Ingeniería Civil Biomédica

URI permanente para esta comunidad

https://hdl.handle.net/20.500.12254/7369

Examinar

Mostrando 1 - 10 de 10

Adipocyte extracellular vesicles (AdEVs) promote a proinflammatory and profibrotic profile in human renal and endothelial cells in vitro
(Springer Nature, 2026-02-23) Carrión, Pablo
OBJECTIVES: In obesity, white adipose tissue (WAT) undergoes hypertrophic and hyperplastic changes that are driven by phenotypical changes in preadipocytes and adipocytes. WAT also causes a chronic inflammatory state that modifies gene expression and the secretome, including the shedding of adipose-derived extracellular vesicles (AdEVs) into the circulation, which may influence distant cell types and modulate their phenotypes. AIM: To evaluate the effects of AdEVs on renal and endothelial cells and determine their impact on gene expression related to inflammation, fibrosis, and endothelial function. METHODS: Human SW872 preadipocytes were differentiated into adipocytes and subsequently characterized. AdEVs were isolated by ultracentrifugation and analyzed according to ISEV guidelines. Recipient human renal (HCD) and endothelial (EA.hy926) cells were exposed to AdEVs for 24 hours. Gene expression of adipokines, cytokines (IL-6, IL-1B), fibrosis markers, neutrophil gelatinaseassociated lipocalin (NGAL), and eNOS was assessed by RT-qPCR and western blotting. RESULTS: Differentiated SW872 cells displayed typical adipocyte morphology and accumulated abundant lipid droplets. Isolated AdEVs showed a donut-like morphology, characteristic size distribution, and expression of CD9 and TSG101, consistent with canonical EV markers. Both renal and endothelial cells internalized PKH67-labeled AdEVs and exhibited increased IL-6 and IL-1B expression (p < 0.05). Renal cells demonstrated increased NGAL mRNA levels, whereas endothelial cells showed reduced eNOS mRNA expression following AdEV exposure (p < 0.05). CONCLUSION: AdEVs from SW872 upregulated cytokine (e.g., IL-6) and NGAL expression in renal cells, while reducing eNOS expression in endothelial cells. These findings suggest that AdEVs may influence early inflammatory and vascular responses inobesity.
Capítulo 3: Conceptos básicos de genética y epigenética
(Ediciones UC, 2026-04) Carvajal, Cristian
Endocrinología Clínica es hoy un manual imprescindible para la formación y el ejercicio de la endocrinología en Chile y Latinoamérica. Tras el éxito de sus versiones anteriores, esta tercera edición surge como respuesta a los acelerados avances diagnósticos y terapéuticos que han transformado el cuidado de las enfermedades hormonales. Con un enfoque docente, claro y orientado a la resolución de problemas clínicos, el libro reúne a destacados especialistas nacionales e internacionales y aborda de manera integral las principales áreas de la disciplina, desde patología tiroidea y diabetes hasta neuroendocrinología, metabolismo óseo, obesidad, radiología y laboratorio clínico. Actualizada, rigurosa y aplicada a la realidad regional, esta obra entrega herramientas clave para el razonamiento clínico, la interpretación de exámenes y la toma de decisiones terapéuticas basadas en evidencia, consolidándose como un texto de referencia para estudiantes, residentes y especialistas.
Classic and “non-classic” apparent mineralocorticoid excess
(Elsevier, 2025) Baudrand, Rene
Hypertension is highly prevalent in the general population. Up to 1/3 of patients display low-renin levels due to aldosterone-mediated mineralocorticoid receptor (MR) activation or cortisol-mediated MR activation. The spectrum of cortisol-mediated MR activation includes the classic apparent mineralocorticoid excess (AME), Cushing syndrome or milder (non-classic) forms of AME, the latter with a much higher prevalence and subtle phenotype. Classic AME is a rare autosomal recessive disorder caused by the presence of a severe dominant autosomal deficiency of 11bHSD2 gene. Non-classic -AME (NC-AME) is mainly associated with partial 11bHSD2 deficiency due to milder genetic variations or epigenetic modifications plus potential actions of endogenous or exogenous inhibitors. Treatment aims to ameliorate MR activation with low-sodium diet and MR antagonists.
Driving hypertension: non-classic apparent mineralocorticoid excess
(Springer Nature, 2025-11-12) Carvajal, Cristian A.
Non-classic apparent mineralocorticoid excess is an underrecognized cause of low-renin hypertension, which is often misdiagnosed as essential hypertension. This condition challenges traditional classifications and highlights the need for mechanism-based diagnostics and medical care. Hypertension remains a leading contributor to global cardiovascular morbidity and mortality. It has a high prevalence, low rate of identifiable causes and is frequently resistant to conventional therapy. Hypertension is traditionally classified as ‘essential’ and multifactorial; however, up to one-third of patients have hypertension with a low-renin phenotype . This subtype has been largely attributed to primary aldosteronism, yet emerging data suggest a broader and more complex spectrum of mineralocorticoid receptor (MR) overactivation. Non-classic apparent mineralocorticoid excess (NC-AME) is one of several overlooked contributors to low-renin hypertension; NC-AME might account for a meaningful proportion of patients who have been misclassified as having essential hypertension.
Feasibility of using ultrasound for drug delivery through micellar systems
(Institute of Electrical and Electronics Engineers (IEEE), 2025-04-02) Marambio, E.
A study of micellar structures subjected to continuous high-intensity ultrasonic perturbation was carried out. The micelles were characterized by high-speed absorption spectrophotometry and the use of fluorophores, such as Rhodamine 123, as a spectroscopic indicator of the micellar kinetic process. It was found that above the critical micellar concentration, the absorbance peak of the fluorophore experiences a 14 nm red shift. Preliminary experiments indicate a reversal of this shift under certain ultrasonic conditions. In subsequent experiments, no effect of high intensity ultrasonic radiation on the micellar systems studied was observed. A dependence of the spectroscopic response of Rh123 on temperature is found, which can be confused with the effect of micelle breaking in solutions. The study presented considers the use of Quillaja Saponaria Molina and Triton X-100 as a surfactant, but it is extensible to other micellar systems.
Hipertensión arterial de origen endocrino en población pediátrica: Rol emergente del exceso aparente de mineralocorticoides no clásico
(Sociedad Chilena de Endocrinología y Diabetes, 2026-01) Tapia-Castillo, Alejandra
La hipertensión arterial (HTA) pediátrica ha aumentado de manera sostenida en las últimas décadas, con una prevalencia estimada de 3–5% a nivel global y hasta 8% en Chile. Lejos de ser una condición benigna, la HTA en niños se asocia a daño temprano en órganos blanco, incluyendo hipertrofia ventricular izquierda, mayor grosor íntima-media carotídeo, rigidez arterial, microalbuminuria y alteraciones neurocognitivas. Mientras en escolares y adolescentes predomina la HTA primaria, en menores de seis años son más frecuentes las causas secundarias, entre ellas las endocrinas, que representan aproximadamente 5–10% de los casos y requieren una evaluación específica. Entre estas causas, el síndrome de Exceso Aparente de Mineralocorticoides (AME) destaca por una activación inapropiada del receptor mineralocorticoide (MR) mediada por cortisol, consecuencia de una actividad reducida o inhibida de la enzima 11β-hidroxiesteroide deshidrogenasa tipo 2 (11β-HSD2). El AME clásico es infrecuente y de presentación grave, asociado a variantes patogénicas en HSD11B2. En contraste, el AME no clásico (NC-AME) constituye una forma más leve y probablemente subdiagnosticada, caracterizada por renina baja, relación cortisol/cortisona elevada, niveles disminuidos de cortisona y aumento de la excreción urinaria de potasio, pudiendo contribuir a HTA en niños previamente considerados con HTA esencial. Los mecanismos propuestos para NCAME incluyen polimorfismos en HSD11B2, alteraciones epigenéticas y la presencia de inhibidores endógenos o exógenos de 11β-HSD2. En niños hipertensos, se han observado alteraciones del metabolismo del cortisol compatibles con una disfunción parcial de esta enzima. Aunque el uso de antagonistas del MR es eficaz en estos casos, el control óptimo de la presión arterial sigue siendo limitado. El NC-AME emerge, así como una causa relevante y subdiagnosticada de HTA pediátrica, subrayando la necesidad de mejorar su reconocimiento, caracterización y abordaje terapéutico.
Influence of estradiol deficiency on the mineralocorticoid receptor response in postmenopausal women: a cross-sectional study
(Taylor & Francis Group, 2025-01) Martínez-García, Alejandra
Objective: Premenopausal women (PreM) have a cardioprotective advantage over postmenopausal women (PostM) due to estrogen. The interaction of estrogen with the mineralocorticoid receptor (MR) pathway remains unexplored. This study aimed to identify changes in aldosterone, renin and sexual steroid levels and MR surrogate biomarkers in PostM that may explain changes in blood pressure and renal damage. Methods: A cross-sectional study was carried out with 47 normotensive and hypertensive Chilean women distributed between PreM and PostM. Clinical, anthropometric and biochemical parameters, including aldosterone, plasma renin activity (PRA) and surrogate markers of MR activity, were assessed. Results: PostM had greater systolic blood pressure (SBP) (p < 0.001) than PreM. A negative correlation was observed between estradiol and fractional excretion of potassium (FEK) (ρ = –0.29; p = 0.023), adjusted for age and SBP. Compared with hypertensive PreM, hypertensive PostM (PostM-HT) showed reduced PRA (p = 0.045) and greater FEK (p = 0.04). Normotensive PostM (Post-NT) exhibited greater SBP (p = 0.03), neutrophil gelatinase-associated lipocalin (NGAL) levels (p = 0.04) and FEK (p = 0.03) than normotensive PreM. Conclusion: Our results suggest enhanced MR sensitivity not only in PostM-HT, as evidenced by lower PRA and elevated FEK, but also in PostM-NT, who exhibited greater FEK and NGAL levels, surrogate markers of MR activation. These results support a novel role of MR activation and cardiovascular risk in PostM women.
Low-renin hypertension in incidental adrenal adenomas and response to aldosterone-targeted therapy: a prospective study
(Elsevier, 2026-06-27) Uslar, Thomas
Background: Incidental adrenal adenomas are common, yet renin status is infrequently assessed in hypertensive patients. Emerging evidence supports a spectrum of renin-independent aldosterone excess associated with adverse cardiovascular risk. Objective and methods: To determine the frequency of a low-renin phenotype in a prospective cohort of hypertensive patients with adrenal adenomas and to evaluate the clinical response to aldosterone-targeted therapy across baseline aldosterone categories. Low-renin phenotype was defined as suppressed renin (PRA <1.0 ng/mL/ h or DRC <10 μIU/mL). Among these patients, plasma aldosterone concentration (PAC) was categorized as 5–10 ng/dL (Group 1), 10–15 ng/dL (Group 2), and >15 ng/dL (Group 3). Patients with suppressed renin were treated with MR antagonists or adrenalectomy and followed longitudinally using PAMO/PASO criteria. Results: Low renin was present in 47% (138/290) of hypertensive patients. Increasing aldosterone levels were associated with higher systolic blood pressure (SBP), resistant hypertension, higher antihypertensive treatment burden, lower potassium, and reduced eGFR (p-trend <0.001). After a mean follow-up of 24±18 months (n = 121), aldosterone-targeted therapy (75% medical, 25% surgical) led to significant reductions in SBP (-18, -26, and -30 mmHg across Groups 1–3; all p < 0.001), decreased medication and significant increases in renin (all p < 0.001), irrespective of aldosterone category. Conclusions: Nearly half of hypertensive patients with adrenal incidentalomas exhibit suppressed renin levels associated with greater blood pressure burden and favorable response to aldosterone-targeted therapy, even in lower aldosterone levels categories. These findings support systematic renin assessment in hypertensive patients with incidental adrenal adenomas and provide a rationale for testing aldosterone-targeted therapy in broader hypertensive populations beyond adrenal adenomas
Primary Aldosteronism in a Hispanic Cohort: Responses to Mineralocorticoid Receptor Antagonism and Remission in a Case
(Oxford University Press, 2025-02) Tapia-Castillo, Alejandra
Background: Primary aldosteronism (PA) is the main cause of secondary arterial hypertension. In this study, we present the medical treatment of Hispanic patients with PA followed for up to 5 years, highlighting the complete cure with pharmacological treatment in one of our patients. Methods: We studied 32 PA patients, followed every 6 months after starting MRA. A clinical response was the normalization of blood pressure (BP) in the absence of other antihypertensive drugs. The biochemical response was considered with normalization of potassium and renin. Responses to treatment were compared using the defined daily dose (DDD). The effect of MRA was evaluated in vitro. The HAC15 cells were cultured and stimulated with aldosterone and spironolactone for 24-72 h, and the apoptotic cell death was measured. Results: At 12 months posttreatment with MRA, 68% of the patients had a total clinical response, and 67% had a total biochemical response. Response to MRA treatment reduced DDD by an average of 74%. Additionally, we observed one PA patient treated with spironolactone after 3 years, he presented a pharmacological cure with normalization of aldosterone and renin without treatment with spironolactone. The in vitro study shows that spironolactone increased early apoptosis by 60% and late apoptosis by 50%. Conclusions: These results suggest the importance of timely diagnosis of PA and specific treatment with MRA, especially in patients with a poor response to treatment. Moreover, remission of PA may occur in some patients after spironolactone treatment due to its suggestive role as an apoptotic agent.
Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines
(Endocrine Society, 2024-09) Uslar, Thomas
Background: It has been postulated that chronic kidney disease (CKD) is a state of relative 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11βHSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range. Methods: Adult participants were recruited at 2 academic centers. A discovery cohort (n = 500) enrolled individuals with estimated glomerular filtration rate (eGFR) ranging from normal to CKD stage 5, in whom serum cortisol-to-cortisone (F/E) was measured as a biomarker of 11βHSD2 activity. A validation cohort (n = 101) enrolled only individuals with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2) in whom 11βHSD2 activity was assessed via serum F/E and 11-hydroxy-to-11-keto androgen (11OH/K) ratios following multiple maneuvers: oral sodium suppression test, dexamethasone suppression test (DST), and ACTH-stimulation test (ACTHstim). Results: In the discovery cohort, lower eGFR was associated with higher F/E (P-trend < .001). Similarly, in the validation cohort, with normal eGFR, an inverse association between eGFR and both F/E and 11OH/K ratios was observed (P-trend < .01), which persisted following DST (P-trend < .001) and ACTHstim (P-trend < .05). The fractional excretion of potassium, a marker of renal MR activity, was higher with higher F/E (P-trend < .01) and with lower eGFR (P-trend < .0001). Conclusion: A continuum of declining 11βHSD2 activity was observed with progressively lower eGFR in individuals spanning a wide spectrum of kidney function, including those with apparently normal kidney function. These findings implicate cortisol-mediated MR activation in the pathophysiology of hypertension and cardiovascular disease in CKD.

Examinar

Examinando Ingeniería Civil Biomédica por Materia "07 - Protección y mejora de la salud humana"

Resultados por página

Opciones de ordenación