RESUMEN
Bryophytes produce rare and bioactive compounds with a broad range of therapeutic potential, and many species are reported in ethnomedicinal uses. However, only a few studies have investigated their potential as natural anti-inflammatory drug candidate compounds. The present study investigates the anti-inflammatory effects of thirty-two species of bryophytes, including mosses and liverworts, on Raw 264.7 murine macrophages stimulated with lipopolysaccharide (LPS) or recombinant human peroxiredoxin (hPrx1). The 70% ethanol extracts of bryophytes were screened for their potential to reduce the production of nitric oxide (NO), an important pro-inflammatory mediator. Among the analyzed extracts, two moss species significantly inhibited LPS-induced NO production without cytotoxic effects. The bioactive extracts of Dicranum majus and Thuidium delicatulum inhibited NO production in a concentration-dependent manner with IC50 values of 1.04 and 1.54 µg/mL, respectively. The crude 70% ethanol and ethyl acetate extracts were then partitioned with different solvents in increasing order of polarity (n-hexane, diethyl ether, chloroform, ethyl acetate, and n-butanol). The fractions were screened for their inhibitory effects on NO production stimulated with LPS at 1 ng/mL or 10 ng/mL. The NO production levels were significantly affected by the fractions of decreasing polarity such as n-hexane and diethyl ether ones. Therefore, the potential of these extracts to inhibit the LPS-induced NO pathway suggests their effective properties in attenuating inflammation and could represent a perspective for the development of innovative therapeutic agents.
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Briófitas , Lipopolisacáridos , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Humanos , Lipopolisacáridos/farmacología , Macrófagos , Ratones , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: The kidney is a major target in primary antiphospholipid syndrome. Several types of nephropathy have been reported, the most frequent being acute or chronic specific vascular nephropathies and membranous nephropathy. CASE PRESENTATION: A 59-year-old male presented in our unit with nephrotic syndrome. He had a history of primary antiphospholipid syndrome with lupus anticoagulant treated with vitamin K antagonist therapy. On admission, antiphospholipid (lupus anticoagulant) and anti-PLA2R antibodies were positive. Screening for secondary etiologies was negative. In the context of primary antiphospholipid syndrome treated with vitamin K antagonist therapy, we did not perform a biopsy and we treated the patient with angiotensin-converting-enzyme inhibitor. No remission was observed at 6 months with persistent anti-PLA2R antibodies while antiphospholipid antibody level became negative. Consequently, kidney biopsy was performed showing both membranous nephropathy with PLA2R in deposits on immunohistochemistry with IgG4 dominance and antiphospholipid syndrome chronic vascular nephropathy. Following that, treatment with rituximab was started with secondarily a decrease in serum PLA2R antibody levels and partial remission. CONCLUSION: We report the first association between primary antiphospholipid syndrome and membranous nephropathy with anti-PLA2R antibodies. Our observations could suggest a causal link between primary antiphospholipid syndrome and PLA2R-related membranous nephropathy. Consequently, it would be interesting to screen for anti-PLA2R antibodies for further cases of nephrotic syndrome in patients with primary antiphospholipid syndrome and to search antiphospholipid antibodies in all membranous nephropathies.
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Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/complicaciones , Glomerulonefritis Membranosa/inmunología , Receptores de Fosfolipasa A2/inmunología , Síndrome Antifosfolípido/sangre , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Mechanical overload and aging are the main risk factors of osteoarthritis (OA). Galectin 3 (GAL3) is important in the formation of primary cilia, organelles that are able to sense mechanical stress. The objectives were to evaluate the role of GAL3 in chondrocyte primary cilium formation and in OA in mice. Chondrocyte primary cilium was detected in vitro by confocal microscopy. OA was induced by aging and partial meniscectomy of wild-type (WT) and Gal3-null 129SvEV mice (Gal3-/-). Primary chondrocytes were isolated from joints of new-born mice. Chondrocyte apoptosis was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase 3 activity and cytochrome c release. Gene expression was assessed by qRT-PCR. GAL3 was localized at the basal body of the chondrocyte primary cilium. Primary cilia of Gal3-/- chondrocytes were frequently abnormal and misshapen. Deletion of Gal3 triggered premature OA during aging and exacerbated joint instability-induced OA. In both aging and surgery-induced OA cartilage, levels of chondrocyte catabolism and hypertrophy markers and apoptosis were more severe in Gal3-/- than WT samples. In vitro, Gal3 knockout favored chondrocyte apoptosis via the mitochondrial pathway. GAL3 is a key regulator of cartilage homeostasis and chondrocyte primary cilium formation in mice. Gal3 deletion promotes OA development.
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Apoptosis/genética , Cartílago Articular/metabolismo , Condrocitos/metabolismo , Cilios/metabolismo , Galectina 3/genética , Mitocondrias/metabolismo , Animales , Animales Recién Nacidos , Cartílago Articular/patología , Caspasa 3/metabolismo , Células Cultivadas , Condrocitos/citología , Galectina 3/deficiencia , Etiquetado Corte-Fin in Situ , Ratones de la Cepa 129 , Ratones Noqueados , Osteoartritis/genética , Osteoartritis/metabolismoRESUMEN
OBJECTIVES: Based on a novel approach suggesting a role of adipose tissue in osteoarthritis (OA), we aimed to determine whether the infrapatellar fat pad (IFP) may affect joint cell functions through adipokines. METHODS: The conditioned media of IFP and subcutaneous adipose tissue from OA patients were used to determine the production of leptin and adiponectin, and to stimulate chondrocytes and fibroblast-like synoviocytes (FLS). Blocking experiments were carried out to evaluate the contribution of adipokines to IFP effects. The gene expression of inflammatory and degradative proteins, growth factors and components of the extracellular matrix, and the production of inflammatory mediators and metalloproteases were determined to evaluate cell response to fat-conditioned media. RESULTS: IFP releases elevated amounts of leptin and adiponectin independently of the body mass index and the gender. The conditioned media from IFP strongly induce the expression of inflammatory genes in both articular cells and the expression of degradative genes in chondrocytes, but remain ineffective in regulating the expression of aggrecan, type 2 collagen or growth factors. Blocking leptin or adiponectin does not change the cell response to IFP. A great variability between patients is found when compared the inflammatory activity of paired samples of IFP and subcutaneous adipose tissue. CONCLUSIONS: IFP may trigger both cartilage destruction and inflammation of the synovium, but not through leptin or adiponectin. The data suggest also that IFP may have specific inflammatory phenotypic features independent from the general phenotype found in obesity.
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Adiponectina/metabolismo , Tejido Adiposo/metabolismo , Cartílago Articular/metabolismo , Citocinas/metabolismo , Inflamación/metabolismo , Leptina/metabolismo , Osteoartritis de la Rodilla/metabolismo , Tejido Adiposo/patología , Anciano , Anciano de 80 o más Años , Cartílago Articular/patología , Cartílago Articular/cirugía , Condrocitos/metabolismo , Condrocitos/patología , Femenino , Humanos , Inflamación/patología , Articulación de la Rodilla/metabolismo , Articulación de la Rodilla/patología , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/cirugíaRESUMEN
OBJECTIVE: Aldosterone (Aldo) is involved in arterial stiffness and heart failure, but the mechanisms have remained unclear. Galectin-3 (Gal-3), a ß-galactoside-binding lectin, plays an important role in inflammation, fibrosis, and heart failure. We investigated here whether Gal-3 is involved in Aldo-induced vascular fibrosis. METHODS AND RESULTS: In rat vascular smooth muscle cells Gal-3 overexpression enhanced specifically collagen type I synthesis. Moreover Gal-3 inhibition by modified citrus pectin or small interfering RNA blocked Aldo-induced collagen type I synthesis. Rats were treated with Aldo-salt combined with spironolactone or modified citrus pectin for 3 weeks. Hypertensive Aldo-treated rats presented vascular hypertrophy, inflammation, fibrosis, and increased aortic Gal-3 expression. Spironolactone or modified citrus pectin treatment reversed all the above effects. Wild-type and Gal-3 knock-out mice were treated with Aldo for 6 hours or 3 weeks. Aldo increased aortic Gal-3 expression, inflammation, and collagen type I in wild-type mice at both the short- and the long-term, whereas no changes occurred in Gal-3 knock-out mice. CONCLUSIONS: Our data indicate that Gal-3 is required for inflammatory and fibrotic responses to Aldo in vascular smooth muscle cells in vitro and in vivo, suggesting a key role for Gal-3 in vascular fibrosis.
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Aldosterona , Galectina 3/metabolismo , Hipertensión/metabolismo , Inflamación/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Animales , Presión Sanguínea , Células Cultivadas , Colágeno Tipo I/biosíntesis , Modelos Animales de Enfermedad , Fibrosis , Galectina 3/antagonistas & inhibidores , Galectina 3/deficiencia , Galectina 3/genética , Humanos , Hipertensión/inducido químicamente , Hipertensión/genética , Hipertensión/patología , Hipertensión/fisiopatología , Hipertensión/prevención & control , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/patología , Inflamación/fisiopatología , Inflamación/prevención & control , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Antagonistas de Receptores de Mineralocorticoides/farmacología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Músculo Liso Vascular/fisiopatología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/patología , Interferencia de ARN , Ratas , Ratas Wistar , Factores de Tiempo , Transfección , Regulación hacia Arriba , Rigidez VascularRESUMEN
Transforming growth factor (TGF)-ß1 stimulates extracellular PP(i) (ePP(i)) generation and promotes chondrocalcinosis, which also occurs secondary to hyperparathyroidism-induced hypercalcemia. We previously demonstrated that ANK was up-regulated by TGF-ß1 activation of ERK1/2 and Ca(2+)-dependent protein kinase C (PKCα). Thus, we investigated mechanisms by which calcium could affect ePP(i) metabolism, especially its main regulating proteins ANK and PC-1 (plasma cell membrane glycoprotein-1). We stimulated articular chondrocytes with TGF-ß1 under extracellular (eCa(2+)) or cytosolic Ca(2+) (cCa(2+)) modulations. We studied ANK, PC-1 expression (quantitative RT-PCR, Western blotting), ePP(i) levels (radiometric assay), and cCa(2+) input (fluorescent probe). Voltage-operated Ca(2+)-channels (VOC) and signaling pathways involved were investigated with selective inhibitors. Finally, Ank promoter activity was evaluated (gene reporter). TGF-ß1 elevated cCa(2+) and ePP(i) levels (by up-regulating Ank and PC-1 mRNA/proteins) in an eCa(2+) dose-dependent manner. TGF-ß1 effects were suppressed by cCa(2+) chelation or L- and T-VOC blockade while being mostly reproduced by ionomycin. In the same experimental conditions, the activation of Ras, the phosphorylation of ERK1/2 and PKCα, and the stimulation of Ank promoter activity were affected similarly. Activation of SP1 (specific protein 1) and ELK-1 (Ets-like protein-1) transcription factors supported the regulatory role of Ca(2+). SP1 or ELK-1 overexpression or blockade experiments demonstrated a major contribution of ELK-1, which acted synergistically with SP1 to activate Ank promoter in response to TGF-ß1. TGF-ß1 promotes input of eCa(2+) through opening of L- and T-VOCs, to potentiate ERK1/2 and PKCα signaling cascades, resulting in an enhanced activation of Ank promoter and ePP(i) production in chondrocyte.
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Calcio/metabolismo , Cartílago Articular/metabolismo , Condrocitos/metabolismo , Difosfatos/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Canales de Calcio/genética , Canales de Calcio/metabolismo , Cartílago Articular/patología , Células Cultivadas , Condrocalcinosis/genética , Condrocalcinosis/metabolismo , Condrocalcinosis/patología , Condrocitos/patología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Transporte Iónico/efectos de los fármacos , Transporte Iónico/genética , Ionomicina/farmacología , Ionóforos/farmacología , Masculino , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Hidrolasas Diéster Fosfóricas/genética , Hidrolasas Diéster Fosfóricas/metabolismo , Regiones Promotoras Genéticas/genética , Proteína Quinasa C-alfa/genética , Proteína Quinasa C-alfa/metabolismo , Pirofosfatasas/genética , Pirofosfatasas/metabolismo , Ratas , Ratas Wistar , Factor de Transcripción Sp1/genética , Factor de Transcripción Sp1/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Proteína Elk-1 con Dominio ets/genética , Proteína Elk-1 con Dominio ets/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
OBJECTIVE: We reported previously that the orphan nuclear receptor, estrogen receptor-related receptor α (ERRα), is expressed in articular chondrocytes and is dysregulated in a mouse model of inflammatory arthritis. The aim of this study, therefore, was to determine whether ERRα is also dysregulated in patients with osteoarthritis (OA). METHODS: ERRα messenger RNA (mRNA) and protein were quantified in normal and OA cartilage samples and in OA chondrocytes in vitro, with and without short-term treatment with a variety of OA-associated factors and signaling pathway agonists and inhibitors. RESULTS: ERRα expression was lower in OA than in normal articular cartilage. Interleukin-1ß (IL-1ß) markedly up-regulated ERRα expression in OA chondrocytes in vitro, and agonist or inhibitor treatment indicated that the up-regulation was dependent on cyclooxygenase 2 (COX-2; NS398), prostaglandin E(2), cAMP (8-bromo-cAMP), and protein kinase A (PKA; KT5720). Treatment with the ERRα inverse agonist XCT790 decreased the expression of SOX9 and the up-regulation of ERRα by IL-1ß, suggesting autoregulation of ERRα in the IL-1ß pathway. Matrix metalloproteinase 13 (MMP-13) expression was also decreased by treatment with XCT790 plus IL-1ß versus IL-1ß alone, and the down-regulation of MMP-13 mRNA and protein observed with XCT790 alone suggests that the up-regulation of MMP-13 by IL-1ß is ERRα-dependent. CONCLUSION: We report the first evidence that ERRα expression is regulated by IL-1ß in COX-2-, cAMP-, and PKA-dependent pathways in OA chondrocytes. We confirmed that SOX9 is an ERRα target gene in human, as in rodent, chondrocytes and identified MMP-13 as a potential new target gene, which suggests that ERRα may both respond to the healing signal and contribute to extracellular degradation in OA cartilage.
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Cartílago Articular/metabolismo , Condrocitos/metabolismo , AMP Cíclico/metabolismo , Interleucina-1beta/metabolismo , Osteoartritis/metabolismo , Prostaglandinas E/metabolismo , Receptores de Estrógenos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Células Cultivadas , AMP Cíclico/genética , Femenino , Humanos , Interleucina-1beta/genética , Masculino , Persona de Mediana Edad , Osteoartritis/genética , Prostaglandinas E/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Estrógenos/genética , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Transducción de Señal/fisiología , Receptor Relacionado con Estrógeno ERRalfaRESUMEN
Psoriasis is a chronic inflammatory disorder affecting skin and joints that results from immunological dysfunction such as enhanced IL-23 induced Th-17 differentiation. IkappaB-Zeta (IκBζ) is an atypical transcriptional factor of the IκB protein family since, contrary to the other family members, it positively regulates NF-κB pathway by being exclusively localized into the nucleus. IκBζ deficiency reduces visible manifestations of experimental psoriasis by diminishing expression of psoriasis-associated genes. It is thus tempting to consider IκBζ as a potential therapeutic target for psoriasis as well as for other IL23/IL17-mediated inflammatory diseases. In this review, we will discuss the regulation of expression of NFKBIZ and its protein IκBζ, its downstream targets, its involvement in pathogenesis of multiple disorders with emphasis on psoriasis and evidences supporting that inhibition of IκBζ may be a promising alternative to current therapeutic managements of psoriasis.
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FN-kappa B , Psoriasis , Humanos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Inflamación/genética , Inflamación/metabolismo , Interleucina-23 , FN-kappa B/genética , FN-kappa B/metabolismo , Psoriasis/genética , Psoriasis/metabolismoRESUMEN
INTRODUCTION: Chronic kidney disease (CKD) affects > 10% of the population but not all CKD patients require referral to a nephrologist. Various recommendations for referral to nephrologists are proposed worldwide. We examined the profile of French patients consulting a nephrologist for the first time and compared these characteristics with the recommendations of the International Kidney Disease: Improving Global Outcomes (KDIGO), the French "Haute Autorité de Santé" (HAS), and the Canadian Kidney Failure Risk Equation (KFRE). METHODS: University Hospital electronic medical records were used to study patients referred for consultation with a nephrologist for the first time from 2016 to 2018. Patient characteristics (age, sex, diabetic status, estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (PCR), etiology reported by the nephrologist) and 1-year patient follow-up were analyzed and compared with the KDIGO, HAS and Canadian-KFRE recommendations for referral to a nephrologist. The stages were defined according to the KDIGO classification, based upon kidney function and proteinuria. RESULTS: The 1,547 included patients had a median age of 71 [61-79] years with 56% males and 37% with diabetes. The main nephropathies were vascular (40%) and glomerular (20%). The KDIGO classification revealed 30%, 47%, 19%, 4% stages G1-2 to G5, and 50%, 22%, 28% stages A1-A3, respectively. According to KDIGO, HAS and KFRE scores, nephrologist referral was indicated for 42%, 57% and 80% of patients respectively, with poor agreement between recommendations. Furthermore, we observed 890 (57%) patients with an eGFR> 30 ml/min and a urine protein to creatinine ratio 0.5 g/g, mostly aged over 65 years (67%); 40% were diabetic, and 57% had a eGFR > 45 ml/min/1.73m2, 56% were diagnosed as vascular nephropathy and 11% with unknown nephropathy. CONCLUSION: These results underline the importance of better identifying patients for referral to a nephrologist and informing general practitioners. Other referral criteria (age and etiology of the nephropathy) are debatable.
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Fallo Renal Crónico , Insuficiencia Renal Crónica , Anciano , Canadá , Creatinina/orina , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Nefrólogos , Pacientes Ambulatorios , Derivación y Consulta , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapiaRESUMEN
INTRODUCTION: Acute Kidney Injury (AKI) is increasingly common in people over 65 years of age, but its causes and management are poorly described. The purpose of this study was to describe the causes, management and prognosis of patients over 65 hospitalised for severe acute kidney injury (AKI) in all departments of a tertiary centre. METHOD: The prospective IRACIBLE (IRA: AKI in French; CIBLE: target in French) cohort included 480 patients hospitalised at a university hospital over 18 months for severe AKI or subgroup of AKIN3 (Acute Kidney Injury Network classification) defined by an acute creatinine increase > 354 µmol/L or managed with acute renal replacement therapy (RRT). The history, aetiology of AKI, management, and prognosis were compared in three age groups: < 65, 65-75, and > 75 years. RESULTS: The study population included 480 subjects (73% men) with a median body mass index (BMI) of 26.6 kg/m2 [23.3, 30.9], 176 (37%) diabetic patients, 124 (26%) patients < 65 years, 150 (31%) 65-75 years and 206 (43%) > 75 years. Increasing age class was associated with more comorbidities, a significantly lower median estimated glomerular filtration rate (eGFR) 6 months before inclusion (82; 62; 46 ml/min/1.73 m2, p < 0.05) and aetiology of AKI, which was more often obstructive (12%; 15%; 23%, p = 0.03) or part of a cardio-renal syndrome (6%; 9%; /15%, p = 0.04). Older patients were less often managed in the intensive care unit (54%; 47%; 24%, p < 0.0001), were less frequently treated by RRT (52%; 43%; 31%, p < 0.001) and received fewer invasive treatments (6%; 9%; 22%, p < 0.0001). Older survivors returned home less often (80%; 73%; 62%, p = 0.05) in favour of transfers to rehabilitation services (10%; 13%; 22%) with higher mortality at 3 months (35%; 32%; 50%, p < 0.0001). CONCLUSION: Older patients hospitalised for severe AKI have a specific profile with more comorbidities, lower baseline renal function, an aetiology of AKI of mainly extra-parenchymal causes and a complex pathway of care with an overall poor prognosis.
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Lesión Renal Aguda , Terapia de Reemplazo Renal , Humanos , Masculino , Anciano , Lactante , Femenino , Estudios Prospectivos , Creatinina , Terapia de Reemplazo Renal/efectos adversos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Unidades de Cuidados Intensivos , Estudios de Cohortes , Factores de Riesgo , Estudios RetrospectivosRESUMEN
Acquired Immune thrombotic thrombocytopenic purpura (iTTP) is considered among clinical situations that needs not only urgent treatment in acute setting but also long term management to prevent relapses. Important progresses have been made in management of these patients that are definitely associated with reduced mortality and relapse rate. However, there are still noticeable percentage of patients that may relapse despite application of modern treatment strategies including preemptive rituximab infusions. Hereby, we share our experience concerning a frequently relapsing iTTP due to development of anti-rituximab antibody. In our case administration of obinutuzumab, a humanized type II anti CD-20 antibody was associated with complete peripheral blood B cell depletion and increasing plasma ADAMTS-13 activity.
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Proteína ADAMTS13/sangre , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígenos CD20/inmunología , Inmunoterapia/métodos , Púrpura Trombocitopénica Trombótica/terapia , Anticuerpos Monoclonales Humanizados/inmunología , Formación de Anticuerpos , Especificidad de Anticuerpos , Subgrupos de Linfocitos B/inmunología , Terapia Combinada , Sustitución de Medicamentos , Femenino , Humanos , Recuento de Linfocitos , Obesidad/complicaciones , Plasma , Intercambio Plasmático , Prednisolona/uso terapéutico , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Recurrencia , Rituximab/inmunología , Rituximab/uso terapéutico , Anticuerpos de Dominio Único/uso terapéutico , Adulto JovenRESUMEN
Nowadays, therapeutic plasmapheresis (TP) is accepted as part of the treatment for specific groups of diseases. The availability of different methods, including double filtration and adsorption, increases selectivity for the removal of substances. However, the use of these techniques requires a thorough understanding of the characteristics and components of plasma. By considering pivotal papers from several databases, the aim of this narrative review is to describe the characteristics of plasma related to apheresis techniques. We have tried to cover the clinical implications including physiology, estimation of plasma volume, viscosity, and a description of its components including the size, volume of distribution, and half-lives of the different substances to be removed or maintained depending on the clinical situation and applied apheresis technique. Applying this knowledge will help us to choose the right method and dosage and improve the efficacy of the procedure by preventing or addressing any complications.
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Eliminación de Componentes Sanguíneos/métodos , Plasma/fisiología , Plasmaféresis/métodos , HumanosRESUMEN
Background: Metformin-associated lactic acidosis (MALA) and metformin-induced lactic acidosis (MILA) remain controversial entities. Metformin toxic effect depends on accumulation to lead to lactic acidosis (LA), particularly during an episode of acute kidney injury (AKI). In MILA, no other condition contributing to LA is found. The aims of this study were to describe the characteristics and prognosis of AKI associated with LA in metformin users and to clarify the role of this drug in the different types of LA.Methods: We performed a French multicenter retrospective study in diabetic patients treated by metformin presenting with LA in a context of AKI in 2015. 126 nephrology units (NU) and 23 intensive care units (ICU) were contacted. We individualized MILA and MALA patients in order to illustrate the role of metformin.Results: We included 173 patients (109 MILA, 64 MALA). 103 patients presented without hemodynamic instability (82 MILA and 21 MALA) whereas 70 patients were shocked including 27 MILA. The shock was associated with death with an odds ratio (OR) of 12.92 (p < .001). Digestive disorders (DD) were strongly associated with MILA (p = .0001). MALA was significantly associated with shock (p < .0001). The mortality rate was higher in MALA (26%) when compared with MILA (7%). Dialysis performed in 133 patients was significantly associated with shock, kalemia, lactate and serum creatinine levels. In multivariate analysis, metformin level was independently associated with pH or lactate level only in MILA patients.Conclusions: MILA is associated with DD and death is due to severe refractory acidosis leading to cardiovascular collapse attributed to metformin accumulation mainly via AKI. MALA patients are more frequently shocked and death is related to their underlying condition, metformin accumulation increasing LA.
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Acidosis Láctica/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Lesión Renal Aguda/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Metformina/sangre , Persona de Mediana Edad , Terapia de Reemplazo Renal , Estudios RetrospectivosRESUMEN
Double filtration plasmapheresis (DFPP) could be an alternative method to simple plasma exchange plasmapheresis in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP). In a retrospective single center case series, we studied clinical presentation, management care, and prognosis of aTTP patients from our academic center treated with DFPP and IV infusion of fresh frozen plasma (FFP) between 2009 and 2018. Nine patients were included for 11 episodes. Median age was 38 years old (IQR 26-53) with 78% women. Six episodes (55%) required admission to the ICU, four of which required mechanical ventilation. Median FFP volume transfused was 35.2 mL/kg/d of session. Response was complete for nine episodes (82%). Four patients presented an early relapse, two a late relapse. Four patients died: one had an active untreated HCV infection, and two were over 80-year-old polymorbid patients. DFPP seems to be an efficient method of therapeutic plasmapheresis in TTP when combined with FFP transfusion and immunosuppressive treatments.
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Transfusión Sanguínea/métodos , Inmunosupresores/uso terapéutico , Intercambio Plasmático , Plasma , Plasmaféresis , Púrpura Trombocitopénica Trombótica , Proteína ADAMTS13/sangre , Adulto , Transfusión Sanguínea/estadística & datos numéricos , Cuidados Críticos/métodos , Cuidados Críticos/estadística & datos numéricos , Femenino , Francia/epidemiología , Humanos , Masculino , Intercambio Plasmático/métodos , Intercambio Plasmático/estadística & datos numéricos , Plasmaféresis/métodos , Plasmaféresis/estadística & datos numéricos , Pronóstico , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/mortalidad , Púrpura Trombocitopénica Trombótica/fisiopatología , Púrpura Trombocitopénica Trombótica/terapia , Recurrencia , Estudios RetrospectivosRESUMEN
We report three original cases of sclerosing encapsulating peritonitis (SEP) which is a rare but severe complication of peritoneal dialysis (PD). In the report of case 1, SEP occurred in a 75-year-old diabetic patient mellitus 18 years after the arrest of PD technique recurrent infectious peritonitis. The switch to hemodialysis was associated with a chronic inflammatory state poorly explained until the discovery of SEP. For case 2, SEP started within seven months after automated PD initiation in a severe septic context leading to leg amputation in a 57-year-old unstable diabetic male. In the last case, 84-year-old woman presented SEP after several peritonitis episodes, including one due to acute pancreatitis. In all cases, SEP was confirmed by open surgery. All patients were treated by visceralysis. The outcome was favorable in two of these three patients. SEP mechanisms, risks factors, prognosis and treatment are discussed with reference to the literature.
Asunto(s)
Diálisis Peritoneal/efectos adversos , Peritonitis/etiología , Enfermedad Aguda , Antagonistas Adrenérgicos beta/efectos adversos , Anciano , Anciano de 80 o más Años , Terapia Combinada , Comorbilidad , Diabetes Mellitus Tipo 2/complicaciones , Resultado Fatal , Humanos , Intestinos/patología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Pancreatitis/complicaciones , Peritonitis/diagnóstico , Peritonitis/microbiología , Peritonitis/patología , Peritonitis/terapia , Complicaciones Posoperatorias , Recurrencia , Factores de Riesgo , Esclerosis/etiología , Esclerosis/patologíaRESUMEN
Purification of recombinant proteins remains a bottleneck for downstream processing. The authors engineered a new galectin 3 truncated form (CRDSAT ), functionally and structurally characterized, with preserved solubility and lectinic activity. Taking advantage of these properties, the authors designed an expression vector (pCARGHO), suitable for CRDSAT -tagged protein expression in prokaryotes. CRDSAT binds to lactose-Sepharose with a high specificity and facilitates solubilization of fusion proteins. This tag is structurally stable and can be easily removed from fusion proteins using TEV protease. Furthermore, due to their basic isoelectric point (pI), CRDSAT , and TEV are efficiently eliminated using cationic exchange chromatography. When pI of the protein of interest (POI) and CRDSAT are close, other chromatographic methods are successfully tested. Using CRDSAT tag, the authors purified several proteins from prokaryote and eukaryote origin and demonstrated as examples, the preservation of both Escherichia coli Thioredoxin 1 and human CDC25Bcd activities. Overall, yields of proteins obtained after tag removal are about 5-50 mg per litre of bacterial culture. Our purification method displays various advantages described herein that may greatly interest academic laboratories, biotechnology, and pharmaceutical companies.
Asunto(s)
Galectina 3/química , Proteínas Recombinantes/química , Tiorredoxinas/química , Fosfatasas cdc25/química , Cromatografía por Intercambio Iónico/métodos , Endopeptidasas/química , Escherichia coli/genética , Galectina 3/genética , Regulación de la Expresión Génica/genética , Vectores Genéticos , Humanos , Lectinas/química , Proteínas Recombinantes/genética , Solubilidad , Tiorredoxinas/genética , Tiorredoxinas/aislamiento & purificación , Fosfatasas cdc25/genética , Fosfatasas cdc25/aislamiento & purificaciónRESUMEN
BACKGROUND: KDIGO (Kidney Disease: Improving Global Outcomes) defines acute kidney injury (AKI) solely by serum creatinine (SCr) and urine output variation. Severe AKI is a syndrome covering various clinical situations. OBJECTIVE: To describe severe AKI heterogeneity by department of hospitalization. DESIGN: This is a prospective observational single-center study. SETTING: Adult patients hospitalized in a French tertiary hospital from August 2016 to December 2017. PATIENTS: All adults with severe AKI, defined by dialysis for AKI or an increase in SCr above 354 µmol/L. MEASUREMENTS: Patient characteristics, clinical and laboratory presentation, AKI cause, medical indication for renal replacement therapy (RRT), planned palliative care, and vital status 30 days after severe AKI. METHODS: A global description of patient characteristics, care, and prognosis and comparison by department of hospitalization: intensive care unit (ICU), nephrology, and others. RESULTS: The study included 480 patients (73% men, median age: 72 years, range: 64-83), with medical histories including cardiovascular disease, diabetes, cancer, and chronic kidney disease. Principal causes were sepsis (104; 22%), hypovolemia (98; 20%), obstructive AKI (84; 18%), acute tubular necrosis (ATN; 74; 15%), and cardiorenal syndrome (51; 11%). Severe AKI was diagnosed in the ICU for 188 (39%) patients, the nephrology department for 130 (27%), and in other wards for 162 (34%). Patient characteristics differed by department for age, comorbidity, cause, and RRT use and indications. Palliative care was planned for 72 (15%) patients, most frequently in other wards. LIMITATIONS: We studied a subgroup of stage 3 KDIGO AKI patients in a single center without cardiac surgery. CONCLUSION: Patients hospitalized for severe AKI have frequent and various comorbidities, different clinical presentations, care, hospitalization in various departments, and different prognosis. The heterogeneity of this severe AKI implies the need for personalized care, which requires prognostic tools that include information besides SCr and diuresis.
CONTEXTE: Le KDIGO définit l'insuffisance rénale aigüe (IRA) uniquement par une variation de la créatinine sérique (SCr) et de la diurèse. L'IRA grave est un syndrome couvrant diverses situations cliniques. OBJECTIF: Décrire l'hétérogénéité de l'IRA grave selon l'unité d'hospitalisation. TYPE D'ÉTUDE: Étude observationnelle prospective menée dans un seul centre. SUJETS: Des adultes hospitalisés entre août 2016 et décembre 2017 dans un centre de soins tertiaires en France. PARTICIPANTS: Tous les adultes atteints d'IRA grave, définie par un traitement de dialyse ou un taux de SCr au-delà de 354 µmol/l. MESURES: Les caractéristiques du patient, le tableau clinique et de laboratoire, l'étiologie de l'IRA, l'indication médicale pour une thérapie de remplacement rénal (TRR), le plan de soins palliatifs et le statut vital 30 jours après l'épisode d'IRA grave. MÉTHODOLOGIE: Une description globale des caractéristiques des patients, des soins et du pronostic, ainsi qu'une comparaison selon l'unité d'hospitalisation: unité de soins intensifs (USI), néphrologie et autres. RÉSULTATS: L'étude portait sur 480 patients (73 % d'hommes) âgés de 64 à 83 ans (âge médian: 72 ans) avec des antécédents incluant maladies cardiovasculaires, diabète, cancer ou insuffisance rénale chronique. Les principales causes de l'IRA grave étaient une septicémie (104, 22 %), une hypovolémie (98, 20 %), une IRA obstructive (84, 18 %), une nécrose tubulaire aigüe (74, 15 %) ou un syndrome cardio-rénal (51, 11 %). Le diagnostic avait été posé à l'USI pour 188 patients (39 %), en néphrologie pour 130 patients (27 %) et dans d'autres unités pour 162 patients (34 %). Les caractéristiques des patients différaient entre les unités de soins en ce qui concerne l'âge, les comorbidités, l'étiologie et les indications de TRR. Un plan de soins palliatifs existait pour 72 patients (15 %), le plus souvent dans les autres unités. LIMITES: Nous avons étudié un sous-groupe de patients atteints d'IRA de stade 3 (classification KDIGO) dans un seul centre sans chirurgie cardiaque. CONCLUSION: Les patients hospitalisés pour une IRA grave présentent des comorbidités, des tableaux cliniques, des soins et des pronostics variés et sont admis dans différentes unités d'hospitalisation. Cette hétérogénéité de l'IRA grave met en relief le besoin de soins personnalisés qui nécessitent des outils pronostics basés sur des informations autres que la SCr et la diurèse.
RESUMEN
Biofilms are known to be responsible for chronic peritoneal dialysis (PD)-related infections. Such infections are still frequent among patients in PD. The aim of this study was to develop a new approach in the prevention of chronic PD-related infection by regular injection of specific formulations containing detachment-promoting agents. A biofilm reactor system reproducing PD-like operating conditions was developed. A first set of experiments allowed the assessment of the anti-biofilm efficacy of various formulations. Then, experiments were performed for a longer duration and selected formulations were tested and compared with taurolidine. Biofilm removal was quantified by calculating the percentage of coverage reduction compared with an untreated control. A regular weekly treatment led to a 97% reduction of the surface coverage although a daily treatment with taurolidine still left 48% of the biomass on the surface. Such treatment is recommended to reduce the frequencies of chronic PD-related infections.