Nefropatía congénita en Schnauzer miniatura

Un Schnauzer miniatura, macho, de 13 meses de edad, presenta un cuadro de vómitos crónicos con historia clínica de gastritis. El examen físico y las pruebas complementarias permiten diagnosticar un cuadro compatible con la nefropatía familiar del Schnauzer miniatura. Se instauró dieta y tratamiento médico hasta que el animal empeoró a los dos meses y medio

Comparison of two radiofrequency-based hemostatic devices: saline-linked bipolar vs. cooled-electrode monopolar

[EN] Purpose To characterize the coagulation zones created by two radiofrequency (RF)-based hemostatic devices: one comprised an internally cooled monopolar electrode and the other comprised externally irrigated bipolar electrodes (saline-linked). Materials and methods RF-induced coagulation zones were created on ex vivo and in vivo porcine models. Computer modeling was used to determine the RF power distribution in the saline-linked device. Results Both external (irrigation) and internal cooling effectively prevented tissue sticking. Under ex vivo conditions in 'painting' application mode, coagulation depth increased with the applied power: 2.8 - 5.6 mm with the 3-mm monopolar electrode, 1.6 - 6.0 mm with the 5-mm monopolar electrode and 0.6 - 3.2 mm with the saline-linked bipolar electrodes. Under in vivo conditions and using spot applications, the 3-mm monopolar electrode created coagulation zones of similar depth to the saline-linked bipolar electrodes (around 3 mm), while the 5-mm monopolar electrode created deeper coagulations (4.5 - 6 mm) with less incidence of popping. The presence of saline around the saline-linked bipolar electrodes meant that a significant percentage of RF power (50 - 80%) was dissipated by heating in the saline layer. Coagulation zones were histologically similar for all the tested devices. Conclusions Both external (irrigation) and internal cooling in hemostatic RF devices effectively prevent tissue sticking and create similar coagulation zones from a histological point of view. Overall, saline-linked bipolar electrodes tend to create shallower coagulations than those created with an internally cooled monopolar electrode.Spanish Ministerio de Ciencia, Innovacion y Universidades MCIN/AEI/10.13039/501100011033 [Grants RTI2018-094357-B-C21 and RTI2018094357-B-C22], "Agencia Nacional de Promocion Cientifica y Tecnologica de Argentina" [PICT-2020-SERIEA-00457], Dr. Irastorza was the recipient of a scholarship from the Programa de Becas Externas Postdoctorales para Jovenes Investigadores del CONICET (Argentina).Moll, X.; Fondevila, D.; García-Arnás, F.; Burdio, F.; Trujillo Guillen, M.; Irastorza, RM.; Berjano, E.... (2022). Comparison of two radiofrequency-based hemostatic devices: saline-linked bipolar vs. cooled-electrode monopolar. International Journal of Hyperthermia. 39(1):1397-1407. https://doi.org/10.1080/02656736.2022.21408401397140739

Nefropatía congénita en Schnauzer miniatura

Un Schnauzer miniatura, macho, de 13 meses de edad, presenta un cuadro de vómitos crónicos con historia clínica de gastritis. El examen físico y las pruebas complementarias permiten diagnosticar un cuadro compatible con la nefropatía familiar del Schnauzer miniatura. Se instauró dieta y tratamiento médico hasta que el animal empeoró a los dos meses y medio

Avoiding neuromuscular stimulation in liver irreversible electroporation using radiofrequency electric fields

Electroporation based treatments typically consist in applying high voltage dc pulses. As an undesired side effect, these dc pulses cause electrical stimulation of excitable tissues such as motor nerves. In the present in vivo study, it was explored the use of bursts of sinusoidal voltage in the frequency range from 50 kHz to 2 MHz to induce irreversible electroporation (IRE) whilst avoiding neuromuscular stimulation. Series of 100 dc pulses or sinusoidal bursts, both with an individual duration of 100 μs, were delivered to rabbit liver through thin needles in a monopolar electrode configuration and thoracic movements were recorded with an accelerometer. Tissue samples were harvested three hours after treatment and later postprocessed to determine the dimensions of the IRE lesions. Thermal damage due to Joule heating was ruled out via computer simulations. Sinusoidal bursts with a frequency equal or above 100 kHz did not cause thoracic movements and induced lesions equivalent to those obtained with conventional dc pulses when the applied voltage amplitude was sufficiently high. IRE efficacy dropped with increasing frequency. For 100 kHz bursts, it was estimated that the electric field threshold for IRE is about 1.4 kV/cm whereas that of dc pulses is about 0.5 kV/cm.This work was supported by the Ministry of Economy and Competitiveness of Spain through the grant TEC2014-52383-C3-R (TEC2014-52383-C3-2-R and TEC2014-52383-C3-3-R)

Inhibition of carnitine palmitoyl-transferase 1A in hepatic stellate cells protects against fibrosis

Background & Aims The pathogenesis of liver fibrosis requires activation of hepatic stellate cells (HSCs); once activated, HSCs lose intracellular fatty acids but the role of fatty acid oxidation and carnitine palmitoyltransferase 1A (CPT1A) in this process remains largely unexplored. Methods CPT1A was found in HSCs of patients with fibrosis. Pharmacological and genetic manipulation of CPT1A were done in HSCs human cell lines and primary HCSs. Finally, we induced fibrosis in mice lacking CPT1A specifically in HSCs. Results Here we show that CPT1A expression is elevated in HSCs of patients with NASH, showing a positive correlation with the fibrosis score. This was corroborated in rodents with fibrosis, as well as in primary human HSCs and LX-2 cells activated by transforming growth factor β1 (TGFβ1) and fetal bovine serum (FBS). Furthermore, both pharmacological and genetic silencing of CPT1A prevent TGFβ1- and FBS-induced HSC activation by reducing mitochondrial activity. The overexpression of CPT1A, induced by saturated fatty acids and reactive oxygen species, triggers mitochondrial function and the expression of fibrogenic markers. Finally, mice lacking CPT1A specifically in HSCs are protected against fibrosis, induced by a choline-deficient high fat diet, a methionine- and choline-deficient diet, or treatment with carbon tetrachloride. Conclusions These results indicate that CPT1A plays a critical role in activation of HSCs and is implicated in the development of liver fibrosis, making it a potentially actionable target for fibrosis treatment. Lay summary We show that CPT1A located in HSCs is elevated in patients and mice models with fibrosis, and that CPT1A induces the activation of these cells. Inhibition of CPT1A ameliorates fibrosis by preventing the activation of HSCs