Resumen El mieloma múltiple es una neoplasia del paciente mayor con una edad media de diagnóstico de 70 años. Los pacientes de edad avanzada con mieloma de alto riesgo genético están poco representados en los estudios clínicos y son un grupo difícil de tratar, con una sobrevida menor a dos años. La edad trae consigo comorbilidades y fragilidad que determinan tolerancia pobre a terapias y mayor mortalidad, obligando a usar tratamientos no intensivos, con el objetivo de controlar la enfermedad y mantener la calidad de vida. En pacientes con mielomas de alto riesgo genético, en cambio, se busca lograr respuestas profundas con el uso de tripletes para superar el efecto adverso de la citogenética. Es así como el tratamiento del mieloma de alto riesgo a edades avanzadas implica requerir tratamientos efectivos en pacientes frágiles y con mala tolerancia a éstos. Se presenta el caso de una paciente de 84 años con mieloma de alto riesgo genético, determinado por la amplificación de 1q21, que recibe tratamientos sucesivos basados en lenalidomida, bortezomib, daratumumab y carfilzomib, lográndose mantener la enfermedad controlada por más de seis años. Este caso documenta que, en pacientes añosos con enfermedad de alto riesgo genético, un tratamiento continuado con drogas efectivas, un ajuste adecuado de dosis y tratamiento de soporte pueden mantener la enfermedad controlada con mínima toxicidad y prolongar la sobrevida del paciente adulto mayor.

Abstract Multiple myeloma is a neoplasm that primarily affects elderly patients, with an average age of diagnosis of 70 years. Elderly patients with high-risk genetic myeloma are underrepresented in clinical studies and pose a challenging group to treat, with a median survival of less than two years. Advanced age brings comorbidities and frailty, which result in poor tolerance to therapies and increased mortality, necessitating the use of less intensive treatments aimed at disease control and maintaining quality of life. In contrast, for high-risk myeloma, deep responses are sought through the use of triplets to overcome the adverse effects of cytogenetics. Thus, treating high-risk myeloma in elderly patients presents the challenge of requiring effective treatments in frail individuals with poor tolerance. We present the case of an 84-year-old patient with high-risk genetic myeloma determined by the amplification of 1q21, who received successive treatments based on lenalidomide, bortezomib, daratumumab, and carfilzomib, successfully maintaining disease control for over six years. This case documents that in elderly patients with high-risk disease, continuous treatment with effective drugs, appropriate dosage adjustments and supportive care can keep the disease under control with minimal toxicity and prolong the survival of the elderly patient.

SUMMARY: As the economy develops and living standards improve, overweight and obesity are increasingly prevalent. Currently, weight-loss medications are primarily administered orally or intravenously, which can result in poor targeting, low bioavailability, frequent administration, and high toxicity and side effects. The study aimed to address these challenges by preparing polylactic acid- polyethylene glycol staple fibers that carry the browning drug pioglitazone hydrochloride using electrostatic spinning and freeze-cutting techniques. Animal experiments were conducted to test the effectiveness of these fibers. Additionally, the study investigated the expression of uncoupling protein genes in rats exposed to different water temperatures by measuring changes in serum urea nitrogen and mRNA expression levels of skeletal muscle uncoupling protein genes. The physiological and genetic effects of low-temperature swimming exercise on changes in energy metabolism in rats were also analyzed at both the individual and molecular levels. The results revealed that serum urea nitrogen remained more stable in hypothermic swimming rats compared to rats in the swimming group. Furthermore, the study observed an induced up-regulation of uncoupling proteins in the skeletal muscle of Wistar rats in response to external temperature stimulation, and the expression of mRNA for skeletal muscle uncoupling proteins significantly increased as the temperature decreased. And the prepared short nanofibers also had a significant promotive effect on uncoupling protein gene, COX7A1, while suppressing the expression of lipogenic gene.

RESUMEN: A medida que la economía se desarrolla y los niveles de vida mejoran, el sobrepeso y la obesidad son cada vez más frecuentes. Actualmente, los medicamentos para bajar de peso se administran principalmente por vía oral o intravenosa, lo que puede resultar en una mala focalización, baja biodisponibilidad, administración frecuente y alta toxicidad y efectos secundarios. El estudio tuvo como objetivo abordar estos desafíos mediante la preparación de fibras cortadas de ácido poliláctico y polietilenglicol que transportan el fármaco pardo clorhidrato de pioglitazona mediante técnicas de hilado electrostático y liofilización. Se realizaron experimentos con animales para probar la eficacia de estas fibras. Además, el estudio investigó la expresión de genes de proteínas desacopladoras en ratas expuestas a diferentes temperaturas del agua midiendo los cambios en el nitrógeno ureico sérico y los niveles de expresión de ARNm de genes de proteínas desacopladoras del músculo esquelético. También se analizaron los efectos fisiológicos y genéticos del ejercicio de natación a baja temperatura sobre los cambios en el metabolismo energético en ratas, tanto a nivel individual como molecular. Los resultados revelaron que el nitrógeno ureico sérico permaneció más estable en ratas nadadoras hipotérmicas en comparación con las ratas del grupo de natación. Además, el estudio observó una regulación positiva inducida de las proteínas desacopladoras en el músculo esquelético de ratas Wistar en respuesta a la estimulación de la temperatura externa, y la expresión de ARNm para las proteínas desacopladoras del músculo esquelético aumentó significativamente a medida que disminuía la temperatura. Además, las nanofibras cortas preparadas también tuvieron un efecto promotor significativo sobre el gen de la proteína de desacoplamiento, COX7A1, al tiempo que suprimieron la expresión del gen lipogénico.

Resumen Introducción. El tacrolimus es un medicamento inmunosupresor ampliamente usado en trasplante hepático, que presenta una gran variabilidad interindividual la cual se considera asociada a la frecuencia de polimorfismos de CYP3A5 y MDR-1. El objetivo de este estudio fue evaluar la frecuencia de los polimorfismos rs776746, rs2032582 y rs1045642 y su asociación con rechazo clínico y toxicidad farmacológica. Métodos. Se incluyeron pacientes inmunosuprimidos con tacrolimus a quienes se les realizó trasplante hepático en el Hospital San Vicente Fundación Rionegro entre 2020 y 2022, con supervivencia mayor a un mes. Se evaluaron las variables clínicas, rechazo agudo y toxicidad farmacológica. Se secuenciaron los genes de estudio mediante PCR, comparando la expresión o no en cada uno de los pacientes. Resultados. Se identificaron 17 pacientes. El 43 % de los pacientes se clasificaron como CYP3A5*1/*1 y CYP3A5*1/*3, entre los cuales se encontró asociación con aumento en la tasa de rechazo agudo clínico, al comparar con los pacientes no expresivos (100 % vs. 44 %, p=0,05); no hubo diferencias en cuanto a la toxicidad farmacológica u otros desenlaces. Se encontró el polimorfismo rs2032582 en un 50 % y el rs1045642 en un 23,5 % de los pacientes, sin embargo, no se identificó asociación con rechazo u otros eventos clínicos. Conclusiones. Se encontró una asociación entre el genotipo CYP3A5*1/*1 y CYP3A5*1/*3 y la tasa de rechazo clínico. Sin embargo, se requiere una muestra más amplia para validar estos datos y plantear modelos de medicina personalizada.

Abstract Introduction. Tacrolimus is an immunosuppressive drug widely used in liver transplantation, which presents great interindividual variability which is considered associated with the frequency of CYP3A5 and MDR-1 polymorphisms. The objective of this study was to evaluate the frequency of the rs776746, rs2032582 and rs1045642 polymorphisms and their association with clinical rejection and drug toxicity. Methods. Immunosuppressed patients with tacrolimus who underwent a liver transplant at the Hospital San Vicente Fundación Rionegro between 2020 and 2022 were included, with survival of more than one month. Clinical variables, acute rejection and pharmacological toxicity were evaluated. The study genes were sequenced by PCR, comparing their expression or not in each of the patients. Results. Seventeen patients were identified. 43% of the patients were classified as CYP3A5*1/*1 and CYP3A5*1/*3, among which an association was found with increased rates of clinical acute rejection when compared with non-expressive patients (100% vs. 44%, p=0.05). There were no differences in drug toxicity or other outcomes. The rs2032582 polymorphism was found in 50% and rs1045642 in 23.5% of patients; however, no association with rejection or other clinical events was identified. Conclusions. An association was found between the CYP3A5*1/*1 and CYP3A5*1/*3 genotype and the clinical rejection rate. However, a larger sample is required to validate these data and propose models of personalized medicine.

Abstract Background: Members of the genus Cupiennius Simon, 1891 are categorized as wandering spiders and are part of the family Trechaleidae. The genomics and proteomics of Cupiennius spiders from North America remain uncharacterized. The present study explores for the first time molecular data from the endemic species Cupiennius chiapanensis Medina, 2006, and also presents new data for Cupiennius salei (Keyserling, 1878), both collected in southern Mexico. Methods: In total, 88 Cupiennius specimens were collected from southern Mexico and morphologically identified. DNA was extracted and the mitochondrial COI fragment was amplified. COI sequences were analyzed, and a phylogenetic tree was inferred for species from the Americas. Genetic diversity was analyzed using haplotype networks and gene distances. Venom was obtained from C. chiapanensis and C. salei by electrostimulation. The venom was separated by HPLC, visualized using SDS-PAGE, and quantified for use in toxicity bioassays in mice and insects. Results: Analysis of COI sequences from C. chiapanensis showed 94% identity with C. salei, while C. salei exhibited 94-97% identity with sequences from Central and South American conspecifics. The venom from C. chiapanensis exhibited toxic activity against crickets. Venoms from C. chiapanensis and C. salei caused death in Anastrepha obliqua flies. Analysis of venom fractions from C. salei and C. chiapanensis revealed molecular masses of a similar size as some previously reported toxins and neurotoxic components. We determined the amino acid sequences of ChiaTx1 and ChiaTx2, toxins that are reported here for the first time and which showed toxicity against mice and insects. Conclusion: Our work is the first to report COI-based DNA barcoding sequences from southern Mexican Cupiennius spiders. Compounds with toxic activity were identified in venom from both species. Background Simon 189 Trechaleidae uncharacterized Medina 2006 Keyserling, Keyserling (Keyserling 1878, 1878 , 1878) Methods total 8 amplified Americas distances C electrostimulation HPLC SDSPAGE, SDSPAGE SDS PAGE, PAGE SDS-PAGE insects Results 94 9497% 9497 97% 97 94-97 conspecifics crickets flies components ChiaTx ChiaTx2 Conclusion COIbased based 18 200 187 9 949 94-9 1 20 94- 2

Resumen Introducción: La toxicidad del plomo se ha relacionado a diferentes patologías en humanos y varias evidencias sugieren una fuerte relación con el daño observado sobre la función reproductiva en humanos y roedores. Método: Se proporcionó a ratones una dosis única de nitrato de plomo (NP) (50mg/kg/pc), los cuales fueron eutanizados siete días postinyección con el objetivo de evaluar los espermatozoides que han salido de los túbulos seminíferos y están en tránsito por el epidídimo; además, se evaluó la fragmentación del ADN espermático mediante el ensayo tunel. Resultados: La disminución del peso corporal en ratones, tratados con NP (p < 0,05), sugiere un efecto tóxico sistémico. Sin embargo, no sucedió lo mismo sobre el sistema reproductivo, debido a que los pesos de los testículos, epidídimos, próstata y vesícula seminal no fueron alterados (p > 0,05); de igual manera, los valores fisiológicos como conteo y movilidad espermática no disminuyeron con el tratamiento (p > 0.05). El tránsito y maduración de los espermatozoides en el epidídimo no sería afectado por el NP, y al no observar aumento en la fragmentación del ADN espermático en el grupo tratado (p > 0,05), la protaminación espermática estaría cumpliendo su rol protector sobre el material genético murino, por lo que no hubo daños genotóxicos por el NP. Conclusión: La administración intraperitoneal de 50mg/kg/pc de NP, por siete días, no causa toxicidad sistémica ni efecto en la espermatogénesis en ratón.

Abstract Introduction: Lead toxicity has been linked to different diseases in humans and several evidences suggest a strong relationship with the observed damage on reproductive function in humans and rodents. Methods: Mice were given a single dose of lead nitrate (NP) (50mg/kg/bw), which were euthanized seven days post-injection with the aim of evaluating sperm to come out from the seminiferous tubules and are in transit through the epididymis. Also, the Tunel test was done to evaluate the sperm DNA fragmentation. Results: The decrease in body weight in mice treated with ln (p < 0.05), suggest a toxic systemic effect. However, the same didn’t happen on the reproductive system because the weights of the testes, epididymis, prostate and seminal vesicles were not altered (p > 0.05), in the same way physiological values such as sperm concentration and motility didn´t decrease with the treatment (p > 0.05). Transit and sperm maturation in the epididymis would not be affected by the ln, and because we did not observe increased sperm DNA fragmentation in the treated group (p > 0.05), sperm protamination would be fulfilling its protective role on murine genetic material avoiding genotoxic damage by ln. Conclusion: The intraperitoneal administration of 50mg/kg/pc of ln for seven days does not cause systemic toxicity or effect on spermatogenesis in mice.

RESUMO O gênero Desmanthus apresenta ampla distribuição ecogeográfica e complexa taxonomia. O Desmanthus pernambucanus (L.) Thellung, popularmente conhecido como Jureminha, é uma leguminosa nativa do Nordeste brasileiro, que se destaca pelo elevado teor de proteína, resistência à seca e por não apresentar toxicidade aos animais. O trabalho foi desenvolvido com o objetivo de avaliar a diversidade genética de 15 progênies oriundas do CSIRO (Commonwealth Scientific and Industrial Research Organization, Austrália), através de intercâmbio de germoplasma, para o enriquecimento do Banco Ativo de Germoplasma de Desmanthus da Embrapa Tabuleiros Costeiros (BAG), em Nossa Senhora das Dores, SE, Brasil. Foram utilizados 15 marcadores ISSR, dos quais oito foram selecionados. As progênies identificadas como 242, 245, 246, 255 e 268 foram as mais distantes geneticamente, e as mais indicadas para serem introduzidas no BAG. taxonomia L. L (L. Thellung Jureminha brasileiro proteína animais 1 Commonwealth Organization Austrália, Austrália , Austrália) germoplasma BAG, BAG (BAG) Dores SE Brasil ISSR selecionados 242 245 246 25 26 geneticamente (L (BAG 24 2

ABSTRACT The genus Desmanthus presents wide ecogeographical distribution and complex taxonomy. Desmanthus pernambucanus (L.) Thellung, popularly known in Brazil as Jureminha, is a leguminous species native to the Northeast region of Brazil, which stands out by its high protein content, resistance to droughts, and by presenting no toxicity to animals. The objective of this work was to evaluate the genetic diversity of 15 progenies from the Commonwealth Scientific and Industrial Research Organization (CSIRO; Australia), through germplasm exchange for enrichment of the Desmanthus genebank of Embrapa Tabuleiros Costeiros, in Nossa Senhora das Dores, SE, Brazil. Fifteen ISSR markers were used, from which 8 were selected. The progenies identified as 242, 245, 246, 255, and 268 were the most genetically distant, and the most recommended to be introduced to the genebank. taxonomy L. L (L. Thellung Jureminha content droughts animals 1 CSIRO (CSIRO Australia, Australia , Australia) Costeiros Dores SE used selected 242 245 246 255 26 distant (L 24 25 2

ABSTRACT Epilepsy is a multifactorial pathology that has allowed the development of various drugs aiming to combat it. This effort was formally initiated in the 1940s when phenytoin began to be used. It eventually turned out to be a drug with great anticonvulsant efficacy. At present, several potentially good new generation anti-seizure medications (ASMs) have been developed. Most of them present more tolerability and less toxic effects. However, they continue to have adverse effects at different levels. In addition, some seizures are difficult to treat with ASMs, representing 30% of the total cases of people who suffer from epilepsy. This review aims to explore the genetic and molecular mechanisms of ASMs neurotoxicity, proposing the study of damage caused by epileptic seizures, in addition to the deterioration generated by anti-seizure drug administration within the central nervous system. It is beyond question that there is a need to develop drugs that lower the lower the risk of secondary and toxic effects of ASMs. Simultaneously, we must find strategies that produce fewer harmful interactions and more health benefits when taking anti-seizure drugs.

RESUMO A salinidade causada pelo excesso de sais na solução do solo é um dos estresses ambientais mais limitantes na agricultura no mundo. Nesse cenário, dentre as estratégias para favorecer a expressão do potencial genético das plantas, destaca-se o uso de bioestimulantes. Objetivou-se avaliar a influência de um bioestimulante à base de extrato de algas marinhas no crescimento, produção de forragem, trocas gasosas e acúmulo de íons sódio e potássio em capim-pangolão Digitaria pentzii, submetido a condições de estresse salino. O experimento foi conduzido de março a julho de 2019, em delineamento de blocos casualizados, em esquema fatorial 2 × 3, com duas concentrações do bioestimulante (0 e 8 mL L-1) e três condutividades elétricas da água de irrigação (0,03; 2 e 4 dS m-1), com quatro repetições. O acúmulo de 50 µmol g-1 de sódio nas folhas correspondeu a uma redução de 0,3 g de matéria seca na produção de lâminas foliares por vaso. O bioestimulante não influenciou as características estruturais do capim-pangolão, acúmulo de fitomassa e condutância estomática, independentemente da salinidade. No nível de 4 dS m-1 na água de irrigação, a toxicidade do estresse iônico devido ao acúmulo de sais na parte aérea do capim-pangolão é mais severa. Esta é a primeira evidência da tolerância “moderada” à salinidade do capim-pangolão em regiões semiáridas.

ABSTRACT Salinity caused by excess salts in soil solutions is one of the most limiting environmental stresses in agriculture worldwide. In this scenario, among strategies that favor the expression of the genetic potential of plants, the use of biostimulants stands out. The objective of this study was to evaluate the influence of a seaweed-based biostimulant on growth, forage production, gas exchange, and accumulation of sodium and potassium ions in pangolão grass (Digitaria pentzii) under saline stress. The experiment was conducted from March to July 2019 using a randomized block design, in a 2 × 3 factorial scheme with two concentrations of biostimulant (0 and 8 mL L-1) and three electrical conductivities of irrigation water (0.03, 2 and 4 dS m-1), with four replicates. The accumulation of 50 µmol g-1 of sodium in leaves corresponded to a reduction of 0.3 g of dry matter in the leaf blade production per plot. The biostimulant did not influence the structural characteristics, phytomass accumulation, or stomatal conductance of the pangolão grass, regardless of salinity. At the level of 4 dS m-1 in irrigation water, the ionic stress toxicity due to the accumulation of salts in the aerial part of pangolão grass was more severe. This is the first evidence of the “moderate” salinity tolerance of pangolão grass in semi-arid regions.

SUMMARY Palmoplantar erythrodysesthesia is an adverse event associated with the administration of docetaxel and fluoropyrimidines. The activity of the enzyme dihydropyrimidine dehydrogenase (DPD) determines the rate of catabolism of 5-Fluorouracil (5-FU) and is subject to interindividual variability and genetic polymorphism. Therefore, patients with DPD deficiency present an increased risk of toxicity. We present the case of a patient treated with docetaxel, oxaliplatin and 5-FU (FLOT scheme) who presented moderate skin toxicity and who was suspected of DPD deficiency.

RESUMEN La eritrodisestesia palmoplantar es una reacción adversa que se asocia a la administración de docetaxel y fluoropirimidinas. La actividad de la enzima dihidropirimidina deshidrogenasa (DPD) determina la tasa de catabolismo del 5-Fluorouracilo (5-FU) y está sujeta a variabilidad interindividual y polimorfismo genético. Por tanto, los pacientes con deficiencia de DPD presentan un mayor riesgo de toxicidad. Presentamos el caso de un paciente tratado con docetaxel, oxaliplatino y 5-FU (esquema FLOT) que presentó toxicidad cutánea moderada y del que se sospechó deficiencia de DPD.

Resumen 16. El metil mercurio (MeHg) es un contaminante ambiental tóxico y nocivo que se bioacumula y biomagnifica en la cadena trófica. La tortuga Trachemys scripta elegans (Tse), considerada centinela de contaminación ambiental debido a su longevidad, posee eritrocitos (RBCs) nucleados con afinidad del 90% por MeHg. Este estudio determinó la citotoxicidad y genotoxicidad in vitro del MeHg sobre RBCs de Tse a concentraciones de 0, 0,5, 0,7, 1, 10, 20, 50 y 100 mg/L-1a las 24 y 96 h de exposición. Los RBCs se aislaron por centrifugación y se emplearon 1,69 x 106 RBCs por tratamiento. Se determinó el porcentaje de viabilidad, concentración letal media (CL50) y se verificaron cambios citológicos a las 24 y 96 h. El ADN fue extraído a las 96 h y se evaluó la genotoxici dad por marcadores RAPDs calculando el porcentaje de polimorfismo, índice de estabilidad genética (GST) y coeficiente de disimilaridad de Jaccard (dJSC). A las 96 h la viabilidad a 0,5, 0,7 y 1 m g L -1 de MeHg fue del 99% y 10, 20, 50 y 100 m g L -1de MeHg fue de 94%, 20% y 0%. La CL50 determinada en 22,55 m g L -1 de MeHg. El análisis celular mostró en las di ferentes concentraciones de MeHg, inclusiones citoplasmáticas, desvanecimiento o ruptura de membrana, núcleos excéntricos y lisis celular. El polimorfismo identificado fue del 85% y 50% y dJSC de 0,5 y 0,63 en 50 a 100 m g L -1de MeHg comparado con el grupo control. La GST disminuyó hasta 42% a 100 m g L -1de MeHg. Se concluye que el MeHg es citotóxico y genotóxico a concentraciones mayores de 10 m g L -1 en RBCs de Tse. Este estudio representa una línea base para estudios en toxicología por Hg en RBCs de Tse.

Abstract 20. Methyl mercury (MeHg) is a xenobiotic that bio- accumulates and bio-magnifies in the food chain. The Trachemys scripta elegans (Tse) turtle is considered a sentinel of environmental pollution because of its longevity. Tse has nucleated erythrocytes (RBCs) with 90% affinity for MeHg. This study determined cyto-toxicity and geno-toxicity in vitro of MeHg on Tse RBCs at concentrations of 0, 0.5, 0.7, 1, 10, 20, 50 and 100 m g L -1 at 24 and 96 h of exposure. The RBCs were isolated by centrifugation and 1.69 x106 RBCs per treatment were used. The percentage of viability, mean lethal concentration (LC50) and cytological changes were determined at 24 and 96 h. It was evaluated the xeno toxicity by RAPDs markers with extracted DNA at 96 h, calculating the percentage of polymorphism, index of genetic stability (GST) and coefficient of Jaccard dissimilarity (dJSC). At 96 h, viability was maintained between 99-0% in 0.5-100 mg L-1 of MeHg. The LC50 was 22.55 mg L-1 MeHg. Cytological abnormalities were presented in 0.7-100 m g L -1 MeHg as crescent shape, cytoplasmic inclusions, membrane fading, eccentric nuclei and cell lysis. The polymorphism was 85-50% and the dJSC was 0.5-0.63 in 50-100 m g L -1 MeHg compared to the control group. GST decreased to 42% at 100 m g L -1MeHg. It is concluded that MeHg is cytotoxic and genotoxic at concentrations greater than 10 mg L-1 in Tse RBCs. This study represents a baseline for Hg toxicological studies in reptile RBCs.

RESUMO Cresce o número de pacientes em tratamento hemodialítico e, com isso, o volume de efluente gerado. Esse efluente possui alta concentração de sais, compostos nitrogenados e matéria orgânica; ainda, pode conter fármacos e microrganismos. No âmbito municipal, o efluente gerado é aportado nas redes de esgoto e lançado em recursos hídricos superficiais. Testes toxicológicos com o uso de sementes fornecem confiáveis respostas, com simplicidade e baixo custo de procedimentos e materiais; todavia, não possibilitam identificar o agente causador de toxidez, mas da toxicidade do conjunto de contaminantes. Diante disso, o objetivo deste trabalho foi avaliar fitotoxicidade, citotoxicidade e genotoxicidade do efluente hemodialítico gerado no maior hospital da região sul do Rio Grande do Sul. Utilizaram-se amostras compostas coletadas no início, meio e fim de cada sessão, em cinco máquinas e diferentes turnos. Foram testados efluente puro e diluído, água para composição do dialisato, dialisato puro e diluído e controle. Os testes de fitotoxicidade foram realizados com sementes de pepino Verde Comprido, alface Regina de Verão e Rabo-de-Galo. Para análises de citogenotoxicidade, utilizaram-se sementes de cebola Baia Periforme. Observou-se que o efluente hemodialítico e o dialisato puros exerceram efeito tóxico em todas as sementes analisadas. Embora o efluente diluído não tenha causado fitotoxicidade na alface e no pepino, testes de citogenotoxicidade mostraram diminuição do índice mitótico e aparecimento de aberrações cromossômicas em células de cebola, indicando toxicidade em nível celular e genético. Esses resultados permitem concluir que tal efluente não pode ser aportado diretamente em recursos hídricos, tampouco reutilizado na irrigação sem tratamento prévio. isso sais orgânica ainda microrganismos municipal superficiais respostas materiais todavia toxidez contaminantes disso Sul Utilizaramse Utilizaram se início sessão turnos controle Comprido RabodeGalo. RabodeGalo Rabo Galo. Galo Rabo-de-Galo utilizaramse utilizaram Periforme Observouse Observou analisadas genético prévio

ABSTRACT The number of patients undergoing hemodialysis treatment increases and, consequently, the volume of effluent generated. This effluent presents high concentration of salts, nitrogen, and organic matter; furthermore, it may contain drugs and microorganisms. At the municipal level, hemodialysis effluent is piped to sewage networks and discharged to surface water. Toxicological tests using seeds provide reliable answers, with simplicity and low cost of procedures and materials; however, it does not allow to identify the agent that causes toxicity, but the toxicity of the set of contaminants. In this sense, the objective of this work was to evaluate phytotoxicity, cytotoxicity, and genotoxicity of the hemodialysis effluent generated in the largest hospital of the southern region of Rio Grande do Sul. Composite samples collected at the beginning, middle and end of each session on five machines and different shifts were used. Pure and diluted effluent, water for the composition of the dialysate, pure and diluted dialysate and control were tested. The phytotoxicity tests were performed with seeds of Verde Comprido cucumber, and Regina de Verão and Rabo-de-Galo lettuce. For cytogenotoxicity analyses, Baia Periforme onion seeds were used. It was observed that the pure hemodialysis effluent and dialysate had a toxic effect on all analyzed seeds. Although the diluted effluent did not cause phytotoxicity in lettuce and cucumber, cytogenotoxicity tests showed a decrease in mitotic index and appearance of chromosomal aberrations in onion cells, indicating toxicity at a cellular and genetic level. These results allow to conclude that this effluent cannot be directly dumped into water resources, nor can it be reused in irrigation without prior treatment. consequently salts nitrogen matter furthermore microorganisms level answers materials however contaminants sense cytotoxicity Sul beginning used tested cucumber RabodeGalo Rabo Galo analyses cells resources

Abstract Duchenne muscular dystrophy (DMD) is a severe disease with no cure caused by a genetic abnormality, promoting progressive muscle degeneration. Corticosteroids are used drugs in treatment associated with adverse effects. The extract of Miconia ferruginata (Melastomataceae) (MF) has demonstrated potent antioxidant and anti-inflammatory potential in vitro. This study used a DMD model (mdx) to determine the toxic dose of this plant and found a possible non-toxic dose with therapeutic effects. The mdx groups received an intraperitoneal injection of 0 (control group), 50, 100, 200, 300, and 2000 mg kg-1 of the aqueous leaf extract following a single-dose acute toxicity protocol and were observed for 14 days. The range of toxicity of the extract and LD50 were determined. Histopathological analysis, the quantification of fibrosis, and immunohistochemical analysis of the tissues were performed. The results demonstrated that 2000 mg kg-1 was highly toxic, inducing histopathological changes in the tissues evaluated, with 100% mortality in 48 hours. The other doses caused no behavioral changes or signs of toxicity. The MF extract led reduction in histopathological changes, fibrosis, and inflammation, a reduction in HSP70 and an increase in MCL-1 proteins. Doses of 50-200 mg kg-1 demonstrated regenerative tissue and anti-inflammatory potential.

Abstract Classical galactosemia is caused by the genetic deficiency of galactose-1-phosphate-urydyl-transferase resulting in clinical symptoms development during the first weeks of life including jaundice, hypotonia, lethargy, emesis, hepatomegaly, among others. Currently, dietary restriction of galactose is considered the standard for classical galactosemia management. For several years, severe dietary galactose restriction was considered necessary, implying restriction not only of dairy products, but also fruits, vegetables, legumes, and viscera. Such management failed to improve or prevent the appearance of long-term complications, by contrast, such restrictive approach may lead to nutritional deficiencies development. Thus, the last consensus suggests guidelines that are more flexible. In addition, the lack of knowledge regarding the physiopathology of the disease, and the toxicity threshold of the metabolites accumulated, make even more difficult to propose novel and more effective therapeutic approaches. This review summarizes the current state of knowledge regarding classical galactosemia in terms of physiopathology, long-term complications, newborn screening and genetic variants and their implications on galactosemia treatment, summed to the challenges that researchers working on this disease must address in future studies including the analysis of galactose content in foods, galactose tolerance threshold and search for novel therapeutic targets.

Abstract The conservation of plant genetic resources is fundamental for the development of agriculture. The development of efficient cryopreservation protocols has become an effective tool to preserve cells, tissues and organs of different plant species. We sought here to develop an efficient method of cryopreservation of Eucalyptus grandis employing the V cryo-plate technique. This experiment examined the exposure of shoot tips to three different cryoprotectants (PVS2, PVS3, and PVS4). The cryoprotectants PVS2 and PVS4 proved to be more efficient among the cryoprotectants tested, as 44.4% of the shoot tips immersed in those solutions survived, and 31.1% generated new shoots. Ethylene glycol was found to be a key compound for the successful cryopreservation of shoot tips, in light of its low toxicity as compared to other cryoprotective compounds. Thus, the methodology developed here represents an effective method for the conservation of E. grandis germplasm through cryopreservation and the use of the V cryo-plate technique.

Resumen: Antecedentes y Objetivos: Pyrodinium es un género monotípico con dos variedades, var. bahamense en el Atlántico, no tóxica, y var. compressum en el Indo-Pacífico y tóxica. Hallazgos recientes de toxicidad por envenenamiento paralitico por mariscos (PSP), en poblaciones de P. bahamense var. bahamense, debilitaron el interés por aceptarlas como independientes, e incluso investigar la posibilidad de cripticismo. En los pocos estudios que han incorporado evidencia molecular en el tratamiento de las variedades, su independencia taxonómica sigue siendo negada, a pesar de la evidente y consistente separación genética presentada en todos los análisis. Por lo tanto, el objetivo de este estudio fue reconocer, desde la evidencia genética, la independencia taxonómica de las dos variedades de Pyrodinium: P. bahamense var. compressum y var. bahamense. Métodos: A partir de tres marcadores moleculares (Lcf, LSU, SSU) de secuencias disponibles en el Genbank, se construyeron redes de parsimonia estadística y un análisis filogenético concatenado. Resultados clave: En todos los análisis, se obtuvo de manera consistente una estructura genética para P. bahamense var. bahamense y otra para P. bahamense var. compressum. Además, la correspondencia de haplotipos y ribotipos resultantes fue siempre la misma, tanto en redes como en la filogenia; es decir, las muestras del Océano Pacífico siempre se colocaron en un grupo distinto al de las secuencias del Océano Atlántico. Conclusiones: La evidencia proporcionada en este estudio demostró que existe un aislamiento reproductivo entre ambas variedades, e incluso la posible presencia de una tercera variedad aún no descrita, por lo cual proponemos la validez e independencia taxonómica de P. bahamense var. compressum y P. bahamense var. bahamense.

Abstract: Background and Aims: Pyrodinium is a monotypic genus with two varieties, var. bahamense in the Atlantic, non-toxic, and var. compressum in the Indo-Pacific and toxic. Recent findings of Paralytic Shellfish Poisoning (PSP) toxicity in populations of P. bahamense var. bahamense weakened the interest in accepting both varieties as independent, and even investigating the possibility of crypticism between them. In the few studies that have involved molecular evidence in the treatment of varieties, their taxonomic independence continues to be denied, despite the evident and consistent genetic separation shown in all analyses. Therefore, the aim of this study was to recognize, based on genetic evidence, the taxonomic independence of the two varieties of Pyrodinium: P. bahamense var. compressum and var. bahamense. Methods: Based on three molecular markers (Lcf, LSU, SSU) of sequences available in Genbank, statistical parsimony networks and a concatenated phylogenetic analysis were constructed. Key results: In all analyses, a genetic structure was consistently obtained for P. bahamense var. bahamense and another one for P. bahamense var. compressum. Furthermore, the correspondence of the resulting haplotypes and ribotypes was always the same in both networks and phylogeny, i.e., the samples from the Pacific Ocean were always placed in a different group than those from the Atlantic Ocean. Conclusions: The evidence provided in this study demonstrated the reproductive isolation between both varieties, and even the possible presence of a not yet described third variety, as a consequence of which we propose the validity and taxonomic independence of P. bahamense var. compressum and P. bahamense var. bahamense.