Top 100 Most Cited Papers on Multimodality Imaging for Complex Congenital Heart Disease. A Bibliometric Analysis.

Complex congenital heart disease (CCHD) is a group of heart defects present at birth. Some imaging methods can support the diagnosis of these pathologies, such as echocardiography, computed tomography, and magnetic resonance imaging. This study aimed to perform a bibliometric analysis of the top 100 articles cited on CCHD. Articles from 2013 to 2023 found in Scopus were scanned using 15 CCHD topics titles crossed with echocardiography, computed tomography, and magnetic resonance imaging. Duplicated manuscripts were eliminated using Microsoft Excel software, and the publications were ranked according to their citation count. This study selected and analyzed the top 100 most cited English-language papers. The top 100 most cited publications accumulated 16,563 citations. The manuscript with the most citations obtained 1086, representing 6.55% of the total citations. The year 2014 had the highest number of publications, with 27 papers. The first authors had affiliations from 44 countries; the United States was the country that contributed the most, with 54 manuscripts. Boston Children's Hospital was the institution that provided more articles to the top 100. Finally, the Ebstein anomaly was the topic with the highest number of citations. This study identified the 100 most cited on CCHD, and the results obtained can provide practical guidance to clinicians and researchers to familiarize themselves with the most influential publications in this field.

Deforestation increases the abundance of rodents and their ectoparasites in the Lacandon forest, Southern Mexico

Introduction: Tropical forests provide important ecosystem services, including disease control. However, few studies have focused on how deforestation affects species more suitable to be zoonotic vectors. Objective: To evaluate how deforestation affects the abundance and species richness of rodents and their associated ectoparasites in a tropical ecosystem. Methods: We captured rodents in 6 landscape units, 1 km² each, with 0.7; 5; 40; 46; 78 and 95 % tree cover, in Marques de Comillas, Chiapas, Southern Mexico. In each unit we set 90 Sherman traps that were active 24 hours for 7 days during two sampling seasons (October 2019, and September 2020). We manually extracted ectoparasites from all captured rodents. Results: We captured 70 rodents of five species: Sigmodon toltecus, Heteromys desmarestianus, Ototylomys phyllotis, Peromyscus mexicanus, and Oryzomys couesi. Rodent abundance increased with forest loss (R²= 0.706, P= 0.022). The greatest richness of rodent species occurred in sites with intermediate forest cover (40 and 78 %). The most abundant species were: S. toltecus (N= 45) followed by O. couesi (N= 9), these species dominated in sites with less forest cover. We recorded a total of 23 ectoparasite species, three of them known to be zoonotic vectors: Amblyomma sp., Ornithonyssus bacoti, and Androlaelaps fahrenholzi. Conclusions: The ongoing loss of forests promotes the proliferation of zoonotic disease vectors in this tropical ecosystem, which can potentially increase the frequency of affectation among the local population.

Introducción: Un servicio particularmente importante que brindan los bosques tropicales es el control de enfermedades. Sin embargo, pocos estudios se han enfocado en analizar cómo este servicio es afectado por la deforestación. Objetivo: Evaluar el efecto de la deforestación en la abundancia y riqueza de especies de roedores y de sus ectoparásitos en Marqués de Comillas, en el sureste de México. Métodos: Capturamos roedores en 6 unidades del paisaje (UP), cada una de 1 km², con distintos porcentajes de cobertura vegetal (0.7, 5, 40, 46, 78 y 95 %). En cada UP colocamos 90 trampas Sherman, que permanecieron activas las 24 horas por 7 días durante dos muestreos en octubre 2019 y septiembre 2020. Todos los roedores capturados fueron revisados para detectar ectoparásitos en su pelaje que fueron recolectados para su posterior identificación en el laboratorio. Resultados: Capturamos 70 roedores de cinco especies: Sigmodon toltecus, Heteromys desmarestianus, Ototylomys phyllotis, Peromyscus mexicanus y Oryzomys couesi. La abundancia de roedores aumentó con la pérdida de bosque (R² = 0.706, P = 0.022). La mayor riqueza de especies de roedores se presentó en sitios con cobertura forestal intermedia (40 y 78 %). Las especies más abundantes fueron: S. toltecus (N = 45) seguido de O. couesi (N = 9), estas especies dominaron en los sitios con menor cobertura forestal. Registramos un total de 23 ectoparásitos diferentes, identificamos 15 a nivel de especie y ocho a nivel de género. Los sitios con menor cobertura forestal presentaron la menor riqueza de especies de ectoparásitos. Detectamos tres especies de ectoparásitos (Amblyomma sp., Ornithonyssus bacoti y Androlaelaps fahrenholzi) que se sabe que son vectores de enfermedades zoonóticas. Conclusión: Encontramos que la deforestación está promoviendo un aumento en la proliferación de vectores de enfermedades zoonóticas lo que, a su vez, tiene el potencial de incrementar las afectaciones de la población local.

Multi-synaptic boutons are a feature of CA1 hippocampal connections in the stratum oriens.

Excitatory synapses are typically described as single synaptic boutons (SSBs), where one presynaptic bouton contacts a single postsynaptic spine. Using serial section block-face scanning electron microscopy, we found that this textbook definition of the synapse does not fully apply to the CA1 region of the hippocampus. Roughly half of all excitatory synapses in the stratum oriens involved multi-synaptic boutons (MSBs), where a single presynaptic bouton containing multiple active zones contacted many postsynaptic spines (from 2 to 7) on the basal dendrites of different cells. The fraction of MSBs increased during development (from postnatal day 22 [P22] to P100) and decreased with distance from the soma. Curiously, synaptic properties such as active zone (AZ) or postsynaptic density (PSD) size exhibited less within-MSB variation when compared with neighboring SSBs, features that were confirmed by super-resolution light microscopy. Computer simulations suggest that these properties favor synchronous activity in CA1 networks.

El despegue de la sanidad leonesa en la segunda mitad de los años sesenta del siglo XX. La construcción de los grandes hospitales privados / The acknowledgement of health service of León in the second half of the sixties of the twentieth century. The building of the large and private hospitals

En una época de precariedad sanitaria e inexistencia de camas hospitalarias, la capital de la provincia leonesa, siguiendo la estela de lo que ocurría en el resto del país, asistió, en la segunda mitad de los años sesenta del siglo XX, a la construcción de cinco hospitales, uno de titularidad pública y cuatro de titularidad privada, a los que dedicaremos este artículo. Objetivo principal: Evaluar la importancia de la década de los sesenta del siglo XX en el desarrollo sanitario de la capital de la provincia española de León. Metodología: Se ha realizado un estudio histórico descriptivo de las instalaciones sanitarias al inicio y al final de la década. Resultados principales: Se dotó de más de 900 camas sanitarias de titularidad privada y 280 de titularidad pública, además de un hospital antituberculoso y todo ello en el corto periodo de diez años. En solo cinco años, la oferta de camas privadas prácticamente se triplicó. Conclusión principal: La sanidad leonesa dio un salto cuantitativo y cualitativo para ofrecer a los ciudadanos instalaciones hospitalarias de titularidad privada que complementarían, en su caso, a la Seguridad Social y competirían con ella en la oferta de especialidades médicas y tecnología. (AU)

In the second half of the sixties of the twentieth century during the period of health precariousness and lack of hospital beds, the capital of the province of León, which kept up with the other cities of Spain, put up five hospitals, on the one hand, a hospital of public ownership, and the other, four hospitals of private ownership, which will be looked into this article. Main target: Analysing the importance of the sixties of the twentieth century during the health development of the capital of the Spanish province of León. Methodology: We have made a developing a historical-descriptive study of the sanitary facilities at the beginning and end of this decade. Main results: 900 hospital beds of private ownership and 280 of public ownership, besides an antitubercular hospital were put up in so short a period of ten years. In five years, the amount of private beds almost tripled. Main conclusion: The health service of León made a quantitative and qualitative leap, which provides the citizens hospital facilities of private ownership. This will be complementary with social security and will compare with her in the amount of medical specialities and technology. (AU)

El despegue de la sanidad leonesa en la segunda mitad de los años sesenta del siglo XX. La construcción de los grandes hospitales privados / The acknowledgement of health service of León in the second half of the sixties of the twentieth century. The building of the large and private hospitals

En una época de precariedad sanitaria e inexistencia de camas hospitalarias, la capital de la provincia leonesa, siguiendo la estela de lo que ocurría en el resto del país, asistió, en la segunda mitad de los años sesenta del siglo XX, a la construcción de cinco hospitales, uno de titularidad pública y cuatro de titularidad privada, a los que dedicaremos este artículo. Objetivo principal: Evaluar la importancia de la década de los sesenta del siglo XX en el desarrollo sanitario de la capital de la provincia española de León. Metodología: Se ha realizado un estudio histórico descriptivo de las instalaciones sanitarias al inicio y al final de la década. Resultados principales: Se dotó de más de 900 camas sanitarias de titularidad privada y 280 de titularidad pública, además de un hospital antituberculoso y todo ello en el corto periodo de diez años. En solo cinco años, la oferta de camas privadas prácticamente se triplicó. Conclusión principal: La sanidad leonesa dio un salto cuantitativo y cualitativo para ofrecer a los ciudadanos instalaciones hospitalarias de titularidad privada que complementarían, en su caso, a la Seguridad Social y competirían con ella en la oferta de especialidades médicas y tecnología (AU)

In the second half of the sixties of the twentieth century during the period of health precariousness and lack of hospital beds, the capital of the province of León, which kept up with the other cities of Spain, put up five hospitals, on the one hand, a hospital of public ownership, and the other, four hospitals of private ownership, which will be looked into this article. Main target: Analysing the importance of the sixties of the twentieth century during the health development of the capital of the Spanish province of León. Methodology: We have made a developing a historical-descriptive study of the sanitary facilities at the beginning and end of this decade. Main results: 900 hospital beds of private ownership and 280 of public ownership, besides an antitubercular hospital were put up in so short a period of ten years. In five years, the amount of private beds almost tripled. Main conclusion: The health service of León made a quantitative and qualitative leap, which provides the citizens hospital facilities of private ownership. This will be complementary with social security and will compare with her in the amount of medical specialities and technology (AU)

Characterization of hypotensive and vasorelaxant effects of PHAR-DBH-Me a new cannabinoid receptor agonist.

The effect of PHAR-DBH-Me, a cannabinoid receptor agonist, on different cardiovascular responses in adult male rats was analyzed. The blood pressure was measured directly and indirectly. The coronary flow was measured by Langendorff preparation, and vasomotor responses induced by PHAR-DBH-Me in aortic rings precontracted with phenylephrine (PHEN) were analyzed. The intravenous injection of the compound PHAR-DBH-Me (0.018-185 µg/kg) resulted in decreased blood pressure; maximum effect was observed at the dose of 1,850 µg/kg. A concentration-dependent increase in the coronary flow was observed in a Langendorff preparation. In the aortic rings, with and without endothelium, pre-contracted with PHEN (10-6 M), the addition of PHAR-DBH-Me to the superfusion solution (10-12-10-5 M), produced a vasodilator response, which depends on the concentration and presence of the endothelium. L-NAME inhibited these effects. Addition of CB1 receptor antagonist (AM 251) did not modify the response, while CB2 receptor antagonist (AM630) decreased the potency of relaxation elicited by PHAR-DBH-Me. Indomethacin shifted the curve concentration-response to the left and produced an increase in the magnitude of the maximum endothelium dependent response to this compound. The maximum effect of PHAR-DBH-Me was observed with the concentration of 10-5 M. These results show that PHAR-DBH-Me has a concentration-dependent and endothelium-dependent vasodilator effect through CB2 receptor. This vasodilation is probably mediated by the synthesis/release of NO. On the other hand, it is suggested that PHAR-DBH-Me also induces the release of a vasoconstrictor prostanoid.

A MATLAB App for calculating the age-dependent degree of erosion of monogenetic scoria cones from DEM data.

We present a MATLAB App aimed to characterize the degree of erosion of monogenetic scoria cones from two independent sets of morphometric parameters. One quantifies the shape and size of undulations in DEM level contours through a novel parameter, the Average Erosion Index (AEI), using Elliptical Fourier Descriptors to calculate the wavelength spectra of undulations in selected contours over an ample range of resolutions of the database. The other is a more conventional set of parameters characterizing the vertical profiles of cones. This algorithm permits correcting those parameters for terrain inclination.•These methods aim for a consistent assessment of the erosion-related relative ages of volcanoes in extensive monogenetic fields, from DEM data.•The age-related degree of erosion is revealed by two main parameters: The Average Erosion Index (AEI), calculated from the Elliptic Fourier Descriptor spectrum of a scoria cone contour lines; and the aspect ratio of a scoria cone vertical profile, considering terrain inclinations, if it is assumed that all cones acquired the same morphology at the time of their formation eruptions.•The Method provides erosion metrics from a sizable range of DEM resolutions. For age-related applications, it is recommended to use resolutions better than 12 m.

Pediatric multisystem SARS COV2 with versus without cardiac involvement: a multicenter study from Latin America.

Latin America (LATAM) children offer special insight into Severe Acute Respiratory Syndrome Coronavirus 2 (SARS COV2) due to high-risk race/ethnicity, variability in medical resources, diverse socioeconomic background, and numerous involved organ systems. This multinational study of LATAM youth examined the distinguishing features of acute or late multisystem SARS COV2 with versus without cardiac involvement. A consecutive sample of youth 0-18 years old (N = 98;50% male) presenting with multisystem SARS COV2 to 32 centers in 10 Latin American countries participating in a pediatric cardiac multi-imaging society were grouped as with versus without cardiac involvement, defined as abnormal echocardiographic findings or arrhythmia. Collected clinical data were analyzed by Student's t-test or Fisher's exact test. Cardiac (N = 48, 50% male) versus no cardiac (N = 50, 50% male) were similar in age; weight; nonrespiratory symptoms; and medical history. The cardiac group had 1 death and symptoms including coronary artery dilation, ejection fraction <50%, pericardial effusion, peripheral edema, arrhythmia, and pulmonary artery thrombus. The cardiac group had higher risk of ICU admission (77% vs 54%, p = 0.02); invasive ventilation (23% vs 4%,p = 0.007); vasoactive infusions (27% vs 4%, p = 0.002); prominent respiratory symptoms (60% vs 36%, p < 0.03); abnormal chest imaging (69% vs 34%, p = 0.001); troponin (33% vs 12%, p = 0.01); alanine aminotransferase (33% vs 12%, p = 0.02); and thrombocytopenia (46% vs 22%, p = 0.02). Receiver operating curve analysis showed that abnormal laboratories had 94% sensitivity and 98% negative predictive value on the need for ICU interventions.Conclusion: In LATAM children with multisystem SARS COV2, cardiac involvement was prevalent. Cardiac involvement was more likely to require ICU interventions, certain abnormal labs, and respiratory involvement. What is Known: • SARS COV2 can be asymptomatic in children but in some cases can have serious multisystemic involvement. • Hispanic ethnicity is purportedly at high risk of SARS COV2 in nations where they are often disadvantaged minority populations. What is New: • Latin American children presenting with multisystem SARS COV2 frequently have cardiac involvement which was associated with ICU interventions; prominent respiratory symptoms; abnormal chest X-ray; elevated troponin, ALT, and thrombocytopenia. • Elevated troponin, ALT or thrombocytopenia had high sensitivity and negative predictive value on the need for intensive care interventions.

Evaluación cardiovascular de pacientes sometidos a tratamientos oncológicos en una clínica de supervivientes de cáncer infantil en México / Cardiovascular evaluation of patients undergoing cancer treatments at a clinic for childhood cancer survivors in Mexico

Resumen Objetivo: Describir los efectos cardiovasculares del tratamiento del cáncer infantil en supervivientes mediante métodos clínicos, electrocardiográficos y ecocardiográficos. Material y métodos: Estudio transversal y observacional de casos y controles de 34 pacientes de una clínica de supervivientes de cáncer infantil, evaluados de forma clínica, con electrocardiograma, ecocardiografía convencional y strain. Edad promedio de 13.03 años; dosis acumulada de antracíclicos promedio de 219.5 mg/m2; siete además con radiación a tórax. Análisis con pruebas T de Student y regresión lineal. Resultados: Fracción de expulsión izquierda preservada en supervivientes. Strain longitudinal izquierdo en dos, tres cámaras y circunferencial disminuido en supervivientes (p < 0.05). Los enfermos sometidos a radioterapia y antracíclicos mostraron un incremento de la frecuencia cardíaca, disminución de la fracción de expulsión y fracción de acortamiento izquierdos (< 0.05). Ventrículo derecho sin cambios significativos. Discusión y conclusiones: Existe un gran número de supervivientes de cáncer infantil tratados con cardiotóxicos y radioterapia; éstos pueden experimentar cambios en el strain miocárdico ventricular (aun con fracción de expulsión normal) o arritmias, como lo muestra el grupo estudiado, que concuerda con protocolos internacionales previos. Es importante su evaluación cardiovascular completa para predecir el riesgo de insuficiencia cardíaca como parte de un seguimiento protocolizado en clínicas de cardiooncología bien establecidas.

Abstract Objective: To describe the cardiovascular effects of childhood cancer treatment in survivors through clinical, electrocardiogram and echocardiographic methods. Material and methods: Prospective, observational case-control study of 34 patients of a Childhood Cancer Survivors Clinic, evaluated clinically, with electrocardiogram, with conventional echocardiography and strain. Average age 13.03 years; cumulative average anthracyclic dose 219.5 mg/m2; seven also with chest radiation. Analysis with student T tests and linear regression. Results: Left ejection fraction in survivors was preserved. Longitudinal left strain in 2, 3 chambers and circumferential was decreased in survivors (p < 0.05). Those undergoing radiotherapy and anthracyclic presented increased heart rate, ejection fraction and left shortening fraction decreased (< 0.05). Right ventricle without significant changes. Discussion and conclusions: There are a large number of childhood cancer survivors treated with cardiotoxics and radiotherapy. They may present changes in ventricular myocardial strain (even with normal ejection fraction) and/or arrhythmias, as evidenced in the group studied, which is consistent with previous international studies. Its complete cardiovascular evaluation is important to predict the risk of heart failure as part of a protocolized follow-up in well-established cardio oncology clinics.

A meta-analysis of infants' word-form recognition.

Recognizing word forms is an important step on infants' way toward mastering their native language. The present study takes a meta-analytic approach to assess overarching questions on the literature of early word-form recognition. Specifically, we investigated the extent to which there is cross-linguistic evidence for an early recognition lexicon, and how it may be influenced by infant age, language background, and familiarity of the selected stimuli (approximated by parent-reported word knowledge). Our meta-analysis-with open data access on metalab.stanford.edu-was based on 32 experiments in 16 different published or unpublished studies on infants 5-15 months of age. We found an overall significant effect of word-form familiarity on infants' responses. This effect increased with age and was higher for infants learning Romance languages than other languages. We further found that younger, but not older, infants showed higher effect sizes for more familiar word lists. These insights should help researchers plan future studies on word-form recognition.

A multi-lab study of bilingual infants: Exploring the preference for infant-directed speech.

From the earliest months of life, infants prefer listening to and learn better from infant-directed speech (IDS) than adult-directed speech (ADS). Yet, IDS differs within communities, across languages, and across cultures, both in form and in prevalence. This large-scale, multi-site study used the diversity of bilingual infant experiences to explore the impact of different types of linguistic experience on infants' IDS preference. As part of the multi-lab ManyBabies 1 project, we compared lab-matched samples of 333 bilingual and 385 monolingual infants' preference for North-American English IDS (cf. ManyBabies Consortium, 2020: ManyBabies 1), tested in 17 labs in 7 countries. Those infants were tested in two age groups: 6-9 months (the younger sample) and 12-15 months (the older sample). We found that bilingual and monolingual infants both preferred IDS to ADS, and did not differ in terms of the overall magnitude of this preference. However, amongst bilingual infants who were acquiring North-American English (NAE) as a native language, greater exposure to NAE was associated with a stronger IDS preference, extending the previous finding from ManyBabies 1 that monolinguals learning NAE as a native language showed a stronger preference than infants unexposed to NAE. Together, our findings indicate that IDS preference likely makes a similar contribution to monolingual and bilingual development, and that infants are exquisitely sensitive to the nature and frequency of different types of language input in their early environments.

Estudio y seguimiento cardiovascular de niños y adolescentes sometidos a tratamientos oncohematológicos. ¿Por qué, cómo y cuándo? / Study and cardiovascular follow-up of children and adolescents undergoing oncohematological treatments. Why, how and when?

Resumen Estudio de revisión de diversas publicaciones internacionales en la literatura médica relacionados con la evaluación cardiovascular en pacientes en edad pediátrica sometidos a algún tipo de tratamiento oncohematológico, previendo factores de riesgo que en conjunto con la quimioterapia y/o radioterapia merman el adecuado funcionamiento cardiovascular de forma particular.

Abstract Review of several international publications in the medical literature related to cardiovascular evaluation in pediatric patients undergoing some type of onco-hematological treatment, providing risk factors that together with chemo and/or radiotherapy, impair adequate cardiovascular function in a particular way.

Study and cardiovascular follow-up of children and adolescents undergoing oncohematological treatments. Why, how and when? / Estudio y seguimiento cardiovascular de niños y adolescentes sometidos a tratamientos oncohematológicos. ¿Por qué, cómo y cuándo?

Review of several international publications in the medical literature related to cardiovascular evaluation in pediatric patients undergoing some type of onco-hematological treatment, providing risk factors that together with chemo and/or radiotherapy, impair adequate cardiovascular function in a particular way.

Estudio de revisión de diversas publicaciones internacionales en la literatura médica relacionados con la evaluación cardiovascular en pacientes en edad pediátrica sometidos a algún tipo de tratamiento oncohematológico, previendo factores de riesgo que en conjunto con la quimioterapia y/o radioterapia merman el adecuado funcionamiento cardiovascular de forma particular.

[Cardiovascular evaluation of patients undergoing cancer treatments at a clinic for childhood cancer survivors in Mexico]. / Evaluación cardiovascular de pacientes sometidos a tratamientos oncológicos en una clínica de supervivientes de cáncer infantil en México

Objetivo: Describir los efectos cardiovasculares del tratamiento del cáncer infantil en supervivientes mediante métodos clínicos, electrocardiográficos y ecocardiográficos. Material y métodos: Estudio transversal y observacional de casos y controles de 34 pacientes de una clínica de supervivientes de cáncer infantil, evaluados de forma clínica, con electrocardiograma, ecocardiografía convencional y strain. Edad promedio de 13.03 años; dosis acumulada de antracíclicos promedio de 219.5 mg/m2; siete además con radiación a tórax. Análisis con pruebas T de Student y regresión lineal. Resultados: Fracción de expulsión izquierda preservada en supervivientes. Strain longitudinal izquierdo en dos, tres cámaras y circunferencial disminuido en supervivientes (p < 0.05). Los enfermos sometidos a radioterapia y antracíclicos mostraron un incremento de la frecuencia cardíaca, disminución de la fracción de expulsión y fracción de acortamiento izquierdos (< 0.05). Ventrículo derecho sin cambios significativos. Discusión y conclusiones: Existe un gran número de supervivientes de cáncer infantil tratados con cardiotóxicos y radioterapia; éstos pueden experimentar cambios en el strain miocárdico ventricular (aun con fracción de expulsión normal) o arritmias, como lo muestra el grupo estudiado, que concuerda con protocolos internacionales previos. Es importante su evaluación cardiovascular completa para predecir el riesgo de insuficiencia cardíaca como parte de un seguimiento protocolizado en clínicas de cardiooncología bien establecidas.

Dual language input and the impact of language separation on early lexical development.

We examined properties of the input and the environment that characterize bilingual exposure in 11-month-old infants with a regular exposure to French and an additional language, and their possible effects on receptive vocabulary size. Using a diary method, we found that a majority of the families roughly followed a one-parent-one-language approach. Yet, the two languages co-occurred to various extents within the same half-hour both within and across speakers. We used exploratory correlation analyses to examine potential effects of the dual input on the size of infants' vocabularies. The results revealed some evidence for an impact of language separation by speakers.

Effects of Oleamide on the Vasomotor Responses in the Rat.

Introduction: Cardiovascular effects of endocannabinoids (eCBs) have generated considerable interest since it has been suggested that the eCB system could become the new pharmacological target, either by blocking its activity or by promoting its effects on several cardiovascular diseases such as hypovolemic and septic shock or hypertension. The purpose of this study was to examine the effects of oleamide on several vasomotor responses in adult rats. Materials and Methods: Blood pressure (BP) was measured both directly and indirectly. Coronary flow was quantified with Langendorf preparation, and the vasomotor responses induced by oleamide were analyzed in the aortic rings. Results: Oleamide induced a decrease in BP, by both direct and indirect methods, which were dose dependent. An increase in coronary flow was observed with Langendorf preparation depending on the dose. Oleamide produced a vasodilator response in aortic rings pre-contracted with phenylephrine (10-5 M), which was concentration and endothelium dependent. This relaxing effect was of minor magnitude than that induced with the same dose on BP. L-NAME did not modify these effects. However, indomethacin induced a shift to the left of the concentration-response curve to oleamide and an increase in the magnitude of maximum vasodilation in rings with endothelium. Oleamide produced the maximal relaxant response at 10-5 M concentration. Conclusions: Oleamide has both in vivo and in vitro vasodilator effects. Vasodilator effects could be mediated by compounds synthesized/released by the endothelium (hyperpolarizing factor) or acting directly on vascular smooth muscle in aortic rings. The TRPV1 and CB1R receptors could mediate these effects. Finally, the results suggest that oleamide probably induces the synthesis/release of a vasoconstrictor prostanoid.

Expression of the Biologically Active Insulin Analog SCI-57 in Nicotiana Benthamiana.

Diabetes mellitus is a growing problem worldwide; however, only 23% of low-income countries have access to insulin, and ironically it costs higher in such countries than high-income ones. Therefore, new strategies for insulin and insulin analogs production are urgently required to improve low-cost access to therapeutic products, so as to contain the diabetes epidemic. SCI-57 is an insulin analog with a greater affinity for the insulin receptor and lower thermal degradation than native insulin. It also shows native mitogenicity and insulin-like biological activity. In this work, SCI-57 was transiently expressed in the Nicotiana benthamiana (Nb) plant, and we also evaluated some of its relevant biological effects. An expression plasmid was engineered to translate an N-terminal ubiquitin and C-terminal endoplasmic reticulum-targeting signal KDEL, in order to increase protein expression and stability. Likewise, the effect of co-expression of influenza M2 ion channel (M2) on the expression of insulin analog SCI-57 (SCI-57/M2) was evaluated. Although using M2 increases yield, it tends to alter the SCI-57 amino acid sequence, possibly promoting the formation of oligomers. Purification of SCI-57 was achieved by FPLC cation exchange and ultrafiltration of N. benthamiana leaf extract (NLE). SCI-57 exerts its anti-diabetic properties by stimulating glucose uptake in adipocytes, without affecting the lipid accumulation process. Expression of the insulin analog in agroinfiltrated plants was confirmed by SDS-PAGE, RP-HPLC, and MS. Proteome changes related to the expression of heterologous proteins on N. benthamiana were not observed; up-regulated proteins were related to the agroinfiltration process. Our results demonstrate the potential for producing a biologically active insulin analog, SCI-57, by transient expression in Nb.

Aminoguanidine reduces diabetes-associated cardiac fibrosis.

Aminoguanidine (AG) inhibits advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP) accumulated as a result of excessive oxidative stress in diabetes. However, the molecular mechanism by which AG reduces AGE-associated damage in diabetes is not well understood. Thus, we investigated whether AG supplementation mitigates oxidative-associated cardiac fibrosis in rats with type 2 diabetes mellitus (T2DM). Forty-five male Wistar rats were divided into three groups: Control, T2DM and T2DM+AG. Rats were fed with a high-fat, high-carbohydrate diet (HFCD) for 2 weeks and rendered diabetic using low-dose streptozotocin (STZ) (20 mg/kg), and one group was treated with AG (20 mg/kg) up to 25 weeks. In vitro experiments were performed in primary rat myofibroblasts to confirm the antioxidant and antifibrotic effects of AG and to determine if blocking the receptor for AGEs (RAGE) prevents the fibrogenic response in myofibroblasts. Diabetic rats exhibited an increase in cardiac fibrosis resulting from HFCD and STZ injections. By contrast, AG treatment significantly reduced cardiac fibrosis, α-smooth muscle actin (αSMA) and oxidative-associated Nox4 and Nos2 mRNA expression. In vitro challenge of myofibroblasts with AG under T2DM conditions reduced intra- and extracellular collagen type I expression and Pdgfb, Tgfß1 and Col1a1 mRNAs, albeit with similar expression of Tnfα and Il6 mRNAs. This was accompanied by reduced phosphorylation of ERK1/2 and SMAD2/3 but not of AKT1/2/3 and STAT pathways. RAGE blockade further attenuated collagen type I expression in AG-treated myofibroblasts. Thus, AG reduces oxidative stress-associated cardiac fibrosis by reducing pERK1/2, pSMAD2/3 and collagen type I expression via AGE/RAGE signaling in T2DM.