Terapia de conversión en cáncer gástrico: experiencia del Instituto Nacional de Cancerología de Colombia / Conversion therapy in gastric cancer: experience at Instituto Nacional de Cancerología de Colombia

RESUMEN Antecedentes: el cáncer gástrico (CG) representa un problema de salud pública en Colombia y el mundo. Dado que la mayoría de los pacientes se encuentran en estadios avanzados en el momento del diagnóstico. desarrollar estrategias de manejo. como la terapia de conversión (TC). es una necesidad cada vez mayor en su tratamiento. Objetivo: estimar los resultados con la TC en el tratamiento de pacientes con CG avanzado en el Instituto Nacional de Cancerología de Colombia (INC). Material y métodos: serie de casos de pacientes con adenocarcinoma gástrico incurable llevados a quimioterapia de inducción y cirugía con intención curativa. entre los años 2010 y 2021. Se revisaron de forma retrospectiva los datos clínico-patológicos y de supervivencia. La supervivencia global (SG) se calculó desde la fecha de la primera quimioterapia hasta la muerte. Las funciones de supervivencia se estimaron con tablas de vida y por el método de Kaplan-Meier y se realizaron curvas de supervivencia a 3 y 5 años. Resultados: se analizaron los datos de 23 pacientes con edad promedio de 56 años. 17 (74%) fueron varones. El criterio de irresecabilidad más frecuente fue un tumor T4b en 13 casos (56.5%). Todos recibieron TC. La mediana de seguimiento fue de 28 meses. Se documentaron 11 recurrencias (52%). La mediana de supervivencia fue de 41.2 meses y la SG a 3 y 5 años de 57.7% y 38.5%. respectivamente. Conclusiones: la TC permitió obtener una SG aceptable de pacientes seleccionados con CG avanzado incurable. Esta estrategia requiere una cuidadosa selección y manejo multidisciplinario en centros oncológicos de referencia.

ABSTRACT Background: Gastric cancer (GC) represents a public health problem in Colombia and worldwide. Since most patients are at advanced stages at the time of diagnosis. it is necessary to develop management strategies as conversion therapy (CT). Objective: The aim of this study was to estimate the results of CT for treating patients with advanced and GC at Instituto Nacional de Cancerología de Colombia (INC). Material and methods: We included patients with incurable gastric cancer who underwent induction chemotherapy and intended curative surgery between 2010 and 2021. The clinical and pathological data and survival of the patients included were retrospectively reviewed. Overall survival (OS) was calculated from the time of initiation of chemotherapy until the date of death. Survival functions were estimated using the life table and Kaplan-Meier methods. and survival curves at 3 and 5 years were constructed. Results: 23 patients were analyzed; mean age was 56 years. and 17 (74%) were men. The most common criterion indicating unresectability was a T4b tumor in 13 cases (56.5%). All the patients underwent CT. Median follow-up was 28 months. Eleven patients developed disease recurrence (52%). Median survival was 41.2 months. and 3- and 5-year OS was 57.7% and 38.5%. respectively. Conclusions: CT provided an acceptable OS rate for selected patients with incurable advanced GC. This strategy requires an adequate selection of patients and multidisciplinary management in reference oncology centers.

Formulation and technology of oxymatrine-astragaloside IV coloaded liposomes based on quality by design / 药学学报

To optimize the formulation and technology of oxymatrine-astragaloside IV coloaded liposomes (Om-As-Lip) based on quality by design (QbD) principles, and further to verify the feasibility of its amplification process, Om-As-Lip was prepared by ethanol injection combined with pH gradient method. The critical material attributions of Om-As-Lip were evaluated by dual-risk analysis tools and Plackett-Burman design (PBD). The formulation of Om-As-Lip was further optimized with the Box-Behnken design (BBD). The design space was also established based on the contour plots of BBD. In order to further investigate the amplification process of Om-As-Lip, the critical process parameters of high-pressure homogenization (HPH) were optimized by single-factor test, and the quality of the final product was also evaluated. The results of risk analysis and PBD confirmed that the astragaloside concentration, cholesterol concentration, and phospholipid ratio (HSPC∶SPC) were the ctitical material attributes. The model established by BBD had a good predictability, and the optimized mass ratio of As to phospholipids was 1∶40, cholesterol to phospholipids was 1∶10, HSPC to SPC was 51∶9. The design space of Om-As-Lip was as follows: the ratio of cholesterol to phospholipids was 1∶12-1∶5 and HSPC to SPC was 1∶7-17∶3. The optimized high-pressure homogenization pressure was 600 bar, temperature was 4 ℃, and cycle times was 6 times for HPH-Om-As-Lip. The quality of Om-As-Lip prepared based on the QbD concept can meet the expected CQAs, and the formulation and technology established can provide a reliable experimental basis for its future development and applications.

Evaluación del desempeño cognitivo en escolares y adolescentes con diabetes mellitus tipo 1 / Evaluation of cognitive performance in children and adolescents with type 1 diabetes mellitus

Resumen El objetivo del trabajo fue evaluar el funcionamiento cognitivo de niños y adolescentes con diabetes mellitus tipo 1 (DM1) de la consulta de Endocrinología del IAHULA, y compararlo al de niños no diabéticos, así como investigar la posible influencia de factores relacionados con la enfermedad sobre la cognición. Se realizó un estudio observacional analítico, transversal, que incluyó un grupo de 30 pacientes con DM1 de 8 a 16 años de edad (16 varones) y un grupo control de 30 individuos pareados por edad, género, escolaridad y condición socioeconómica. Se realizó interrogatorio y revisión de historias clínicas para obtener datos sobre las características clínicas y el tratamiento de la DM1. Se les aplicó el test WISC IV para evaluar cognición y cociente intelectual (CI). La edad promedio de los pacientes fue de 13,27 ± 2,31 años, la mitad de ellos masculinos. Se encontraron puntajes menores en los distintos dominios del WISC IV en el grupo con DM1 al compararlos con los del grupo control (p<0,01). El CI fue menor en los niños con DM1 que en los controles (75,47 ± 13,87 frente a 88,57±11,06; p=0,0001); así mismo, se observó con mayor frecuencia un puntaje del CI inferior al percentil 10 en los pacientes con DM1 en comparación con los controles (63,3% frente a 33,3%; p=0,02; Odds ratio: 3,45; IC95%: 1,19-9,99). Se concluyó que la DM1 impacta negativamente el desempeño cognitivo de niños y adolescentes. Se recomienda la evaluación cognitiva de estos pacientes, ya que podría repercutir en su vida diaria.

Abstract The study aimed to evaluate the cognitive functioning of children and adolescents with type 1 diabetes mellitus (T1DM) recruited from the IAHULA Endocrinology Outpatient Unit and to compare it to that of non-diabetics as to investigate the influence on cognition of factors related to the disease. An analytical, cross-sectional observational study was carried out on a group of 30 patients with T1DM between 8 and 16 years of age and on a control group of 30 individuals matched by age, gender, education, and socioeconomic status. Interrogation and review of medical records to obtain data on the clinical characteristics and treatment of T1DM were conducted. The WISC IV test was then applied to evaluate cognition and intellectual coefficient (IQ). The average age of the diabetic patients was 13.27±2.31 years, and half of them were male. Lower scores were found in the different domains of the WISC IV in the group with T1DM (p<0.01). The IQ was found to be lower in children with T1DM than in controls (75.47±13.87 vs. 88.57±11.06; p=0.0001). Likewise, a higher frequency of IQ scores below the 10th percentile was observed in the diabetic children (63.3% vs. 33.3%; p=0.02; Odds ratio: 3.45; 95%CI: 1.19-9.99). It was concluded that T1DM negatively impacts the cognitive performance of children and adolescents. Cognitive evaluation of these patients is recommended, as it could affect their daily life.

AngioVac System for Infective Endocarditis: A New Treatment for an Old Disease

Three different patients presented to our institution with right-sided infective endocarditis (IE). All three were found to have vegetation on the tricuspid valve. These patients were started on appropriate antimicrobial therapy according to their blood cultures sensitivities. Despite this management, the patients� clinical status did not improve solely on antimicrobials. Surgery was, therefore, indicated to remove the vegetations. Traditionally, the appropriate management would have been invasive surgery. However, these patients were subjected to a novel treatment in our institution for right?sided IE: percutaneous mechanical vegetation debulking with an AngioVac system. After this procedure, all three patients� clinical status improved drastically. This new less invasive approach seems to offer the same results as the traditional invasive surgery, with faster recovery time. More comparative studies are needed to confirm this idea.

Fast Skeletal Muscle Troponin and Tropomyosin as a Dietary Source of Antidiabetic and Antihypertensive Bioactive Peptides: An In Silico Study / Troponina y Tropomiosina de Músculo Esquelético como Fuente Alimentaria de Péptidos Bioactivos Antidiabéticos y Antihipertensivos: Estudio In Silico

Background: The nutraceutical properties of food hydrolysates rely on multiple biochemical interactions involving the modulation of enzymes and cellular receptors. Numerous bioactive peptides released from troponin and tropomyosin digestion have been identified. Their characterization has mostly been performed by hydrolysis catalyzed by proteases unrelated to the human digestive system. Objective: This study aimed to determine the bioactive profile of beef, pork, and chicken meat by analyzing the frequency and pharmacokinetics of biopeptides released from troponin and tropomyosin. Methods:In silico digestion and biopeptide release frequency were studied by three parameters; bioactive fragments release frequency (AE), frequency percentage (W), and mean occurrence (AS), all stated on the BIOPEP-UWM platform. Further on, hydrolysis end-products were screened based on gastrointestinal-absorption probability and pharmacokinetic profiling performed on SwissADME, SwissTargetPrediction, and ADME/Tlab bioinformatics web tools. Statistical analyses were performed using a one-way ANOVA test. Results: Dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibiting biopeptides exhibited the highest release frequency. Moreover, W and ASparameters showed no significant difference (p>0.05) between the myofibrillar isoforms assessed. Seven biopeptides were classified as highly absorbable and reported optimal drug-likeness compliance. Although biopeptides hold good pharmacokinetic properties, the therapeutic potency of biopeptides showed to be lower than those of DPP-IV and ACE-inhibiting drugs. Conclusions: Troponin and tropomyosin are rich dietary sources of bioactive peptides, mainly DPP-IV and ACE inhibitors. Digestion end-products are mainly dipeptides with optimal pharmacokinetic and drug-like properties, suggesting a potential therapeutic application in hypertensive and hyperglycemic disorders

Antecedentes: Las propiedades nutracéuticas de los hidrolizados de alimentos dependen de múltiples interacciones bioquímicos que involucran la modulación de enzimas y receptores celulares. Se han identificado numerosos péptidos bioactivos liberados de la digestión de troponina y tropomiosina, pero su caracterización se ha llevado a cabo principalmente por hidrólisis catalizada por proteasas ajenas al sistema digestivo humano. Objetivo: Este estudio tuvo como objetivo determinar el perfil bioactivo de la carne de res, cerdo y pollo mediante el análisis de la frecuencia y farmacocinética de los biopéptidos liberados de la troponina y la tropomiosina. Métodos: Se estudió la digestión in silico y la frecuencia de liberación de biopéptidos mediante dos parámetros; frecuencia de liberación de fragmentos bioactivos (AE), frecuencia porcentual (W) y ocurrencia media (AS), ambos indicados en la plataforma BIOPEP-UWM. Más adelante, los productos finales de la hidrólisis se examinaron en función de la probabilidad de absorción gastrointestinal y el perfil farmacocinético realizado en las herramientas bioinformáticas SwissADME, SwissTargetPrediction y ADME/Tlab. El análisis estadístico se llevó a cabo mediante una prueba ANOVA de una vía. Resultados: Los biopéptidos inhibidores de la dipeptidil peptidasa IV (DPP-IV) y la enzima convertidora de angiotensina (ECA) exhibieron la mayor frecuencia de liberación. Además, los parámetros W y ASno mostraron diferencias significativas (p> 0.05) entre las isoformas miofibrilares evaluadas. Siete biopéptidos se clasificaron como altamente absorbibles e informaron un cumplimiento óptimo de similitud con el fármaco. Aunque los biopéptidos tienen propiedades farmacocinéticas adecuadas, su potencia terapéutica demostró ser menor que la de los fármacos inhibidores de la DPP-IV y la ACE. Conclusiones: La troponina y la tropomiosina son una fuente dietética rica en péptidos bioactivos, principalmente DPP-IV e inhibidores de la ACE. Los productos finales de la digestión son principalmente dipéptidos con propiedades farmacocinéticas óptimas y similares a la de los fármacos, lo que sugiere una aplicación terapéutica factible en trastornos hipertensivos e hiperglicémicos

Manejo ortoplástico de fractura expuesta de pierna grave: a propósito de un caso / Orthoplastic management of severe open fractures: case report / Tratamento ortoplástico das fraturas expostas grave: relato de caso

Las fracturas expuestas de pierna son lesiones frecuentes, sus principales complicaciones son la infección y la dificultad en la consolidación ósea. El abordaje ortoplástico implica llevar a cabo principios y prácticas de ambas especialidades en forma conjunta, evitando el tratamiento por separado de los problemas que surgen de estas lesiones graves y así intentar disminuir al mínimo las complicaciones. Nuestro objetivo es transmitir la importancia del enfoque ortoplástico en las fracturas expuestas. Se reporta el caso de un paciente adulto, con una fractura de pierna, tibia y peroné expuesta, que requirió múltiples procedimientos quirúrgicos en vistas a preservar el miembro. Fueron necesarias variadas estrategias para controlar la infección ósea y reconstruir las partes blandas y óseas. Con el estímulo de la movilidad del tobillo y pie, se logró comenzar a restituir la función del miembro desde el inicio; permitiendo, a las 6 semanas de evolución, el apoyo del miembro mediante una fijación ósea estable. A los 24 meses de seguimiento clínico y radiográfico evidenciamos paciente y familia satisfechos con un excelente resultado funcional según score ASAMI. Se concluye que en pacientes con fracturas expuestas graves, es clave el abordaje ortoplástico para lograr mejores resultados.

Open leg fractures are frequent injuries; the infection and difficulty in bone healing are their main complications. The orthoplastic approach involves carrying out principles and practices of both specialties together, avoiding separate treatment of the problems that arise from these serious injuries and thus minimizing complications. The objective of the article is to convey the importance of the orthoplastic approach in open fractures. We report the case of an adult patient, with an open fractured leg, to required multiple surgical procedures to preserve the limb. Various strategies were necessary to cure the bone infection and reconstruct the soft tissue and bone. The limb function restore was possible promoting the ankle and foot mobility from the beginning and it allowed weight-bearing on the limb through stable bone fixation, at 6 weeks of evolution. We evidenced a patient and family satisfied with an excellent functional result according to the ASAMI score, at 24 moths of clinical and radiographic follow-up. It is concluding that in patients with severe open fractures, the orthoplastic approach is key to obtain better results.

As fraturas expostas da perna são lesões frequentes, suas principais complicações são infecção e dificuldade de consolidação óssea. A abordagem ortoplástica envolve a realização conjunta de princípios e práticas de ambos ases especialidades, evitando o tratamento separado dos problemas decorrentes dessas lesões graves e minimizando assim as complicações. Nosso objetivo é transmitir a importância da abordagem ortoplástica nas fraturas expostas. É relatado o caso de um paciente adulto, com fratura de perna, tíbia e fíbula expostas, necessitando de múltiplos procedimentos cirúrgicos para preservação do membro. Várias estratégias foram necessárias para curar a infecção óssea e reconstruir os tecidos moles e o osso. Foi possível começar a restaurar a função do membro desde o início, com a estimulação da mobilidade do tornozelo e do pé; com 6 semanas de evolução, concedendo cargas ao membro por meio de fixação óssea estável. Apresentou boa evolução, aos 24 meses de acompanhamento clínico y radiográfico, constatamos a satisfação do paciente e família. com um excelente resultado funcional de acordo a pontuação ASAMI. Conclui-sé que em pacientes com fraturas expostas graves, a abordagem ortoplástica é fundamental para obter melhores resultados.

Astragaloside IV alleviates lung inflammation in Klebsiella pneumonia rats by suppressing TGF-β1/Smad pathway

Astragaloside IV is a biologically active substance derived from the traditional Chinese medicine Astragalus mambranaceus Bunge, and has antioxidant, anti-inflammatory, and anti-apoptotic properties. In this study, we aimed to investigate the effects of astragaloside IV on Klebsiella pneumonia rats and the underlying mechanisms. Klebsiella pneumoniae (K. pneumoniae) rats were treated with different dosages of astragaloside IV (5, 10, and 20 mg/kg) by intragastric administration. The levels of pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) were determined. Pathological changes of lung tissue were inspected by HE staining. The expression of transforming growth factor (TGF)-β1 in lung tissue was determined with immunohistochemistry, and the expression levels of TGF-β1, p-Smad2/Smad2, p-Smad3/Smad3, IκBα/p-IκBα, and p65/p-p65 in lung tissue were determined by western blot. The mechanism was further investigated with TGF-β1 inhibitor SB-431542. Astragaloside IV reduced the elevated levels of pro-inflammatory cytokines caused by K. pneumoniae and improved lung tissue damage in a dose-dependent manner. Astragaloside IV also decreased the expression of TGF-β1/Smad signaling pathway-related proteins and decreased the protein levels of inflammation-related p-IκBα and p65 in lung tissues induced by K. pneumoniae. Additionally, it was found that the effects of 20 mg/kg astragaloside IV were similar to SB-431542, which could improve pulmonary fibrosis induced by K. pneumoniae, decrease the levels of TGF-β1/Smad signaling pathway-related proteins in lung, and reduce inflammation at the same time. Astragaloside IV could alleviate the inflammation of rat pneumonia induced by K. pneumoniae through suppressing the TGF-β1/Smad pathway.

REEP1 Preserves Motor Function in SOD1G93A Mice by Improving Mitochondrial Function via Interaction with NDUFA4 / 神经科学通报·英文版

A decline in the activities of oxidative phosphorylation (OXPHOS) complexes has been consistently reported in amyotrophic lateral sclerosis (ALS) patients and animal models of ALS, although the underlying molecular mechanisms are still elusive. Here, we report that receptor expression enhancing protein 1 (REEP1) acts as an important regulator of complex IV assembly, which is pivotal to preserving motor neurons in SOD1G93A mice. We found the expression of REEP1 was greatly reduced in transgenic SOD1G93A mice with ALS. Moreover, forced expression of REEP1 in the spinal cord extended the lifespan, decelerated symptom progression, and improved the motor performance of SOD1G93A mice. The neuromuscular synaptic loss, gliosis, and even motor neuron loss in SOD1G93A mice were alleviated by increased REEP1 through augmentation of mitochondrial function. Mechanistically, REEP1 associates with NDUFA4, and plays an important role in preserving the integrity of mitochondrial complex IV. Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.

Astragaloside IV for Heart Failure: Preclinical Evidence and Possible Mechanisms, A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF).@*METHODS@#PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0.@*RESULTS@#Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model).@*CONCLUSIONS@#AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.

Multiplicity of infection of Plasmodium knowlesi in Malaysia: an application of Pkmsp-1 block IV

@#In Malaysia presently, the main cause of human malaria is by the zoonotic monkey parasite Plasmodium knowlesi. A previous study has suggested that the P. knowlesi merozoite surface protein 1 (Pkmsp-1) block IV to be a suitable multiplicity of infection (MOI) genotyping marker for knowlesimalaria. This study therefore aimed to investigate the usefulness of Pkmsp-1 block IV in assessing the MOI of P. knowlesi in clinical isolates from Malaysia. Two allele-specific PCR primer pairs targeting the two allelic families of block IV (T1 and T2) were designed, and used to genotype P. knowlesi in 200 blood samples (100 from Peninsular Malaysia and 100 from Malaysian Borneo). Results showed that the mean MOI in Malaysian Borneo was slightly higher as compared to Peninsular Malaysia (1.58 and 1.40, respectively). Almost half of the total blood samples from Malaysian Borneo (52%) had polyclonal infections (i.e., more than one allele of any family type) as compared to Peninsular Malaysia (33%) samples. The T1 allelic family was more prevalent in Peninsular Malaysia (n=75) than in Malaysian Borneo (n=60). The T2 allelic family, however, was more prevalent in the Malaysian Borneo (n=87 vs n=53 respectively). This study shows that the single locus Pkmsp-1 block IV can serve as a simple alternative genetic marker for estimating knowlesi malaria MOI in a population. Future MOI studies should focus on macaque populations as macaques are the natural host of P. knowlesi.

Astragaloside IV improves podocyte injury and mitochondrial dysfunction induced by high glucose and inhibits Notch pathway activation / 西安交通大学学报(医学版)

【Objective】 To investigate the protection of astragaloside IV from high glucose induced podocyte injury and mitochondrial dysfunction and its molecular mechanisms. 【Methods】 The model of podocyte injury induced by high glucose (30 mmol/L glucose) was established, and the model cells were treated with low, medium and high doses of astragaloside IV respectively; cell activity was detected by CCK-8. Apoptosis was detected by TUNEL staining. Mitochondrial membrane potential was detected by JC-1 fluorescence probe. ATP content was detected by the kit. The expression levels of apoptosis and podocyte injury related proteins and Notch pathway related proteins were detected by Western blotting. 【Results】 Compared with the control group, cell activity was decreased, apoptosis level was increased (P<0.05), anti-apoptotic protein (Bcl2) expression was decreased, and apoptosis protein (Bax, cleaved-caspase 9, cleaved-caspase 3) expressions were increased (all P<0.05) in HG group. Compared with HG group, HG+AS-IV improved cell activity and apoptosis level induced by high glucose (P<0.05), increased expression of anti-apoptotic protein (Bcl2), and decreased expressions of apoptotic protein (Bax, cleaved-caspase 9, and cleaved-caspase 3) (all P<0.05). Compared with the control group, mitochondrial dysfunction occurred in HG group, JC-1 monomer content increased, and ATP content decreased (all P<0.05). Compared with HG group, HG+AS-IV improved mitochondrial dysfunction, increased JC-1 polymer content and ATP content (P<0.05). In addition, compared with the control group, the expression of Notch pathway-related protein was decreased in HG group (P<0.05). Compared with HG group, Notch pathway-related protein expression was increased in HG+AS-IV group (all P<0.05). Molecular docking results showed that AS-IV could bind Notch1. 【Conclusion】 Astragaloside IV can improve podocyte injury and mitochondrial dysfunction induced by high glucose, possibly by inhibiting Notch pathway activation.

Extracellular Expression and Purification of Spider Neurotoxin Hainantoxin-IV in Escherichia coli / 中国生物化学与分子生物学报

The spider neurotoxin hainantoxin-IV(HNTX-IV), which is isolated from the crude venom of the spider Selenocosia hainana, can specifically inhibit the tetrodotoxin-sensitive(TTX-S) sodium channel, and can selectively inhibit Voltage-gated sodium channel(VGSC) Na

Astragaloside IV inhibits Ang H-induced cell proliferation and collagen expression in cardiac fibroblasts by activating short-chain acyl-CoA dehydrogenase / 中国药理学通报

Aim To explore the effect of astragaloside IV (AS-IV) on cell proliferation and collagen expression in cardiac fibroblasts (CFs) of rats induced with angiotensin II (Ang II) and its mechanism. Methods CFs were pretreated with short-chain acyl-CoA dehydrogenase (SCAD) siRNA1186 for 12 h and then co-treated with Ang TJ and AS-IV for 36 h. The expressions of SCAD, α-SMA, collagen I and collagen III in CFs were detected by Western blot. mRNA expression levels of SCAD, a-SMA, collagen I and collagen III in CFs were detected by quantitative real-time PCR. The SCAD enzymatic activity, the content of ATP, hydroxyproline and free fatty acid were measured by detection kits. Results The expression of α-SMA, collagen I and collagen III were up-regulated (all P < 0. 01) in CFs induced by Ang II compared with the control cells, and the expression and enzymatic activity of SCAD significantly decreased (P < 0. 01, P< 0. 05). The content of ATP decreased (P < 0.01), and the content of hydroxyproline and free fatty acids increased (all P < 0.01). Compared with Ang II group, SCAD expression and enzymatic activity, and ATP content were significantly increased (all P < 0.01) in Ang II + AS-TV group, but the content of hydroxyproline and free fatty acids, and the expression of α-SMA, collagen I and collagen III significantly decreased (all P < 0.01). However, compared with the Ang II + NC group, there was no significant difference in all indices in the Ang II + SiRNA1186 + AS-TV group. The protective effect of AS-TV on Ang II -induced cell proliferation and collagen expression in CFs was eliminated by the interference of SCAD SiRNA1186. Conclusions AS-IV may inhibit Ang II-induced cell proliferation and collagen expression in CFs by activating SCAD.

Hallazgos ecocardiográficos de pacientes pediátricos con mucopolisacaridosis tipo IV-A con mutación c. 901G> T en el gen GALNS en un centro de salud de cuarto nivel de Colombia en el periodo de 2012-2019 / Echocardiographic findings in pediatric patients with Mucopolysaccharidosis IV-A with mutation c.901G>T in the GALNS gene in a fourth level health center in Colombia between 2012-2019

La mucopolisacaridosis tipo IV-A es un trastorno de almacenamiento lisosómico poco frecuente, cuya manifestación clínica más evidente es la disostosis múltiple. Alteraciones multiorgánicas se han descrito en este tipo de pacientes, sin embargo, las manifestaciones cardiovasculares no han sido descritas con gran énfasis. Esta investigación tuvo como objetivo principal describir los hallazgos ecocardiográficos en pacientes pediátricos con mucopolisacaridosis tipo IV-A con mutación c.90iG>T en el gen GALNS. Se realizó un estudio descriptivo de serie de casos que incluyó pacientes con diagnóstico confirmado (clínico, bioquímico y molecular) de mucopolisacaridosis tipo IV-A; los pacientes asistieron a una institución hospitalaria en Pereira, Colombia, entre 2012 y 2019, donde se valoraron parámetros ecocardiográficos. Se incluyeron diez pacientes con edades comprendidas entre 3 y 18 años, media de 10. Las anomalías cardiacas identificadas fueron regurgitación mitral trivial RM en 4 de 10 pacientes, dilatación del anillo aórtico en 9 de 10, dilatación de la aorta ascendente, dilatación del arco transverso y del istmo aórtico en 1 de 10, área subaórtica levemente engrosada sin estenosis e hipertrofia ventricular izquierda concéntrica leve en 1 de 10 pacientes. La función ventricular fue normal en todos los pacientes. Los hallazgos ecocardiográficos más frecuentes fueron dilatación del anillo aórtico y regurgitación trivial de la válvula mitral, adicionalmente, pueden encontrarse válvulas mitral y aórtica engrosadas e hipertrofia ventricular izquierda, por lo que es importante una valoración periódica por cardiología pediátrica.

Mucopolysaccharidosis IV-A is a rare lysosomal storage disorder, whose most evident clinical manifestation is multiple dysostosis. Multiorgan disorders have been described in this type of patients, however, the Cardiovascular manifestations have not been described with greater emphasis. The main objective of this research was to describe the echocardiographic findings in pediatric patients with type IV-A mucopolysaccharidosis with c.901G>T mutation in the GALNS gene. A descriptive case series study was carried out, which included patients with a confirmed diagnosis (clinical, biochemical and molecular) of mucopolysaccharidosis type IV-A; the patients were attended a hospital institution in Pereira, Colombia, between 2012 and 2019, where echocardiography parameters were evaluated. Ten patients with ages ranging from 3 to 18 years, average 10, were included. The cardiac abnormalities identified were trivial mitral regurgitation in 4 of 10 patients, aortic annulus dilation in 9 of 10, dilatation of the ascending aorta, dilatation of the transverse arch and aortic isthmus in 1 of 10, slightly thickened subaortic area without stenosis and mild concentric left ventricular hypertrophy in 1 of 10 patients. Ventricular function was normal in all patients. The most frequent echocardiography findings were dilatation of the aortic annulus and trivial regurgitation of the mitral valve, additionally, thickened mitral and aortic valves and left ventricular hypertrophy may be found, so periodic evaluation by pediatric cardiology is important.

Síndrome de Alport: Rol de la semiología y la genética

El síndrome de Alport es una enfermedad renal progresiva por alteración de la membrana basal glomerular secundaria a mutación en los genes COL4A4, COL4A5 y COL4A6 del colágeno tipo IV, con 3 patrones hereditarios: ligado al cromosoma X, autosómico dominante y autosómico recesivo. No existe tratamiento específico para el síndrome de Alport, el objetivo del tratamiento es evitar la progresión rápida a enfermedad renal crónica y mejorar la calidad de vida del paciente. Se reporta el caso de una femenina de 5 años que acudió al cuarto de urgencias con historia de dolor abdominal y edema en miembros inferiores con hematuria microscópica, resto de exámenes de laboratorio y gabinete con hallazgos sugestivos de apendicitis aguda. Se realizó diagnóstico de apendicitis aguda y síndrome nefrítico, sin embargo, debido a la persistencia de hematuria con proteinuria e historia familiar de hematuria, se sospecha de síndrome de Alport.  Inició tratamiento con inhibidores de la enzima convertidora de angiotensina y se realizó biopsia renal reportada sin alteraciones a la microscopía de luz sin reporte de microscopía electrónica. Cursó con proteinuria en rango nefrótico, inicia tratamiento con corticoides e inhibidores de calcineurina sin respuesta. Se obtiene reporte de panel genético confirmatorio de Alport y se suspende inmunosupresión. (provisto por Infomedic International)

Alport syndrome is a progressive kidney disease, due to alterations of the glomerular basement membrane secondary to mutations in the COL4A4, COL4A5 and COL 4A6 genes of type IV collagen with three hereditary patterns: X-linked, autosomal dominant and autosomal recessive. There is no specific treatment for Alport Syndrome. The main goal of the therapeutic options is to prevent rapid progression to chronic kidney disease and improve the patient's quality of life. The report of a 5-year-old female, who attended the emergency room with abdominal pain, edema in the lower limbs and microscopic hematuria, the rest of the laboratory and clinical studies with findings suggestive of acute appendicitis. A diagnosis of acute appendicitis and nephritic syndrome was made, however, due to the persistence of hematuria and family history, Alport syndrome was suspected. Treatment with angiotensin-converting enzyme inhibitors was started and renal biopsy was performed, reported minimal change and without electron microscopy report. The patient quickly progressed to nephrotic range proteinuria and started corticosteroids and calcineurin inhibitors without response.  A confirmatory genetic panel was performed, Alport syndrome was diagnosed, and immunosuppression was suspended. (provided by Infomedic International)

An interesting case of acute pancreatits

Hypertriglyceridemia(HTG)is the third most common cause of acute pancreatitis but it is relatively rare and requires a highlevel of clinic suspicion. We report a 30 years old male with no co-morbidities who is a non-alcoholic, non-smoker presented with epigastric pain associated with vomiting for two days. His vitals were stable and systemic examination wasunremarkable. Serum lipase levels were elevated [7365 U/l(<40 U/l)]. Computed Tomography of the abdomen suggested acute pancreatitis with extensive peri-pancreatic inflammatory changes with no evidence of pancreatic necrosis. Serum triglycerides were found to be elevated (3450 mg/dl). A diagnosis of HTGinduced acute pancreatitis was made. During evaluation he was found to be diabetic. He was treated with intravenous fluids, IV insulin infusion, and other supportive measures. He was started on statins, fenofibrate and omega3 fatty acids. His condition improved and triglyceride levels after two days were in a declining trend and he was discharged on the same. He was currently under follow up and his serum amylase, serum lipase, serum triglycerides were normal. This case report provides insight into rare cause of acute pancreatitis-HTGwhich if diagnosed at the earliest can be treated promptly.

Manejo anestésico de una gestante con síndrome de Morquio / Anesthetic Management for a pregnant woman with Morquio syndrome Sobre los autores:

Introducción: El síndrome de Morquio es una enfermedad hereditaria autosómica recesiva con distintos grados de afectación al metabolismo de los glúcidos, lo que genera incapacidad para romper los enlaces de las cadenas largas de glucosamiglicanos, esto provoca acumulación de mucopolisacáridos en distintos tejidos del cuerpo humano. Objetivo: Describir el manejo anestésico de una gestante con síndrome de Morquio. Presentación del caso: Gestante primigesta de 30 años de edad, de raza negra, de 103 cm de estatura y 33 Kg de peso. Acude a consulta preoperatoria por presentar embarazo a término, baja talla y se realizó interrupción del embarazo por vía alta. Se procede a la valoración preanestésica donde se recoge antecedentes de enfermedad genética e ingreso previo por presentar cifras elevadas de tensión arterial. La paciente padecía de alergia a la dipirona. Conclusiones: Los pacientes con mucopolisacaridosis tienen una alta incidencia de dificultad para la ventilación y la intubación endotraqueal asociada con insuficiencia cardiopulmonar. La afectación de la columna presenta dificultades adicionales para los anestesiólogos. Cualquier cirugía electiva requiere una evaluación preoperatoria de los factores de riesgo anestesiológicos y la disponibilidad de un espectro de equipos para el manejo de las vías respiratorias. La anestesia debe ser realizada por un equipo con experiencia en el manejo de la vía aérea(AU)

Introduction: Morquio syndrome is an autosomal recessive hereditary disease that affects, to different extents, carbohydrate metabolism, which obstructs the ability to break bonds of long chains of glycosaminoglycans, causing mucopolysaccharides accumulation in different tissues of the human body. Objective: To describe the anesthetic management of a pregnant woman with Morquio syndrome. Case presentation: This is the case of a 30-year-old primigravid pregnant woman, of black skin, 103 cm of height and 33 kg of weight. She came for preoperative consultation because she was pregnant at term and had low body size; the pregnancy was terminated through the abdominal route. A preanesthetic assessment was performed, which permitted to observe a history of genetic disease and previous admission for high blood pressure. The patient was allergic to dipyrone. Conclusions: Among patients with mucopolysaccharidosis, there is a high incidence of difficulty for ventilation and endotracheal intubation associated with cardiopulmonary insufficiency. Spinal involvement represents additional difficulties for anesthesiologists. Any elective surgery requires preoperative assessment of anesthesiologic risk factors and the availability of a spectrum of airway management equipment. Anesthetic managment should be performed by a team experienced in airway management(AU)

Prematurity and functional gastrointestinal disorders in infancy: a cross-sectional study

ABSTRACT BACKGROUND: Functional gastrointestinal disorders (FGIDs) are defined as a variable combination of chronic or recurrent gastrointestinal symptoms that are not explained by structural or biochemical abnormalities. Their relationship with prematurity has been increasingly studied. OBJECTIVE: To compare the frequency of FGIDs in preterm and term infants and to evaluate whether invasive procedures during the neonatal period in preterm infants are associated with greater likelihood of FGIDs in the first two years of life. DESIGN AND SETTING: Controlled nested cross-sectional study conducted in a Brazilian university hospital. METHODS: This was a controlled nested cross-sectional study on a retrospective cohort of infants born preterm who were compared with infants born at term regarding the presence of FGIDs. Medical consultations were conducted by a single pediatric gastroenterologist to obtain information on the gestational and neonatal periods and on clinical manifestations of the digestive tract. The Rome IV criteria for the diagnosis of FGIDs were used. RESULTS: A total of 197 infants (< 24 months), including 99 preterm and 98 term infants, were studied. Infant regurgitation was more prevalent in term infants (35.1% and 15.6%; P < 0.001). The frequencies of other FGIDs (infant colic, functional constipation, functional diarrhea and infant dyschezia) in preterm infants did not differ from those of term infants (P > 0.05). No relationship was found between invasive procedures during the neonatal period and development of FGIDs in preterm infants. CONCLUSION: Infants born preterm did not have higher frequency of FGIDs in the first two years of life.

Prevalencia de desórdenes gastrointestinales funcionales en adolescentes

RESUMEN Introducción: Los desórdenes gastrointestinales funcionales pediátricos, comprenden un conjunto de síntomas gastrointestinales crónicos o recurrentes, no explicados por anomalías estructurales o bioquímicas, con interferencia importante en la calidad de vida del niño y su familia. Objetivo: Determinar la prevalencia de los desórdenes gastrointestinales funcionales en adolescentes. Métodos: Estudio observacional, descriptivo de corte transversal, prospectivo con 318 adolescentes pertenecientes a los centros de enseñanza del reparto Camilo Cienfuegos del municipio Habana del Este, en el período comprendido entre marzo 2020 y enero del 2021. Las variables utilizadas fueron edad, sexo, antecedentes personales de dengue, antecedentes familiares de desórdenes gastrointestinales familiares, primogénito, padres separados, hijo único, prematuridad y nacimiento por cesárea. Se utilizó el cuestionario para síntomas digestivos pediátricos, basado en los criterios de Roma IV. Resultados: Un total de 93 estudiantes, para 29,2 % cumplieron los criterios diagnósticos de Roma IV para algún desorden gastrointestinal funcional. Se encontró predominio del sexo femenino (34,3 %) y del grupo de 10-12 años (30 %). El estreñimiento funcional se diagnosticó en 22,7 % de los adolescentes, seguido de la dispepsia funcional en 3,5 %. Conclusiones: Los desórdenes gastrointestinales funcionales son comunes en los adolescentes del estudio. El estreñimiento funcional es el trastorno más frecuente. Los desórdenes gastrointestinales funcionales se presentan de forma significativa en adolescentes del sexo femenino.

ABSTRACT Introduction: Pediatric functional gastrointestinal disorders comprise a set of chronic or recurrent gastrointestinal symptoms, not explained by structural or biochemical abnormalities, with significant interference in the quality of life of the child and his/her family. Objective: Determine the prevalence of functional gastrointestinal disorders in adolescents. Methods: Observational, descriptive cross-sectional, prospective study with 318 adolescents belonging to the educational centers of Camilo Cienfuegos neighborhood, Habana del Este municipality, in the period between March 2020 and January 2021. The variables used were age, sex, personal history of dengue, family history of gastrointestinal disorders, firstborn, separated parents, only child, prematurity and birth by cesarean section. The questionnaire for pediatric digestive symptoms, based on the Rome IV criteria, was used. Results: A total of 93 students (29.2%) met the diagnostic criteria of Rome IV for some functional gastrointestinal disorder. A predominance of the female sex (34.3%) and the group of 10-12 years (30%) was found. Functional constipation was diagnosed in 22.7% of adolescents, followed by functional dyspepsia (3.5%). Conclusions: Functional gastrointestinal disorders are common in the studied adolescents. Functional constipation is the most common disorder. Functional gastrointestinal disorders occur significantly in female adolescents.

Uma revisão sistemática e meta-análise em escolares e adolescentes com Distúrbios gastrointestinais funcionáis de acordo com os critérios de Roma IV / A systematic review and meta-analysis in schoolchildren and adolescents with functional gastrointestinal disorders according to rome iv criteria

ABSTRACT Objective: To determine the prevalence of functional gastrointestinal disorders (FGIDs) in children according to Rome IV criteria. Methods: We included cohorts and observational descriptive studies, including information for the prevalence of FGIDs according to Rome IV criteria in children 4 to 18 years old. We searched the MEDLINE (Ovid), EMBASE, LILACS, and CENTRAL databases from May 2016 to nowadays. Gray literature and other databases were also consulted. The risk of bias was assessed using the STROBE Statement. The results were reported in forest plots of the estimated effects of the included studies with a 95% confidence interval (95%CI). Results: We included 14 studies involving a total of 17427 participants. Three studies were conducted in Europe, two in North America, and nine in Latin America. Most studies were school-based (n=14670, 84.18%), participants were mostly female (55.49%), white (51.73%), 8 to 18 years old (77.64%), and assisted to a public school (81.53%). Thirteen studies used the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS-RIV) to assess FGIDs. We found a global prevalence for FGIDs of 23% (95%CI 21-25%, I2 99%). Main disorders were functional constipation (FC) with 12% (95%CI 11-15%) followed by functional dyspepsia (FD) (5%, 95%CI 11-15%) and irritable bowel syndrome (IBS) (3%, 95%CI 2-4%). The prevalence of FGIDs was higher in the Americas, representing 23.67% (95%CI 21.2-26.2%, I2 91.3%). Conclusion: FGIDs are present in one of four children and adolescents, representing a common condition in this age group the central disorders were FC, FD, and IBS.

RESUMO Objetivo: Determinar a prevalência de distúrbios gastrointestinais funcionáis (DGF) em crianças de acordo com os critérios de Roma IV. Métodos: Incluímos coortes e estudos observacionais descritivos, incluindo informações para a prevalência de DGF de acordo com os critérios de Roma IV em crianças de 4 a 18 anos. Pesquisamos nas bases de dados MEDLINE (Ovid), EMBASE, LILACS e CENTRAL de maio de 2016 até os dias atuais. A literatura cinzenta e outras bases de dados também foram consultadas. O risco de viés foi avaliado usando a Declaração STROBE. Os resultados foram relatados em parcelas florestais dos efeitos estimados dos estudos incluídos com um intervalo de confiança de 95% (95%IC). Resultados: Foram incluídos 14 estudos envolvendo um total de 17.427 participantes. Três estudos foram realizados na Europa, dois na América do Norte e nove na América Latina. A maioria dos estudos foi de base escolar (n=14.670, 84,18%), os participantes eram em sua maioria do sexo feminino (55,49%), brancos (51,73%), de 8 a 18 anos (77,64%) e atendidos em escola pública (81,53%). Treze estudos usaram o Questionário de Sintomas Gastrointestinais Pediátricos (QPGS-RIV) para avaliar DGF. Encontramos uma prevalência global de DGF de 23% (95%IC 21-25%, I2 99%). Os principais distúrbios foram constipação funcional (CF) com 12% (95%IC 11-15%) seguido de dispepsia funcional (DF) (5%, 95%IC 11-15%) e síndrome do intestino irritável (SII) (3%, 95%IC 2-4%). A prevalência de DGF foi maior nas Américas, representando 23,67% (95%IC 21, 2-26,2%, I2 91,3%). Conclusão: DGF estão presentes em uma de quatro crianças e adolescentes, representando uma condição comum nessa faixa etária. Os distúrbios centrais foram CF, DF e SII.