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Burning mouth syndrome (BMS) is a chronic oral pain syndrome that primarily affects peri- and postmenopausal women. It is characterized by oral mucosal burning and may be associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. The etiology of the disease process is unknown, but is thought to be neuropathic in origin. The goal of this systematic review was to assess the efficacy of the various treatments for BMS. Literature searches were conducted through PubMed, Web of Science, and Cochrane Library databases, which identified 22 randomized controlled trials. Eight studies examined alpha-lipoic acid (ALA), three clonazepam, three psychotherapy, and two capsaicin, which all showed modest evidence of potentially decreasing pain/burning. Gabapentin was seen in one study to work alone and synergistically with ALA. Other treatments included vitamins, benzydamine hydrochloride, bupivacaine, Catuama, olive oil, trazodone, urea, and Hypericum perforatum. Of these other treatments, Catuama and bupivacaine were the only ones with significant positive results in symptom improvement. ALA, topical clonazepam, gabapentin, and psychotherapy may provide modest relief of pain in BMS. Gabapentin may also boost the effect of ALA. Capsaicin is limited by its side effects. Catuama showed potential for benefit. Future studies with standardized methodology and outcomes containing more patients are needed.
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Antioxidantes/uso terapéutico , Síndrome de Boca Ardiente/tratamiento farmacológico , Clonazepam/uso terapéutico , Moduladores del GABA/uso terapéutico , Ácido Tióctico/uso terapéutico , Aminas/uso terapéutico , Analgésicos/uso terapéutico , Síndrome de Boca Ardiente/terapia , Capsaicina/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Gabapentina , Humanos , Dimensión del Dolor , Psicoterapia , Fármacos del Sistema Sensorial/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
Pendrin is a membrane transporter encoded by solute carrier family26A4 (SLC26A4). Mutations in this gene are known to cause hearing loss, and recent data from animal studies indicate a link between pendrin expression and hypertension; although, this association in humans is unclear. To clarify this issue, we investigated the influence of pendrin on blood pressure by analyzing demographic and biochemical data - including blood pressure and urinary electrolyte excretion - in patients with bi-allelic SLC26A4 mutations. Systolic and diastolic blood pressure and the left ventricular hypertrophy index were lower in subjects with pendrin mutations than in controls. In addition, fractional excretion of Na+ and Cl- was increased and serum renin, angiotensin I and II levels were higher in subjects with pendrin mutations as compared to controls. Thus, patients with impaired pendrin function are likely to be resistant to high blood pressure due to enhanced urinary Na+ /Cl- excretion. These results suggest that pendrin may regulate blood pressure through increased urinary salt excretion.
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Presión Sanguínea/genética , Hipertensión/genética , Hipertrofia Ventricular Izquierda/genética , Proteínas de Transporte de Membrana/genética , Adolescente , Adulto , Angiotensina I/sangre , Angiotensina II/sangre , Animales , Cloruros/orina , Electrólitos/orina , Femenino , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Hipertensión/orina , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/orina , Masculino , Proteínas de Transporte de Membrana/biosíntesis , Mutación , Renina/sangre , Sodio/orina , Transportadores de Sulfato , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Elevated serum uric acid (UA) is known to be associated with stroke. However, there is little information on the association between serum UA levels and cerebral microbleed (CMB), a precursor of stroke. Therefore, we investigated the association between UA and CMB in a general population taking into consideration sex-related differences. METHODS: The subjects in this cross-sectional study consisted of 2686 individuals of 40-79 years of age (1403 men and 1283 women) who underwent regular health screenings, including brain magnetic resonance imaging, at Seoul National University Hospital Health Promotion Center. Subjects were categorized into three groups according to tertiles of UA levels by sex. The presence and location of CMB were assessed by gradient-recalled echo magnetic resonance imaging. RESULTS: The prevalence of CMB was 3.8%. In multivariate logistic regression analysis by sex, the highest tertile of UA in male subjects was independently associated with the presence of CMB compared with the lowest tertile of UA (adjusted odds ratio, 2.46; P = 0.013). Meanwhile, the highest tertile of UA in female subjects was inversely associated with CMB compared with the lowest tertile of UA (adjusted odds ratio, 0.39; P = 0.040). CONCLUSIONS: High serum UA value was associated with higher prevalence of CMB in male, but lower prevalence of CMB in female subjects.
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Hemorragia Cerebral/sangre , Accidente Cerebrovascular/sangre , Ácido Úrico/sangre , Adulto , Anciano , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Prevalencia , Factores Sexuales , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. PATIENTS AND METHODS: From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. RESULTS: The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. CONCLUSIONS: We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process.
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Neoplasias de la Mama/epidemiología , Supervivientes de Cáncer , Pronóstico , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Receptor alfa de Estrógeno/genética , Femenino , Humanos , Antígeno Ki-67/genética , Metástasis Linfática/genética , Metástasis Linfática/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Receptores de Progesterona/genéticaRESUMEN
PURPOSE: The efficacy and safety of treatment with alfuzosin 10 mg plus propiverine 10 or 20 mg in men with lower urinary tract symptoms (LUTS) and an overactive bladder were investigated. MATERIALS AND METHODS: In this parallel-arm, prospective, multicentre, single-blind study, men who were ≥ 40 years old, had an International Prostate Symptom Score (IPSS) of ≥ 8, an Overactive Bladder Symptom Score (OABSS) of ≥ 3 and an OABSS urgency item score of ≥ 2 were randomised in a 1 : 1 :1 ratio to receive alfuzosin 10 mg alone (Group A) or with propiverine 10 mg (Group B) or 20 mg (Group C) for 8 weeks. Four and 8 weeks after commencing treatment, OABSS was measured along with IPSS, maximal urinary flow rate (Qmax ) and postvoid residual volume (PVR). Adverse events were recorded. RESULTS: A total of 135 men, including 43 in Group A, 48 in Group B and 44 in Group C, completed the study. Relative to baseline, all groups demonstrated significant reductions in OABSS and the IPSS after eight treatment weeks (p < 0.005). The improvement of OABSS in Group C was significantly greater than Group A and B (Group A: 0.70 ± 1.94; Group B: 2.50 ± 2.98; Group C: 4.30 ± 3.40; p < 0.005). An observed improvement of Qmax and PVR in the three groups did not achieve statistical significance. Overall adverse event rates were higher in Group C but not significant compared with others. CONCLUSION: In patients with LUTS and overactive bladder, combined therapy with alfuzosin 10 mg plus propiverine 20 mg was significantly more effective than alfuzosin monotherapy and propiverine 10 mg combined therapy in terms of improving OABSS while not significantly affecting Qmax or PVR.
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Bencilatos/uso terapéutico , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Quinazolinas/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Agentes Urológicos/uso terapéutico , Bencilatos/administración & dosificación , Bencilatos/efectos adversos , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Método Simple Ciego , Resultado del Tratamiento , Agentes Urológicos/administración & dosificación , Agentes Urológicos/efectos adversosRESUMEN
White organic light-emitting devices (OLEDs) were fabricated by combining a blue OLED with a color conversion layer made of mixed Y3Al5O12:Ce3+ green and Ca2AlO19:Mn4+ red phosphors. The X-ray diffraction patterns showed that Ce3+ ions in the Y3Al5O12:Ce3+ phosphors completely substituted for the Y3+ ions and the Mn4+ ions in the CaAl12O19:Mn4+ phosphors completely substituted for the Ca2+ ions. Electroluminescence spectra at 11 V for the OLEDs fabricated utilizing a color conversion layer showed that the Commission Internationale de l'Eclairage coordinates for the Y3Al5O12:Ce3+ and CaAl12O19:Mn4+ phosphors mixed at the ratio of 1:5 and 1:10 were (0.31, 0.34) and (0.32, 0.37), respectively, indicative of a good white color.
RESUMEN
White organic light-emitting devices (WOLEDs) were fabricated by combining a blue emitting organic light-emitting devices (OLEDs) and a color conversion layer made of yttrium aluminum garnet phosphors and CdSe/ZnS quantum dots (QDs) embedded into polymethylmethacrylate. When the ratio of phosphors and QDs changed, a good color balance was achieved at a ratio of 1:5, and the maximum luminance of 18.21 cd/m2 was obtained. As the applied voltage varied from 12 to 16 V, Commission Internationale de l'Eclairage coordinates shifted only slightly from (0.32, 0.34) to (0.30, 0.33), indicating a good color stability.
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The potential of enhanced biological phosphorus removal (EBPR) in biological nutrient removal (BNR) systems critically depends on the availability and types of volatile fatty acids (VFAs) in sewage. Although the characteristics of VFAs in sewage are strongly related with the biochemical transformations in the sewer system, they have not been studied thoroughly in terms of BNR process design. We have investigated the characteristics of VFAs in influent of nine sewage treatment plants which represent typical small to very large sewer systems in Korea. We found that influent total VFACOD (VFA as chemical oxygen demand) concentrations ranged from 20.4 to 65.2 mg/L. Acetic acid was a predominant VFA in sewage, and the propionic acid (HPr) portion averaged 38.7% of total VFACOD. However the sewage from longer sewer systems showed more HPr content, indicating that type of VFA varied with the total sewer length. The finding is a particularly important consideration for BNR process design since availability of HPr positively behaved to suppress the unfavorable growth of glycogen-accumulating organisms. The implication of these findings for BNR process design is discussed in this paper.
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Ácidos Grasos Volátiles/química , Ingeniería Sanitaria/métodos , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos/métodos , República de CoreaRESUMEN
OBJECTIVES: Dietary fiber intake is associated with a lower risk of diabetes, cardiovascular disease, and cancer. However, it is unknown whether dietary fiber has a beneficial effect on preventing the development of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Using the UK Biobank prospective cohort, 110,412 participants who completed at least one dietary questionnaire and had an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, urinary albumin-to-creatinine ratio <30 mg/g, and no history of CKD were included. The primary exposure was total dietary fiber density, calculated by dividing the absolute amount of daily total fiber intake by total energy intake (g/1,000 kcal). We separately examined soluble and insoluble fiber densities as additional predictors. The primary outcome was incident CKD based on diagnosis codes. RESULTS: A total of 3,507 (3.2%) participants developed incident CKD during a median follow-up of 9.9 years. In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for incident CKD were 0.85 (0.77-0.94), 0.78 (0.70-0.86), and 0.76 (0.68-0.86), respectively, for the second, third, and highest quartiles of dietary fiber density (reference: lowest quartile). In a continuous model, the aHR for each +∆1.0g/1,000 kcal increase in dietary fiber density was 0.97 (95% CI, 0.95-0.99). This pattern of associations was similar for both soluble and insoluble fiber densities and did not differ across subgroups of sex, age, body mass index, hypertension, diabetes, smoking, and inflammation. CONCLUSION: Increased fiber intake was associated with a lower risk of CKD in this large well-characterized cohort.
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Diabetes Mellitus , Insuficiencia Renal Crónica , Humanos , Estudios Prospectivos , Bancos de Muestras Biológicas , Factores de Riesgo , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Tasa de Filtración Glomerular , Fibras de la Dieta , Reino Unido/epidemiologíaRESUMEN
AIMS/HYPOTHESIS: Translationally controlled tumour protein (TCTP) is thought to be involved in cell growth by regulating mTOR complex 1 (mTORC1) signalling. As diabetes characteristically induces podocyte hypertrophy and mTORC1 has been implicated in this process, TCTP may have a role in the pathogenesis of diabetes-induced podocyte hypertrophy. METHODS: We investigated the effects and molecular mechanisms of TCTP in diabetic mice and in high glucose-stimulated cultured podocytes. To characterise the role of TCTP, we conducted lentivirus-mediated gene silencing of TCTP both in vivo and in vitro. RESULTS: Glomerular production of TCTP was significantly higher in streptozotocin induced-diabetic DBA/2J mice than in control animals. Double-immunofluorescence staining for TCTP and synaptopodin revealed that podocyte was the principal cell responsible for this increase. TCTP knockdown attenuated the activation of mTORC1 downstream effectors and the overproduction of cyclin-dependent kinase inhibitors (CKIs) in diabetic glomeruli, along with a reduction in proteinuria and a decrease in the sizes of podocytes as well as glomeruli. In addition, knockdown of TCTP in db/db mice prevented the development of diabetic nephropathy, as indicated by the amelioration of proteinuria, mesangial expansion, podocytopenia and glomerulosclerosis. In accordance with the in vivo data, TCTP inhibition abrogated high glucose-induced hypertrophy in cultured podocytes, which was accompanied by the downregulation of mTORC1 effectors and CKIs. CONCLUSIONS/INTERPRETATION: These findings suggest that TCTP might play an important role in the process of podocyte hypertrophy under diabetic conditions via the regulation of mTORC1 activity and the induction of cell-cycle arrest.
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Biomarcadores de Tumor/metabolismo , Aumento de la Célula , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Nefropatías Diabéticas/metabolismo , Podocitos/patología , Animales , Quinasas Ciclina-Dependientes/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/patología , Silenciador del Gen , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Proteínas de Microfilamentos/metabolismo , Complejos Multiproteicos , Podocitos/metabolismo , Proteínas/metabolismo , Serina-Treonina Quinasas TOR , Proteína Tumoral Controlada Traslacionalmente 1RESUMEN
Interleukin-10 (IL-10) has an important role in the homeostatic regulation of autoreactive T-cell repertoire. We hypothesized that endogenous IL-10 would regulate the severity of ß-tubulin-induced experimental autoimmune hearing loss (EAHL) and that exogenous IL-10 would abrogate it. BALB/c wild-type (WT) and homozygous IL-10-deficient mice (IL-10(-/-)) underwent ß-tubulin immunization to develop EAHL; some IL-10 mice with EAHL were administered IL-10 DNA at the peak of EAHL. Auditory brainstem responses were examined over time. EAHL developed progressively in both WT and IL-10(-/-) mice. However, the severity of hearing loss in the IL-10(-/-) mice was significantly greater than that in WT animals. Moreover, disease severity was associated with a significantly enhanced interferon-γ level and loss of hair cells in IL-10(-/-) mice. IL-10 administered to EAHL IL-10(-/-) mice promoted IL-10 expression. Consequently, hearing significantly improved by protecting hair cells in established EAHL. Importantly, IL-10 treatment suppressed proliferation of antigen-specific T-helper type 1 (Th1) cells, and the suppression can be attributed to inducing IL-10-secreting regulatory T cells that suppressed autoreactive T cells. We demonstrated that the lack of IL-10 exacerbated hearing loss, and the exogenous administration of IL-10 improved hearing. Mechanistically, our results indicate that IL-10 is capable of controlling autoimmune reaction severity by suppressing Th1-type proinflammatory responses and inducing IL-10-secreting regulatory T cells.
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Enfermedades Autoinmunes/inducido químicamente , Técnicas de Transferencia de Gen , Pérdida Auditiva/inducido químicamente , Interleucina-10/genética , Animales , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Pérdida Auditiva/inmunología , Humanos , Interferón gamma , Interleucina-10/deficiencia , Ratones , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células TH1/inmunología , Células TH1/metabolismo , Tubulina (Proteína)/administración & dosificación , Tubulina (Proteína)/inmunologíaRESUMEN
BACKGROUND: One-fourth of the US population is sensitized to the German cockroach. Primary German cockroach allergen Bla g 1 is detected in 63% of homes and 52% of childcare facilities in the United States. No effective treatment or vaccination strategies are yet available. OBJECTIVES: We evaluated the prophylactic and therapeutic efficacy of a plasmid DNA-mediated vaccination using the Bla g 1 gene in a mouse model of allergic inflammatory airway disease. METHODS: A plasmid DNA vector coding for the Bla g 1 allergen controlled by cytomegalovirus promoter was constructed. To estimate the protective efficacy, BALB/c mice were given three injections of plasmid DNA-Bla g 1 prior to sensitization with two priming doses of recombinant Bla g 1 (rBla g 1) antigens, followed by nebulized rBla g 1 challenge. In the therapeutic approach, sensitization was followed by administering Bla g 1 DNA vaccine. RESULTS: Bla g 1 vaccination significantly reduced allergen-induced airway inflammation, even after mice were presensitized and a Th2-dominant response was established. The Bla g 1 vaccination significantly reduced total inflammatory cell infiltrate, eosinophilia, secretion of Th2 cytokines IL-4 and IL-5 in bronchoalveolar lavage fluid, allergen-induced inflammatory infiltrates in the lungs, and Bla g 1-specific IgE in serum upon challenge with rBla g 1. Importantly, Bla g 1 DNA vaccination was able to induce IL-10-secreting regulatory T cells that could suppress the allergen-specific Th2 cells. CONCLUSION: DNA vaccination showed protective and therapeutic efficacy against a clinically relevant allergen Bla g 1.
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Antígenos de Plantas/inmunología , Cucarachas/inmunología , Hipersensibilidad Respiratoria/terapia , Vacunas de ADN/uso terapéutico , Alérgenos , Animales , Antígenos de Plantas/genética , Citocinas/sangre , Citocinas/inmunología , Femenino , Expresión Génica , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Inyecciones Intramusculares , Ratones , Ratones Endogámicos BALB C , Hipersensibilidad Respiratoria/tratamiento farmacológico , Hipersensibilidad Respiratoria/prevención & control , Linfocitos T Reguladores/inmunología , Vacunas de ADN/administración & dosificaciónRESUMEN
Aim: To compare the improvement in erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) as well as safety of tadalafil dosed at 20 mg on-demand and 5 mg once daily among ED patients. Materials and methods: A total of 194 ED patients visited between March 2010 and June 2011 were recruited. Out of 194 individuals, 168 (86.6%) met inclusion criteria after completing the two-week screening period (V0). The Patients were randomly allocated into two groups: (i) 20 mg of tadalafil as needed (Group 1: n = 84, 50.0%) and (ii) 5 mg of tadalafil once daily (Group 2: n = 84, 50.0%). Blood pressure (BP), heart rate (HR) and the five-item version of the International Index of Erectile Function (IIEF-5) were assessed immediately before initiation of treatment (V1) and after four (V2) and twelve weeks of treatment (V3). In men with an IPSS of ≥ 8 at V1, IPSS, maximal flow rate (Qmax) and post-void residual volume (PVR) were also assessed. Results: Of the 168 patients, 134 (79.8%; Group 1: n = 68, 81.0%; Group 2: n = 66, 78.6%) patients completed the trial. IIEF-5 improved in both groups, and the mean change was larger in Group 2 at V3 (4.9 ± 4.2 vs. 6.5 ± 4.5; p = 0.032) Similarly, though IPSS (with ≥ 8, n = 88, 65.7%; Group 1: n = 44, 64.7%; Group 2: n = 44, 66.7%) improved in both groups, the mean change was larger in Group 2 at V3 (-2.8 ± 4.3 vs. -4.8 ± 4.1; p = 0.026). Qmax and PVR did not differ significantly in either group. Conclusions: Once daily tadalafil was more efficacious in treating both ED and LUTS than on-demand dosing. However, no differences were observed between the two dosing schedules with regard to the improvement in LUTS when stratified by improvement in ED. The side effects were insignificant for both dosing schedules.
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AIMS: In patients with immunoglobulin A (IgA) nephropathy, postnatal renal outcomes vary depending on kidney function and proteinuria. However, whether a decrease in proteinuria prior to conception improves postnatal maternal renal outcomes is unknown. METHODS: This was a single-center retrospective study. A total of 52 pregnant women with biopsy-proven IgA nephropathy were enrolled in the study between January 2004 and December 2009. We collected data on proteinuria, which had been measured 1 year prior to conception, at conception, during pregnancy, and postnatally. The study outcomes included changes in estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: The median serum creatinine, eGFR, and proteinuria levels at conception were 0.8 (0.5 - 2.6) mg/dl, 91.2 (24.1 - 157.0) ml/min, 0.7 (0.0 - 3.5) g/g, respectively. Compared with values measured at conception, serum creatinine (0.8 - 1.0 mg/dl, p < 0.01) and proteinuria (0.7 - 1.5 g/g, p < 0.01) increased significantly postnatally, while eGFR decreased (91.2 - 77.8 ml/min, p < 0.01). In a multiple linear regression analysis, proteinuria at conception were independently associated with a faster decline in postnatal maternal eGFR (ß = 4.50, p < 0.05). In addition, a less decline in maternal eGFR was observed in patients with a reduction in proteinuria (> 30%) prior to pregnancy, compared with those with a less reduction (≤ 30%). As for newborn outcomes, preterm delivery, caesarean section, low birth weight < 2,500 g, and need for neonatal intensive care were 15.4%, 46.2%, 25.0% and 7.7%, respectively. CONCLUSIONS: This study showed that in women with IgA nephropathy, proteinuria was significantly associated with the deterioration of postnatal maternal renal outcomes. Our study also suggests that a strategy for reducing proteinuria prior to pregnancy is required to preserve kidney function after delivery.
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Glomerulonefritis por IGA/fisiopatología , Riñón/fisiopatología , Complicaciones del Embarazo/fisiopatología , Proteinuria/complicaciones , Adulto , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Presión Sanguínea , Femenino , Tasa de Filtración Glomerular , Humanos , Recién Nacido , Embarazo , Estudios RetrospectivosRESUMEN
Immunization of two cynomolugus and three rhesus monkeys with purified type II collagen resulted in the development of polyarthritis. Arthritis first became clinically apparent 7 wk after primary immunization and persisted for 16 mo. Radiologic examination of the limbs demonstrated soft tissue swelling with severe joint destruction including loss of cartilage and bone. Involved joints eventually became ankylosed with permanent loss of some motion. All of the monkeys developed a response to the immunizing collagen as determined by ELISA of serum for antibodies. Arthritis was associated with weight loss and constitutional symptoms, including lethargy and refusal to eat. One monkey became so debilitated that it was necessary to euthanize it. Histologic examination of the joints showed synovial hypertrophy with pannus formation. A control monkey immunized with type I collagen suffered no apparent ill effects.
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Anticuerpos/análisis , Artritis Experimental/inmunología , Artritis/inmunología , Colágeno/inmunología , Animales , Artritis Experimental/diagnóstico por imagen , Artritis Experimental/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Articulaciones/patología , Macaca fascicularis , Macaca mulatta , Masculino , Orquiectomía , RadiografíaRESUMEN
Free light chains isolated from specifically purified antibody have been shown to bind specific hapten. This proves that part of the binding site does exist on the light chain. The light chains were obtained from antibody directed against the 4-azonaphthalene-1-sulfonate group, and the binding of the simple hapten 4-anilinonaphthalene-1-sulfonate was determined by the fluorescence-enhancement technique. Since this hapten undergoes a striking increase in fluorescence on binding to light chains (and also on binding to specific antibody), the presence of small amounts of bound hapten could be determined, even in the presence of the high concentrations of unbound hapten required because of the low binding constant.
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Anticuerpos , Reacciones Antígeno-Anticuerpo , Haptenos , Péptidos , Compuestos de Anilina , Compuestos Azo , Fluorescencia , Fluorometría , Naftalenos , Ácidos SulfónicosRESUMEN
Endolymphatic hydrops was induced in guinea pigs by immunizing them with native bovine type II collagen. Histopathologic changes consisted of moderate extension of the Reissner's membrane, spiral ganglion degeneration, atrophied organ of Corti, and mild atrophy of the surface epithelium in the endolymphatic duct. These findings suggest that an immune response directed against type II collagen--a type of collagen found in the membranous labyrinth, subepithelial layer of the endolymphatic duct, spiral ligament, and enchondral layer of the otic capsule--may induce endolymphatic hydrops.
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Enfermedades Autoinmunes/inmunología , Colágeno/inmunología , Endolinfa/inmunología , Enfermedades del Laberinto/inmunología , Líquidos Laberínticos/inmunología , Animales , Colágeno/clasificación , Modelos Animales de Enfermedad , Edema/inmunología , Cobayas , Enfermedades del Laberinto/patologíaRESUMEN
Antibodies to collagen types I, II, and IV were measured in patients with otosclerosis and patients with Meniere's disease. Levels of antibodies to type II collagen were significantly higher in these patients than in control subjects, while no differences were found among levels of antibodies to collagen type I or type IV. These observations suggest a possible role for type II collagen autoimmunity in the etiology of otosclerosis and Meniere's disease.
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Enfermedades Autoinmunes/inmunología , Colágeno/inmunología , Enfermedad de Meniere/inmunología , Osteosclerosis/inmunología , Autoanticuerpos/análisis , Colágeno/clasificación , HumanosRESUMEN
Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report that SMPDL3b excess, as observed in podocytes in diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival insulin signaling by interfering with insulin receptor isoforms binding to caveolin-1 in the PM. SMPDL3b excess affects the production of active sphingolipids resulting in decreased ceramide-1-phosphate (C1P) content as observed in human podocytes in vitro and in kidney cortexes of diabetic db/db mice in vivo. Podocyte-specific Smpdl3b deficiency in db/db mice is sufficient to restore kidney cortex C1P content and to protect from DKD. Exogenous administration of C1P restores IR signaling in vitro and prevents established DKD progression in vivo. Taken together, we identify SMPDL3b as a modulator of insulin signaling and demonstrate that supplementation with exogenous C1P may represent a lipid therapeutic strategy to treat diabetic complications such as DKD.
Asunto(s)
Antígenos CD/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3/metabolismo , Nefropatías Diabéticas/patología , Insulina/metabolismo , Receptor de Insulina/metabolismo , Esfingomielina Fosfodiesterasa/metabolismo , Animales , Caveolina 1/metabolismo , Línea Celular , Membrana Celular/metabolismo , Ceramidas/metabolismo , Ceramidas/uso terapéutico , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3/genética , Nefropatías Diabéticas/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Noqueados , Podocitos/citología , Podocitos/metabolismo , Isoformas de Proteínas/metabolismo , Transducción de Señal , Resultado del TratamientoRESUMEN
We propose the unique structure of highly dispersible single-walled carbon nanotubes (SWCNTs) in various solvents and polymers using the ZnO nano particle template. Buckled nanospring-shaped carbon nanotubes (NS-CNTs) were synthesized by a chemical reaction of ZnO nanoparticles with acid-treated SWCNTs and then dissolving ZnO through chemical etching. The unique structure of distorted hexagonal NS-CNTs encircled around ZnO nanoparticles was formed by the bending of SWCNTs caused by the agglomeration of chemically adsorbed Zn(OH)2, which is further crystallized as the polycrystalline ZnO inner core. The highly dispersible NS-CNTs could be incorporated in the poly[(vinylidenefluoride-co-trifluoroethylene] [P(VDF-TrFE)] copolymer, one of widely studied ferro- and piezo-electric polymer, up to the value of 15 wt% as nanofillers. The relative dielectric constant (K) of polymer nanocomposite, at 1 kHz, was greatly enhanced from 12.7 to the value of 62.5 at 11 wt% of NS-CNTs, corresponding to a 492% increase compared to that of pristine P(VDF-TrFE) with only a small dielectric loss tangent (D) of 0.1.