Simultaneous removal of crude oil and heavy metals by highly adapted bacterial strain Cutibacterium sp. NL2 isolated from Algerian oilfield

Investigating the ability of bacteria to simultaneously enhance hydrocarbon removal and reduce heavy metals’ toxicity is necessary to design more effective bioremediation strategies. A bacterium (NL2 strain) isolated from an Algerian oilfield was cultivated on crude oil as sole carbon and energy sources. Molecular analyses of the 16S rRNA gene sequence placed the strain within the Cutibacterium genera. This isolate was able to tolerate up to 60% of crude oil as sole carbon source. Chemical analyses (GC-MS) evidenced that strain NL2 was able to degrade 92.22% of crude oil (at optimal growing conditions: pH 10, 44 °C, 50 g L−1 NaCl, and 20% of crude oil (v/v) as sole carbon source) in only 7 days. NL2 isolate was also able to produce biosurfactants with reduction of surface tension of growing media (29.4 mN m−1). On the other hand, NL2 strain was able to tolerate high lead (Pb) and copper (Cu) concentrations (up to 60 mM). In fact, NL2 cultivated in the presence of 20% of crude oil, and 0.48 mM of Pb was able to reduce Pb concentration by a 41.36%. In turn, when cultivated on high Pb concentration (15 mM), the strain was able to remove 35.19% of it and 86.25% of crude oil, both in a time frame of 7 days. Our findings suggest that Cutibacterium strain NL2 is able to efficiently use and remove a wide range of crude oil substrates in presence of high Pb concentration. Accordingly, NL2 strain is of extreme interest from a biotechnological standpoint. (AU)

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH–AEG–SEPD–SEOM–GETECCU / Manejo de las toxicidades digestivas secundarias al tratamiento con inhibidores de checkpoint: documento de posicionamiento de la AEEH-AEG-SEPD-SEOM-GETECCU

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.(AU)

El descubrimiento de los inhibidores de checkpoint inmunológicos (ICI) es uno de los logros más importantes en los últimos años en Oncología. Sin embargo, su uso en aumento ha conlllevado a un incremento de los efectos adversos inmunomediados (irAEs). Los eventos hepáticos y gastrointestinales incluyen la hepatitis, colitis y síntomas de tracto digestivo superior, que son de los irAEs más frecuentes, con incidencias entre el 2 y 40%, ésta última en paciente tratados con combo de ICI. Basados en la evidencia científica tanto de ensayo clínicos randomizados como de estudio de vida real, este documento de consenso aporta recomendaciones sobre el diagnóstico, tratamiento y pronóstico de los efectos adversos hepáticos y gastrointestinales asociados con la inmunoterapia.(AU)

Biofouling inhibition by Staphylococcus aureus extracts and their potential use for paints / Inhibición de la bioincrustación por extractos de Staphylococcus aureus y su uso potencial para pinturas

For the control of biofouling, some paints based on compounds that are toxic to marine organisms have been used. There is an intensive search for biodegradable solutions that are friendly to non-target organisms. Bacteria have been shown to be a source of compounds with antifouling potential. In this work, the antifouling activity of a strain of Staphylococcus aureus was evaluated. Extracts activity against biofilm-forming bacteria and the toxicity against Artemia franciscana were evaluated. The extracts were incorporated in a hard gel and a paint matrix, and they were exposed to the sea. In both the laboratory and field, we found that the compounds produced by S. aureus have antifouling activity. The non-toxicity of the tested extracts against Artemia franciscana nauplii suggests that the extracts obtained from S. aureus could have a low ecological impact over non-target organisms. Significant differences were found in the percentage of organisms cover in hard gels with extracts and control. After 90 days, important differences were also observed between the percentage of organisms cover of the paints that contained extracts and the control. Dichloromethane extract is the most effective for the inhibition or delay of the settlement of organisms For this reason, they could be used in matrices with different applications, such as in the shipping industry, aquaculture, or any other in which biofouling is a cause of inconvenience.(AU)

Phytotoxic and cytogenotoxic assessment of glyphosate on Lactuca sativa L / Avaliação fitotóxica e citogenotóxica do glifosato em Lactuca sativa L

The active ingredient glyphosate is the most commercialized herbicide on the world market due to its capability in eliminating weeds. However, it can harm the development of non-target organisms and threaten environmental quality. This study analyzed the effects of potentially toxic concentrations of glyphosate on germination, growth, cell cycle and genomic stability of Lactuca sativa L., and identified the most sensitive variables for assessing the toxicity of this herbicide to this biomonitor. Seeds of L. sativa were germinated in Petri dishes containing a sheet of filter paper moistened with 5 mL of a concentration of glyphosate (1.34, 3.35, 6.70, 10.05, 13.40 mg L-1). Controls consisted of distilled water (negative) and 3 mg L-1 CuSO4 (positive). Macroscopic and microscopic variables were analyzed. The germination of L. sativa was not affected by the concentrations of glyphosate. Root length and shoot height of the plants and the mitotic index decreased from the lowest concentration tested on. The chromosomal anomaly index and frequency of micronuclei increased by 3.2 and 22 times, respectively, with the presence of the lowest concentration of glyphosate compared to the negative control. The observed phytotoxic and cytogenotoxic effects demonstrate the negative influence that glyphosate has on the development of L. sativa. Root length and microscopic variables showed the highest sensitivity. This study warns of the possible harmful effects that glyphosate can have on non-target organisms and suggests greater control over the use of this herbicide to mitigate its environmental impact.

O ingrediente ativo glifosato é o herbicida mais comercializado do mercado mundial, pela sua capacidade de eliminar as plantas daninhas. No entanto, ele pode prejudicar o desenvolvimento dos organismos não-alvo e ameaçar a qualidade do ambiente. O estudo teve como objetivo analisar os efeitos de concentrações potencialmente tóxicas de glifosato sobre a germinação, o crescimento, o ciclo celular e a estabilidade genômica de Lactuca sativa L., e identificar as variáveis mais sensíveis para avaliar a toxicidade deste herbicida ao biomonitor. Sementes de L. sativa foram germinadas em placas de Petri contendo uma folha de papel-filtro umedecida com 5 mL das concentrações de glifosato (1,34, 3,35, 6,70, 10,05, 13,40 mg L-1). Os controles consistiram em água destilada (negativo) e 3 mg L-1 de CuSO4 (positivo). Variáveis macroscópicas e microscópicas foram analisadas. A germinação de L. sativa não foi afetada pelas concentrações de glifosato. O comprimento da raiz e a altura da parte aérea das plantas e o índice mitótico reduziram desde a menor concentração testada. O índice de anomalias cromossômicas e a frequência de micronúcleos aumentaram, respectivamente, 3,2 e 22 vezes na presença da menor concentração de glifosato em comparação ao controle negativo. Os efeitos fitotóxicos e citogenotóxicos observados demonstram a interferência negativa do herbicida no desenvolvimento de L. sativa. O comprimento da raiz e as variáveis microscópicas foram as que apresentaram maior sensibilidade. Este estudo alerta sobre os possíveis efeitos prejudiciais que o glifosato pode provocar nos organismos não-alvo, sugerindo um maior controle quanto à utilização deste herbicida, a fim de mitigar o seu impacto ambiental.

Neurite óptica relacionada ao uso de imatinibe / Optic neuritis related to the use of imatinib

O mesilato de imatinibe é o primeiro inibidor oral de tirosina quinase que atua impedindo a proliferação celular da linhagem de células mieloides que expressam o gene BCR-ABL, sendo usado no tratamento de leucemia mieloide crônica. O advento dos inibidores da tirosina quinase revolucionou o tratamento destes pacientes, apresentando efeitos colaterais relatados como citopenias, edemas, efeitos gastrointestinais e manifestações neurológicas. As manifestações neurológicas são raras, podendo ocorrer em qualquer momento do tratamento e permanecendo após sua interrupção, sugerindo risco cumulativo de neurotoxicidade. Esse relato de caso, visa estabelecer a relação do processo de desmielinização do sistema nervoso central ocorrendo após o início do tratamento com imatinibe. Apresentando um caso raro de neurite óptica devido ao uso crônico de mesilato de imatinibe no tratamento de leucemia mieloide crônica, na ausência de outros fatores de risco. Como conclusão, oferece evidências clínicas da associação de inibidores da tirosina quinase com neurotoxicidade, embora não possa estabelecer a causa. Mais estudos são necessários para elucidar a potencial relação do uso do imatinibe com a neurite óptica

Imatinib mesylate is the first oral tyrosine kinase inhibitor that works by preventing cell proliferation of the myeloid cell line that expresses the BCR-ABL gene, used in the treatment of chronic myeloid leukemia. The advent of tyrosine kinase inhibitors has revolutionized the treatment of these patients, with side effects such as cytopenias, edema, gastrointestinal effects and neurological manifestations. Neurological manifestations are rare and can occur at any time during treatment and persist after its interruption, suggesting a cumulative risk of neurotoxicity. This case report aims to establish the relationship between the demyelination process of the central nervous system occurring after the start of treatment with imatinib. Presents a rare case of optic neuritis due to the chronic use of imatinib mesylate in the treatment of chronic myeloid leukemia, in the absence of other risk factors. In conclusion, it offers clinical evidence of the association of tyrosine kinase inhibitors with neurotoxicity, although it cannot establish the cause. More studies are needed to elucidate the potential relationship between the use of imatinib and optic neuritis

Utilidad de la app Abeona Health® para la participación del paciente en la identificación de toxicidad inducida por quimioterapia según la clasificación CTCAE / Utility of the Abeona Health® app for patient participation in the identification of chemotherapy- induced toxicity according to the CTCAE classification

Fundamentos: Desde 2003, el Instituto Nacional del Cáncer (NCI) de los Estados Unidos de América ha sido uno de los líderes mundiales en la clasificación de los Efectos Adversos (EA). Actualmente, los teléfonos inteligentes permiten, entre otras muchas cosas, la monitorización de estos EA de la quimioterapia desde el domicilio para mejorar la seguridad y la calidad de vida de los pacientes. El objetivo de este estudio fue realizar un análisis comparativo descriptivo del contenido de los EA de la aplicación Abeona Health® y la última versión de los CTCAE (Common Terminology Criteria for Adverse Events). Métodos: Se utilizó la app Abeona Health® y la guía CTCAE v5. Posteriormente, se analizaron los EA más recurrentes en el tratamiento quimioterápico, según la NCI y la Sociedad Española de Oncología Médica (SEOM) y, finalmente, si los pacientes podían identificarlos. Resultados: El CTCAE v5 recoge 837 EA, donde 225 son signos y síntomas. El NCI clasifica cincuenta y cinco signos y síntomas como los más recurrentes, y la SEOM dieciséis, de los cuales quince coinciden con el NCI. La aplicaciónAbeona Health® dispone de siete EA, y todos se incluyen en el CTCAE v5. De estos siete, seis aparecen en las listas de EA más recurrentes del NCI y cuatro en la de la SEOM, todos ellos identificables por el paciente. Conclusiones: Laapp de Abeona Health® se considera adecuada para la participación del paciente en su autocuidado, si biense podrían ampliar algunos campos.(AU)

Bbackground: Since 2003, the National Cancer Institute (NCI) of the United States of America has been one of the world leaders in classifying adverse effects (AEs). Currently, smartphones allow, among many other things, the monitoring of these AEs of chemotherapy from home to improve the safety and quality of life of patients. The aim was to perform a descriptive comparative analysis of the AEs content of the Abeona Health® app and the latest version of the CTCAE (Common Terminology Criteria for Adverse Events). Methods: The Abeona Health® app and the CTCAE v5 guide were used. Subsequently, the most recurrent AEs in the existing chemotherapy treatment were analysed according to the NCI and the Spanish Society of Medical Oncology (SEOM) and finally, whether patients could identify them. Results: The CTCAE v5 (collects 837 AEs), where two hundred and twenty-five are signs and symptoms. The NCI classifies fifty-five signs and symptoms as the most recurrent, and the SEOM sixteen, of which fifteen coincide with the NCI. The Abeona Health® application has seven AEs, all included in the CTCAE v5. Of these seven, six appear in the NCI lists of most recurrent AEs and four in the SEOM list, all identifiable by the patient. Conclusions: TheAbeona Health® app is considered adequate for the patient participation in their self-care, although somefields could be expanded.(AU)

Characterization of bacterial diversity and capacity to remove lead of a consortium from mining soil / Caracterización de la diversidad bacteriana y capacidad de remoción de plomo de un consorcio en suelo minero

Introduction: At present, the presence of lead (Pb2+) continues to be a problem in water bodies due to its continuous use and high toxicity. The aim of this study was to investigate the bacterial diversity of a potential consortium used as a biosorbent for the removal of lead in an aqueous solution. Methods: The minimum inhibitory concentration and the mean lethal dose of the consortium were determined, and then the optimal variables of pH and temperature for the removal process were obtained. With the optimal conditions, the kinetic behavior was evaluated, and adjustments were made to different mathematical models. A Fourier transform infrared spectroscopy analysis was performed to determine the functional groups of the biomass participating in the removal process, and the diversity of the bacterial consortium was evaluated during Pb2+ removal by an Ion Torrent Personal Genome Machine System. Results: It was found that the intraparticle diffusion model was the one that described the adsorption kinetics showing a higher rate constant with a higher concentration of Pb2+, while the Langmuir model was that explained the isotherm at 35 °C, defining a maximum adsorption load for the consortium of 54 mg/g. In addition, it was found that Pb2+ modified the diversity and abundance of the bacterial consortium, detecting genera such as Pseudomonas, Enterobacter, Citrobacter, among others. Conclusions: Thus, it can be concluded that the bacterial consortium from mining soil was a biosorbent with the ability to tolerate high concentrations of Pb2+ exposure. The population dynamics during adsorption showed enrichment of Proteobacteria phyla, with a wide range of bacterial families and genera capable of resisting and removing Pb2+ in solution.(AU)

Influencia de la hiperfiltración glomerular en la menor toxicidad hematológica inducida por linezolid / Influence of augmented renal clearance on the lower incidence of linezolid-related hematological toxicity

Objetivos linezolid es una oxazolidina frecuentemente implicada en el desarrollo de toxicidad hematológica, siendo el aclaramiento renal el mecanismo mayoritario en su eliminación. Se evaluó la influencia de la hiperfiltración glomerular en la toxicidad hematológica inducida por linezolid en pacientes con aclaramiento incrementado frente a pacientes con función renal normal. Material y métodos se diseñó un estudio observacional y retrospectivo en pacientes hospitalizados, tratados al menos 5 días con linezolid entre 2014 y 2019. Se compararon pacientes con aclaramiento de creatinina incrementado (≥130 mL/min) y normal (60–90 mL/min). Se definió la toxicidad hematológica como el descenso en plaquetas y hemoglobina del 25% y en neutrófilos del 50% frente a los valores basales. Se clasificó el grado de toxicidad según Common Terminology Criteria for Adverse Events v5 y se comparó la incidencia entre ambos grupos mediante Chi-cuadrado y Fisher. Así mismo, se calculó el porcentaje de disminución de los 3 parámetros y su asociación mediante el test de Mann–Whitney y se registraron las interrupciones y transfusiones asociadas.Resultados se evaluaron 30 pacientes hiperfiltradores y 38 normofiltradores. El 16,66% de hiperfiltradores presentó toxicidad hematológica frente al 44,74% (p = 0,014). La trombocitopenia fue del 13,33 vs. 36,84% (p = 0,051), la anemia del 3,3 vs. 10,52% (p = 0,374) y la neutropenia del 10 vs. 23,68% (p = 0,204). La mediana del porcentaje de descenso plaquetario en hiperfiltradores frente a normofiltradores fue del −10,36 (−193,33–62,03) vs. 2,68 (−163,16–82,71) (p = 0,333), de hemoglobina 2,50 (−12,12–25,93) vs. 9,09 (−17,72–30,63) (p = 0,047) y de neutrófilos 9,14 (−73,91–76,47) vs. 27,33 (−86,66–90,90) (p = 0,093). El 10,5% con filtrado normal presentó toxicidad grado 3 o superior, el 2,6% interrumpió el tratamiento y el 5,2% requirieron transfusiones... (AU)

Objectives Linezolid is an oxazolidin commonly related to the development of hematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced hematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. Material and methods A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014–2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60–90 mL/min) were compared. Hematological toxicity was defined as a decrease of 25% in platelets, of 25% in hemoglobin and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of hematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentaje disminution of all three parameters was calculated and compared by Mann–Whitney test and treatment interruption and tranfusion requirements were registered. Results 30 ARC patients and 38 reference patients were included. Hematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (p = 0.014); thrombocytopenia in 13.33% vs 36.84% (p = 0.051), anemia in 3.3% vs 10.52% (p = 0.374) and neutropenia in 10% vs 23.68% (p = 0.204). Median percentaje of platelets decrease in ARC patients was −10.36 (−193.33–62.03) vs 2.68 (−163.16–82.71) in reference patients (p = 0.333), while hemoglobin decrease was 2.50 (−12.12–25.93) vs 9.09 (−17.72–30.63) (p = 0.047) and neutrophils decrease was 9.14 (−73.91–76.47) vs 27.33 (−86.66–90.90) (p = 0.093). 10.5% of normal renal function patients reported at least one adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had tranfusion requirements... (AU)

Variantes genéticas y actividad enzimática de la citidin desaminasa: relación con la toxicidad a la capecitabina y recomendación de ajuste de las dosis / Genetic variants and enzyme activity in citidin deaminase: Relationship with capecitabine toxicity and recommendation for dose adjustment

Objetivo: la capecitabina es un fármaco antineoplásico utilizado en el tratamiento del cáncer de mama y de colon que puede dar lugar a una toxicidad grave, llegando a ser mortal en algunos pacientes. La variabilidad interindividual de esta toxicidad es debida en gran medida a las variaciones genéticas en los genes diana y las enzimas de metabolismo de este fármaco, como la timidilato sintasa y la dihidropirimidina deshidrogenasa. La enzima citidin desaminasa (CDA), imprescindible en la activación de la capecitabina, también presenta diversas variantes asociadas con un mayor riesgo de toxicidad al tratamiento, aunque su papel como biomarcador aún no está claramente definido. Por ello, nuestro objetivo principal es estudiar la asociación entre la presencia de las variantes genéticas en el gen CDA, su actividad enzimática y el desarrollo de la toxicidad grave en los pacientes tratados con capecitabina, cuya dosis inicial se haya ajustado con base en el perfil genético del gen de la dihidropirimidina deshidrogenasa (DPYD). Método: estudio de cohortes observacional multicéntrico prospectivo, centrado en el análisis de la asociación genotipo-fenotipo de la enzima CDA. Tras la fase experimental, se desarrollará un algoritmo que permita determinar el ajuste necesario de las dosis para disminuir el riesgo de toxicidad del tratamiento en función del genotipo CDA, elaborando una guía clínica para la dosificación de la capecitabina en función de las variantes genéticas en DPYD y CDA. Con base en esta guía, se creará una herramienta bioinformática que genere el informe farmacoterapéutico de manera automática, facilitando la implementación del consejo farmacogenético en la práctica clínica. Esta herramienta proporcionará un gran respaldo en la toma de decisiones farmacoterapéuticas basadas en el perfil genético del paciente, incorporando la medicina de precisión en la rutina clínica. ... (AU)

Objective: Capecitabine, an antineoplastic drug used in the treatment of breast and colon cancer, can cause severe, even fatal toxicity in some patients. The interindividual variability of this toxicity is largely due to genetic variations in target genes and enzymes of metabolism of this drug, such as thymidylate synthase and dihydropyrimidine dehydrogenase. The enzyme cytidine deaminase (CDA), involved in the activation of capecitabine, also has several variants associated with an increased risk of toxicity to treatment, although its role as a biomarker is not yet clearly defined.Therefore, our main objective is to study the association between the presence of genetic variants in CDA gen, CDA enzymatic activity and the development of severe toxicity in patients treated with capecitabine whose initial dose was adjusted based on the genetic profile of the dihydropyrimidine dehydrogenase gen (DPYD). Method: Prospective multicenter observational cohort study, focused on the analysis of the genotype-phenotype association of the CDA enzyme.After the experimental phase, an algorithm will be developed to determine the dose adjustment needed to reduce the risk of treatment toxicity according to CDA genotype, developing a clinical guide for capecitabine dosing according to genetic variants in DPYD and CDA. Based on this guide, a Bioinformatics Tool will be created to generate the pharmacotherapeutic report automatically, facilitating the implementation of pharmacogenetic advice in clinical practice. This tool will be a great support in making pharmacotherapeutic decisions based on the patient's genetic profile, incorporating precision medicine into clinical routine. Once the usefulness of this tool has been validated, it will be offered free of charge to facilitate the implementation of pharmacogenetics in hospital centers and equitably benefit all patients on capecitabine treatment. (AU)

Uso indebido de bupropión por insuflación nasal con desenlace fatal: reporte de un caso y revisión / Abuse of bupropion by nasal insufflation with fatal outcome: report of a case and review

Introducción. El bupropión es la única catinona sintética aprobada por la FDA, con una creciente popularidad en la práctica clínica debido a su amplio rango de acción y la falta de efectos secundarios sexuales. Sin embargo, su efecto estimulante similar al de las anfetaminas ha hecho crecer la preocupación respecto a su uso recreativo. Objetivos y métodos. En este manuscrito informamos un caso de uso indebido de bupropión mediante insuflación nasal con desenlace fatal y realizamos una breve revisión deluso recreativo de bupropión. Resultados. Presentamos el caso de un hombre de unos50 años, con abuso prolongado de bupropión principalmente por insuflación nasal, que falleció súbitamente unas dos semanas después de ser dado de alta por un infarto agudo de miocardio tipo 2 secundario a sobredosis de bupropión. A lo largo de las últimas décadas, varios estudios han informado un uso indebido cada vez mayor de bupropión por vías no orales, especialmente a través de la insuflación nasal, y el uso intravenoso, particularmente en pacientes con antecedentes de abuso de sustancias, adolescentes o en entornos penitenciarios. A pesar de que la mayoría de los pacientes tienen efectos secundarios de leves a moderados, consecuencias devastadoras, tales como convulsiones refractarias o shock cardiogénico refractario, pueden ocurrir en caso de sobredosis, lo que exige un reconocimiento oportuno y un enfoque rápido para prevenir estos resultados importantes. En caso de sobredosis, no existe un antídoto específico disponible ni un tratamiento curativo aprobado, su manejo se centra en el tratamiento de los síntomas. Conclusiones. El bupropión es un antidepresivo eficaz, sin embargo, tiene potencial para uso recreativo, especialmente en grupos de alto riesgo. Este documento alerta a todos los médicos sobre el problema emergente relacionado con el uso indebido de bupropión y agrega algunas ideas sobre su reconocimiento y manejo oportunos. (AU)

Severe and refractory gastrointestinal toxicity due to immune checkpoint inhibitors: clinical experience in a tertiary referral hospital

Introduction: immune checkpoint inhibitors (ICI) are increasingly used to treat several types of cancer. These drugs lead to a wide range of toxicities. Immune-related gastrointestinal adverse events are common and potentially severe. In this manuscript, we recount the real clinical experience in a tertiary center. Methods: a retrospective and observational study was conducted in adult patients under ICI treatment. Included patients had been referred to the Gastrointestinal Service of Hospital Universitario Vall d’Hebron for evaluation of severe toxicities, from January 2017 to January 2020, for whom the clinical, epidemiological and evolutive data were collected. Results: a total of 18 patients were included. Fifty-five percent received anti-programmed cell death protein 1 (PD-1)/ anti-programmed death-ligand 1 (anti PD-L1), 11 % received anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and 33 % received both treatments. The toxicities were manifested as enterocolitis, microscopic colitis and gastritis. Upper gastrointestinal endoscopy was performed in seven patients; all were proved to have histological changes on duodenum biopsies. Treatment was stopped in all patients and steroids were initiated. Sixty-six per cent achieved clinical remission with steroids. Five patients received anti-TNF treatment (infliximab). Only one of the five had responded. Two anti-TNF refractory patients received ustekinumab, with an appropriate clinical response. One patient received apheresis granulocyte as concomitant treatment. A patient with a steroid-dependent course started vedolizumab. Three patients had other immune-related adverse events. Conclusion: gastrointestinal immune-related adverse events are acquiring a higher profile in daily practice and gastroenterologists play an even greater role in the management of these patients. (AU)

Chemical characterization, cytotoxicity, antimicrobial and antioxidant potential of Justicia pectoralis Jacq and Croton jacobinensis Baill extracts

Abstract In this research, aqueous and ethanolic extracts from Justicia pectoralis Jacq and Croton Jacobinensis Baill were characterized. The UPLC-QTOF-MSE analysis was performed on the extracts identified, predominantly, flavonoids, tannins and acids. The extracts did not indicate toxicity in human epithelial cells. C. jacobinensis presented a concentration of phenolics 60.5% higher than J. pectoralis in all scenarios evaluated and, for both samples, the hydroalcoholic extract at 70% exhibited the best efficiency in the extraction (14501.3 and 32521.5 mg GAE 100 g-1 for J. pectoralis and C. jacobinensis, respectively). The antioxidant activity presented a positive correlation with the concentration of phenolics, being 1.186,1 and 1.507,9 µM of Trolox for J. pectoralis and C. jacobinensis at 70% of ethanol; however, it was not verified statistical difference between the ethanolic solutions (p < 0.05). The antimicrobial activity of J. pectoralis extracts was highlighted once was the most effective against gram-positive bacteria. The results suggest that both J. pectoralis and C. jacobinensis extracts present the potential to be applied as natural additives due to their antioxidant and antimicrobial activity and safety. Thus, it is suggesting the development of studies that could investigate the interaction of these plant extracts with food matrices is required

Protective effect of nebivolol on rat ovary exposed to deltamethrin toxicity

Purpose: We aimed to investigate the antioxidant activity of nebivolol against possible damage to the ovarian tissue due to the application of deltamethrin as a toxic agent, by evaluating histopathological proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNF-α) signal molecules immunohistochemically. Methods: The animals were divided into three groups as control, deltamethrin and deltamethrin + nebivolol groups. Vaginal smears were taken after the animals were mated and detected on the first day of pregnancy. After the sixth day, deltamethrin (0.5 mL of 30 mg/kg BW undiluted ULV), and 2 mL of sterile nebivolol solution were administered intraperitoneally every day for 6-21 periods. After routine histopathological follow-up, the ovarian tissue was stained with hematoxylin and eosin stain. Results: Control group showed normal histology of ovarium. In deltamethrin group, hyperplasic cells, degenerative follicles, pyknotic nuclei, inflammation and hemorrhagic areas were observed. Nebivolol treatment restored these pathologies. Deltamethrin treatment increased TNF-α and PCNA reaction. However, nebivolol decreased the expression. Conclusions: It was thought that deltamethrin toxicity adversely affected follicle development by inducing degeneration and apoptotic process in preantral and antra follicle cells, and nebivolol administration might reduce inflammation and slow down the apoptotic signal in the nuclear phase and regulate reorganization.

Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model

Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis.

Neurotoxicidad de plaguicidas. Breve actualización / Neurotoxicity of pesticides. Brief update

Introducción: Los plaguicidas son necesarios para en el desarrollo de la sociedad actual, aunque suponen un riesgo para la salud pública, el ecosistema, la salud humana, de las personas expuestas directa e indirectamente a través de la cadena alimentaria y/o el medio ambiente. De hecho, cada vez son más los estudios que muestran una neurotoxicidad derivada de una intoxicación aguda y/o crónica por exposición a plaguicidas.Método: Se realizó una breve revisión bibliográfica sobre la toxicidad de estos productos químicos, en relación al daño que pueden causar en el sistema nervioso. Se examinaron artículos científicos publicados en inglés y español, mediante la búsqueda en las bases de datos como: Scielo, Medline, Springer, Scopus y Science Direct, de artículos que fueron divulgados durante el periodo comprendido entre el año 2017 y 2022, según los criterios establecidos por la declaración PRISMA.Resultados: Los plaguicidas suponen uno de los contaminantes ambientales más utilizados, que pueden generar numerosos beneficios para la agricultura; sin embargo, se relacionan cada vez más, con una neurotoxicidad derivada de una exposición crónica, que cursa con el desarrollo de enfermedades crónicas neurodegenerativas.Conclusiones: Se necesitan más estudios que aborden la neurotoxicidad inducida por exposición a plaguicidas, así como, la necesidad de reforzar todos los sistemas de prevención, control y medidas que garanticen la salud de la población expuesta.(AU)

Introduction: Pesticides are necessary for the development of today's society, although they pose a risk to public health, the ecosystem, human health, people directly and indirectly exposed through the food chain and/or the environment. . In fact, more and more studies show neurotoxicity derived from acute and/or chronic poisoning due to exposure to pesticides.Method: A brief bibliographical review on the toxicity of these chemical products was carried out, in relation to the damage they can cause in the nervous system. Scientific articles published in English and Spanish were examined, by searching databases such as: Scielo, Medline, Springer, Scopus and Science Direct, of articles that were disclosed during the period between 2017 and 2022, according to the criteria established by the PRISMA statement.Results: Pesticides are one of the most widely used environmental contaminants, which can generate numerous benefits for agriculture; however, they are increasingly related to neurotoxicity derived from chronic exposure, which occurs with the development of chronic neurodegenerative diseases.Conclusions: More studies are needed to address neurotoxicity induced by exposure to pesticides, as well as the need to strengthen all systems of prevention, control, and measures that guarantee the health of the exposed population.(AU)

Bioremediation potential of hexavalent chromium-resistant Arthrobacter globiformis 151B: study of the uptake of cesium and other alkali ions / Potencial de biorremediación de Arthrobacter globiformis 151B resistente al cromo hexavalente: estudio de la captación de cesio y otros iones alcalinos

Cesium (Cs+) enters environments largely because of global release into the environment from weapons testing and accidents such as Fukushima Daiichi and Chernobyl nuclear waste. Even at low concentrations, Cs+ is highly toxic to ecological receptors because of its physicochemical similarity to macronutrient potassium (K+). We investigated the uptake and accumulation of Cs+ by Arthrobacter globiformis strain 151B in reference to three similar alkali metal cations rubidium (Rb+), sodium (Na+), and potassium (K+). The impact of hexavalent chromium (Cr+6) as a co-contaminant was also evaluated. A. globiformis 151B accumulated Cs+ and Cr6+ in a time-dependent fashion. In contrast, the uptake and accumulation of Rb+ did not exhibit any trends. An exposure to Cs+, Rb+, and Cr+6 triggered a drastic increase in K+ and Na+ uptake by the bacterial cells. That was followed by the efflux of K+ and Na+, suggesting a Cs+ “substitution.” Two-dimensional gel-electrophoresis of bacterial cell proteomes with the following mass-spectrometry of differentially expressed bands revealed that incubation of bacterial cells with Cs+ induced changes in the expression of proteins involved in the maintenance of cellular homeostasis and reactive oxygen species removal. The ability of A. globiformis 151B to mediate the uptake and accumulation of cesium and hexavalent chromium suggests that it possesses wide-range bioremediation potential.(AU)

Análisis de los costes asociados al seguimiento de pacientes con VIH que discontinúan el tratamiento antirretroviral por falta de eficacia o toxicidad inaceptable en España / Analysis of the costs associated with the follow-up of HIV patients discontinuing antiretroviral treatment due to lack of effectiveness or unacceptable toxicity in Spain

Objetivo: Estimar el uso de recursos y costes asociados al seguimientode pacientes con infección por el virus de la inmunodeficiencia humanatras discontinuación del tratamiento antirretroviral actual debido a faltade efectividad o toxicidad inaceptable y cambio a un nuevo tratamientoantirretroviral, comparado con el seguimiento habitual de los pacientescon tratamiento antirretroviral, desde la perspectiva del Sistema Nacionalde Salud español.Método: Se identificó el uso de recursos (pruebas clínicas, visitasmédicas, visitas a la farmacia hospitalaria) asociado al seguimiento depacientes con infección por el virus de la inmunodeficiencia humana entres perfiles de pacientes (estable, discontinuación y cambio por faltade efectividad, discontinuación y cambio por toxicidad inaceptable), apartir de las guías de práctica clínica y un panel de expertos multidisciplinar (n = 5). Los expertos consensuaron los principales eventos adversos que conducían a la discontinuación, agrupándolos en: alteracionesgastrointestinales, renales, óseas, musculoesqueléticas, dermatológicas,hepáticas y del perfil lipídico, trastornos neuropsiquiátricos y sexuales.Los costes unitarios se identificaron a partir de bases de datos oficiales de costes sanitarios y de la literatura. Se estimó el coste (€, 2020) delseguimiento en cada perfil de paciente, sin incluir el coste derivado deltratamiento antirretroviral, en un horizonte temporal de dos años.Resultados: El coste por paciente a dos años se estimó en 4.148 €(pruebas: 2.293 €; visitas: 1.855 €) para el seguimiento del pacienteestable. (AU)

Objective: To assess the use of resources and the costs associatedwith following up patients infected with the human immunodeficiency virusafter discontinuation of an antiretroviral treatment and initiation of a newone due to a lack of effectiveness or unacceptable toxicity, as comparedto the costs involved in the routine follow-up of patients on antiretroviraltreatment, from the Spanish National Health System perspective.Method: The use of resources (clinical tests, medical visits, and hospitalpharmacy visits) associated with following three profiles of patients infected with the human immunodeficiency virus (stable ones, those discontinuing an existing antiretroviral treatment and being switched to a newone due to a lack of effectiveness, and those discontinuing an existingantiretroviral treatment and being switched to a new one due to unacceptable toxicity) was identified, based on clinical practice guidelinesand the findings of a multidisciplinary expert panel (n = 5). The expertsagreed on the main adverse events leading to discontinuation, classifyingthem into gastrointestinal, renal, osseous, musculoskeletal, dermatological,hepatic, lipid profile-related, neuropsychiatric and sexual alterations. Unitcosts were identified from official healthcare costs databases. The cost (€, 2020) of following up each patient profile was estimated, excludingthe cost of the antiretroviral treatment itself, with a time horizon of twoyears.Results: The per-patient cost of following up stable patients over twoyears was estimated at €4,148 (tests: €2,293; visits: €1,855). Patientfollow-up after discontinuation of an existing antiretroviral treatment andinitiation of a different one due to a lack of effectiveness was estimatedat €5,434 (tests: €2,777; visits: €2,657). (AU)