Caffeic acid and caffeine attenuate toxicity associated with malonic or methylmalonic acid exposure in Drosophila melanogaster.

The deficiency in the activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MCM, EC 5.4.99.2) leads to a condition called methylmalonic academia, which is characterised by the accumulation of methylmalonic (MMA), malonic (MA) or other organic acids. Importantly, we have recently found that supplementation with Ilex paraguariensis aqueous extract offered protection against toxicity associated with MMA or MA exposure to Drosophila melanogaster. Of note, caffeic acid (CA) and caffeine (CAF) were the major phytochemicals found in our Ilex paraguariensis crude extract. Therefore, here, we have exploited CA and/or CAF to test the hypothesis that supplementation with the isolated compounds (either alone or combined) could exert a protective effect against MMA or MA-induced toxicity in flies. Therefore, flies were exposed to MA (5 mM) or MMA (5 mM) and concomitantly treated with CA (1.39 µg/mL), CAF (1.27 µg/mL) or CA + CAF for 10 days for survival, and for 4 days for behavioural and biochemical assays. CA, CAF and CA + CAF treatments completely abolished the mortality associated with either MMA or MA exposure. Moreover, CA and CAF, either alone or combined, completely abolished behavioural changes, and completely protect against changes in thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT) activity and MTT reduction ability, associated with MA or MMA exposure. In turn, CAF restored SOD activity in the head of flies exposed to MA or MMA. However, CA and CAF (either alone or combined) significantly decreased acetylcholinesterase (AChE) activity per se, while CAF alone protected from changes in AChE activity (in head tissue) associated with MA or MMA. Finally, CA and/or CAF were able to protect from a decrease in glucose and triglyceride levels associated with both MA and MMA exposures in haemolymph. Together, our data confirm the hypothesis that supplementation with CA and/or CAF offers protection against detrimental changes associated with MMA or MA exposure in flies, being responsible, at least in part, for the protective effect of I. paraguariensis crude extract which was reported previously.

Ilex paraguariensis Attenuates Changes in Mortality, Behavioral and Biochemical Parameters Associated to Methyl Malonate or Malonate Exposure in Drosophila melanogaster.

Methylmalonic acidemia is a genetic disease characterized by accumulation of organic acids, such as methylmalonic (MMA) and malonic (MA) acids. Considering that the accumulation of MMA and MA causes several damages due to oxidative stress, antioxidants are thought to play a pivotal role in preventing deleterious effects associated with exposure to such compounds. Ilex paraguariensis (IP) was used here to test the hypothesis that supplementation with the aqueous extract of this plant could exert protective effect against MMA or MA induced mortality, behavioral and/or biochemical changes in Drosophila melanogaster (DM). Initially, a curve time- and dose-response to MMA (1-10 mM), MA (1-10 mM) and IP (63-500 µM) was performed. Thereafter, flies were concomitantly exposed to MA (5 mM), MMA (5 mM) and/or IP (250 µg/mL) during 15 days for survival assay, and for 48 hs to MA (1 or 5 mM), MMA (1 or 5 mM) and/or IP (250 µg/mL) for subsequent investigations. Both MMA and MA exposure resulted in higher incidence of mortality, a worse performance in the negative geotaxis assay and increased locomotion in open-field test as compared with control group. Furthermore, a marked increase in non-protein thiol (NPSH) and in thiobarbituric acid reactive substances (TBARS) levels, decrease in superoxide dismutase (SOD), catalase and acetylcholinesterase (AChE) activities, and decrease in MTT and resazurin reduction were noted in MMA or MA treated groups. IP treatment offered significant protection against all alterations associated to MMA or MA exposure. This study confirm the hypothesis that supplementation with IP offers protection against changes associated to MMA or MA exposure in DM, due, at least in part, to its antioxidant effect.

Cellular Responses in Drosophila melanogaster Following Teratogen Exposure.

Studies focusing on the teratogenicity of a series of new chemicals that are produced in a daily basis represent an important focus in toxicological/pharmaceutical research, particularly due to the risks arising from occupational exposure of the subjects. However, the complex mating procedures, scheduling of treatments, requirements for trained personnel, and elevated costs of traditional teratological assays with mammals hamper this type of assessments. Accordingly, the use of Drosophila melanogaster as a model for teratological studies has received considerable attention. Here some general protocols about Drosophila exposure-at different stages of their life cycle-to any chemical with putative teratological activity are presented. Importantly, some details about D. melanogaster embryonic, larval, pupal, or adult endpoints, that can be used to assess teratogenicity using flies as a model organism, are presented.

Treatment with pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) differently affects survival, locomotor activity, and biochemical markers in Drosophila melanogaster.

PTZ is a convulsive agent that acts via selective blockage of GABAA receptor channels, whereas 4-AP leads to a convulsive episode via blockage of K+ channels. However, the mechanism(s) by which pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) cause toxicity to Drosophila melanogaster needs to be properly explored, once it will help in establishing an alternative model for development of proper therapeutic strategies and also to counteract the changes associated with exposure to both epileptic drugs. For the purpose, we investigated the effects of exposure (48 h) to PTZ (60 mM) and/or 4-AP (20 mM) on survival, locomotor performance, and biochemical markers in the body and/or head of flies. 4-AP-fed flies presented a higher incidence of mortality and a worse performance in the open field test as compared to non-treated flies. 4-AP also caused a significant increase in the reactive species (RS) and protein carbonyl (PC) content in the body and head. Also a significant increase in catalase and acetylcholinesterase (AChE) activities was observed in the body. In the same vein, PTZ exposure resulted in a significant increase in RS, thiobarbituric acid reactive substances (TBARS), PC content, and catalase activity in the body. PTZ exposure also caused a significant increase in AChE activity both in body and head. It is important to note that PTZ-treated flies also down-regulated the NRF2 expression. Moreover, both 4AP- and PTZ-fed flies presented a significant decrease in MTT reduction, down-regulation, and inhibition of SOD in body. However, SOD was significantly more active in the head of both 4-AP and PTZ-treated flies. Our findings provide evidence regarding the toxicological potential of both PTZ and/or 4-AP to flies. This model will help in decoding the underlying toxicological mechanisms of the stated drugs. It will also help to properly investigate the therapeutic strategies and to counteract the drastic changes associated with both epileptogenic drugs.

Ilex paraguariensis crude extract acts on protection and reversion from damage induced by t-butyl hydroperoxide in human erythrocytes: a comparative study with isolated caffeic and/or chlorogenic acids.

BACKGROUND: Studies comparing the effects of phytochemicals under different regimens of exposure are necessary to give a better indication about their mechanism(s) of protection. Hence, in the present study, we investigated the preventive (pre-incubation), protective (co-incubation) and/or remediative (post-incubation) activity of chlorogenic acid and caffeic acids, in comparison with Ilex paraguariensis crude extract, against t-butyl hydroperoxide (t-BHP)-induced damage to human erythrocytes. RESULTS: We found that both caffeic and chlorogenic acids were able to prevent and revert the hemolysis associated with t-BHP exposure. By contrast, isolated compounds (alone or in combination) presented no effect on basal and/or t-BHP-induced non-protein thiol (NPSH) oxidation or production of thiobarbituric acid reactive substances (TBBARS). In turn, I. paraguariensis extract was effective to prevent, protect and revert the hemolysis associated with t-BHP exposure. Moreover, I. paraguariensis significantly protects and reverts t-BHP-induced NPSH oxidation and TBARS production. CONCLUSIONS: We have found that I. paraguariensis extract acts better with respect to the protection and reversion of t-BHP-associated changes, whereas isolated compounds are more active in preventing and reverting t-BHP pro-hemolytic action. Moreover, our data suggest that the pro-hemolytic activity of t-BHP may occur via mechanism(s) other(s) than lipid peroxidation and/or NPSH oxidation. © 2016 Society of Chemical Industry.

Alteraciones de la saturación de oxígeno arterial en pacientes que se someten a endoscopía de tubo digestivo alto / Alterations in oxygen saturation of patients submitted to upper gastrointestinal endoscopy

Este trabajo estudia los cambios en la saturación de oxígeno arterial en los pacientes que son sometidos a endoscopía del tubo digestivo alto; la extensión de la desaturación después de la sedación con diazepam, la relación de desaturación con el grado de función respiratoria del paciente y la comparación de dos tipos de instrumentos endoscópicos Olympus (XQ y K10). Noventa y nueve pacientes consecutivos sometidos a endoscopía de tubo digestivo alto electiva y de urgencia fueron monitorizados con oxímetro de pulso antes de la sedación, durante el procedimiento y al final del mismo. No encontramos desaturación clínicamente significativa en ninguno de los casos estudiados

Manejo perioperatorio del paciente con miastenia gravis sometido a timectomía / Perioperative management of patients with myasthenia gravis subjected to thymectomy

En un estudio retrospectivo se revisó una serie de 34 pacientes (27 mujeres y 7 hombres) sometidos a timectomía transesternal como parte del tratamiento para la miastenia gravis en un período de 3 años. El manejo preoperatorio incluyó anticolinesferásicos (31 pacientes), esteroides (16 pacientes) y 9 procedimientos de plasmaféresis. Se analizó el manejo anestésico, con especial énfase en la suspensión del anticolinesterásico y empleo de relajantes musculares. Doce pacientes requirieron de ventilación mecánica prolongada en el postoperatorio y se determinó la eficacia pronóstica de los criterios reportados en la literatura que la predecir. Ocurrieron complicaciones en 19 pacientes y la mortalidad fue del 8.88%. Se sugiere en base a esta experiencia el manejo perioperatorio del paciente con miastenia gravis

Empacamiento abdominal como manejo de la hemorragia masiva transosperatoria / Abdominal packing as management of massive postoperative bleeding: report of a case

Se informa un caso de trombocitopenia post-transfusión de sangre de banco; se manifestó por hemorragia intra-abdominal masiva, de múltiples sitios que fue imposible de controlar con los métodos usuales de hemostasis. Se llevó a cabo empacamiento abdominal total con compresas abdominales con lo que se controló satisfactoriamente la hemoragia y 36 horas después se llevó a cabo cirugía para la extracción de las empresas, evolucionando adecuadamente. Se demuestra la utilidad de este procedimiento como medida heroica en este tipo de sangrado transoperatorio

Obstrucción arterial aguda de los miembros / Acute arterial obstruction of the limbs

Se presentan los resultados obtenidos en una serie consecutiva de 165 pacientes con oclusión arterial aguda de los miembros (102 embolias y 63 trombosis) sometidos a 186 operaciones de urgencia en los últimos 9 años. Del análisis de nuestra casuística se desprende que existe una buena posibilidad de salvar un miembro isquemiado, en la medida en que se tome a tiempo la correcta decisión de encarar su adecuado tratamiento quirúrgico de urgencia.

Obstrucción arterial aguda de los miembros / Acute arterial obstruction of the limbs

Se presentan los resultados obtenidos en una serie consecutiva de 165 pacientes con oclusión arterial aguda de los miembros (102 embolias y 63 trombosis) sometidos a 186 operaciones de urgencia en los últimos 9 años. Del análisis de nuestra casuística se desprende que existe una buena posibilidad de salvar un miembro isquemiado, en la medida en que se tome a tiempo la correcta decisión de encarar su adecuado tratamiento quirúrgico de urgencia.(AU)