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1.
Int J Mol Sci ; 25(12)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38928186

RESUMEN

The inflammasome regulates the innate inflammatory response and is involved in autoimmune diseases. In this study, we explored the levels of IL-18 and IL-1ß in serum and urine and the influence of various single-nucleotide polymorphisms (SNPs) on kidney lesions at diagnosis in patients with ANCA-associated vasculitis (AAV) and their clinical outcomes. Ninety-two patients with renal AAV were recruited, and blood and urine were collected at diagnosis. Serum and urine cytokine levels were measured by ELISA. DNA was extracted and genotyped using TaqMan assays for SNPs in several inflammasome genes. Lower serum IL-18 (p = 0.049) and the IL-18 rs187238 G-carrier genotype (p = 0.042) were associated with severe fibrosis. The IL-18 rs1946518 TT genotype was associated with an increased risk of relapse (p = 0.05), whereas GG was related to better renal outcomes (p = 0.031). The rs187238 GG genotype was identified as a risk factor for mortality within the first year after AAV diagnosis, independent of the requirement for dialysis or lung involvement (p = 0.013). We suggest that decreased cytokine levels could be a surrogate marker of scarring and chronicity of the renal lesions, together with the rs187238 GG genotype. If our results are validated, the rs1946518 TT genotype predicts the risk of relapse and renal outcomes during follow-up.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Inflamasomas , Interleucina-18 , Interleucina-1beta , Polimorfismo de Nucleótido Simple , Humanos , Interleucina-18/genética , Interleucina-18/sangre , Masculino , Femenino , Inflamasomas/genética , Persona de Mediana Edad , Interleucina-1beta/genética , Interleucina-1beta/sangre , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/genética , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Anciano , Riñón/patología , Riñón/metabolismo , Genotipo , Adulto , Proteína con Dominio Pirina 3 de la Familia NLR/genética
2.
J Transl Med ; 22(1): 421, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702780

RESUMEN

INTRODUCTION: Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2-5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients. METHODS: Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression. RESULTS: Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity. CONCLUSIONS: Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.


Asunto(s)
Quimiocina CCL2 , Cisplatino , Inhibidores de Puntos de Control Inmunológico , Ratones Endogámicos C57BL , Nefritis Intersticial , Receptor de Muerte Celular Programada 1 , Animales , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/farmacología , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Nefritis Intersticial/orina , Nefritis Intersticial/patología , Nefritis Intersticial/inducido químicamente , Quimiocina CCL2/orina , Quimiocina CCL2/metabolismo , Cisplatino/efectos adversos , Humanos , Masculino , Femenino , Glomérulos Renales/patología , Glomérulos Renales/efectos de los fármacos , Antígeno B7-H1/metabolismo , Ratones , Persona de Mediana Edad , Anciano , Enfermedad Aguda
3.
Mol Cancer Ther ; 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38670552

RESUMEN

Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC is highly aggressive and limited therapeutic options lead to poor prognosis for patients. HPN328 is a tri-specific T cell activating construct (TriTAC) consisting of three binding domains: a CD3 binder for T cell engagement, an albumin binder for half-life extension, and a DLL3 binder for tumor cell engagement. In vitro assays, rodent models and non-human primates were used to assess the activity of HPN328. HPN328 induces potent dose-dependent killing of DLL3-expressing SCLC cell lines in vitro concomitant with T cell activation and cytokine release. In an NCI-H82 xenograft model with established tumors, HPN328 treatment led to T cell recruitment and anti-tumor activity. In an immunocompetent mouse model expressing a human CD3ε epitope, mice previously treated with HPN328 withstood tumor rechallenge, demonstrating long-term anti-tumor immunity. When repeat doses were administered to cynomolgus monkeys, HPN328 was well tolerated up to 10 mg/kg. Pharmacodynamic changes, such as transient cytokine elevation, were observed, consistent with the expected mechanism of action of T cell engagers. HPN328 exhibited linear pharmacokinetic in the given dose range with a serum half-life of 78 to 187 hours, supporting weekly or less frequent administration of HPN328 in humans. Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3 expressing malignancies.

4.
Kidney Int ; 106(1): 67-84, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38428734

RESUMEN

Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS.


Asunto(s)
Glomeruloesclerosis Focal y Segmentaria , Receptores de Hialuranos , Factor Estimulante de Colonias de Macrófagos , Podocitos , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Glomeruloesclerosis Focal y Segmentaria/genética , Animales , Humanos , Podocitos/metabolismo , Podocitos/patología , Factor Estimulante de Colonias de Macrófagos/metabolismo , Factor Estimulante de Colonias de Macrófagos/genética , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/genética , Ratones , Proliferación Celular/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Células Epiteliales/efectos de los fármacos , Receptor de Factor Estimulante de Colonias de Macrófagos/metabolismo , Receptor de Factor Estimulante de Colonias de Macrófagos/genética , Glomérulos Renales/patología , Glomérulos Renales/metabolismo , Masculino , Modelos Animales de Enfermedad , Células Cultivadas , Femenino , Regulación hacia Arriba , Movimiento Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal , Ratones Endogámicos C57BL , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos
5.
PLoS One ; 18(12): e0288012, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38117794

RESUMEN

School engagement is considered an effective college dropout antidote; therefore, understanding the construct, its underpinnings, and its effects remains critical for scholars. Although several scholars have offered multiple scales to measure engagement, their use has been hindered by significant limitations. This study sought to develop a scale to measure academic engagement by unifying and improving existing work and theories that resulted in a three-dimensional measurement model (behavioral, emotional, and cognitive). The items included were validated by a group of experts who ensured that the wording of the items captured the uniqueness of the college experience. A sample of 992 Mexican college students was used to test the fit of a second-order three-dimensional factor model of school engagement. The sample was randomly split in two for model cross-validation. Confirmatory factor analyses confirmed that student engagement is a three-dimensional construct, with evidence that supports the hypothesized second-order engagement factor structure (behavioral, emotional, and cognitive). The stability of these models was confirmed by using an independent sample. Measurement invariance by gender was found in this model. Then, differences in latent factor means were analyzed. Finally, the scale showed discriminant and concurrent validity. These results indicate that the scale is theoretically and psychometrically grounded for measuring college students' school engagement.


Asunto(s)
Instituciones Académicas , Estudiantes , Humanos , Psicometría , Estudiantes/psicología , Universidades , Emociones , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
6.
Rev Esc Enferm USP ; 57(spe): e20230024, 2023.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37819676

RESUMEN

OBJECTIVE: To describe the construction process of an intercultural care program for international migrants in northwestern Mexico. METHOD: Report of professional experiences, according to what was suggested by Daltro and Faria. RESULTS: The development and evolution of care for international migrants has favored the elaboration of a community-like Social Service Program for students of a public university in northwestern Mexico, so that intercultural health and health care for this population become part of the curricular training of the new generations of nursing graduates, in a context in which international migration is a topic of great social and cultural relevance. CONCLUSION: The construction and application of the Salud-Migrante program will enhance compliance with international recommendations on universal health for migrants, promoting respect for identity and cultural diversity in their actions.


Asunto(s)
Migrantes , Humanos , México , Atención a la Salud
7.
Glob Public Health ; 18(1): 2267632, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-37820047

RESUMEN

Prevention capacity of local health organisations is associated with the performance and outcomes in public health. In Colombia, where cardiovascular disease is the leading cause of morbidity and mortality, there is limited knowledge about the capacity of local health departments to prevent this condition. Efforts are needed to address problems, potential solutions and expected outcomes regarding cardiovascular disease. In this study, a conceptual model for cardiovascular disease prevention capacity in Colombian local health departments was developed, a questionnaire based on this model was validated, the overall cardiovascular disease prevention capacity in a subsample of these organisations was measured, and the association between cardiovascular disease prevention capacity and political, population, and organisational factors was examined. Once the acceptable performance of the questionnaire was verified, variability in cardiovascular prevention capacity was found among a subsample of local health departments. Furthermore, this study provides primary evidence regarding the association between the size of local health departments and overall cardiovascular disease prevention capacity in Colombia. Future studies should focus on measuring this capacity on a larger scale and developing, implementing, and evaluating interventions aimed at strengthening cardiovascular prevention capacity in Colombian local jurisdictions.


Asunto(s)
Enfermedades Cardiovasculares , Humanos , Colombia , Enfermedades Cardiovasculares/prevención & control , Salud Pública , Encuestas y Cuestionarios
8.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1535916

RESUMEN

Within the broad range of therapeutic options for managing functional gastrointestinal disorders, recently redefined as Disorders of Gut-Brain Interaction (DGBI) by the Rome Foundation in the Rome IV criteria, certain medications with antidepressant, anxiolytic, or antipsychotic effects are commonly employed. These drugs, now referred to as neuromodulators by the Rome Foundation, target the neurogastroenterological dysfunction associated with these disorders. Consequently, their clinical utility as psychiatric medications can now be leveraged to benefit patients with DGBI. This narrative review aims to provide an updated and specific overview of the indications for neuromodulators in the primary DGBI. The first section of this review focuses on the rationale and justification for their use.


En el amplio espectro de las opciones terapéuticas para el manejo de los trastornos funcionales digestivos, que se han redefinido por la Fundación Roma en los criterios Roma IV como trastornos de la interacción cerebro-intestino (TICI), algunos medicamentos con efectos antidepresivos, ansiolíticos o antipsicóticos se utilizan con mayor frecuencia. Estos medicamentos, que actúan en la disfunción neurogastroenterológica de estos trastornos, también han sido renombrados por la Fundación Roma como neuromoduladores, para que ahora puedan aprovecharse sus beneficios terapéuticos en este ámbito clínico, debido a su utilización como medicamentos psiquiátricos. Esta revisión narrativa tiene por objeto actualizar y precisar las indicaciones de los neuromoduladores en los principales TICI, y en esta primera sección se aborda la racionalidad y justificación para su utilización.

9.
Top Curr Chem (Cham) ; 381(4): 15, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37160833

RESUMEN

Hydrogen peroxide is a powerful and green oxidant that allows for the oxidation of a wide span of organic and inorganic substrates in liquid media under mild reaction conditions, and forms only molecular water and oxygen as end products. Hydrogen peroxide is therefore used in a wide range of applications, for which the well-documented and established anthraquinone autoxidation process is by far the dominating production method at the industrial scale. As this method is highly energy consuming and environmentally costly, the search for more sustainable synthesis methods is of high interest. To this end, the article reviews the basis and the recent development of the photocatalytic synthesis of hydrogen peroxide. Different oxygen reduction and water oxidation mechanisms are discussed, as well as several kinetic models, and the influence of the main key reaction parameters is itemized. A large range of photocatalytic materials is reviewed, with emphasis on titania-based photocatalysts and on high-prospect graphitic carbon nitride-based systems that take advantage of advanced bulk and surface synthetic approaches. Strategies for enhancing the performances of solar-driven photocatalysts are reported, and the search for new, alternative, photocatalytic materials is detailed. Finally, the promise of in situ photocatalytic synthesis of hydrogen peroxide for water treatment and organic synthesis is described, as well as its coupling with enzymes and the direct in situ synthesis of other technical peroxides.


Asunto(s)
Peróxido de Hidrógeno , Oxígeno , Peróxidos , Industrias , Cinética
10.
Clin Kidney J ; 16(4): 693-700, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37007690

RESUMEN

Background: CD163 and calprotectin have been proposed as biomarkers of active renal vasculitis. This study aimed to determine whether the combination of serum/urine calprotectin (s/uCalprotectin) and urinary soluble CD163 (suCD163) increases their individual performance as activity biomarkers. Methods: We included 138 patients diagnosed with ANCA vasculitis (n = 52 diagnostic phase, n = 86 remission). The study population was divided into the inception (n = 101) and the validation cohorts (n = 37). We determined the s/uCalprotectin and suCD163 concentration using enzyme-linked immunoassay at the diagnostic or at the remission phase. Receiver operating characteristic (ROC) curves were conducted to assess the biomarkers' classificatory values. We elaborated a combinatorial biomarker model in the inception cohort. The ideal cutoffs were used in the validation cohort to confirm the model's accuracy in the distinction between active disease and remission. We added the classical ANCA vasculitis activity biomarkers to the model to increase the classificatory performance. Results: The concentrations of sCalprotectin and suCD163 were higher in the diagnostic compared with the remission phase (P = .013 and P < .0001). According to the ROC curves, sCalprotectin and suCD163 were accurate biomarkers to discern activity [area under the curve 0.73 (0.59-0.86), P = .015 and 0.88 (0.79-0.97), P < .0001]. The combinatory model with the best performance in terms of sensitivity, specificity and likelihood ratio included sCalprotectin, suCD163 and haematuria. Regarding the inception and the validation cohort, we obtained a sensitivity, specificity and likelihood ratio of 97%, 90% and 9.7, and 78%, 94% and 13, respectively. Conclusions: In patients with ANCA vasculitis, a predictive model combining sCalprotectin, suCD163 and haematuria could be useful in detecting active kidney disease.

11.
Curr Biol ; 33(6): R210-R214, 2023 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-36977378

RESUMEN

The plant cuticle is one of the key innovations that allowed plants to colonize terrestrial ecosystems. By limiting molecular diffusion, the cuticle provides an interface that ensures controlled interactions between plant surfaces and their environments. It confers diverse and sometimes astonishing properties upon plant surfaces at both the molecular level (from water and nutrient exchange capacities to almost complete impermeability), to the macroscopic level (from water repellence to iridescence). It takes the form of a continuous modification of the outer cell wall of the plant epidermis from early in plant development (surrounding the epidermis of the developing plant embryo) and is actively maintained and modified throughout the growth and development of most plant aerial organs - including non-woody stems, flowers, leaves, and even the root cap of emerging primary and lateral roots. The cuticle was first identified as a distinct structure in the early 19th century, and has since been the focus of intense research that, while revealing the fundamental role of the cuticle in the life of terrestrial plants, has also highlighted many unresolved mysteries regarding cuticle biogenesis and structure.


Asunto(s)
Ecosistema , Plantas , Hojas de la Planta , Flores , Agua , Epidermis de la Planta
12.
Rev. Esc. Enferm. USP ; 57(spe): e20230024, 2023.
Artículo en Inglés, Español | LILACS, BDENF - Enfermería | ID: biblio-1514782

RESUMEN

ABSTRACT Objective: To describe the construction process of an intercultural care program for international migrants in northwestern Mexico. Method: Report of professional experiences, according to what was suggested by Daltro and Faria. Results: The development and evolution of care for international migrants has favored the elaboration of a community-like Social Service Program for students of a public university in northwestern Mexico, so that intercultural health and health care for this population become part of the curricular training of the new generations of nursing graduates, in a context in which international migration is a topic of great social and cultural relevance. Conclusion: The construction and application of the Salud-Migrante program will enhance compliance with international recommendations on universal health for migrants, promoting respect for identity and cultural diversity in their actions.


RESUMO Objetivo: Descrever o processo de construção de um programa de atendimento intercultural para migrantes internacionais no noroeste do México. Método: Relato de experiências profissionais, conforme sugerido por Daltro e Faria. Resultados: O desenvolvimento e a evolução do atendimento aos migrantes internacionais favoreceu a estruturação de um Programa de Serviço Social de tipo comunitário para estudantes de uma universidade pública do noroeste do México, de modo que a saúde intercultural e a atenção à saúde dessa população tornem-se parte da formação curricular do novas gerações de graduados em enfermagem, em um contexto em que a migração internacional é um tema de grande relevância social e cultural. Conclusão: A construção e aplicação do programa Salud-Migrante fortalecerá o cumprimento das recomendações internacionais sobre saúde universal para migrantes, promovendo o respeito à identidade e à diversidade cultural em suas ações.


RESUMEN Objetivo: Describir el proceso de construcción de un programa de cuidado intercultural a personas migrantes internacionales en el noroeste de México. Método: Relato de experiencias profesionales, acorde a lo sugerido por Daltro y Faria. Resultados: El desarrollo y evolución del cuidado a personas migrantes internacionales ha favorecido la estructuración de un Programa de Servicio Social de tipo comunitario para estudiantes de una universidad pública en el noroeste de México, por lo que la salud intercultural y el cuidado a la salud a esta población se vuelve parte en la formación curricular de las nuevas generaciones de licenciados en enfermería, en un contexto en que la migración internacional es tema de gran relevancia social y cultural. Conclusión: La construcción y aplicación del programa Salud-Migrante fortalecerán el cumplimiento de las recomendaciones internacionales en materia de salud universal para personas migrantes, promoviendo en sus acciones el respeto a la identidad y diversidad cultural.


Asunto(s)
Emigrantes e Inmigrantes , Asistencia Sanitaria Culturalmente Competente , Competencia Cultural , Atención de Enfermería
13.
J Clin Med ; 11(13)2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35806939

RESUMEN

With the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), studies are describing cases of glomerulonephritis arising after vaccination. We present the first case of a kidney transplant patient who, after mRNA vaccination against SARS-CoV-2, developed nephrotic proteinuria and renal dysfunction, with a biopsy diagnostic of collapsing glomerulonephritis. No other triggers for this glomerulonephritis were identified. Antibodies against the spike protein were negative, but the patient developed a specific T-cell response. The close time between vaccination and the proteinuria suggests a possible determinant role of vaccination. We should be aware of nephropathies appearing after COVID-19 vaccination in kidney transplant recipients also.

14.
Nephron ; 146(6): 564-572, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35640535

RESUMEN

mRNA-based vaccines have dramatically shifted the course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. IgA nephropathy (IgAN) flare is the most reported renal adverse effect after the administration of these vaccines. Unraveling the mechanistic pathways leading to these flares is necessary to confirm a causal association. Herein, we report 2 cases of IgAN flare after SARS-CoV-2 vaccination in patients previously diagnosed with IgAN. We describe and compare the clinical and analytical features of the disease at the time of the diagnostic with the post-vaccine flare. In addition, we obtained serum and urine of these patients at the moment of the flare and determined the levels of IL-2, TNF-α, and IFNγ using a multiplex bead-based assay. As diseased controls, we included n = 13 patients diagnosed with IgAN who had available serum and urine samples at the moment of the diagnostic stored in our biobank. We also included 6 healthy controls. Compared to the first episode, postvaccination flares were more severe in terms of peak serum creatinine, albuminuria, and urinary erythrocyte count. The histological lesions found at the biopsy performed during the post-vaccine flare were similar to those found at the diagnostic. One of the patients who suffered a post-vaccine flare showed increased serum IL-2 and TNFα compared to the IgAN-diseased controls and the healthy controls. In conclusion, although several cases of post-vaccine IgAN flares have been reported, there are no mechanistic studies on the occurrence of these flares. We here suggest that hyperactivation of the Th1 pathway may be involved, but larger studies with more refined methods for numerical and functional Th1 lymphocytes evaluation are required.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/efectos adversos , ARN Mensajero , Citocinas , Interleucina-2 , SARS-CoV-2
15.
Int J Mol Sci ; 23(8)2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35457026

RESUMEN

The inflammasome is an immune multiprotein complex that activates pro-caspase 1 in response to inflammation-inducing stimuli and it leads to IL-1ß and IL-18 proinflammatory cytokine production. NLRP1 and NLRP3 inflammasomes are the best characterized and they have been related to several autoimmune diseases. It is well known that the kidney expresses inflammasome genes, which can influence the development of some glomerulonephritis, such as lupus nephritis, ANCA glomerulonephritis, IgA nephropathy and anti-GBM nephropathy. Polymorphisms of these genes have also been described to play a role in autoimmune and kidney diseases. In this review, we describe the main characteristics, activation mechanisms, regulation and functions of the different inflammasomes. Moreover, we discuss the latest findings about the role of the inflammasome in several glomerulonephritis from three different points of view: in vitro, animal and human studies.


Asunto(s)
Glomerulonefritis , Inflamasomas , Animales , Caspasa 1 , Femenino , Glomerulonefritis/genética , Humanos , Inflamación , Interleucina-1beta , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/genética
16.
Kidney360 ; 3(2): 293-306, 2022 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-35373130

RESUMEN

Background: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN. Methods: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use. Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P<0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR. Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Lesión Renal Aguda/complicaciones , COVID-19/epidemiología , Estudios de Seguimiento , Humanos , Sistema de Registros , SARS-CoV-2
17.
Nephron ; 146(2): 121-137, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34915506

RESUMEN

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens, proteinase 3 (PR3), and myeloperoxidase (MPO), typically involves small blood vessels of the respiratory tract and kidneys. It includes distinct clinical syndromes: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA. GPA is commonly associated with PR3-ANCA, while MPA is associated with MPO-ANCA. AAVs have a complex pathogenesis, influenced by genetics and environmental factors. There is evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation and injury, with effector T cells and activation of the alternative pathway of the complement also involved. Advances in immunosuppressive treatment have drastically reduced mortality of AAV in the past decades, opting for a more individualized approach. Careful assessment of ANCA specificity, disease activity, organ damage, and quality of life allows for a tailored immunosuppressive therapy. Contemporary AAV treatment is characterized by regimens that minimize the cumulative exposure to glucocorticoids and cyclophosphamide, and novel approaches including complement blockage and immunosuppressant combinations might be the standard of care in the future. In this review, we examine the pathogenesis, clinical approach, and evidence-based treatment options for the management of AAV patients.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Granulomatosis con Poliangitis , Anticuerpos Anticitoplasma de Neutrófilos , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Humanos , Mieloblastina , Calidad de Vida
18.
J Clin Med ; 10(13)2021 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-34279469

RESUMEN

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) diagnosis lays on histological assessment through a kidney biopsy, given the absence of accurate non-invasive biomarkers. The aim of this study was to evaluate the accuracy of different urinary inflammation-related cytokines for the diagnostic of ATIN and its distinction from acute tubular necrosis (ATN). METHODS: We included 33 patients (ATIN (n = 21), ATN (n = 12)), and 6 healthy controls (HC). We determined the urinary levels of 10 inflammation-related cytokines using a multiplex bead-based Luminex assay at the time of biopsy and after therapy, and registered main clinical, analytical and histological data. RESULTS: At the time of biopsy, urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFα and MCP-1 were significantly higher in ATIN compared to HC. A positive correlation between the extent of the tubulointerstitial cellular infiltrates in kidney biopsies and the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10, IL17, IFNα, MCP1 and EGF was observed. Notably, I-TAC/CXCL11, IL-6 and MCP-1 were significantly higher in ATIN than in ATN, with I-TAC/CXCL11 as the best discriminative classifier AUC (0.77, 95% CI 0.57-0.95, p = 0.02). A combinatory model of these three urinary cytokines increased the accuracy in the distinction of ATIN/ATN compared to the individual biomarkers. The best model resulted when combining the three cytokines with blood eosinophil and urinary leukocyte counts (LR = 9.76). Follow-up samples from 11ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/CXCL9 and CXCL10 levels. CONCLUSIONS: Urinary I-TAC/CXCL11, CXCL10, IL6 and MCP-1 levels accurately distinguish patients developing ATIN from ATN and healthy individuals and may serve as novel non-invasive biomarkers in this disease.

19.
Enferm. clín. (Ed. impr.) ; 31(3): 148-155, May-Jun. 2021. tab
Artículo en Español | IBECS | ID: ibc-220576

RESUMEN

Objetivo: Determinar la relación entre el apoyo social en redes sociales y factores de riesgo de sobrepeso u obesidad, tomando en cuenta estilos de vida saludable y barreras percibidas en adolescentes. Método: Estudio descriptivo y correlacional de corte transversal con adolescentes de una preparatoria pública de Nuevo León, México. Se realizaron mediciones antropométricas para obtener el índice de masa corporal, conductuales para barreras percibidas en alimentación saludable y actividad física, además de estilos de vida saludables. Resultados: Participaron 188 adolescentes, predominó el sexo masculino con 55,9%. La edad media fue de 16,1 años. El 52,1% tuvo sobrepeso, menos de la mitad de los adolescentes reportó contar con sus amigos en redes sociales (37,8%). El 52% de los participantes con exceso de peso necesita cambios en su alimentación y la mayoría reportó actividad física baja (82,7%). Se observa una correlación entre apoyo social en redes sociales y barreras percibidas de actividad física en adolescentes con exceso de peso (r2 0,144; p < 0,05). Conclusiones: La mayoría de los adolescentes no llevan una dieta adecuada ni realizan actividad física recomendada, una de las principales causas es la falta de motivación como barrera percibida. Las redes sociales constituyen una herramienta para que el personal de enfermería coadyuve en la promoción de la salud y lleve a cabo intervenciones dirigidas a prevenir la enfermedad en un contexto global en transición hacia lo digital.(AU)


Aim: To determine the relationship between social support in social networks and risk factors of overweight and obesity including healthy lifestyles and perceived barriers in adolescents. Method: Descriptive and cross-sectional study with adolescents from a public high school in Nuevo León, Mexico. Anthropometric measurements were determined to obtain body mass index, behavioural measurements for perceived barriers to healthy eating and physical activity, as well as healthy lifestyles. Results: A total of 188 adolescents participated, male sex predominated at 55.9%, mean age was 16.1 years. From them, 52.1% were overweight, less than half of the adolescents reported having friends on social networks (37.8%); 52% of overweight participants need changes in their diet and the majority reported low physical activity (82.7%). There is a correlation between social support in social networks and perceived barriers to physical activity in overweight adolescents (r2 0.144; p < 0.05). Conclusions: Most of the adolescents do not have an adequate diet or perform recommended physical activity, one of the main causes is lack of motivation as a perceived barrier. Social networks represent a tool for nursing staff to promote health and develop interventions aimed at preventing disease in a global context in digital transition.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Conducta del Adolescente , Factores de Riesgo , Red Social , Apoyo Social , Sobrepeso , Obesidad , México , Estudios Transversales , Epidemiología Descriptiva
20.
Int J Pharm ; 603: 120695, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33984454

RESUMEN

The antimicrobial lysozyme (Lys) was electrostatically incorporated to negatively charged crosslinked poly(glycidyl methacrylate) (c-PGMA) macromolecular assemblies. The resulting material was characterized by AFM, infrared spectra, water contact angle measurements and the staining with the primary amino specific dye fluorescamine. c-PGMA nanoparticles were successfully loaded with Lys reaching ratios of 27.3 ± 4.0 and 22.5 ± 1.7 mg Lys/g polymer for c-PGMA suspensions and functionalized glass substrates, respectively. Lys-loaded c-PGMA caused clear inhibition zones on S. aureus and E. coli in comparison to neat c-PGMA. c-PGMA functionalized surfaces were intrinsically resistant to colonization, but the incorporation of Lys added resistance to bacterial attachment and allowed keeping surfaces clean of bacterial cells for both strains. A relatively rapid release (24 h) of Lys was observed at physiological pH (7.4). In addition, c-PGMA functionalized substrates could be reloaded several times without losing capacity. c-PGMA macromolecular assemblies did not display cytotoxicity to human dermal fibroblasts as shown in 24 h MTT assays. This work demonstrated that c-PGMA assemblies display durable antibacterial activity, biocompatibility, and full reloading capacity with antimicrobial peptides. c-PGMA functionalized materials have potential application as nanocarriers for anti-infective uses.


Asunto(s)
Muramidasa , Staphylococcus aureus , Antibacterianos/farmacología , Escherichia coli , Humanos , Ácidos Polimetacrílicos
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