Doble synergetic anticancer activity through a combined chemo-photodynamic therapy and bioimaging of a novel Cas-ZnONPs all-in-one system.

A strategy for cancer treatment was implemented, based on chemo-photodynamic therapy, utilizing a novel formulation, low-cost system called Cas-ZnONPs. This system consisted of the incorporation of Casiopeina III-ia (CasIII-ia), a hydrophilic copper coordination compound with well-documented anti-neoplastic activity, on Zinc oxide nanoparticles (ZnONPs) with apoptotic activity and lipophilicity, allowing them to permeate biological barriers. Additionally, ZnONPs exhibited fluorescence, with emission at different wavelengths depending on their agglomeration and enabling real-time tracking biodistribution. Also, ZnONPs served as a sensitizer, generating reactive oxygen species (ROS) in situ. In in vitro studies on HeLa and MDA-MB-231 cell lines, a synergistic effect was observed with the impregnated CasIII-ia on ZnONPs. The anticancer activity had an increase in cellular inhibition, depending on the dose of exposure to UV-vis irradiation. In in vivo studies utilized zebrafish models for xenotransplanting stained MDA-MB-231 cells and testing the effectiveness of Cas-ZnONPs treatment. The treatment successfully eliminated cancer cells, both when combined with Photodynamic Therapy (PDT) and when used alone. However, a significantly higher concentration (50 times) of Cas-ZnONPs was required in the absence of PDT. This demonstrates the potential of Cas-ZnONPs in cancer treatment, especially when combined with PDT.

Fluorescent Probe as Dual-Organelle Localizer Through Differential Proton Gradients Between Lipid Droplets and Mitochondria.

Dual-organelle molecular localizers represent powerful new tools allowing the exploration of interorganelle physical contacts and subcellular chemical communication. Here, we describe new dynamic molecular probes to localize mitochondria and lipid droplets taking advantage of the differential proton gradients present in these organelles as well as the activity of mitochondrial esterase. We unveil their potential utility when organelle retention mechanisms and proton gradients are synchronized, an insight that has not been documented previously. Our discoveries indicate that dual-organelle probes serve as a valuable multiplexing assay during starvation-induced autophagy. The pioneering molecular mechanism they employ opens doors to avoid using labile esters such as acetoxymethyl derivatives which are not optimal in imaging microscopy assays.

Exploring the self-assembly dynamics of novel steroid-coumarin conjugates: a comprehensive spectroscopic and solid-state investigation.

The design, synthesis, and characterization of seven novel steroid-coumarin conjugates with diverse steroidal nuclei as lipophilic fluorescent materials for bioimaging applications are presented. The conjugates were synthesized through amidation, characterized using spectroscopic and spectrometric methods, and their main photophysical properties were determined. Dioxane : water titration experiments revealed their ability to self-assemble, forming J-aggregates as evidenced by new spectral bands at higher wavelengths. Monocrystal X-ray diffraction analysis disclosed distinctive aggregation patterns exhibiting J- or H-aggregates for selected compounds. Bioimaging studies demonstrated cell membrane localization for most conjugates, with some of them displaying an interesting selectivity for lipid droplets. Notably, the presence of the steroid fragments significantly influenced both the self-assembly patterns and the cellular localization of the fluorescent probes.

Exploring mitochondrial targeting: an innovative fluorescent probe reveals Nernstian potential and partitioning combination.

This study introduces a paradigm-shifting approach to optimize mitochondrial targeting. Employing a new fluorescent probe strategy, we unravel a combined influence of both Nernst potential (Ψ) and partitioning (P) contributions. Through the synthesis of new benz[e]indolinium-derived probes, our findings redefine the landscape of mitochondrial localization by optimizing the efficacy of mitochondrial probe retention in primary cortical neurons undergoing normoxia and oxygen-glucose deprivation. This methodology not only advances our understanding of subcellular dynamics, but also holds promise for transformative applications in biomedical research and therapeutic development.

La dieta como fuente de sulfuro de hidrógeno y sus efectos en la salud y la enfermedad / Diet as a source of hydrogen sulfide and its effects on health and disease

Conocido originalmente por sus efectos deletéreos en la salud, recientemente se ha reconocido al sulfuro de hidrógeno (H2S) como un gasotransmisor de importancia biológica, al igual que el óxido nítrico y el monóxido de carbono. El H2S puede producirse de forma endógena en lascélulas de mamíferos por dos vías: la vía enzimática y la vía no enzimática. Cuando se produce por la vía enzimática, su síntesis se lleva a cabo apartir de los aminoácidos L-cisteína o metionina mediante transulfuración y transmetilación. También se puede producir el H2S a partir donadores de grupos sulfuro como, por ejemplo, compuestos orgánicos que se encuentran presentes en algunos vegetales. Actualmente es bien conocido el papel del H2S como protector a nivel cerebral y cardiaco, y cada vez adquiere mayor relevancia su estudio como coadyuvante terapéutico en padecimientos metabólicos como la obesidad y la diabetes mellitus de tipo 2. El objetivo de esta revisión es examinar cómo impacta el aporte de donadores y precursores del sulfuro de hidrógeno por la dieta en la salud y la enfermedad. (AU)

Initially known for its deleterious health effects, hydrogen sulfide (H2S) has recently been recognized as a biologically important gas carrier, likenitric oxide and carbon monoxide. H2S is produced endogenously in mammalian cells by enzymatic and non-enzymatic pathways. When it isproduced by the enzymatic pathway, its synthesis is carried out from the amino acid L-cysteine through the transsulfuration pathway. It can alsobe produced endogenously from exogenous compounds that function as H2S donors as, for example, the naturally occurring organic donors foundin some plants. Currently, the role of H2S is well known as brain and cardiac protector, and its research as a therapeutic adjuvant in metabolicdiseases such as obesity and type-2 diabetes is becoming increasingly important. The objective of this review is to examine how the contributionof donors and precursors of hydrogen sulfide by the diet impacts health and disease. (AU)

[Diet as a source of hydrogen sulfide and its effects on health and disease]. / La dieta como fuente de sulfuro de hidrógeno y sus efectos en la salud y la enfermedad.

Introduction: Initially known for its deleterious health effects, hydrogen sulfide (H2S) has recently been recognized as a biologically important gas carrier, like nitric oxide and carbon monoxide. H2S is produced endogenously in mammalian cells by enzymatic and non-enzymatic pathways. When it is produced by the enzymatic pathway, its synthesis is carried out from the amino acid L-cysteine through the transsulfuration pathway. It can also be produced endogenously from exogenous compounds that function as H2S donors as, for example, the naturally occurring organic donors found in some plants. Currently, the role of S2H is well known as brain and cardiac protector, and its research as a therapeutic adjuvant in metabolic diseases such as obesity and type-2 diabetes is becoming increasingly important. The objective of this review is to examine how the contribution of donors and precursors of hydrogen sulfide by the diet impacts health and disease.

Introducción: Conocido originalmente por sus efectos deletéreos en la salud, recientemente se ha reconocido al sulfuro de hidrógeno (H2S) como un gasotransmisor de importancia biológica, al igual que el óxido nítrico y el monóxido de carbono. El H2S puede producirse de forma endógena en las células de mamíferos por dos vías: la vía enzimática y la vía no enzimática. Cuando se produce por la vía enzimática, su síntesis se lleva a cabo a partir de los aminoácidos L-cisteína o metionina mediante transulfuración y transmetilación. También se puede producir el H2S a partir donadores de grupos sulfuro como, por ejemplo, compuestos orgánicos que se encuentran presentes en algunos vegetales. Actualmente es bien conocido el papel del H2S como protector a nivel cerebral y cardiaco, y cada vez adquiere mayor relevancia su estudio como coadyuvante terapéutico en padecimientos metabólicos como la obesidad y la diabetes mellitus de tipo 2. El objetivo de esta revisión es examinar cómo impacta el aporte de donadores y precursores del sulfuro de hidrogeno por la dieta en la salud y la enfermedad.

Fluorescent Probe for in Vivo Partitioning into Dynamic Lipid Droplets Enables Monitoring of Water Permeability-Induced Edema.

Lipid droplets (LDs) are intracellular organelles found in most cell types from adipocytes to cancer cells. Although recent investigations have implicated LDs in numerous diseases, the current available methods to monitor them in vertebrate models rely on static imaging using fluorescent dyes, limiting the investigation of their rapid in vivo dynamics. Here, we report a fluorophore chemistry approach to enable in vivo LD dynamic monitoring using a Nernstian partitioning mechanism. Interestingly, the effect of atorvastatin and osmotic treatments toward LDs revealed an unprecedented dynamic enhancement. Then, using a designed molecular probe with an optimized response to hydration and LD dynamics applied to Zebrafish developing pericardial and yolk-sac edema, which represents a tractable model of a human cardiovascular disease, we also provide a unique dual method to detect disease evolution and recovery.

Coumel tachycardia in children.

BACKGROUND: Coumel tachycardia is an infrequent form of supraventricular tachycardia (SVT) that usually occurs in infants and children. It is a tachycardia mediated by an accessory pathway with retrograde slow conduction that explains the classic ECG pattern with long RP' interval and negative P waves in leads II, III, and aVF. In this study, we describe the clinical course and management of Coumel tachycardia in children. CASE REPORT: We conducted a retrospective review of five consecutive pediatric patients, mean age 11 ± 3 years (range 6 to 14). The first episode of SVT was at a mean age of 10.4 ± 4.8 years (range 2 to 14) with a mean evolution of 7.4 ± 9.4 months (range 1 to 24). Pharmacological therapy was unsuccessful despite the combination of antiarrhythmic drugs. The tachycardia was incessant with a density > 85% by 24-hour Holter monitoring; one patient developed tachycardia-induced cardiomyopathy. All children underwent successful radiofrequency catheter ablation, mean 5 ± 3 applications (range 1 to 8) with a single session and with no complications. After a mean follow-up of 24 ± 16 months, all patients were asymptomatic and recurrence-free without antiarrhythmic treatment. CONCLUSIONS: Coumel tachycardia is clinically persistent and usually refractory to antiarrhythmic treatment with substantial risk of tachycardia-mediated cardiomyopathy. Catheter ablation is effective and safe in children; thus, it should be indicated promptly and based on individual selection.

INTRODUCCIÓN: La taquicardia de Coumel es una forma poco frecuente de taquicardia supraventricular que suele presentarse en lactantes. Es una taquicardia mediada por una vía accesoria de conducción lenta retrógrada que explica el patrón ECG clásico con intervalo RP' largo y ondas P negativas en las derivaciones II, III y aVF. En este trabajo se describe el curso clínico y el manejo de la taquicardia de Coumel en niños. CASO CLÍNICO: Se llevó a cabo una revisión retrospectiva de cinco pacientes pediátricos consecutivos, con una media de edad de 11 ± 3 años (intervalos 6 a 14). El primer episodio de taquicardia 10.4 ± 4.8 años con evolución de 7.4 ± 9.4 meses. El tratamiento farmacológico fue ineficaz a pesar de la combinación de antiarrítmicos. La taquicardia era incesante con una densidad > 85% por Holter-24h; un paciente desarrolló miocardiopatía inducida por taquicardia. Todos los niños fueron sometidos a ablación con catéter y radiofrecuencia con éxito, y un promedio de 5 ± 3 aplicaciones en una sola sesión y sin complicaciones. Después de un seguimiento de 24 ± 16 meses, todos los pacientes fueron asintomáticos y libres de recurrencia sin tratamiento antiarrítmico. CONCLUSIONES: La taquicardia de Coumel es clínicamente persistente y generalmente refractaria al tratamiento antiarrítmico con un riesgo sustancial de miocardiopatía mediada por taquicardia. La ablación con catéter es eficaz y segura en niños, por lo que debe indicarse de forma temprana y en lactantes de una selección individual.

[Guidelines on atopic dermatitis for Mexico (GUIDAMEX): using the ADAPTE methodology]. / Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE.

With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.

Con el avance de los conocimientos en relación con la fisiopatogenia de la dermatitis atópica (DA) se han desarrollado varias formas terapéuticas nuevas. Asimismo, existen nuevos lineamientos para el autocuidado. Por otro lado, aún existe un subdiagnóstico de la DA en México. Así, se vio la necesidad de desarrollar una guía nacional, con base amplia entre las diferentes agrupaciones médicos que atienden pacientes con DA. Se desarrolló la Guía de DA para México (GUIDAMEX) con la metodología ADAPTE, con el aval y la participación de diez sociedades médicas nacionales, desde médicos del primer contacto hasta alergólogos y dermatólogos. A lo largo del escrito se contestan preguntas clínicas clave que llevan a recomendaciones y sugerencias para el diagnóstico de la DA (incluyendo diagnóstico diferencial con síndromes de inmunodeficiencia), el reconocer de las comorbilidades y complicaciones, las medidas generales (tratamiento no farmacológico) incluyendo la educación terapéutica, el tratamiento de los brotes y el tratamiento de mantenimiento. Este último abarca las medidas generales de evitar agravantes, el tratamiento de primera línea reparador de la barrera cutánea, de segunda línea (manejo proactivo tópico), hasta la fototerapia y el tratamiento sistémico de la tercera línea, incluyendo dupilumab y los inhibidores de la cinasa de Jano.

Scale-up of hydrothermal processing: Liquid hot water and pilot-scale tubular steam explosion batch reactor for bioethanol production using macroalgae Sargassum spp biomass.

Sargassum spp. is a biomass that can potentially use as an alternative for bioethanol production. Hydrothermal processes (liquid hot water and steam explosion pretreatment) were carried out at different operational conditions. Enzymatic hydrolysis performed a preliminary test with different ratios 1:1 and 1:2 (cellulases and hemicellulases) of enzyme loading, once selected 1:2 ratio was obtained conversion yield of 99.91% and therefore carried a scale-up in stirred bioreactor getting 95.92% saccharification yield. Pre-simultaneous saccharification and fermentation strategy was performed in a continuous stirred tank bioreactor (CSTBR), producing ethanol yield of 57.69%, and for simultaneous saccharification and fermentation strategy was performed in a bubble column reactor was 71.37% ethanol yield. The energy efficiency was analyzed in different scenarios; the best data was 30.19 (gsugar/MJ) in the bioreactor enzymatic hydrolysis process. This development allows for establishing the conditions for a third-generation biorefinery on a circular bioeconomy using Sargassum biomass.

Coumel tachycardia in children / Taquicardia de Coumel en niños

Abstract Background: Coumel tachycardia is an infrequent form of supraventricular tachycardia (SVT) that usually occurs in infants and children. It is a tachycardia mediated by an accessory pathway with retrograde slow conduction that explains the classic ECG pattern with long RP' interval and negative P waves in leads II, III, and aVF. In this study, we describe the clinical course and management of Coumel tachycardia in children. Case report: We conducted a retrospective review of five consecutive pediatric patients, mean age 11 ± 3 years (range 6 to 14). The first episode of SVT was at a mean age of 10.4 ± 4.8 years (range 2 to 14) with a mean evolution of 7.4 ± 9.4 months (range 1 to 24). Pharmacological therapy was unsuccessful despite the combination of antiarrhythmic drugs. The tachycardia was incessant with a density > 85% by 24-hour Holter monitoring; one patient developed tachycardia-induced cardiomyopathy. All children underwent successful radiofrequency catheter ablation, mean 5 ± 3 applications (range 1 to 8) with a single session and with no complications. After a mean follow-up of 24 ± 16 months, all patients were asymptomatic and recurrence-free without antiarrhythmic treatment. Conclusions: Coumel tachycardia is clinically persistent and usually refractory to antiarrhythmic treatment with substantial risk of tachycardia-mediated cardiomyopathy. Catheter ablation is effective and safe in children; thus, it should be indicated promptly and based on individual selection.

Resumen Introducción: La taquicardia de Coumel es una forma poco frecuente de taquicardia supraventricular que suele presentarse en lactantes. Es una taquicardia mediada por una vía accesoria de conducción lenta retrógrada que explica el patrón ECG clásico con intervalo RP' largo y ondas P negativas en las derivaciones II, III y aVF. En este trabajo se describe el curso clínico y el manejo de la taquicardia de Coumel en niños. Caso clínico: Se llevó a cabo una revisión retrospectiva de cinco pacientes pediátricos consecutivos, con una media de edad de 11 ± 3 años (intervalos 6 a 14). El primer episodio de taquicardia 10.4 ± 4.8 años con evolución de 7.4 ± 9.4 meses. El tratamiento farmacológico fue ineficaz a pesar de la combinación de antiarrítmicos. La taquicardia era incesante con una densidad > 85% por Holter-24h; un paciente desarrolló miocardiopatía inducida por taquicardia. Todos los niños fueron sometidos a ablación con catéter y radiofrecuencia con éxito, y un promedio de 5 ± 3 aplicaciones en una sola sesión y sin complicaciones. Después de un seguimiento de 24 ± 16 meses, todos los pacientes fueron asintomáticos y libres de recurrencia sin tratamiento antiarrítmico. Conclusiones: La taquicardia de Coumel es clínicamente persistente y generalmente refractaria al tratamiento antiarrítmico con un riesgo sustancial de miocardiopatía mediada por taquicardia. La ablación con catéter es eficaz y segura en niños, por lo que debe indicarse de forma temprana y en lactantes de una selección individual.

Idiopathic left fascicular ventricular tachycardia in children and adolescents.

BACKGROUND: Idiopathic ventricular tachycardia (VT) in children with structurally normal hearts is generally unrelated to the risk of sudden arrhythmic death. Still, it may be associated with deterioration in the quality of life. VT involving the fascicular conduction system is the most typical form of idiopathic left VT. In this retrospective study, we describe the experience of the clinical presentation, catheter ablation, and long-term follow-up of left fascicular VT in children. METHODS: An electrophysiological study was performed on consecutive children at a single tertiary center. Clinical fascicular left VT was induced by programmed stimulation, and catheter ablation was guided searching for Purkinje potentials. RESULTS: We included 18 patients (0.8 patients/year): 14 (77.8%) males and four females. The mean age of the first VT episode was 8.5 ± 5 years. Intravenous verapamil administration was effective for paroxysmal fascicular VT but not for prevention of recurrences. The mean age at the time of catheter ablation was 11.1 ± 3.8 years (8 months-16 years). The mean weight was 36.8 ± 16.4 kg (8.7-58 kg). A 100% success rate was observed with catheter ablation after repeated procedures without major complications. Mean follow-up was 2.0 ± 1.2 years (1.0-4.0 years, median 1.5), with permanent success in all patients and no antiarrhythmic drug administration. CONCLUSIONS: Fascicular VT has an adverse clinical course in children. In most cases, this condition is drug refractory. Catheter ablation is successful and safe treatment and should represent the first-line approach in symptomatic children.

INTRODUCCIÓN: La taquicardia ventricular (TV) idiopática en niños con corazón estructuralmente normal generalmente no se relaciona con el riesgo de muerte súbita arrítmica, pero puede asociarse con deterioro de la calidad de vida. La TV que involucra el sistema de conducción fascicular es la forma más común de TV izquierda idiopática. En este estudio retrospectivo se describe la experiencia de presentación clínica, ablación con catéter y seguimiento a largo plazo de TV fascicular en niños. MÉTODOS: Se llevó a cabo un estudio electrofisiológico en niños consecutivos en un centro terciario. La TV fascicular clínica se indujo mediante la estimulación programada y la ablación con catéter fue guiada buscando el registro de potenciales de Purkinje. RESULTADOS: Se incluyeron 18 pacientes (0.8 pacientes/año): 14 (77.8%) de sexo masculino y cuatro de sexo femenino. La media de edad a la cual ocurrió el primer episodio fue de 8.5 ± 5 años. La administración intravenosa de verapamilo fue eficaz para la TV fascicular paroxística, pero no para prevención de recurrencias. La media de edad de la ablación con catéter fue de 11.1 ± 3.8 años (8 meses-16 años). La media del peso fue 36.8 ± 16.4 kg (8.7-58 kg). Se observó el 100% de éxito con la ablación con catéter después de procedimientos repetidos sin complicaciones mayores. La media de seguimiento fue de 2.0 ± 1.2 años (1.0-4.0, mediana de 1.5 años) con éxito permanente en todos los pacientes y sin administración de fármacos antiarrítmicos. CONCLUSIONES: En niños, el curso clínico de la TV fascicular es adverso. Además, en la mayoría de los casos, esta condición es refractaria a fármacos. La ablación con catéter resulta exitosa y segura y debe representar el abordaje de primera línea en niños sintomáticos.

Mitochondria-Assisted Photooxidation to Track Singlet Oxygen at Homeostatic Membrane Microviscosity.

Using intracellular-controlled photochemistry to track dynamic organelle processes is gaining attention due to its broad applications. However, most of the employed molecular probes usually require toxic photosensitizers and complex bioanalytical protocols. Here, the synthesis and performance of two new subcellular probes (MitoT1 and MitoT2) are described. The probes undergo photooxidation in the damaged tissue of zebrafish, a model system for tissue regeneration studies. Using high-resolution confocal microscopy and fluorescence spectroscopy, we combine the mentioned photoinduced interconversion at the homeostatic membrane viscosity to track singlet oxygen activity selectively. The continuous and real-time biosensing method reported here provides a new approach for simultaneously detecting endogenous singlet oxygen and viscosity status.

Idiopathic left fascicular ventricular tachycardia in children and adolescents / Taquicardia ventricular fascicular izquierda idiopática en niños y adolescentes

Abstract Background: Idiopathic ventricular tachycardia (VT) in children with structurally normal hearts is generally unrelated to the risk of sudden arrhythmic death. Still, it may be associated with deterioration in the quality of life. VT involving the fascicular conduction system is the most typical form of idiopathic left VT. In this retrospective study, we describe the experience of the clinical presentation, catheter ablation, and long-term follow-up of left fascicular VT in children. Methods: An electrophysiological study was performed on consecutive children at a single tertiary center. Clinical fascicular left VT was induced by programmed stimulation, and catheter ablation was guided searching for Purkinje potentials. Results: We included 18 patients (0.8 patients/year): 14 (77.8%) males and four females. The mean age of the first VT episode was 8.5 ± 5 years. Intravenous verapamil administration was effective for paroxysmal fascicular VT but not for prevention of recurrences. The mean age at the time of catheter ablation was 11.1 ± 3.8 years (8 months-16 years). The mean weight was 36.8 ± 16.4 kg (8.7-58 kg). A 100% success rate was observed with catheter ablation after repeated procedures without major complications. Mean follow-up was 2.0 ± 1.2 years (1.0-4.0 years, median 1.5), with permanent success in all patients and no antiarrhythmic drug administration. Conclusions: Fascicular VT has an adverse clinical course in children. In most cases, this condition is drug refractory. Catheter ablation is successful and safe treatment and should represent the first-line approach in symptomatic children.

Resumen Introducción: La taquicardia ventricular (TV) idiopática en niños con corazón estructuralmente normal generalmente no se relaciona con el riesgo de muerte súbita arrítmica, pero puede asociarse con deterioro de la calidad de vida. La TV que involucra el sistema de conducción fascicular es la forma más común de TV izquierda idiopática. En este estudio retrospectivo se describe la experiencia de presentación clínica, ablación con catéter y seguimiento a largo plazo de TV fascicular en niños. Métodos: Se llevó a cabo un estudio electrofisiológico en niños consecutivos en un centro terciario. La TV fascicular clínica se indujo mediante la estimulación programada y la ablación con catéter fue guiada buscando el registro de potenciales de Purkinje. Resultados: Se incluyeron 18 pacientes (0.8 pacientes/año): 14 (77.8%) de sexo masculino y cuatro de sexo femenino. La media de edad a la cual ocurrió el primer episodio fue de 8.5 ± 5 años. La administración intravenosa de verapamilo fue eficaz para la TV fascicular paroxística, pero no para prevención de recurrencias. La media de edad de la ablación con catéter fue de 11.1 ± 3.8 años (8 meses-16 años). La media del peso fue 36.8 ± 16.4 kg (8.7-58 kg). Se observó el 100% de éxito con la ablación con catéter después de procedimientos repetidos sin complicaciones mayores. La media de seguimiento fue de 2.0 ± 1.2 años (1.0-4.0, mediana de 1.5 años) con éxito permanente en todos los pacientes y sin administración de fármacos antiarrítmicos. Conclusiones: En niños, el curso clínico de la TV fascicular es adverso. Además, en la mayoría de los casos, esta condición es refractaria a fármacos. La ablación con catéter resulta exitosa y segura y debe representar el abordaje de primera línea en niños sintomáticos.

Functional Nanocarriers for Delivering Itraconazole Against Fungal Intracellular Infections.

Infectious diseases caused by intracellular microorganisms represent a significant challenge in medical care due to interactions among drugs during coinfections and the development of resistance in microorganisms, limiting existing therapies. This work reports on itraconazole (ITZ) encapsulated into functional polymeric nanoparticles for their targeted and controlled release into macrophages to fight intracellular infections. NPs are based on poly (lactic acid-co-glycolic acid) (PLGA) polymers of different compositions, molecular weights, and lactic acid-to-glycolic acid ratios. They were self-assembled using the high-energy nanoemulsion method and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry. It was studied how the polymer-to-drug ratio, changes in the aqueous phase pH, and type and concentration of surfactant affected nanocarriers' formation, drug-loading capacity, and encapsulation efficiency. Results showed that drug-loading capacity and encapsulation efficiency reached 6.7 and 80%, respectively, by lowering the pH to 5.0 and using a mixture of surfactants. Optimized formulation showed an initial immediate ITZ release, followed by a prolonged release phase that fitted better with a Fickian diffusion kinetic model and high stability at 4 and 37°C. NPs functionalized by using the adsorption and carbodiimide methods had different efficiencies, the carbodiimide approach being more efficient, stable, and reproducible. Furthermore, linking F4/80 and mannose to the NPs was demonstrated to increase J774A.1 macrophages' uptake. Overall, in vitro assays showed the nanosystem's efficacy to eliminate the Histoplasma capsulatum fungus and pave the way to design highly efficient nanocarriers for drug delivery against intracellular infections.

Fluorescent probe for early mitochondrial voltage dynamics.

Mitochondrial voltage dynamics plays a crucial role in cell healthy and disease. Here, a new fluorescent probe to monitor mitochondrial early voltage variations is described. The slowly permeant probe is retained in mitochondria during measurements to avoid interferences from natural membrane potential by incorporating an hydrolizable ester function. Voltage, local polarity, pH parameters and transmembrane dynamics were found to be deeply correlated opening a approach in mitochondrial sensing.

Polysaccharides Release in a Laboratory-Scale Batch Hydrothermal Pretreatment of Wheat Straw under Rigorous Isothermal Operation.

Hydrothermal pretreatment (HP) is an eco-friendly process for deconstructing lignocellulosic biomass (LCB) that plays a key role in ensuring the profitability of producing biofuels or bioproducts in a biorefinery. At the laboratory scale, HP is usually carried out under non-isothermal regimes with poor temperature control. In contrast, HP is usually carried out under isothermal conditions at the commercial scale. Consequently, significant discrepancies in the values of polysaccharide releases are found in the literature. Therefore, laboratory-scale HP data are not trustworthy if scale-up or retrofitting of HP at larger scales is required. This contribution presents the results of laboratory-scale batch HP for wheat straw in terms of xylan and glucan release that were obtained with rigorous temperature control under isothermal conditions during the reaction stage. The heating and cooling stages were carried out with fast rates (43 and -40 °C/min, respectively), minimizing non-isothermal reaction periods. Therefore, the polysaccharide release results can be associated exclusively with the isothermic reaction stage and can be considered as a reliable source of information for HP at commercial scales. The highest amount of xylan release was 4.8 g/L or 43% obtained at 180 °C and 20 min, while the glucan release exhibited a maximum of 1.2 g/L or 5.5%. at 160 °C/180 °C and 30 min.

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections.

Polymeric nanocarriers (PNs) have demonstrated to be a promising alternative to treat intracellular infections. They have outstanding performance in delivering antimicrobials intracellularly to reach an adequate dose level and improve their therapeutic efficacy. PNs offer opportunities for preventing unwanted drug interactions and degradation before reaching the target cell of tissue and thus decreasing the development of resistance in microorganisms. The use of PNs has the potential to reduce the dose and adverse side effects, providing better efficiency and effectiveness of therapeutic regimens, especially in drugs having high toxicity, low solubility in the physiological environment and low bioavailability. This review provides an overview of nanoparticles made of different polymeric precursors and the main methodologies to nanofabricate platforms of tuned physicochemical and morphological properties and surface chemistry for controlled release of antimicrobials in the target. It highlights the versatility of these nanosystems and their challenges and opportunities to deliver antimicrobial drugs to treat intracellular infections and mentions nanotoxicology aspects and future outlooks.

Tuning the Cell Uptake and Subcellular Distribution in BODIPY-Carboranyl Dyads: An Experimental and Theoretical Study.

A set of BODIPY-carboranyl dyads synthesized by a Sonogashira cross-coupling reaction, where different C-substituted ortho- and meta-carboranyl fragments have been linked to a BODIPY fluorophore is described. Chemical, photophysical and physicochemical analyses are presented, including NMR and single XRD experiments, optical absorption/emission studies and partition coefficient (log P) measurements. These studies, supported by DFT computations (M06-2X/6-31G**), provide an explanation to the largely divergent cell income that these fluorescent carboranyl-based fluorophores display, for which a structural or physicochemical explanation remains elusive. By studying the cell uptake efficiency and subcellular localization for our set of dyads on living HeLa cells, we tracked the origins of these differences to significant variations in their static dipole moments and partition coefficients, which tune their ability to interact with lipophilic microenvironments in cells. Remarkably, m-carboranyl-BODIPY derivatives with a higher lipophilicity are much better internalised by cells than their homologous with o-carborane, suggesting that m-isomers are potentially better theranostic agents for in vitro bioimaging and boron carriers for boron neutron capture therapy.