RESUMEN
OBJECTIVE: Nucleic acid-based vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are effective in the general population. However, it is unknown whether this is true in Asian patients with autoimmune rheumatic diseases (ARDs) who have received various combinations of disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We designed a large prospective observational study recruiting 228 patients with ARDs in a tertiary rheumatology centre in Taiwan. Altogether, 142 received biological or targeted synthetic DMARDs and 86 received only conventional synthetic (cs) DMARDs. Serum levels of immunoglobulin G antibody against SARS-CoV-2 spike proteins were measured 2-6 weeks after COVID-19 vaccination with mRNA-1273 (Moderna®) or ChAdOx1 nCoV-19 (Oxford/AstraZeneca®). The immunomodulatory therapies were not modified before or after vaccination. RESULTS: Overall, 194 patients (85.09%) exhibited antibodies (758.33 ± 808.43 ng/mL) but 34 patients did not (103.24 ± 41.08 ng/mL). Patients with systemic lupus erythematosus or rheumatoid arthritis had significantly lower humoral responses to COVID-19 vaccination than those with other ARDs (p < 0.05). There was no significant difference in immunogenicity among patients on different csDMARD treatments. Compared to patients treated with only csDMARDs, those on rituximab or abatacept therapy had significantly lower immune response to the vaccination (p = 0.008 and p = 0.035, respectively). Patients who were treated with anti-tumour necrosis factor-α or interleukin-6 inhibitor exhibited higher titres of vaccination antibodies than those treated with direct lymphocyte inhibitors. CONCLUSIONS: mRNA-1273 and ChAdOx1 nCoV-19 vaccines were immunogenic in the majority of ARD patients. Rituximab and abatacept were associated with significantly diminished COVID-19 vaccination immunogenicity.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Enfermedades Autoinmunes , COVID-19 , Síndrome de Dificultad Respiratoria , Enfermedades Reumáticas , Humanos , SARS-CoV-2 , Vacunas contra la COVID-19/uso terapéutico , ChAdOx1 nCoV-19 , Vacuna nCoV-2019 mRNA-1273 , COVID-19/prevención & control , Abatacept/uso terapéutico , Inmunosupresores/uso terapéutico , Rituximab/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Vacunación , Anticuerpos Antivirales , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
Cyfluthrin is a pyrethroid insecticide and common household pesticide. The effect of cyfluthrin on Ca2+-related physiology in human osteosarcoma is unclear. This study investigated the effect of cyfluthrin on cytosolic-free Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells. Cyfluthrin concentration-dependently induced [Ca2+]i rises. Cyfluthrin-induced Ca2+ entry was confirmed by the Mn2+-induced quench of fura-2 fluorescence. Cyfluthrin at concentrations of 10-100 µM induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 50%. Cyfluthrin (100 µM) induced Mn2+ influx suggesting Ca2+ entry. Cyfluthrin-induced Ca2+ entry was inhibited 50% by protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) and inhibitor (GF109203X) and also by three inhibitors of store-operated Ca2+ channels: nifedipine, econazole, and SKF96365. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) completely inhibited cyfluthrin-evoked [Ca2+]i rises. Conversely, treatment with cyfluthrin abolished TG-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with 1-[6-[((17ß)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dion abolished cyfluthrin-induced [Ca2+]i rises. Cyfluthrin at 25-65 µM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. Together, in MG63 cells, cyfluthrin induced [Ca2+]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Cyfluthrin also caused Ca2+-independent cell death.
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Insecticidas/toxicidad , Nitrilos/toxicidad , Piretrinas/toxicidad , Calcio/análisis , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Osteosarcoma , Fosfolipasas de Tipo C/metabolismoRESUMEN
Bifenthrin, a commonly used pyrethroid pesticide, evokes various toxicological effects in different models. However, the effect of bifenthrin on cytosolic-free Ca2+ level ([Ca2+]i) and cytotoxicity in human prostate cancer cells is unclear. This study examined whether bifenthrin altered Ca2+ homeostasis and cell viability in PC3 human prostate cancer cells. [Ca2+]i in suspended cells were measured using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 assay. Bifenthrin (100-400 µM) concentration-dependently induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 30%. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished bifenthrin-evoked [Ca2+]i rises. Conversely, treatment with bifenthrin abolished BHQ-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 significantly inhibited bifenthrin-induced [Ca2+]i rises. Mn2+ has been shown to enter cells through similar mechanisms as Ca2+ but quenches fura-2 fluorescence at all excitation wavelengths. Bifenthrin (400 µM)-induced Mn2+ influx implicates that Ca2+ entry occurred. Bifenthrin-induced Ca2+ entry was inhibited by 30% by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate) and inhibitor (GF109203X) and three inhibitors of store-operated Ca2+ channels: nifedipine, econazole, and SKF96365. Bifenthrin at 175-275 µM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetra acetic acid-acetoxymethyl ester. Together, in PC3 cells, bifenthrin-induced [Ca2+]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Bifenthrin also caused Ca2+-independent cell death.
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Calcio/metabolismo , Plaguicidas/toxicidad , Piretrinas/toxicidad , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Humanos , Células PC-3RESUMEN
Gate-controllable spin-orbit coupling is often one requisite for spintronic devices. For practical spin field-effect transistors, another essential requirement is ballistic spin transport, where the spin precession length is shorter than the mean free path such that the gate-controlled spin precession is not randomized by disorder. In this letter, we report the observation of a gate-induced crossover from weak localization to weak anti-localization in the magneto-resistance of a high-mobility two-dimensional hole gas in a strained germanium quantum well. From the magneto-resistance, we extract the phase-coherence time, spin-orbit precession time, spin-orbit energy splitting, and cubic Rashba coefficient over a wide density range. The mobility and the mean free path increase with increasing hole density, while the spin precession length decreases due to increasingly stronger spin-orbit coupling. As the density becomes larger than â¼6 × 1011 cm-2, the spin precession length becomes shorter than the mean free path, and the system enters the ballistic spin transport regime. We also report here the numerical methods and code developed for calculating the magneto-resistance in the ballistic regime, where the commonly used HLN and ILP models for analyzing weak localization and anti-localization are not valid. These results pave the way toward silicon-compatible spintronic devices.
RESUMEN
Amitriptyline is a widely used tricyclic antidepressant, which acts primarily as a serotonin-norepinephrine reuptake inhibitor. This study examined the effect of amitriptyline on Ca2+ homeostasis and its related mechanism in MG63 human osteosarcoma cells. Amitriptyline evoked cytosolic-free Ca2+ concentrations ([Ca2+]i) rises concentration dependently. Amitriptyline-evoked Ca2+ entry was confirmed by Mn2+-induced quench of fura-2 fluorescence. This entry was inhibited by Ca2+ entry modulators nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate but was not affected by the PKC inhibitor GF109203X. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) inhibited amitriptyline-evoked [Ca2+]i rises by 95%. Conversely, treatment with amitriptyline abolished TG-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 inhibited amitriptyline-evoked [Ca2+]i rises by 70%. Amitriptyline killed cells at 200-500 µM in a concentration-dependent fashion. Chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane- N, N, N', N'-tetraacetic acid/AM did not reverse amitriptyline-induced cytotoxicity. Collectively, our data suggest that in MG63 cells, amitriptyline induced [Ca2+]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-regulated store-operated Ca2+ entry. Amitriptyline also induced Ca2+-disassociated cell death.
Asunto(s)
Amitriptilina/toxicidad , Antidepresivos Tricíclicos/toxicidad , Neoplasias Óseas/metabolismo , Señalización del Calcio/efectos de los fármacos , Calcio/metabolismo , Osteosarcoma/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Humanos , Osteosarcoma/patología , Proteína Quinasa C/metabolismo , Factores de Tiempo , Fosfolipasas de Tipo C/metabolismoRESUMEN
OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease and usually requires immunosuppressive therapy, which is a major cause of viral reactivation. The incidence and antiviral response in SLE patients with hepatitis C virus (HCV) reactivation is unclear and needs to be investigated. METHODS: One hundred and sixty-six SLE patients with antibody to HCV (anti-HCV) status were retrospectively reviewed regarding the events of HCV reactivation. Patients with HCV reactivation were treated with pegylated interferon plus ribavirin treatment. The virological response and relapse rate were evaluated. RESULTS: Twenty-six patients were positive for anti-HCV. During a mean 8.4 years of follow-up, 10 (38.5%) cases developed HCV reactivation. No clear relationship was noted between immunosuppressive therapy and the HCV reactivation. Eight patients underwent antiviral therapy and the rapid virological response (RVR), early virological response, and sustained virological response (SVR) rates were 37.5%, 87.5%, and 75.0%, respectively. However, late relapse (reappearance of HCV RNA in serum after archiving SVR) was found in two (33.3%) of six patients achieving SVR. The two cases were HCV genotype 1 b concurrent with corticosteroid treatment. CONCLUSIONS: HCV reactivation in anti-HCV-positive SLE patients was possibly associated with glucocorticoids. The virological response to interferon plus ribavirin treatment is not inferior to the general population. However, monitoring HCV RNA after SVR is necessary for patients concurrent with corticosteroid treatment due to the risk of late relapse.
Asunto(s)
Antivirales/uso terapéutico , Glucocorticoides/efectos adversos , Hepacivirus/fisiología , Hepatitis C Crónica/tratamiento farmacológico , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Activación Viral/efectos de los fármacos , Adulto , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Hepatitis C Crónica/genética , Hepatitis C Crónica/mortalidad , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Interferón-alfa/uso terapéutico , Lupus Eritematoso Sistémico/virología , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Recurrencia , Estudios Retrospectivos , Ribavirina/uso terapéutico , Carga Viral/efectos de los fármacosRESUMEN
Naproxen is an anti-inflammatory drug that affects cellular calcium ion (Ca(2+)) homeostasis and viability in different cells. This study explored the effect of naproxen on [Ca(2+)](i) and viability in Madin-Darby canine kidney cells (MDCK) canine renal tubular cells. At concentrations between 50 µM and 300 µM, naproxen induced [Ca(2+)](i) rises in a concentration-dependent manner. This Ca(2+) signal was reduced partly when extracellular Ca(2+) was removed. The Ca(2+) signal was inhibited by a Ca(2+) channel blocker nifedipine but not by store-operated Ca(2+) channel inhibitors (econazole and SKF96365), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, and a PKC inhibitor GF109203X. In Ca(2+)-free medium, pretreatment with 2,5-di-tert-butylhydroquinone or thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+) pumps, partly inhibited naproxen-induced Ca(2+) signal. Inhibition of phospholipase C with U73122 did not alter naproxen-evoked [Ca(2+)](i) rises. At concentrations between 15 µM and 30 µM, naproxen killed cells in a concentration-dependent manner, which was not reversed by prechelating cytosolic Ca(2+) with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl. Annexin V/propidium iodide staining data suggest that naproxen induced apoptosis. Together, in MDCK renal tubular cells, naproxen induced [Ca(2+)](i) rises by inducing Ca(2+) release from multiple stores that included the endoplasmic reticulum and Ca(2+) entry via nifedipine-sensitive Ca(2+) channels. Naproxen induced cell death that involved apoptosis.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Calcio/metabolismo , Células de Riñón Canino Madin Darby/efectos de los fármacos , Naproxeno/farmacología , Animales , Bloqueadores de los Canales de Calcio/farmacología , Muerte Celular/efectos de los fármacos , Perros , Imidazoles/farmacología , Indoles/farmacología , Células de Riñón Canino Madin Darby/metabolismo , Maleimidas/farmacología , Nifedipino/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
Resveratrol is a natural compound that affects cellular calcium (Ca(2+)) homeostasis and viability in different cells. This study examined the effect of resveratrol on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in OC2 human oral cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i, and water-soluble tetrazolium-1 was used to measure viability. Resveratrol evoked concentration-dependent increase in [Ca(2+)]i. The response was reduced by removing extracellular Ca(2+). Resveratrol also caused manganese-induced fura-2 fluorescence quench. Resveratrol-evoked Ca(2+) entry was inhibited by nifedipine and the protein kinase C (PKC) inhibitor GF109203X but was not altered by econazole, SKF96365, and the PKC activator phorbol 12-myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished resveratrol-evoked [Ca(2+)]i rise. Conversely, treatment with resveratrol inhibited BHQ-evoked [Ca(2+)]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished resveratrol-evoked [Ca(2+)]i rise. At 20-100 µM, resveratrol decreased cell viability, which was not affected by chelating cytosolic Ca(2+)with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. Annexin V-fluorescein isothiocyanate staining data suggest that resveratrol at 20-40 µM induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, resveratrol induced [Ca(2+)]i rise by evoking PLC-dependent Ca(2+) release from the endoplasmic reticulum and by causing Ca(2+) entry via nifedipine-sensitive, PKC-regulated mechanisms. Resveratrol also caused Ca(2+)-independent apoptosis.
Asunto(s)
Calcio/metabolismo , Estilbenos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citosol/metabolismo , Humanos , Neoplasias de la Boca , Proteína Quinasa C/metabolismo , Resveratrol , Fosfolipasas de Tipo C/metabolismoRESUMEN
SUMMARY: In patients with systemic lupus erythematosus (SLE), low bone mineral density (BMD) is associated with increased age, prolonged disease, low body mass index (BMI), and overlap with rheumatoid arthritis (RA). Elevated fibroblast growth factor (FGF)-23 in cyclosporine A (CsA) users with SLE are associated with decreased active vitamin D and osteocalcin. INTRODUCTION: The objective of this study was to investigate the steroid and CsA effect on bone metabolism and serum FGF-23 in SLE patients. METHODS: Seventy-two SLE patients and 10 age- and sex-matched healthy individuals underwent blood tests for bone metabolic biomarkers and FGF-23, and lumbar spine dual-energy X-ray absorptiometry for BMD. RESULTS: Comparisons between patients and controls were made in premenopausal women/men younger than 50 years and postmenopausal women/men older than 50 years separately. SLE patients had more frequent low Z-score (≤-2.0, 8.5 vs. 0%), osteopenia (-2.5Asunto(s)
Remodelación Ósea/fisiología
, Ciclosporina/uso terapéutico
, Factores de Crecimiento de Fibroblastos/sangre
, Glucocorticoides/uso terapéutico
, Inmunosupresores/uso terapéutico
, Lupus Eritematoso Sistémico/tratamiento farmacológico
, Absorciometría de Fotón
, Adulto
, Biomarcadores/sangre
, Enfermedades Óseas Metabólicas/complicaciones
, Remodelación Ósea/efectos de los fármacos
, Estudios de Casos y Controles
, Estudios Transversales
, Ciclosporina/farmacología
, Femenino
, Factor-23 de Crecimiento de Fibroblastos
, Factores de Crecimiento de Fibroblastos/efectos de los fármacos
, Glucocorticoides/farmacología
, Humanos
, Inmunosupresores/farmacología
, Vértebras Lumbares/diagnóstico por imagen
, Lupus Eritematoso Sistémico/complicaciones
, Masculino
, Persona de Mediana Edad
, Osteoporosis/complicaciones
, Premenopausia
, Resultado del Tratamiento
RESUMEN
Celecoxib has been shown to have antitumor effect in previous studies but the mechanisms are unclear. The effect of celecoxib on cytosolic Ca(2+) concentrations ([Ca(2+)]i) and viability in HA59T human hepatoma cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)]i. Celecoxib at concentrations of 10-50 µM induced a [Ca(2+)]i rise in a concentration-dependent manner. The response was reduced by 80% by removing Ca(2+). Celecoxib induced Mn(2+) influx, leading to quenching of fura-2 fluorescence. Celecoxib-evoked Ca(2+) entry was suppressed by nifedipine, econazole, SK&F96365, and protein kinase C modulators. In the absence of extracellular Ca(2+), incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin nearly abolished celecoxib-induced [Ca(2+)]i rise. Incubation with celecoxib abolished thapsigargin-induced [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 abolished celecoxib-induced [Ca(2+)]i rise. At 1-50 µM, celecoxib inhibited cell viability by less than 20%, which was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Celecoxib (10-50 µM) also induced apoptosis. In sum, in HA59T hepatoma cells, celecoxib induced a [Ca(2+)]i rise by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via protein kinase C-sensitive store-operated Ca(2+) channels. Celecoxib also caused cell death via apoptosis.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Pirazoles/farmacología , Sulfonamidas/farmacología , Carcinoma Hepatocelular , Celecoxib , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Humanos , Neoplasias Hepáticas , Proteína Quinasa C/metabolismo , Fosfolipasas de Tipo C/metabolismoRESUMEN
A novel technique was developed to remove osseointegrated implants without enlarging the bony socket. Immediate replacement was performed simultaneously using a same-size implant with good primary stability. The prosthesis was delivered after 6 months of healing with good loading function. Good bone stability was found at the 12-month follow-up.
Asunto(s)
Implantes Dentales , Remoción de Dispositivos/métodos , Carga Inmediata del Implante Dental , Adulto , Implantación Dental Endoósea , Humanos , Masculino , Mandíbula/cirugía , Oseointegración , TitanioRESUMEN
The effect of the natural product diindolylmethane (DIM) on cytosolic Ca(2+) concentrations ([Ca(2+)]i) and viability in MDCK renal tubular cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)]i. DIM at concentrations 1-50 µM induced a [Ca(2+)]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca(2+). DIM induced Mn(2+) influx leading to quenching of fura-2 fluorescence. DIM-evoked Ca(2+) entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca(2+), incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) greatly inhibited DIM-induced [Ca(2+)]i rise. Incubation with DIM abolished TG or BHQ-induced [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 reduced DIM-induced [Ca(2+)]i rise by 50%. At 1, 10, 40 and 50 µM, DIM slightly enhanced cell proliferation. The effect of 50 µM DIM was reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. In sum, in MDCK cells, DIM induced a [Ca(2+)]i rise by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via protein kinase C-sensitive store-operated Ca(2+) channels. DIM did not induce cell death.
Asunto(s)
Productos Biológicos/farmacología , Calcio/metabolismo , Indoles/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Perros , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Homeostasis/efectos de los fármacos , Túbulos Renales/citología , Células de Riñón Canino Madin Darby , Fosfolipasas de Tipo C/metabolismoRESUMEN
The effect of the natural compound phenethyl isothiocyanate (PEITC) on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) and viability in MDCK renal cells is unknown. This study explored whether PEITC changed [Ca(2+)](i) in MDCK cells using the Ca(2+)-sensitive fluorescent dye fura-2. PEITC at 200-700 µM increased [Ca(2+)](i) in a concentration-dependent manner. The signal was reduced by removing extracellular Ca(2+). PEITC-induced Ca(2+) influx was inhibited by nifedipine, econazole, SK&F 96365 and protein kinase C modulators. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) inhibited PEITC-induced rise in [Ca(2+)](i). Incubation with PEITC also inhibited TG or BHQ-induced rise in [Ca(2+)](i). Inhibition of phospholipase C with U73122 abolished PEITC-induced rise in [Ca(2+)](i). At 15-75 µM, PEITC decreased viability. The cytotoxic effect of PEITC was enhanced by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester. Annexin V-FITC data suggest that 20 and 50 µM PEITC induced apoptosis. At 10 and 15 µM, PEITC did not increase reactive oxygen species (ROS) production. Together, in renal tubular cells, PEITC-induced rise in [Ca(2+)](i) by inducing phospholipase C-dependent Ca(2+) release from endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. PEITC induced apoptosis in a concentration-dependent, ROS/Ca(2+)-independent manner.
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Calcio/metabolismo , Inhibidores Enzimáticos/toxicidad , Isotiocianatos/toxicidad , Túbulos Renales/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Señalización del Calcio/fisiología , Supervivencia Celular/efectos de los fármacos , Citosol/efectos de los fármacos , Citosol/metabolismo , Perros , Econazol/farmacología , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Imidazoles/farmacología , Túbulos Renales/metabolismo , Túbulos Renales/patología , Células de Riñón Canino Madin Darby , Nifedipino/farmacología , Tapsigargina/farmacologíaRESUMEN
Protein-losing enteropathy (PLE) and autoimmune oophoritis are unusual manifestations of systemic lupus erythematosus (SLE). Autoimmune oophoritis may result in menstrual disturbance and spontaneous premature ovarian failure. However, there is no validated examination to confirm the diagnosis and it is easily neglected in patients with ovarian insufficiency. A 31-year-old woman with SLE presented with PLE and autoimmune oophoritis during the long course of flares and remissions in her lupus activity. The synchronism implied the association between the two. Moreover, both conditions simultaneously had a good response to cyclosporine A (CsA) therapy.
Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Ooforitis/etiología , Poliendocrinopatías Autoinmunes/etiología , Enteropatías Perdedoras de Proteínas/etiología , Adulto , Ciclosporina/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/fisiopatología , Ooforitis/diagnóstico , Poliendocrinopatías Autoinmunes/diagnóstico , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Insuficiencia Ovárica Primaria/etiología , Enteropatías Perdedoras de Proteínas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to diagnose microvascular invasion in patients with solitary hepatocellular carcinoma (HCC) from pre-operative CT imaging. METHODS: 102 patients with solitary HCC who underwent curative hepatectomy were retrospectively included in our study. The pre-operative 3-phase CT imaging and laboratory data for the 102 patients were reviewed. Tumour size, tumour margin, peritumoral enhancement and α-fetoprotein level were assessed. Surgical pathology was reviewed; tumour differentiation, liver fibrosis score and microvascular invasion were recorded. RESULTS: The histopathological results revealed that 50 HCCs were positive and the other 52 were negative for microvascular invasion. Univariate analysis revealed that tumour size (p = 0.036), higher Edmondson-Steiner grade (p = 0.047) and non-smooth tumour margin (p < 0.001) showed statistically significant associations with microvascular invasion. Multivariate logistic regression analysis showed that non-smooth tumour margin had a statistically significant association with microvascular invasion only (p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the non-smooth tumour margin in the prediction of microvascular invasion were 66%, 86.5%, 82.5% and 72.6%, respectively. CONCLUSION: Non-smooth tumour margin in pre-operative CT had a statistically significant association with microvascular invasion. More aggressive treatment should be considered in HCC patients with suspected positive microvascular invasion.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Tomografía Computarizada por Rayos X , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Microvasos , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
BACKGROUND: HLA-Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA-Cw*06. OBJECTIVES: To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated. METHODS: We conducted a case-control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA-B and HLA-C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high-need patients with moderate to severe psoriasis) and B (general patients with psoriasis). RESULTS: The frequencies of HLA-B*60, HLA-B*75, HLA-Cw*06 and HLA-Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA-Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc=0·04). HLA-B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA-Cw*01/HLA-B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA-Cw*01+ and HLA-Cw*01- individuals in the alefacept treatment group, and between HLA-B*37+ and HLA-B*37-, and HLA-B*58+ and HLA-B*58- individuals in the efalizumab treatment group. CONCLUSIONS: In addition to HLA-Cw*06, the HLA-Cw*01/HLA-B*46 haplotype was also increased in Chinese patients with psoriasis. High-need patients with psoriasis had a lower frequency of HLA-Cw*06 but a higher prevalence of HLA-B*46 compared with general patients with psoriasis in our population.
Asunto(s)
Antígenos HLA-B/genética , Antígenos HLA-C/genética , Polimorfismo Genético/genética , Psoriasis/genética , Adolescente , Adulto , Alefacept , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Estudios de Casos y Controles , China/etnología , Enfermedad Crónica , Fármacos Dermatológicos/uso terapéutico , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Antígenos HLA-A/genética , Humanos , Masculino , Psoriasis/tratamiento farmacológico , Psoriasis/etnología , Proteínas Recombinantes de Fusión/uso terapéutico , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Mould-induced atopic respiratory diseases are a worldwide problem. Characterization of fungal allergens is of major clinical importance. OBJECTIVE: We identified a novel transaldolase family allergen of Cladosporium and Penicillium species. METHODS: Fungal allergens were identified by immunoblotting, peptide mass mapping and partial sequencing, cDNA cloning and IgE epitope mapping. RESULTS: A 36.5 kDa IgE-binding component in a partially purified C. cladosporioides preparation was identified. Mass spectrometric analyses suggest that this novel IgE-reacting allergen is a transaldolase. A corresponding full-length 1246 bp cDNA encoding a polypeptide of 325 residues was isolated. The newly identified transaldolase allergen has been designated as Cla c 14.0101. The cDNA encoding the Pencillium chrysogenum transaldolase was isolated by RT-PCR according to the cDNA sequence encoding a P. chrysogenum Wisconsin 54-1255 hypothetical protein. The purified rCla c 14.0101 protein reacted with IgE antibodies in 10 (38%) of 26 Cladosporium cladosporioides-sensitized asthmatic patients. Nine of the 10 rCla c 14.0101-positive sera have IgE binding against the recombinant Penicillium transaldolase (rPen ch 35.0101). Among the eight fungal transaldolase-positive sera tested, three showed IgE binding against the recombinant human transaldolase. To determine cross-reactivity between the Cladosporium and Penicillium fungi, IgE cross-reactivity was detected between these two fungal transaldolase allergens by inhibition assays. Both the N- and the C-terminal fragments of Cla c 14.0101 were recognized by IgE antibodies. The C-terminal IgE-reacting determinant was narrowed down to a region encompassing Thr257 to Ser278 of Cla c 14.0101. It was mapped onto a loop-like structure of a 3D model constructed for Cla c 14.0101. CONCLUSION AND CLINICAL RELEVANCE: We identified transaldolase as a novel and IgE cross-reactive allergen family of C. cladosporioides and P. chrysogenum. In addition, an IgE-reacting fragment (Thr257 to Ser278) was pinpointed to a loop-like structure on Cla c 14.0101. Results obtained provide important information in clinical mould allergy.
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Alérgenos/inmunología , Antígenos Fúngicos/inmunología , Asma/inmunología , Cladosporium/inmunología , Inmunoglobulina E/inmunología , Penicillium chrysogenum/inmunología , Transaldolasa/inmunología , Alérgenos/sangre , Antígenos Fúngicos/sangre , Asma/sangre , Asma/microbiología , Cladosporium/enzimología , Humanos , Inmunoglobulina E/sangre , Penicillium chrysogenum/enzimología , Transaldolasa/sangreRESUMEN
OBJECTIVE: To evaluate new classification criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only. METHODS: In this Assessment of SpondyloArthritis international Society (ASAS) study, two prespecified sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard. RESULTS: In all, 24 ASAS centres included 266 patients, with a final diagnosis of SpA being made in 66.2%. After adjustments a final set of criteria showed the best balance between sensitivity (77.8%) and specificity (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, inflammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, inflammatory back pain in the past, family history of SpA. The new criteria performed better than modified versions of the ESSG (sensitivity 62.5%, specificity 81.1%) and the Amor criteria (sensitivity 39.8%, specificity 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specificity 83.3%) than the modified ESSG (sensitivity 79.1%, specificity 68.8%) and Amor criteria (sensitivity 67.5%, specificity 86.7%), respectively. CONCLUSIONS: The new ASAS classification criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.
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Espondiloartritis/clasificación , Adulto , Artritis Reactiva/clasificación , Artritis Reactiva/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Cooperación Internacional , Masculino , Persona de Mediana Edad , Psoriasis/complicaciones , Sacroileítis/complicaciones , Sensibilidad y Especificidad , Espondiloartritis/complicaciones , Espondiloartritis/diagnóstico , Espondilitis Anquilosante/clasificación , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/diagnóstico , Uveítis/complicaciones , Adulto JovenRESUMEN
Systemic lupus erythematosus (SLE) is an autoimmune disease with higher morbidity and mortality among ethnic Chinese patients than Whites. Corticosteroid and other immunosuppressive drugs, including cyclophosphamide, azathioprine, and hydroxychloroquine are traditional therapies for this disease. Since the year 2000, mycophenolate mofetil and rituximab have been widely used in refractory SLE or severe lupus nephritis. Because the high disease activity remains, even after active therapy, and serious side effects from Western medicines may develop, more than 40% of SLE patients in Western countries are pursuing complementary and alternative therapies (CATs). CAT remedies are multiplex, and include herbal medicines, diets and vitamins, acupuncture, chiropractice, folk medicine, massage, spiritual healing, etc. Many herbal formulas have been used but in general their efficacy in treating lupus is doubted because of the lack of strong evidence. Tripterygium (T2) has demonstrated good efficacy in rheumatoid arthritis (RA) and SLE, but widespread use is limited due to the side effects. Through randomized clinical trials, we hope in the future that some Chinese medicines may be found helpful as CATs for SLE.
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Terapias Complementarias/métodos , Lupus Eritematoso Sistémico/terapia , Pueblo Asiatico , Salud Global , Humanos , Lupus Eritematoso Sistémico/etnología , Morbilidad/tendenciasRESUMEN
The purpose of this study was to determine the percentage of signal intensity loss (PSIL) threshold for the characterisation of focal liver lesions among patients with chronic liver disease. 55 nodules in 49 patients with chronic liver disease who underwent ferucarbotran-enhanced MR studies were included. Among the 49 patients, 40 had liver cirrhosis and 9 had chronic hepatitis. 8 haemangiomas, 3 focal nodular hyperplasia, 9 dysplastic nodules and 12 well, 19 moderately and 4 poorly differentiated hepatocellular carcinomas (HCCs) were revealed. The PSIL, signal-to-noise ratio and contrast-to-noise ratio of each lesion type were calculated. The diagnostic performance of PSIL on ferucarbotran-enhanced T(2) weighted images (PSIL(T2WI)) and T(2) weighted fat-suppression images (PSIL(FS-T2WI)) that characterised hepatic tumours was compared with receiver operating characteristic (ROC) analysis. Using ROC analysis, the diagnostic performance of PSIL(FS-T2WI) was superior to that of PSIL(T2WI) (p = 0.01). The mean PSIL(FS-T2WI) of the benign lesions was significantly higher than that of HCC (p<0.001), and the mean PSIL(FS-T2WI) of well-differentiated HCC was significantly higher than that of moderately/poorly differentiated HCCs (p = 0.001). With a PSIL(FS-T2WI) threshold of 40% in lesions characterising ferucarbotran-enhanced FS-T2WI, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 88.6%, 95%, 90.9%, 96.9% and 82.6%, respectively. In conclusion, with ferucarbotran-enhanced FS-T2WI, a PSIL(FS-T2WI) threshold of 40% for characterising focal liver nodules among patients with chronic liver disease is recommended. It is useful for distinguishing HCC from benign nodules.