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.

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.

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

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.

Carboxyhemoglobinemia as a laboratory finding in an outpatient

Resumen El monóxido de carbono (CO) es un gas producido principalmente por combustión incompleta de hidrocarburos. La intoxicación por exposición ambiental puede presentarse con síntomas inespecíficos y constituye la causa más importante de aumento de carboxihemoglobina (COHb). Su nivel en sangre depende de la duración de la exposición, la ventilación minuto y las concentraciones de CO y oxígeno en el ambiente. La elevada toxicidad radica en la hipoxia tisular que se genera. Se presenta el caso de un paciente masculino, 73 años, en seguimiento en el hospital por neumonía intersticial no específica como patología de base. En un control de laboratorio se encontró 11,9% de COHb, sin exposición a tabaco. No utilizaba calefacción a gas sino un panel cerámico eléctrico, recientemente pintado con esmalte sintético. La suspensión del uso del panel normalizó la COHb. El CO, producto de descomposición térmica del esmalte sintético, explica la causa de la intoxicación.

Abstract Carbon monoxide (CO) is a gas produced mainly by incomplete combustion of hydrocarbons. Poisoning from environmental exposure can present with nonspecific symptoms and is the most important cause of increased carboxyhemoglobin (COHb). Its blood level depends on the duration of exposure, minute ventilation, and the concentrations of CO and oxygen in the environment. The high toxicity lies in the tissue hypoxia that is generated. The case of a male patient, 73 years old, under follow-up in the hospital for non-specific interstitial pneumonia as the underlying pathology was presented. In a laboratory control, COHb 11,9% was found. There was no exposure to tobacco and there was no use of gas heating but of an electric ceramic panel, recently painted with synthetic enamel type paint. The suspension of the use of the panel normalised the COHb. The CO product of thermal decomposition of synthetic enamel explains the cause of poisoning.

Resumo O monóxido de carbono (CO) é um gás produzido principalmente pela combustão incompleta de hidrocarbonetos. A intoxicação por exposição ambiental pode se apresentar com sintomas inespecíficos e é a causa mais importante de aumento da carboxihemoglobina (COHb). Seu nível em sangue depende do tempo de exposição, da ventilação minuto e das concentrações de CO e oxigênio no ambiente. A alta toxicidade está na hipóxia tecidual gerada. Apresentamos o caso de um paciente do sexo masculino, 73 anos, em acompanhamento hospitalar por pneumonia intersticial inespecífica como patologia de bas. Em um controle laboratorial, achou-se 11,9% de COHb, sem exposição ao tabaco. Não utilizava aquecimento a gás e sim um painel elétrico cerâmico, recentemente pintado com esmalte sintético. A suspensão do uso do painel normalizou o COHb. O CO produto da decomposição térmica do esmalte sintético explica a causa da intoxicação.

Linking toxicity and predation in a venomous arthropod: the case of Tityus fuhrmanni (Scorpiones: Buthidae), a generalist predator scorpion

Background: Scorpions are arachnids that have a generalist diet, which use venom to subdue their prey. The study of their trophic ecology and capture behavior is still limited compared to other organisms, and aspects such as trophic specialization in this group have been little explored. Methods: In order to determine the relationship between feeding behavior and venom toxicity in the scorpion species Tityus fuhrmanni, 33 specimens were offered prey with different morphologies and defense mechanisms: spiders, cockroaches and crickets. In each of the experiments we recorded the following aspects: acceptance rate, immobilization time and the number of capture attempts. The median lethal dose of T. fuhrmanni venom against the three different types of prey was also evaluated. Results: We found that this species does not have a marked difference in acceptance for any of the evaluated prey, but the number of capture attempts of spiders is higher when compared to the other types of prey. The immobilization time is shorter in spiders compared to other prey and the LD50 was higher for cockroaches. Conclusions: These results indicate that T. fuhrmanni is a scorpion with a generalist diet, has a venom with a different potency among prey and is capable of discriminating between prey types and employing distinct strategies to subdue them.(AU)

Biological properties of Schinus terebinthifolia Raddi essential oil

Abstract Schinus terebinthifolia Raddi green fruits essential oil (EO) was evaluated regarding its phytochemical profile, antimicrobial and cytotoxic activities, and toxicity. Gas chromatography with mass spectrometry was applied to identify its constituents, thereafter the minimum inhibitory concentration, minimum bactericidal and fungicidal concentrations, and its antibiofilm activity were evaluated. The EO cytotoxicity was assessed in tumor and non-tumor human cells, and in vivo toxicity was evaluated in a Galleria mellonella model. The major constituents of S. terebinthifolia EO were alpha-phellandrene and beta-phellandrene. The EO had a weak activity against all strains of Candida albicans (MIC 1000µg/mL) and had no activity against non-albicans strains, bacteria, and C. albicans biofilm. Cytostatic activity against all tumor cell lines was shown. Additionally, cell viability remained at EO concentrations up to 62.5 µg/mL. At 16 mg/mL, 50% hemolysis was observed, and it had low toxicity in vivo. Overall, the S. terebinthifolia EO was characterized by low antimicrobial and antibiofilm activities, with no evidence of toxicity to human tumor and non-tumor cells

The benefit of Silybum marianum in ethanol-induced reprotoxicity of male Wistar rat

Abstract This study investigates the toxic effects of ethanol (Eth) on the reproductive system of male rats and the possible protective role of Silybum marianum seeds-infused solution (SMI) over six consecutive weeks of administration. Animals were divided into the following groups: control, SMI positive control (200 mg/kg/day), Eth1 (1 g/kg/day), Eth2 (2 g/kg/day), Eth1+SMI, and Eth2+SMI. Plasma testosterone concentration, epididymal spermatozoa biology, and testicular and epididymal MDA, GSH and GPx levels were evaluated. The results indicated a significant decrease in testis and epididymis weight, testosterone level, sperm concentration, sperm vitality and sperm motility (total motility, progressive motility, curvilinear velocity, straight-line velocity, velocity average path, beat cross frequency, and lateral head displacement) in both Eth1 and Eth2 compared to the control groups and the combined-treatment groups (Eth1+SMI and Eth2+SMI). Furthermore, results showed a significant elevation in MDA concentration with a significant decrease of testicular and epididymal GSH concentration and GPx activity in theEth1 and Eth2 groups compared to the combined-treatment groups. The administration of SMI succeeded in improving the parameters cited above in the combined-treatment groups compared to the Eth1 and Eth2 groups, and bring them to the levels seen in the control groups. To conclude, SMI has clearly protected reproductive indices against ethanol-induced reprotoxicity in male rats

Cytotoxicity and antibacterial activity of bleached turmeric hydro-alcoholic extract versus sodium hypochlorite as an endodontic irrigant: in vitro study / Citotoxicidade e atividade antibacteriana do extrato hidroalcoólico de cúrcuma branqueado versus hipoclorito de sódio como irrigante endodôntico: estudo in vitro

Objetivo: Avaliar a citotoxicidade e o efeito antibacteriano do extrato hidroalcoólico de cúrcuma branqueado comparado ao hipoclorito de sódio como irrigante endodôntico. Material e Métodos: A citotoxicidade foi avaliada em fibroblastos de pele humana usando o ensaio MTT. Os irrigantes foram testados em intervalos de tempo de 1, 5 e 15 minutos. Após o tempo de contato, a solução de MTT foi adicionada e as placas de poços foram incubadas. Após o período de incubação, a densidade óptica foi lida e correlacionada com a porcentagem de viabilidade celular. A eficiência antibacteriana foi avaliada usando o teste de contato direto. Cada irrigante endodôntico foi adicionado à suspensão fresca de Enterococcus faecalis e ao meio de infusão cérebro-coração e então incubados por 48 horas. Após o período de incubação, as leituras de densidade óptica foram obtidas e lidas por leitor de ELISA a 620 nm. Resultados: Os resultados do teste de citotoxicidade revelaram que o extrato de cúrcuma branqueado apresentou porcentagem de viabilidade celular significativamente maior do que o hipoclorito de sódio (NaOCl) em todos os intervalos de tempo (p<0,001). No entanto, no grupo de intervenção, a porcentagem de viabilidade celular diminuiu significativamente ao longo do tempo. Os resultados do teste antibacteriano mostraram inibição bacteriana por ambos os grupos com diferença não significativa entre os dois grupos testados (p<0,05). Conclusão:O extrato hidroalcoólico de cúrcuma branqueado pode representar uma alternativa fitoterápica irrigante endodôntico para evitar os efeitos tóxicos indesejáveis do NaOCl devido à sua menor citotoxicidade e efeito antibacteriano proeminente contra Enterococcus faecalis (AU)

Objective: To evaluate the cytotoxicity and antibacterial effect of bleached turmeric hydro-alcoholic extract compared to sodium hypochlorite as an endodontic irrigant. Material and Methods: Cytotoxicity was evaluated on human skin fibroblasts using MTT assay. The irrigants were tested at 1, 5- and 15-minutes time intervals. After contact time, MTT solution was added and well plates were incubated. After the incubation period, optical density was read and correlated with cell viability percent. Antibacterial efficiency was evaluated using direct contact test. Each endodontic irrigant was added to fresh Enterococcus faecalis suspension and brain heart infusion media then incubated for 48 hours. After incubation period, optical density readings were obtained and read by ELISA reader at 620 nm. Results:Results of cytotoxicity test revealed that bleached turmeric extract had significant higher cell viability percent than Sodium hypochlorite (NaOCl) at all time intervals (p<0.001). However, in the intervention group, cell viability percent significantly decreased over time. Results of antibacterial test showed bacterial inhibition by both groups with non-significant difference between the two tested groups (p<0.05). Conclusion: Bleached turmeric hydro-alcoholic extract can represent an herbal alternative endodontic irrigant to avoid the undesirable toxic effects of NaOCl due to its less cytotoxicity and prominent antibacterial effect against Enterococcus faecalis. (AU)

Alteraciones histológicas hepáticas provocadas por la ingesta crónica de glutamato monosódico / Histological liver changes caused by chronic intake of monosodium glutamate

ntroducción. El glutamato es un aminoácido que está implicado en numerosas reacciones relacionadas con el metabolismo hepático, por lo que la sobreactivación de los receptores de glutamato por acción de la ingesta de glutamato monosódico (GMS) proveniente de la dieta, podría llevar a daño del tejido hepático. Este estudio se realizó con el objetivo de evaluar los cambios histológicos producidos en el hígado de ratas sometidas a la administración crónica de GMS. Metodología. Se trabajó con dos lotes de animales, uno experimental y otro control, cada uno de ellos constituido por seis ratas machos cepa Wistar de cinco semanas de edad. Al grupo experimental se le administró diariamente 0,1 g de queso de bajas calorías que contenía GMS monohidrato de 99% de pureza (grado alimentario puro), diluido en 50 µL de agua desionizada (0,3 g/100 g de peso corporal). Al grupo control se le administró la misma cantidad de sodio que el que contenía el GMS del grupo tratado, pero bajo la forma de NaCl. Al concluir el tratamiento, las ratas pertenecientes a ambos grupos se pesaron y sacrificaron, y se les extrajo el hígado para el estudio histológico. Se obtuvieron cortes histológicos que fueron coloreados con hematoxilina-eosina, PAS y coloración con tricrómico de Masson. El análisis de los cortes histológicos se llevó a cabo por observación directa en microscopio óptico con objetivo de 40x. Resultados. Se observó en general, conservación y apariencia normal de las características histológicas de los acinos hepáticos en el grupo control, en tanto que el hígado de las ratas tratadas con GMS presentó diferentes grados de degeneración hidrópica, cantidades variables de cuerpos hialinos eosinófilos, infiltración inflamatoria de células mononucleares y necrosis focal, principalmente en la zona 1 del acino hepático. Conclusión. Los resultados encontrados permiten aportar evidencias en torno a las alteraciones histopatológicas que la ingesta crónica de GMS provoca sobre el tejido hepático. Se recomienda alertar a la población para reducir la ingesta de alimentos que poseen GMS como saborizante.

Introduction. Glutamate is an amino acid that is involved in numerous reactions related to liver metabolism, so the overactivation of glutamate receptors due to the ingestion of monosodium glutamate (MSG) from the diet could lead to liver tissue damage. The aim of this study was to evaluate the histological changes produced in the liver of rats subjected to chronic administration of MSG. Methodology. Two sets of animals were used, an experimental and a control group, each consisting of six five-week-old Wistar male rats. The experimental group was administered 0.1 g of low-calorie cheese containing 99% purity MSG monohydrate (pure food grade) diluted in 50 µL of deionized water (0.3 g/100 g of weight) daily. The control group was administered the same amount of sodium as that contained in the MSG of the treated group, but in the form of NaCl. At the end of the treatment, the rats belonging to both groups were weighed and sacrificed, and their liver was removed for histological analysis. Histological sections were obtained and stained with hematoxylineosin, PAS and Masson's trichrome. The analysis of the histological sections was carried out by direct observation with an optical microscope and a 40x objective. Results. In general, conservation and normal appearance of the histological characteristics of the liver acini were observed in the control group, while the liver of the rats treated with MSG presented different degrees of hydropic degeneration, variable amounts of eosinophilic hyaline bodies, inflammatory infiltration of mononuclear cells and focal necrosis, that affected mainly zone 1 of the liver acinus. Conclusion. The results allow us to provide evidence about the histopathological alterations that the chronic intake of MSG causes on the liver tissue. It is recommended to alert the population to reduce the intake of foods that have GMS for flavoring.

Hepatotoxicidad por talidomida: caso clínico y revisión de la literatura / Hepatotoxicity by thalidomide: case report and literature review

La talidomida fue desarrollada e introducida al mercado por los laboratorios Grünenthal en 1953, siendo usada principalmente como sedante y también para el tratamiento de las náuseas durante el embarazo. Los informes dan cuenta de aproximadamente 10.000 niños que nacieron con focomelia, dando lugar a la denominada "tragedia de la talidomida", que obligó a su retiro del mercado en 1962. Luego de casi 60 años, es nuevamente utilizada en otros campos de la medicina, entre ellos, para el tratamiento de la lepra y del mieloma múltiple, debido a sus propiedades antinflamatorias, inmunomoduladoras y antiangiogénicas, con expresas advertencias sobre su utilización durante el embarazo; no obstante, con su nuevo uso han sido reportados múltiples efectos adversos, entre los que se encuentra la hepatitis aguda o crónica inducida por este fármaco. Se presenta el caso de una paciente de 34 años con lepra, que estaba en tratamiento con talidomida desde hacía 4 años para combatir las lesiones de piel asociadas a esta enfermedad. Presentó malestar general, vómito, pérdida de peso, artralgias, ictericia, edemas de miembros inferiores, ascitis, coluria y acolia. Se sospechó toxicidad por talidomida, por lo que se suspendió su uso, y se trató con ácido ursodesoxicólico y N-acetilcisteína con mejoría sintomática y de laboratorio, desde la primera semana hasta los 41 días de seguimiento. Las entidades clínicas para las cuales se aprobó talidomida en 1998, pueden traer nuevos problemas y desafíos clínicos. Este caso muestra hepatotoxicidad crónica por talidomida, situación que hasta el momento no se había reportado en la literatura.

Thalidomide was developed and introduced to the market by Grünenthal laboratories in 1953, being used mainly as a sedative and also for the treatment of nausea during pregnancy. Reports give account of approximately 10,000 children who were born with phocomelia, giving rise to the so-called "thalidomide tragedy", which forced its withdrawal from the market in 1962. After almost 60 years, it is usedagain in other fields of medicine, including the treatment of leprosy and multiple myeloma, due to its anti-inflammatory, immunomodulatory and anti-angiogenic properties, with clear warnings about its use during pregnancy; however, multiple adverse effects have been reported in patients with leprosy and multiple myeloma, including acute or chronic hepatitis. We present the case of a 34-year-old patient with leprosy, who had been on thalidomide therapy for 4 years to treat skin lesions associated with this disease. She presented general malaise, vomiting, weight loss, arthralgia, jaundice, lower limb edema, ascites, choluria and acholia. Thalidomide toxicity was suspected, so its use was suspended, and treatment with ursodeoxycholic acid and N-acetylcysteine was initiated, with symptomatic and laboratory improvement from the first week up until 41 days of follow-up. The new range of medical conditions for which thalidomide was approved for in 1998 may bring clinical challenges. This case shows chronic hepatotoxicity due to thalidomide, a situation that had not been reported previously in the literature.

Chemical and biological properties of nordihydroguaiaretic acid

Nordihydroguaiaretic acid (NDGA) is a natural product obtained by the alkaline extraction of dried plants of Larrea tridentata species. Due to the biological properties presented, such as antioxidant, anti-inflammatory, antiviral and cytotoxic capacity, this compound is being increasingly studied. In this review, it was evaluated the benefits of NDGA against different animal models. Besides that, it was found that this compound has antitumor activity similar to its synthetic derivative terameprocol in prostate tumors. The hypoglycemic effect may be evidenced by the inhibition of sugar uptake by NDGA; in obesity, studies have observed that NDGA presented a positive regulatory effect for Peroxisome proliferator-activated receptors (PPAR-α) involved in the oxidation of hepatic fatty acids and reduced the expression of lipogenic genes. Regarding its antioxidant potential, its mechanism is related to the ability to in vitro scavenging reactive substances. Although there are several studies demonstrating the benefits of using NDGA, there are also reports of its toxicity, mainly of liver damage and nephrotoxicity

Bidirectional Ventricular Tachycardia Due to Digitalis Intoxication

Bidirectional ventricular tachycardia (BDVT) is defined by beat-to-beat alternation of the QRS axis on the electrocardiogram. Its diagnosis is uncommon, and the most characteristic etiology is digitalis intoxication (DI). We report the case of a patient with heart failure of valve origin admitted for sepsis that progressed to BDVT and death, associated with DI.

Toxicidad por metformina, más allá de la falla renal y la acidosis láctica: reporte de dos casos / Metformin toxicity, beyond renal failure and lactic acidosis: report of 2 cases / Toxicidade da metformina, além de insuficiência renal e acidose láctica: relato de dois casos

El suicidio es un problema de salud pública grave, vincula frecuentemente al consumo de medicamentos. La metformina es un fármaco antihiperglicemiante de fácil acceso y la sobredosis implica riesgos metabólicos, entre ellos, la acidosis láctica es el principal. Teniendo en cuenta la frecuencia de su consumo, es necesario que el personal de salud conozca los riesgos que implica la intoxicación y los signos y síntomas iniciales, pues del manejo adecuado dependerá un pronóstico favorable. El objetivo de este reporte es evidenciar los riesgos metabólicos renales-hemodinámicos, asociados a la toxicidad por metformina, además de resaltar la necesidad de considerar el uso temprano de la terapia de remplazo renal y de concientizar a los clínicos de que exponer a los pacientes a un medicamento, es también exponerlo a efectos adversos o a abuso con fines autolesivos.

Suicide is a serious public health problem that increases worldwide. In Medellín, its incidence is on the rise, and the most frequent mechanism is the ingestion of drugs. Metformin is an antihyperglycemic medication that is easily accessible and frequently used, because it is part of the first line of management of type 2 diabetes mellitus. One of the complications associated with its use is lactic acidosis, which can lead to serious toxicity. Therefore, it is necessary for the health personnel to be aware of the signs and symptoms that can initially appear in the case of intoxication, since a favorable prognosis depends on adequate management. The objective of this report is to present two clinical cases that evidence the wide spectrum of toxicity secondary to the use of metformin and to review the available evidence of the approach to this poisoning, emphasizing the importance of early use of renal replacement therapy.

O suicídio é um grave problema de saúde pública, frequentemente relacionado ao consu-mo de drogas. A metformina é um anti-hiperglicêmico de fácil acesso e a sobredosagem envolve riscos metabólicos, entre eles, a acidose láctica é o principal. Considerando a frequência de seu consumo, é necessário que o pessoal de saúde conheça os riscos das intoxicações e os sinais e sintomas iniciais, pois um prognóstico favorável dependerá de manejo adequado. O objetivo deste relatório é demonstrar os riscos metabólicos renais-hemodinâmicos associados à toxicidade da metformina, além de destacar a necessidade de considerar o uso precoce da terapia de substituição renal e alertar os médicos sobre o que expor os pacientes a um medicamento. a efeitos adversos ou abuso para fins autolesivos.

Evaluación de la toxicidad de chalconas sintéticas con potencial anti-Leishmania en ratones BALB/c / Toxicity assessment of synthetic chalcones with antileishmanial potential in BALB/c mice

RESUMEN Objetivo: Evaluar la toxicidad de tres chalconas sintéticas administradas por vía intraperitoneal en ratones BALB/c. Materiales y métodos: La dosis letal media (DL50) se estimó por el método Up-and-Down de Dixon. La toxicidad subcrónica de las chalconas se evaluó a 20 y 40 mg/kg por 21 días. Se evaluó el efecto tóxico a nivel de comportamiento, fisiológico, bioquímico e histológico. Resultados: La chalcona 43 generó moco en las heces, daño visceral (hígado) y alteración en el coeficiente de órganos (riñón, p = 0,037 y cerebro, p = 0,008) en comparación con el grupo control. Además, en el análisis histológico se observó que esta chalcona produjo edema, inflamación y necrosis en los órganos evaluados, aunque no hubo diferencia significativa con el control. Todos los parámetros bioquímicos no difirieron significativamente entre los grupos de tratamiento a dosis de 40 mg/kg y el control. Conclusiones: La DL50 para las tres chalconas fue superior a 550 mg/kg de peso corporal. Las chalconas 40 y 42 son relativamente no tóxicas. Ambas pueden considerarse seguras para la aplicación vía intraperitoneal en ratones BALB/c y, en consecuencia, son posibles candidatas para ser usadas en el tratamiento contra las leishmaniosis.

ABSTRACT Objective: To evaluate the toxicity of three synthetic chalcones administered intraperitoneally to BALB/c mice. Materials and methods: The median lethal dose (LD50) was estimated by Dixon's Up-and-Down method. Subchronic toxicity of chalcones was evaluated at 20 and 40 mg/kg for 21 days. Behavioral, physiological, biochemical, and histological toxic effects were evaluated. Results: Chalcone 43 produced mucus in feces, visceral damage (liver) and alterations in organ coefficient (kidney, p = 0.037 and brain, p = 0.008) when compared to the control group. In addition, histological analysis showed that this chalcone produced edema, inflammation and necrosis in the evaluated organs, although there was no significant difference with the control. None of the biochemical parameters differed significantly between the treatment groups at 40 mg/kg dose and the control. Conclusions: The LD50 for all three chalcones was greater than 550 mg/kg of body weight. Chalcones 40 and 42 were found to be relatively non-toxic. Both can be considered safe for intraperitoneal application in BALB/c mice and, consequently, are potential candidates for use in the treatment of leishmaniasis.

Colecistectomía videolaparoscópica en el Hospital Militar Docente Dr. Mario Muñoz Monroy, Matanzas, 2014-2017 / Video laparoscopic cholecistectomy in the Military Hospital of Matanzas. 2014-2017

RESUMEN Introducción: en enero de 2000, comenzó la cirugía videolaparoscópica en el Hospital Militar Docente Dr. Mario Muñoz Monroy, de la ciudad de Matanzas. El equipo quirúrgico, en esa época, lo constituían cirujanos con varios años de experiencia y con una sólida formación en cirugía convencional. También poseían habilidades demostradas en la realización de colecistectomía a cielo abierto. A partir de 2011, una nueva generación de cirujanos desarrolló la cirugía mínimamente invasiva, con poca experiencia en cirugía a cielo abierto. Por lo tanto, se presentó la contradicción de que cada vez menos cirujanos tenían la experiencia técnica que requieren los casos más difíciles. Objetivo: determinar la seguridad en la realización de la colecistectomía laparoscópica. Materiales y métodos: Investigación observacional, descriptiva y retrospectiva de los pacientes intervenidos de afecciones biliares benignas, por la técnica de colecistectomía laparoscópica, entre enero de 2014 y diciembre de 2017. Resultados: fueron colecistectomizados 2 016 pacientes. De ellos, 1 759 (87 %) correspondieron al sexo femenino, y 257 (13 %) al masculino. Comorbilidades presentes en el 46,3 %. Cirugías: electivas, 1 801; urgentes, 215. Eventos adversos, 38 (1,88 %). Conversiones, 28 (1,3 %). Mortalidad operatoria, 5 (0,24 %). Conclusiones: resultan seguras las colecistectomías laparoscópicas por el bajo índice de eventos adversos, conversiones y mortalidad operatoria (AU).

ABSTRACT Introduction: video laparoscopic surgery began in January 2000, at the Dr. Mario Muñoz Monroy Military Hospital. The surgical team, at that time, were surgeons with years of experience and a solid training in conventional surgery. They also had demonstrated skills in performing open cholecystectomy. Starting in 2011, a new generation of surgeons developed minimally invasive surgery, with little experience in open surgery. Therefore, it arose the paradox that fewer and fewer surgeons had the technical experience required in the most difficult cases. Objective: to determine the safety in performing laparoscopic cholecystectomy. Materials and methods: retrospective, descriptive and observational research of the patients who underwent surgeries of benign biliary conditions, by the technique of laparoscopic cholecystectomy in the period January 2014- December 2017. Results: 1759 patients were cholecystectomized. 87.25% were female ones and 257 (13%) were male: Comorbidities were present in 46.3%. 1 801 were elective surgeries; emergency surgeries were 215. There were 38 (1.88%) adverse events and 28 (1.3%) conversions. The operatory mortality was 5 (0.24%). Conclusions: laparoscopic cholecystectomy are safe because of the low index of adverse events, conversion and operatory mortality (AU).

Alterações eletrocardiográficas em pacientes com Leishmaniose Tegumentar Americana tratados com antimoniato de meglumina: revisão integrativa / Electrocardiographic changes in patients with American tegumentary leishmaniasis treated with meglumine antimoniate: integrative review

Introdução: a Leishmaniose Tegumentar Americana (LTA) é uma infecção zoonótica cujo tratamento é realizado com a droga antimoniato de meglumina (AM). Objetivo: Relatar as alterações eletrocardiográficas decorrentes do uso de AM em pacientes com LTA. Metodologia: foi realizada uma revisão integrativa da literatura por meio das bases de dados BIREME, PUBMED, COCHRANE, SCIELO e literatura cinzenta, usando como estratégia de busca o cruzamento dos seguintes descritores, nos idiomas português e inglês: leishmaniose cutânea, eletrocardiografia, meglumina e toxicidade. Não foi estipulado um intervalo temporal para que um maior número de publicações fosse obtido. Resultados: foram encontrados 134 artigos, desses apenas 09 atenderam aos critérios de inclusão. As principais alterações eletrocardiográficas encontradas durante a terapêutica foram as alterações de repolarização ventricular, com destaque para o prolongamento do intervalo QT corrigido pela frequência cardíaca. Já entre as alterações mais graves em termos de morbimortalidade, destacam-se as arritmias ventriculares complexas, principalmente a Torsade de pointes. Discussão: em todos os artigos selecionados foram encontradas alterações ao eletrocardiograma (ECG) durante o tratamento com AM, sendo recomendado em todos os pacientes, o acompanhamento eletrocardiográfico. Apenas um estudo excluiu as alterações do ECG basal, presença de comorbidades e uso de drogas cardiotóxicas sendo esses possíveis vieses para avaliação da toxicidade cardíaca diretamente provocada pelo antimonial. Conclusão: considerando as alterações na repolarização ventricular e as possíveis arritmias ventriculares em pacientes em tratamento para LTA em uso de AM, o acompanhamento eletrocardiográfico é recomendado durante a terapêutica de todos esses pacientes, sendo útil para prevenção de complicações cardiovasculares importantes.

Introduction: American Tegumentary Leishmaniasis (ATL) is a zoonotic infection whose treatment is carried out with the meglumine antimoniate drug (AM). Objective: To report the electrocardiographic changes resulting from the use of AM in patients with ATL. Methodology: an integrative literature review was carried out using the BIREME, PUBMED, COCHRANE, SCIELO and gray literature databases, using as a search strategy the crossing of the following descriptors, in Portuguese and English: cutaneous leishmaniasis, electrocardiography, meglumine and toxicity. A time interval was not stipulated in order to obtain a greater number of publications. Results: we found 134 articles, of which only 9 met the inclusion criteria. The main electrocardiographic changes found during therapy were changes in ventricular repolarization, with emphasis on the prolongation of the QT interval corrected by heart rate. Already the most serious changes in terms of morbidity and mortality, complex ventricular arrhythmias, especially Torsade de pointes, stand out. Discussion: changes in the electrocardiogram (ECG) were found in all selected articles during treatment with AM, with electrocardiographic monitoring being recommended in all patients. Only one study excluded: changes in the baseline ECG, the presence of comorbidities and / or use of cardiotoxic drugs, these being possible biases to assess cardiac toxicity directly caused by the antimonial. Conclusion: considering the changes in ventricular repolarization and possible ventricular arrhythmias in patients undergoing treatment for ATL using AM, electrocardiographic monitoring is recommended during the therapy of all these patients, being useful for the prevention of important cardiovascular complications.

Facilitating the gut brain axis by probiotic bacteria to modulate neuroimmune response on lead exposed zebra fish models

Unravelling the efficacy of gut biome has a major impact on health. An unbalanced microbiome composition is linked to many common illnesses such as gut dysbiosis, mental deformities and immunological imbalance. An optimistic influence on the gut biome can be made by consumingprobiotics. This would stimulate neuroprotection and immunomodulation intended by heavy metals pollution. Lead is a major source of neurotoxin that can induce neural deformities. Lactobacillusspecies isolated from curd were characterized to confirm its specificity. Zebra fish was reared at standard conditions and preclinical assessment on the intensity of induced neurotoxin lead was performed. The embryo toxic assay, immunomodulation effects and animal behavioural models endorsed the consequence of neurotoxicity. Different concentrations of bacterial isolate with standard antidepressant was considered for analysing the vigour of toxicity and its influence on cognitive behaviour by novel tank diving method. The restrain in the animal behaviour was also conferred by all the test samples with a decreased bottom dwelling time which was authenticated with haematology and histopathological studies. The alterations in morphology of the lymphocytes were balanced by the treated test samples. This study paves a twofold potential of probiotic as neuroprotectant and immune modulator against heavy metal toxicity.

In vivo protective effect of cinnamon aqueous extract in carbon tetrachloride-treated male albino rats

The liver as an organ is important for the metabolism of drugs and toxins. However, it is not immune from environmental insults. Exposure of liver cells to carbon tetrachloride (CCl4) results in the generation of tricholoromethyl radicals, which induce liver toxicity. This study aims at investigating the ameliorative effect of the cinnamon aqueous extract (CAE) against CCl4-induced hepatotoxicity in male albino rats. Hepatotoxicity was induced in rats through the intraperitoneal administration of 0.5 mL kg-1body weight of CCl4. The analyses of the results obtained showed significant reduction in the levels of serum biochemical markers for 400 and 600 mg kg-1bw of CAE protected rats as compared with CCl4group. In addition, CAE administration reversed liver tissue damaged via increased antioxidants markers. Histopathological examination of CAE treatment on rats showed improved changes to the liver damage caused by CCl4 with no evidence of steatosis and inflammation. This result hence suggests that CAE has marked hepatoprotective and healing activities against CCl4-induced liver damage and could serve as a suitable candidate in drug discovery for the treatment of liver toxicity.