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1.
Artigo em Inglês | MEDLINE | ID: mdl-30854008

RESUMO

Objective: To observe the effects of electroacupuncture (EA) at different acupoints on the expression of N-methyl-D-aspartate receptor (NMDA receptor ) and behaviors in irritable bowel syndrome (IBS) rats. Methods: Wistar rats were randomly divided into blank control group (blank group, n=10) and model preparation group (n=50); experimental rat model of IBS was established by the "neonatal maternal separation and acetic acid enema" combined with "colorectal distension stimulation" method. A total of 50 IBS rats were randomly assigned to five groups of 10 each: model group, Yintang (GV29) group, Neiguan (PC6) group, Tianshu (ST25) group, and Zusanli (ST36) group. Rats in four treatment groups, aged 9 weeks old, were treated with EA by HANS with a sparse-dense wave with a frequency of 2/100 Hz, current of 0.1-0.3mA, and 20 min/stimulation, every other day for a total of 5 sessions. After treatment, the abdominal visceral sensitivity was evaluated by abdominal withdrawal reflex (AWR), and the psychological and emotional behavior of rats were evaluated by the open-field test (OFT). The expression of NMDA receptors in anterior cingulate cortex (ACC) was detected by Quantitative Real-time PCR, and the positive expression of NMDA receptors in colon was detected by immunohistochemistry. Results: The IBS rat's abdomen is more sensitive and irritable; NR1, NR2A, and NR2B in ACC and NR1 and NR2B in colon of rats significantly increased in the model group versus the normal group (P<0.01) and were inhibited in all treatment groups (P<0.01, P<0.05). Additionally, NR2A and NR2B in ACC reduced more in GV29 group (P<0.01) than in other treatment groups (P all<0.05) compared with the model group. The expression of NR2B in colon was significantly inhibited in ST36 group (P<0.01) and inhibited in GV29 group and ST25 group (P all <0.05) compared with the model group. And the expression of NR2B in colon was more inhibited in ST36 group than in PC6 group (P<0.01). Conclusions: EA at different acupoints could obviously relieve abdominal pain and abnormal behaviors in IBS rats in different degrees of effects. The effect of abdominal pain-relief, from greatest to least, is ST25, ST36, GV29, and PC6, while the effect of relieving abnormal behaviors caused by IBS, from greatest to least, is GV29, PC6, ST36, and ST25. There are significant differences in the expressions of NMDA receptors in ACC and colon among different acupoints. This difference should be related to the location distribution and indications of acupoints.

2.
Phytomedicine ; 52: 272-283, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599908

RESUMO

BACKGROUND: Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out. PURPOSE: To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism. METHODS: LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting. RESULTS: LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 µM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1ß, PGE2 and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment. CONCLUSION: The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Animais , Berberina/análogos & derivados , Carragenina/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Zhen Ci Yan Jiu ; 43(1): 25-9, 2018 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-29383890

RESUMO

OBJECTIVE: To observe and compare the effects of electroacupuncture (EA) at "Tianshu" (ST 25) and "Neiguan" (PC 6) for colonic motility and the expression of colon dopamine D 2 in irritable bowel syndrome (IBS) rats, and to explore the specificity of different meridians and different acupoints. METHODS: Forty Wistar newborn rats were randomly divided into blank, model, Tianshu and Neiguan groups. Separation of mother and child and acetic acid coloclyster combined with colorectal distension were used to establish IBS model in the model, Tianshu and Neiguan groups. At the age of 9 weeks, EA at bilateral ST 25 and PC 6 were applied in the corresponding groups 5 times, once every other day. After the intervention, the Bristol fecal score, the latent period of abdominal retraction reflex and the number of contraction waves were recorded. The expression of dopamine D 2 receptor was detected by immunohistochemistry. RESULTS: Compared with the blank group, the Bristol fecal score of the model group was higher (P<0.01), the 1st contraction wave latent period was shorter (P<0.01), the number of contraction waves in 90 s increased (P<0.01), the immunoreactive expression of D 2 receptor in colon decreased (P<0.01). Compared with the model group, the Bristol fecal scores of the Tianshu and Neiguan groups decreased (P<0.01), the 1st contraction wave latent periods were longer (P<0.01), the numbers of contraction waves in 90 s decreased (P<0.01), the positive expressions of D 2 receptor in colon increased (P<0.01, P<0.05). Compared with the Tianshu group, the immunoreactive expression of D 2 receptor in the Neiguan group decreased (P<0.01). CONCLUSION: EA at ST 25 and PC 6 can improve the symptoms of colonic motility in IBS rats. The effect of EA at ST 25 is better, which indicates that different meridians and different acupoints play specific effects.


Assuntos
Eletroacupuntura , Síndrome do Intestino Irritável , Pontos de Acupuntura , Animais , Humanos , Ratos , Ratos Sprague-Dawley , Ratos Wistar
4.
Zhen Ci Yan Jiu ; 42(2): 136-40, 2017 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-29071961

RESUMO

OBJECTIVE: To observe the ethology and expression of transient receptor potential vanilloid-1(TRPV 1) in colon of irritable bowel syndrome (IBS) rats treated by electroacupuncture (EA) at "Yintang" (GV 29) and "Tianshu" (ST 25), so as to explore the different effectiveness of different acupoints and its related mechanism underlying improvement of the symptoms of somatopsychic illness. METHODS: Thirty-two neonatal Wistar rats were randomly divided into blank control group, model group, Yintang (GV 29) group, and Tianshu (ST 25) group (n=8 in each group). IBS model was established by neonatal maternal separation and acetic acid enema combined with colon and rectum expansion stimulation. Rats of the GV 29 and ST 25 groups were given EA treatment at age of 9 weeks old, 20 minutes, once every other day for 5 times. Latency of the 1st time contraction wave and numbers of contractive wave in 90 s were recorded to evaluate abdominal visceral sensitivity by abdominal withdrawal reflex. Horizontal and vertical movements were observed to assess the emotional and psychological behavior of rats by open field test. TRPV 1 expression in colon was detected by immunohistochemistry method. RESULTS: Compared with the black control group, latency of the 1st time contractive wave was significantly shortened and the wave numbers in 90 s were increased significantly in the model group (P<0.01), while the numbers of vertical and horizontal movements were also significantly reduced (P<0.01), accompanied with increased TRPV 1 expression in the colon (P<0.05). Compared with the model group, After EA intervention, the levels of the above-mentioned 5 indexes were significantly reversed in the GV 29 and ST 25 groups (P<0.01,P<0.05), except the number of horizontal movement in the ST 25 group (P>0.05). The expression level of TRPV 1 was significantly lower in the ST 25 group than in the GV 29 group (P<0.01). CONCLUSIONS: EA at GV 29 and ST 25 can alleviate the abdominal pain and improve the mental and emotional disorders in IBS rats. GV 29 has a better effect on relieving the depressive-like psychoemotional behavior of IBS rats, while ST 25 is more effective in treating abdominal pain. There is significantly different influence on TRPV 1 expression in colon between these two treatment groups, which may contribute to their different effect in pain relieving.


Assuntos
Pontos de Acupuntura , Eletroacupuntura , Síndrome do Intestino Irritável/terapia , Canais de Cátion TRPV/genética , Animais , Colo/metabolismo , Humanos , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/metabolismo , Masculino , Ratos , Ratos Wistar , Canais de Cátion TRPV/metabolismo
5.
Eur J Pharmacol ; 811: 222-231, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28648405

RESUMO

Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results exhibited that CFB exerted a dose-dependent suppression on ear edema induced by xylene, significantly mitigated the aggravation of vascular permeability caused by acetic acid and paw edema induced by carrageenan. Additionally, CFB significantly suppressed the productions of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and tumor necrosis factor (TNF-α) in the drug-treated groups as compared with the vehicle group after treatment with carrageenan. Signaling events of nuclear factor-κB (NF-κB) translocation, such as p-IKKα, p-IKKß, p-IκBα and p65 (nucleus) were significantly inactivated, while inhibitor of nuclear factor κBα (IκBα) and p65 (cytosolic) were markedly up-regulated by CFB. Furthermore, CFB also significantly suppressed the mitogen-activated protein kinase (MAPK) pathway by blocking the phosphorylation of p-p38 (phospho-p38 mitogen-activated protein kinases) and p-JNK (phospho-c-jun N-terminal kinase) but not p-ERK (phospho-extracellular signal-regulated kinase). Hence, CFB efficiently prevented inflammation, at least partially, via inhibition of NF-κB and MAPK pathways. These findings provided a pioneering pharmacological basis for the anti-inflammatory effect of CFB and suggested CFB might be a potential candidate for the therapy of inflammatory disorders.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/análogos & derivados , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Ácido Acético/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Berberina/farmacologia , Berberina/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
PLoS One ; 12(1): e0168944, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28045966

RESUMO

In this paper, we evaluated the anti-Helicobacter pylori activity and the possible inhibitory effect on its associated urease by Palmatine (Pal) from Coptis chinensis, and explored the potential underlying mechanism. Results indicated that Pal exerted inhibitory effect on four tested H. pylori strains (ATCC 43504, NCTC 26695, SS1 and ICDC 111001) by the agar dilution test with minimum inhibitory concentration (MIC) values ranging from 100 to 200 µg/mL under neutral environment (pH 7.4), and from 75 to 100 µg/mL under acidic conditions (pH 5.3), respectively. Pal was observed to significantly inhibit both H. pylori urease (HPU) and jack bean urease (JBU) in a dose-dependent manner, with IC50 values of 0.53 ± 0.01 mM and 0.03 ± 0.00 mM, respectively, as compared with acetohydroxamic acid, a well-known urease inhibitor (0.07 ± 0.01 mM for HPU and 0.02 ± 0.00 mM for JBU, respectively). Kinetic analyses showed that the type of urease inhibition by Pal was noncompetitive for both HPU and JBU. Higher effectiveness of thiol protectors against urease inhibition than the competitive Ni2+ binding inhibitors was observed, indicating the essential role of the active-site sulfhydryl group in the urease inhibition by Pal. DTT reactivation assay indicated that the inhibition on the two ureases was reversible, further supporting that sulfhydryl group should be obligatory for urease inhibition by Pal. Furthermore, molecular docking study indicated that Pal interacted with the important sulfhydryl groups and inhibited the active enzymatic conformation through N-H ∙ π interaction, but did not interact with the active site Ni2+. Taken together, Pal was an effective inhibitor of H. pylori and its urease targeting the sulfhydryl groups, representing a promising candidate as novel urease inhibitor. This investigation also gave additional scientific support to the use of C. chinensis to treat H. pylori-related gastrointestinal diseases in traditional Chinese medicine. Pal might be a potentially beneficial therapy for gastritis and peptic ulcers induced by H. pylori infection and other urease-related diseases.


Assuntos
Antibacterianos/farmacologia , Alcaloides de Berberina/farmacologia , Coptis/química , Gastroenteropatias/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Urease/antagonistas & inibidores , Domínio Catalítico , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/enzimologia , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Níquel/química , Extratos Vegetais/metabolismo , Especificidade da Espécie , Compostos de Sulfidrila/química , Urease/metabolismo
7.
J Otol ; 10(1): 29-38, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29937779

RESUMO

Objective: To explore the value of a combined computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating profound sensorineural deafness patients before cochlear implant (CI) surgery. Methods: A retrospective analysis of 1012 cases of profound sensorineural deafness that received CI was performed. Results: A total of 96 cases were diagnosed with inner ear abnormalities including large vestibular aqueduct syndrome (LVAS, n = 61), Michel deformity (n = 3), cochlear incomplete partition I (n = 2), cochlear incomplete partition II (n = 6), cochlear hypoplasia with vestibular malformation (n = 3), cochlear ossification (n = 3), bilateral internal auditory canal obstruction (n = 5) and internal auditory canal stenosis (n = 2). Conclusion: High resolution CT (HRCT) can display bony structures while MRI can image the membranous labyrinth in preoperative evaluation for cochlear implantation. The combination of these two modalities provides reliable anatomical information regarding the bony and membranous labyrinths, as well as the auditory nerve.

8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 42(5): 550-5, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24167137

RESUMO

OBJECTIVE: To investigate the effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats. METHODS: Thirty six spontaneously hypertensive rats (SHR) were divided into 3 groups with 12 animals in each group: SHR control group,operation group and sham operation group. Bilateral renal sympathectomy or sham operation were performed in operation and sham groups,respectively; another 12 WKY rats served as normal controls. The blood pressure and body weight were examined weekly. The animals were sacrificed at w1 and w6, rat hearts were collected and left ventricular mass index (LVMI) was calculated. The expression of TLR4,TNF-α and IL-6 in heart tissue were detected by immunohistochemistry and Western blot. RESULTS: The systolic blood pressure [(201.67 ± 11.09) mmHg compared with (140.0 ± 10.86)mmHg,P<0.05],diastolic blood pressure [(144.50 ± 10.48)mmHg compared with (78.50 ± 7.32)mmHg,P<0.05], LVMI (2.44 ± 0.05 compared with 1.93 ± 0.05,P<0.05),the expression of TLR4 (0.298 ± 0.004 compared with 0.126 ± 0.004, P<0.05), NF-κB (0.249 ± 0.006 compared with 0.195 ± 0.005, P<0.05),TNF-α(0.323 ± 0.004 compared with 0.146 ± 0.004,P <0.05), IL-6 (0.283 ± 0.005 compared with 0.207 ± 0.006, P<0.05) in SHR control group were significantly higher than those in WKY group. Compared to sham operation group,the systolic blood pressure (157.30 ± 9.35 compared with 197.30 ± 11.5, P<0.05),diastolic blood pressure (112.50 ± 6.25 compared with 146.80 ± 7.6, P<0.05),LVMI (2.32 ± 0.04 compared with 2.57 ± 0.09, P<0.05, TLR4 (0.198 ± 0.006 compared with 0.317 ± 0.008, P<0.05), NF-κB (0.208 ± 0.006 compared with 0.332 ± 0.007, P<0.05), TNF-α(0.27 ± 0.009 compared with 0.375 ± 0.004,P<0.05), IL-6 (0.218 ± 0.004 compared with 0.376 ± 0.009, P<0.05) in operation group were all decreased at w1 after sympathectomy. Six weeks after the operation,there were no significant differences in systolic blood pressure (197.50 ± 12.13 compared with 208.83 ± 10.23,P>0.05) and diastolic blood pressure (150.33 ± 7.74 compared with 151.50 ± 8.22, P>0.05) between denervated and sham-operated SHRs; however,the LVMI (2.46 ± 0.07 compared with 2.81 ± 0.05,P<0.05) and the expression of TLR4(0.301 ± 0.009 compared with 0.567 ± 0.006, P<0.05), NF-κB (0.251 ± 0.004 compared with 0.476 ± 0.009,P<0.05),TNF-α(0.324 ± 0.005 compared with 0.535 ± 0.006, P<0.05,IL-6 (0.285 ± 0.009 compared with 0.549 ± 0.007, P<0.05) in operation group were still significantly lower than those in sham operation group. CONCLUSION: Renal sympathetic denervation can significantly delay the progression of LVH in SHR, which may associated with lowering blood pressure and decreasing expression of TLR4, NF-κB,TNF-α, IL-6 in myocardial tissue.


Assuntos
Hipertrofia Ventricular Esquerda/cirurgia , Simpatectomia , Animais , Pressão Sanguínea , Interleucina-6/metabolismo , Rim/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 13(11): 893-5, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22099199

RESUMO

OBJECTIVE: To study the relationship of the incidence of bronchial dysplasia (bronchial anomalous origin and bronchial stenosis) with congenital heart disease. METHODS: A total of 185 children with congenital heart disease or bronchial dysplasia were enrolled. Bronchial dysplasia was identified by the 64-MSCT conventional scanning or thin slice scanning with three-dimensional reconstruction. RESULTS: Forty-five children (25.3%) had coexisting bronchial dysplasia and congenital heart disease. The incidence rate of bronchial dysplasia in children with congenital heart disease associated with ventricular septal defect was higher than in those without ventricular septal defect (33.7% vs 15.0%; P<0.05). There were no significant differences in the incidence rate of bronchial dysplasia between the children with congenital heart disease who had a large vascular malformation and who did not. CONCLUSIONS: Bronchial dysplasia often occurs in children with congenital heart disease. It is necessary to perform a tracheobronchial CT scanning with three-dimensional reconstruction to identify tracheobronchial dysplasia in children with congenital heart disease, especially associated with ventricular septal defect.


Assuntos
Brônquios/anormalidades , Cardiopatias Congênitas/diagnóstico por imagem , Adolescente , Brônquios/embriologia , Criança , Pré-Escolar , Feminino , Humanos , Imagem Tridimensional , Lactente , Masculino , Tomografia Computadorizada por Raios X
10.
Zhonghua Yi Xue Za Zhi ; 84(15): 1265-9, 2004 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-15387963

RESUMO

OBJECTIVE: To establish a new technique for evaluation of the tensile property of articular cartilage using digital speckle correlation method (DSCM). METHODS: Three specimens of whole layer articular cartilage of the size of 10 mm x 4 mm were prepared from the cartilage of head of femur replaced from a 52-year-old male suffering from fracture of neck of femur (old control), the amputated tibia plateau of a 16-year-old female suffering from osteosarcoma (young control), and the cartilage of head of femur of a 19-year-old female suffering from spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) and then underwent DSCM in U and V fields. RESULTS: The specimens of the 2 controls showed a smooth surface of cartilage and homologous deformation while the specimen of the SEDT-PA patient showed a rough surface of cartilage and deformation with increased undulation. Under a changed loading of 3.3 N the values of average strain of cartilage were 3800, 8800, and 9500 micro epsilon, and the values of tensile elastic modularity were 227.23, 89.59, and 127.25 MPa respectively for the old control, young control, and SEDT-PA patient. The numbers of pixel in U field after 20 pixels were moved in the X direction were significantly different between the old control subject and the SEDT-PA patient (0.101 +/- 0.022 vs 0.220 +/- 0.053, P = 0.023). The numbers of pixel in V field after 20 pixels were moved in the Y direction were significantly different among the old control subject and the SEDT-PA patient. Differences were also significant among the three kinds of cartilage (0.055 +/- 0.018, 0.196 +/- 0.057 vs 0.658 +/- 0.144, both P < 0.05). CONCLUSION: DSCM is a reliable technique to measure the tensile property of articular cartilage, especially for evaluation of small specimens. SEDT-PA is characterized by a dramatic decrease of tensile property, causing destruction and loss of the articular cartilage.


Assuntos
Artropatia Neurogênica/fisiopatologia , Cartilagem Articular/fisiopatologia , Diagnóstico por Imagem/métodos , Osteocondrodisplasias/fisiopatologia , Adulto , Artropatia Neurogênica/complicações , Elasticidade , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Osteocondrodisplasias/complicações , Estresse Mecânico , Resistência à Tração , Suporte de Carga/fisiologia
11.
Zhonghua Yi Xue Za Zhi ; 84(21): 1796-803, 2004 Nov 02.
Artigo em Chinês | MEDLINE | ID: mdl-15631777

RESUMO

OBJECTIVE: To characterize the clinical manifestations, features of roentgenography and MR imaging, and the pathology of articular cartilage and matrix of spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA), to screen the mutations of the disease-causing CCN6 gene, and try to elucidate the molecular pathogenesis of SEDT-PA. METHODS: A questionnaire survey on the clinical manifestations and history was conducted among a pedigree of SEDT-PA with 57 persons (53 living members) in tolal, including 2 probands, a 19-year old female and a 9-year old male. Physical examination and roentgenography and MR imaging were used on the 2 probands to characterize the features of their joints and articular cartilage. The femoral head extracted during replacement of hip of the proband 1 underwent hematoxylin-eosin staining and toludine blue (TB) staining to observe the pathological changes and ultra-microstructure of the articular chondrocytes and cartilage matrix using electron microscopy. Peripheral blood samples were collected from these 53 living members and 100 healthy controls. PCR was used to examine and sequence the exons of CCN6. 3D-conformational illustration of mutant CCN6 proteins were predicted using the Prospect Software. RESULTS: The clinical manifestations, radiology, and MR imaging established the diagnosis of SEDT-PA. Pathologic examination demonstrated that the articular cartilage chondrocytes became hyper-proliferative and immature, while the density and diameter of matrix collagens were dramatically decreased. Mutation studies showed the two probands carried a deletion (840delT) mutation in maternal allele, that caused the truncated CCN6 protein to miss 43 residues in C-terminus; and a substitution mutation (1000T-->C, Ser334Pro) in paternal allele, which was also inherited down to other 4 members in the SEDT-PA kindred. The predicted 3D-conformational changes of the truncated mutant and the Ser334Pro mutant CCN6 proteins demonstrated that in comparison with the wild CCN6 protein, the single long peptide loop in the region from signal peptide to the beginning 24 amino acid residues in the first domain (IGFBP) was subjected to folding into two smaller cross-loops accompanied with a much shorter C-terminus in 840 delT truncated mutant CCN6 protein, and no substantial 3D-conformational change of Ser334Pro mutant CCN6 protein was detected except for the C-terminal peptide towards the opposite direction. CONCLUSION: Novel 840delT mutation of CCN6 gene is the leading cause of SEDT-PA though coexistence of T1000C substitution is necessary for the clinical onset of SEDT-PA, in which marked abnormalities of cartilage chondrocytes and matrix are morphologically and functionally presented.


Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Proteínas de Neoplasias/genética , Osteoartrite/genética , Osteocondrodisplasias/genética , Mutação Puntual , Adulto , Sequência de Bases , Proteínas de Sinalização Intercelular CCN , Criança , Análise Mutacional de DNA , Feminino , Humanos , Dados de Sequência Molecular , Osteoartrite/epidemiologia , Osteoartrite/patologia , Osteocondrodisplasias/patologia , Osteocondrodisplasias/fisiopatologia , Linhagem
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