RESUMEN
The microbial toxin ß-N-methylamino-L-alanine (BMAA), which is derived from cyanobacteria, targets neuronal mitochondria, leading to the activation of neuronal innate immunity and, consequently, neurodegeneration. Although known to modulate brain inflammation, the precise role of aberrant microglial function in the neurodegenerative process remains elusive. To determine if neurons signal microglial cells, we treated primary cortical neurons with BMAA and then co-cultured them with the N9 microglial cell line. Our observations indicate that microglial cell activation requires initial neuronal priming. Contrary to what was observed in cortical neurons, BMAA was not able to activate inflammatory pathways in N9 cells. We observed that microglial activation is dependent on mitochondrial dysfunction signaled by BMAA-treated neurons. In this scenario, the NLRP3 pro-inflammatory pathway is activated due to mitochondrial impairment in N9 cells. These results demonstrate that microglia activation in the presence of BMAA is dependent on neuronal signaling. This study provides evidence that neurons may trigger microglia activation and subsequent neuroinflammation. In addition, we demonstrate that microglial activation may have a protective role in ameliorating neuronal innate immune activation, at least in the initial phase. This work challenges the current understanding of neuroinflammation by assigning the primary role to neurons.
Asunto(s)
Aminoácidos Diaminos , Toxinas de Cianobacterias , Microglía , Mitocondrias , Neuronas , Microglía/metabolismo , Microglía/efectos de los fármacos , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Ratones , Aminoácidos Diaminos/farmacología , Línea Celular , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Técnicas de Cocultivo , Inmunidad Innata/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células CultivadasRESUMEN
Abstract We report the first known occurrence of Panstrongylus megistus (Burmeister, 1835) (Hemiptera, Reduviidae, Triatominae) in the Metropolitan Region of São Paulo, Brazil. In 2018, adult specimens were sent by residents to the competent authorities and, in the inspection of the property, a large focus associated with a marsupial nest was found. This finding reinforces the importance of the species in the state of São Paulo, serves as an alert for epidemiological surveillance and extends the species colonization area in the state of São Paulo.
Resumo Relatamos a primeira ocorrência de Panstrongylus megistus (Burmeister, 1835) (Hemiptera, Reduviidae, Triatominae) na Região Metropolitana de São Paulo, Brasil. Em 2018, espécimes adultos foram enviados por residentes e a pesquisa na propriedade constatou a presença de um grande foco associado a um ninho marsupial. Este achado reforça a importância da espécie no estado de São Paulo, serve de alerta para a vigilância epidemiológica e amplia a área de colonização da espécie no estado de São Paulo.
Asunto(s)
Animales , Panstrongylus , Triatominae , Reduviidae , BrasilRESUMEN
Foram avaliados os efeitos tóxicos do metavanadato de sódio (MV), pentóxido de vanádio (PV) e sulfato de oxovanádio (SV), potenciais fármacos antidiabéticos, em embriões e adultos de zebrafish (Danio rerio). Os embriões foram expostos a concentrações de 10-1000µg/mL para avaliação da CL50 96h e seus efeitos teratogênicos. Os adultos foram expostos a 10 e 20µg/mL dos mesmos compostos para se avaliarem alterações comportamentais relacionadas à exposição química e à mortalidade. A CL50 96h foi de 22,48, 53,62 e 74,14µg/mL para MV, SV e PV, respectivamente. Houve 100% de mortalidade nas concentrações de 400-1000µg/mL dos três compostos. Os efeitos teratogênicos mais observados (P<0,05) nos embriões foram edemas de pericárdio e saco vitelínico. Foram constatados, nos animais adultos expostos aos compostos de vanádio, maior batimento opercular e congestão nos arcos branquiais. A exibição dos comportamentos Flutuar e Descansar nos adultos expostos foi significativa (P<0,05), como também a exibição do comportamento Respiração Aérea. Pode-se concluir que a exposição química aos compostos de vanádio causou efeitos tóxicos em embriões e adultos de zebrafish com alta mortalidade. Diante disso, o seu uso como potencial fármaco antidiabético deve ser mais bem estudado em razão do efeito tóxico dessas substâncias.(AU)
The toxic effects of sodium metavanadate (MV), vanadium pentoxide (PV) and oxovanadium sulfate (SV), potential antidiabetic drug, on embryos and adults of zebrafish (Danio rerio) were evaluated. Embryos were exposed to concentrations of 10-1000µg/mL for evaluation of 96-h LC50 and their teratogenic effects. Adults were exposed to 10 and 20µg/mL of the same compounds to evaluate behavioral changes related to chemical exposure and mortality. The 96-h LC50 were 22.48, 53.62, and 74.14µg/mL for MV, SV, and PV, respectively. Mortality of 100% was observed at the concentrations of 400-1000µg/mL of the three compounds. The teratogenic effects most observed (P<0.05) were pericardial and yolk sac edemas. Adult animals exposed to the vanadium compounds had higher opercular beats and congestion in the gill arches. The exhibition of behaviors Floating and Resting in the exposed adults was significant (P<0.05), as well as the Air breathing behavior. Chemical exposure to vanadium compounds caused toxic effects in embryos and adults of zebrafish with high mortality. In conclusion, its use as a potential antidiabetic drug should be better studied due to the toxic effect.(AU)
Asunto(s)
Animales , Conducta Animal , Factores Biológicos/toxicidad , Compuestos de Vanadio/toxicidad , Peces/fisiología , Investigaciones con EmbrionesRESUMEN
Abstract We report the first known occurrence of Panstrongylus megistus (Burmeister, 1835) (Hemiptera, Reduviidae, Triatominae) in the Metropolitan Region of São Paulo, Brazil. In 2018, adult specimens were sent by residents to the competent authorities and, in the inspection of the property, a large focus associated with a marsupial nest was found. This finding reinforces the importance of the species in the state of São Paulo, serves as an alert for epidemiological surveillance and extends the species colonization area in the state of São Paulo.
Resumo Relatamos a primeira ocorrência de Panstrongylus megistus (Burmeister, 1835) (Hemiptera, Reduviidae, Triatominae) na Região Metropolitana de São Paulo, Brasil. Em 2018, espécimes adultos foram enviados por residentes e a pesquisa na propriedade constatou a presença de um grande foco associado a um ninho marsupial. Este achado reforça a importância da espécie no estado de São Paulo, serve de alerta para a vigilância epidemiológica e amplia a área de colonização da espécie no estado de São Paulo.
RESUMEN
The population of wild animals is regulated by many biotic and abiotic factors, and parasites are a biotic factor that affects the dynamic and density of host populations. From 2002 to 2014, 62 wild animals from the biomes Pantanal, Amazon, and "Cerrado" (or Savanna), which died in attendance in the veterinary hospital or have been road-killed, underwent necropsy for parasitological examination. Overall, 36 species of parasites were identified from 24 host species. Among the parasites, the most prevalent order was Oxyurida (29.1%), followed by Strongylida (20.9%), Spirurida (19.4%), Ascaridida (16.2%), Pentastomida (3.2%), Echinostomida (3.2%), Gygantorhynchia (3.2%), Rhabditida (1.6%), Plagiorchiida (1.6%), and Monilimorfida (1.6%), especially nematodes, which have more biotic potential and is more easily adapted to the environment than other classes. The occurrence of endoparasites was observed more frequently in endothermic than ectothermic animals, and herein is reported eleven new host occurrences for endoparasites in wild animals. The study has contributed to the knowledge on the biodiversity of parasites in wild animals from three biomes in central-western Brazil.(AU)
Populações de animais selvagens são reguladas por diversos fatores bióticos e abióticos, e parasitas são um fator biótico que afetam a dinâmica e a densidade de populações. De 2002 até 2014, 62 animais silvestres provenientes dos biomas Pantanal, Amazônia e Cerrado, que vieram a óbito no atendimento do hospital veterinário ou foram encontrados atropelados em rodovias, foram submetidos à necropsia parasitológica. Ao todo 36 espécies de parasitas foram identificadas em 24 espécies de hospedeiros. Entre os parasitas, a ordem mais prevalente foi Oxyurida (29,1%), seguida por Strongylida (20,9%), Spirurida (19,4%), Ascaridida (16,2%), Pentastomida (3,2%), Echinostomida (3,2%), Gygantorhynchia (3,2%), Rhabditida (1,6%), Plagiorchiida (1,6%) e Monilimorfida (1,6%), destacando-se os nematódeos, por seu maior potencial biótico e facilidade de adaptação ao meio do que as demais classes. A maior ocorrência de endoparasitas foi observada em animais endotérmicos que ectotérmicos, e este estudo registra onze novas ocorrências de hospedeiros para endoparasitas de animais selvagens. O estudo contribui para o conhecimento da biodiversidade de parasitas em animais silvestres dos três biomas do Centro-Oeste do Brasil.(AU)
Asunto(s)
Animales , Factores Abióticos/análisis , Animales Salvajes/parasitología , Factores Bióticos/análisis , Nematodos , Parásitos , Biodiversidad , Conservación de los Recursos Naturales , Ecosistema , Enfermedades Parasitarias en AnimalesRESUMEN
The rat models currently employed for studies of nerve regeneration present distinct disadvantages. We propose a new technique of stretch-induced nerve injury, used here to evaluate the influence of gabapentin (GBP) on nerve regeneration. Male Wistar rats (300 g; n=36) underwent surgery and exposure of the median nerve in the right forelimbs, either with or without nerve injury. The technique was performed using distal and proximal clamps separated by a distance of 2 cm and a sliding distance of 3 mm. The nerve was compressed and stretched for 5 s until the bands of Fontana disappeared. The animals were evaluated in relation to functional, biochemical and histological parameters. Stretching of the median nerve led to complete loss of motor function up to 12 days after the lesion (P<0.001), compared to non-injured nerves, as assessed in the grasping test. Grasping force in the nerve-injured animals did not return to control values up to 30 days after surgery (P<0.05). Nerve injury also caused an increase in the time of sensory recovery, as well as in the electrical and mechanical stimulation tests. Treatment of the animals with GBP promoted an improvement in the morphometric analysis of median nerve cross-sections compared with the operated vehicle group, as observed in the area of myelinated fibers or connective tissue (P<0.001), in the density of myelinated fibers/mm2 (P<0.05) and in the degeneration fragments (P<0.01). Stretch-induced nerve injury seems to be a simple and relevant model for evaluating nerve regeneration.
RESUMEN
Solallum acanthodes. popularmente conhecido como "jurubeba", foi estudada com o objetivo de avaliar suas propriedades antinocicept i vas nos modelos de nociccpção induzida pela I'ormalina e glutamato. Para isto foi utilizado o extrato elanólico dos frutos (EES) da planta. Os resultados apresentaram altos níveis de significância, demonstrando o potencial analgésico de S. acanthodes.
Solanum acanthodes, popularly known as "jurubcba", was studied with the objective to evaluatc its antinocíccptivc propcrties In lhe models aI' fonnalin-induced nociceptive and glutamate. For this lhe cthanolic extract of lhe fruits (E.ES) of the plant was used. The results had prescnlcd high lcvcls 01' significance, demonstrating lhe analgesic potcntial of S. acanthodes.
RESUMEN
Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the galbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallblader and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03x10(-8) M>propinox 1.25x10(-7) M> verapamil 6.63x10(-6)M> (-) scopolamine-n-butyl1 bromide 5.4x10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antisplasmodic action of the drug involved binding to muscarinic receptors or calciumatagonist sites. The inhibition constant (Ki) of proponix for muscarinic receptors of guinea pig ileum smoth muscle, which contains a mixed M2-M3 receptor population, was 1.6x10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0x10(-4) M, for cardiac receptors (M1) was 1.0x10(-4)M, for receptors (M2) 1.2x10(-6)M and from salivary gland receptors (M3) 1.5x10(-6)M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9x10(-5)M for propinox and 2.2x10(-7)M for verapamil. For the phenylakylamine binding sites Ki were: 5.0x10(-6)M for propinox and 3.5x10(-8)M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2x10(-6)M. The following may be concluded: 1- The antispasmodic activity of propinox in isolated human galbladder was was comparatively less potent than of atropine and more potent than those verapamil and (-) scopolamine-n-butyl bromide. 2- Propinox showed binding to muscarinic and calcium receptors that can be related to its antisplasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.- The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.
Asunto(s)
Humanos , Vesícula Biliar/efectos de los fármacos , Parasimpatolíticos/farmacología , Receptores Muscarínicos , Atropina/farmacología , Sitios de Unión , Bromuro de Butilescopolamonio/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Carbacol/farmacología , Agonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacología , Verapamilo/farmacologíaRESUMEN
Postnatal depression is a significant problem affecting 10-15 percent of mothers in many countries and has been the subject of an increasing number of publications. Prenatal depression has been studied less. The aims of the present investigation were: 1) to obtain information on the prevalence of prenatal and postnatal depression in low income Brazilian women by using an instrument already employed in several countries, i.e., the Edinburgh Postnatal Depression Scale (EPDS); 2) to evaluate the risk factors involved in prenatal and postnatal depression in Brazil. The study groups included 33 pregnant women interviewed at home during the second and third trimesters of pregnancy, and once a month during the first six months after delivery. Questions on life events and the mother's relationship with the baby were posed during each visit. Depressed pregnant women received less support from their partners than non-depressed pregnant women (36.4 vs 72.2 percent, P<0.05; Fisher exact test). Black women predominated among pre- and postnatally depressed subjects. Postnatal depression was associated with lower parity (0.4 ñ 0.5 vs 1.1 ñ 1.0, P<0.05; Student t -test). Thus, the period of pregnancy may be susceptible to socio-environmental factors that induce depression, such as the lack of affective support from the partner. The prevalence rate of 12 percent observed for depression in the third month postpartum is comparable to that of studies from other countries
Asunto(s)
Humanos , Femenino , Embarazo , Adulto , Depresión , Depresión Posparto , Pobreza , Brasil , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Prevalencia , Factores de RiesgoRESUMEN
This study conducted to compare the analgesic action of Lysine Clonixinate (LC) vs Paracetamol/Codeine association (PC) in the treatment of postepisiotomy pain in primiparae women: 131 primiparous patients with moderate-to-severe postepisiotomy pain were enrolled in a double blind dummy design study and randomly allocated to either treatment with fixed doses of LC 125 mg or Paracetamol 500 mg+Codeine 30 mg 6 qh during 24 hours. Intensity of spontaneous pain and pain on walking was assessed according to a visual analog scale (VAS) and patientÝs assessment before receiving treatment and after 1, 2, 6 and 24 hours. Intensity of spontaneous pain was reduced in 24 hours from 4.28+2.11 to 1.73+1.46 (P<0.0001) in the LC group and from 4.78+2.08 to 1.90+1.72 in the PC- treated group (p<0.0001); with no significant differences between treatments. 54 percent of the patients treated with LC and 55 percent of those receiving PC showed onset of analgesic action 30 minutes following dose administration. PatientÝs final global assessment revealed that 95 percent of LC-treated patients and 96 percent of the PC group showed total or partial pain relief during the first treatment day. No sleep disturbances were seen during the night in 75 percent of patients. Only one patient reveiving LC showed nausea not requiring treatment discontinuation. It is concluded that both treatments are equally effective to relieve moderate-to-severe postepisiotomy pain.
Asunto(s)
Femenino , Humanos , Adulto , Acetaminofén/uso terapéutico , Analgésicos/uso terapéutico , Clonixina/uso terapéutico , Codeína/uso terapéutico , Episiotomía/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Acetaminofén , Análisis de Varianza , Clonixina , Codeína , Método Doble Ciego , Factores de TiempoRESUMEN
The efficacy tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post-and menstrual periods: possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptons. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24,24/24 and only 2 out of the patients, respectively. Concomitant symptons consisted in headache (12), mastalgia (14) and disconfort (12). Results were obtained by averaging the data from the 3 tratment periods with each drug. Menstrual pain was reduced from 2.9 + 0.7 to 1.9 + 0.7 with P administration and to 0.66 + 0.4 with the administration of LC, a highly significant difference between tratments (p<0.0001). Premenstrual pain was reduced nonsignificantly from 0.79 per cent to 0.58 per cent with P administration and significantly to 0.29 per cent with administration of LC (p<0.001). Intramenstrual pain affection all patients at baseline was reduced significantly by 8 per cent with P and also significantly by 50 per cent with LC p<0.001). No differences were encontered in encomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p<0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported.
Asunto(s)
Adulto , Humanos , Femenino , Inhibidores de la Ciclooxigenasa/uso terapéutico , Dismenorrea/tratamiento farmacológico , Lisina/uso terapéutico , Ciclo Menstrual/metabolismo , Estudios Cruzados , Método Doble Ciego , Ciclo Menstrual/efectos de los fármacosRESUMEN
Experimental studies in rats have demonstrated that lactating females have blood ethanol levels five times lower than those observed in non-lactating rats. The purpose of the present study was to verify if this phenomenon also occurs in human beings. Five lactating (L) and five control (C) women received, after formal agreement to the experimental procedure, 0.4 g/kg of ethanol as vodka (Stolichnaya, USSR), between 9:00 and 10:15 a.m. Blood and milk samples were collected 10, 20, 40, 60, 90, 150 and 180 min after ethanol ingestion. Ethanol levels in blood and milk were measured by gas chromatography using the head space technique. Results indicated that: time to reach maximal blood levels was significantly longer in the L group (L: 48.0 +/- 10.9, C: 31.2 +/- 16.4 min, means +/- SD), area under the curve was smaller when group L was compared to group C (L: 3821.5 +/- 1240.5, C: 5154.8 +/- 1313.7 mg per cent x min, means +/- SD), ethanol blood levels (mg/dl) at 150 and 180 min were significantly lower in the L group (150: L, 10.5 +/- 5.6; C, 18.7 +/- 6.8; 180: L, 3.9 +/- 2.8; C, 13.2 +/- 6.4, means +/- SD). Concentration of ethanol in milk was similar to concentration in blood. These results indicate the importance of lactation for ethanol pharmacokinetics and raise questions about the pharmacokinetics of other drugs ingested by lactating women
Asunto(s)
Humanos , Femenino , Embarazo , Adulto , Etanol/farmacología , Lactancia/metabolismo , Etanol/sangre , Leche Humana/químicaRESUMEN
Con el fin de evaluar los hallazgos ecocardiográficos en pacientes con calcificación del anillo mitral (CAM) (Fig 1) se estudiaron los ecocardiogramas en modo M de 57 pacientes con diagnóstico de CAM por ese método. Para evaluar la prevalencia en ambos sexos se consideró un grupo de 100 pacientes consecutivos mayores de 50 años derivados para estudio ecocardiográfico. Las mediciones ecocardiográficas se compararon con las de 100 ecocardiogramas normales correspondientes a pacientes de sexo y edad similar. La CAM aislada (CAMA) se presentó más frecuentemente en mujeres que en varones (p <0,01). La CAMA se observó a edad más temprana que la CAM asociada a esclerosis valvular aórtica (EVA) o insuficiencia aórtica (IA) en el sexo femenino (p < 0,01). La edad de pacientes varones con CAMA, CAM e IA, y CAM y EVA fue menor que la de las mujeres, siendo la diferencia estadísticamente significativa en el último caso (p < 0,01). La CAM se presentó en forma aislado en 28% de los casos y asociada a EVA en 47%, a IA en 19%, a estenosis aórtica (EA) en 47% y a enfermedad aórtica (Enf A) en 2%. Las medias del diámetro diastólico del ventrículo izquierdo (DDVI) y de la aurícula izquierda (AI) fueron mayores en los grupos con CAMA, CAM y EVA y CAM e IA en comparación con el grupo control en ambos sexos (p < 0,05). El septum interventricular en diástole (SIVD) fue superior en la CAMA, CAM y EVA, y CAM e IA en comparación con el grupo control pero la diferencia fue estadísticamente significativa sólo en el sexo femenino (p < 0,05). Se hallaron las siguientes alteraciones individuales: aumento de la AI 40%, disminución de la fracción de acortamiento 30%, aumento del DDVI 30%, del SIVD 30%, de la pared posterior en diástole 16% y del ventrículo derecho 4%. Estas alteraciones fueron más frecuentes en los pacientes con CAM asociada a EVA, IA, EA o Enf A que en CAMA
Asunto(s)
Persona de Mediana Edad , Humanos , Masculino , Femenino , Calcinosis/fisiopatología , Enfermedades de las Válvulas Cardíacas/fisiopatología , Ecocardiografía , Válvula Mitral/fisiopatologíaRESUMEN
Se llevó a cabo una experiencia educacional de complementación de las unidades temáticas de Patología con clases teóricas sobre aspectos clínicos dictados por docentes de Medicina Interna. El diseño controlado del estudio permitió verificar en las evaluaciones con pruebas estructuradas sobre Patología una diferencia significativa o favor de los alumnos que participaron en las clases sobre clínica. La experiencia piloto contó con la aceptación y colaboración de docentes y alumnos