RESUMEN
BACKGROUND: Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPIcr) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts. OBJECTIVE: To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPIcr equation without race. DESIGN: Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD. PATIENTS: A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set. METHODS: The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations. RESULTS: The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR). CONCLUSION: The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.
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Creatinina , Tasa de Filtración Glomerular , Redes Neurales de la Computación , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Adulto , Creatinina/sangre , China/epidemiología , Anciano , Vejiga Urinaria Neurogénica/fisiopatología , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Neurogénica/diagnóstico , Vejiga Urinaria Neurogénica/sangre , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Pentetato de Tecnecio Tc 99mRESUMEN
INTRODUCTION: Although intradialytic exercise is considered a form of "nonpharmacological medicine" for patients receiving maintenance hemodialysis (MHD), this practice has not been widely implemented in most dialysis centers because of clinical limitations. We, therefore, aimed to design an intradialytic exercise training program to improve the implementation of this practice and determine its impact on physical performance and cardiovascular risk factors in patients receiving MHD. METHODS: A total of 132 MHD patients at 4 outpatient dialysis units were enrolled and assigned randomly into exercise (n = 67) and control groups (n = 65). During a 2-year period, patients in the exercise group participated in 20-min exercise training sessions within dialysis sessions on 3 days per week. All patients underwent assessments of physical function (6-min walk test) and cardiovascular risk factors (blood pressure [BP], total cholesterol [TC], low-density lipoprotein [LDL], high-sensitivity C-reactive protein [hsCRP], albumin [Alb], hemoglobin [Hb], and erythropoietin [EPO] dose) at the baseline and annually thereafter. RESULTS: Of the participants, 50.8% had completed the study after 2 years. No statistically significant intragroup or intergroup differences were observed in the measures of 6MD, BP, TC, hsCRP, Alb, Hb, and EPO dose. CONCLUSION: The results suggest that although this low-intensity, nonprogressive intradialytic exercise program may be practical, it was not sufficient to improve physiological function and reduce cardiovascular disease risk factors in patients receiving MHD.
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Enfermedades Cardiovasculares/etiología , Diálisis Renal , Adulto , Ejercicio Físico , Estudios de Factibilidad , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Rendimiento Físico Funcional , Proyectos Piloto , Diálisis Renal/efectos adversosRESUMEN
Background: The liver plays a central role in the synthesis and metabolism of homocysteine (Hcy). The present study aimed to determine the prognostic role of serum Hcy levels in patients with HBV-related acute-on-chronic liver failure (AoCLF). Methods: Fifty-two AoCLF and 52 chronic hepatitis B (CHB) patients were recruited. The virological parameters and biochemical examination of blood were obtained after 12 hours of fasting. In the AoCLF group, the relationships between the prognosis and the Hcy level were analyzed. The primary end-point was 3-month in-hospital mortality. Results: A significantly higher Hcy level was detected in AoCLF patients than in the healthy controls (HCs) and CHB groups (both p < 0.01). The Hcy level was positively correlated with the model of end-stage liver disease (MELD) score and the creatinine levels and was inversely correlated with the estimated glomerular filtration rate. Moreover, Hcy levels at presentation were higher among non-survivors than survivors in AoCLF patients. Multivariate analysis suggested that both Hcy level and MELD score were independent predictors of 3-month mortality in patients with AoCLF (p < 0.001). Conclusions: Serum Hcy level measured at admission may serve as a biomarker for 3-month mortality rate in patients with HBV-AoCLF.
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Insuficiencia Hepática Crónica Agudizada/sangre , Biomarcadores/sangre , Hepatitis B Crónica/sangre , Homocisteína/sangre , Insuficiencia Hepática Crónica Agudizada/complicaciones , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adulto , Femenino , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Mortalidad Hospitalaria , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios ProspectivosRESUMEN
The aim of the present study is to investigate the expressions of ATP-sensitive K(+) channels (KATP) in pulmonary artery smooth muscle cells (PASMCs) and the relationship with p38 MAPK signal pathway in rats. Male SD rat PASMCs were cultured in vitro, and a model of hypoxia and hypercapnia was reconstructed. PASMCs were divided to normal (N), hypoxia-hypercapnia (H), hypoxia-hypercapnia+DMSO incubation (HD), hypoxia-hypercapnia+SB203580 (inhibitor of p38 MAPK pathway) incubation (HS) and hypoxia-hypercapnia+Anisomycin (agonist of p38 MAPK pathway) incubation (HA) groups. Western blot was used to detect the protein expression of SUR2B and Kir6.1; semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of SUR2B and Kir6.1. The results demonstrated that: (1) Compared with N, H, HD and HS groups, the expressions of Kir6.1 mRNA and protein in PASMCs of HA group were decreased significantly (P < 0.01), but there were no differences among N, H, HD and HS groups (P > 0.05); (2) Compared with N group, the expressions of SUR2B mRNA and protein in H, HD, HS and HA groups were increased significantly (P < 0.05), but there were no differences among H, HD, HS and HA groups (P > 0.05). The results imply that: (1) Hypoxia-hypercapnia, SB203580 didn't change the expressions of Kir6.1 mRNA and protein in PASMCs, but Anisomycin decreased the expressions of Kir6.1 mRNA and protein, so Kir6.1 may be regulated by the other subfamily of MAPK pathway; (2) Hypoxia-hypercapnia raised SUR2B mRNA and protein expressions in PASMCs, but SB203580 and Anisomycin did not affect the changes, so the increasing of SUR2B mRNA and protein induced by hypoxia-hypercapnia may be not depend on p38 MAPK pathway.
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Canales KATP/metabolismo , Sistema de Señalización de MAP Quinasas , Miocitos del Músculo Liso/metabolismo , Animales , Anisomicina/farmacología , Hipoxia de la Célula , Células Cultivadas , Hipercapnia , Imidazoles/farmacología , Masculino , Arteria Pulmonar/citología , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Sulfonilureas/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidoresRESUMEN
The aim of the present study was to investigate the roles of calcium-activated chloride channels (Cl(Ca)) in the two-phase hypoxic pulmonary vasoconstriction (HPV). The second pulmonary artery branches were dissected from male Sprague-Dawley rats, and the changes in vascular tone were measured by using routine blood vascular perfusion in vitro. The result showed that, under normoxic conditions, Cl(Ca) inhibitors (NFA and IAA-94) significantly relaxed second pulmonary artery contracted by norepinephrine (P < 0.01), but merely had effects on KCl-induced second pulmonary artery contractions. A biphasic contraction response was induced in second pulmonary artery ring pre-contracted with norepinephrine exposed to hypoxic conditions for at least one hour, but no biphasic contraction was observed in pulmonary rings pre-contracted with KCl. NFA and IAA-94 significantly attenuated phase II sustained hypoxic contraction (P < 0.01), and also attenuated phase I vasodilation, but had little effect on phase I contraction. These results suggest that Cl(Ca) is an important component forming phase II contraction in secondary pulmonary artery, but not involved in phase I contraction.
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Canales de Cloruro/fisiología , Hipoxia/fisiopatología , Arteria Pulmonar/fisiopatología , Vasoconstricción , Animales , Glicolatos/farmacología , Masculino , Norepinefrina/farmacología , Ratas , Ratas Sprague-Dawley , VasodilataciónRESUMEN
Background: Golgi phosphoprotein-3 (GOLPH 3) is involved in the development of several human cancers. However, the clinical significance and biological role of GOLPH 3 in ovarian cancer (OC) remains unknown. Methods: The expression of GOLPH 3 in OC cell lines was quantified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The role of GOLPH 3 in tumorigenicity, migration, and invasion of OC cell lines by small interference RNA, scratch wound-healing assays, and transwell assays was detected. In addition, western blotting was used to determine whether GOLPH 3 is associated with the PI3K/AKT/mTOR signaling pathway. Furthermore, RT-qPCR verified whether GOLPH 3 is associated with drug resistance. Results: GOLPH 3-positive expression rate was higher in OC. Downregulation of GOLPH 3 markedly inhibited the migration and invasion and may be related to the PI3K/AKT/mTOR signal pathway. Moreover, the result of the experiment proved that GOLPH 3 enhances the sensitivity of OC to cisplatin by regulating ATP7A/B. GOLPH 3 promoted the invasion and migration of OC, and the mechanism may be related to the PI3K/Akt/mTOR pathway. In addition, inhibition of GOLPH 3 increased the sensitivity of OC cells to cisplatin, which may be associated with ATP7A/B. Conclusion: This study found that GOLPH3 may promote the migration and invasion of OC cells through PI3K/Akt/mTOR pathway. At the same time, low expression of GOLPH3 increased the sensitivity of OC cells to cisplatin.
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Cisplatino , Proteínas de la Membrana , Neoplasias Ováricas , Carcinoma Epitelial de Ovario , Movimiento Celular/genética , Proliferación Celular , Cisplatino/farmacología , Resistencia a Antineoplásicos , Femenino , Humanos , Proteínas de la Membrana/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfoproteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genéticaRESUMEN
OBJECTIVES: The aim of the study was to explore motivators for and barriers to exercise rehabilitation in hemodialysis patients and the barriers perceived by the hemodialysis center staff. DESIGN: A cross-sectional study was performed in five hemodialysis centers using patient questionnaires designed for this study to evaluate the motivators for and barriers to exercise rehabilitation. Questionnaires were not yet validated. RESULTS: Of the 471 recruited patients, 63.3% were willing to participant in exercise rehabilitation. The greatest motivators included improving quality of life (98.0%) and wanting to be healthier (98.0%). Perceived barriers included discomfort (59.0%), concerns regarding safety (36.7%), and disinterest (27.0%). Among these, unwillingness, disinterest, and having peripheral arterial disease were independent risk factors of lack of participation in exercise rehabilitation. The most common perceived barriers among the 90 employees that participated were lack of professional guidance and advice from rehabilitation therapists (93.1%), lack of exercise rehabilitation knowledge (86.2%), and lack of special exercise equipment (86.2%). CONCLUSIONS: Most patients were willing to exercise to improve their health and quality of life. Barriers to exercise rehabilitation included patient and staff factors. It is essential to establish a rehabilitation team within dialysis centers, including general staff and rehabilitation therapists. These centers require improved rehabilitation policies and access to specialized rehabilitation equipment.
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Actitud Frente a la Salud , Terapia por Ejercicio/psicología , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , China , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Motivación , Encuestas y CuestionariosRESUMEN
The clinical epidemiological features of cognitive impairment in Chinese older adult patients undergoing hemodialysis are not clear, we aimed to identify the extent and patterns of cognitive impairment among those patients. We conducted a cross-sectional study of 613 hemodialysis patients aged 50 to 80 from 11 centers in Beijing. A neuropsychological battery of 11 tests covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied, patients were classified as none, mild, or major cognitive impairment according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria for cognitive impairment. Compared with Chinese population norms, 37.2% of the participants had mild cognitive impairment, 43.7% had major cognitive impairment. Memory and language were the most severe impaired domains in the mild cognitive impairment group, attention and visuospatial function domains were the most serious impaired domains in the major cognitive impairment group. Concomitant impairment across multiple cognitive domains was common. Factors associated with major cognitive impairment included age, education level, history of stroke and hypertension, dialysis vintage, and single-pool Kt/V. There is a high frequency of cognitive impairment in Chinese older adult hemodialysis patients, with varying severity and concomitant impairment across multiple domains.
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Disfunción Cognitiva/epidemiología , Diálisis Renal , Anciano , Disfunción Cognitiva/fisiopatología , Estudios Transversales , Función Ejecutiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
AIM: Currently, the widely adopted renal dynamic imaging in clinical practice uses Gates' method to calculate the glomerular filtration rate (GFR), but many researchers have proven that Gates' method may result in bias. Thus, this article explores alternative improved formulae to calculate GFR by renal dynamic imaging. METHODS: Three hundred and sixty-seven patients were selected and their GFR values were measured using renal dynamic imaging and the two-plasma method with 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) as the imaging agent. With the two-plasma GFR as reference value, two equations were obtained from linear and non-linear regression analyses between the renal uptake percentage and two-plasma GFR. The 367 patients were divided into two random groups, with the first group used to derive the regression formulae and the second to verify the formulae. Finally, all patients were studied to derive the formulae to calculate GFR. The comparison of our formulae with the commonly used Gates' formula was conducted by the Bland-Altman method. RESULTS: The linear and non-linear GFR formulae were as follows: GFR (ml/min/1.73 m2)=(631.633 x renal uptake percentage - 2.040) x 1.73/BSA (BSA, body surface area) and GFR (ml/min/1.73 m2)=(-1996.585 x renal uptake percentage2 + 1013.526 x renal uptake percentage - 12.739) x 1.73/BSA, respectively. The biases of the GFR values calculated using the linear and non-linear formulae and Gates' formula relative to the two-plasma GFR were -2.5 +/- 19.1 ml/min/1.73 m2, -2.0 +/- 19.3 ml/min/1.73 m2 and 3.4 +/- 19.4 ml/min/1.73 m2, respectively. CONCLUSIONS: The GFR values calculated using our new formulae correlate better with the reference GFR value than does GFR calculated by Gates' formula, and the GFR values measured using the non-linear formula are more accurate than those obtained using the linear formula.
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Algoritmos , Tasa de Filtración Glomerular , Interpretación de Imagen Asistida por Computador/métodos , Enfermedades Renales/diagnóstico , Renografía por Radioisótopo/métodos , Pentetato de Tecnecio Tc 99m , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Enfermedades Renales/metabolismo , Masculino , Persona de Mediana Edad , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Pentetato de Tecnecio Tc 99m/farmacocinéticaRESUMEN
OBJECTIVE: To investigate the expression of mRNA and protein of Calcium activated chloride channel (CLCA2) in hypoxic pulmonary artery smooth muscle cell (PASMCs) of rat and it's relationship with ERK1/2 signal pathway. METHODS: PASMCs were randomly divided into 5 groups including normal group(N group), hypoxia group(H group), DMSO group(D group), U0126 group (U group) and Staurosporine aglycone group(SA group). The protein expression of CLCA2 in PASMCs was detected by Western blot.The mRNA expression of CLCA2 was detected by half quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The mRNA and protein expressions of CLCA2 in H group were significantly higher than N group (P<0.01). Comparing with D group,the mRNA and protein expressions of CLCA2 were significantly increased in U group (P<0.01),the mRNA expression of CLCA2 in SA group was obviously decreased (P<0.01) with slightly decreasing of its protein expression. CONCLUSIONS: Hypoxia promotes the expressions of mRNA and protein of CLCA2 in rat PASMCs. The ERK1/2 pathway activator Staurosporine aglycone reduces the mRNA and protein expression of CLCA2 in rats PASMCs and the ERK1/2 pathway inhibitor U0126 induces the upregulation of the mRNA and protein expressiosn of CLCA2 in rats PASMCs.
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Canales de Cloruro/metabolismo , Sistema de Señalización de MAP Quinasas , Miocitos del Músculo Liso/metabolismo , Animales , Carbazoles/farmacología , Hipoxia de la Célula , Células Cultivadas , Alcaloides Indólicos/farmacología , Músculo Liso Vascular/citología , Arteria Pulmonar/citología , RatasRESUMEN
BACKGROUND: To evaluate whether the Modification of Diet in Renal Disease (MDRD) equations could be applied accurately to Chinese patients with chronic kidney disease (CKD), glomerular filtration rates (GFRs) estimated by using MDRD equation 7 (7GFR), the abbreviated MDRD equation (aGFR), and the Cockcroft-Gault equation (cGFR) were compared in patients with different stages of CKD. METHODS: The study enrolled patients with CKD diagnosed according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative guidelines. All patients were older than 18 years and without acute renal function deterioration, edema, skeletal muscle atrophy, or amputation. Sex, age, body height, and body weight were recorded, and plasma creatinine levels were measured by means of Jaffe's kinetic method using a Hitachi 7600 analyzer (Hitachi, Tokyo, Japan; reagents from Roche Diagnostics, Mannheim, Germany). Creatinine, urea, and albumin were measured in a single clinical laboratory. Dual plasma sampling of technetium Tc 99m-labeled diethylene triamine pentaacetic acid plasma clearance was used as the reference standard GFR (sGFR) for comparison of 7GFRs, aGFRs, and cGFRs at different stages of CKD. RESULTS: The study enrolled 261 patients, including 146 men and 115 women. Causes of CKD included primary or secondary glomerular disease, obstructive kidney disease, chronic tubulointerstitial disease, and others. Values for 7GFR, aGFR, and cGFR were significantly greater than for sGFR in patients with CKD stages 4 to 5 (the lower the sGFR, the greater the difference); whereas 7GFR, aGFR, and cGFR were significantly lower than sGFR in patients with CKD stage 1. CONCLUSION: Our results show that in a Chinese population with CKD, MDRD equation 7 and the abbreviated MDRD equation overestimated GFR in patients with CKD stages 4 to 5 and underestimated GFR in those with CKD stage 1. These results indicate that careful modification of these equations may be necessary in Chinese populations with CKD.
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Algoritmos , Tasa de Filtración Glomerular , Enfermedades Renales/fisiopatología , Adulto , Anciano , China/epidemiología , Creatinina/sangre , Progresión de la Enfermedad , Femenino , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Cintigrafía , Radiofármacos/farmacocinética , Albúmina Sérica/análisis , Pentetato de Tecnecio Tc 99m/farmacocinética , Urea/sangreRESUMEN
OBJECTIVE: To understand the applicability of MDRD equation in Chinese patients with chronic kidney disease (CKD). Glomerular filtration rate (GFR) estimated with MDRD equation, abbreviated MDRD equation and Cockcroft-Gault equation was compared with (99m)Tc-DTPA plasma clearance by dual plasma sampling method in different stages of CKD. METHODS: CKD were diagnosed according to K/DOQI guideline.298 patients with CKD were selected. Patients'sex, age, height and body weight were recorded and plasma creatinine, urea nitrogen and albumin were measured in a single clinical laboratory. (99m)Tc-DTPA plasma clearance was calculated and standardized by body surface area (sGFR). GFRs estimated with MDRD equation 7, abbreviated MDRD equation and Cockcroft-Gault equation (7GFR, aGFR and cGFR) were compared with sGFR in different stages of CKD. RESULTS: There were 165 male and 133 female in the selected 298 patients with CKD;the average age was (52.5 +/- 15.5) years. There was significant difference between the GFRs of the 3 equations with sGFR in different stages of CKD (P < 0.001). 7GFR, aGFR and cGFR were significantly higher than sGFR in CKD stages 5-4; the lower the sGFR, the more the differences. 7GFR, aGFR and cGFR were significantly lower than sGFR in CKD stage 2-1; the higher the sGFR, the more the differences. CONCLUSION: Our results showed that in Chinese population with CKD, MDRD equation 7, abbreviated MDRD equation and Cockcroft-Gault equation overestimate actual GFR in CKD stages 4-5 and underestimate GFR in CKD stages 1-2. These results indicate that MDRD equation and its modifications for estimation of GFR should be amended when applying to Chinese patients with CKD in clinical practice.
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Algoritmos , Tasa de Filtración Glomerular , Enfermedades Renales/fisiopatología , Adulto , Anciano , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , IncertidumbreRESUMEN
OBJECTIVE: To find an applicable condition of the single-plasma-sample method (SPSM) to measure the glomerular filtration(GFR) with (99m)Tcj Diethylene Triamine Pentaacetic Acid ((99m)Tc-DTPA), and predict the value of (99m)Tc-DTPA plasma clearance by dual plasma sample method (DPSM ) from that by SPSM. METHODS: Three hundred and thirty five patients with chronic kidney disease (CKD) were selected (192 males and 143 females). The average age was 51.91+/-14.76 years. The GFR was determined simultaneously by 2 methods: (1) SPSM (sGFR); (2) DPSM (tGFR), using DPSM as reference standard, sGFR calculated from the different SPSM was compared with tGFR. An equation was developed to predict tGFR from sGFR. GFR estimated by abbreviated Modification of Diet in Renal Disease (MDRD) equation (aGFR) was evaluated as the criterion in selection of DPSM and SPSM. The condition that DPSM could be substituted by SPSM in GFR measurement was given. RESULTS: When tGFR >or= 30 mL/(minx1.73 m(2)), all of the sGFR were significantly correlated with tGFR. Among them, Watson modified Christensen and Groth's equation at sample time=240 min tended to be the most accurate (r=0.977, RMSE=10.91), and tGFR could be predicted from sGFR using the equation: Predicted tGFR [mL/(minx1.73 m(2))]=7.755 4+0.789 3xsGFR+0.002 4 xsGFR2 (n=297, r2=0.959 1, P<0.001). When aGFR was less than 50 mL/(minx1.73 m(2)), the diagnostic sensitivity of tGFR<30 mL/(minx1.73 m(2)) was 94.7%, and recommended as the criterion in selection of DPSM and SPSM. CONCLUSION: When aGFR >or=50 mL/(minx1.73 m(2)), DPSM can be substituted by SPSM in GFR measurement.
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Creatinina/sangre , Enfermedades Renales/sangre , Renografía por Radioisótopo/métodos , Radiofármacos/sangre , Pentetato de Tecnecio Tc 99m/sangre , Algoritmos , Enfermedad Crónica , Femenino , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/fisiopatología , Masculino , Tasa de Depuración Metabólica , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Pentetato de Tecnecio Tc 99m/farmacocinéticaRESUMEN
OBJECTIVE: The tumor suppressor gene, Ras-association domain family (RASSF)2A, is inactivated by promoter hypermethylation in many cancers. The current study was performed to evaluate the methylation status of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and correlations with gene expression and clinicopathologic characteristics. METHOD: We detected methylation of the RASSF2A gene in tissues and corresponding plasma samples from 47 EOC patients and 14 patients with benign ovarian tumors and 10 with normal ovarian tissues. The methylation status was determined by methylation-specific PCR while gene expression of mRNA was examined by RT-PCR. The EOC cell line, SKOV3, was treated with 5-aza-2'-deoxycytidine (5-aza- dC). RESULTS: RASSF2A mRNA expression was significantly low in EOC tissues. The frequency of aberrant methylation of RASSF2A was 51.1% in EOC tissues and 36.2% in corresponding plasma samples, whereas such hypermethylation was not detected in the benign ovarial tumors and normal ovarian samples. The expression of RASSF2A mRNA was significantly down-regulated or lost in the methylated group compared to the unmethylated group (p<0.05). After treatment with 5-aza-dC, RASSF2A mRNA expression was significantly restored in the Skov3 cell line. CONCLUSION: Epigenetic inactivation of RASSF2A through aberrant promoter methylation may play an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be a valuable molecular marker for the early detection of EOC.
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Metilación de ADN/genética , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/genética , Proteínas Supresoras de Tumor/genética , Azacitidina/análogos & derivados , Azacitidina/farmacología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Decitabina , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Regiones Promotoras Genéticas , ARN Mensajero/biosíntesis , Proteínas Supresoras de Tumor/sangre , Proteínas Supresoras de Tumor/metabolismoRESUMEN
OBJECTIVE: To investigate the role and significance of ATP-sensitive K+ channels in the pathological process of hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV) and the relationship with ERK1/2 signal pathway in rats. METHODS: We made the third pulmonary artery rings of SD rats, used the model of pulmonary artery rings perfusion in vitro. Under acute hypoxia hypercapnia condition, and observed the effects of the three stages of HHPV incubated by glybenclamide(Gly) and the combined application of Gly and U0126. At the same time, the values of rings' tension changes were recorded via the method of hypoxia hypercapnia conditions reactivity. RESULTS: Under the normoxia condition, the values of the third pulmonary artery rings tension were relatively stable, but under the hypoxia hypercapnia condition, we observed a biphasic pulmonary artery contractile response compared with N group (P < 0.05, P < 0.01). When the third pulmonary artery rings incubated by Gly, it's phase II persistent vasoconstriction was enhanced compared with the H group (P < 0.05, P < 0.01), and the phase I vasoconstriction was also heightened. Moreover, under the hypoxia hypercapnia condition, U0126 could significantly relieve the phase II persistent vasoconstriction compared with HD group (P < 0.05, P < 0.01) induced by Gly, but the phase I acute vasoconstriction and the phase I vasodilation had no changes (P > 0.05). CONCLUSION: Gly may mediate HHPV via activating ERK1/2 signal transduction pathway.
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Gliburida/farmacología , Hipoxia/fisiopatología , Sistema de Señalización de MAP Quinasas/fisiología , Vasoconstricción/efectos de los fármacos , Animales , Hipercapnia/metabolismo , Hipercapnia/fisiopatología , Hipoxia/metabolismo , Técnicas In Vitro , Masculino , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the effects of ischemic postconditioning (IPostC) on pneumocyte apoptosis after lung ischemia/reperfusion injury in rats. METHODS: Adult male SD rats were randomly divided into 3 groups based upon the intervention (n = 8): control group (C), lung ischemic reperfusion group (LIR), LIR+ IPostC group (IPostC). At the end of the experiment, blood specimens drawn from the arteria carotis were tested for the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO); the pneumocyte apoptosis index (AI) was achieved by tennrminal deoxynucleotidyl transferase mediated dUTP nick end abeling (TUNEL); the expression of Bcl-2, Bax protein in lung tissue was accessed by quantitative immunohistochemistry (MHC) and Bcl-2, Bax mRNA by RT-PCR. RESULTS: IPostC could significantly attenuate the MDA level, MPO activity and improve SOD activity in blood serum which was comparable to I/R and significantly reduced the number of TUNEL-positive cells compared with I/R group, expressed as Al (% total nuclei) from (39.0 +/- 3.46) to (8.0 +/- 0.88) (P < 0.01). The protein and mRNA expression of Bcl-2 and Bax showed that IPO significantly attenuated the ischemia/reperfusion-upregulated expression of Bax protein but improved the expression of Bcl-2 that improved the Bcl-2/Bax ratio (P < 0.01) . CONCLUSION: IPostC may attenuate pneumocyte apoptosis in LIRI by up-regulating expression of Bcl-2/Bax ratio and by inhibiting oxidant generation and neutrophils filtration.
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Células Epiteliales Alveolares/citología , Apoptosis , Poscondicionamiento Isquémico , Lesión Pulmonar/fisiopatología , Daño por Reperfusión/fisiopatología , Animales , Pulmón/metabolismo , Pulmón/patología , Masculino , Malondialdehído/metabolismo , Peroxidasa/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of chloride channel blocker--niflumic acid (NFA) on the pathological process of hypoxia hypercapnia-induced pulmonary vasoconstriction in rats. METHODS: We used the model of hypoxia hypercapnia-induced pulmonary vasoconstriction rats, and divided the second, third branch pulmonary artery rings randomly into four groups (n = 8): control group (N group), hypoxia hypercapnia group (H group), DMSO incubation group (HD group), niflumic acid group (NFA group). Under acute hypoxia hypercapnia conditions, we observed the effects of the three stages of hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV) incubated by NFA in the second, third brach pulmonary artery rings. At the same time, the values of rings' tension changings were recorded via the method of hypoxia hypercapnia conditions reactivity. And investigated the effect of NFA to HHPV. RESULTS: (1) Under the hypoxia hypercapnia condition, we observed a biphasic pulmonary artery contractile (the phase I rapid contraction and vasodilation; the phase II sustained contraction) response in both the second and the third branch pulmonary artery rings compared with the control group (P < 0.05 , P < 0.01); (2) The second and third pulmonary artery rings incubated by NFA which phase II persistent vasoconstriction were significantly attenuated compared with the H group (P < 0.05 , P < 0.01). CONCLUSION: The blocker of the chloride channels attenuates the second and third branch pulmonary artery rings constriction in rat, especially the phase II persistent vasoconstriction, so then have an antagonistic effect on HHPV.
Asunto(s)
Hipercapnia/fisiopatología , Hipoxia/fisiopatología , Ácido Niflúmico/farmacología , Vasoconstricción/efectos de los fármacos , Animales , Canales de Cloruro/antagonistas & inhibidores , Arteria Pulmonar/fisiopatología , Circulación Pulmonar , RatasRESUMEN
OBJECTIVE: To investigate the role of p38 MAPK on ischemic postconditioning (IPO) attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury (LIRI). METHODS: Forty adult male SD rats were randomly divided into 5 groups based upon the intervention (n = 8): control group (C), LIR group (I/R), LIR + IPO group (IPO), IPO + solution control group (D), IPO + SB203580 group (SB). Left lung tissue was isolated after the 2 hours of reperfusion, the ratio of wet lung weight to dry lung weight (W/D), and total lung water content (TLW) were measured. The histological structure of the left lung was observed under light and electron transmission microscopes, and scored by alveolar damage index of quantitative assessment (IQA). Apoptosis index (AI) of lung tissue was determined by terminal deoxynuleotidyl transferase mediated dUTP nick end and labeling (TUNEL) method. The mRNA expression and protein levels of and Bax were measured by RT-PCR and quantitative immunohistochemistry (IHC). RESULTS: Compared with C group, W/D, TLW, IQA, AI and the expression of Bax of I/R were significantly increased, the expression of Bcl-2 and Bcl-2/Bax were significantly decreased (P < 0.05, P < 0.01), and was obviously morphological abnormality in lung tissue. Compared with I/R group, all the indexes of IPO except for the expression of Bcl-2 and Bcl-2/ Bax were obviously reduced, the expression of Bcl-2 and Bcl-2/Bax were increased (P < 0.05, P < 0.01). All the indexes between D and IPO were little or not significant( P > 0.05). The expression of Bcl-2 and Bcl-2/Bax of SB were significantly increased and other indexes were reduced than those of IPO (P < 0.05, P < 0.01). CONCLUSION: IPO may attenuate pneumocyte apoptosis in LIRI by inactivation of p38 MAPK, up-regulating expression of Bcl-2/Bax ratio.
Asunto(s)
Células Epiteliales Alveolares/citología , Apoptosis , Poscondicionamiento Isquémico , Pulmón/irrigación sanguínea , Daño por Reperfusión/prevención & control , Animales , Modelos Animales de Enfermedad , Pulmón/enzimología , Pulmón/patología , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Proteína X Asociada a bcl-2/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: The renal dynamic imaging method (modified Gate's method) with (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) is simple and less time consuming for glomerular filtration rate (GFR) estimation than other methods. However, its diagnostic performance as a surrogate marker of GFR is questioned increasingly. Recently, the modified Modification of Diet in Renal Disease (MDRD) study equation based on data from Chinese patients of chronic kidney disease (CKD) showed significant performance improvement. In the present study, the renal dynamic imaging methods and the modified abbreviated MDRD equation were compared with the plasma clearance method. METHODS: Four hundred and eighty two patients with CKD were selected. GFR were estimated simultaneously using three methods: (i) modified Gate's method (gGFR); (ii) the modified abbreviated MDRD equation (c-aGFR) and (iii) dual plasma sampling method (rGFR). Using rGFR as the reference method, gGFR and c-aGFR were compared with rGFR in each stage of CKD. RESULTS: Both gGFR and c-aGFR were correlated well with rGFR (r(gGFR) = 0.81 and r(c-aGFR) = 0.90, P < 0.001). In the overall performance, c-aGFR had less bias (849.5 vs 933.1 arbitrary units), higher precision (57 vs 78.4 ml/min/1.73 m(2)) and higher accuracy than gGFR. For gGFR, the 15, 30 and 50% accuracies were 32.4, 56.0 and 79.1%, respectively; for c-aGFR, the corresponding accuracy rose to 43.2%, 75.5% and 90.9%, respectively. In each stage of CKD, the modified abbreviated MDRD equation also outperformed the modified Gate's method in the GFR estimation. CONCLUSION: Our results indicated that the performance of the renal dynamic imaging in total GFR estimation was not better than the modified abbreviated MDRD equation in our patient group, and should not be used as a surrogate marker of GFR, especially in clinical trials. We presume that the dynamic renal imaging methods for estimation of GFR can be improved by using proper reference GFR, more adequate background subtraction and soft-tissue attenuation correction, in a relatively larger sample size.