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OBJECTIVE: While the prevalence of radiographic and symptomatic osteoarthritis (OA) is higher in women, male mice are more frequently used in animal experiments to explore its pathogenesis or drug efficacy. In this study, we examined whether sexual dimorphism affects pain and joint degeneration in destabilization of the medial meniscus (DMM) mouse model. METHODS: DMM or sham surgery was performed on the knee of male and female C57BL/6 mice. Joint damage was assessed by safranin O staining and scored using the Osteoarthritis Research Society International (OARSI) scoring system. Von Frey hair, incapacitance, and rotarod tests were conducted to measure joint pain. The analgesic effect of capsazepine (CPZ), a TRPV1 antagonist, was compared between male and female mice. RESULTS: Histology and OARSI scoring analysis showed that cartilage degeneration developed, and progressed in both male and female DMM groups, however, damage was less severe in females at the late stage of OA. Pain behavior, as measured by mechanical allodynia, was displayed for longer in male DMM mice compared to females. Incapacitance data showed that CPZ significantly reduced DMM-induced pain in male mice but not in female mice. Immunofluorescence microscopy analysis demonstrated that DMM surgery increased the expression of TRPV1 in both female and male dorsal root ganglion (DRG). Injection of CPZ significantly suppressed TRPV1 expression in the DRG of male mice only. CONCLUSION: Joint damage develops comparably in both female and male mice after DMM although it progresses less in females. There was a subtle sex difference in pain behaviors and analgesic efficacy of a TRPV1 antagonist, which was accompanied by a differential regulation of TPRV1.
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Conducta Animal , Cartílago Articular/patología , Osteoartritis/patología , Dolor/etiología , Factores Sexuales , Animales , Capsaicina/análogos & derivados , Capsaicina/farmacología , Modelos Animales de Enfermedad , Femenino , Ganglios Espinales/metabolismo , Masculino , Ratones Endogámicos C57BL , Microscopía Fluorescente , Osteoartritis/tratamiento farmacológico , Fármacos del Sistema Sensorial/farmacología , Rodilla de Cuadrúpedos/patología , Canales Catiónicos TRPV/metabolismoRESUMEN
OBJECTIVE: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN: A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING: Tertiary referral hospitals in South Korea. POPULATION: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS: Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE: Preterm birth (PTB) before 37 weeks of gestation. RESULTS: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT: Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.
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Nacimiento Prematuro/prevención & control , Progestinas/administración & dosificación , Administración Intravaginal , Adulto , Femenino , Humanos , Inyecciones Intramusculares , Metaanálisis como Asunto , Embarazo , Embarazo de Alto RiesgoRESUMEN
AIM: To explore the involvement of TLR5 in pulp inflammation and to examine the effects of TLR5 activation with its ligand, FlaB protein, on pro-inflammatory gene expression. METHODOLOGY: TLR5 expression in dental pulp tissues and human dental pulp cells (hDPCs) were determined by immunohistochemistry, immunocytochemistry, Western blots and RT-PCR analyses. To examine the role of TLR5, hDPCs were treated with recombinant FlaB protein (500 ng mL-1 ) to activate the receptor or with a small interfering RNA against TLR5 (si-TLR5) to downregulate the receptor. After exposure to FlaB, the expression of inflammation-related proteins was screened using a protein array kit. Western blots or qRT-PCR analyses were performed to identify changes in the expression of uPA (urokinase plasminogen activator), TIMPs (tissue inhibitor of metalloproteinases), and IL-6 and to determine their signalling pathways. Statistical analysis was performed using one-way analysis of variance (anova) with Tukey post hoc test; P < 0.05 was considered statistically significant. RESULT: TLR5 expression was identified in pulp tissues and hDPCs. In the protein array analysis, treatment with FlaB significantly increased uPA expression (P < 0.01) and significantly decreased TIMP1/4 (P < 0.05). FlaB treatment also significantly increased expression of the inflammatory marker IL-6 (P < 0.01). FlaB treatment increased phosphorylation of the NF-κB p65 subunit, JNK, p38 and ERK. Chemical inhibitors of NF-κB (Bay11-7082), p38 (SB202190) or ERK (U0126) decreased the FlaB induction of uPA expression. Downregulation of TLR5 expression by siRNA decreased the FlaB induction of uPA protein and p65 phosphorylation. CONCLUSION: TLR5 activation with FlaB treatment induced the expression of uPA via the NF-κB and MAPK signalling pathways. Flagellin-bearing oral bacteria may cause pulp inflammation through TLR5. The findings provide new clues to control pulpal diseases by targeting TLR5 signalling pathways.
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FN-kappa B , Activador de Plasminógeno de Tipo Uroquinasa , Pulpa Dental , Humanos , Mediadores de Inflamación , Plasminógeno , Receptor Toll-Like 5RESUMEN
OBJECTIVE: We investigated the effects of 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) on xylosyltransferase-1 (XT-1), an essential anabolic enzyme that catalyzes the initial and rate-determining step in glycosaminoglycan chain synthesis, in human primary chondrocytes. METHODS: Proteoglycan and XT-1 expression in cartilage tissue was analyzed using safranin O staining and immunohistochemistry. The effects of 29-kDa FN-f on XT-1 expression and its relevant signaling pathway were analyzed by quantitative real-time-PCR, immunoblotting, chromatin immunoprecipitation, and immunoprecipitation assays. The receptors for 29-kDa FN-f were investigated using small interference RNA and blocking antibodies. RESULTS: The expression of XT-1 was significantly lower in human osteoarthritis cartilage than in normal cartilage. Intra-articular injection of 29-kDa FN-f reduced proteoglycan levels and XT-1 expression in murine cartilage. In addition, in 29-kDa FN-f-treated cells, XT-1 expression was significantly suppressed at both the mRNA and protein levels, modulated by the transcription factors specificity protein 1 (Sp1), Sp3, and activator protein 1 (AP-1). The 29-kDa FN-f suppressed the binding of Sp1 to the promoter region of XT-1 and enhanced the binding of Sp3 and AP-1. Inhibition of mitogen-activated protein kinase and nuclear factor kappa B signaling pathways restored the 29-kDa FN-f-inhibited XT-1 expression, along with the altered expression of Sp1 and Sp3. Blockading toll-like receptor 2 (TLR-2) and integrin α5ß1 via siRNA and blocking antibodies revealed that the effects of 29-kDa FN-f on XT-1 expression were mediated through the TLR-2 and integrin α5ß1 signaling pathways. CONCLUSION: These results demonstrate that 29-kDa FN-f negatively affects cartilage anabolism by regulating glycosaminoglycan formation through XT-1.
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Cartílago Articular/enzimología , Condrocitos/enzimología , Inhibidores Enzimáticos/farmacología , Fibronectinas/farmacología , Osteoartritis de la Rodilla/enzimología , Pentosiltransferasa/antagonistas & inhibidores , Anciano , Animales , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Células Cultivadas , Condrocitos/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/patología , Pentosiltransferasa/biosíntesis , Pentosiltransferasa/genética , Pentosiltransferasa/metabolismo , Fragmentos de Péptidos/farmacología , ARN Mensajero/genética , Transducción de Señal/efectos de los fármacos , Factor de Transcripción Sp1/genética , Factor de Transcripción Sp1/metabolismo , Factor de Transcripción Sp3/genética , Factor de Transcripción Sp3/metabolismo , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Transcripción Genética , UDP Xilosa Proteína XilosiltransferasaRESUMEN
Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands (LGs), not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knockout mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of LG-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.
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Células Acinares/inmunología , Síndromes de Ojo Seco/inmunología , Ojo/patología , Interleucinas/metabolismo , Aparato Lagrimal/fisiología , Membrana Mucosa/inmunología , Células Th17/inmunología , Adulto , Anciano , Animales , Estudios Transversales , Femenino , Humanos , Interleucina-17/metabolismo , Interleucinas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Quimera por Trasplante , Interleucina-22RESUMEN
BACKGROUND AND AIMS: Retinopathy and vascular calcification (VC) are representative markers of microvascular and macrovascular dysfunction in patients with chronic kidney disease (CKD). However, their relationship and combined effects on clinical outcomes remain undetermined. METHODS AND RESULTS: We included 523 patients with nondialysis-dependent CKD stage 3-5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. Simple radiographs were analyzed for the presence of VC. The clinical significance of VC of the abdominal aorta and iliofemoral artery (apVC) and retinopathy was evaluated in terms of the rate of renal function decline and composite of any cardiovascular event or death. CKD patients with retinopathy showed higher prevalence of apVC than those without retinopathy (25.6% vs. 12.5%, P < 0.001).The presence of retinopathy was independently associated with apVC (OR 2.13, 95% CI 1.31, 3.49). In multivariate analysis, compared with subjects with neither apVC nor retinopathy, the coexistence of both apVC and retinopathy were independently associated with rapid renal function decline (ß = -1.51; 95% CI -2.40, -0.61), whereas apVC or retinopathy alone were not. Compared with subjects with neither apVC nor retinopathy, the HRs for composite end points were 1.05 (95% CI 0.48, 2.27), 1.79 (95% CI 1.14, 2.80), and 2.07 (95% CI 1.17, 3.67) for patients with apVC only, those with retinopathy only, and those with both apVC and retinopathy, respectively. CONCLUSION: The coexistence of VC and retinopathy was independently associated with CKD progression and cardiovascular events or deaths, and its combined effect was stronger than any separate condition.
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Retinopatía Diabética/epidemiología , Retinopatía Hipertensiva/epidemiología , Insuficiencia Renal Crónica/epidemiología , Neovascularización Retiniana , Calcificación Vascular/epidemiología , Anciano , Distribución de Chi-Cuadrado , Comorbilidad , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/mortalidad , Retinopatía Diabética/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Retinopatía Hipertensiva/diagnóstico , Retinopatía Hipertensiva/mortalidad , Retinopatía Hipertensiva/patología , Estimación de Kaplan-Meier , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Prevalencia , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/fisiopatología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/mortalidadRESUMEN
Threshold switching is a phenomenon where the resistivity of an insulating material changes and the insulator exhibits metallic behavior. This could be explained by phase transformation in oxide materials; however, this behavior is also seen in amorphous insulators. In this study, through an ex-situ experiment using transmission electron microscopy (TEM), we proved that threshold switching of amorphous NbO2 accompanies local crystallization. The change in I-V characteristics after electroforming was examined by evaluating the concentration profile. Atom probe tomography (APT) combined with in-situ TEM probing technique was performed to understand the threshold switching in amorphous NbO2. The local crystallization in amorphous NbO2 was validated by the observed difference in time-of-flight (ToF) between amorphous and crystalline NbO2. We concluded that the slower ToF of amorphous NbO2 (a-NbO2) compared with crystalline NbO2 (c-NbO2) is due to the resistivity difference and trap-assisted recombination.
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An association has been suggested between Marfan syndrome (MFS) and the nodular bronchiectatic form of lung disease caused by non-tuberculous mycobacteria (NTM). We evaluated the prevalence of bronchiectasis in 79 adult patients with MFS using computed tomography (CT) imaging. Airway dilation indicative of bronchiectasis (22/79, 28%) and bronchioloectasis (10/79, 13%) were relatively common, although the extent of dilation was not severe and was frequently confined to a single lobe. However, bronchiolitis was evident in only three patients (4%), and no patient was diagnosed with NTM lung disease.
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Bronquiectasia/epidemiología , Síndrome de Marfan/complicaciones , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Micobacterias no Tuberculosas/aislamiento & purificación , Adulto , Bronquiectasia/microbiología , Bronquiolitis/epidemiología , Bronquiolitis/microbiología , Femenino , Humanos , Masculino , Síndrome de Marfan/microbiología , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/microbiología , Prevalencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Rapid and sensitive detection methods for three species of Curtovirus were developed using a loop-mediated isothermal amplification (LAMP) technique. A universal primer set for detecting the three main species of Curtovirus at the same time, and three kinds of species-specific primer sets were designed and used for LAMP reactions. Results from the LAMP reactions were visualized both by color changes after adding SYBR Green I staining dye and by DNA laddering on agarose gel electrophoresis. The optimal conditions for the curtovirus LAMP reaction were confirmed at 60°C for the universal primers and at 62°C for the three species-specific primer sets. Amplification of curtoviruses by LAMP reaction was ten-fold more sensitive than that by polymerase chain reaction. Primers designed for curtovirus detection in this study did not anneal to or amplify DNA from other DNA or RNA viruses (tomato yellow leaf curl virus, tomato spotted wilt virus, and potato virus Y). Taken together, the primer sets and reaction conditions developed in this study show that the LAMP technique could be a useful tool to detect the three species of Curtovirus simultaneously and distinguish them in the laboratory and the field.
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Geminiviridae/aislamiento & purificación , Nicotiana/virología , Técnicas de Amplificación de Ácido Nucleico/métodos , Enfermedades de las Plantas/virología , Cartilla de ADN/genética , Geminiviridae/clasificación , Geminiviridae/genéticaRESUMEN
BACKGROUND: Before cell or tissue transplantation, cells or tissues have to be maintained for a certain period in vitro using culture medium and methods. Most culture media contain substances such as pH indicators and buffers. It is not known whether some of these substances are safe for subsequent application in the transplantation of cells or tissues into the human body. We investigated culture media and methods with respect to the safety of the components in future transplantation applications. METHODS: A modified culture medium--medical fluid-based culture medium (FCM)--was designed by using various fluids and injectable drugs that are already currently permitted for use in clinical medicine. Medium components necessary for optimal cell growth were obtained from approved drugs. FCM was manufactured with adjusted final concentrations of the medium components similar to those in commercial Dulbecco's modified Eagle's medium (DMEM). In particular, 1029.40 mg/L amino acids, approximately 88.85 mg/L vitamins, 13,525.77 mg/L inorganic salts, and 4500 mg/L D-glucose comprise the high-glucose FCM. Next, human fat synovium-derived mesenchymal stem cells and rat H9c2 (2-1) cells were cultured under 2 conditions: (1) DMEM-high glucose (HG), an original commercial medium, and (2) optimized FCM-HG. We assessed the morphologies and proliferation rates of these cells. RESULTS: We observed that FCM-HG was able to induce the growth of FS-MSC and commercially available H9c2 cell. The morphologies and proliferation patterns of these cells cultured under FCM-HG showed no differences compared with cells grown in DMEM-HG. CONCLUSION: Our data suggest that FCM, which we developed for the first time according to the concept of drug repositioning, was a useful culture medium, especially in cultured cells intended for human cell transplantation.
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Trasplante de Células , Células Cultivadas , Medios de Cultivo , HumanosRESUMEN
INTRODUCTION: Cord blood (CB) is an important source of hematopoietic stem cells and reflects the hematologic status of neonates. ABX Pentra DX 120 (Horiba Medical, Montpellier, France) and Sysmex XE-2100 (Sysmex, Kobe, Japan) were compared in 200 CB specimens. METHODS: Complete blood count parameters including white blood cell (WBC) differential counts were compared between the two analyzers. Double differential matrix (DDX) by ABX Pentra DX 120 and hematopoietic progenitor cell (HPC) by Sysmex XE-2100 were compared with CD34(+) cells by flow cytometry. RESULTS: Most of the parameters showed acceptable correlation between the two analyzers. Although WBC differential of both analyzers showed acceptable correlation with manual counts, mononuclear cells (MNC) by ABX Pentra DX 120 better correlated with manual count than MNC by Sysmex XE-2100. NRBC by Sysmex XE-2100 better correlated with manual count than NRBC by ABX Pentra DX 120. ABX Pentra DX 120 showed better flagging performances. DDX better correlated with CD34(+) cells than HPC. CONCLUSION: Although the results from both analyzers are mostly interchangeable and reliable in CB specimens, flagging performance of ABX Pentra DX 120 seems to be superior to that of Sysmex XE-2100. DDX by ABX Pentra DX 120 would be valuable to evaluate the quality of CB for further therapeutic utilization.
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Antígenos CD34/metabolismo , Sangre Fetal/citología , Citometría de Flujo/instrumentación , Citometría de Flujo/normas , Adulto , Recuento de Células Sanguíneas/instrumentación , Recuento de Células Sanguíneas/métodos , Recuento de Células Sanguíneas/normas , Femenino , Citometría de Flujo/métodos , Células Madre Hematopoyéticas/metabolismo , Humanos , Recién Nacido , Persona de Mediana Edad , Adulto JovenRESUMEN
AIM: This case report describes the successful autotransplantation of mandibular molars after application of orthodontic forces and discusses the advantages of this technique, that is, pre-application of an orthodontic force for autotransplantation. SUMMARY: After clinical and radiographic examination, autotransplantation was planned with the patient's written informed consent. An orthodontic force was applied, and the surgical procedure was performed after tooth mobility had increased. Root canal treatment was performed within 2 weeks of autotransplantation. At the 1-year follow-up, the transplanted teeth revealed asymptomatic and healthy periodontal conditions. KEY LEARNING POINTS: Autotransplantation is the surgical movement of a tooth from its original location to another site. The pre-application of orthodontic force technique was recently introduced for autogenous tooth transplantation. Pre-application of an orthodontic force may be a useful treatment option for autotransplantation.
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Análisis del Estrés Dental , Diente Molar/trasplante , Técnicas de Movimiento Dental , Adulto , Femenino , Humanos , Mandíbula , Persona de Mediana Edad , Cuidados Preoperatorios , Movilidad Dentaria , Trasplante AutólogoRESUMEN
Cisplatin, a chemotherapeutic agent for treating various solid tumors, produces hearing loss in approximately half a million cancer patients annually in the United States. In the course of developing a new protective agent against cisplatin-induced ototoxicity, we have been interested in a novel synthetic compound, 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR-22332). The effect of KR-22332 on cisplatin-induced cytotoxicity was analyzed in vitro in an organ of Corti-derived cell line (HEI-OC1), and in vivo in a zebrafish and rat model. Cisplatin-induced apoptosis, reactive oxygen species (ROS) generation and altered mitochondrial membrane potential (MMP) in HEI-OC1 cells were observed. KR-22332 significantly inhibited cisplatin-induced apoptosis, change of MMP, and intracellular ROS generation. KR-22332 markedly attenuated the cisplatin-induced loss and changes of auditory neuromasts in the zebrafish. Transtympanic administration of KR-22332 in a rat model was protective against cisplatin-induced hearing loss, as determined by click-evoked auditory brainstem response (p<0.01). Tissue terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of rat cochlea demonstrated that KR-22332 blocked cisplatin-induced apoptosis. In addition, transtympanic administration of KR-22332 inhibited cisplatin-induced nicotinamide adenine dinucleotide phosphate-oxidase 3 (NOX3) overexpression in the rat cochlea. KR-22332 significantly reduced the expression of p-53, mitogen-activated protein kinases, caspase 3, and tumor necrosis factor-α compared to their significant increase after cisplatin treatment. The results of this study suggest that KR-22332 may prevent ototoxicity caused by the administration of cisplatin through the inhibition of mitochondrial dysfunction and the suppression of ROS generation. These novel findings implicate KR-22332 as a potential candidate for protective agent against cisplatin-induced ototoxicity.
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Cisplatino/toxicidad , Pérdida Auditiva/prevención & control , Fármacos Neuroprotectores/farmacología , Quinolonas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Caspasa 3/metabolismo , Línea Celular , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Pérdida Auditiva/fisiopatología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Ratones , NADPH Oxidasas/metabolismo , Fármacos Neuroprotectores/química , Órgano Espiral/efectos de los fármacos , Órgano Espiral/fisiopatología , Quinolonas/síntesis química , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Pez CebraRESUMEN
OBJECTIVE: The aim of this study was to assess the long-term risks of chronic kidney disease and arterial hypertension in living kidney donors. METHODS: Donors who were followed for more than 1 year after nephrectomy were included. We assessed each donor's blood pressure, urine protein, and estimated glomerular filtration rate (eGFR). RESULTS: The follow-up rate was 11% (154 out of 1,356 donors), only 19% of whom were followed by nephrologists. Blood pressure had increased from 113/75 to 116/77 mm Hg (P < .01), urinary protein excretion after donation did not increase, and renal function was well preserved after donor nephrectomy. However, 33 patients (21.4%) showed a decreased eGFR of <60 mL/min/1.73 m(2), and 3 donors developed end-stage renal disease that required renal replacement therapy. CONCLUSIONS: The follow-up rate of living donors after donation was low, and we observed an increased risk of developing chronic kidney disease after donation.
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Hipertensión/epidemiología , Fallo Renal Crónico/epidemiología , Donadores Vivos , Presión Sanguínea , Tasa de Filtración Glomerular , Humanos , Hipertensión/fisiopatología , Fallo Renal Crónico/fisiopatología , Proteinuria/fisiopatología , Factores de RiesgoRESUMEN
BACKGROUND: Rifampin (RFP) is a first-line antituberculosis drug, but it increases the risk of acute rejection (AR) in transplant recipients. This study evaluated whether quinolone (QNL) can replace RFP in renal transplant recipients with tuberculosis. METHODS: One hundred nine patients with active tuberculosis were included. Patients consisted of RFP (n = 91) and QNL (n = 18) groups based on the initial treatment regimen. Patients with RFP-associated adverse effects were subdivided into RFP-maintenance (RFP-M; n = 18) and QNL-conversion (QNL-C; n = 8) groups. Clinical outcomes were compared between groups. RESULTS: The incidence of AR was higher in the RFP group than in the QNL group (24.2% vs 5.6%). The QNL group showed significantly higher 10-year graft survival rates than the RFP group (88.1% vs 66.5%; P = .022). The QNL-C group showed significantly higher 10-year graft survival rates than the RFP-M group (87.5% vs 27.8%; P = .011). The rate of complete functional recovery after AR was higher in the QNL-C group than in the RFP-M group (50% vs 22.2%). CONCLUSIONS: A QNL-based regimen may be safe and effective for treatment of tuberculosis and may lower the risk of graft failure in renal transplant recipients.
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Antituberculosos/uso terapéutico , Trasplante de Riñón , Quinolonas/uso terapéutico , Tuberculosis/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Radiation-induced toxicity limits the delivery of high-dose radiation to head and neck lesions. The aim of this study was to investigate the effectiveness of epicatechin (EC), a minor component of green tea extract, on radiation-induced ototoxicity in vitro and in vivo. The effect of EC on radiation-induced cytotoxicity was analyzed in the organ of Corti-derived cell lines, HEI-OC1 and UB-OC1. The cell viability, apoptosis, reactive oxygen species generation, and mitochondrial membrane potential as well as changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of hearing protection and drug toxicity of EC were explored in a zebrafish and rat model. Radiation-induced apoptosis and altered mitochondrial membrane potential in HEI-OC1 and UB-OC1 were observed. EC inhibited radiation-induced apoptosis and intracellular reactive oxygen species generation. EC markedly attenuated the radiation-induced embryotoxicity and protected against radiation-induced loss and changes of auditory neuromast in the zebrafish. In addition, intratympanic administration of EC was protective against radiation-induced hearing loss in the rat model, as determined by click-evoked auditory brainstem (P<0.01). EC significantly reduced the expression of p-JNK, p-ERK cleaved caspase-3, and cleaved PARP compared to their significant increase after radiation treatment. The results of this study suggest that EC significantly inhibited radiation-induced apoptosis in auditory hair cells and may be a safe and effective candidate treatment for the prevention of radiation-induced ototoxicity.
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Catequina/farmacología , Células Ciliadas Auditivas/efectos de los fármacos , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Supervivencia Celular/efectos de los fármacos , Femenino , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/efectos de la radiación , Pérdida Auditiva/etiología , Pérdida Auditiva/prevención & control , Etiquetado Corte-Fin in Situ , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Pez CebraRESUMEN
OBJECTIVES: This study aimed to evaluate the efficacy and safety of interventional management for various intractable complications following caesarean section. METHODS: Between August 2005 and September 2009, 18 consecutive women were referred to interventional radiology for treatment of complications developing after caesarean section. Complications included vaginal bleeding (n = 14), haemoperitoneum with abdominal wall haematoma (n = 2), caesarean scar pregnancy (CSP) (n = 1) and post-caesarean fluid collection (n = 1). RESULTS: 17 women underwent transcatheter arterial embolisation (TAE) with a variety of embolic materials, and two women underwent percutaneous drainage (PCD) for fluid collection and haemoperitoneum. 5 of the 14 women with vaginal bleeding had extravasation of contrast media on angiography; the other 9 had no visible bleeding foci. The two women with haemoperitoneum with abdominal wall haematoma had injury to the inferior epigastric artery from angiography. TAE and PCD were successfully performed in both women. The CSP was successfully managed and the serum ß-human chorionic gonadotropin (ß-hCG) level finally normalised. Hysterectomy or dilatation and curretage was required in women with placenta accrete and undetectable bleeding foci. CONCLUSION: Interventional management including TAE and PCD is effective and safe in controlling complications following caesarean section. Use of these procedures can help avoid high-risk surgery, but subsequent procedures including hysterectomy may be required in cases of placental abnormalities and undetectable bleeding foci.
Asunto(s)
Cesárea/efectos adversos , Cicatriz/diagnóstico por imagen , Hematoma/diagnóstico por imagen , Hemoperitoneo/diagnóstico por imagen , Hemorragia Posoperatoria/diagnóstico por imagen , Radiología Intervencionista/métodos , Pared Abdominal , Adulto , Cicatriz/cirugía , Drenaje/métodos , Embolización Terapéutica/métodos , Exudados y Transudados/diagnóstico por imagen , Femenino , Hematoma/terapia , Hemoperitoneo/terapia , Humanos , Histerectomía/métodos , Cavidad Peritoneal/diagnóstico por imagen , Hemorragia Posoperatoria/terapia , Embarazo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Cisplatin, a widely used chemotherapeutic drug, causes ototoxicity in a large percentage of patients. The purpose of this study was to determine the efficacy of epicatechin (EC) as an otoprotective agent to prevent cisplatin toxicity and to investigate the molecular mechanism of EC. The effects of EC on cisplatin-induced ototoxicity were investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 and in a rat model. In addition, signaling mechanisms were investigated, specifically those involving MAP kinase. Cisplatin induced apoptosis and demonstrated, conjugation of annexin V/PI in FACS, and an increase of subG1 in HEI-OC1. EC protected HEI-OC1 against cisplatin and showed inhibition of cisplatin-induced apoptosis of the HEI-OC1 by transmission electron microscopy. Intratympanic administration of EC protected against cisplatin-induced ototoxicity in the rat model, as determined by auditory brainstem responses. EC inhibited activation of JNK, ERK, cytochrome-c and caspase-3 by cisplatin. An ERK Inhibitor, cisplatin-induced ototoxicity in a dose dependent manner but a JNK inhibitor did not. The results of this study suggest that EC may provide a mechanism by which ototoxicity caused by the administration of cisplatin can be reduced through the inhibition of ERK. EC may have clinical use as a chemopreventive agent that prevents cisplatin ototoxicity.