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Diabetic retinopathy (DR) is a microvascular complication of diabetes and one of the most common causes of blindness in active stage. This study is performed to explore the effects of microRNA-21 (miR-21) on retinal vascular endothelial cell (RVEC) viability and angiogenesis in rats with DR via the phosphatidylinositiol 3-kinase/protein kinase B (PI3K/Akt)/vascular endothelial growth factor (VEGF) signaling pathway by binding to phosphatase and tensin homolog (PTEN). Sprague Dawley (SD) rats were used for establishment of DR models. Target relationship between miR-21 and PTEN was assessed by bioinformatics prediction in combination with dual-luciferase reporter gene assay. Identification of expression of miR-21, PTEN and PI3K/Akt/VEGF signaling pathway-related genes in the retinal tissues was then conducted. In order to assess the contributory role of miR-21 in DR, the RVECs were transfected with mimic or inhibitor of miR-21, or siRNA-PTEN, followed by the detection of expression of PTEN and PI3K/Akt/VEGF-related genes, as well as the measurement of cell viability, cell cycle and apoptosis. Increased expression of miR-21 and PI3K/Akt/VEGF related genes, along with a reduced expression of PTEN was observed in the retinal tissues of DR rats. PTEN was targeted and negatively regulated by miR-21, while the PI3K/Akt/VEGF signaling pathway was activated by miR-21. RVECs transfected with miR-21 inhibitor exhibited promoted viability and angiogenesis, and inhibited apoptosis. To conclude, our results indicated that miR-21 overexpression could potentially stimulate RVEC viability and angiogenesis in rats with DR through activation of the PI3K/Akt/VEGF signaling pathway via repressing PTEN expression, highlighting the potential of miR-21 as a target for DR treatment.
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Retinopatía Diabética/metabolismo , Células Endoteliales/patología , MicroARNs/genética , Neovascularización Patológica/prevención & control , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Apoptosis , Western Blotting , Proliferación Celular , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/genética , Células Endoteliales/metabolismo , Represión Epigenética/fisiología , Citometría de Flujo , Inmunohistoquímica , Masculino , Neovascularización Patológica/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Ratas Sprague-Dawley , Vasos Retinianos/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/fisiología , Transfección , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
PURPOSE: The peripheral cornea contains mature and immature resident dendritic cells (DCs) while the central cornea is exclusively equipped with immature DCs. There must be some factors that cause immature DCs. This study investigated whether corneal stroma cells (CSCs) inhibit DC maturation by secreting cytokines. METHODS: The messenger ribonucleic acid (mRNA) and protein level of transforming growth factor beta 2 (TGF-ß(2)) was analyzed using reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Immature DCs were induced to mature in the presence of lipopolysaccharide (LPS) and with concentrations of CSC culture supernatant (containing and not containing neutralizing TGF-ß(2) antibodies). Then, the DC phenotypic and functional maturation were analyzed. RESULTS: CSCs exhibited positive expressions of TGF-ß(2) mRNA and secreted high concentrations of TGF-ß(2) protein. In the presence of LPS, DCs, which were treated with a CSC culture supernatant, displayed reduced expressions of cluster of differentiation 80 (CD80), CD86, and major histocompatibility complex II (MHC II) in a dose-dependent manner. Moreover, treated DCs showed lower T-cell stimulation capacity and a higher endocytosis function. However, these phenotypic and functional modifications were partially reversed after the application of neutralizing TGF-ß(2) antibodies. CONCLUSIONS: This study demonstrates that CSCs can partially inhibit LPS-induced DC maturation through TGF-ß(2) secretion in vitro.
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Comunicación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Sustancia Propia/efectos de los fármacos , Células Dendríticas/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Animales , Anticuerpos Neutralizantes/farmacología , Antígeno B7-1/genética , Antígeno B7-1/inmunología , Antígeno B7-2/genética , Antígeno B7-2/inmunología , Comunicación Celular/genética , Comunicación Celular/inmunología , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Células Cultivadas , Sustancia Propia/citología , Sustancia Propia/inmunología , Medios de Cultivo Condicionados/farmacología , Células Dendríticas/citología , Células Dendríticas/inmunología , Relación Dosis-Respuesta Inmunológica , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Lipopolisacáridos/farmacología , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , ARN Mensajero/biosíntesis , ARN Mensajero/inmunología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/inmunología , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
The present study was conducted to investigate the relationship between the anti-stress and hepato-protective effects of Schisandra Lignans Extract (SLE) on stress-induced liver damage. Seven weeks old male mice were fixed in a restraint tube for 18 h to induce liver damage. SLE was orally administered to animals for 5 days at dosages of 100 and 200 mg/kg/day before exposed to restraint stress. Oral administration of SLE significantly reduced restraint-induced liver damage in experimental animal. SLE was further found to significantly alleviate the provocation of corticosterone in stressed mice. SLE also significantly decreased oxidative damage and increased anti-oxidative capability of liver cells by preventing the over production and accumulation of free radicals. In conclusion, the protective effects of SLE on stress-induced liver damage were confirmed, and the correlation between hepatoprotective and anti-stress effects of schisandra lignans was possible related to its alleviation on the malignant effects of stressors for bio-homeostasis, such as balance of oxidation and reduction in cells.
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BACKGROUND: Mesenchymal stem cells can be isolated from various tissues besides bone marrow and can differentiate into cells of three germ layers. Recent studies indicate that some cells in corneal stroma express stem cell markers and can also differentiate into chondrocytes and neurocytes. This study was carried out to investigate whether mesenchymal stem cells reside in the murine corneal stroma. METHODS: Corneas of BALB/c mice were treated with collagenase digestion after the epithelium and endothelium were removed. Then the single cells were harvested and further identified by reverse transcription polymerase chain reaction (RT-PCR). After the immunophenotype of passage 2 corneal stroma-derived cells was analyzed by flow cytometry, attempts were made to differentiate these cells into adipocytes and osteocytes using conditioned medium. Following induction, cells were evaluated by RT-PCR, oil red O and Alizarin Red staining. RESULTS: Isolated single cells were of stromal origin, not of epithelial or endothelial. Passage 2 corneal stroma-derived cells exhibited the spindle-shaped morphology and expressed CD29, CD90, CD105, and CD71; but were negative for CD34 and CD45. In addition, these cells showed the potentiality of differentiating into adipocytes and osteocytes, which was confirmed by RT-PCR and staining. CONCLUSION: This study demonstrates the presence of mesenchymal stem cell-like cells in the murine corneal stroma. Further analysis of these cells will aid elucidation of the mechanisms of some keratopathies, and these cells may be a source for bioengineering of corneal tissue and for cell-based therapeutics.
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Sustancia Propia/citología , Células Madre Mesenquimatosas/citología , Animales , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Diferenciación Celular , Células Cultivadas , Citometría de Flujo , Inmunofenotipificación , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Posterior scleritis is a rare inflammatory ocular disease, characterized by severe and painful inflammation of the sclera. It is often misdiagnosed or underdiagnosed, due to its general and varying clinical presentation profile, which primarily involves pain and visual impairment but which can include eyelid edema, choroidal folds, serous retinal detachment, disc edema, hard exudates in fovea and subretinal mass. We report here a case of posterior scleritis, with symptoms of eye pain and red eye, initially misdiagnosed as acute conjunctivitis. CASE SUMMARY: A 56-year-old man presented to a local hospital with complaint of pain and redness in the right eye. The initial diagnosis was acute conjunctivitis and he was given antibiotic eyedrops. Upon week-long continuance of the symptoms despite treatment, he presented to our hospital. Initial examination revealed a shallow anterior chamber in the right eye and vision reduction to 0.6. Further testing by optical coherence tomography, ultrasound biomicroscopy, and fundus photography indicated diagnosis of posterior scleritis. The patient was given methylprednisolone (oral) on a tapered reduction schedule (starting with 70 mg/d). According to the peaks and troughs of symptoms, compound betamethasone injection was administered into the bulb, culminating in discontinuation of the oral corticosteroid. Subsequent optical coherence tomography showed the subretinal fluid near the optic disc to be completely absorbed after treatment. CONCLUSION: Posterior scleritis should be among the differential diagnosis of eye pain and redness, and diagnosis requires further ophthalmic accessory examination, such as by optical coherence tomography.
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Fungal keratitis is a relatively common ocular disease requiring positive medical management combined with surgical intervention. Interleukin-17 (IL-17) was reported to promote the activation and mobilization of neutrophile granulocyte to foci of inflammation. This study investigated the effect of IL-17 production from Th17 cells on the progression of fungal keratitis. A mouse model of fungal keratitis induced by Candida albicans was successfully constructed to detect infiltration of inflammatory cells in corneal tissues by hematoxylin-eosin (HE) staining and immunohistochemistry. Fungal load capacity of mouse cornea was also detected. The regulatory role of IL-17 in fungal keratitis with the involvement of CX43 was investigated with the relevant expression of inflammatory factors detected and activation of vascular endothelial cells assessed. Furthermore, in vivo experiment was also performed to confirm the role of CX43 in keratitis. Mice with fungal keratitis showed increased level of inflammatory cytokines and infiltration of inflammatory cells. Silencing IL-17 in Th17 cells and overexpressing CX43 could inhibit the activation of vascular endothelial cells. Besides, CX43 knockdown in vivo alleviated fungal keratitis in mice. The possible mechanism of the above findings could be IL-17 inhibiting the level of CX43 through the AKT signaling pathway. Taken together, IL-17 could inhibit the occurrence and development of fungal keratitis by suppressing CX43 expression through the AKT signaling pathway. Therefore, this study provides a potential target for the treatment of fungal keratitis.
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Candidiasis/metabolismo , Conexina 43/metabolismo , Endotelio Vascular/metabolismo , Infecciones Fúngicas del Ojo/metabolismo , Interleucina-17/biosíntesis , Queratitis/metabolismo , Células Th17/inmunología , Animales , Candida albicans , Candidiasis/inmunología , Candidiasis/patología , Células Cultivadas , Conexina 43/antagonistas & inhibidores , Conexina 43/genética , Córnea/irrigación sanguínea , Córnea/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Infecciones Fúngicas del Ojo/inmunología , Infecciones Fúngicas del Ojo/patología , Femenino , Interleucina-17/genética , Queratitis/inmunología , Queratitis/patología , Ratones , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
PURPOSE: We have introduced a method of modified posterior short-segment pedicle screw fixation and evaluated its clinical effects in treating lumbar burst fractures with incomplete neurological deficits. METHODS: The data from 22 patients with lumbar burst fracture and incomplete neurological deficits who had undergone modified posterior short-segment instrumentation with Schanz screw fixation from January 2012 to February 2018 in our clinic were evaluated in the present retrospective study. All Schanz screws were implanted in an oblique downward direction into the vertebrae above and below the injured vertebra (insertion depth, 90%-100%). The implants were removed â¼1 year after surgery. Neurological function, back pain, anterior and posterior body height ratio, kyphosis angle, percentage of canal compromise, fracture severity, and treatment-related complications were evaluated. RESULTS: Technical success was achieved in all 22 patients. No infection, instrument loosening or failure, or breakage was observed. Statistically significant improvements with regard to the anterior body height (P < 0.05) and posterior body height (P < 0.05) ratios, kyphosis angle, and percentage of canal compromise (P < 0.05) were observed at 1 week postoperatively or the final follow-up visit. No correction loss had occurred at the final follow-up examination. Postoperatively, all patients with neurological deficits had functional improvement equivalent to ≥1 grade on the American Spinal Injury Association impairment scale and fracture union. Back pain was greatly improved postoperatively. CONCLUSIONS: Short-segment Schanz screw fixation implanted in an oblique downward direction seems to be a promising method for lumbar burst fractures with incomplete neurological deficits because it provided good clinical and radiographic outcomes.
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Fijación Interna de Fracturas/instrumentación , Vértebras Lumbares/lesiones , Enfermedades del Sistema Nervioso/etiología , Tornillos Pediculares , Fracturas de la Columna Vertebral/cirugía , Accidentes por Caídas , Accidentes de Tránsito , Adulto , Dolor de Espalda/etiología , Dolor de Espalda/cirugía , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Femenino , Fijación Interna de Fracturas/métodos , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/cirugía , Tempo Operativo , Cuidados Posoperatorios , Radiografía , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Tiempo de Tratamiento/estadística & datos numéricos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To develop a scientific and reproducible degenerative disc rat model for the study on the cervical disc and study the rule of migration associated with the chondrocytes in the nucleus pulposus. METHOD: The degenerative cervical disc animal model was developed in 40 infancy SD rats by means of forelimb amputation. Thirty-six normal rats in the same age served as the control. When the rats in the experimental group were 3, 6, 9 and 12 months (named E3, E6, E9 and E12 group respectively) and in the control group were 4, 8, 12 and 16 months (named C4, C8, C12 and C16 group respectively) postoperatively, the vertebral columns from C4-5 to C6-7 were removed and observed under radiographic and histological examination after the rats were sacrificed. RESULT: Light microscopy revealed that aging rat undergoes a chronological transition from a notochordal to a fibrocartilaginous NP. The chondrocytes found in mature nucleus pulposus originate and migrate from the cartilage endplate. The origin of chondrocytes proceeded in a centripetal direction from the periphery toward the center of the NP. In the periphery of NP, chondrocytes migrate along collagen fibers; in the center part of NP, chondrocytes migrate from endplate to NP in a parallel or vertical direction. Overload on the cervical spine elicited by this surgical intervention accelerated the process and resulted in cervical intervertebral disc degeneration thereafter. CONCLUSION: The availability of this experimental model should be valuable for comprehensive understanding of the pathogenesis of cervical degeneration. The degeneration process of the bipedal rats'discs is in agreement with that of human beings. Chondrocytes in the rat NP originated and migrated from the cartilage endplate. There are different rules of the chondrocytes migrating from endplate associated with different period of degeneration and different region of nucleus pulposus.
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Movimiento Celular , Modelos Animales de Enfermedad , Disco Intervertebral/patología , Enfermedades de la Columna Vertebral/patología , Animales , Cartílago/citología , Vértebras Cervicales , Condrocitos/citología , Masculino , Placa Motora/citología , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To observe the clinical effect of heat sensitive moxibustion (HSM) and its regularity of acupoint heat-sensitization in the treatment of allergic rhinitis (AR) patients. METHODS: Seventy patients with AR were randomly divided into HSM and manual acupuncture groups (nï¼35/group). For patients of the HSM group, acupoints Yintang (EX-HN 3), bilateral Yingxiang (LI 20), Shangxing (GV 23), Tongtian (BL 7), Feishu (BL 13), Hegu (LI 4), etc. were used, and for patients of the manual acupuncture group, bilateral LI 20 and LI 4, Bitong (EX-HN 8) and EX-HN 3 were needled and stimulated with uniform reinforcing-reducing needling method. The treatment was conducted once every other day, for 20 days, with 3 days' interval between two 10 days. The symptoms of sneezing, running nose, nasal obstruction, and nasal itching were scored as 1, 2 and 3 points according to their severity. The signs of turbinate-nose cavity bottom/nasal septum correlation, morphological state (swelling or not) of inferior nasal concha and color of nasal mucosa, appearance (deviation or polyp) of the middle turbinate and nasal septum were scored as 1, 2 and 3 points according to their severity. The total score equaled to symptom score plus nasal sign score. The distribution of heat sensitization acupoints for effectively improving AR were recorded. RESULTS: The total effective rate of 82.86%(29/35) in the HSM group had no marked difference in comparison with that of 74.29%(26/35) in the manual acupuncture group (P>0.05). After the treatment, the total scores of symptoms and nasal signs of both HSM and manual acupuncture groups were significantly reduced in comparison with their own individual pre-treatment (P<0.01), and those in the HSM group were significantly decrased than those in the manual acupuncture group (P<0.05). In 35 patients of the HSM group, among the detected 57 acupoints, the most frequently sensitive acupoints were LI 20, EX-HN 3, EX-HN 8, Shangyintang, BL 13, Shenque(CV 8), GV 23, Fengchi(GB 20), Die'e and Dazhui (GV 14) in sequence, mainly covering the Governor Vessel, Large Intestine Meridian of Hand-yangming(LI), and Bladder Meridian of Foot-taiyang(BL), and characterized by heat conduction, heat diffusion, diathermancy, non-thermal (mainly itching) sensation, thermal sensation mainly in the deep tissue and in the distant part rather than in the body surface and the local part. CONCLUSIONS: HSM has a positive effect on improvement of AR, when applied, acupoints LI 20, EX-HN 3, EX-HN 8, Shangyintang, BL 13, CV 8, GV 23, GB 20, Die'e and GV 14 are highly recommended.
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Terapia por Acupuntura , Moxibustión , Rinitis Alérgica , Calor , Humanos , Rinitis Alérgica/terapiaRESUMEN
OBJECTIVE: To explore the relationship between plasma redox status and atherosclerosis. METHODS: IVUS was performed in common carotid in the neck of 167 patients with heart diseases. Patients were divided into three groups: plaque-forming group (A, n = 79), intima-thickening group (B, n = 52) and control group (C, n = 36). Plasma glutathione (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (reduced form NADPH and oxidized form NADP(+)), oxidized low density lipoprotein (ox-LDL) and malondialdehyde (MDA) were measured in all patients. The GSH/GSSG and NADPH/NADP(+) redox potential were calculated according to Nernst equation, and correlation analysis performed. RESULTS: GSH and GSH/GSSG gradually reduced and GSH/GSSG redox potential gradually increased in proportion to the thickening of artery intima (from Group C to Group A, P < 0.05). Similar but milder results were shown for NADPH and NADPH/NADP(+) redox status. The products of oxidative stress ox-LDL and MDA also increased significantly (P < 0.05) in proportion to the thickening of artery intima. GSH/GSSG redox potential is positively correlated to ox-LDL (P < 0.05). The redox status shifted to oxidizing direction in proportion to the intima thickness. CONCLUSION: The imbalance of plasma redox status deviating to oxidation might be implicated in oxidized injury of lipid, intima thickening and atherosclerosis progress.
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Enfermedades de las Arterias Carótidas/patología , Disulfuro de Glutatión/sangre , NADP/sangre , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de las Arterias Carótidas/fisiopatología , Femenino , Humanos , Lipoproteínas LDL/sangre , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Oxidación-ReducciónRESUMEN
OBJECTIVE: To explore the effects of Xuezhikang Capsules (ZXKC) and probucol on blood lipids, vascular endothelial functions and redox status in patients with coronary heart disease. METHODS: One hundred and twelve patients with coronary heart disease were randomly divided into XZKC-treated group and probucol-treated group, 56 in each. Before and after 8-week treatment, the blood levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), nitric oxide (NO), endothelin-1 (ET-1), reduced glutathione (GSH) and oxidized glutathione (GSSG) were all measured in both groups. The GSH/GSSG redox potential (Eh) was calculated according to the Nernst equation. RESULTS: In the XZKC-treated group, the blood levels of TC, LDL-C and TG were significantly decreased after 8-week treatment as compared with those before treatment. The blood levels of TC and LDL-C were also significantly decreased in the probucol-treated group as compared with those before treatment. In the XZKC-treated group, the blood levels of ET-1 and GSSG and the GSH/GSSG Eh after treatment were all significantly lower than those before treatment, whereas the blood levels of GSH and NO, the NO/ET-1 ratio, and the GSH/GSSG ratio after treatment were all significantly higher than those before treatment. CONCLUSION: The XZKC or probucol treatment can yield a significant decrease in blood lipids in patients with coronary heart disease. Furthermore, XZKC exerts effective protection on vascular endothelial function, and can make GSH/GSSG redox status shift towards deoxidation.
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Enfermedad Coronaria/tratamiento farmacológico , Endotelina-1/sangre , Endotelio Vascular/fisiopatología , Glutatión/sangre , Fitoterapia , Anciano , Cápsulas , Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad Coronaria/fisiopatología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/sangre , Oxidación-Reducción , Triglicéridos/sangreRESUMEN
Previous studies suggested that neurotrophins play a role in the diabetic retinopathy (DR). We therefore evaluated the role of plasma brain derived neurotrophic factor (BDNF) levels in Chinese type 2 diabetic patients with and without diabetic retinopathy (DR). Plasma levels of BDNF were determined in type 2 diabetic patients (N=344). At baseline, the demographical and clinical data were taken. Multivariate analyses were performed using logistic regression models. Receiver operating characteristic curves (ROC) was used to test the overall predict accuracy of BDNF and other markers. Diabetic patients with DR and vision-threatening diabetic retinopathy (VTDR) had significantly lower BDNF levels on admission (P<0.0001 both). BDNF improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.76 (95% confidence interval [CI], 0.71-0.82) to 0.89 (95% CI, 0.82-0.95; P<0.01) and for VDTR from 0.84 (95% CI, 0.78-0.92) to 0.95 (95% CI, 0.90-0.98; P<0.01). Multivariate logistic regression analysis adjusted for common risk factors showed that plasma BDNF levels≤12.4 ng/mL(1(rd) quartiles) was an independent marker of DR (OR=3.92; 95%CI: 2.31-6.56) and VTDR (OR=4.88; 95%CI: 2.21-9.30). The present study demonstrated that decreased plasma levels of BDNF were independent markers for DR and VDTR in Chinese type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications.
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Pueblo Asiatico , Factor Neurotrófico Derivado del Encéfalo/sangre , Diabetes Mellitus Tipo 2/sangre , Retinopatía Diabética/sangre , Adulto , Anciano , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Curva ROC , Factores de RiesgoRESUMEN
The influence of the vitamin D receptor (VDR) gene for the risk of osteoporosis remains to be elucidated. The aim of the present study was to understand the distribution of various single-nucleotide polymorphisms (SNPs) within the VDR gene and its association with the risk of osteoporosis. In total, 378 subjects without a genetic relationship were recruited to the study between January 2013 and July 2015. The subjects were divided into three groups, which were the normal (n=234), osteoporosis (n=65) and osteoporosis with osteoporotic fracture (n=79) groups. Three pertinent SNPs of the VDR gene rs17879735 (ApaI, Allele A/a, SNP C>A) were examined with polymerase chain reaction-restriction fragment length polymorphism. The bone mineral density (BMD) of the lumbar spine (L2-L4), femoral neck, Ward's and Tro was measured using dual-energy X-ray absorptiometry. The distributions of genotype frequencies aa, AA and Aa were 48.68, 42.86 and 8.46%, separately. Following analysis of each site, BMD, body mass index (BMI) and age, BMD for each site was negatively correlated with age (P<0.01) and positively correlated with BMI (P<0.01). Correction analysis revealed that there were significant differences in the Ward's triangle BMD among each genotype (P<0.05), in which the aa genotype exhibited the lower BMD (P<0.05). No significant difference was identified among the different genotypes in the occurrence of osteoporosis with osteoporotic fracture (P>0.05). In conclusion, these indicated that the VDR gene ApaI polymorphisms had an important role in the osteoporosis risk.
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OBJECTIVE: To research on the conservative methods used to preserve the femoral head of patients with osteonecrosis of the femoral head. METHODS: In these series surgical procedures the osteonecrotic lesion was removed and various vascularized bone blocks or periosteal flaps with its nutrient vessels were transferred to regain sphericity of the femoral head and reinforce the sequestrum. The current study assessed 1005 patients (1226 hips) operated on from 1989 to 2002 with an average follow-up of 5.1 years (range, 1.5-15 years). The mean age of the patients was 37.4 years (range, 17-65 years). RESULTS: Sixty-one hips (57 patients) had conversion surgery to a total hip arthroplasty because of progressive collapse or severe pain, or both. In the patients without failure, postoperative Harris hip score improved significantly. Of the 1174 reconstructions that were in situ, 1041 (89.4%) were clinically successful, and 878 (75.4%) were radiologically successful. In relation to the stage of necrosis according to the classification system of Ficat and Alert, good results were achieved in 95.3% of the patients with stages II disease, 87.9% with stages III and 60.8% with stages IV. CONCLUSIONS: Conservative methods of vascularized bone block or periosteal flap transfer should be considered in active symptomatic patients to preserve the femoral head. In addition, the earlier the stages of the disease the better outcome could be obtained.
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Necrosis de la Cabeza Femoral/cirugía , Adolescente , Adulto , Anciano , Trasplante Óseo/métodos , Femenino , Fémur/cirugía , Estudios de Seguimiento , Humanos , Masculino , Microcirugia , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Prostaglandin E2 (PGE(2)) is a key modulator of dendritic cells (DCs) function, and cornea-derived transforming growth factor beta 2 (TGF-ß(2)) promotes the generation of phenotypically and functionally immature DCs. Therefore, this study was carried out to investigate whether PGE(2) is involved in the suppressive effect on DCs maturation mediated by corneal stroma cells (CSCs) and whether PGE(2) and TGF-ß(2) have additive effects in this immunosuppressive mechanism. METHODS: Bone marrow-derived DCs (BM-DCs), splenic T cells and CSCs culture supernatant were obtained from mice via various protocols. After that, the level of PGE(2) in CSCs culture supernatant was analyzed by enzyme-linked immunosorbent assay. Then, immature BM-DCs pretreated by E-prostanoid 2 receptor antagonist AH6809 or dimethyl sulfoxide were induced to mature in the presence of lipopolysaccharide, with or without CSCs culture supernatant. In parallel experiments, neutralizing TGF-ß(2) antibody or normal goat IgG was added into the supernatant. Next, the cellular surface markers for DCs maturation, including CD80, CD86, and major histocompatibility complex class II (MHCII), were analyzed by flow cytometry; the capability of stimulating the proliferation of T lymphocytes was evaluated by allogeneic mixed lymphocyte reactions and the function of endocytosis was assessed by fluorescein isothiocyanate-dextran uptake. RESULTS: Higher concentration of PGE(2) was detected in CSCs culture supernatant than in the fresh medium. In addition, compared with control group, after treated with the supernatant in the mature stage, BM-DCs displayed lower expression of CD80, CD86 and MHC II, lower T cell stimulatory capacity and higher endocytosis function. However, after the application of AH6809, BM-DCs partially regained T cell stimulatory capacity and expression of CD86 and MHC II, but partially lost endocytic activity. Moreover, after the application of AH6809 and neutralizing TGF-ß(2) antibody, the result of statistical analysis indicated that there was a statistical difference of interaction in the expression of MHC II and T cell stimulatory capacity. CONCLUSIONS: PGE(2) contributes to the suppressive effect on BM-DCs maturation mediated by CSCs in vitro, and PGE(2) and TGF-ß(2) have additive effects on the immunosuppression of BM-DCs.
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Células de la Médula Ósea/citología , Sustancia Propia/citología , Sustancia Propia/metabolismo , Células Dendríticas/citología , Animales , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Células Dendríticas/efectos de los fármacos , Dimetilsulfóxido/farmacología , Dinoprostona/antagonistas & inhibidores , Dinoprostona/metabolismo , Citometría de Flujo , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Factor de Crecimiento Transformador beta2/metabolismo , Xantonas/farmacologíaRESUMEN
PURPOSE: The aqueous humor (AH) contains numerous immunosuppressive molecules that contribute to the ocular immune privilege. Here, we mimic an inflammatory environment to analyze the inhibitory effects of the AH on lipopolysaccharide (LPS)-induced maturation of dendritic cells (DC). METHODS: Different concentrations of AH were added to dendritic cell cultures together with LPS. Dendritic cell surface markers CD80, CD86, and MHC-II were assessed by use of flow cytometry. Endocytic capability and mixed lymphocyte reaction were measured as functional maturation. RESULTS: AH inhibited LPS-induced DC maturation, resulting in down-regulated expression of CD80, CD86, MHC-II, enhancement of endocytic capacity, and reduced T cell activation. Neutralizing transforming growth factor beta 2 (TGF-ß(2)) in AH can totally reverse the inhibitory effect. Treatment with prostaglandin E2 (PGE(2)) antagonist alone had no effect on DC maturation. However, blocking of both TGF-ß(2) and PGE(2) in the AH resulted in synergistic suppression of the inhibiting effect of AH. CONCLUSIONS: These results reveal that TGF-ß(2) in the AH is of crucial importance in maintaining DC in the immature state. Further experiments will clarify the immune role of PGE(2) in AH.
Asunto(s)
Humor Acuoso/fisiología , Células Dendríticas/efectos de los fármacos , Dinoprostona/fisiología , Lipopolisacáridos/toxicidad , Factor de Crecimiento Transformador beta2/fisiología , Animales , Anticuerpos Neutralizantes/farmacología , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Células Cultivadas , Células Dendríticas/inmunología , Dextranos/metabolismo , Dinoprostona/antagonistas & inhibidores , Regulación hacia Abajo , Endocitosis/fisiología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Antígenos de Histocompatibilidad Clase II/metabolismo , Activación de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Antagonistas de Prostaglandina/farmacología , Porcinos , Linfocitos T/inmunología , Factor de Crecimiento Transformador beta2/antagonistas & inhibidores , Xantonas/farmacologíaRESUMEN
OBJECTIVE: To evaluate the value of CT and MRI in the diagnosis of avascular necrosis of the vertebral body (ANV). METHODS: Twelve ANV patients were retrospectively analysed by their medical history, clinic manifestation, CT and MRI. Twelve AVN patients were treated with percutaneous vertebroplasty (PVP). The pain level of each patient was assessed, both before and after the procedure, using a visual analogue scale (VAS). RESULTS: All the patients had ANV in the thoracolumbar spine. The intravertebral vaccum phenomenon (VP), with gas or fluid-like collection, was seen on computed tomographic (CT) images and magnetic resonance images (MRI). In the early stages, the VP zone was characterized by fluid-like collection, and was low intensity on T1, high intensity on T2. In the latter stages, the margin of VP zone had sclerotic change on CT scan. VAS score decreased from preoperative (9.08 +/- 0.76) to (2.33 +/- 1.43) at 3 days after PVP. CONCLUSION: ANV must be considered as a possible diagnosis of VP secondary to osteoporotic vertebral fractures. Both CT and MRI could provide reliable diagnostic proof for ANV. PVP is proved to be an effective and safe procedure for the treatment of ANV, and could provid quick pain relief.
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Vértebras Lumbares/patología , Osteonecrosis/diagnóstico , Vértebras Torácicas/patología , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteonecrosis/etiología , Osteonecrosis/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate the clinical efficacy of posterior short-segment pedicle screw fixation combined reduction of central end-plate by end-plate expand clamp and vertebroplasty with calcium phosphate cement for the treatment of thoracolumbar burst fractures. METHODS: Thirty patients with thoracolumbar burst fractures were treated with posterior pedicle screw fixation combined reduction of central end-plate by end-plate expand clamp and vertebroplasty with calcium phosphate cement. There were 22 males and 8 females with an average of 47 years (range from 25 to 71 years). Segment of fracture had 1 case in T11, 5 in T12, 14 in L1, 8 in L2, 2 in L3, 1 in L4, 1 in L5. According to Denis typing, 4 cases were type A, 25 type B, 1 type C, 1 type D, 1 type E. The relative anterior height of vertebral body and the vertebral angle were measured before and after operation and during the follow-up period (8 months after operation) through X-ray, the failure of internal fixation and recurrent kyphosis were evaluated during the follow-up period. Vertebral intracorporeal gap was measured by CT images after operation and the central end-plate fracture and reduction were observed by the reconstructed CT images (sagittal and coronary) before and after operation. RESULTS: All patients were followed up from 8 to 15 months with an average of 12 months. Relative anterior height of vertebral body and vertebral angle were well restored after operation, and there was no significant change between after operation and 8 months after operation. Preoperative,postoperative and 8 months after operation, relative anterior height of vertebral body respectively was 40.1%, 98.2%, 97.8%, vertebral angle respectively was 18.30, 2.70, 3.20. No failure of internal fixation and recurrent kyphosis were found during the follow-up period. The vertebral intracorporeal gap was about 3.1% and reduction of central endplate fracture was satisfactory. CONCLUSION: Posterior short-segment pedicle screw fixation combined with vertebroplasty with calcium phosphate cement can provide excellent reduction of post-traumatic segmental kyphosis and restore vertebral body height in the fracture level, prevent the failure of internal fixation which is an ideal method for the treatment of thoracolumbar burst fractures.
Asunto(s)
Tornillos Óseos , Fijación Interna de Fracturas/métodos , Vértebras Lumbares/lesiones , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/lesiones , Vertebroplastia/métodos , Adulto , Anciano , Cementos para Huesos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Atherosclerosis is a chronic inflammatory disease. Accumulated evidences suggest a deep involvement of oxidative damage in the development of atherosclerosis, but little is discussed over the relationship between plasma glutathione redox status as the most important intrinsic antioxidant defensive mechanism and the atherosclerosis. METHODS: A total of 132 patients suspected with atherosclerosis were assigned to three groups by high frequency ultrasonic examination of the carotid artery. With the thickness of intima of the carotid artery as an index of degree of atherosclerosis progression, 56 were included in plaque-forming group (A), 42 in carotid artery intima-thickening group (B), and 34 in normal carotid artery intima-thickness group (C). All patients were subjected to the measurement of plasma glutathione (GSH) (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (NADP) (reduced form NADPH and oxidized form NADP(+)), oxidized low density lipoprotein (oxLDL), and malondialdehyde (MDA). The GSH/GSSG and NADPH/NADP(+) redox potentials were calculated according to the Nernst equation, and their correlation with intima thickness and oxLDL was analyzed. RESULTS: With the thickening of artery intima (from group C to A), GSH concentration and the ratio of GSH/GSSG gradually reduced, and GSSG and GSH/GSSG redox potential gradually increased (more positive) (P < 0.05). The NADPH and NADPH/NADP(+) redox status also showed similar but milder changes. The products of oxidative stress oxLDL and MDA increased significantly along with the thickening of artery intima (P < 0.05). The analysis of the relationship between GSH/GSSG redox potential, intima thickness, and oxLDL showed positive correlations (P < 0.05). The plasma GSH/GSSG redox status was positively correlated with the intima thickness of the carotid artery and the oxidized injury of LDL. The redox status shifted to oxidizing direction along with the intima thickening and plaque-forming. CONCLUSION: Elevated peroxidative glutathione redox status was deeply implicated in atherosclerosis progressing, and it may be a sensitive and reliable index for monitoring oxidative status in atherosclerosis.