RESUMEN
Renal iron overload is a common complication of diabetes that leads to oxidative stress and mitochondrial dysfunction in the kidneys. This study investigated the effects of iron chelation using deferiprone on mitochondrial dysfunction and oxidative stress in the renal cortex of a murine model of type 2 diabetes. Diabetic rats were treated with deferiprone (50 mg/kg BW) for 16 weeks. Our results show that iron chelation with deferiprone significantly increased the nuclear accumulation of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes. This led to enhanced antioxidant capacity, reduced production of reactive oxygen species, and improved mitochondrial bioenergetic function in diabetic rats. However, chronic iron chelation led to altered mitochondrial respiration and increased oxidative stress in non-diabetic rats. In conclusion, our findings suggest that iron chelation with deferiprone protects mitochondrial bioenergetics and mitigates oxidative stress in the renal cortex, involving the NRF2 pathway in type 2 diabetes.
RESUMEN
Introduction: Continuous Positive Airway Pressure (CPAP) constitutes the most effective treatment for Obstructive Sleep Apnea (OSA). Automatic titration systems (ATS) are predominantly used to achieve adaptation to the equipment. Home CPAP devices allow telemonitoring (TM) of the same parameters as those provided by ATS but with access to continuous usage data. Under this premise, we conducted a study on the potential validity of TM for home CPAP devices as a titration system, its direct impact on proper adaptation (AD) to the equipment, and secondarily on the healthcare resources employed to achieve it. Material and methods: An observational study involving 318 patients with OSA who were titrated using TM to achieve AD to CPAP. Patients with OSA were consecutively recruited and evaluated at 1, 3, and 6 months after initiating treatment. Results were compared with a historical group of 307 patients with OSA who achieved AD to CPAP using ATS. Additionally, we assessed the impact on required healthcare resources. Results: Patients with OSA who initiated CPAP treatment with TM over the first six months showed a similar AD rate compared to the historical group titrated using ATS, with lower resource usage in the TM group. Conclusion: Data provided by TM of home CPAP devices allow for titration and achieving similar AD as with ATS in non-complex patients.
RESUMEN
Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage.
Asunto(s)
Ceramidas , Nanopartículas del Metal , Ratas Wistar , Titanio , Óxido de Zinc , Animales , Óxido de Zinc/toxicidad , Titanio/toxicidad , Titanio/efectos adversos , Ratas , Ceramidas/metabolismo , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Masculino , Administración Oral , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patologíaRESUMEN
In this study, we investigated whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein may modify angiotensin-converting enzyme 2 (ACE2) activity in the plasma, heart, kidney, liver, lung, and six brain regions (amygdala, brain stem, cortex, hippocampus, hypothalamus, and striatum) of diabetic and hypertensive rats. We determine ACE2 activity in the plasma and lysates of heart, kidney, liver, lung, and six brain regions. MLN-4760 inhibits ACE2 activity in the plasma and all organs. On the other hand, soluble ACE2 (sACE2) activity increased in the plasma of diabetic rats, and there was no change in the plasma of hypertensive rats. ACE2 activity was augmented in the liver, brain stem, and striatum, while it decreased in the kidney, amygdala, cortex, and hippocampus of diabetic rats. ACE2 activity increased in the kidney, liver, and lung, while it decreased in the heart, amygdala, cortex, and hypothalamus of hypertensive rats. We measured the ACE2 content via enzyme-linked immunosorbent assay and found that ACE2 protein levels increased in the heart, while it decreased in the plasma, kidney, brain stem, cortex, hippocampus, hypothalamus, and striatum of diabetic rats. ACE2 protein levels decreased in the brain stem, cortex, hippocampus, and hypothalamus of hypertensive rats. Our data showed that the spike protein enhanced ACE2 activity in the liver and lungs of diabetic rats, as well as in the heart and three of the brain regions (cortex, hypothalamus, and striatum) of hypertensive rats.
Asunto(s)
Enzima Convertidora de Angiotensina 2 , Hipertensión , Glicoproteína de la Espiga del Coronavirus , Animales , Enzima Convertidora de Angiotensina 2/metabolismo , Ratas , Glicoproteína de la Espiga del Coronavirus/metabolismo , Masculino , Hipertensión/metabolismo , SARS-CoV-2 , Diabetes Mellitus Experimental/metabolismo , Encéfalo/metabolismo , Encéfalo/enzimología , COVID-19/metabolismo , COVID-19/virología , Carboxipeptidasas/metabolismo , Riñón/metabolismo , Riñón/enzimología , Humanos , Imidazoles , Leucina/análogos & derivadosRESUMEN
Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations.
Asunto(s)
Fibroblastos , Glucósidos , Mitocondrias , Enfermedades Mitocondriales , Niacinamida , Estilbenos , Respuesta de Proteína Desplegada , Humanos , Respuesta de Proteína Desplegada/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Estilbenos/farmacología , Glucósidos/farmacología , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/tratamiento farmacológico , Enfermedades Mitocondriales/genética , Niacinamida/farmacología , Mutación , Fenotipo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Neuronas/metabolismo , Neuronas/efectos de los fármacosRESUMEN
Hypertension is a major risk of morbidity and mortality in patients when it is uncontrolled. In spite of improved therapies currently available for blood pressure control, their complications are far away from being accomplished. Therefore, chronic renal failure is frequently observed in hypertensive patients. Thus, insights on mechanisms that may contribute to arterial pressure control should be studied to prevent life-threatening cardiovascular disorders. Purinergic receptors have been recognized in the physiopathology of hypertension; this review summarizes their participation in the renal abnormalities of the kidney in hypertension. Several studies have suggested the activation of renal purinergic receptors under an elevated interstitial ATP milieu as a fundamental pathway that leads to generation and maintained hypertension. Elevated ATP concentration alters fundamental mechanisms involved in the long-term control of blood pressure such as pressure natriuresis, autoregulation of glomerular filtration rate and renal blood flow, as well as increased tubule-glomerular feedback responses, overall, these alterations decrease sodium excretion; in addition, the expression of ATP receptors is modified. Under a genetical background, ATP induces the production of vasoactive compounds, decreases renal function and induces tubulointerstitial injury before glomerular damage. Simultaneously, a deleterious interaction between angiotensin II and purinergic receptors lead to the progression of renal damage.
La hipertensión arterial descontrolada es un factor de riesgo muy relevante para el desarrollo de complicaciones cardiovasculares graves. A pesar de los recursos disponibles en la actualidad, el control de la hipertensión arterial y sus complicaciones dista mucho de lograrse. Por ello, sus secuelas continúan siendo catastróficas, como la insuficiencia renal crónica. De ahí la relevancia de reconocer factores que pudieran modificarse para evitar esta complicación. Recientemente se ha propuesto que los receptores purinérgicos contribuyen en forma importante en las alteraciones renales que ocurren en la hipertensión arterial; en esta revisión se resume brevemente su papel. En varios estudios se ha demostrado que cuando existen concentraciones elevadas de ATP en el intersticio renal, la activación de los receptores purinérgicos constituye una vía fundamental en la generación y la persistencia de hipertensión arterial. Las concentraciones elevadas de ATP alteran mecanismos fundamentales asociados en el control de la presión arterial, como el mecanismo de natriuresis de presión, la autorregulación del flujo renal y la filtración glomerular, así como el aumento en la sensibilidad del mecanismo de retroalimentación tubuloglomerular. La alteración de estos mecanismos contribuye a la disminución de la excreción urinaria de sodio. Además, se modifica la expresión de receptores de ATP (purinérgicos). Bajo la influencia de alteraciones genéticas, el ATP estimula la producción de compuestos vasoactivos y en conjunto producen una disminución de la función renal y lesión tubulointersticial antes de que se lesione el glomérulo. Al mismo tiempo, la interacción de la angiotensina II y los receptores purinérgicos favorece la progresión del daño renal.
RESUMEN
Tuning the 8-anilino-1-naphthalenesulfonic acid (ANS) structure usually requires harsh conditions and long reaction times, which can result in low yields. Herein, ANS was modified to form an ANS group of uniform materials based on organic salts (GUMBOS), prepared with simple metathesis reactions and distinct cations, namely tetrabutylammonium (N4444), tetrahexylammonium (N6666), and tetrabutylphosphonium (P4444). These ANS-based GUMBOS were investigated as fluorescent probes for membrane binding studies with four proteins having distinct physicochemical properties. Liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine were employed as membrane models as a result of their ability to mimic the structure and chemical composition of cell membranes. Changes in fluorescence intensity were used to monitor protein binding to liposomes, and adsorption data were fitted to a Freundlich-like isotherm. It was determined that [N4444][ANS] and [P4444][ANS] GUMBOS have enhanced optical properties and lipophilicity as compared to parent ANS. As a result, these two GUMBOS were selected for subsequent protein-membrane binding studies. Both [N4444][ANS] and [P4444][ANS] GUMBOS and parent ANS independently reached membrane saturation within the same concentration range. Furthermore, distinct fluorescence responses were observed upon the addition of proteins to each probe, which demonstrates the impact of properties such as lipophilicity on the binding process. The relative maintenance of binding cooperativity and maximum fluorescence intensity suggests that proteins compete with ANS-based probes for the same membrane binding sites. Finally, this GUMBOS-based approach is simple, rapid, and involves relatively small amounts of reagents, making it attractive for high-throughput purposes. These results presented herein can also provide relevant information for designing GUMBOS with ameliorated properties.
Asunto(s)
Naftalenosulfonatos de Anilina , Liposomas , Unión Proteica , Naftalenosulfonatos de Anilina/química , Liposomas/química , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Materiales Biomiméticos/química , Sales (Química)/química , Compuestos de Amonio Cuaternario/químicaRESUMEN
High sodium intake is decisive in the incidence increase and prevalence of hypertension, which has an impact on skeletal muscle functionality. Diazoxide is an antihypertensive agent that inhibits insulin secretion and is an opener of KATP channels (adosine triphosphate sensitive potasium channels). For this reason, it is hypothesized that moderate-intensity exercise and diazoxide improve skeletal muscle function by reducing the oxidants in hypertensive rats. Male Wistar rats were assigned into eight groups: control (CTRL), diazoxide (DZX), exercise (EX), exercise + diazoxide (EX + DZX), hypertension (HTN), hypertension + diazoxide (HTN + DZX), hypertension + exercise (HTN + EX), and hypertension + exercise + diazoxide (HTN + EX + DZX). To induce hypertension, the rats received 8% NaCl dissolved in water orally for 30 days; in the following 8 weeks, 4% NaCl was supplied to maintain the pathology. The treatment with physical exercise of moderate intensity lasted 8 weeks. The administration dose of diazoxide was 35 mg/kg intraperitoneally for 14 days. Tension recording was performed on the extensor digitorum longus and the soleus muscle. Muscle homogenates were used to measure oxidants using fluorescent probe and the activity of antioxidant systems. Diazoxide and moderate-intensity exercise reduced oxidants and increased antioxidant defenses.
Asunto(s)
Antioxidantes , Diazóxido , Hipertensión , Músculo Esquelético , Condicionamiento Físico Animal , Ratas Wistar , Animales , Diazóxido/farmacología , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Hipertensión/metabolismo , Hipertensión/fisiopatología , Condicionamiento Físico Animal/fisiología , Ratas , Antioxidantes/metabolismo , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Oxidantes/metabolismoRESUMEN
Introducción: La esofagectomía es actualmente el tratamiento curativo del cáncer de esófago. El objetivo de este trabajo es conocer los resultados de la esofaguectomía mínimamente invasiva a corto y medio plazo en pacientes intervenidos de carcinoma epidermoide y adenocarcinoma de esófago en nuestro hospital. Material y Métodos: Se recogieron 19 pacientes desde enero de 2020 hasta junio de 2021 y se realizó el seguimiento a todos ellos durante 20 meses. Se recogieron diferentes variables relacionadas con el paciente, el tumor, la cirugía y referentes al postoperatorio. Los datos fueron almacenados y procesados usando el software estadístico R-Comander asumiendo un error α de 0,05. Resultados: La mediana de estancia hospitalaria total fue de 29 días. Seis pacientes, precisaron de reingreso en Reanimación: dos por shock séptico secundario a la fuga de anastomosis grado III, uno por hemorragia digestiva alta y los tres por insuficiencia respiratoria. A los 90 días reingresaron un 5,3% del total de pacientes. No se produjeron fallecimientos en los tres meses siguientes a la cirugía. Todos los pacientes presentaron una supervivencia mayor de seis meses. La supervivencia global a seis, 12 y 18 meses se sitúa en 100, 84 y 63%. La supervivencia libre de enfermedad a los tres meses fue del 84%, a los 6 meses del 63% y al año el 58%. Discusión: Los resultados obtenidos en nuestro estudio coinciden con lo que hay reflejado en la literatura. Por tanto, la esofagectomía mínimamente invasiva es una técnica efectiva en el tratamiento del cáncer de esófago.
Introduction: Oesophagectomy is currently the curative treatment for oesophageal cancer. The aim of this study is to know the results of minimally invasive oesophagectomy in the short and medium term in patients operated on for squamous cell carcinoma and adenocarcinoma of the oesophagus in our hospital. Material and Methods: 19 patients were collected from January 2020 to June 2021 and all of them were followed up for 20 months. Different variables related to the patient, tumour, surgery and postoperative period were collected. Data were stored and processed using R-Comander statistical software assuming an α-error of 0.05. Results: The median total hospital stay was 29 days. Six patients required readmission to resuscitation: two for septic shock secondary to grade III anastomotic leak, one for upper gastrointestinal haemorrhage and three for respiratory failure. At 90 days, 5.3% of the total number of patients were re-admitted. There were no deaths in the three months following surgery. All patients had a survival of more than six months. Overall survival at six, 12 and 18 months was 100, 84 and 63%. Disease-free survival at three months was 84%, at six months 63% and at one year 58%. Discussion: The results obtained in our study coincide with those reported in the literature. Minimally invasive oesophagectomy is therefore an effective technique in the treatment of oesophageal cancer.
RESUMEN
Objetivo: La transformación quística acinar del páncreas es una patología poco frecuente y que afecta en su mayoría a mujeres de mediana edad. Material y Métodos: Presentamos el caso de dicha patología en un varón joven que debutó con dolor en hipocondrio izquierdo y en la pruebas de imagen se evidenció una lesión quística en cola pancreática de 50x45mm, con calcificaciones lineales. Se realizó pancreatectomía distal. Resultados: El diagnóstico anatomopatológico informó de transformación quística acinar. Discusión: Dada la dificultad de un diagnóstico preoperatorio, es frecuente someter al paciente a una intervención quirúrgica con una elevada morbilidad, a pesar de tratarse de una lesión benigna, ya que se siguen las indicaciones quirúrgicas para otras patologías quísticas pancreáticas. La presencia de mutaciones y el hecho de que algunos de ellos también presentan cambios epiteliales mucinosos, justificaría el debatir la posibilidad de mantener a estos pacientes bajo vigilancia a largo plazo.
Objective: Acinar cystic transformation of the pancreas is a rare pathology that affects mostly middle-aged women. Material and Methods: We present a case of this pathology in a young man who presented with pain in the left hypochondrium and imaging tests revealed a cystic lesion in the pancreatic tail measuring 50x45mm, with linear calcifications. Distal pancreatectomy was performed. Results: The anatomopatho-logical diagnosis was acinar cystic transformation. Discussion: given the difficulty of a preoperative diagnosis, the patient is often subjected to surgery with high morbidity, despite being a benign lesion, as surgical indications for other pancreatic cystic pathologies are followed. The presence of mutations and the fact that some of them also present mucinous epithelial changes would justify discussing the possibility of keeping these patients under long-term surveillance.
RESUMEN
Traumatic nerve injuries are nowadays a significant clinical challenge and new substitutes with adequate biological and mechanical properties are in need. In this context, fibrin-agarose hydrogels (FA) have shown the possibility to generate tubular scaffolds with promising results for nerve repair. However, to be clinically viable, these scaffolds need to possess enhanced mechanical properties. In this line, genipin (GP) crosslinking has demonstrated to improve biomechanical properties with good biological properties compared to other crosslinkers. In this study, we evaluated the impact of different GP concentrations (0.05, 0.1 and 0.2% (m/v)) and reaction times (6, 12, 24, 72â¯h) on bioartificial nerve substitutes (BNS) consisting of nanostructured FA scaffolds. First, crosslinked BNS were studied histologically, ultrastructurally and biomechanically and then, its biocompatibility and immunomodulatory effects were ex vivo assessed with a macrophage cell line. Results showed that GP was able to improve the biomechanical resistance of BNS, which were dependent on both the GP treatment time and concentration without altering the structure. Moreover, biocompatibility analyses on macrophages confirmed high cell viability and a minimal reduction of their metabolic activity by WST-1. In addition, GP-crosslinked BNS effectively directed macrophage polarization from a pro-inflammatory (M1) towards a pro-regenerative (M2) phenotype, which was in line with the cytokines release profile. In conclusion, this study considers time and dose-dependent effects of GP in FA substitutes which exhibited increased biomechanical properties while reducing immunogenicity and promoting pro-regenerative macrophage shift. These tubular substitutes could be useful for nerve application or even other tissue engineering applications such as urethra.
Asunto(s)
Reactivos de Enlaces Cruzados , Iridoides , Macrófagos , Andamios del Tejido , Iridoides/farmacología , Animales , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Andamios del Tejido/química , Reactivos de Enlaces Cruzados/química , Reactivos de Enlaces Cruzados/farmacología , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Fenómenos Biomecánicos , Supervivencia Celular/efectos de los fármacos , Fibrina/metabolismo , Sefarosa/química , Sefarosa/farmacología , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Células RAW 264.7RESUMEN
BACKGROUND: Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis, caused by mutations in the ECM1 gene. This results in the deposition of periodic acid-Schiff (PAS)-positive, hyaline-like material on the skin, mucosae and internal organs. OBJECTIVES: To present a case report of LP and a systematic review to synthesize the scientific literature on the management of this uncommon and frequently missed diagnosis. METHODS: We present a case report of a 48-year-old man with LP who exhibited significant improvement after oral acitretin therapy. To address the lack of large case-control studies on LP treatment, we performed a systematic review of the literature following the PRISMA 2020 criteria. The search was conducted in PubMed, Web of Science, Cochrane and Scopus databases from inception until June 2023. To assess the methodological quality of case reports and case series, we used the Joanna Briggs Collaboration critical appraisal tool. RESULTS: We included 25 studies that met eligibility criteria. Data from 44 patients with a histopathologically confirmed diagnosis were analysed. Treatment ranged from systemic therapies (acitretin, etretinate, dimethyl sulfoxide, corticosteroids, penicillamine) to surgical or laser procedures. Regarding methodological quality, the main discrepancies arose in the reporting of participant characteristics and treatment interventions. CONCLUSIONS: Low-dose oral acitretin could have potential in managing LP, exhibiting fewer side-effects compared with other therapeutic agents. Further research is needed to establish more comprehensive and evidence-based treatment guidelines.
Asunto(s)
Acitretina , Proteinosis Lipoidea de Urbach y Wiethe , Humanos , Proteinosis Lipoidea de Urbach y Wiethe/genética , Proteinosis Lipoidea de Urbach y Wiethe/patología , Proteinosis Lipoidea de Urbach y Wiethe/tratamiento farmacológico , Proteinosis Lipoidea de Urbach y Wiethe/diagnóstico , Masculino , Acitretina/uso terapéutico , Persona de Mediana Edad , Queratolíticos/uso terapéutico , Resultado del TratamientoRESUMEN
Nitric oxide (NO) is a small vasodilator playing a key role in the pathogenesis of portal hypertension. Here, we assessed the potential therapeutic effect of a NO donor targeted to the liver by poly(beta-amino ester) nanoparticles (pBAE NPs) in experimental cirrhosis. Retinol-functionalized NO donor pBAE NPs (Ret pBAE NPs) were synthetized with the aim of actively targeting the liver. Administration of Ret pBAE NPs resulted in uptake and transfection by the liver and spleen. NPs were not found in other organs or the systemic circulation. Treatment with NO donor Ret pBAE NPs (30 mg/ kg body weight) significantly decreased aspartate aminotransferase, lactate dehydrogenase and portal pressure (9.75 ± 0.64 mmHg) compared to control NPs (13.4 ± 0.53 mmHg) in cirrhotic rats. There were no effects on mean arterial pressure and cardiac output. Liver-targeted NO donor NPs reduced collagen fibers and steatosis, activation of hepatic stellate cells and mRNA expression of profibrogenic and proinflammatory genes. Finally, Ret pBAE NPs displayed efficient transfection in human liver slices. Overall, liver-specific NO donor NPs effectively target the liver and mitigated inflammation and portal hypertension in cirrhotic rats. The use of Ret pBAE may prove to be an effective therapeutic strategy to treat advanced liver disease.
Asunto(s)
Hipertensión Portal , Cirrosis Hepática Experimental , Nanopartículas , Ratas , Humanos , Animales , Óxido Nítrico/metabolismo , Hígado , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática Experimental/metabolismo , Donantes de Óxido Nítrico/farmacología , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
Wearing masks to prevent infectious diseases, especially during the COVID-19 pandemic, is common. However, concerns arise about inhalation exposure to microplastics (MPs) when disposable masks are improperly reused. In this study, we assessed whether disposable masks release inhalable MPs when reused in simulated wearing conditions. All experiments were conducted using a controlled test chamber setup with a constant inspiratory flow. Commercially available medical masks with a three-layer material, composition comprising polypropylene (PP in the outer and middle layers) and polyethylene (PE in the inner layer), were used as the test material. Brand-new masks with and without hand rubbing, as well as reused medical masks, were tested. Physical properties (number, size, and shape) and chemical composition (polymers) were identified using various analytical techniques such as fluorescence staining, fluorescence microscopy, and micro-Fourier Transform Infrared Spectroscopy (µFTIR). Scanning Electron Microscopy (SEM) was used to scrutinize the surface structure of reused masks across different layers, elucidating the mechanism behind the MP generation. The findings revealed that brand-new masks subjected to hand rubbing exhibited a higher cumulative count of MPs, averaging approximately 1.5 times more than those without hand rubbing. Fragments remained the predominant shape across all selected size classes among the released MPs from reused masks, primarily through a physical abrasion mechanism, accounting for >90 % of the total MPs. The numbers of PE particles were higher than PP particles, indicating that the inner layer of the mask contributed more inhalable MPs than the middle and outer layers combined. The released MPs from reused masks reached their peak after 8 h of wearing. This implies that regularly replacing masks serves as a preventive measure and mitigates associated health risks of inhalation exposure to MPs.
Asunto(s)
Exposición por Inhalación , Contaminantes Químicos del Agua , Humanos , Exposición por Inhalación/prevención & control , Máscaras , Microplásticos , Pandemias , Plásticos , PolietilenoRESUMEN
The objective of this study was to investigate whether the activity of enzymes involved in sphingolipid catabolism could be biomarkers to predict early renal damage in streptozotocin (STZ)-induced diabetic rats and Angiotensin II (Ang II)-induced hypertension rats. Diabetic and hypertensive rats had no changes in plasma creatinine concentration. However, transmission electron microscopy (TEM) analysis showed slight ultrastructural changes in the glomeruli and tubular epithelial cells from diabetic and hypertensive rats. Our results show that the acid sphingomyelinase (aSMase) and neutral sphingomyelinase (nSMase) activity increased in the urine of diabetic rats and decreased in hypertensive rats. Only neutral ceramidase (nCDase) activity increased in the urine of diabetic rats. Furthermore, the immunofluorescence demonstrated positive staining for the nSMase, nCDase, and sphingosine kinase (SphK1) in glomerular mesangial cells, proximal tubule, ascending thin limb of the loop of Henle, thick ascending limb of Henle's loop, and principal cells of the collecting duct in the kidney. In conclusion, our results suggest that aSMase and nCDase activity in urine could be a novel predictor of early slight ultrastructural changes in the nephron, aSMase and nCDase as glomerular injury biomarkers, and nSMase as a tubular injury biomarker in diabetic and hypertensive rats.
Asunto(s)
Diabetes Mellitus Experimental , Hipertensión , Ratas , Animales , Esfingomielina Fosfodiesterasa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Riñón/metabolismo , Nefronas/metabolismo , EsfingolípidosRESUMEN
(1) Background: Previous studies have enriched high-density lipoproteins (HDL) using cholesteryl esters in rabbits with a three-quarter reduction in functional renal mass, suggesting that the kidneys participate in the cholesterol homeostasis of these lipoproteins. However, the possible role of the kidneys in lipoprotein metabolism is still controversial. To understand the role of the kidneys in regulating the HDL lipid content, we determined the turnover of HDL-cholesteryl esters in rabbits with a three-quarter renal mass reduction. (2) Methods: HDL subclass characterization was conducted, and the kinetics of plasma HDL-cholesteryl esters, labeled with tritium, were studied in rabbits with a 75% reduction in functional renal mass (Ntx). (3) Results: The reduced renal mass triggered the enrichment of cholesterol, specifically cholesteryl esters, in HDL subclasses. The exchange of cholesteryl esters between HDL and apo B-containing lipoproteins (VLDL/LDL) was not significantly modified in Ntx rabbits. Moreover, the cholesteryl esters of HDL and VLDL/LDL fluxes from the plasmatic compartment tended to decrease, but they only reached statistical significance when both fluxes were added to the Nxt group. Accordingly, the fractional catabolic rate (FCR) of the HDL-cholesteryl esters was lower in Ntx rabbits, concomitantly with its accumulation in HDL subclasses, probably because of the reduced mass of renal cells requiring this lipid from lipoproteins.
Asunto(s)
Ésteres del Colesterol , Lipoproteínas HDL , Animales , Conejos , Lipoproteínas HDL/metabolismo , Ésteres del Colesterol/metabolismo , Colesterol/metabolismo , Lipoproteínas/metabolismo , Proteínas de Transferencia de Ésteres de ColesterolRESUMEN
OBJECTIVE: To determine the role of the arterial splenomesenteric anastomosis (ASMA) vascular reconstruction technique in terms of arterial vascular complications in pancreas transplant (PT) recipients. SUMMARY BACKGROUND DATA: The ASMA technique was first described in 1992 by Hospital Clínic Barcelona group. Regardless that the iliac Y-graft technique is the most frequently used worldwide, evidence of arterial complications and implications of using a different back-table reconstruction is conspicuously absent in the literature. METHODS: Descriptive review of 407 PTs performed at a single center (1999-2019) by analyzing the type of arterial reconstruction technique, focusing on ASMA. The endpoints were the management of arterial complications and long-term patient and graft survival. RESULTS: ASMA was performed in 376 cases (92.4%) and a Y-graft in 31 cases (7.6%). A total of 34 arterial complications (8.3%) were diagnosed. In the ASMA group (n=30, 7.9%) they comprised: 15 acute thrombosis; 4 stenosis; 1 pseudoaneurysm and 10 diverse chronic arterial complications while in the Y-graft group (n=4, 12.9%) 3 acute thrombosis and 1 chronic artery-duodenal fistula occurred. Graft salvage was achieved in 16 patients (53.3%) from the ASMA group and in 2 (50%) from the Y-graft. After a median follow-up of 129.2 (IQR 25-75%, 77.2 -182) months the overall graft and patient survival for the whole cohort at 1, 5, and 10 years was 86.7%, 79.5%, 70.5%, and 98.5%, 95.3%, 92.5%, respectively. CONCLUSIONS: The ASMA proves to be a safe and more easily reproducible technique and should therefore be considered for first-line back-table reconstruction in the PT population.
RESUMEN
Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich's Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR's role as a promising therapeutic target in combating these devastating disorders.