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BACKGROUND: In total hip arthroplasty (THA) for severe dislocations such as Crowe type IV developmental dysplasia of the hip (DDH), sufficient bone volume for stable fixation of the acetabular component can be achieved by placing a reinforcing bone graft prepared from the resected femoral head into the deficient acetabulum. The purpose of the current study was to examine the long-term survivorship of uncemented THA in conjunction with a bulk femoral head autograft in patients who have Crowe type IV DDH. METHODS: A total of 35 patients (42 hips) who have Crowe type IV DDH and underwent THA using uncemented cup fixation with bulk femoral head autografting were followed up for a mean period of 15.0 years (range, 10.0 to 20.0) postoperatively. Anteroposterior pelvic radiographs were used for measurements such as the horizontal coverage of the grafted bone and the center-edge angle. Kaplan-Meier survivorship analyses were performed with revision of the acetabular component as the endpoint. RESULTS: The Kaplan-Meier analysis indicated 15-year survival rates of 90.4%. The mean horizontal coverage of grafted bone was 46.1% (range, 23.7 to 66.0), and there were 16 cases with horizontal coverage of ≥ 50%. There was no difference in the appearance of a thin (< 1 mm) radiolucency line around the cup between cases with < 50% versus ≥ 50% of the horizontal coverage of grafted bone (4 versus 2 hips; P = .446). Trabecular bridging and remodeling were seen in all cases after mean periods of 4.1 and 9.0 months postoperatively, respectively. Trabecular reorientation was seen in 41 of 42 hips (97.6%) at a mean follow-up of 19.9 months. CONCLUSIONS: Acetabular reconstruction with femoral bulk bone grafting for Crowe type IV DDH resulted in high survival rates and was a good method to restore bone stock and obtain long-term fixation.
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OBJECTIVES: We investigated whether the maintenance of routine assessment of patient index data 3 (RAPID3) remission for one year (RAPID3-MR) may predict good radiographic outcomes. We also compared radiographic progression to prognostic factors among patients with RAPID3-MR, with the maintenance of clinical disease activity index remission for one year (CDAI-MR) or with the maintenance of 28 joint count disease activity score remission for one year (DAS28-MR). METHODS: Of 1220 patients with available clinical data, 92 with RAPID3-MR, 80 with RAPID3-NMR (not satisfying RAPID3-MR), 45 with CDAI-MR, and 75 with DAS28-MR were retrospectively investigated. CDAI and DAS28 for clinical outcomes and the modified total Sharp score (mTSS) for radiographic joint damage were investigated for at least one year. RESULTS: RAPID3, CDAI, DAS28, and their categories remained unchanged or significantly improved in RAPID3-MR patients but significantly deteriorated in RAPID3-NMR patients. The mean annual ΔmTSS was significantly lower in RAPID3-MR patients (0.12 ± 0.55) than in RAPID3-NMR patients (0.54 ± 1.27) (p = 0.025). There was no significant difference among RAPID3-MR patients, CDAI-MR patients (0.06 ± 0.85), and DAS28-MR patients (0.11 ± 0.89). The baseline mTSS (p = 0.038) and monotherapy with nonbiological disease-modifying antirheumatic drugs (p = 0.033) were good prognostic factors in RAPID3-MR patients. CONCLUSIONS: One-year RAPID3 remission maintenance may predict good radiographic outcomes.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Adulto , Artritis Reumatoide/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
We examined how doctors evaluate the results of C. DIFF QUIK CHEK COMPLETE (COMPLETE) in the diagnosis and treatment of Clostridium difficile infection (CDI). A total of 887 stool samples submitted from 2012 to 2013 were examined with COMPLETE. Requested specimens among samples with discrepant results were inoculated onto CCMA plates and incubated under anaerobic conditions for 48 h, then retested by COMPLETE if positive culture results were obtained. Of the 887 specimens, 198 (22.3%) were glutamate dehydrogenase-positive and 73(8.3%) were toxin-positive. Of the 125 specimens yielding discrepant results, 106 specimens were cultured and retested, with 46 (43.4%, 46/106) proving toxin-positive. As a result, the total number of toxin-positive results increased from 73 (8.3%, 73/887) to 119 (13.4%, 119/887). This change was significant (p<0.01). We analyzed the relationship between doctor's decision-making and timing of receiving CD test results in 81 specimens among the discrepant results. Twenty-four patients started treatment just after obtaining the first test result (29.6%, 24/81) and the toxin-positive ratio of the second test was 62.5% (15/24). The decision to start treatment was made after obtaining results of the second test in 48 patients, of whom 13 (16.0%, 13/81) started treatment, and the toxin-positive ratio was 37.5% (18/48). The difference in toxin ratio was significant (p < 0.05). The increase in toxin-positive ratio in the final report facilitates diagnosis in patients with CDL Many doctors, however, started treatment before obtaining results from the second test, suggesting that the 3-day delay in report results represents a drawback for this system.
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Toxinas Bacterianas/análisis , Clostridioides difficile , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Glutamato Deshidrogenasa/análisis , Antígenos Bacterianos/análisis , Humanos , Técnicas para Inmunoenzimas/métodosRESUMEN
BACKGROUND: Smoking cessation reduces the risk of cardiovascular disease (CVD) and improves clinical outcomes in public health. We studied the effect of smoking cessation on high-density lipoprotein (HDL) functionality. METHODSâANDâRESULTS: We randomly treated 32 smokers with varenicline or a transdermal nicotine patch as part of a 12-week smoking cessation program (The VN-SEESAW Study). The plasma lipid profiles, plasma and HDL malondialdehyde (MDA) levels, HDL subfractions as analyzed by capillary isotachophoresis, cholesterol efflux capacity, and antiinflammatory activity of HDL were measured before and after the anti-smoking intervention. After smoking cessation, HDL-C, apoA-I levels and HDL subfractions were not significantly different from the respective baseline values. However, cholesterol efflux capacity and the HDL inflammatory index (HII) were significantly improved after smoking cessation. The changes in both parameters (%∆ cholesterol efflux capacity and ∆HII) were also significantly improved in the successful smoking cessation group compared with the unsuccessful group. The changes in cholesterol efflux capacity and HII also correlated with those in end-expiratory CO concentration and MDA in HDL, respectively. CONCLUSIONS: Our findings indicate that smoking cessation leads to improved HDL functionality, increased cholesterol efflux capacity and decreased HII, without changing HDL-C or apoA-I levels or HDL subfractions. This may be one of the mechanisms by which smoking cessation improves the risk of CVD.
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Lipoproteínas HDL/sangre , Cese del Hábito de Fumar , Fumar/sangre , 1-Alquil-2-acetilglicerofosfocolina Esterasa/sangre , Administración Cutánea , Adulto , Apolipoproteína A-I/sangre , Benzazepinas/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Colesterol/metabolismo , HDL-Colesterol/sangre , Agonistas Colinérgicos/uso terapéutico , Femenino , Humanos , Inflamación , Peroxidación de Lípido/efectos de los fármacos , Lípidos/sangre , Macrófagos/metabolismo , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Nicotina/administración & dosificación , Nicotina/uso terapéutico , Oxidación-Reducción , Quinoxalinas/uso terapéutico , Receptores Nicotínicos , Factores de Riesgo , VareniclinaRESUMEN
OBJECTIVE: To identify the factors having the greatest effect on the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36v2) score after total hip arthroplasty (THA). DESIGN: Retrospective review. SETTING: Private 150-bed hospital. PARTICIPANTS: Patients (N=659) who underwent initial THA for osteoarthritis (OA) of the hip between April 2007 and January 2009. A total of 138 patients who fulfilled the inclusion criteria were seen at the first follow-up, while 108 patients were included in the second follow-up; all 30 patients excluded at the second follow-up underwent contralateral THA between follow-ups. The average time ± SD from surgery to first follow-up was 195.1±67.7 days, and that to second follow-up was 443.0±108.5 days. Patients' average age ± SD was 61.1±9.9 years at first follow-up and 61.3±10.3 years at second follow-up. Women accounted for 85.5% of patients at first follow-up and 85.2% at second follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Eight subscales of the SF-36v2, age, sex, body mass index, complications, living alone, contralateral hip OA, range of hip joint motion, walking aids, and preoperative mental health (MH) values from the SF-36v2. RESULTS: Canonical correlation analysis showed that contralateral hip OA had a major effect on the SF-36v2 score at the first follow-up. At the second follow-up, excluding the 30 patients who had undergone contralateral THA, physical function measured by the SF-36v2 was strongly affected by age, and other items were strongly affected by preoperative MH. CONCLUSIONS: When using the SF-36v2 as an assessment scale after THA, adjustments should be made for contralateral hip OA. Moreover, age and preoperative MH should also be considered.
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Artroplastia de Reemplazo de Cadera , Osteoartritis de la Cadera/psicología , Satisfacción del Paciente , Calidad de Vida , Encuestas y Cuestionarios , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Análisis Multivariante , Osteoartritis de la Cadera/cirugía , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Introduction: Denosumab is generally used for 5-10 years to treat postmenopausal osteoporosis. Although atypical fractures caused by bisphosphonate use are well known, reports of denosumab-associated femur fractures are rare. Case Report: Herein, a 75-year-old woman suffered an atypical periprosthetic femoral fracture 31 months after receiving denosumab. The fracture occurred transverse to the stem tip with lateral cortical thickening. The patient underwent revision surgery for conversion to a longer cemented stem. The fracture site healed 10 months after revision surgery. Conclusion: As far as we know, there have been no reports of a case on periprosthetic atypical femur fracture associated with denosumab. Our study shows the potential of periprosthetic atypical femoral fractures in patients using denosumab for a long time.
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Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2 diabetes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin phosphate increases plasma glucagon-like peptide-1 (GLP-1) concentrations and is used to treat Type 2 diabetes. GLP-1 plays an important role in regulating insulin secretion and expression via the GLP-1 receptor (GLP-1R), which is expressed in pancreatic islets as well as freshly isolated human monocytes and THP-1 cells. Here, we identified a direct role of GLP-1 and DPP-4 inhibition in HDL function. Cholesterol efflux was measured in cultivated phorbol 12-myristate 13-acetate-treated THP-1 cells radiolabeled with 3H-cholesterol and stimulated with liver X receptor/retinoid X receptor agonists. Contrary to vildagliptin, sitagliptin phosphate together with GLP-1 significantly (p < 0.01) elevated apolipoprotein (apo)A1-mediated cholesterol efflux in a dose-dependent manner. The sitagliptin-induced increase in cholesterol efflux did not occur in the absence of GLP-1. In contrast, adenosine triphosphate-binding cassette transporter A1 (ABCA1) mRNA and protein expressions in the whole cell fraction were not changed by sitagliptin in the presence of GLP-1, although sitagliptin treatment significantly increased ABCA1 protein expression in the membrane fraction. Furthermore, the sitagliptin-induced, elevated efflux in the presence of GLP-1 was significantly decreased by a GLP-1R antagonist, an effect that was not observed with a protein kinase A inhibitor. To our knowledge, the present study reports for the first time that sitagliptin elevates cholesterol efflux in cultivated macrophages and may exert anti-atherosclerotic actions that are independent of improvements in glucose metabolism. Our results suggest that sitagliptin enhances HDL function by inducing a de novo HDL synthesis via cholesterol efflux.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Humanos , Fosfato de Sitagliptina , Diabetes Mellitus Tipo 2/metabolismo , Células THP-1 , Hipoglucemiantes , Péptido 1 Similar al Glucagón/metabolismo , Colesterol/metabolismo , Dipeptidil-Peptidasas y Tripeptidil-PeptidasasRESUMEN
Policosanol supplementation has been reported to increase high-density lipoprotein (HDL)-cholesterol (HDL-C). However, the association between Cuban policosanol supplementation and HDL cholesterol efflux capacity (CEC), an important function of HDL, remains unclear. We performed a lipoprotein analysis investigating 32 Japanese healthy participants (placebo, n = 17 or policosanol supplementation for 12 weeks, n = 15) from a randomized Cuban policosanol clinical trial. First, HDL CEC and HDL-related factors were measured before and after policosanol supplementation. Then, through electron microscopy after ultracentrifugation and high-performance liquid chromatography, HDL morphology and subclass were analyzed, respectively. Finally, the effects of policosanol supplementation regarding HDL function, HDL-related factors, and HDL morphology/component were examined. Cuban policosanol considerably increased the HDL CEC and HDL-C and apolipoprotein A-I (ApoA-I) levels. Furthermore, policosanol supplementation led to larger HDL particles, increased cholesterol content in larger HDL particles, and reduced triglyceride content in smaller HDL particles. In participants with high baseline HDL-C levels, the policosanol effects for HDL CEC are observed. HDL CEC fluctuation induced by policosanol was highly associated with HDL-C and ApoA-I changes. In conclusion, for the first time, we demonstrated that policosanol supplementation increased the HDL CEC in healthy participants.
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Lecithin-cholesterol acyltransferase (LCAT) plays a significant role in the progression from premature to mature high-density lipoprotein (HDL) in circulation. Consequently, primary or secondary LCAT deletion or reduction naturally results in low serum HDL cholesterol levels. Recently, rare cases of acquired HDL deficiency with LCAT autoantibodies have been reported, mainly from Japan, where LCAT autoantibodies of immunoglobulin G (IgG) caused the HDL deficiency. Here to our knowledge, we report for the first time two cases of acquired HDL deficiency caused by IgG4 linked LCAT autoantibodies with or without a high serum IgG4 level. Furthermore, these cases can extend to a new concept of "IgG4 autoimmune disease" from the viewpoint of verifying the serum autoantibody and/or renal histopathology.
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Deficiencia de la Lecitina Colesterol Aciltransferasa , Lecitinas , Humanos , Esterol O-Aciltransferasa , Autoanticuerpos , Fosfatidilcolina-Esterol O-Aciltransferasa , Lipoproteínas HDL , Inmunoglobulina G , HDL-ColesterolRESUMEN
In humans, hypertension is considered a state of oxidative stress that can contribute to the development of atherosclerosis and other hypertension-induced organ damages. The objective of this study was to evaluate oxidative status, antioxidant activities, and oxidative stress by-products among Indian patients with various stages of hypertension. Lipid profile, enzymatic and non-enzymatic antioxidants, lipid peroxidation as thiobarbituric acid reactive substances (TBARS), C-reactive protein, electrolytes, and minerals were analyzed in the blood of newly diagnosed prehypertensives, stage I and II hypertensives (n = 20 in each group) and were compared to their age-matched normotensives. Elevated levels of lipid profile (except high density lipoprotein cholesterol [HDL-C]) were observed in stage I and II hypertensive patients. Enzymatic and non-enzymatic antioxidants were significantly (P < 0.05) lower, while TBARS and C-reactive protein were higher in prehypertensives, and stage I and II hypertensives. Significant (P <0.05) changes were also observed in the plasma Na(+) and K(+) concentrations among the hypertensive groups. Serum levels of zinc, copper, and magnesium were significantly (P < 0.05) lower in prehypertensives, and stage I and II hypertensives as compared to normotensives. The study indicated a strong association between blood pressure (BP) and oxidative stress-related parameters and suggests a possible role of oxidative stress in the development of elevated BP.
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Antioxidantes/metabolismo , Hipertensión/sangre , Hipertensión/etiología , Estrés Oxidativo , Adulto , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Humanos , Hipertensión/clasificación , India , Peroxidación de Lípido , Lípidos/sangre , Masculino , Persona de Mediana Edad , Proyectos Piloto , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
OBJECTIVE: Preoperative factors related to perceived leg length discrepancy (PLLD) after total hip arthroplasty (THA) are not well studied. This study aimed to examine the preoperative factors, including hip abductor modulus, related to PLLD one month after THA. METHODS: The study included 73 patients diagnosed with osteoarthritis secondary to developmental dysplasia of the hip and a posterior approach to surgery. Multiple logistic regression analysis was performed using the presence or absence of PLLD as the dependent variable and preoperative hip abductor's modulus of elasticity, pain, hip abduction range of motion, hip abductor muscle strength and pelvic obliquity as the independent variable. Additionally, receiver operating characteristic curves were used for the extracted variables for calculating the cutoffs, sensitivity, specificity and area under the curve (AUC) to determine the presence or absence of PLLD. The significance level was set at p<0.05. RESULTS: The hip abductor modulus (odds ratio=1.13; 95% confidence interval=1.06-1.21; p<0.001) was selected as a preoperative factor. The cutoff value to determine the presence or absence of a PLLD was 16.32 kPa. The sensitivity and specificity were 81.8% and 72.5%, respectively, and the AUC was 0.8137. CONCLUSION: The hip abductor muscle elastic modulus affected PLLD one month after THA. If the preoperative hip abductor elastic modulus is higher than the cutoff value, it may affect the appearance of PLLD at one month postoperatively.
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This longitudinal observational study investigated the relationship between changes in spinal sagittal alignment and changes in lower extremity coronal alignment. A total of 58 female volunteers who visited our institution at least twice during the 1992 to 1997 and 2015 to 2019 periods were investigated. We reviewed whole-spine radiographs and lower extremity radiographs and measured standard spinal sagittal parameters including pelvic incidence [PI], lumbar lordosis [LL], pelvic tilt [PT], sacral slope [SS] and sagittal vertical axis [SVA], and coronal lower extremity parameters including femorotibial angle (FTA), hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA) and mechanical lateral distal tibial angle (mLDTA). Lumbar spondylosis and knee osteoarthritis were assessed using the Kellgren-Lawrence (KL) grading system at baseline and at final follow-up. We investigated the correlation between changes in spinal sagittal alignment and lower extremity alignment and changes in lumbar spondylosis. The mean age [standard deviation (SD)] was 48.3 (6.3) years at first visit and 70.2 (6.3) years at final follow-up. There was a correlation between changes in PI-LL and FTA (R = 0.449, P < 0.001) and between PI-LL and HKA (R = 0.412, P = 0.001). There was a correlation between changes in lumbar spondylosis at L3/4 (R = 0.383, P = 0.004) and L4/5 (R = 0.333, P = 0.012) and the knee joints. Changes in lumbar spondylosis at L3/4 and L4/5 were related to changes in KOA. Successful management of ASD must include evaluation of the state of lower extremity alignment, not only in the sagittal phase, but also the coronal phase.
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Cifosis/diagnóstico por imagen , Lordosis/diagnóstico por imagen , Extremidad Inferior/diagnóstico por imagen , Postura/fisiología , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Cifosis/fisiopatología , Estudios Longitudinales , Lordosis/fisiopatología , Extremidad Inferior/fisiopatología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Sacro/diagnóstico por imagen , Sacro/fisiopatología , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/fisiopatologíaRESUMEN
Ischemic limbs with infected heel ulcers are often difficult to salvage. We present a case of an 82-year-old woman who had bilateral heel ulcers owing to chronic limb-threatening ischemia. She underwent right femoral-terminal posterior tibial artery bypass surgery, but right calcaneus osteomyelitis occurred and inhibited wound healing. She underwent partial calcanectomy (PC), and her right heel healed six months after the bypass surgery. The ulcer on her left foot also healed after distal bypass and PC. We describe our experience with a patient who needed PC to cure her heel ulcers.
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Apolipoprotein E epsilon4 is an independent risk factor for Alzheimer's disease (AD) and is the main constituent of high-density lipoprotein (HDL) as a source of cholesterol in the brain. ATP-binding cassette transporter G4 (ABCG4) is one of the membrane cholesterol transporter which is implicated in HDL-mediated cholesterol efflux, but its precise localization and function in the brain has been unclear. In AD brain, ABCG4 protein was highly expressed in microglial cell that was closely located to senile plaques, whereas in non-neurological cases positive cells were not seen in cortical and nigral tissues. As well as the ABCG4 protein, ABCG4 mRNA signal was detected in microglial cell closely located to senile plaque of AD brain by in situ hybridization histochemistry. These results suggest that upregulated ABCG4 in microglia may accelerate the lipidation of apoE and HDL in the AD brain. This is the first report to show that ABCG4 is highly expressed in microglia on AD brain.
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Transportadoras de Casetes de Unión a ATP/biosíntesis , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Expresión Génica , Microglía/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Apolipoproteínas E/metabolismo , Western Blotting , Encéfalo/patología , HDL-Colesterol/metabolismo , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Placa Amiloide/patología , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección , Regulación hacia ArribaRESUMEN
BACKGROUND: Critical limb ischemia with osteomyelitis is so difficult to treat that even appropriate revascularization and wound therapy cannot achieve limb salvage because of uncontrollable infection. It is still difficult to judge the possibility of limb salvage before revascularization. CASE PRESENTATION: A 73-year-old male complained of a small ulcer on his left toe, which was treated with multiple endovascular therapy. After failed endovascular therapy, he suffered extensive tissue loss with tibial osteomyelitis. We carried out staged surgery that was composed of dual bypass to the sural artery and posterior tibial artery. After intensive debridement and wound care, insertion of a subsequent free gracilis muscle flap to cover the exposed tibial bone was performed, achieving functional limb salvage. CONCLUSION: Even in the threatened limb with extensive tissue loss and osteomyelitis, intensive and multidisciplinary treatment with staged revascularization, muscle transfer, and appropriate wound care achieved functional limb salvage.
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ATP-binding cassette transporters (ABC) G1 and ABCA1 are membrane cholesterol transporters and have been implicated to mediate cholesterol efflux from cells in the presence of high density lipoproteins and its major protein constituent apolipoprotein A-I, respectively. We previously demonstrated that unsaturated fatty acids suppress the stimulatory effects of oxysterols and retinoids on ABCA1 gene transcription. We here demonstrate that unsaturated fatty acids significantly suppress the stimulatory effects of oxysterols and retinoids on the expression of ABCG1 mRNA and protein and the activity of the wild-type human ABCG1 promoter as well as ABCA1. Mutation or deletion of the DR4 element within the ABCG1 or ABCA1 promoters, to which the transcriptional inducers LXR and RXR bind, abolished the suppressive effects of unsaturated fatty acids. Our observations provide the first evidence that unsaturated fatty acids suppress ABCG1 gene expression by a mechanism which involves the binding of LXR/RXR to the promoters. Suppression of both the ABCA1 and ABCG1 genes may indicate that unsaturated fatty acids suppress not only cholesterol efflux to apoA-I and thereby nascent HDL formation but also HDL-dependent cholesterol efflux from vascular cells.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Ácidos Grasos Insaturados/fisiología , Regulación de la Expresión Génica/fisiología , Lipoproteínas/metabolismo , Regiones Promotoras Genéticas/fisiología , Transportador 1 de Casete de Unión a ATP , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1 , Transportadoras de Casetes de Unión a ATP/genética , Animales , Línea Celular , LDL-Colesterol/metabolismo , Proteínas de Unión al ADN/fisiología , Humanos , Lipoproteínas/genética , Receptores X del Hígado , Ratones , Receptores Nucleares Huérfanos , Mutación Puntual , Receptores Citoplasmáticos y Nucleares/fisiología , Receptores X Retinoide/fisiologíaRESUMEN
Introduction We previously showed that articular chondrocytes (ACs) have immune privilege and immunomodulatory functions like those of mesenchymal stem cells. To elucidate these mechanisms, we focused on interleukin-2 (IL-2), which plays critical roles in lymphocyte mitogenic activity. The purpose of this study was to explore whether ACs affect the role of IL-2 underlying immunomodulatory functions. Material and Methods Irradiated human ACs from osteoarthritis donors were used. Third-party ACs were added to the mixed lymphocyte reaction (MLR) with or without recombinant human IL-2 (rhIL-2), and the levels of IL-2 and the soluble form of the IL-2 receptor α (sIL-2Rα) protein in supernatant were measured by enzyme-linked immunosorbent assay. Recombinant human IL-2 (rhIL-2) was also added to the MLR. To detect the expression of IL-2 receptor α (CD25) on lymphocytes in the MLR, flow cytometric analysis was performed. Last, ACs and allogeneic activated CD4+ T cell were co-cultured, and the expression of CD25 on activated T cells was examined by flow cytometry. Results Third-party ACs significantly inhibited the MLR and reduced the level of sIL-2Rα in a dose-dependent manner, but did not affect the concentration of IL-2. Exogenous rhIL-2 accelerated MLR but did not rescue the inhibitory effect of ACs. ACs inhibited the expression of CD25 on activated CD4+ T cells. Discussion Our results showed that third-party ACs inhibited the proliferation of allogeneic activated lymphocytes, thereby inhibiting production sIL-2Rα, although ACs did not affect IL-2 secretion from lymphocytes. Also, ACs inhibited CD25 expression on activated CD4+ T cells. Thus, ACs inhibited the immune response of allogeneic lymphocytes by inducing IL-2 nonresponsiveness.
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BACKGROUND/OBJECTIVE: HDL has various atheroprotective functions and improves endothelial function. Apolipoprotein A-I (apoA-I) is a major protein of HDL and plays a crucial role in HDL functions. We developed a novel apoA-I mimetic peptide, FAMP (Fukuoka University ApoA-I Mimetic Peptide). It is unclear whether an apoA-I mimetic peptide can promote neovascularization in vivo. Here, we investigated the effect of FAMP on endothelial nitric oxide synthase (eNOS) activation and angiogenesis in a murine hindlimb ischemia model. METHODS AND RESULTS: Intramuscular administration of FAMP significantly enhanced blood flow recovery and increased capillary density in the ischemic limb of mice fed a high-cholesterol diet (HCD). In a gait analysis, FAMP ameliorated functional recovery compared with that in the control group. FAMP significantly activated Akt, ERK, and eNOS phosphorylation in endothelial cells, and improved the migratory functions of human aortic endothelial cells (HAECs). LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited the activation of eNOS by FAMP. FAMP had no beneficial effects on blood flow recovery in eNOS(-/-) mice. CONCLUSIONS: FAMP promoted recovery from hindlimb ischemia through a nitric oxide (NO)-related pathway by activation of a PI3K/Akt pathway. FAMP may become a new therapeutic agent for the future clinical treatment of critical limb ischemia (CLI).
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Apolipoproteína A-I/uso terapéutico , Materiales Biomiméticos/uso terapéutico , Miembro Posterior/irrigación sanguínea , Isquemia/tratamiento farmacológico , Óxido Nítrico/metabolismo , Fragmentos de Péptidos/uso terapéutico , Secuencia de Aminoácidos , Animales , Apolipoproteína A-I/genética , Apolipoproteína A-I/farmacología , Materiales Biomiméticos/farmacología , Células Cultivadas , Miembro Posterior/efectos de los fármacos , Humanos , Isquemia/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/farmacología , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Coronal imbalance of the pelvis is recognized to lead to the development of degenerative lumbar scoliosis. We hypothesized that an abrupt change of pelvic obliquity may show a reproducible trend of coronal compensation in the lumbosacral spine. The aim of the study was to classify the change of coronal alignment of spine after THA. METHODS: This is a retrospective study based on the radiological analysis of 195 patients who underwent THA between 2009 and 2010. The mean age at surgery was 61.5 years old, and minimum follow up period was 24 months. Pelvic obliquity (POb) and Cobb's angle of lumbar scoliosis (LS) in coronal plane were measured. Over 3.5 degrees of change in POb was regarded as ΔPOb(+) and over 10 degrees of lumbar scoliosis was regarded as LS(+). The change of LS were classified into 3 subtypes; ΔLS(+), over 5 degrees of progress in LS, ΔLS(-), over 5 degrees of improvement in LS, and ΔLS(n), changes in LS within 5 degrees. RESULTS: Over 3.5 degrees of change in POb was significantly correlated with the change in LS. Among195 patients, 120 patients improved their pelvic obliquity (ΔPOb(+)), and 75 patients did not have an improved pelvic obliquity (ΔPOb(-)). 99 patients out of 120 ΔPOb(+) patients did not show changes (54, ΔLS(n)) or improvement in scoliosis (45, ΔLS(-)).The remaining 21 patients showed progress or development of de novo scoliosis. Patients who failed to compensate for the POb change at lumbosacral area developed de novo lumbar scoliosis (7 cases), showed progression in lumbar scoliosis (7 cases) or developed coronal trunk shift over 20mm (7 cases). CONCLUSIONS: The patterns of compensation in lumbar or lumbosacral spine in coronal plane after leg lengthening THA were classified with regards to pelvic obliquity and Cobb's angle. 89.2% of 195 patients showed acceptable compensation in lumbar spine, 21 patients developed coronal imbalance. THA therefore is considered to be safe, as regards to spinal balance in coronal plane. However we have to keep in mind that preoperative rigid scoliosis could have a risk in progress for spinal imbalance.