Variantes genómicas asociadas a errores congénitos en el metabolismo de los carbohidratos en el suroccidente colombiano

Introducción: Los Errores Innatos del Metabolismo (EIM) de carbohidratos son el resultado de la interrupción de las vías catabólicas o anabólicas de diferentes carbohidratos, siendo la fructosa, la galactosa y el glucógeno los más comunes y pertenecen a un grupo heterogéneo de trastornos que pueden ser hereditarios o pueden ocurrir como resultado de variantes genéticas espontáneas. En los EIM, están las vías de los carbohidratos alteradas, tanto las vías catabólicas como las anabólicas, incluyendo el metabolismo de la fructosa, galactosa y glucógeno, dando lugar a un grupo heterogéneo de trastornos. Sin embargo, los datos sobre estas patologías en Colombia son escasos. Nuestro estudio tuvo como objetivo identificar variantes genómicas asociadas a EIM por carbohidratos en población del suroccidente colombiano carente de diagnóstico clínico. Resultados: Realizamos un estudio transversal, secuenciando 320 exomas y clasificando las variantes de acuerdo a guías estándar. Identificamos 286 variantes, incluyendo 206 nuevas y 73 variantes benignas o probablemente benignas. En particular, seis variantes en genes como GALT, GAK1, ALDOB, GAA y SLC2A1 tenían un significado incierto, y una variante patogénica en el gen GALT se asoció con la galactosemia clásica. Curiosamente, el 18% eran intrónicas, el 5% con sentido erroneo, el 10% sinónimas y el 67% variantes no notificadas. Conclusiones: Estos hallazgos ponen de relieve la necesidad de programas de diagnóstico precoz para aplicar tratamientos específicos, incluido el manejo transdisciplinar para minimizar la morbilidad y la mortalidad. El consejo genético y la educación sobre el riesgo son cruciales, facilitando enfoques de medicina anticipatoria y preventiva, avanzando así en la medicina de precisión.   (provisto por Infomedic International)

Introduction: Carbohydrate Inborn Errors of Metabolism (IEMs) result from disruption of the catabolic or anabolic pathways of different carbohydrates, fructose, galactose and glycogen being the most common and belong to a heterogeneous group of disorders that may be inherited or may occur as a result of spontaneous genetic variants. In IEM, there are altered carbohydrate pathways, both catabolic and anabolic pathways, including fructose, galactose and glycogen metabolism, resulting in a heterogeneous group of disorders. However, data on these pathologies in Colombia are scarce. The aim of our study was to identify genomic variants associated with carbohydrate IEM in the southwestern Colombian population lacking clinical diagnosis. Results: We performed a cross-sectional study, sequencing 320 exomes and classifying variants according to standard guidelines. We identified 286 variants, including 206 new variants and 73 benign or probably benign variants. Notably, six variants in genes such as GALT, GAK1, ALDOB, GAA and SLC2A1 were of uncertain significance, and one pathogenic variant in the GALT gene was associated with classic galactosemia. Interestingly, 18% were intronic, 5% missense, 10% synonymous, and 67% unreported variants. Conclusions: These findings highlight the need for early diagnostic programs to implement targeted treatments, including transdisciplinary management to minimize morbidity and mortality. Genetic counseling and risk education are crucial, facilitating anticipatory and preventive medicine approaches, thus advancing precision medicine. (provided by Infomedic International)

In silico evaluation of the gene expression profile of syndecan-4 in different breast tumor subtypes / Avaliação in silico do perfil de expressão gênica do sindecam-4 nos diferentes subtipos de tumores de mama

INTRODUCTION: Breast cancer is one of the main causes of death in women. Luminal tumors A and B show good response with hormonal treatments, tumors that overexpress HER-2 can be treated with monoclonal antibodies, whereas triple negative tumors have few treatments available because they present low or absent expression of hormone receptors and HER-2, in addition, they present worse tumor progression. Syndecans are heparan sulfate proteoglycans that have the function of interacting with growth factors, cytokines, and extracellular matrix, thus modulating important processes in tumor progression. OBJECTIVE: Analyze the expression of syndecan-4 in different subtypes of breast tumors. METHODS: Bioinformatics is a useful tool for the study of new biomarkers. In the present study, the TCGA database (514 patients) and Metabric (1,898 patients) were analyzed using the cBioportal software. Gene expression data were analyzed by RNA-Seq and Microarray from biopsies of breast tumors. RESULTS: An alteration in syndecan-4 gene expression was observed among the different subtypes of breast tumors. Patients with a triple-negative tumor had decreased expression for syndecan-4 in both databases. CONCLUSION: Syndecan-4 is a potential biomarker for breast tumor prognosis since decreased expression of syndecan-4 is related to triple-negative breast cancer.

INTRODUÇÃO: O câncer de mama corresponde a uma das principais causas de morte em mulheres. Os tumores luminais A e B apresentam boa resposta com tratamentos hormonais, os tumores que superexpressam HER-2 podem ser tratados com anticorpos monoclonais, já os tumores triplo-negativos apresentam poucos tratamentos disponíveis por apresentarem expressão baixa ou ausente dos receptores hormonais e HER-2, além de pior progressão tumoral. Os sindecans são proteoglicanos de heparam sulfato que tem função de interagir com fatores de crescimento, citocinas e matriz extracelular, modulando assim processos importantes na progressão tumoral. OBJETIVO: Analisar a expressão o sindecam-4 nos diferentes subtipos de tumores de mama. MÉTODOS: A bioinformática vem se mostrando útil para estudo de novos biomarcadores. No presente estudo, foi analisado o banco de dados TCGA (514 pacientes) e Metabric (1898 pacientes) utilizando o software cBioportal. Foram analisados os dados de expressão gênica por RNA-Seq e Microarray. RESULTADOS: Foi verificada alteração de expressão gênica do sindecam-4 entre os diferentes subtipos de tumores de mama. Pacientes com tumor triplo-negativo tiveram a expressão diminuída para sindecam-4 em ambos os bancos de dados. CONCLUSÃO: Foi verificado que sindecam-4 parece ser um potencial biomarcador em tumores de mama, a expressão diminuída de sindecam-4 parece estar relacionada a um pior prognóstico.

Cribado prenatal de aneuploidías mediante análisis de ácido desoxirribonucleíco libre total circulante en plasma materno. Revisión narrativa / Prenatal screening for aneuploidies by analysis of circulating total free deoxyribonucleic acid in maternal plasma. Narrative review

La prueba prenatal no invasiva es un método de cribado de aneuploidías fetales y de resultar con riesgo alto debe ser confirmado a través de prueba genética diagnóstica. Es la prueba de detección más sensible y específica para las aneuploidías fetales comunes y minimiza la realización de técnicas invasivas, solo para las gestantes con riesgo elevado. Se debe realizar asesoramiento genético pre- y poscribado. Este estudio tiene como objetivo describir los fundamentos básicos de la prueba prenatal no invasiva mediante el análisis del ácido desoxirribonucleíco libre circulante en plasma materno para cribado de aneuploidías, y de los métodos primordiales y avances en biología molecular incluyendo las tecnologías de secuenciación de nueva generación, que lo han facilitado, considerando sus beneficios y limitaciones al aplicarla en la práctica clínica, en este campo que cambia con tanta rapidez(AU)

The non-invasive prenatal test is a screening method for fetal aneuploidies and if the result is at high risk, it must be confirmed through diagnostic genetic test. It is the most sensitive and specific detection test for common fetal aneuploidies and minimizes the use of invasive techniques, only for pregnant women at high risk. Genetic counseling should be performed before and after screening. This study aims to describe the basic fundamentals of non-invasive prenatal testing by analyzing free circulating deoxyribonucleic acid in maternal plasma for aneuploidy screening, and the primary methods and advances in molecular biology, including next-generation sequencing technologies, which have facilitated it, considering its benefits and limitations when applying it in clinical practice, in this rapidly changing field(AU)

Utilidad de GeneXpert MTB/RIF en el diagnóstico de tuberculosis frente a la baciloscopia / Utility of GeneXpert MTB/RIF in the Diagnosis of Tuberculosis Compared to Sputum Smear Microscopy

Introducción: La implementación de un método diagnóstico adecuado y eficiente es crucial para la detección temprana de la tuberculosis. Esto no solo permite un control efectivo de la enfermedad para evitar su transmisión y progresión hacia estadios más graves, además previene el desarrollo de resistencia a los fármacos en los pacientes.Objetivo: Evaluar la utilidad de la prueba molecular GeneXpert MTB/RIF en el diag-nóstico de Mycobacterium tuberculosis complex, en comparación con la bacilos-copia, utilizando el cultivo como referencia.Material y Métodos: Se realizó un estudio descriptivo, observacional y no expe-rimental de corte transversal, se incluyeron 253 muestras de pacientes de ambos sexos y de variados rangos de edad, que fueron evaluadas mediante baciloscopia, GeneXpert MTB/RIF y cultivo. El estudio se centró en muestras procesadas en un Hospital público de la ciudad de Quito durante el período de enero de 2021 a mayo de 2022Resultados: La prueba molecular GeneXpert MTB/RIF mostró una sensibilidad del 94,7% y una especificidad del 93,9% para el diagnóstico de Mycobacterium tu-berculosis complex. Además, se identificó un caso de resistencia a la rifampicina.Conclusión: Este estudio confirma la eficacia de la prueba molecular GeneXpert MTB/RIF sobre la baciloscopia para el diagnóstico oportuno de Mycobacterium tu-berculosis complex. Sin embargo, es esencial considerar las diversas condiciones de las muestras y pacientes para optimizar la precisión diagnóstica

Introduction: Implementing an appropriate and efficient diagnostic method is cru-cial for the early detection of tuberculosis. This not only allows for effective control of the disease to prevent its transmission and progression to more severe stages but also prevents the development of drug resistance in patients.Objective: To evaluate the utility of the GeneXpert MTB/RIF molecular test in diag-nosing Mycobacterium tuberculosis complex, compared to sputum smear micros-copy, using culture as the reference. Material and Methods: A descriptive, observational, and non-experimental cross-sectional study was conducted, including 253 samples from patients of both sexes and various age ranges, which were assessed using sputum smear micros-copy, GeneXpert MTB/RIF, and culture. The study focused on samples processed at a Quito ́s Public Hospital during the period from January 2021 to May 2022.Results: The GeneXpert MTB/RIF molecular test showed a sensitivity of 94.7% and a specificity of 93.9% for the diagnosis of Mycobacterium tuberculosis com-plex. Additionally, a case of resistance to rifampicin was identified.Conclusion: This study confirms the effectiveness of the GeneXpert MTB/RIF mo-lecular test over sputum smear microscopy for the timely diagnosis of tuberculosis. However, it is essential to consider the diverse conditions of the samples and pa-tients to optimize diagnostic accuracy

Hipertensión pulmonar y leiomiomas uterinos, ¿existe relación causal? Serie de casos y revisión fisiopatológica / Pulmonary Hypertension and Uterine Leiomyomas, Is there a Causal Relationship? Case Series and Pathophysiological Review

Introducción: Los leiomiomas uterinos son un tipo de neoplasia benigna de frecuente aparición en mujeres de edad reproductiva, relacionados con enfermedad tromboem- bólica venosa. Este vínculo surge del efecto producido por la compresión de fibromas que genera estasis venosa en la región pelviana. Sin embargo, este pareciera no ser el único factor que lo relaciona con el desarrollo posterior de hipertensión pulmonar, sino que su presencia es gatillo de una serie de fenómenos que influyen sobre la vasculatu - ra pulmonar y también a nivel sistémico. Método: Revisión de una serie de casos (seis) atendidos en nuestra unidad, seguido de una revisión sobre la relación entre leiomio- mas y distintas formas de hipertensión pulmonar con una revisión desde la fisiopatología. Resultado y conclusiones: Encontramos sustento bibliográfico en los múltiples caminos fisiopatológicos que relacionan los mediadores vasculares comunes, que parecieran ser el punto clave en la relación entre estas dos patologías.

Introduction: Uterine leiomyomas are a type of benign neoplasm that frequently appears in women of reproductive age, related to venous thromboembolic disease. This link arises from the effect produced by the compression of fibroids, which generates venous stasis in the pelvic region. However, this seems not to be the only factor that re- lates it to the subsequent development of pulmonary hypertension, but rather its presence is a trigger for a series of phenomena that influence the pulmonary vasculature and also at a systemic level. Method: Review of a series of cases (six) cared for in our unit, followed by a review on the relationship between leiomyomas and different forms of pulmonary hypertension with a review from the pathophysiology. Result and conclusions: We found bibliographic support in the multiple pathophysiological paths that relate the common vascular mediators, which appear to be the key point in the relationship between these two pathologies.

La matriz extracelular en la curación de las heridas cutáneas. Aspectos físicos, químicos y biológicos / Extracellular matrix in healing of cutaneous wounds. Physical, chemical and biological aspects

Se revisan los nuevos conocimientos sobre la matriz extracelular (MEC), que han permitido descubrir su importante rol en la cicatrización de las heridas cutáneas. Se describen sus características morfofisiológicas y cómo interviene en la curación de las heridas cutáneas. Se presentan cuatro casos clínicos en los que se aplicó este enfoque terapéutico: los sustitutos de piel y la "cura húmeda"

We review the new knowledge about the extracellular ma-trix (ECM) that has allowed us to discover its important role in the healing of cutaneous wounds. The morpho-physiological characteristics of ECM and its role in the healing of cutaneous wounds are described. Four clinical cases are presented where this therapeutic approach was applied: the skin substitutes and the "moist wound healing".

Borderline ovarian tumors: a review of its biology, molecular profile, and management / Tumores borderline de ovário: uma revisão de sua biologia, perfil molecular e manejo

Borderline ovarian tumors typically exhibit indolent behavior and boast a favorable prognosis; however, a subset of patients experiences disease recurrence and progression to low-grade ovarian carcinoma. The complex biology underlying these phenomena has been illuminated through molecular analyses. KRAS and BRAF mutations have emerged as recurrent ?ndings in borderline ovarian tumors. Speci?cally, KRAS mutations have been linked to a higher risk of recurrence and progression to low-grade ovarian carcinoma, while BRAF mutations seem to confer a protective e?ect, inducing a senescent state that mitigates the likelihood of progression. In this comprehensive review, we explore the biology and the molecular pro?le of borderline ovarian tumors, shedding light on recent discoveries that have enriched our comprehension. Additionally, we discuss the current state of borderline ovarian tumors management. Surgery remains the cornerstone of treatment. While cytotoxic therapies role is limited so far, molecular characterization emphasizes the imminent potential for personalized therapeutic approaches.

Os tumores borderline de ovário geralmente exibem comportamento indolente e apresentam prognóstico favorável; no entanto, um subconjunto de pacientes apresenta recorrência da doença e progressão para carcinoma de ovário de baixo grau. A biologia complexa subjacente a estes fenômenos foi iluminada através de análises moleculares. Mutações KRAS e BRAF surgiram como achados recorrentes em tumores borderline de ovário. Especificamente, as mutações KRAS têm sido associadas a um maior risco de recorrência e progressão para carcinoma de ovário de baixo grau, enquanto as mutações BRAF parecem conferir um efeito protetor, induzindo um estado senescente que mitiga a probabilidade de progressão. Nesta revisão abrangente, exploramos a biologia e o perfil molecular dos tumores borderline de ovário, lançando luz sobre descobertas recentes que enriqueceram nossa compreensão. Além disso, discutimos o estado atual do manejo de tumores borderline de ovário. A cirurgia continua sendo o pilar de tratamento. Embora o papel das terapias citotóxicas seja limitado até o momento, a caracterização molecular enfatiza o potencial iminente para abordagens terapêuticas personalizadas.

Beak deformity in three bird species from the southwest of the Brazilian Amazon / Deformidad del pico en tres especies de aves del sudoeste de la Amazonia brasileña

Abstract Beak deformity have a frequency of 0.5% in wild bird populations. In addition to being rare, beak deformities are also poorly reported in the Brazilian scientific literature. Here we report beak deformities in the species: Dendrocincla merula, Amazona ochrocephala and Pheugopedius genibarbis, all of which occurred in southwestern Brazilian Amazon. Dendrocolaptids make intensive use of their beaks in the search for insects and small vertebrates, where they explore in cracks in wood with lateral blows. In the case presented here, this behaviour may have been the cause of the breakage of the tip of this individual's maxilla. In Brazilian territory, few species of parrots were recorded with deformity in the beak and in the individual in this work, everything indicates that Amazona ochrocephala was a captive animal, as it was excessively thin and its diet probably had a low content of vitamins and calcium, where their deficiency even when the animal was a puppy may have contributed to the deformity of the maxilla. Cases of beak deformities in species of the Troglodytidae family are rare, but the individual in this work presented an unusual curvature in the maxilla not observed in other individuals in museum collections. Only with more reports will we be able to better understand the occurrence and causes of these beak deformities in wild birds.

Resumen La deformidad del pico es una característica rara y tiene una frecuencia baja, con 0.5% de casos en poblaciones de aves silvestres. Además de ser raras, las deformidades del pico también son escasamente reportadas en la literatura científica brasileña. Reportamos aquí deformidades en los picos de aves de las especies: Dendrocincla merula, Amazona ochrocephala y Pheugopedius genibarbis, en los cuales todos los registros ocurrieron en el sudoeste de la Amazonia brasileña. Los dendrocoláptidos hacen uso intensivo del pico en la búsqueda de insectos y pequeños vertebrados, explorando en grietas de la madera con golpes laterales. En el caso aquí presentado, este comportamiento de exploración pudo haber sido la causa de la rotura de la punta del maxilar de este individuo. En el territorio brasileño, pocas especies de loros fueron registradas con deformidad en el pico y en el individuo de este trabajo, todo indica que Amazona ochrocephala era un animal de cautiverio, ya que estaba excesivamente delgado y su dieta probablemente tenía un bajo contenido de vitaminas y calcio, donde su deficiencia incluso cuando el animal era un joven puede haber contribuido a la deformidad del maxilar. Los casos de deformidades del pico en especies de la familia Troglodytidae son raros, pero el individuo de este trabajo presentaba una curvatura inusual en el maxilar no observada en otros individuos de esta especie depositados en la colección científica. Sólo con más informes podremos entender mejor la ocurrencia y las causas de estas deformidades del pico en aves silvestres.

Identificação de Potenciais Biomarcadores Cruciais em IAMCSST por Meio de Análise Bioinformática Integrada / Identification of Potential Crucial Biomarkers in STEMI Through Integrated Bioinformatic Analysis

Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de -log2fold change- > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.

Abstract Background ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. Objectives In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. Methods We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of -log2fold change- > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. Results 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. Conclusions This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI.

Pathophysiology of posttraumatic ankle osteoarthritis: a multicenter perspective / Fisiopatologia da osteoartrite pós-traumática do tornozelo: perspectiva multicêntrica

ABSTRACT Besides the acute injury and trauma-induced macroscopic alterations, the evolution to posttraumatic ankle osteoarthritis (PTOA) is a complex process progressing at the tissue and molecular level. Furthermore, changes in the molecular pathways affect chondrocyte viability. Treatment modalities for PTOA focal or confined disease include innovative techniques. Objective: Our purpose is to increase medical awareness based on scientific evidence of pathophysiology, molecular biology, and treatment of post-traumatic ankle osteoarthritis. Methods: To support the perspectives of the experts, evidence from the scientific literature respected the PRISMA guidelines and the PICOS search strategy was used. We included case-control, cohort, experimental studies and case reports, written in English. Results: The authors were homogeneously exposed to 282 selected abstracts and 114 full articles directly related to post-traumatic osteoarthritis after malleolar fractures. Conclusion: The pathophysiological factors involved in posttraumatic ankle osteoarthritis, such as biological, structural, mechanical, and molecular changes must be studied together, as the interaction between these factors determines the risk of progression of PTOA. Inhibition of a single catabolic molecule or cascade probably is not sufficient to alter the natural progression of the pathological process. Evidence level V, expert opinion.

RESUMO A evolução para a osteoartrite pós-traumática do tornozelo (PTOA) a partir da lesão aguda e das alterações macroscópicas induzidas pelo trauma é um processo complexo, que progride em nível tecidual e molecular. Além disso, as alterações nas vias moleculares afetam a viabilidade dos condrócitos. As modalidades focais ou confinadas de tratamento para PTOA incluem técnicas inovadoras. Objetivo: Nosso objetivo é aumentar a conscientização médica, com base em evidências científicas de fisiopatologia, biologia molecular e tratamento da osteoartrite pós-traumática do tornozelo. Métodos: Para o embasamento das perspectivas dos autores experts, as evidências da literatura científica respeitaram as diretrizes Prisma e a estratégia de busca Picos foi empregada. Incluímos estudos de caso-controle, de coorte, experimentais e relatos de caso, escritos em inglês. Resultados: Os autores foram expostos de forma homogênea a 282 resumos e 114 artigos completos, diretamente relacionados à osteoartrite pós-traumática após fraturas maleolares. Conclusão: Os fatores fisiopatológicos envolvidos na osteoartrite pós-traumática do tornozelo, como alterações biológicas, estruturais, mecânicas e moleculares, devem ser estudados em conjunto, pois a interação entre esses fatores determina o risco de progressão da PTOA. A inibição de uma única molécula catabólica ou cascata provavelmente não é suficiente para alterar a progressão natural do processo patológico. Nível de evidência V, opinião do especialista.

Understanding distribution and survey gaps of Mammals from the Atlantic Forest and Cerrado Biomes / Compreendendo Lacunas na Distribuição e Amostragem de Mamíferos dos Biomas da Mata Atlântica e Cerrado

Abstract The Atlantic Forest and Cerrado (Brazilian Savannah) contain a large number of endemic species and high species diversity, particularly for medium and large-bodied mammals. However, there is no large-scale assessment of these animals and their spatial distribution. Our study synthesises the literature on medium and large-bodied mammal surveys in the Cerrado and Atlantic Forest to provide insights into their distributions across large spatial scales and identify knowledge gaps to guide future research. We synthesised papers published in three databases, focusing on mammals weighing more than 1kg. Of the 84 papers we found, the majority (57.14%) were on mammals in the Atlantic Forest, while 42.85% were on mammals found in the Cerrado. We gathered records for 116 species, the most common of which were Cerdocyon thous (Linnaeus, 1766), Procyon cancrivorus (Cuvier, 1798) and Chrysocyon brachyurus (Illiger, 1815) (Cerrado); Dasypus novemcinctus (Linnaeus, 1758), Cerdocyon thous (Linnaeus, 1766) and Nasua nasua (Linnaeus, 1766; Atlantic Forest). Our study allowed us to access, for the first time in the Atlantic Forest and Cerrado, the information available about medium and large-bodied mammals. We also highlight important sampling gaps, especially concerning the northern parts of both biomes that we need to address, as well as the differences in density of sampling points that are caused by a smaller concentration of sampling efforts in the Atlantic Forest than what we found in Cerrado. As a consequence, larger extensions of Cerrado present knowledge gaps concerning mammal surveys that need to be investigated in future research.

Resumo A Mata Atlântica e o Cerrado brasileiro abrigam uma enorme quantidade de espécies endêmicas e alta diversidade de espécies, especialmente de mamíferos de médio e grande porte. No entanto, não há uma avaliação em larga escala desses animais e de sua distribuição espacial. Nosso estudo sintetiza a literatura sobre levantamentos de mamíferos de médio e grande porte no Cerrado e na Mata Atlântica, com o objetivo de fornecer informações sobre suas distribuições em larga escala e identificar lacunas no conhecimento para guiar futuras pesquisas. Sintetizamos artigos publicados em três bases de dados, com foco em mamíferos com peso superior a 1 kg. Dos 84 artigos encontrados, a maioria (57,14%) tratava de mamíferos na Mata Atlântica, enquanto 42,85% abordavam mamíferos encontrados no Cerrado. Coletamos registros para 116 espécies, sendo as mais comuns Cerdocyon thous (Linnaeus, 1766), Procyon cancrivorus (Cuvier, 1798) e Chrysocyon brachyurus (Illiger, 1815) (Cerrado); Dasypus novemcinctus (Linnaeus, 1758), Cerdocyon thous (Linnaeus, 1766) e Nasua nasua (Linnaeus, 1766; Mata Atlântica). Nosso estudo também mostra as lacunas no levantamento especialmente em relação às distribuições ao norte dos biomas, que precisam ser resolvidas, assim como a diferença na densidade de pontos que é causada pela menor concentração de amostragens na Mata Atlântica do que o que encontramos no Cerrado. Como consequência, existem largas extensões do Cerrado que apresentam lacunas no levantamento de mamíferos que precisam ser investigados em pesquisas futuras.

La Food and Agricultural Organization y la institucionalización de la biología pesquera en Brasil, 1955-1978: complejidades de la circulación del conocimiento científico / The Food and Agricultural Organization and the institutionalization of fishery biology in Brazil, 1955-1978: complexities of the circulation of scientific knowledge

Resumen Este trabajo analiza el programa de asistencia técnica a la investigación y el desarrollo pesquero, implementado por la Food and Agriculture Organization (FAO) en Brasil, entre 1955 y 1978. Nos interrogamos cuáles son las motivaciones de los países desarrollados, de la FAO y de Brasil para movilizar ese conocimiento y cómo se construyó el soporte socio-institucional para su afincamiento. Siguiendo el itinerario de los expertos y atendiendo a las características del campo de la biología pesquera, mostramos cómo se construyeron, de manera simultánea, el campo de investigación, la política y la actividad pesquera brasileñas. Para eso, recurrimos a los informes de varios expertos de la FAO y de organismos públicos brasileños.

Abstract This paper analyzes the technical assistance program for research and fishery development, implemented by the Food and Agriculture Organization (FAO) in Brazil, between 1955 and 1978. We argue what were the motivations of the developed countries, the FAO and Brazil to mobilize this knowledge and how the socio-institutional support for its achievement was built. Following the itinerary of experts and attending to the characteristics of the field of fishing biology, we show how the Brazilian field of research, policies and fishing activity were built simultaneously. For this purpose, we used reports from several experts from the FAO and Brazilian public bodies.

Análisis de los sitios de unión de la ivermectina en la estructura de importinas α humanas

La ivermectina demostró importantes acciones antivirales ante varios virus con genoma de ARN, inclusive contra el SARS-CoV-2. Este fármaco inhibe la actividad del heterodímero importina α/ß1, sin embargo, se desconoce los blancos específicos de interacción de la molécula. Objetivos: analizar in silico los blancos de interacción de la ivermectina en interacción con la estructura de la importina α humana, utilizando la estrategia del acoplamiento molecular. Métodos: se realizaron simulaciones del acoplamiento utilizando un modelo semiflexible y el algoritmo Broyden-Fletcher-Goldfarb-Shanno entre las estructuras de ivermectina y la importina α. Resultados: los datos obtenidos revelan una mayor afinidad de interacción de la ivermectina a la región mayor de unión (armadillo ARM2-ARM4) de las importinas α humanas, con energías de unión favorables de -9,5 a -8,0 kcal.mol-1. Los aminoácidos activos de importancia en las uniones fueron el Triptófano, Asparagina y Arginina, los cuales también son fundamentales para el reconocimiento de secuencias NLS (secuencias de localización nuclear) de las proteínas virales. También se registró afinidades por los dominios H1-ARM5, H2-ARM6 y H2-ARM7, con energía de unión de -7,5 kcal.mol-1. Conclusiones: los hallazgos demuestran que la ivermectina presenta afinidades de unión favorables a la región mayor de unión (ARM2-ARM4) de las importinas a el cual es un sitio importante de unión a proteínas virales.

Ivermectin has demonstrated significant antiviral actions against several RNA-genome viruses, including SARS-CoV-2. This drug inhibits the activity of the α/ß1 importin heterodimer; however, the specific interaction targets of the molecule are unknown yet. Objectives: to analyze in silico the interaction targets of ivermectin interacting with the human α-importin structure using the molecular docking strategy. Methods: simulations of the molecular docking were carried out using a semi-flexible model and the Broyden-Fletcher-Goldfarb- Shanno algorithm between the structures of ivermectin and importin α. Results: data obtained reveal a higher interaction affinity of ivermectin to the major binding region (armadillo ARM2-ARM4) of human importins α, with favorable binding energies of -9,5 to -8,0 kcal.mol-1. The active amino acids of importance in the bindings were Tryptophan, Asparagine and Arginine, which are also critical for the recognition of NLS sequences (nuclear location sequences) of viral proteins. Affinities for H1-ARM5, H2-ARM6 and H2-ARM7 domains were also recorded, with binding energy of -7,5 kcal.mol-1. Conclusions: the findings demonstrate that ivermectin exhibits favorable binding affinities to the major binding region (ARM2-ARM4) of importins a which is an important viral protein binding site.

Survey of Portulacaceae family flora in Taif, Saudi Arabia

Abstract The presence of weeds in areas of agricultural activities is a hinderance to the development of these activities. It is important to take advantage of the vast open spaces suitable for agriculture and provide food security for humans, and also it is an important indicator for determining the feasibility of growing crops, benefiting from yield and determining the percentage of loss, clearing fields through agricultural practices, that protect crops from weed attack and agricultural practice method must be followed that will reduce weed presence. This study was conducted during the years 2018 to 2020 to evaluate Portulacaceae of Flora in the Taif area in the Kingdom of Saudi Arabia at different altitudes (Area 1 =1700 m, Area 2 =1500 m, Area 3 =1500 m, Area 4 =500 m Area 5 = 2200 m, and Area 6 = 2200 m). The results show that there were 2,816 individuals of Portulaca oleracea weed, with the highest density found in A 1, followed by A 2, while in A 5 and A 6, no weeds were recorded. The highest density of weeds were in the Pomegranate fields, followed by Grape fields. The lowest density was found in A man field. The results of this study will help to take the necessary measures to combat weeds and its management in areas of agricultural activity, while more studies are needed to survey the ecology of weeds of Taif in The Kingdom of Saudi Arabia.

Resumo A presença de plantas daninhas em áreas de atividades agrícolas é um entrave ao desenvolvimento dessas atividades. É importante aproveitar os vastos espaços abertos adequados para a agricultura e dar segurança alimentar para o homem. Também é um indicador importante para determinar a viabilidade de cultivo de lavouras, beneficiando-se da produtividade e determinando o percentual de perda, desmatando campos agrícolas, práticas que protegem as lavouras do ataque de ervas daninhas, e métodos de práticas agrícolas devem ser seguidos para reduzir a presença de ervas daninhas. Este estudo foi realizado durante os anos de 2018 a 2020 para avaliar Portulacaceae de flora na área de Taif, no Reino da Arábia Saudita, em diferentes altitudes (Área 1 = 1.700 m, Área 2 = 1.500 m, Área 3 = 1.500 m, Área 4 = 500 m, Área 5 = 2.200 m, e Área 6 = 2.200 m). Os resultados mostram que houve 2.816 indivíduos de planta daninha Portulaca oleracea, com a maior densidade encontrada em A 1, seguida de A 2, enquanto em A 5 e A 6, nas plantas daninhas foram registrados. A maior densidade de ervas daninhas estava nos campos de romã, seguido pelos campos de uva. A densidade mais baixa foi encontrada no campo A man. Os resultados deste estudo ajudarão a tomar as medidas necessárias para combater as ervas daninhas e seu manejo em áreas de atividade agrícola, enquanto mais estudos são necessários para levantar a ecologia das ervas daninhas de Taif na Arábia Saudita.

Survey of Portulacaceae family flora in Taif, Saudi Arabia / Levantamento da flora da família Portulacaceae em Taif, Arábia Saudita

Abstract The presence of weeds in areas of agricultural activities is a hinderance to the development of these activities. It is important to take advantage of the vast open spaces suitable for agriculture and provide food security for humans, and also it is an important indicator for determining the feasibility of growing crops, benefiting from yield and determining the percentage of loss, clearing fields through agricultural practices, that protect crops from weed attack and agricultural practice method must be followed that will reduce weed presence. This study was conducted during the years 2018 to 2020 to evaluate Portulacaceae of Flora in the Taif area in the Kingdom of Saudi Arabia at different altitudes (Area 1 =1700 m, Area 2 =1500 m, Area 3 =1500 m, Area 4 =500 m ِ Area 5 = 2200 m, and Area 6 = 2200 m). The results show that there were 2,816 individuals of Portulaca oleracea weed, with the highest density found in A 1, followed by A 2, while in A 5 and A 6, no weeds were recorded. The highest density of weeds were in the Pomegranate fields, followed by Grape fields. The lowest density was found in A man field. The results of this study will help to take the necessary measures to combat weeds and its management in areas of agricultural activity, while more studies are needed to survey the ecology of weeds of Taif in The Kingdom of Saudi Arabia.

Resumo A presença de plantas daninhas em áreas de atividades agrícolas é um entrave ao desenvolvimento dessas atividades. É importante aproveitar os vastos espaços abertos adequados para a agricultura e dar segurança alimentar para o homem. Também é um indicador importante para determinar a viabilidade de cultivo de lavouras, beneficiando-se da produtividade e determinando o percentual de perda, desmatando campos agrícolas, práticas que protegem as lavouras do ataque de ervas daninhas, e métodos de práticas agrícolas devem ser seguidos para reduzir a presença de ervas daninhas. Este estudo foi realizado durante os anos de 2018 a 2020 para avaliar Portulacaceae de flora na área de Taif, no Reino da Arábia Saudita, em diferentes altitudes (Área 1 = 1.700 m, Área 2 = 1.500 m, Área 3 = 1.500 m, Área 4 = 500 m, Área 5 = 2.200 m, e Área 6 = 2.200 m). Os resultados mostram que houve 2.816 indivíduos de planta daninha Portulaca oleracea, com a maior densidade encontrada em A 1, seguida de A 2, enquanto em A 5 e A 6, nas plantas daninhas foram registrados. A maior densidade de ervas daninhas estava nos campos de romã, seguido pelos campos de uva. A densidade mais baixa foi encontrada no campo A man. Os resultados deste estudo ajudarão a tomar as medidas necessárias para combater as ervas daninhas e seu manejo em áreas de atividade agrícola, enquanto mais estudos são necessários para levantar a ecologia das ervas daninhas de Taif na Arábia Saudita.

Flowering time and harvest on floral morphology and production of hermaphrodite flowers in the cashew tree Anacardium occidentale (Anacardiaceae)

Introduction: Morphological parameters of flowering are fundamental in the reproductive process of plants, but this subject is poorly explored in the cashew tree Anacardium occidentale. Objective: To determine the influence of the flowering and harvest period on floral parameters, and to identify association with hermaphrodite flowers in the dwarf cashew. Methods: For the 2018 and 2019 harvests in 120 samples we measured number of male/hermaphrodite/abnormal flowers; panicle biomass, length, maximum width, and ramifications at 30, 45 and 60 days for 360 samples in total. Results: The harvest effect was not significant. Panicle length and width (at 30 days), had the greatest contributions to the production of hermaphrodite flowers. The presence of male flowers (at 45 days), and the panicle length and number of primary branches (at 60 days) were the main factors at their respective periods. Conclusions: The emission of hermaphrodite flowers responds negatively to male flowers. Variations in flowering compromise the production of hermaphrodite flowers and the flowering structure.

Introducción: Parámetros morfológicos de la floración son fundamentales en el proceso reproductivo de las plantas, sin embargo, el tema es poco explorado en el árbol de marañón Anacardium occidentale. Objetivo: Determinar la influencia de la floración y periodos de cosecha sobre parámetros florales, e identificar asociaciones con flores hermafroditas en el marañón enano. Métodos: Para las cosechas de 2018 y 2019 en 120 muestras, medimos el número de flores masculinas/hermafroditas/anormales; biomasa de panícula, largo, ancho máximo, y ramificaciones a los 30, 45 y 60 días, un total de 360 muestras. Resultados: El efecto de la cosecha fue insignificante. Longitud y ancho de la panícula (a los 30 días), tuvo la mayor contribución a la producción de flores hermafroditas. La presencia de flores masculinas (a los 45 días), y el largo de panícula y número de ramas primarias (a los 60 días) fueron los principales factores en sus periodos respectivos. Conclusiones: La emisión de flores hermafroditas responde negativamente a flores masculinas. Variaciones en la floración afecta la producción de flores hermafroditas y estructura de floración.

Integración y consolidación disciplinar en la biología y la psicología. Una perspectiva comparada / Disciplinary Integration and consolidation in Biology and Psychology. A comparative Approach

Resumen En su proceso de definición y consolidación, las ciencias de la vida se enfrentaron con la dicotomía sobre si la mejor manera de aproximarse a su objeto de estudio era seguir el modelo de la física -considerado el modelo científico por excelencia- o desligarse de este. La manera en la que este debate se decantó en cada disciplina tuvo consecuencias en el desarrollo posterior y en los alcances epistemológicos de las nuevas ciencias en consolidación. La comparación de la manera en la que se dio este debate en la biología y la psicología resulta relevante para entender la trayectoria de estas ciencias y sus posibilidades de integración disciplinar: la biología consiguió la unificación disciplinar integrándose alrededor de la teoría evolutiva, mientras que la psicología no consiguió exitosamente esa integración. Esto fue en parte por el intento de conectarse con las ciencias naturales a través de la fisiología, lo que, además, supuso un obstáculo para la comprensión e integración del principio unificador de la biología.

Abstract During the XIX century, different sciences were structured or consolidated in their modern form. Until then, biology, earth sciences, social sciences, and even physics, chemistry, and mathematics did not exist as autonomous disciplines as we know them today. In that century, the notion of "science" was utterly separated from natural philosophy, theology, and other forms of traditional knowledge. The consolidation of scientific disciplines was characterized by deep debates on the possibilities and methods of knowing the natural and human worlds. In their process of consolidation, all life sciences faced a dichotomy related to the best way to approach their object of study: should they follow the model of physics -considered the scientific model par excellence- or not take that model into account? This dichotomy provoked intense debates in all disciplines. The way this debate was resolved had lasting consequences in the subsequent development and the epistemological scope of the new sciences in consolidation. Comparing how this debate took place in biology and psychology is relevant to understanding the disciplinary trajectory followed by each science and the possibilities of integration in each field of knowledge. There is a generalized assumption in the history of psychology that the experimental paradigm adopted extensively in psychology at the end of the XIX century would have placed the discipline under the scientific status of natural sciences. However, in biology and psychology, there was a tension between a physiological-experimental paradigm and a historical-evolutionary paradigm. Understanding those debates within biology, and the comprehension of how biology achieved its disciplinary integration, shows why the experimental connection of psychology with physiology did not mean an explicit connection with the whole of the natural sciences. Disciplinary integration in biology was possible because of adopting the evolutionary principle under a historic paradigm instead of a physical-chemical one. That is why the experimental connection of psychology with physiology eventually became an obstacle for psychology in adopting the unifying principle of biology, the Theory of Evolution, as their basis for disciplinary integration. The first part of this article describes how two branches emerged in the process of consolidation of biology: physiological-experimental and historical-evolutionary. Each one had a different approach to its object of study, but both were necessary to form what is now modern biology. The second part focuses on unifying biology as a field of scientific knowledge, bringing the two branches of this science together under the evolutionary paradigm. The third part outlines the central debates in the consolidation of psychology as a scientific discipline at the end of the XIX century and the beginning of the 20th century. It introduces implications of how these debates on knowledge in psychology developed, as opposed to how it happened in biology. Finally, the difficulties of psychology connecting with the theory of evolution are addressed, as are the impossibility of integrating the different branches of the discipline.

Mecanismos moleculares de la esquizofrenia / Molecular mechanisms of schizophrenia / Mecanismos moleculares da esquizofrenia

La etiología de la esquizofrenia no está totalmente dilucidada. Se conocen más de 100 diferentes loci de genes relacionados con esquizofrenia, la mayoría de los cuales codifican moléculas asociados a los sistemas de neurotransmisores o al neurodesarrollo. Las primeras abarcan receptores de los neurotransmisores como dopamina, GABA o glutamato y de otros neurotransmisores con menor relación, como la serotonina y la acetilcolina. También están implicadas diversas enzimas relacionadas con el metabolismo, cotransportadores y algunas proteínas intracelulares involucradas en la degradación o síntesis de dichos neurotransmisores. Entre las moléculas que intervienen en el neurodesarrollo están los factores neurotróficos (BDNF, DISC1, NRG1) y las proteínas del complemento C3 y C4, que median la respuesta inflamatoria y la poda sináptica durante el desarrollo temprano. Los productos de la producción genética involucrados en la etiología de la esquizofrenia aportan a la vulnerabilidad selectiva o al proceso de lesión que se instaura o progresa en el paciente, por tanto, su estudio es de relevancia para la comprensión de los fenómenos clínicos propios de la enfermedad.

The etiology of schizophrenia is not fully elucidated. More than 100 different gene loci related to schizophrenia are known, most of which encode molecules associated with neurotransmitter systems or neurodevelopment. These include receptors for neurotransmitters such as dopamine, GABA, or glutamate, as well as other neurotransmitters with less direct relevance, such as serotonin and acetylcholine. Various enzymes involved in metabolism, cotransporters, and intracellular proteins involved in the degradation or synthesis of said neurotransmitters are also implicated. Among the molecules involved in neurodevelopment are neurotrophic factors (BDNF, DISC1, NRG1) and complement proteins C3 and C4, which mediate the inflammatory response and synaptic pruning during early development. The genetic products involved in the etiology of schizophrenia contribute to selective vulnerability or the process of injury that is established or progresses in the patient. Therefore, their study is relevant to the understanding of the clinical phenomena associated with the disease.

A etiologia da esquizofrenia não está totalmente elucidada. Mais de 100 diferentes loci de genes relacionados à esquizofrenia são conhecidos, a maioria dos quais codifica moléculas associadas a sistemas de neurotransmissores ou neurodesenvolvimento. O primeiro inclui receptores para neurotransmissores como dopamina, GABA ou glutamato e outros neurotransmissores menos relacionados, como serotonina e acetilcolina. Também estão envolvidas várias enzimas relacionadas com o metabolismo, cotransportadores e algumas proteínas intracelulares envolvidas na degradação ou síntese dos referidos neurotransmissores. Entre as moléculas envolvidas no neurodesenvolvimento estão os fatores neurotróficos (BDNF, DISC1, NRG1) e as proteínas do complemento C3 e C4, que medeiam a resposta inflamatória e a poda sináptica durante o desenvolvimento inicial. Os produtos da produção genética envolvidos na etiologia da esquizofrenia contribuem para a vulnerabilidade seletiva ou para o processo de lesão que se instala ou progride no paciente, portanto, seu estudo é relevante para a compreensão dos fenômenos clínicos da esquizofrenia

Rinovirus y metapneumovirus en pacientes con infección respiratoria aguda grave / Rhinovirus and metapneumovirus in patients with severe acute respiratory infection

Introducción. Los virus son los principales agentes etiológicos en las infecciones respiratorias agudas graves; un alto porcentaje queda sin diagnóstico viral. Objetivo. Describir la frecuencia de rinovirus y metapneumovirus en pacientes pediátricos de una unidad centinela de Mar del Plata con infección respiratoria aguda grave y resultado negativo para virus clásicos por inmunofluorescencia y biología molecular. Población y métodos. Se realizó un estudio descriptivo de corte transversal. Se evaluó la presencia de rinovirus y metapneumovirus por biología molecular en 163 casos negativos para panel respiratorio por técnicas de vigilancia referencial, durante todo el año 2015. Resultados. Se detectó rinovirus en el 51,5 % de los casos, metapneumovirus en el 9,8 % y coinfección rinovirus-metapneumovirus en el 6,1 %. Fueron negativos para ambos virus el 32,5 %. Conclusiones. La selección de muestras sin diagnóstico virológico permitió identificar rinovirus y metapneumovirus como agentes causales de infecciones respiratorias agudas graves pediátricas y su impacto en la morbimortalidad infantil y en nuestro sistema sanitario.

Introduction. Viruses are the main etiologic agents involved in severe acute respiratory tract infections; a viral diagnosis is not established in a high percentage of cases. Objective. To describe the frequency of rhinovirus and metapneumovirus in pediatric patients with severe acute respiratory infection and negative results for typical viruses by immunofluorescence and molecular biology at a sentinel unit of Mar del Plata. Population and methods. This was a descriptive, cross-sectional study. The presence of rhinovirus and metapneumovirus was assessed by molecular biology in 163 cases negative for respiratory panel by referral surveillance techniques throughout 2015. Results. Rhinovirus was detected in 51.5% of cases, metapneumovirus in 9.8%, and coinfection with rhinovirus and metapneumovirus in 6.1%. Results were negative for both viruses in 32.5%. Conclusions. The selection of samples without a viral diagnosis allowed us to identify rhinovirus and metapneumovirus as causative agents of severe acute respiratory infections in children and assess their impact on child morbidity and mortality and on our health care system

Histological Evaluation of the Effect of Alendronate on the Maxillary Bone of Wistar Rats Combined with Orthodontic Movement of Intense Force / Evaluación Histológica del Efecto del Alendronate en el Hueso Maxilar de Ratas Wistar Combinado con Movimiento de Ortodoncia de Fuerzas Intensas

SUMMARY: To evaluate the histological adverse effects of alendronate administered systemically and topically in combination with orthodontic movement by intense force. Thirty-six 24-week-old female Wistar rats, ovariectomized, were used and divided into three groups (n = 12/group): control, locally treated with saline (0.07 ml/kg/week) (group 1) and experimental, treated with alendronic acid systemically (0.07 mg/kg/week) (group 2) and locally (7 mg/kg/week) (group 3). At 14 days, an orthodontic anchor was installed in the right first molar, and a force of 144 cN was applied for 28 days. The samples were processed for histological evaluation. Descriptive statistics, Shapiro-Wilk tests, one-way ANOVA with Bonferroni correction, one-way repeated measures ANOVA and chi-square tests were performed. All tests were statistically significant at p <0.05. The adverse events found in all groups were inflammation and osteoclastic activity. In the bisphosphonate-treated groups, there were statistically significant differences (p = 0.005) in the osteoclastic activity between the two hemiarcates. All rats in group 2 presented paralytic ileus. Compared to local administration, systemic treatment with alendronic acid produces more adverse effects, such as inflammation, fibrinoid necrosis, and osteoclastic activity. During the application of intense forces, it was not possible to show that there is necrosis associated with bisphosphonates.

Evaluar los efectos adversos histológicos del alendronato administrado sistémica y tópicamente en combinación con movimientos ortodóncicos de fuerza intensa. Treinta y seis ratas Wistar hembras de 24 semanas de edad, ovariectomizadas, fueron utilizadas y divididas en tres grupos (n = 12/grupo): control, tratado localmente con solución salina (0,07 ml/kg/semana) (grupo 1) y experimental, tratados con ácido alendrónico por vía sistémica (0,07 mg/kg/semana) (grupo 2) y local (7 mg/kg/semana) (grupo 3). A los 14 días se instaló un anclaje de ortodoncia en el primer molar derecho y se aplicó una fuerza de 144 cN durante 28 días. Las muestras fueron procesadas para evaluación histológica. Se realizó estadística descriptiva, pruebas de Shapiro-Wilk, ANOVA de una vía con corrección de Bonferroni, ANOVA de medidas repetidas de una vía y pruebas de chi-cuadrado. Todas las pruebas fueron estadísticamente significativas con un p <0,05. Los eventos adversos encontrados en todos los grupos fueron inflamación y actividad osteoclástica. En los grupos tratados con bisfosfonatos hubo diferencias estadísticamente significativas (p = 0,005) en la actividad osteoclástica entre los dos hemiarcados. Todas las ratas del grupo 2 presentaron íleo paralítico. En comparación con la administración local, el tratamiento sistémico con ácido alendrónico produce más efectos adversos, como inflamación, necrosis fibrinoide y actividad osteoclástica. Durante la aplicación de fuerzas intensas, no fue posible demostrar que existe necrosis asociada con los bisfosfonatos.