</p><p><b>RESULTS</b>There was no significant difference in CIL between different chemotherapy regimens and various Chinese medical constitutions of breast cancer patients (P > 0.05). Yang deficiency constitution is one risk factor for CIL. The higher the score of yang deficiency constitution, the more severe the CIL.</p><p><b>CONCLUSIONS</b>Yang deficiency constitution was correlated with the degree of CIL. The higher the score of yang deficiency constitution, the greater the risk of III-IV grade CIL in breast cancer patients.</p>


Subject(s)
Breast Neoplasms , Drug Therapy , Drugs, Chinese Herbal , Therapeutic Uses , Female , Humans , Leukopenia , Medicine, Chinese Traditional , Yang Deficiency
4.
Chinese Medical Journal ; (24): 586-592, 2015.
Article in English | WPRIM | ID: wpr-357953

ABSTRACT

<p><b>BACKGROUND</b>Differentiating benign from malignant sinonsal lesions is essential for treatment planning as well as determining the patient's prognosis, but the differentiation is often difficult in clinical practice. The study aimed to determine whether the combination of diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can improve the performance in differentiating benign from malignant sinonasal tumors.</p><p><b>METHODS</b>This retrospective study included 197 consecutive patients with sinonasal tumors (116 malignant tumors and 81 benign tumors). All patients underwent both DW and DCE-MRI in a 3-T magnetic resonance scanner. Two different settings of b values (0,700 and 0,1000 s/mm 2 ) and two different strategies of region of interest (ROI) including whole slice (WS) and partial slice (PS) were used to calculate apparent diffusion coefficients (ADCs). A DW parameter with WS ADCs b0,1000 and two DCE-MRI parameters (time intensity curve [TIC] and time to peak enhancement [Tpeak]) were finally combined to use in differentiating the benign from the malignant tumors in this study.</p><p><b>RESULTS</b>The mean ADCs of malignant sinonasal tumors (WS ADCs b0,1000 = 1.084 × 10-3 mm 2 /s) were significantly lower than those of benign tumors (WS ADCs b0,1000 = 1.617 × 10-3 mm 2 /s, P < 0.001). The accuracy using WS ADCs b0,1000 alone was 83.7% in differentiating the benign from the malignant tumors (85.3% sensitivity, 81.2% specificity, 86.4% positive predictive value [PPV], and 79.5% negative predictive value [NPV]). The accuracy using DCE with Tpeak and TIC alone was 72.1% (69.1% sensitivity, 74.1% specificity, 77.5% PPV, and 65.1% NPV). Using DW-MRI parameter was superior than using DCE parameters in differentiation between benign and malignant sinonasal tumors (P < 0.001). The accuracy was 87.3% (90.5% sensitivity, 82.7% specificity, 88.2% PPV, and 85.9% NPV) using DW-MRI combined with DCE-MRI, which was superior than that using DCE-MRI alone or using DW-MRI alone (both P < 0.001) in differentiating the benign from the malignant tumors.</p><p><b>CONCLUSIONS</b>Diffusion-weighted combined with DCE-MRI can improve imaging performance in differentiating benign from malignant sinonasal tumors, which has the potential to improve diagnostic accuracy and to provide added value in the management for these tumors.</p>


Subject(s)
Adult , Contrast Media , Diffusion Magnetic Resonance Imaging , Methods , Female , Humans , Magnetic Resonance Imaging , Methods , Male , Middle Aged , Paranasal Sinus Neoplasms , Diagnosis , Retrospective Studies
5.
Article in Chinese | WPRIM | ID: wpr-671723

ABSTRACT

Objective To find the changes of haemagglutination inhibition ( HI ) antibody level against A/California/07/2009 (H1N1) within one month after pandemic A/H1N1 influenza vaccine (A/H1N1InfV) vaccination, and to provide data for drawing up immunization protocols against novel influenza . Methods The HI antibodies against A/California/07/2009 (H1N1) in sera from the inoculated subjects were tested by HI test .The geometric mean titer ( GMT) , geometric mean increase ( GMI) , seroconversion (SC) rate, seroprotection (SP) rate of HI antibodies were compared among the sera collected on day 3, 7, 14, 30 post vaccination .Results 961 participants were injected with A/H1N1InfV.In subjects aged 3 to 11 years, the antibody level peaked on day 14 post vaccination, but neither on day 14 nor on day 30, the lower bound of the two -sided 95%CI for the SP rate could fulfill the criteria of the FDA for influenza vac-cine.In subjects aged 12 to 60 years, the antibody level peaked on day 14 post vaccination and the SC rate , SP rate and GMI fulfilled the criteria of the European Medicines Agency ( EMEA) and the FDA for influenza vaccine. In subjects aged more than 60 years, the antibody level peaked on day 30 post vaccination , and the SC rate, SP rate and GMI on day 30 fulfilled the criteria of the EMEA and the FDA .Conclusion One dose A/H1N1InfV vaccination was able to induce enough protection on day 14 for subjects aged 12 to 60 years, on day 30 for subjects aged more than 60 years;however , for subjects aged 3 to 11 years who were antibody-negative at baseline , the lower bound of the two-sided 95%CI for the SP rate on day 14 and day 30 couldn′t fulfill the criteria of the FDA for influenza vaccine .

6.
Article in Chinese | WPRIM | ID: wpr-288546

ABSTRACT

<p><b>OBJECTIVE</b>To find out the metabolite profile of rats' myocardial tissue of cardiac blood stasis syndrome (CBSS), and to analyze the metabolic pathway of CBSS rats' myocardial tissue by observing the changes of phenotypes intervened by Yangxin Tongmai Recipe (YTR).</p><p><b>METHODS</b>Acute myocardial infarction (AMI) rat model of CBSS was prepared by ligating the left anterior descending coronary artery. Meanwhile, the model was interfered with YTR. The metabolites of rats' myocardial tissue were detected in the model group, the YTR group, the sham-operation group, and the blank control group using GC-MS (8 rats in each group). Changes of metabolite contents were analyzed among different groups using principal component analysis (PCA) and least-square analysis.</p><p><b>RESULTS</b>As for PCA: The results of PCA showed that principal component integral (PCI) of the four groups was mainly distributed in the three regions of oval scatterplot. The factor loading gram showed that contents of glycine, fumaric acid, malic acid, glutamic acid, glucose, phosphoric acid, galactopyranose, lysine were changed in the model group. Analysis of partial least square method: PLS regression model showed that obvious linear correlation existed between the model group and the YTR group, which proved the model was reasonably established. The drug intervention was highly positively correlated with glycine, malic acid, glutamic acid, glucose, highly correlated with urea and butanedioic acid, but negatively correlated with lysine. According to VIP value, each variable was closely correlated with the drug intervention in sequence as malic acid, glutamic acid, glycine, glucose, fumaric acid, urea, galactose, tyrosine, lactic acid, and alanine. Results of variability analysis: Obvious changed variability analysis of metabolite difference showed that 10 metabolites such as glycine, etc. obviously decreased in the model group, showing significant difference when compared with the normal group (P<0.01). Compared with the model group, contents of glycine, fumaric acid, malic acid, glutamic acid, glucose, tyrosine,urea, lactic acid, and alanine, etc. obviously increased after drug intervention (P<0.01). Of them, the increment of malic acid, glumatic acid, tyrosine, and urea was less, showing significant difference when compared with that of the normal group. The mean of lysine was slightly lowered after drug intervention, but with insignificant difference when compared with that of the model group. AMI rats of CBSS was closely correlated with myocardial metabolites such as malic acid, glutamic acid, glycine, glucose, fumaric acid, urea, galactopyranose, lactic acid, alanine, and tyrosine, etc.</p><p><b>CONCLUSIONS</b>The metabolite profile of rats' myocardial tissue showed AMI rat model of CBSS was closely correlated with post-hypoxia glucose metabolism disorder. YTR could effectively intervene this process.</p>


Subject(s)
Animals , Drugs, Chinese Herbal , Pharmacology , Heart , Male , Medicine, Chinese Traditional , Metabolome , Metabolomics , Myocardial Infarction , Diagnosis , Metabolism , Myocardium , Metabolism , Principal Component Analysis , Rats , Rats, Sprague-Dawley
7.
Chinese Journal of Cardiology ; (12): 1045-1050, 2012.
Article in Chinese | WPRIM | ID: wpr-292044

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the modulation effects of mesenchymal stem cells (MSC) implantation on the myofibroblasts congregating in the infarct region after myocardial infarction (MI).</p><p><b>METHODS</b>MI was induced in SD rats by left anterior descending coronary artery ligation, and the experimental animals were assigned randomly into the sham group, MI + PBS group and MI + MSC group (myocardial injection of 0.1 ml 2×10(7)/ml in four locations in the infarct region). Echocardiography, hemodynamic examinations and Masson trichrome staining were performed. Implanted MSC differentiation and myofibroblasts congregating in infarct region were investigated by immunofluorescence staining. TGF-β(1)-Smad2 signaling pathway was examined by real-time RT-PCR and Western blot.</p><p><b>RESULTS</b>(1) Four weeks late, heart-weight/body-weight ratio [(3.04 ± 0.16) mg/g vs. (3.34 ± 0.14) mg/g, P < 0.01] and myocardial infarction size [(38.72 ± 2.38)% vs. (46.36 ± 2.81)%, P < 0.01] were significantly reduced in MI + MSC group than in MI + PBS group, while scar thickness of infarct region was thicker [(0.93 ± 0.17) mm vs. (0.65 ± 0.16) mm, P = 0.01], and LVEF was higher [LVEF: (32.5 ± 5.9)% vs. (26.5 ± 4.5)%, P = 0.03] in MI + MSC group than in MI + PBS group. (2) Myofibroblasts congregating in the infarct region was significantly enhanced in MI + MSC group compared with MI + PBS group [(196 ± 20) cells/mm(2) vs. (89 ± 25) cells/mm(2), P < 0.01], and part of implanted MSC expressed α-SMA(+). (3) TGF-β(1) expression and the phosphorylating of Smad2 in the infarct region were significantly upregulated in MI + MSC group compared with MI + PBS group (all P < 0.05).</p><p><b>CONCLUSIONS</b>MSC could improve myocardial function and promote myofibroblasts congregating in the infarct region via activating the TGF-β(1)-Smad2 signaling pathway in this model.</p>


Subject(s)
Animals , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Myocardial Infarction , Metabolism , Therapeutics , Myofibroblasts , Cell Biology , Metabolism , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1 , Metabolism , Ventricular Remodeling
8.
Article in Chinese | WPRIM | ID: wpr-235088

ABSTRACT

<p><b>OBJECTIVE</b>To discuss the influence of nano-silica content which was hydrolyzed by tetraethyl orthosioate (TEOS) on the aluminum borate whisker (AlBw) and silica filler composite resins on flexural properties.</p><p><b>METHODS</b>The nanometer-size silicon dioxide (SiO2) particles were prepared by sol-gel method based on tetraethyl orthosioate. Different proportion of AlBw and SiO2 were fused and attached onto the surface of AlBw through high temperature, then polymerized with resin matrix after surface siliconization and their flexural strength and flexural modulus were determined. The effects of heat treatment to the surface morphology of AlBw and the shapes of the mixture at various proportions were characterized by TEM.</p><p><b>RESULTS</b>The flexural properties of dental composite resins with AlBw-SiO2 compound as inorganic fillers were significantly improved. The flexural property of a new type of dental composite resins was(130.29 +/- 8.38) MPa, when the mass ratio of AlBw and nano-SiO2 particle was 3:1.</p><p><b>CONCLUSION</b>Nano-silica content which was hydrolyzed by tetraethyl orthosioate improved flexural properties of the aluminum borate whisker and silica filler composite resins.</p>


Subject(s)
Acrylic Resins , Aluminum , Animals , Borates , Composite Resins , Materials Testing , Pliability , Polyurethanes , Silanes , Silicon Dioxide , Vibrissae
9.
Chinese Journal of Cardiology ; (12): 840-846, 2011.
Article in Chinese | WPRIM | ID: wpr-268304

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the modulation effects of mesenchymal stem cells (MSCs) implantation on the collagen remodeling in myocardial infarction.</p><p><b>METHODS</b>Acute myocardial infarction (AMI) was induced in SD rats by left anterior descending coronary artery ligation, and the animals were assigned randomly into the Sham group, MI + PBS group and MI + MSCs group. Echocardiography and hemodynamic examinations were performed to evaluate the cardiac function. HE staining and Masson trichrome staining were used to evaluate the myocardial infarction size. Infarcted area and infarcted expansion index were calculated. The expression of collagens in infarcted hearts was evaluated by immunohistochemistry, RT-PCR and Western blot.</p><p><b>RESULTS</b>(1) Infarct area was significantly reduced post MSCs transplantation [MI + MSCs vs. MI + PBS: (38.27 ± 2.70)% vs. (46.20 ± 3.17)%, P < 0.001]. (2) Cardiac function was significantly improved post MSCs transplantation [MI + MSCs vs. MI + PBS: FS(%): 29.98 ± 4.50 vs. 23.43 ± 3.34, P = 0.005; LVSP (mm Hg, 1 mm Hg = 0.133 kPa): 113.63 ± 10.81 vs. 99.25 ± 16.76, P < 0.05; LVEDP (mm Hg): 12.10 ± 4.28 vs. 20.08 ± 4.26, P < 0.05; +dp/dtmax (mm Hg/s): 4616.63 ± 363.34 vs. 3912.75 ± 248.79, P < 0.05; -dp/dtmax (mm Hg/s): 4254.63 ± 324.34 vs. 3530.88 ± 309.71, P < 0.05]. (3) Collagen synthesis was enhanced in infarcted area and decreased in non-infarcted area post MSCs transplantation (P < 0.05).</p><p><b>CONCLUSIONS</b>MSCs transplantation could enhance the collagen synthesis in infarcted area while decrease the deposition of collagen in non-infarcted area in this MI model. This may be one of the mechanisms by which ventricular remodeling is attenuated post MSCs transplantation.</p>


Subject(s)
Animals , Collagen , Metabolism , Disease Models, Animal , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Myocardial Infarction , Metabolism , Rats , Rats, Sprague-Dawley , Ventricular Remodeling
10.
Chinese Medical Journal ; (24): 3277-3281, 2010.
Article in English | WPRIM | ID: wpr-241592

ABSTRACT

<p><b>BACKGROUND</b>Inner retinal oxygenation response (ΔPO(2)) is a worldwide study focus. However, the relevant reports on its radiological measurements are limited. In this study, magnetic resonance imaging (MRI), employing T1 weighted image (T1WI), was used to detect changes in ΔPO(2) following 100% oxygen inhalation in human subjects.</p><p><b>METHODS</b>MRI was performed on a 1.5-T GE scanner system. After obtaining ophthalmologic data, eleven healthy individuals were given room air and 100% oxygen inhalation in order with different intervals. The MRI T1WI data were collected for 50 minutes. Data were analyzed with NIH IMAGE software.</p><p><b>RESULTS</b>ΔPO(2) was not panretinally uniform, and changes in oxygenation response were spatially inhomogeneous. During the initial phase (before 5 minutes) of 100% oxygen inhalation, preretinal vitreous water signals in the region of papilla optica increased rapidly. On the contrary, in other regions signals declined. In a later period (35 minutes), ΔPO(2) was panretinally fluctuated and increased slowly and attained homeostasis. After hyperoxia (45 minutes), delayed-enhancement of preretinal vitreous water signals in regions other than the papilla optica occurred, and then dropped down. There was no significant difference (P > 0.05) at any consecutive time point during and after hyperoixa.</p><p><b>CONCLUSIONS</b>These results reveal that hyperoxia can induce region-specific signal changes in preretinal vitreous water. Regulatory activity of the retinal vessel network may be the mechanism during 100% oxygen inhalation. Moreover, MRI is a valuable tool for investigating ΔPO(2) and exploring the mechanism of retinal oxygenation response physiologically or pathologically in vivo.</p>


Subject(s)
Adult , Female , Humans , Magnetic Resonance Imaging , Methods , Male , Oxygen Consumption , Physiology , Retina , Physiology , Young Adult
11.
Article in Chinese | WPRIM | ID: wpr-680053

ABSTRACT

Objective To evaluate values of magnetic resonance imaging(MRI)in eyes filled with silicone oil.Design Prospective cases series.Participants 40 eyes of 40 patients were filled with silicone oil after ocular injury.Methods MRI was performed in the 40 patients,including axial FSE T_1WI,T_2WI,coronal T_2WI with fat saturation,oblique sagittal T_1WI and axial T_2FLAIR.MRI findings,in- cluding morpbous,signal and complications were analyzed.Oculi axes were measured.Main Outcome Measures Morphous,signal, complications and oculi axes of the eyes filled with silicone oil.Results Affected oculi axis was 2.18cm?0.21cm,normal oculi axis was 2.48cm?0.16cm.The silicone oil in eyes demonstrated isointense signal or slightly hyperintense signal on T_1WI and T_2WI,hypointense signal after fat saturation.Hydrops was found in vitreous cavity in 33 patients,including simple hydrops in 17 patients and complicated other abnormality in 16 patients.Choroidal detachment was found in 11 patients,complicating vitreous hydrops in 5 patients and lo- calized bulge of eyeball wall.Retinal detachments were found in 4 patients,of whom 3 patients complicated with vitreous hydrops.Per- fluorocarbon liquid residual in vitreous cavity,foreign body in anterior chamber,localized thickness of the wall of the globe and meagre- mean of silicone oil in vitreous cavity were found respectively in one patient complicating vitreous hydrops.Except for eye changes, fracture of orbital wall and foreign body in orbit were found in one patient.Conclusions MRI can display the changes of eyes filled with silicone oil,and measure oculi axes biologically and accurately offering important clinical application value.(Ophthalmol CHN,2007,16: 312-315)

12.
Article in Chinese | WPRIM | ID: wpr-263786

ABSTRACT

<p><b>OBJECTIVE</b>To screen the mutations of RET proto-oncogene in sporadic patients with pheochromocytoma.</p><p><b>METHODS</b>Forty-two cases of sporadic pheochromocytoma were tested for mutations of RET gene. Of these 42 DNA samples, 12 were extracted from peripheral blood cells and 30 from paraffin-embedded pheochromocytoma specimens. The PCR product of exon 10 and exon 11 was used to molecular analysis of the RET proto-oncogene.</p><p><b>RESULTS</b>Among 42 patients, 2 were found to have RET gene mutations. One of mutations located at codon 634 (TGC>TAC) in exon 11 of RET proto-oncogene. Another one located at codon 632 (GAG>AAG).</p><p><b>CONCLUSION</b>Some patients with apparently sporadic pheochromacytoma were carrier of mutations, a routine genetic analysis for mutations of RET gene is indicated for these patients.</p>


Subject(s)
Adrenal Gland Neoplasms , Diagnosis , Genetics , Adult , Asian Continental Ancestry Group , Genetics , Base Sequence , China , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Genetics , Genetic Testing , Humans , Male , Middle Aged , Mutation , Pheochromocytoma , Diagnosis , Genetics , Polymerase Chain Reaction , Proto-Oncogene Proteins c-ret , Genetics
13.
Acta Pharmaceutica Sinica ; (12): 1104-1110, 2006.
Article in Chinese | WPRIM | ID: wpr-294880

ABSTRACT

<p><b>AIM</b>The feasibility of intranasal brain targeting drug delivery system via the olfactory pathway from nose to brain was explored.</p><p><b>METHODS</b>Using gellan gum, a cation-sensitive gel forming excipient, huperzine A (Hup A) nasal in situ gel was prepared by pH gradient precipitation method. The pharmacokinetics of Hup A in blood and cerebrospinal fluid (CSF) after intranasal, intravenous and intragastric adminstration to rats was studied using cisternal cannulation for serial CSF sampling and femoral artery cannulation for serial blood sampling. The distributions of Hup A into rat brain tissues following intranasal dosing were compared with those after intravenous and intragastric dosing by tissue homogeneization. The therapeutics effects of Hup A nasal in situ gel on cognitive function were tested in mice and rats with Morris water maze, step down test and step through test.</p><p><b>RESULTS</b>The AUC(0-->6 h) value in plasma obtained after nasal administration was 0.94 of that after intravenous administration, but the AUC(0-->6 h) of CSF after nasal administration was 1.3 and 2.3 times of that after intravenous and intragastric administration. The AUC(0-->6 h), of cerebrum, hippocampus, cerebellum, left olfactory bulb and right olfactory bulb after nasal administration were 1.5, 1.3, 1.0, 1.2 and 1.0 of that after intravenous administration, 2.7, 2.2, 1.9, 3.1 and 2.6 times of that after intragastric administration, respectively. Intranasal adminintration of 17.5-35 microg x kg(-1) showed equal effects after oral adminintration of 70 microg x kg(-1) commercial tablets, which was in good agreement with the results of pharmacokinetics.</p><p><b>CONCLUSION</b>Intranasal administration of huperzine A nasal in situ gel significantly increased the distributions of Hup A into rat brain tissues, especially into cerebrum and hippocampus which should be the target areas of Hup A, and enhanced the brain targeting of Hup A.</p>


Subject(s)
Administration, Intranasal , Alkaloids , Animals , Area Under Curve , Biological Transport , Brain , Metabolism , Cattle , Cognition , Drug Compounding , Methods , Guinea Pigs , Injections, Intravenous , Male , Maze Learning , Mice , Models, Biological , Nasal Mucosa , Metabolism , Neuroprotective Agents , Pharmacokinetics , Pharmacology , Particle Size , Polysaccharides, Bacterial , Chemistry , Random Allocation , Rats , Rats, Sprague-Dawley , Rats, Wistar , Sesquiterpenes , Blood , Cerebrospinal Fluid , Pharmacokinetics
14.
Article in Chinese | WPRIM | ID: wpr-679676

ABSTRACT

Objective To evaluate MR imaging findings of uveal metastases.Methods MR imaging findings of 20 cases with uveal metastases comfirmed by pathology or follow-up were retrospectively analyzed.MR imaging was performed in 20 patients,of which postcontrast T1-weighted imaging was performed in 19 patients including dynamic contrast enhancement scanning in four cases.Results Metastatic tumor was found in the iris and ciliary body in two cases,and in choroid in 18 cases.The tumor demonstrated slightly hypointense signal on Tl-weighted imaging and isointense signal on T2-weighted imaging in two cases,isointense signal on T1-weighted imaging and isointense signal on T2-weighted imaging in nine cases,isointense signal on T_1-weighted imaging and slightly hyperintense signal on T_2-weighted imaging in three cases,isointense signal on T_1-weighted imaging and slightly hypointense signal on T_2- weighted imaging in three cases,slighdy hyperintense signal on T_1-weighted imaging and slightly hypointense signal on T_2-weighted imaging in two cases,and slightly hyperintense signal on T_1-weighted imaging and slightly hyperintense signal on T_2-weighted imaging in one case.The tumor appeared as mild thickness of the wall of the globe in eight cases,a crescent mass in three cases,a fusiform mass in seven cases,and a nodule in two cases.Nineteen patients showed moderate or marked enhancement on postcontrast T_1-weighted imaging.The time-intensity curve of dynamic contrast enhancement in four patients suggested a rapid enhancement and slow washout pattern.Retinal detachment was observed in 11 patients and abnormal signal intensity within the vitreous body was seen in two cases.Conclusion MRI can display the location,shape, signal characteristics,and enhancement pattern of uveal metastases,contributing to diagnosis and differential diagnosis.

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