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@#AIM:To quantitatively evaluate the macular microvasculature and visual function in patients with macular edema secondary to retinal vein occlusion(RVO)by optical coherence tomography angiography(OCTA)combined with microperimetry. <p>METHODS: Totally 36 patients(36 eyes)with monocular RVO complicated with macular edema were enrolled, including 15 patients(15 eyes)in central retinal vein occlusion(CRVO)group and 21 patients(21 eyes)in branch retinal vein occlusion(BRVO)group(all with superior temporal vein occlusion), 15 age-matched healthy subjects(24 eyes)were included as controls. OCTA was used to scan macular retina in the range of 3mm×3mm in all three groups and measure the vascular density(VD)of superficial capillary plexus(SCP)and deep capillary plexus(DCP), the area of foveal avascular zone(FAZ)and the central retinal thicknes(CRT); the retinal mean sensitivity(RMS)at 10°was measured by MP-3 microperimetry. VD and RMS in BRVO group were further divided into lesion area(superior), non-lesion area(inferior)VD and RMS. The lesion area and non-lesion area of the control group were divided according to corresponding regions of the BRVO group. The changes of above indexes in CRVO group and BRVO group were compared with control group respectively, and the correlation between RMS and VD, CRT and FAZ areas in CRVO group and BRVO group was analyzed.<p>RESULTS:The overall VD(SCP and DCP)in CRVO group were lower than those in control group(<i>t</i>= -2.536, <i>P</i>=0.016; <i>t</i>= -8.834, <i>P</i><0.001); the area of FAZ was larger than that in control group(<i>t</i>=3.354, <i>P</i>=0.002); the CRT was thicker than that in control group(<i>t</i>=13.888, <i>P</i><0.001); the overall RMS was significantly lower than that in control group(<i>t</i>= -6.250, <i>P</i><0.001). The overall VD(SCP and DCP)in BRVO group were decreased compared to those in control group(<i>t</i>= -5.186, <i>P</i><0.001; <i>t</i>= -5.238, <i>P</i><0.001); the VD of SCP and DCP in the affected sector were decreased compared to those in the corresponding sector of the control group(<i>t</i>= -5.611, <i>P</i><0.001; <i>t</i>= -6.940, <i>P</i><0.001); the VD in the unaffected sector was significantly less than that in the corresponding sector of the control group only in DCP, but not in SCP(<i>t</i>= -3.047, <i>P</i>=0.004; <i>t</i>= -1.459, <i>P</i>=0.156); the area of FAZ was larger than that in control group(<i>t</i>=2.722, <i>P</i>=0.011); the CRT was thicker than that in control group(<i>t</i>=7.764, <i>P</i><0.001); the overall RMS was significantly lower than that in control group(<i>t</i>= -10.931, <i>P</i><0.001); the RMS in both the affected sector and the unaffected sector were lower than those in the corresponding sector of the control group(<i>t</i>= -13.183, <i>P</i><0.001; <i>t</i>= -8.074, <i>P</i><0.001). In CRVO group,the overall VD of SCP and DCP was positively correlated with the overall RMS(<i>r</i>=0.571, <i>P</i>=0.026; <i>r</i>=0.813, <i>P</i><0.001)and the area of FAZ and CRT was negatively correlated with the overall RMS(<i>r</i>= -0.621, <i>P</i>=0.014; <i>r</i>= -0.533, <i>P</i>=0.041). In BRVO group,the overall VD of SCP and DCP was positively correlated with the overall RMS(<i>r</i>=0.465, <i>P</i>=0.034; <i>r</i>=0.611, <i>P</i>=0.003), and the CRT was negatively correlated with the overall RMS(<i>r</i>= -0.547, <i>P</i>=0.01), while there was no correlation between the area of FAZ and the overall RMS(<i>r</i>= -0.421, <i>P</i>=0.057).<p>CONCLUSION: The combined application of OCTA and microperimetry can corresponding quantitatively evaluate the structure and function of macular area in patients with macular edema secondary to retinal vein occlusion, providing more detailed information for clinical decision makers to explain the disease well.
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Objective: To study the relative molecular mass and composition of Ligustrum lucidum polysaccharide purified by dialysis, and provide the theories for the relationship between the biological activity and the internal composition. Methods: In this paper, L. lucidum as an object was studied. Polysaccharide was isolated by water extraction and ethyl alcohol precipitation and purified by Sevage method, hydrogen peroxide and dialysis. After the acidolysis of trifluoroacetic acid, the molecular weight was measured by GPC, and the composition of polysaccharide was analyzed by HPLC-RID. Results: The Mw of polysaccharide was 10 721, and the Mn of polysaccharide was 10 673. L. lucidum polysaccharide consisted of glucose, rhamnose, and arabinose, the molar ratio of these monosaccharide was 9.148.105.18. Conclusion: The purified polysaccharide composition is more homogeneous, and the monosaccharides of polysaccharides was easily analyzed by HPLC-RID without column derivatization.
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Talaromyces marneffei is the only dimorphic species in its genus and causes a fatal systemic mycosis named talaromycosis. Our previous study indicated that knockdown of AcuD gene (encodes isocitrate lyase of glyoxylate bypass) of T. marneffei by RNA interference approach attenuated the virulence of T. marneffei, while the virulence of the AcuD knockout strains was not studied. In this study, T. marneffei-zebrafish infection model was successfully established through hindbrain microinjection with different amounts of T. marneffei yeast cells. After co-incubated at 28°C, the increasing T. marneffei inoculum doses result in greater larval mortality; and hyphae generation might be one virulence factor involved in T. marneffei-zebrafish infection. Moreover, the results demonstrated that the virulence of the ΔAcuD was significantly attenuated in this Zebrafish infection model.
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Técnicas de Inativação de Genes , Hifas , Isocitrato Liase , Microinjeções , Mortalidade , Rombencéfalo , Interferência de RNA , Talaromyces , Virulência , Leveduras , Peixe-ZebraRESUMO
Objective To investigate the unusual drug-induced International Normalized Ratio(INR) change in elderly patients with warfarin treatment and its related mechanism. Methods A retrospective analysis was performed in 41 cases of elderly patients with unusual drug-induced INR change from 2011 to 2015 in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology. Results INR was increased unusually in 37 cases(90.2%) and was decreased unusually in 4 cases(9.8%).Intravenous drugs(80.5%) were prone to cause unusual INR change.Prostaglandin,antifungal drugs,antiarrhythmic drugs and lipid soluble vitamins were the commonly used drugs that induced adverse reaction,accounting for 26.8%,29.3%,29.3% and 9.8%,respectively. Conclusion Unusual drug-induced INR change is not rare in elderly patients with warfarin treatment during hospitalization.When other drugs are prescribed,INR should be measured more frequently and the dose of warfarin should be adjusted promptly.
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Objective To investigate prevalence of healthcare-associated infection(HAI) and community associated infection(CAD in hospitalized patients in Hebei Province.Methods A certain day from August 17 to August 28,2015 was selected as the survey day,unified questionnaires were formulated,the prevalence of HAI and CAI in hospitalized patients in secondary and above comprehensive hospitals in Hebei Province was surveyed,pathogens causing infection were analyzed and compared.Results A total of 65 065 patients in 253 hospitals were surveyed,prevalence rates of HAI and CAI were 2.89% and 16.84% respectively.The top three sites of HAI were respiratory tract(61.32%),urinary tract(12.49%),and surgical site(9.83%),the top three sites of CAI were respiratory tract (56.70%),urinary tract(10.89%),and gastrointestinal tract(8.35%).Distribution of sites of HAI and CAI was significantly different(P<0.01).The top 5 pathogens were of the same species,but ranked differently,the main bacteria causing HAI was Pseudomonas aeruginosa (22.69%),CAI was Escherichia coli (23.79%).There was significant difference in the distribution of pathogens between HAI and CAI (P<0.01).There were significant differences in pathogenic species causing respiratory tract,gastrointestinal tract,urinary tract,and intra abdominal infection(all P<0.05).Isolation rates of extended spectrum β-lactamase-producing/carbapenem-resistant Klebsiella pneumoniae,methicillin-resistant Staphylococcus aureus between HAI and CAI were all significantly different(all P <0.001).Conclusion Incidence of infection,infection sites,as well as constituent of pathogens and multidrugresistant organisms between HAI and CAI are varied,besides monitoring on HAI,monitoring on drug resistance of pathogens causing CAI should be paid attention,so as to provide scientific basis for rational antimicrobial use in clinical practice.
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The present study aimed to clone and express the EmLDH gene of Echinococcus multilocularis in Qinghai Province,identifying immunogenicity of EmLDH recombinant protein and evaluating its immune diagnostic value preliminarily.EmLDH genes were cloned by RT-PCR technology and linked into pET15b vector.Recombinant expression pET15b-EmLDH vectors were constructed and transformed into E.coli Rosetta (DE3) competent cells.Recombinant proteins were induced and expressed.Expression forms of recombinant proteins were detected by SDS-PAGE.Recombinant proteins were purified by affinity chromatography of Ni-IDA resin.Immunogenicity of recombinant proteins was identified by Western blotting.Serum samples from patients with alveolar echinococcosis (57 cases),cystic echinococcosis (33 cases),and healthy persons (50 cases) were examined by ELISA,which evaluated preliminarily immune diagnosis effect of EmLDH recombinant proteins.Results showed that EmLDH gene was cloned successfully and the recombinant proteins were expressed and purified.Results of Western blotting showed EmLDH recombinant proteins were recognised by serum samples from patients with alveolar echinococcosis and cystic echinococcosis,but not by serum samples from healthy persons.Results of ELISA showed that diagnostic sensitivities of EmLDH recombinant protein reacted with serum samples from patients with alveolar echinococcosis and cystic echinococcosis were 84.21% and 84.85 % respectively.EmLDH recombinant proteins of Echinococcus multilocularis have high immunogenicity and good immune diagnostic value for echinococcosis.
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To investigate the effect of Tanreqing injection on immune activity of peripheral blood lymphocytes of patients with lung cancer. The peripheral blood lymphocytes of patients with lung cancer and healthy persons were separated by the density gradient centrifugation method for subsequent experiments, with those from healthy persons as the positive control. The effect of Tanreqing injection on stimulating the proliferation of lymphocytes with phytohemagglutinin (PHA) was determined by MTT method. The effect of Tanreqing injection on the lymphocyte secretions of IFN-γ and TNF-α and the subset ratio of lymphocytes cultured separately or with Tanreqing injection of different concentrations were examined by ELISA and flow cytometry (FCM) respectively. In addition, the LDH release assay was used to detect the cytotoxicity of cytotoxic T cells (CTL) and natural killer cells (NK). According to the findings, all of immunological indexes of lymphocytes from patients with lung cancer were weaker than that of healthy persons, but with the obvious increases in proliferation activity and IFN-γ and TNF-α secretions of lymphocytes co-cultured with Tanreqing Injection (P < 0.05). Among lymphocyte subsets co-cultured with Tanreqing Injection, CD3+, CD3+ CD4+ and CD3- CD16 + 56+ cell ratios notably increased, whereas CD4+ CD25+ Treg cell ratio obviously decreased (P < 0.05). In the meantime, Tanreqing injection can markedly promote the cytotoxicities of CTL and NK (P < 0.05). In conclusion, Tanreqing injection shows a significant effect in promoting the immune activity of lymphocytes from patients with lung cancer and their anti-tumor immunity.
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Humanos , Proliferação de Células , Células Cultivadas , Medicamentos de Ervas Chinesas , Interferon gama , Genética , Alergia e Imunologia , Células Matadoras Naturais , Alergia e Imunologia , Neoplasias Pulmonares , Tratamento Farmacológico , Genética , Alergia e Imunologia , Linfócitos T Citotóxicos , Alergia e Imunologia , Fator de Necrose Tumoral alfa , Genética , Alergia e ImunologiaRESUMO
Objective To investigate the effect of atorvastatin on atherosclerosis formation of common carotid artery and its possible mechanism. Methods A total of 36 male apolipoprotein E gene knockout (ApoE-/-) mice were randomly divided into 3 groups: a control group, a model group, and an atorvastatin group. The mice of the control group were fed with normal diet and received a sham operation, while the mice in the model group and the atorvastatin group were given high fat diet and received a right common carotid artery cannulation. At 5 weeks after procedure, the mice in the model group and the atorvastatin group were intragastric administration of normal saline and atorvastatin (10 mg/kg daily), respectively. At 8 weeks after procedure, the blood from femoral arteries was obtained for biochemical detection, then right common carotid arteries were taken out for histopathological study. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of NF-κB mRNA in the plaques. Western blotting was used to detect phosphorylated NF-κB p65. Results The lipid levels in the model group and the atorvastatin group were significant higher than those in the control group (al P 0. 05 ). The histopathological study showed that the obvious plaque formation and the necrotic core and neovessels in plaques were observed in the model group; obviously thickened intima and more intact endothelial cel s in the vessel wal were observed in the atorvastatin group. The plaque burden in the model group and the atorvastatin group was significantly higher than that in the control group (al P<0. 001), while the plaque burden in the atorvastatin group was significantly less than that in the model group (P<0. 001). Real-time fluorescence quantitative PCR detection showed that the expression levels of NF-κB mRNA in the model group and the atorvastatin group were significantly higher than that in the control group (al P<0. 001), and the expression level of NF-κB mRNA in the atorvastatin group was significant lower than that in the model group (P= 0. 022). Western blotting showed that the expression level of the phosphorylated NF-κB p65 was significantly higher than that of the control group (P<0. 001), and the expression level of the phosphorylated NF-κB p65 was significantly lower than that in the model group (P<0. 001). Conclusions Atorvastatin may reduce atherosclerosis in the common carotid artery in ApoE-/-) mice by down-regulating NF-κB.
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Objective To understand the children health care and the prevention of lead pollution in Panyu in the future by re-search on the detection result of blood lead from Panyu children during 2011 and 2012.Methods The detection of whole blood lead was by atomic absorption spectrometer from body examination in 6 308 children in Panyu Center Hospital be-tween 2011 and 2012:①The blood lead result from assigned children were divided into five age groups:infancy group (1~12 months,1 511 cases),toddler age group (1~2 years,1 558 cases),preschool age group (3~6 years,1 704 cases),school age group (7~11 years,1 076 cases)and adolescence group (12~18 years,459 cases).②Based on different age group,each group was separated by male and female.③According to the detection year,each group was also put into 2011 and 2012 re-spectively.Results The overall level of children blood lead in Panyu,Guangzhou in 2011 and 2012 was 37.01±29.18μg/L, and the total poisoning rate was 1.2 9%.Along with the growth of age,the overall level of children blood lead was in up-wards trend but the poisoning rate kept in a stable level beginning from infant stage.The blood lead level of boys in Panyu was 38.87±30.18μg/L,and the poisoning rate was 1.91%;the blood lead level of girls was 34.13±27.32μg/L,and the poisoning rate was 1.29%.The blood lead levels and the poisoning rates of boys were higher than girl’s in most of age groups.Conclusion Compared with other big cities like Guangzhou,the blood lead level of children in Panyu was declined but it’s not the standard performance,and there’s a certain extent of lead pollution.So in addition to reinforce pollution con-trol from government,parents and children should enhance the knowledge,education and precaution of lead poisoning.
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Psoriasis vulgaris (PV) is a common autoimmune disease that involves the dysfunction of CD4+CD25+ regulatory T cells. FOXP3 is a key transcription factor in the development and function of CD4+CD25+ regulatory T cells. Previous studies have demonstrated a genetic association between the FOXP3 gene and some autoimmune diseases. To elucidate the association between the FOXP3 gene and the risk of PV, 408 patients diagnosed with PV and 363 age and sex-matched healthy controls from a cohort of the Chinese majority Han population were recruited. Four single nucleotide polymorphisms (rs2232365, rs3761547, rs3761548 and rs3761549) of the FOXP3 gene were analyzed using the polymerase chain reaction and ligase detection reaction. The major allele of three single nucleotide polymorphisms (SNPs — rs2232365 A, rs3761547 A and rs3761549 C) were associated with an increased risk of PV in a clinical subgroup of female patients, who were less than 40 yrs of age, had a family history of the disease and did not have disease complications (p < 0.05 for all parameters). The haplotype was structured between rs3761547 and rs3761549. An increased risk of PV was observed in haplotype A/A-T/T (p = 0.0055; adjusted OR = 3.188; 95% CI = 0.4354-23.34) and A/G-C/C (p = 0.0082; adjusted OR = 1.288; 95% CI = 0.1529-10.85) between rs3761547 and rs3761549. A synergistic effect was found among the three SNPs. Subjects with the rs2232365AA- rs3761547 AG + GG genotype were more susceptible to PV (p = 0.0393; OR = 2.90; 95% CI = 1.05-7.97). No correlation was found between rs3761548 and the onset of PV. Therefore, the FOXP3 polymorphisms appear to contribute to the risk of psoriasis among the Chinese majority Han population. These findings may aid in our understanding of the pathogenesis of psoriasis
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Adulto , Povo Asiático/genética , China/epidemiologia , Estudos de Coortes , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Inteínas/genética , Polimorfismo de Nucleotídeo Único/genética , Psoríase/epidemiologia , Psoríase/genética , RiscoRESUMO
Cardiac hypertrophy is an independent risk factor for sudden cardiac death in clinical settings and the incidence of sudden cardiac death and ventricular arrhythmias are closely related. The aim of this study was to determine the effects of the calmodulin-dependent protein kinase (CaMK) II inhibitor, KN-93, on L-type calcium current (I(Ca, L)) and early after-depolarizations (EADs) in hypertrophic cardiomyocytes. A rabbit model of myocardial hypertrophy was constructed through abdominal aortic coarctation (LVH group). The control group (sham group) received a sham operation, in which the abdominal aortic was dissected but not coarcted. Eight weeks later, the degree of left ventricular hypertrophy (LVH) was evaluated using echocardiography. Individual cardiomyocyte was isolated through collagenase digestion. Action potentials (APs) and I(Ca, L) were recorded using the perforated patch clamp technique. APs were recorded under current clamp conditions and I(Ca, L) was recorded under voltage clamp conditions. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were observed under the conditions of low potassium (2 mmol/L), low magnesium (0.25 mmol/L) Tyrode's solution perfusion, and slow frequency (0.25-0.5 Hz) electrical stimulation. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were also evaluated after treatment with different concentrations of KN-92 (KN-92 group) and KN-93 (KN-93 group). Eight weeks later, the model was successfully established. Under the conditions of low potassium, low magnesium Tyrode's solution perfusion, and slow frequency electrical stimulation, the incidence of EADs was 0/12, 11/12, 10/12, and 5/12 in sham group, LVH group, KN-92 group (0.5 μmol/L), and KN-93 group (0.5 μmol/L), respectively. When the drug concentration was increased to 1 μmol/L in KN-92 group and KN-93 group, the incidence of EADs was 10/12 and 2/12, respectively. At 0 mV, the current density was 6.7±1.0 and 6.3±0.7 PA·PF(-1) in LVH group and sham group, respectively (P>0.05, n=12). When the drug concentration was 0.5 μmol/L in KN-92 and KN-93 groups, the peak I(Ca, L) at 0 mV was decreased by (9.4±2.8)% and (10.5±3.0)% in the hypertrophic cardiomyocytes of the two groups, respectively (P>0.05, n=12). When the drug concentration was increased to 1 μmol/L, the peak I(Ca, L) values were lowered by (13.4±3.7)% and (40±4.9)%, respectively (P<0.01, n=12). KN-93, a specific inhibitor of CaMKII, can effectively inhibit the occurrence of EADs in hypertrophic cardiomyocytes partially by suppressing I(Ca, L), which may be the main action mechanism of KN-93 antagonizing the occurrence of ventricular arrhythmias in hypertrophic myocardium.
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Animais , Feminino , Coelhos , Benzilaminas , Farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Metabolismo , Cardiomegalia , Metabolismo , Miócitos Cardíacos , Metabolismo , Fisiologia , Sulfonamidas , FarmacologiaRESUMO
The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
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Animais , Masculino , Coelhos , Antiarrítmicos , Antibióticos Antineoplásicos , Carbazóis , Cardiomiopatias , Doxorrubicina , Frequência Cardíaca , Metoprolol , Estresse Oxidativo , Propanolaminas , Resultado do Tratamento , Fibrilação VentricularRESUMO
BACKGROUND: Calcium calmodulin-dependent kinase Ⅱ (CaMKⅡ) can be more active in patients with left ventricular hypertrophy (LVH), which in turn causes phosphorylation of ryanodine receptors, resulting in inactivation and the instability of intracellular calcium homeostasis. The present study aimed to determine the effect of CaMKⅡ–ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia. METHODS: Forty New Zealand rabbits were randomized into four groups (10 per group): sham group, LVH group, KN-93 group (LVH+KN-93), and ryanodine group (LVH+ryanodine). Rabbits in the LVH, KN-93, and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta, while those in the sham group did not undergo the coarctation. After eight weeks, action potentials (APs) were recorded simultaneously in the endocardium and epicardium, and a transmural electrocardiogram (ECG) was also recorded in the rabbit left ventricular wedge model. Drugs were administered to the animals in the KN-93 and ryanodine groups, and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline (1 mol/L) and high-frequency stimulation. RESULTS: The frequency (animals/group) of triggered APs was 0/10 in the sham group, 10/10 in the LVH group, 4/10 in the KN-93 group, and 1/10 in the ryanodine group. The frequencies of ventricular tachycardia were 0/10, 9/10, 3/10, and 1/10, respectively. The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10, 7/10, 2/10, and 1/10, respectively. The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group (P<0.05). CONCLUSIONS: KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH. The CaMKⅡ–ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.
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Objective To determine the effect of calmodulin-dependent kinase Ⅱ (CaMK Ⅱ ) -ryanodinereceptor pathway signaling in rabbits with left ventricular bypertrophy (LVH) and triggered ventricular arrhythmia.Methods Forty New Zealand rabbits were randomized into four groups ( n =10 per group):the sham operation group,LVH group,KN-93 (CaMKⅡ inhibitor) group (LVH + KN-93),and the ryanodinegroup ( LVH + ryanodine).Rabbits in the LVH,KN-93,and ryanodinegroups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while the rabbits in the sham operation group did not have the coarctation.After eight weeks,action potentials (APs) were recorded simultaneously in the endocardium and epicardium,and transmural electrocardiogram (ECG) was also recorded in the wedge shaped models of rabbits' left ventricular myocardium.Drugs were administered to animals in the KN-93 and ryanodinegroups respectively,and the frequency of triggered APs and ventricular tachycardia were recorded after isoprenaline ( 1 μmol/L),and high-frequency electrical stimulation were given to rabbits.Results The incidences (animals/group) of triggered APs were:sham,0/10 ; LVH,10/10; KN-93,4/10; and ryanodine,1/10.The incidences of ventricular tachycardia induced were 0/10,9/10,3/10,and 1/10,respectively.The incidences of triggered ventricular arrhythmias in the KN-93 group and ryanodine groups tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The incidences of triggered ventricular arrhythmias in the KN-93 group and ryanodine groups were much lower than that in the LVH group (P < 0.05).Conclusions KN-93 and ryanodinecan effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMK Ⅱ-ryanodine signaling pathway can be used as a novel target site of treating ventricular arrhythmia.
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Objective To summarize the clinical efficacy of three dimensional conformal radiotherapy with concomitant intrathecal injection followed by systemic chemotherapy in the treatment of high-risk medulloblastoma (MB). Methods The clinical data of 20 patients with high-risk MB,admitted to our hospital from January 2005 to January 2008 and certified postoperatively by pathological examination, were retrospectively analyzed in our study; 15 of them were found tumors in the cerebrospinal fluid and MRI indicated 5 were with nodular cultivation in the spinal cord.Three-dimensional conformal radiation therapy was done for all the patients with the same techniques:28-36 Gy to the whole cranialspinal axis followed by a boost of 18 Gy. All the patients received intrathecal injection with cytarabine and amethopterin concomitantly followed by systemic chemotherapy with nimustine and temozolomide. The treatment efficacy was concluded. Results The mean follow-up was 48.5 months.Three months after treatment,the complete remission (CR) was achieved in 18 (90.0%),and partial remission in 1 (5.0%),and stabilization in 1 (5.0%).Four patients were failed of treatment and died; 1 had recurrence in the region,and 3 had spinal cord planting progress.The median survival time was 53 months; and 3-y overall survival and 3-y disease-free survival were 80.0% and 75.5%,respectively.The major side effects occurred in hematological system and digestive system.No grade Ⅳ bone marrow suppression was noted. Conclusion Three-dimensional conformal radiotherapy and intrathecal injection followed by systemic chemotherapy for high-risk MB is safe and feasible,enjoying good prognosis.
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The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
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Cardiac hypertrophy is an independent risk factor for sudden cardiac death in clinical settings and the incidence of sudden cardiac death and ventricular arrhythmias are closely related. The aim of this study was to determine the effects of the calmodulin-dependent protein kinase (CaMK) II inhibitor, KN-93, on L-type calcium current (I(Ca, L)) and early after-depolarizations (EADs) in hypertrophic cardiomyocytes. A rabbit model of myocardial hypertrophy was constructed through abdominal aortic coarctation (LVH group). The control group (sham group) received a sham operation, in which the abdominal aortic was dissected but not coarcted. Eight weeks later, the degree of left ventricular hypertrophy (LVH) was evaluated using echocardiography. Individual cardiomyocyte was isolated through collagenase digestion. Action potentials (APs) and I(Ca, L) were recorded using the perforated patch clamp technique. APs were recorded under current clamp conditions and I(Ca, L) was recorded under voltage clamp conditions. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were observed under the conditions of low potassium (2 mmol/L), low magnesium (0.25 mmol/L) Tyrode's solution perfusion, and slow frequency (0.25-0.5 Hz) electrical stimulation. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were also evaluated after treatment with different concentrations of KN-92 (KN-92 group) and KN-93 (KN-93 group). Eight weeks later, the model was successfully established. Under the conditions of low potassium, low magnesium Tyrode's solution perfusion, and slow frequency electrical stimulation, the incidence of EADs was 0/12, 11/12, 10/12, and 5/12 in sham group, LVH group, KN-92 group (0.5 μmol/L), and KN-93 group (0.5 μmol/L), respectively. When the drug concentration was increased to 1 μmol/L in KN-92 group and KN-93 group, the incidence of EADs was 10/12 and 2/12, respectively. At 0 mV, the current density was 6.7±1.0 and 6.3±0.7 PA·PF(-1) in LVH group and sham group, respectively (P>0.05, n=12). When the drug concentration was 0.5 μmol/L in KN-92 and KN-93 groups, the peak I(Ca, L) at 0 mV was decreased by (9.4±2.8)% and (10.5±3.0)% in the hypertrophic cardiomyocytes of the two groups, respectively (P>0.05, n=12). When the drug concentration was increased to 1 μmol/L, the peak I(Ca, L) values were lowered by (13.4±3.7)% and (40±4.9)%, respectively (P<0.01, n=12). KN-93, a specific inhibitor of CaMKII, can effectively inhibit the occurrence of EADs in hypertrophic cardiomyocytes partially by suppressing I(Ca, L), which may be the main action mechanism of KN-93 antagonizing the occurrence of ventricular arrhythmias in hypertrophic myocardium.
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The genomic DNA extracted from chicken embryo fibroblasts (CEF) of SPF chickens from three chicken farms was used as template to amplify the ALV proviral DNA by PCR with four pairs of primers, high positive detection rates of gag - gene (29/46), pol - gene (27/46), env - gene (24/46) and LTR fragment (31/46) were achieved. Eight continuous and overlapping fragments were amplified from one DNA sample with 8 pairs of primers according to published sequences, then cloned into the TA vector and se quenced. The complete sequence of the whole genome of ALV strain SD0501 was established and analyzed with DNAstar software. Comparisons of SD0501 sequence with that of other representative endogenous avian virus strains demonstrated that the genomes of ALV were relatively conservative, the nucleotide identity of all the strains was over 99.1%, and env - gene was over 98.5%. However, a low identity was demonstrated among the representative strains of different subgroups, especially, the env - gene showed obvious difference, the corresponding identity was as low as 56.3% - 91.5%.
Assuntos
Animais , Embrião de Galinha , Vírus da Leucose Aviária , Genética , Sequência de Bases , Genoma Viral , Reação em Cadeia da Polimerase , Provírus , Genética , Análise de Sequência de DNA , Organismos Livres de Patógenos Específicos , Sequências Repetidas TerminaisRESUMO
The isolate GN52 of Riemerrella anatipestifer was passaged on the Martin Medium successively according to the optimum condition. The experiments included Gram staining, biochemical test, drug sensitivity test and animal experiments were carried out on the bacteria of 3rd, 11th, 21st, 31st, 41st, 51st and 61st generations. It indicated that the bacterial morphs, biochemical character, drug resistance of the strain had no obvious change, but the virulence showed a trend of reduction.
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<p><b>OBJECTIVE</b>To examine the changes of radiosensitivity of CNE1, a well differentiated squamous cell line of nasopharyngeal carcinoma (NPC), and CNE2, a poorly differentiated squamous cell line of NPC, after treatment with chemotherapeutic agents.</p><p><b>METHODS</b>CNE1 and CNE2 cells with and without treated by adriamycin (ADM) were irradiated by X-ray and the radiosensitivity changes of ADM-treated cells were analyzed according to the cell survival curve generated by colony formation assay.</p><p><b>RESULT AND CONCLUSION</b>Radiosensitivity of CNE1 cells increased after ADM treatment, but that of CNE2 cells decreased, suggesting that different treatment regimens should be planned for advanced squamous cell NPC of different pathological types.</p>