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SUMMARY OBJECTIVE: This study aimed to evaluate the relationship between the toxicity of cyclin-dependent kinase 4/6 inhibitors and body mass index and body surface area. METHODS: A total of 83 patients were included in the study. Patients were divided into 4 groups as 18-24.9, 25-29.9, 30-39.9, and >40 kg/m2 according to body mass index and into two groups as below and above 1.77 according to body surface area. The relationship between body mass index and body surface area and side effects was evaluated. RESULTS: No statistically significant difference was found between body mass index groups and side effects. Grade 3 neutropenia was more common in patients on palbociclib with a body surface area≤1.77. In our study, it was revealed that less hematological side effects can be encountered when body surface area is taken into account.

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Introducción: múltiples agentes quimioterapéuticos que se usan comúnmente pueden causar síndrome de Fanconi (SF) completo o parcial. El SF es una tubulopatía proximal que produce alteraciones electrolíticas y ácido-básicas, donde se evidencia pérdida de glucosa, aminoácidos, calcio, fósforo, potasio, ácido úrico y se produce acidosis metabólica por pérdida de bicarbonato. El SF usualmente no es reportado y muchas veces no se realiza el diagnóstico. Objetivo: resaltar la importancia del monitoreo urinario y sérico en pacientes que estén sometidos a quimioterapia, así como describir la literatura reciente acerca de la asociación entre agentes quimioterapéuticos y síndrome de Fanconi parcial o completo. Presentación de los casos: se presenta una serie de casos de pacientes pediátricos oncológicos con función renal preservada, donde se produjeron diferentes manifestaciones de nefrotoxicidad tubular proximal secundaria a agentes quimioterapéuticos como antimetabolitos, agentes alquilantes y antraciclinas. Discusión y conclusión: el espectro del SF puede ir de una tubulopatía proximal generalizada o completa a alteraciones parciales en la reabsorción de electrolitos. Se debe reconocer la importancia del monitoreo sérico y urinario en pacientes con lesiones tumorales que van a ser sometidos a quimioterapias con agentes potencialmente nefrotóxicos; asimismo, tener en cuenta la dosis, la frecuencia y la combinación de agentes quimioterapéuticos, con el fin de prevenir y tratar complicaciones de toxicidad renal, incluyendo SF completo o parcial.

Introduction: Several commonly used chemotherapeutic agents can cause complete or partial Fanconi syndrome (FS). FS is a proximal tubulopathy that produces electrolyte and acid base disorders where there is loss of glucose, amino acids, calcium, phosphorus, potassium, uric acid and metabolic acidosis occurs due to loss of bicarbonate. FS is not usually reported, and the diagnosis is often misled. Purpose: To highlight the importance of urinary and serum monitoring in patients undergoing chemotherapy, as well as describe the recent literature about the association between chemotherapeutic agents and partial or complete Fanconi syndrome. Case presentation: A series of cases of pediatric oncology patients with preserved renal function is presented in which different manifestations of proximal tubular nephrotoxicity occurred secondary to chemotherapeutic agents such as antimetabolites, alkylating agents, and anthracyclines. Discussion and conclusion: The spectrum of FS can range from a generalized or complete proximal tubulopathy to partial alterations in electrolyte reabsorption. The importance of serum and urinary monitoring should be recognized in patients with tumor lesions who will undergo chemotherapies with potentially nephrotoxic agents; the dosage, frequency and combination of chemotherapeutic agents should be taken into account, in order to prevent and treat the complications of renal toxicity including complete or partial SF.

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ABSTRACT Introduction: Methotrexate is a drug with chemotherapeutic properties frequently used for the treatment of certain types of cancer. The following is a clinical case which, to the best of the authors' knowledge, is the first report in Colombia on nephrotoxicity caused by this drug and describes the consequences as well as the treatment provided at a quaternary care hospital. Case report: A 71-year-old patient with a diagnosis of non-Hodgkin's lymphoma with normal renal function underwent chemotherapy (high-dose methotrexate intravenously) and developed stage 3 acute renal failure according to the KDIGO guidelines, which was most likely related to methotrexate intake. The patient received treatment with intravenous fluids and sodium bicarbonate as promoters of urine excretion of the toxin, and oral calcium folinate following the institutional protocol. The patient was discharged with recovery of kidney function and improved creatinine and urea nitrogen levels. Conclusion: The treatment given to the patient in this case report shows that although methotrexate nephrotoxicity is a potentially serious entity, it can have a good prognosis if treated promptly.

RESUMEN Introducción. El metotrexato es un fármaco con propiedades quimioterapéuticas usado de forma frecuente para el tratamiento de ciertos tipos de cáncer. A continuación, se presenta un caso clínico que, a conocimiento de los autores, es el primer reporte en Colombia sobre nefrotoxicidad por este medicamento, así como sus consecuencias y el manejo que se le dio en un hospital de cuarto nivel. Presentación del caso. Hombre de 71 años con diagnóstico de linfoma no Hodgkin y función renal normal, quien se sometió a tratamiento quimioterapéutico (metotrexato a altas dosis por vía endovenosa) y desarrolló insuficiencia renal aguda estadio 3 según las guías KDIGO, la cual muy probablemente se relacionaba al consumo de metotrexato. El paciente recibió manejo con líquidos endovenosos y bicarbonato de sodio como promotores de la eliminación renal del tóxico, así como folinato cálcico oral, según el protocolo institucional, con lo cual se logró la recuperación de su función renal y que los niveles de niveles de creatinina y nitrógeno ureico mejoraran. Conclusiones. El manejo del paciente reportado demuestra que aunque la nefrotoxicidad por metotrexato es una entidad potencialmente grave, puede tener un buen pronóstico si se maneja oportunamente.

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OBJECTIVE: This study aims to investigate the relationship between the pre-operative indocyanine green (ICG) test, the chemotherapy-associated liver injury (CALI), and the development of severe post-operative complications (POC) in patients operated of colorectal liver metastases (CRLMs). MATERIALS AND METHODS: Sixty-nine patients previously treated with chemotherapy and submitted to liver resection for CRLM were retrospectively studied. Two pathologists independently reviewed the pathological specimens and assessed the presence of CALI. The correlation between ICG clearance and specific pathological features was analyzed. In addition, a logistic regression analysis was performed to seek for pre-operative factors associated with severe complications. RESULTS: After a mean of 10.6 (± 7.5) chemotherapy cycles, 44 patients (63.8%) developed CALI. ICG retention rate at 15 min (ICG-R15) was not statistically different between patients with and without CALI and it could only discriminate the presence of centrilobular fibrosis. Rate of severe complications was almost 6-fold in patients with CALI compared to patients without CALI (p = 0.024). ICG-R15 ≥ 10% was the only independent risk factor associated with severe POC at multivariable logistic regression (OR = 4.075 95% CI: 1.077-15.422, p = 0.039). CONCLUSIONS: Pre-operative ICG clearance test, although not useful to identify patients with hepatic drug toxicity, is a strong predictor for the development of severe post-hepatectomy complications.

OBJETIVO: Investigar la relación entre el test de aclaramiento del verde de indocianina (ICG) preoperatorio, las alteraciones patológicas derivadas de la quimioterapia (CALI) y el desarrollo de complicaciones posoperatorias en los pacientes sometidos a resección hepática por metástasis de cáncer colorrectal (MCCR). MATERIAL Y MÉTODOS: Sesenta y nueve pacientes previamente tratados con quimioterapia y operados de MCCR se estudiaron de manera retrospectiva. Dos patólogas revisaron independientemente el parénquima hepático no tumoral de los especímenes y determinaron la presencia de daño quimio-inducido. Se analizó la correlación entre el aclaramiento de ICG y las diferentes alteraciones anatomo-patológicas encontradas. Además, se realizó un análisis de regresión logística para identificar los factores preoperatorios asociados con las complicaciones posoperatorias. RESULTADOS: Tras una media de 10.6 (± 7.5) ciclos de quimioterapia, 44 pacientes (63.8%) desarrollaron CALI. La tasa de retención de ICG a los 15 minutos (ICG-R15) no fue estadísticamente diferente entre los pacientes con y sin CALI y solo pudo discriminar la presencia de fibrosis centrolobulillar. La tasa de complicaciones severas posoperatorias fue 6 veces superior en los pacientes con CALI, comparada con aquella de los pacientes sin CALI (p = 0.024). Un ICG-R15 ≥ 10% fue el único factor de riesgo independiente asociado a complicaciones severas (OR = 4.075 95% CI: 1.077-15.422, p = 0.039). CONCLUSIONES: La prueba preoperatoria de aclaramiento del ICG, a pesar de no identificar eficazmente los pacientes con daño por quimioterapia, es un fuerte predictor de desarrollo de complicaciones severas posoperatorias.

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BACKGROUND: Tuberculosis is one of the most common causes of hospitalisation in patients with HIV. Despite this, hospital outcomes of patients with this co-infection have rarely been described since antiretroviral therapy became widely available. METHODS: Prospective cohort study of HIV-infected adult patients hospitalised with TB in six referral hospitals in Medellin, Colombia, from August 2014 to July 2015. RESULTS: Among 128 HIV-infected patients hospitalised with tuberculosis, the mean age was 38.4 years; 79.7% were men. HIV was diagnosed on admission in 28.9% of patients. The median CD4 + T-cell count was 125 (±158 SD) cells/µL. Only 47.3% of patients with a known diagnosis of HIV upon admission were on antiretroviral therapy, and only 11.1% had a tuberculin skin test in the previous year. Drug toxicity due to tuberculosis medications occurred in 11.7% of patients. Mean length of stay was 23.2 days, and 10.7% of patients were readmitted. Mortality was 5.5%. CONCLUSIONS: Hospital mortality attributable to tuberculosis in patients with HIV is low in reference hospitals in Colombia. Cases of tuberculosis in HIV-infected patients occur mainly in patients with advanced HIV, or not on antiretroviral therapy, despite a known diagnosis of HIV. Only one of every 10 patients in this cohort had active screening for latent tuberculosis, possibly reflecting missed treatment opportunities.

CONTEXTE: La tuberculose (TB) est l'une des causes les plus courantes d'hospitalisation chez les patients VIH positifs. Malgré cela, les résultats hospitaliers des patients atteints de cette coinfection ont rarement été décrits depuis que le traitement antirétroviral est devenu largement disponible. MÉTHODES: Etude de cohorte prospective de patients adultes infectés par le VIH hospitalisés pour TB dans six hôpitaux de référence à Medellin, en Colombie, d'août 2014 à juillet 2015. RÉSULTATS: Sur 128 patients infectés par le VIH hospitalisés pour TB, l'âge moyen était de 38,4 ans; 79,7% étaient des hommes. Le VIH a été diagnostiqué à l'admission chez 28,9% des patients. Le nombre médian de lymphocytes T CD4+ était de 125 (±158 SD) cellules/µL. Seuls 47,3% des patients dont le diagnostic de VIH était connu lors de leur admission étaient sous traitement antirétroviral et 11,1% seulement avaient subi un test cutané à la tuberculine l'année précédente. Une toxicité médicamenteuse due aux médicaments antituberculeux est survenue chez 11,7% des patients. La durée moyenne de séjour était de 23,2 jours et 10,7% des patients ont été réadmis. La mortalité était de 5,5%. CONCLUSIONS: La mortalité hospitalière attribuable à la TB chez les patients VIH positifs est faible dans les hôpitaux de référence en Colombie. Les cas de TB chez les patients infectés par le VIH surviennent principalement chez les patients à un stade avancé du VIH, ou qui ne sont pas sous traitement antirétroviral, malgré un diagnostic connu de VIH. Seul un patient sur 10 de cette cohorte a subi un dépistage actif de la TB latente, ce qui reflète peut-être des opportunités de traitement manquées.

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There is no effective therapy against COVID-19 available so far. In the last months, different drugs have been tested as potential treatments for COVID-19, exhibiting high toxicity and low efficacy. Therefore, nanotechnology can be applied to improve the therapeutic action and minimize the toxicity of loaded drugs. In this review, we summarized the drugs tested as COVID-19 treatment and the advantages of antiviral nanostructured drug-delivery systems. Such systems have demonstrated low in vitro toxicity with better in vitro antiviral activity than free drugs. We believe that this approach should inspire novel nanostructured drug-delivery systems developments to find efficient COVID-19 treatments. Here, we discuss the remaining challenges for such promising nanosystems to be approved for clinical use.

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Sibutramine is a non-selective serotonin-norepinephrine reuptake inhibitor orally administered for weight loss. In a previous study, we showed pharmacological mechanisms involved in the reduction of sperm quality and fertility of rats exposed for 30 days to this anorexigen in the light phase of the light-dark (l/d) cycle. It is already known that rodents are nightlife animals, with higher metabolic activity during the dark phase than in the light phase of the light-dark (l/d) cycle. Thus, the present study aimed to investigate whether the deleterious effects on reproductive parameters after sibutramine administration would be enhanced after a shorter period of exposure during the dark phase of the l/d cycle. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/d) or vehicle for 15 days during the dark phase of the l/d cycle. Sibutramine treatment decreased final body and reproductive organ weights, as well as serum testosterone levels. Sperm transit time through the epididymis was accelerated, and sperm concentration and motility were diminished in the sibutramine-exposed rats. The decrease in sperm concentration was also verified in the epididymal histological sections. In conclusion, the deleterious effects of sibutramine on reproductive parameters of male rats were enhanced when the exposure occurred in the dark phase of the l/d cycle, even after a short exposure duration. Our results reinforce the impact of timing on drug therapeutic action.

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There are a variety of less common diffuse liver diseases that can be asymptomatic or cause severe liver dysfunction. For the majority of them, the association of clinical, laboratory, and imaging findings are needed to narrow the differential diagnosis. In this article, we will review and describe the rarer diffuse liver diseases including drug-related liver disease, inflammatory and infectious diseases, and deposition disorders such as amyloidosis, glycogen storage disease, Wilson's disease, and alpha-1 antitrypsin deficiency. Abdominal radiologists should be familiar with the imaging features of different types of diffuse liver diseases to help the multidisciplinary team involved in the treatment of these patients. The data related to some of these conditions are scarce and sometimes experimental, but we want to demonstrate to the reader the value of imaging techniques in their analysis and introduce the potential of new imaging methods.

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Hepatic diseases leading to fibrosis affect millions of individuals worldwide and are a major public health challenge. Although, there have been many advances in understanding hepatic fibrogenesis, an effective therapy remains elusive. Studies focus primarily on activation of the hepatic stellate cells (HSCs), the principal fibrogenic cells in the liver; however, fewer numbers of studies have examined molecular mechanisms that deactivate HSC, controlling the profibrogenic phenotype. In the present study, we evaluated cellular and molecular actions of the chemical triclosan (TCS) in reverting activated HSCs to a quiesced phenotype. We demonstrated that the inhibition of the enzyme fatty acid synthase by TCS in activated HSCs promotes survival of the cells and triggers cellular and molecular changes that promote cellular phenotypic reversion, offering potentially new therapeutic directions.

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Xylazine and acepromazine are drugs used exclusively in veterinary medicine. Xylazine is used as a sedative, analgesic, and tranquilizer while acepromazine is used as a sedative, pre-anesthetic, and anesthetic adjuvant. In vitro drug toxicity experimentation is essential to predict possible damage associated with treatment. This study was carried out to evaluate and compare the in vitro effects of acepromazine and xylazine on cell viability. Equine Dermis cells lines were used to examine different drug concentrations (0.02 mg/mL, 0.01 mg/mL, 0.005 mg/mL and 0.0025 mg/mL). An MTT assay was carried out to reveal cell viability. Both tested drugs reduced the viability of ED cells at 0.02 and 0.01 mg/mL. At 0.005 mg/mL, only acepromazine presented an effect. These results corroborate previous studies with xylazine. On the other hand, this is the first report about acepromazine and cell viability. Previous studies suggest that the mechanisms involved in reducing cell viability are apoptosis for xylazine and the activation of the autophagic pathway for acepromazine. Both mechanisms have been seen in other drugs of the same classes. These findings reveal that both acepromazine and xylazine cause concentration-dependent cytotoxicity in vitro. Future experiments could further elucidate the mechanisms by which this effect happens and thus circumvent the risk of potential tissue damag

Xilazina e acepromazina sãofármacos usados exclusivamente em medicina veterinária. A xilazina é usada como sedativo, analgésico e tranquilizante, enquanto a acepromazina é usada como sedativo, pré-anestésico e adjuvante anestésico. A experimentação de toxicidade de fármacos in vitroé essencial para prever possíveis danos associados ao tratamento. Nesse sentido, este estudo foi realizado com o objetivo de avaliar e comparar in vitroos efeitos da acepromazina e da xilazina na viabilidade celular. Células da linhagem Equine Dermis (ED) foram usadas para examinar diferentes concentrações de fármacos (0,02 mg/mL, 0,01 mg/mL, 0,005 mg/mL e 0,0025 mg/mL). O ensaio de MTT foi realizado para revelar a viabilidade celular. Ambos os fármacos testados reduziram a viabilidade das células ED em 0,02 e 0,01 mg/mL. A 0,005 mg/mL, apenas acepromazina apresentou efeito. Esses resultados corroboram estudos anteriores com xilazina. Por outro lado, este é o primeiro estudo sobre acepromazina e viabilidade celular. Estudos anteriores sugerem que os mecanismos envolvidos na redução da viabilidade celular são a apoptose para a xilazina, e a ativação da via autofágica para a acepromazina, ambos mecanismos observados em medicamentos dasmesmasclasses. Esses achados revelam que tanto a acepromazina quanto a xilazina causamcitotoxicidade in vitrodependente da concentração. Expeimentosfuturos podem elucidar ainda mais os mecanismos pelos quais esse efeito acontece e, assim, contornar o risco de possíveis danos aos tecidos.

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Xylazine and acepromazine are drugs used exclusively in veterinary medicine. Xylazine is used as a sedative, analgesic, and tranquilizer while acepromazine is used as a sedative, pre-anesthetic, and anesthetic adjuvant. In vitro drug toxicity experimentation is essential to predict possible damage associated with treatment. This study was carried out to evaluate and compare the in vitro effects of acepromazine and xylazine on cell viability. Equine Dermis cells lines were used to examine different drug concentrations (0.02 mg/mL, 0.01 mg/mL, 0.005 mg/mL and 0.0025 mg/mL). An MTT assay was carried out to reveal cell viability. Both tested drugs reduced the viability of ED cells at 0.02 and 0.01 mg/mL. At 0.005 mg/mL, only acepromazine presented an effect. These results corroborate previous studies with xylazine. On the other hand, this is the first report about acepromazine and cell viability. Previous studies suggest that the mechanisms involved in reducing cell viability are apoptosis for xylazine and the activation of the autophagic pathway for acepromazine. Both mechanisms have been seen in other drugs of the same classes. These findings reveal that both acepromazine and xylazine cause concentration-dependent cytotoxicity in vitro. Future experiments could further elucidate the mechanisms by which this effect happens and thus circumvent the risk of potential tissue damag(AU)

Xilazina e acepromazina sãofármacos usados exclusivamente em medicina veterinária. A xilazina é usada como sedativo, analgésico e tranquilizante, enquanto a acepromazina é usada como sedativo, pré-anestésico e adjuvante anestésico. A experimentação de toxicidade de fármacos in vitroé essencial para prever possíveis danos associados ao tratamento. Nesse sentido, este estudo foi realizado com o objetivo de avaliar e comparar in vitroos efeitos da acepromazina e da xilazina na viabilidade celular. Células da linhagem Equine Dermis (ED) foram usadas para examinar diferentes concentrações de fármacos (0,02 mg/mL, 0,01 mg/mL, 0,005 mg/mL e 0,0025 mg/mL). O ensaio de MTT foi realizado para revelar a viabilidade celular. Ambos os fármacos testados reduziram a viabilidade das células ED em 0,02 e 0,01 mg/mL. A 0,005 mg/mL, apenas acepromazina apresentou efeito. Esses resultados corroboram estudos anteriores com xilazina. Por outro lado, este é o primeiro estudo sobre acepromazina e viabilidade celular. Estudos anteriores sugerem que os mecanismos envolvidos na redução da viabilidade celular são a apoptose para a xilazina, e a ativação da via autofágica para a acepromazina, ambos mecanismos observados em medicamentos dasmesmasclasses. Esses achados revelam que tanto a acepromazina quanto a xilazina causamcitotoxicidade in vitrodependente da concentração. Expeimentosfuturos podem elucidar ainda mais os mecanismos pelos quais esse efeito acontece e, assim, contornar o risco de possíveis danos aos tecidos.(AU)

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The identification of biomarkers for toxicity is becoming increasingly important for drug discovery and development. This chapter describes the preparation and utilization of primary rat hepatocytes as a cellular model of steatosis. A protocol is presented for dosing the cells with the steatosis-inducing compound amiodarone, along with the conduction of assays for measuring lipid accumulation and mitochondrial function. A differential solubility extraction procedure is also presented, which can be used for proteomic profiling analysis.

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[This corrects the article DOI: 10.11604/pamj.2017.28.318.14333.].

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La nafazolina es un fármaco utilizado como descongestivo, generalmente, en pacientes adultos. Su indicación en pediatría no es frecuente; su uso está aprobado a partir de los 12 años por los efectos tóxicos que posee. La intoxicación en niños genera un cuadro clínico potencialmente grave. Se caracteriza por la aparición inmediata de hipotonía, deterioro del sensorio, hipotermia y bradicardia con grado variable de compromiso clínico. Si bien es una intoxicación infrecuente, la anamnesis y el manejo inicial del paciente son la clave en su evolución. Se presenta a un niño de 4 años que, por un error terapéutico, recibió este fármaco y se destaca la instauración rápida y potencialmente grave del cuadro clínico.

Naphazoline is a drug commonly used as a decongestant in adult patients. Its indication in Pediatrics is not frequent, being approved its use from the age of 12 for the toxic effects it possesses. Intoxication in children generates a potentially serious clinical picture. It is characterized by the immediate appearance of hypotonia, deterioration of the sensory, hypothermia and bradycardia of variable degree of clinical compromise. Although it is an infrequent intoxication, the anamnesis and the initial management of the patient are the key in the evolution. We present a 4-year-old boy who, as a therapeutic error, receives this drug, emphasizing the rapid and potentially severe establishment of the clinical picture.

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Naphazoline is a drug commonly used as a decongestant in adult patients. Its indication in Pediatrics is not frequent, being approved its use from the age of 12 for the toxic effects it possesses. Intoxication in children generates a potentially serious clinical picture. It is characterized by the immediate appearance of hypotonia, deterioration of the sensory, hypothermia and bradycardia of variable degree of clinical compromise. Although it is an infrequent intoxication, the anamnesis and the initial management of the patient are the key in the evolution. We present a 4-year-old boy who, as a therapeutic error, receives this drug, emphasizing the rapid and potentially severe establishment of the clinical picture.

La nafazolina es un fármaco utilizado como descongestivo, generalmente, en pacientes adultos. Su indicación en pediatría no es frecuente; su uso está aprobado a partir de los 12 años por los efectos tóxicos que posee. La intoxicación en niños genera un cuadro clínico potencialmente grave. Se caracteriza por la aparición inmediata de hipotonía, deterioro del sensorio, hipotermia y bradicardia con grado variable de compromiso clínico. Si bien es una intoxicación infrecuente, la anamnesis y el manejo inicial del paciente son la clave en su evolución. Se presenta a un niño de 4 años que, por un error terapéutico, recibió este fármaco y se destaca la instauración rápida y potencialmente grave del cuadro clínico.

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OBJECTIVES: Patients receiving treatment for tuberculosis are at risk of developing acute liver failure due to the hepatotoxicity of antitubercular drugs. We aimed to describe our experience with liver transplantation from deceased donors in this situation. METHODS: We identified patients undergoing transplantation for acute liver failure due to antitubercular drugs in our prospectively maintained database. RESULTS: Of 81 patients undergoing transplantation for acute liver failure, 8 cases were attributed to antitubercular drugs during the period of 2006-2016. Regarding the time of tuberculosis treatment until the onset of jaundice, patients were on antitubercular drugs for a mean of 64.7 days (21-155 days). The model for end-stage liver disease (MELD) score of patients ranged from 32 to 47 (median 38), and seven patients underwent transplantation under vasopressors. The 1-year survival was 50%. Three patients died during the week following transplantation due to septic shock (including a patient with acute liver failure due to hepatic/disseminated tuberculosis), and the remaining patient died 2 months after transplantation due to pulmonary infection. There were 2 cases of mild rejection and 1 case of moderate rejection. Of the surviving patients, all were considered cured of tuberculosis after alternative drugs were given. CONCLUSION: Patients arrived very sick and displayed poor survival after deceased donor transplantation.

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The antiparasitic activity of 3-hydroxykynurenine (3-HK), one of the major tryptophan catabolites of the kynurenine pathway, against both Trypanosoma cruzi evolutive forms that are important for human infection, trypomastigotes (Tps) and amastigotes (Am), possible targets in the parasite and the drug toxicity to mammalian cells have been investigated. 3-HK showed a potent activity against Am with IC50 values in the micromolar concentration range, while the IC50 values to cause Tps death was ∼6000-times higher, indicating that the replicative form present in the vertebrate hosts is much more susceptible to 3-HK than bloodstream Tps. In addition, 3-HK showed activity against Tps and Am, at concentrations that did not exhibit toxicity to mammalian cells. Ultrastructural analysis and flow cytometry studies indicated that Am and Tps mitochondrion and nuclei contain 3-HK targets. The potency and selectivity of 3-HK, which is generated during T. cruzi infection in human and mice, suggest that 3-HK may be a suitable candidate for drug research and development for Chagas disease.

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BACKGROUND: This study aims to investigate renal toxicities of Polymyxin B and Vancomycin among critically ill patients and risk factors for acute kidney injury (AKI). METHODS: This is a cross-sectional study conducted with patients admitted to an intensive care unit (ICU) of a tertiary hospital in Brazil. Patients were divided into two groups: those who used association of Polymyxin B + Vancomycin (Group I) and those who used only Polymyxin B (Group II). Risk factors for AKI were also analyzed. RESULTS: A total of 115 patients were included. Mean age was 59.2 ± 16.1 years, and 52.2% were males. Group I presented higher GFR (117.1 ± 70.5 vs. 91.5 ± 50 ml/min/1.73 m², p = 0.02) as well as lower creatinine (0.9 ± 0.82 vs. 1.0 ± 0.59 mg/dL, p = 0.014) and urea (51.8 ± 23.7 vs. 94.5 ± 4.9 mg/dL, p = 0.006) than group II on admission. Group I also manifested significantly higher incidence of AKI than group II (62.7% vs. 28.5%, p = 0.005), even when stratified according to RIFLE criteria ('Risk' 33.9% vs. 10.7%; 'Injury' 10.2% vs. 8.9%; 'Failure' 18.6% vs. 8.9%; p = 0.03). Accumulated Polymyxin B dose > 10 million IU was an independent predictor for AKI (OR = 2.72, 95% CI = 1.13-6.51, p = 0.024). CONCLUSIONS: Although patients who received Polymyxin B plus vancomycin had more favorable clinical profile and higher previous GFR, they presented a higher AKI incidence than those patients who received Polymyxin B alone. Cumulative Polymyxin B dose > 10 million IU was independently associated to AKI.

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ABSTRACT Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. We performed a systematic review of randomized controlled trials using lamotrigine as a monotherapy to quantify the incidence of cutaneous reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis. Of a total of 4,364 papers regarding lamotrigine, 122 studies met our inclusion and exclusion criteria. In total, 18,698 patients were included with 1,570 (8.3%) of patients experiencing an adverse dermatologic reaction. The incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis was 0.04%.

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AIM: Studies examining the association between mortality and anticholinergic burden in the geriatric population are conflicting and are absent in the Mexican American population. The present study aimed to determine whether higher anticholinergic burden increases mortality in a cohort representative of community-based older Mexican Americans in the USA. METHODS: This retrospective cohort database study used the Hispanic Established Populations for the Epidemiologic Study of the Elderly cohort. The primary outcome, mortality, was assessed beginning at the second interview in 1995 until the fifth interview in 2005. Medications were classified for anticholinergic burden according to the modified-Anticholinergic Drug Scale and were summed across all reported medications creating a measure of total anticholinergic burden. Anticholinergic burden was tested for association with mortality using survival analysis. RESULTS: The 1497 older adults reporting medication usage were included. Survival analysis showed a statistically significant (P < 0.05) relationship between anticholinergic burden and increased mortality. CONCLUSIONS: Anticholinergic burden is associated with increased mortality in Southwestern Mexican American older adults who report taking prescription or non prescription medications. These findings suggest that anticholinergic burden might be a risk factor for mortality in this selected population, with additional studies required to further define the risk. Geriatr Gerontol Int 2017; 17: 1515-1521.

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