Resumen Introducción. El cultivo del cacao en las zonas tropicales es una alternativa comercial de interés agroecológico, que permite la diversificación productiva y el manejo sustentable de los suelos al emplear abonado orgánico. Objetivo. Evaluar el desarrollo de cuatro variedades de cacao (INIFAP 4, INIFAP 8, INIFAP 9 y Almendra Blanca) en las condiciones climatológicas de la región de Úrsulo Galván, Veracruz, México. Materiales y métodos. Se realizó un experimento, entre invierno (diciembre 2021) y verano (junio 2022), bajo un diseño completamente al azar, distribuido en cuatro tratamientos y diez repeticiones. El manejo agronómico fue convencional, se agregaron 10 kg de composta por árbol, seguidos de 3 kg de vermicompost. A los cuatro meses del estudio se incorporaron 50 g de urea, 50 g de difosfato de amonio y 50 g de cloruro de potasio. El estudio incluyó análisis de varianza y pruebas de Tukey (α 0,05). Resultados. Se encontró igualdad estadística para altura, diámetro y número de ramas. La respuesta del cacao a temperatura, precipitación, humedad relativa y viento, demostró que afectaron la expresión de su potencial productivo, así como su morfología y rendimiento, no adaptándose a las condiciones climáticas en estudio. Conclusión. El desarrollo de las variedades en estudio fue homogéneo, con base en las condiciones climatológicas de la región Úrsulo Galván, destacándose la variedad Almendra Blanca.

Abstract Introduction. Cocoa cultivation in tropical areas is a commercially viable agroecological alternative that allows for productive diversification and sustainable soil management through the use of organic fertilization. Objective. To evaluate the development of four cocoa varieties (INIFAP 4, INIFAP 8, INIFAP 9, and Almendra Blanca) under the climatic conditions of the Úrsulo Galván region, Veracruz, Mexico. Materials and methods. An experiment was conducted between winter (December 2021) and summer (June 2022), using a completely randomized design with four treatments and ten replications. Conventional agronomic management was employed, with the addition of 10 kg of compost per tree, followed by 3 kg of vermicompost. At four months into the study, 50 g of urea, 50 g of ammonium diphosphate, and 50 g of potassium chloride were incorporated. The study included analysis of variance and Tukey’s tests (α 0.05). Results. Statistical equality was found for height, diameter, and number of branches. The cocoa’s response to temperature, precipitation, relative humidity, and wind showed that these factors influenced the expression of its productive potential, as well as its morphology and yield, without adapting to the climatic conditions under study. Conclusion. The development of the studied varieties was homogeneous based on the climatic conditions of the Ursulo Galvan region, with the Almendra Blanca variety standing out.

Resumen Este trabajo presenta la síntesis de nanopartículas de difosfato de potasio-hierro, KFeP2O7, implantadas sobre carbón activado preparado a partir de restos de olote de maíz. La composición química y la estructura del compósito de carbono activado/difosfato de potasio-hierro (AC/KFP) se analizó mediante Difracción de Rayos X, Microscopía Electrónica de Barrido y Microscopía Electrónica de Transmisión. Se realizaron pruebas complementarias para determinar las características de la superficie, como el área de la superficie y el punto de carga cero (pHpzc). Además, la valoración ácido-base permitió determinar la densidad de sitios de superficie del compósito AC/KFP. Adicionalmente, las propiedades adsortivas del compósito AC/KFP frente a U (VI) fueron evaluadas utilizando el método de lotes.

Abstract This work deals with the synthesis of nanoparticles of iron-potassium diphosphate, KFeP2O7, implanted on activated carbon produced from corncob debris. The chemical composition and structure of activated carbon/potassium-iron diphosphate (AC/KFP) composite was analyzed by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Complementary tests were conducted to determine surface characteristics such as surface area and point of zero charge (pHpzc). Further, the acid-base titration enabled to determine the surface sites density of AC/KFP composite. Adsorptive properties of AC/KFP composite vis à vis U(VI) was then tested using the batch method.

Abstract Introduction: Sticky platelet syndrome (SPS) is a prothrombotic condition characterized by increased platelet aggregation that causes arterial and venous thrombosis. Its diagnosis is reached by identifying increased aggregation using low concentrations of adenosine diphosphate and epinephrine in platelet aggregation tests. Objectives: To identify common mutations through exome sequencing in two patients from the same family diagnosed with SPS and, thus, contribute to the molecular study of this disease. Materials and methods: Descriptive study. In January 2018, exome sequencing was performed in a 10-year-old patient treated at Fundación HOMI (Bogotá D.C., Colombia), index case, and in one of his adult first-degree relatives, both with a history of thrombotic disease and diagnosed with SPS. Exome sequencing was performed at the Complexo Hospitalario Universitario de Santiago de Compostela (Spain) using the SureSelect Clinical Research Exome V2 software by Agilent. Results: Exome sequencing led to detect genetic variants in both cases when compared with the reference sequence. The following variant was identified in the two samples: a cytosine to thymine transition at position c.236 (NM_000174.4) of the glycoprotein (GP)Ib-IX-V complex platelet membrane receptor, which causes a heterozygous transition of the amino acid threonine to isoleucine (i.e., a transition from hydrophilic amino acid to a hydrophobic amino acid) at position p. 79 of the extracellular leucine-rich repeat domain of GPIba subunit of the (GP)Ib-IX complex, involving a conformational change of the main receptor of ligands IB alpha, which might result in platelet hyperaggregation and thrombosis. This variant has not been described in patients with SPS to date. Conclusion: The mutation identified in both samples could be related to SPS considering the importance of glycoprotein IX in platelet function.

Resumen Introducción. El síndrome de plaqueta pegajosa (SPP) es una condición protrombótica caracterizada por un incremento de la agregabilidad plaquetaria que causa trombosis arterial y venosa. Su diagnóstico se realiza al identificar el aumento de la agregabilidad utilizando bajas concentraciones de adenosín difosfato y epinefrina en pruebas de agregación plaquetaria. Objetivos. Identificar mutaciones comunes mediante secuenciación del exoma en dos pacientes de una misma familia con diagnóstico de SPP y, de esta forma, contribuir al estudio molecular de esta enfermedad. Materiales y métodos. Estudio descriptivo en el que se realizó secuenciación del exoma en un paciente de 10 años atendido en la Fundación HOMI (Bogotá, Colombia), caso índice, y en uno de sus familiares adultos en primer grado, ambos con antecedente de enfermedad trombótica y diagnosticados con SPP. La secuenciación del exoma se realizó en el Complexo Hospitalario Universitario de Santiago de Compostela (España) con el programa SureSelect Clinical Research Exome V2 de Agilent. Resultados. En la secuenciación del exoma se detectaron variantes genéticas en ambos casos en comparación con la secuencia de referencia. En las muestras de ambos pacientes se identificó una variante heterocigota consistente en una transición de citosina a timina en la posición c.236 (NM_000174.4) que provoca el cambio del aminoácido treonina por isoleucina en la posición p.79 del dominio extracelular repetitivo rico en leucina (subunidad GPIba del complejo de la glicoproteína Ib-IX-V) y que podría provocar el cambio conformacional del receptor principal del ligando Ib alfa, así como hiperagregación plaquetaria y trombosis. Esta variante no ha sido descrita previamente en pacientes con SPP. Conclusión. La mutación identificada en las muestras estudiadas podría estar relacionada con el SPP considerando la importancia de la glicoproteína IX en las funciones plaquetarias.

Breast cancer is the leading cause of cancer death in Chilean women and worldwide. It is a heterogeneous disease and four different subtypes have been identified based on clinical, histological and molecular features, which correlate with different treatment tumor sensitivity. Triple negative breast cancer is characterized by its aggressiveness, early relapse, and a greater tendency to present in advanced stages. It frequently affects young women, with cancer family history, especially breast or ovarian cancer. The approved systemic therapy for triple negative breast cancer is chemotherapy; however, recently, targeted therapies with checkpoint inhibitors and polyadenosine diphosphate ribose polymerase inhibitors have been shown to be effective in selected patients and have been added to the therapeutic arsenal for triple negative breast cancer. Given the appearance of these new strategies, it seems relevant to understand the heterogeneity of this disease, the mechanisms of action behind new therapies, clinical results, and the criteria to select patients for molecular therapies. We present a review of the current systemic therapy of this breast cancer subtype.

Resumen El cáncer de mama (CM) es la principal causa de muerte por cáncer en mujeres chilenas. Es una enfermedad heterogénea, en la cual se han identificado cuatro subtipos básicos, determinados según características clínicas, histológicas y moleculares, los que se relacionan a estrategias terapéuticas. El CM triple negativo (CMTN) se caracteriza por su agresividad, recaída temprana y mayor tendencia a presentarse en etapas avanzadas. Frecuentemente afecta a mujeres jóvenes o con antecedentes familiares de CM u ovario. La única terapia sistémica aprobada para el CMTN es la quimioterapia; sin embargo, recientemente terapias moleculares con inhibidores de puntos de control inmune e inhibidores de la poli-adenosina difosfato ribosa polimerasa, han mostrado eficacia en pacientes seleccionados, y se han agregado al arsenal terapéutico para CMTN. Dada la aparición de estas nuevas estrategias, parece relevante entender la heterogeneidad de esta enfermedad, los mecanismos de acción de las nuevas terapias, resultados clínicos y criterios de selección de pacientes para terapias moleculares. Presentamos una revisión de la terapia sistémica actual del CMTN.

Abstract Mammals experience some degree of hypoxia during their lifetime. In response to hypoxic challenge, mammalian cells orchestrate specific responses at transcriptional and posttranslational level, which lead to changes in purine metabolites in order to cope with threatening conditions. The aim of this study was to evaluate the response of the enzymes involved in purine metabolism at human muscle cells under hypoxic conditions. Muscle cells in culture were exposed to hypoxia and the enzymatic activity of inosine monophosphate dehydrogenase (IMPDH), xanthine oxidase (XO), purine nucleoside phosphorylase (PNP) and hypoxanthine guanine phosphoribosyl transferase (HGPRT) as well as their transcript expression were quantified under normoxic and hypoxic conditions. Purine metabolite (hypoxanthine (HX), xanthine (X), uric acid (UA), inosine monophosphate (IMP), inosine, nicotinamide adenine dinucleotide (NAD+), adenosine, adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), guanosine diphosphate (GDP) and guanosine triphosphate (GTP)) concentrations were also quantified. Significant reduction of IMPDH activity as well as in HX and IMP concentrations (p < 0.05) were observed after hypoxia, suggesting a decrease in the purines de novo synthesis. After hypoxia a global reduction of transcripts was observed, suggesting a reduction of the metabolic machinery of purine metabolism to new steady states that balance ATP demand and ATP supply pathways.

Resumen Los mamíferos experimentan cierto grado de hipoxia durante su vida. Como respuesta al reto de hipoxia, las células de mamíferos orquestan respuestas específicas a nivel transcripcional y postraduccional que conducen a cambios en los metabolitos de purinas para hacer frente a las condiciones amenazantes. El objetivo de este estudio fue evaluar la respuesta de las enzimas involucradas en el metabolismo de las purinas de células musculares humanas a condiciones hipóxicas. Las células musculares en cultivo se expusieron a hipoxia y la actividad enzimática de la inosina monofosfato deshidrogenasa (IMPDH), la xantina oxidasa (XO), la purina nucleósido fosforilasa (PNP) y la hipoxantina guanina fosforribosil transferasa (HGPRT), así como su expresión de transcripción, se cuantificaron bajo condiciones de normoxia e hipoxia. Los metabolitos de purina (hipoxantina (HX), xantina (X), ácido úrico (UA), monofosfato de inosina (IMP), inosina, dinucleótido de nicotinamida y adenina (NAD+), adenosina, monofosfato de adenosina (AMP), difosfato de adenosina (ADP), trifosfato de adenosina (ATP), difosfato de guanosina (GDP) y trifosfato de guanosina (GTP)) también se cuantificaron. Se observó una reducción significativa de la actividad de IMPDH y de las concentraciones de HX e IMP (p < 0.05) después de la hipoxia, lo que sugiere una disminución de la síntesis de novo de purinas. Después de la hipoxia, se observó una reducción global de la expresión transcripcional, lo que sugiere una reducción de la maquinaria metabólica del metabolismo de las purinas a nuevos estados estacionarios que equilibran la demanda de ATP y las vías de suministro de ATP.

ABSTRACT Introduction: Platelets contribute to hemostasis and inherited or acquired interruption; in its biochemical processes it can alter platelet function. These aggregation disorders have been associated with genetic diseases with connective tissue involvement such as Ehlers-Danlos syndrome, whose differential diagnosis with the spectrum of joint hypermobility is clinically and molecularly difficult. These entities with involvement of the collagen fibers and different clinical repercussions require differentials in their clinical diagnosis. Methods: 353 medical records of patients attended in the Genetics service of the William Soler Pediatric Hospital from September 2009 to 2012, with a diagnosis of joint hypermobility by Beighton and Ehlers-Danlos criteria according to Villefranche (1997) were reviewed. Patients aged 5-18 years were included with documented results of the platelet aggregation study, assessed by specialists in hematology. Results: Platelet aggregation disorders were found in 79 of 86 patients (92%). In 7 cases with hypermobility of 65 with this diagnosis (10%), the results were negative. The 21 with Ehlers-Danlos syndrome had affectations with platelet phospholipids. Joint hypermobility was associated with the combination adenosine diphosphate (ADP) -epinephrine and the Ehlers-Danlos with the combination ADP-epinephrine-collagen-phospholipids. Conclusions: Patients with joint hypermobility showed an association to granule release defects with agonists such as ADP-epinephrine and Ehlers-Danlos with the availability of phospholipids, related to platelet shape change. This result can be a tool to know the platelet functional endophenotype as a differential element in collagen fiber disorders.

RESUMEN Introducción: Las plaquetas contribuyen a la hemostasia y la interrupción heredada o adquirida; en sus procesos bioquímicos pueden alterar la función plaquetaria. Estos trastornos de agregación se han asociado a enfermedades genéticas con afectación del tejido conectivo como el síndrome Ehlers-Danlos, cuyo diagnóstico diferencial con el espectro de hipermovilidad articular resulta difícil clínica y molecularmente. Estas entidades con afectación en las fibras colágenas y diferente repercusión clínica precisan diferenciales en su diagnóstico clínico. Métodos: Se revisaron 353 historias clínicas de pacientes atendidos en el Servicio de Genética del Hospital Pediátrico William Soler desde septiembre del 2009 al 2012, con diagnóstico de hipermovilidad articular por criterios de Beighton y de Ehlers-Danlos según Villefranche (1997). Se incluyó a los pacientes de 5-18 años con resultados documentados del estudio de agregación plaquetaria, valorados por especialistas en hematología. Resultados: Se encontraron trastornos de agregación plaquetaria en 79 de 86 pacientes (92 %). En 7 casos con hipermovilidad de 65 con este diagnóstico (10 %), los resultados fueron negativos. Los 21 con síndrome Ehlers-Danlos tuvieron afectaciones con los fosfolípidos plaquetarios. La hipermovilidad articular estuvo asociada a la combinación difosfato de adenosina (ADP)-epinefrina y el Ehlers-Danlos a la combinación ADP-epinefrina-colágeno-fosfolípidos. Conclusiones: Los pacientes con hipermovilidad articular mostraron asociación a defectos de liberación de gránulos con agonistas como el ADP-epinefrina y los Ehlers-Danlos con la disponibilidad de los fosfolípidos, relacionados con el cambio de forma plaquetaria. Este resultado puede ser una herramienta para conocer el endofenotipo funcional plaquetario como elemento diferencial en los trastornos de la fibra colágena.

RESUMO Em pacientes com fibrilação atrial, a anticoagulação padrão com antagonista da vitamina K mais terapia antiplaquetária dupla (DAPT) com inibidor de P2Y12 e aspirina é o padrão de tratamento após intervenção coronária percutânea (ICP). Enquanto essa terapia reduz o risco de trombose e derrame, aumenta o risco de sangramento. Não está claro se o efeito antiplaquetário da aspirina e do clopidogrel pode piorar a fibrilação atrial (FA). OBJETIVO Analisar a resistência à aspirina plaquetária (AR) e ao clopidogrel (CR) em pacientes coronarianos agudos (SCA) com base no ritmo sinusal (SR) e na FA. MÉTODOS Neste estudo prospectivo, foram incluídos 543 pacientes (idade média: 62±12 anos; intervalo: 26-89 anos) em uso de aspirina e clopidogrel após o diagnóstico de síndrome coronariana aguda. AR e CR foram analisados por um dispositivo Multiplate® MP-0120, utilizando o método de agregometria de sangue total. RESULTADOS Os pacientes com FA apresentaram valores significativamente maiores para idade, volume médio de plaquetas e proteína C reativa de alta sensibilidade (p<0,01 para cada parâmetro). Da mesma forma, a agregação induzida por ácido araquidônico (Aspi) foi maior nos pacientes com FA em comparação com os pacientes com SR (666±218 vs. 187±179, p<0,001). Entre os pacientes com SCA, significativamente mais pacientes do sexo feminino apresentaram FA (p<0,001). A incidência de hipertensão no grupo FA foi maior em comparação com o grupo SR (p<0,001). No entanto, os níveis de difosfato de adenosina não foram expressivamente significativos nos dois grupos. CONCLUSÃO Nossos achados indicam que o efeito inibitório plaquetário da aspirina foi pior em pacientes com FA, sugerindo que a eficácia da aspirina pode ser menor na profilaxia do tromboembolismo, com maior risco de sangramento.

SUMMARY In patients with atrial fibrillation, standard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is the standard of care after percutaneous coronary intervention (PCI). While this therapy reduces the risk of thrombosis and stroke, it increases the risk of bleeding. It is unclear whether the antiplatelet effect of aspirin and clopidogrel may worsen atrial fibrillation (AF). OBJECTIVE Thus we aimed to analyze platelet aspirin resistance (AR) and clopidogrel resistance (CR) in acute coronary (ACS) patients based on sinus rhythm (SR) and AF. METHODS In this prospective trial, we included 543 patients (mean age: 62± 12 years; range: 26 - 89 years) who were on aspirin and clopidogrel therapy after the diagnosis of acute coronary syndrome. AR and CR were analyzed by a Multiplate® MP-0120 device by using the method of whole blood aggregometry. RESULTS AF patients had significantly higher age, mean platelet volume, and High-Sensitivity C-Reactive Protein (p< 0.01 for each parameter). Similarly, Arachidonic-acid induced (ASPI) aggregation was higher in AF patients compared to SR patients (666±218 vs. 187±179, p<0.001). Among the ACS patients, significantly more female patients had AF (p<0.001). The incidence of hypertension in the AF group was higher compared to the SR group (p<0.001). However, adenosine diphosphate levels were not at a significant level in the two groups. CONCLUSION Our findings indicate that the platelet inhibitory effect of Aspirin was worse for patients with AF, suggesting that the effectiveness of aspirin may be less in the prophylaxis of thromboembolism and more a bleeding risk.

RESUMO OBJETIVO O objetivo deste estudo foi investigar os efeitos da síndrome do baixo triiodotironina (LT3S) na função plaquetária e nos fatores de coagulação em pacientes com síndrome nefrótica (SN). MÉTODOS Pacientes com síndrome nefrótica primária foram divididos em dois grupos, função tireoidiana normal (grupo A) e LT3S (grupo B), com base na presença ou não de LT3S. Indivíduos saudáveis foram selecionados como grupo de controle (grupo C). A função de coagulação do sangue foi analisada em cada grupo. A função de ativação plaquetária (CD62P, CD63) foi determinada por citometria de fluxo. A taxa de agregação plaquetária foi detectada por um método óptico usando adenosina difosfato e ácido araquidônico como indutores. RESULTADOS A proporção de síndrome nefrótica primária com LT3S foi de 23,2% (69/298). Em comparação com o grupo C, o grupo A apresentou níveis mais altos de CD62P e PAgTADP, e o grupo B apresentou maiores CD62P, CD63, PAgTAA e PAgTADP; a diferença teve significância estatística (P < 0,05). Não houve diferença significativa na patologia renal entre o grupo A e o grupo B (X2 = 4,957, P = 0,421). Em comparação com o grupo A, a proteína em urina de 24 horas, CD63, PAgTAA e PAgTADP foram maiores no grupo B, já APTT e Alb foram mais baixos. A diferença apresentou significância estatística (P < 0,05). A análise de regressão logística mostrou uma associação entre LT3S e CD36 (OR: 3,516; 95% IC: 1,742~8,186; P = 0,004) e PAgTAA (OR: 0,442; 95% IC: 1,001~1,251; P = 0,037). CONCLUSÃO Pacientes com síndrome nefrótica estão propensos à síndrome do baixo triiodotironina (LT3S). Pacientes com LT3S podem ter ativação plaquetária anormal e aumento da agregação plaquetária.

SUMMARY OBJECTIVE The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.

RESUMO Objetivo: Investigar a frequência da retinopatia tóxica em pacientes com lúpus eritematoso e artrite reumatóide com uso crônico de difosfato de cloroquina ou hidroxicloroquina, através de tomografia de coerência óptica de domínio espectral e os resultados dos exames oftalmológicos (acuidade visual - tabela de Snellen, teste de visão de cor - tabela de Ishihara, fundoscopia e retinografia - red free). Métodos: Foi realizado um estudo transversal envolvendo a avaliação oftalmológica de pacientes em uso regular de difosfato de cloroquina ou hidroxicloroquina por um período de um ano ou mais. Os pacientes responderam a um questionário sobre a sua opinião e regularidade do tratamento. Os mesmos pacientes realizaram exame oftalmológico clínico e tomografia de coerência óptica de domínio espectral. Resultados: A prevalência de retinopatia tóxica por antimaláricos foi de 4,15% (9 dos 217 pacientes), 7,4% (4 de 54 pacientes) após uso de difosfato de cloroquina e 0,82% (1 de 121 pacientes) após uso de hidroxicloroquina. Apenas os pacientes com maculopatia em fase avançada apresentaram alterações durante os exames clínicos: teste de visão de cores alterado em 11,1%, e a acuidade visual e fundoscopia foram alteradas em 33,3%. A identificação de retinopatia tóxica precoce, detectada em seis pacientes, foi possível por meio da tomografia de coerência óptica de domínio espectral. A duração média do tempo de uso de drogas antimaláricas entre os pacientes com retinopatia tóxica foi de 10,4 anos. Apenas 31% dos pacientes relataram algum sintoma durante o tratamento e apesar de 24% terem medo de usar a medicação, eles o fizeram conforme prescrito. Conclusão: O uso da tomografia de coerência óptica de domínio espectral foi essencial para o diagnóstico de retinopatia tóxica antimalárica em estágio inicial em pacientes com as seguintes características: uso assintomático, antimalárico 7 dias por semana por um período maior que cinco anos e exame oftalmológico clínico normal.

ABSTRACT Purpose: To investigate the frequency of toxic retinopathy in patients with lupus erythematosus and rheumatoid arthritis with long-term use of chloroquine diphosphate or hydroxychloroquine through spectral domain optical coherence tomography and the outcomes of ophthalmological exams (visual acuity - Snellen’s table, color vision test - Ishihara’s table, fundoscopy, and retinography - red-free). Methods: A cross-sectional study was carried out involving the ophthalmologic evaluation of patients using regular chloroquine diphosphate or hydroxychloroquine for a period of 1 year or longer. The patients completed a questionnaire on their opinions and treatment regularity. The same patients underwent ophthalmologic examination and spectral domain optical coherence tomography. Results: The prevalence of toxic retinopathy caused by antimalarials was 4.15% (9 of 217 patients), 7.4% (4 of 54 patients) following chloroquine diphosphate usage, and 0.82% (1 of 121 patients) following hydroxychloroquine usage. Only patients with advanced stage maculopathy presented abnormalities during the ophthalmologic exam: the color vision test was altered in 11.1%, and visual acuity and fundoscopy were altered in 33.3%. Identification of early toxic retinopathy, detected in six patients, was possible using spectral domain optical coherence tomography. The mean duration of antimalarial drug usage among patients with toxic retinopathy was 10.4 years. Only 31% of the patients reported some symptoms during treatment, and although 24% were afraid to use the medication, they did so as prescribed. Conclusion: Use of spectral domain optical coherence tomography was essential for the diagnosis of early-stage antimalarial toxic retinopathy in patients with the following characteristics: asymptomatic, antimalarial use 7 days a week for a period of more than 5 years, and normal clinical ophthalmologic examination.

RESUMO Objetivo Doenças nutricionais, como síndrome metabólica, distúrbios cardiovasculares, inflamação crônica ou mesmo câncer, são observadas em pessoas que sustentam seu estilo de vida na dieta ocidental, caracterizada pela alta ingestão de calorias. Dado que a origem dessas doenças é a estrutura degradada do ácido desoxirribonucleico, o presente estudo investigou se a dieta ocidental produzia dano oxidativo endógeno ao ácido desoxirribonucleico, apoptose ou inflamação. Métodos Foram utilizados 28 ratos Wistar machos, com idade entre 10-12 semanas, divididos em quatro grupos. Os ratos do grupo controle receberam a dieta padrão, ao passo que os ratos restantes receberam uma das três dietas seguintes por quatro semanas: uma dieta rica em gordura contendo 35% de gordura; uma dieta rica em sacarose contendo 69% de sacarose; e dieta ocidental compreendendo os dois tipos de dietas. Após o tratamento soro 8-hidroxi-2-desoxiguanosina, poli (adenosina difosfato ribose) polimerase-1, quitinase-3-like proteína 1, uroquinase solúvel tipo de receptor ativador de plasminogênio, os níveis do ligante Fas e do citocromo c foram medidos. Resultados Não foram observadas alterações nos níveis séricos de uroquinase solúvel tipo de receptor ativador de plasminogênio, ligante Fas e citocromo c, enquanto um aumento estatisticamente significativo nos níveis séricos de 8-hidroxi-2-desoxiguanosina, poli (adenosina difosfato ribose) polimerase-1 e quitinase-3-like proteína 1 foi encontrado apenas em ratos que receberam dieta ocidental. Conclusão Os resultados mostram que a dieta ocidental produziu danos no ácido desoxirribonucleico oxidativo endógeno, o que aumentou os níveis séricos de poli (adenosina difosfato ribose) polimerase-1, levando à inflamação.

ABSTRACT Objective Nutritional diseases such as metabolic syndrome, cardiovascular disorder, chronic inflammation or even cancer are observed in people who sustain their lifestyle by Western diet due to high calorie intake. The origin of these diseases are the degraded deoxyribonucleic acid structure. In this study, we investigated whether Western diet produced endogenous oxidative deoxyribonucleic acid damage, apoptosis or inflammation. Methods Twenty-eight male Wistar rats, aged 10-12 weeks, were divided into four groups. The rats in control group received the standard diet and the remaining rats were given one of the following three diets for four weeks: a high-fat diet containing 35% fat, a high-sucrose diet containing 69% sucrose and Western diet comprising both two types of diets. After treatment the serum 8-hydroxy-2-deoxyguanosine, poly (adenosine diphosphate ribose) polymerase-1, chitinase-3-like protein 1, soluble urokinase-type plasminogen activator receptor, Fas ligand and cytochrome c levels were measured. Results It was observed no changes in the serum soluble urokinase-type plasminogen activator receptor, Fas ligand and cytochrome c levels whereas a statistically significant increase in the serum 8-hydroxy-2-deoxyguanosine, poly (adenosine diphosphate ribose) polymerase-1 and chitinase-3-like protein 1 levels were found only in rats that were given Western diet. Conclusion The findings show that Western diet produced endogenous oxidative deoxyribonucleic acid damage, which then increased serum poly (adenosine diphosphate ribose) polymerase-1 levels, eventually leading to inflammation.

Resumen El síndrome de la plaqueta pegajosa en un trastorno cualitativo plaquetario en el que bajas concentraciones de epinefrina y adenosina difosfato producen hiperagregabilidad plaquetaria considerable. Se ha especulado mucho sobre la etiología de este trastorno sin que sean claros sus mecanismos fisiopatológicos. Desde el punto de vista clínico, se asocia a trombosis arteriales y venosas recurrentes en pacientes jóvenes, pérdidas gestacionales, otras complicaciones obstétricas y cefalea recurrente.En la literatura se ha descrito su presentación familiar, lo que hace sospechar su comportamiento hereditario autosómico dominante; también se ha reportado un fenotipo adquirido de la enfermedad en algunas poblaciones especiales como pacientes con enfermedad renal crónica en terapia de reemplazo renal o posterior al trasplante renal y en pacientes con cuadros inflamatorios o inmunosupresión. Se expone el caso de una paciente con antecedente de cefalea de difícil manejo, síndrome hipertensivo asociado al embarazo y mortinato, con síndrome del nodo enfermo y disautonomía manejadas con implantación de marcapasos definitivo bicameral con sensor CLS, que desarrolló trombosis de la vena subclavia, asociada al electrodo de marcapasos, recurrente a pesar de anticoagulación con warfarina y rivaroxabán e incluso a pesar de antiagregación con ácido acetilsalicílico, con posterior diagnóstico de síndrome de la plaqueta pegajosa.

Abstract Sticky platelet syndrome is a qualitative platelet disorder in which low concentrations of adrenaline and adenosine diphosphate produce considerable platelet hyperaggregability. There has been much speculation on the origin of this disorder as its pathophysiological mechanisms of action are not yet clear. From a clinical point of view, it is associated with recurrent arterial and venous thrombosis in young patients, miscarriages, other obstetric complications and recurrent headaches.Its familial presentation has been described in the literature, suspecting that it is of a dominant autosomal hereditary nature. An acquired phenotype of the disease has also been reported in some particular patients, such as patients with chronic kidney disease on renal replacement therapy or after a kidney transplant, as well as in patients with inflammatory processes or immunosuppression. The case is presented of a patient with a history of difficult to manage headaches, a hypertensive syndrome associated with the pregnancy, and a foetal death. She also had sick sinus node syndrome and dysautonomia managed with a definitive dual-chamber pacemaker with a CLS sensor. There was then a thrombosis in the subclavian vein associated with the pacemaker electrode, being recurrent despite anticoagulation with warfarin and rivaroxaban, and even despite anti-aggregation treatment with acetyl salicylic acid. She was subsequently diagnosed with sticky platelet syndrome.

In plants, the first committed step of the carotenoid biosynthetic pathway is catalyzed by the enzyme phytoene synthase (PSY). PSY catalyzes the condensation of two molecules of geranyl-geranyl diphosphate to produce phytoene, a colorless carotenoid. Overexpression of bacterial (CrtB) and plant PSY genes have increased seed carotenoid content in several plant species. In many instances, the choice of transgene has proven crucial in achieving higher carotenoid levels in transgenic plants. In rapeseed, overexpression of CrtB increased seed carotenoid levels 50 fold but the overexpression of a plant or endogenous PSY has not been reported to date. In this study, the aim was to further increase seed carotenoid content by over-expressing one of the six endogenous PSY genes present in this crop. Using an Agrobacterium-mediated transformation, we introduced a binary vector containing BnaC.PSYa coding region under the control of the soybean lectin promoter (pCambia2300-Lec:: BnaC.PSYa-6XHys) into Brassica napus cv. Westar. Six fertile transgenic events were recovered and confirmed by PCR analysis. Transgene expression was followed by conventional and quantitative real time RT-PCR in T3 seeds at 30 and 60 days post anthesis (dpa). All events over-expressed BnaC.PSYa-6XHys and no silencing of the PSY gene family members was detected. However, seed carotenoid profiling and quantification by HPLC revealed that only a minimal increase (2X) in carotenoid content was obtained. Future strategies to maximize seed carotenoid content in rapeseed are discussed.

En plantas, el primer paso en la biosíntesis de los carotenoides es catalizado por la enzima fitoeno sintetasa (PSY). PSY cataliza la condensación de dos moléculas de geranil-geranil difosfato para producir fitoeno sintasa, un carotenoide incoloro. La sobreexpresión de genes PSY bacterianos (CrtB) y vegetales han aumentado el contenido de carotenoides en varias especies de plantas. En muchos casos, la elección del transgén ha demostrado ser crucial para alcanzar niveles más altos de carotenoides en plantas transgénicas. En colza, la sobreexpresión de CrtB aumentó los niveles de carotenoides en semilla 50 veces pero la sobreexpresión de un PSY de origen vegetal no ha sido reportada. De esta manera, el objetivo de este estudio fue sobreexpresar en semilla uno de los seis genes PSY endógenos presentes en este cultivo para lograr un mayor incremento en el contenido de carotenoides. Usando Agrobacterium tumefaciens, Brassica napus cv. Westar fue transformado con un vector binario que contiene la región codificante del gen BnaC.PSYa bajo el control del promotor de Lectina de soja (pCambia2300-Lec::BnaC.PSYa-6XHys). Seis eventos transgénicos fértiles fueron confirmados por análisis de PCR. La expresión del transgen fue evaluada por RT-PCR convencional y cuantitativa en tiempo real en semillas T3 a 30 y 60 días post antesis (dpa). Todos los eventos sobreexpresaron BnaC.PSYa-6XHys y no se detectó silenciamiento de los miembros de la familia PSY. Sin embargo, la cuantificación por HPLC reveló una leve modificación (2X) en el contenido de carotenoides. Estrategias futuras para maximizar el contenido de carotenoides en semillas de colza son discutidas.

RESUMEN Antecedentes: Algunas especies de la familia Lauraceae poseen metabolitos secundarios que ejercen efectos antiplaquetarios. Estudios de las hojas de Nectandra amazonum Nees. han mostrado esa actividad, pero no se conoce sobre las propiedades antiagregantes de su corteza. Objetivos: Evaluar el efecto antiagregante plaquetario de la fracción etanólica obtenida de la corteza de Nectandra amazonum Nees. (N.V. “laurel amarillo”, Lauraceae) aplicando el método turbidimétrico de Born. Métodos: En el tamizaje antiagregante se comparó la fracción de N. amazonum (0,1 mg/mL) con ácido acetil salicílico (ASA 0,5 mM, como estándar de referencia) y dimetilsulfóxido (DMSO, 0,1%, como control) en plaquetas humanas estimuladas con adenosin difosfato (ADP, 2 μM), epinefrina (EPI, 1 uM (uno micromolar)), colágeno (COLL, 1 μg/mL) y ácido araquidónico (AA, 0,2 mg/mL). Posteriormente, el estudio se enfocó en la determinación de la potencia antiagregante de la fracción mediante curvas de concentración - respuesta (desde 1 μg/mL hasta 0,4 mg/mL) para obtener los valores respectivos de pIC50 (-log CI50). Resultados: En el grupo control se alcanzaron altos valores de agregación plaquetaria (96% AA, 89% EPI, 85% COLL, 77% ADP). La fracción de N. amazonum redujo significativamente la agregación (6% AA, 45% EPI, 10% COLL, 21% ADP), con valores próximos a los obtenidos con ASA (17% AA, 21% EPI, 10% COLL, 20% ADP). De acuerdo con las curvas de concentración - respuesta, los valores de pIC50 arrojaron el siguiente orden de potencia: AA, 4,90 > ADP, 4,51 > COLL, 4,33 > EPI, 3,85. Conclusiones: Estos resultados sugieren que la fracción etanólica de N. amazonum Nees ejerce efectos antiplaquetarios relacionados especialmente con la cascada metabólica del ácido araquidónico..

ABSTRACT Background: Some species of the Lauraceae family are known to produce secondary metabolites that have antiplatelet properties. Studies on the leaves of Nectandra amazonum Nees. have shown antiaggregant activity but the bark of this species has not been studied. Objectives: To assess the antiplatelet effect of the ethanolic fraction obtained from the bark of Nectandra amazonum Nees. (N.V. “laurel amarillo”, Lauraceae) applying the “Born” turbidimetric method. Methods: The screening test compared the effects of a fraction of N. amazonum (0.1 mg/mL), acetylsalicylic acid (ASA, 0.5 mM, as reference standard) and dimethylsulphoxide (DMSO, 0.1%, as control) on human platelets stimulated with adenosine diphosphate (ADP, 2 μM), epinephrine (EPI, 1 uM (one micromolar)), collagen (COLL, 1 μg/mL) and arachidonic acid (AA, 0.2 mg/mL). Subsequently, the study focused on determining the antiaggregant potency of the N. amazonum fraction through concentration - response curves (from 1 μg/mL to 0.4 mg/mL), obtaining pIC50 (-log IC50) values against the platelet agonists. Results: Control platelets attained the highest percentage values of aggregation (96% AA, 89% EPI, 85% COLL, and 77% ADP). The N. amazonum fraction significantly reduced the aggregation effects (6% AA, 45% EPI, 10% COLL, 21% ADP), with values close to those obtained with ASA (17% AA, 21% EPI, 10% COLL, 20% ADP). According to concentration - response curves, the pIC50 values of the ethanolic fraction indicated the following order of potency: AA, 4.90 > ADP, 4.51 > COLL, 4.33 > EPI, 3.85. Conclusions: These results suggest that the N. amazonum Nees. ethanolic fraction elicited antiplatelet effects mainly related to the inhibition of the arachidonic acid pathway.

Objetivo Elaborar recomendações para o diagnóstico, manejo e tratamento da nefrite lúpica no Brasil. Método Revisão extensa da literatura com seleção dos artigos com base na força de evidência científica e opinião dos membros da Comissão de Lúpus Eritematoso Sistêmico da Sociedade Brasileira de Reumatologia. Resultados e conclusões 1) A biópsia renal deve ser feita sempre que possível e houver indicação e quando não for possível, o tratamento deve ser orientado com base na inferência da clase histológica. 2) Devem ser implementados medidas e cuidados idealmente antes do início do tratamento, com ênfase na atenção ao risco de infecção. 3) Devem-se compartilhar riscos e benefícios do tratamento com pacientes e familiares. 4) O uso da hidroxicloroquina (preferencialmente) ou difosfato de cloroquina é recomendado para todos os pacientes (exceto contraindicação) durante as fases de indução e manutenção. 5) A avaliação da eficácia do tratamento deve ser feita com critérios objetivos de resposta (remissão completa/remissão parcial/refratariedade). 6) Os IECA e/ou BRA são recomendados como antiproteinúricos para todos os pacientes (exceto contraindicação). 7) A identificação de sinais clínicos e/ou laboratoriais sugestivos de GN laboratoriais sugestivos de glomerulonefrite proliferativa ou membranosa deve indicar início imediato de terapia específica incluindo corticosteroides e agente imunossupressor, mesmo que não seja possível comprovação histológica. 8) O tempo de uso dos imunossupressores deve ser no mínimo de 36 meses, mas eles podem ser mantidos por períodos mais longos. A sua suspensão só deve ser feita quando o paciente atingir e mantiver remissão completa sustentada. 9) Deve-se considerar nefrite lúpica refratária quando a remissão completa ou parcial não for alcançada após 12 meses de tratamento adequado, quando uma nova biópsia renal deve ser considerada para auxiliar na identificação da causa da refratariedade e decisão terapêutica.

Objective To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. Method Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. Results and conclusions (1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. (2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. (3) Risks and benefits of treatment should be shared with the patient and his/her family. (4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. (5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). (6) Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers are recommended as antiproteinuric agents for all patients (unless contraindicated). (7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including corticosteroids and an immunosuppressive agent, even though histological confirmation is not possible. (8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient could achieve and maintain a sustained and complete remission. (9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision.

The sticky platelet syndrome is an autosomal dominant platelet disorder considered one of the most frequent causes of thrombotic events. It is supposed that the specific fault can be localized to the platelet surface receptor and is characterized by an abnormal increase in aggregability adenosine diphosphate and/or epinephrine. In studies on this entity a high incidence has been described, but this was calculated in patients who have had previous thrombotic events (thromboembolic disease, myocardial infarction and stroke), family history or risk factors for this kind of events, while its incidence in a population of women of childbearing age with two or more pregnancy losses and no previous history is unknown.During our research a total of 126 female patients with at least two miscarriages were studied; 27 of them showed platelet hypersensitivity to adenosine diphosphate and epinephrine by testing aggregometry, which represents 21 % positivity in the population studied. It is significant that the sticky platelet syndrome was predominantly of type II (hypersensitivity with epinephrine). In conclusion, we consider important to remark that with the monitoring and opportune treatment during pregnancy, four of the patients included in our study gave birth four healthy children despite the sticky platelet syndrome.

El síndrome de las plaquetas pegajosas es un trastorno plaquetario autosómico dominante considerado como una de las causas más frecuentes de eventos trombóticos. Se cree que el defecto específico puede estar localizado en los receptores de la superficie plaquetaria y está caracterizado por un incremento anormal en la agregabilidad de las plaquetas con difosfato de adenosina, epinefrina, o ambos. En estudios realizados acerca de esta entidad se ha descrito una elevada incidencia, pero esta se ha calculado en pacientes que han tenido episodios trombóticos previos (enfermedad tromboembólica, infarto agudo del miocardio y accidente cerebrovascular), antecedentes familiares o tienen factores de riesgo para este tipo de eventos, mientras que su incidencia en una población de mujeres en edad fértil, con dos o más pérdidas de embarazo y sin antecedentes es desconocida. En el presente trabajo se estudiaron un total de 126 pacientes femeninas con al menos dos pérdidas de embarazo; de ellas, 27 resultaron positivas al estudio de hipersensibilidad plaquetaria con difosfato de adenosina y epinefrina mediante pruebas de agregometría, lo que representa el 21 % de positividad en la población estudiada. Es significativo que la clase de síndrome de plaqueta pegajosa predominante fue de tipo II (hipersensibilidad con epinefrina). Finalmente, destacar que el seguimiento y tratamiento oportuno durante la gestación en las pacientes incluidas en el estudio ha permitido el nacimiento de 4 niños saludables de madres con síndrome de plaquetas pegajosas.