10 research outputs found
Perfil dos pacientes colonizados por enterobactérias produtoras de KPC em hospital terciário de Porto Alegre, Brasil
Introdução: Enterobactérias produtoras de carbapenemase do tipo Klebsiella pneumoniae (KPC) são cada vez mais identificadas em pacientes hospitalizados, porém pouco se conhece sobre o perfil e o prognóstico dos pacientes colonizados por elas. Este estudo objetiva avaliar o perfil epidemiológico e a mortalidade total intra-hospitalar dos pacientes colonizados por KPC em um centro de referência.
Métodos: Estudo de coorte retrospectivo em adultos colonizados por KPC em internação clínica de novembro/2012 a março/2013 no Hospital Nossa Senhora da Conceição, Porto Alegre (RS). Foram definidos como colonizados pacientes com exame de rastreio (swab) positivo para bactérias produtoras de KPC durante a internação.
Resultados: Foram incluídos 75 pacientes, sendo 40 homens, com mediana de 52 anos. O tempo desde o início da internação até a positivação do swab apresentou uma mediana e amplitude interquartil de 18 (9-33) dias, com período de internação de 36 (24-56) dias. Foi identificado uso de cateter central em 93%, sondagem vesical de demora 88%, sondagem nasogástrica/nasoentérica 87%, ventilação mecânica 81% e hemodiálise 40%. Dois terços dos pacientes apresentaram pelo menos um evento infeccioso após a colonização. O escore de Charlson (OR 1,53 por cada ponto; IC95% 1,25-1,97) e diálise prévia (OR 4,35; IC95% 1,39-15,37) foram preditores independentes de mortalidade. Óbito ocorreu em 56% dos pacientes (n=42).
Conclusão: Pacientes colonizados por KPC apresentam mortalidade total intra-hospitalar elevada. Comorbidades prévias à colonização foram associadas com mortalidade. O presente estudo não permite definir qual o papel da colonização no desfecho clínico dos pacientes
Les bases moléculaires et cellulaires de la protection conférée par l’antagoniste du récepteur D1 de la dopamine, SCH23390, contre les effets toxiques de la méthamphétamine dans le cerveau de rat
La méthamphétamine (METH) est une drogue stimulante qui peut causer des déficiences des fonctions cognitives et des dommages irréversibles dans le cerveau des utilisateurs. Il est important de comprendre les mécanismes moléculaires de la toxicité de la drogue pour pouvoir développer des traitements pour contrer les effets toxiques de la METH. Plusieurs études dans notre laboratoire et autres ont montré qu’une seule dose élevée de METH (30-40 mg/kg de poids corporel) suffit à endommager l’arborisation terminale des neurones dopaminergiques dans le striatum et le cortex chez les rongeurs, de même qu’elle peut causer l’activation des signaux apoptotiques produits a partir du réticulum endoplasmique (RE) et de la mitochondrie dans le striatum. De ce fait, le but de cette thèse était d’analyser si la dose toxique de 40 mg/kg de METH injectée par faibles doses répétées (4 fois, avec des intervalles de 2 heures), appelée « binge METH », peut aussi causer des stress cellulaires du RE et de la mitochondrie dans le striatum. Des travaux récents ont suggéré que les récepteurs D1 et D2 de la dopamine pourraient être les intermédiaires de l’apoptose des neurones dans le striatum causée par l’administration d’une unique toxique dose de METH. Nous avons alors émis l’hypothèse que les messages cellulaires diriges par la stimulation des récepteurs D1 et D2 de la dopamine pourraient être à l’ origine des effets toxiques du « binge modele ». Le rôle des récepteurs de la dopamine sur l’activation des signaux de l’apoptose a été examiné en utilisant des antagonistes de ces récepteurs. Dans cette dissertation, je donne la preuve que « binge METH » affecte l’expression des immediate early genes de façon différente. Il semble que ces effets soient dépendants de la stimulation du récepteur D1. Un autre volet de cette dissertation a analysé les effets de « binge METH » sur l’expression de gènes impliqués dans la réponse au stress du RE et à l’altération de la fonction de la mitochondrie. Le prétraitement avec l’antagoniste du récepteur D1 de la dopamine, SCH23390, a complètement bloqué l’apparition de ces stress cellulaires après les injections de METH, alors que l’antagoniste du récepteur D2, raclopride, a eu des effets minimes. SCH23390 a aussi bloqué l’effet de METH à causer l’augmentation de la température corporelle des animaux, mais pas raclopride. Cependant, les deux antagonistes ont protégés contre les pertes dans plusieurs marqueurs des neurones de dopamine et sérotonine dans le striatum. De plus, SCH23390, mais non raclopride, a aussi protégé les neurones de sérotonine dans le cortex. Durant mes travaux, j’ai aussi identifié qu’il y a une augmentation de l’ARN messager de activin βA, la protéine TGF-β et Smad2 phosphorylée après les injections de METH. Ces effets sont réduits suite à un prétraitement par SCH23390 ; cependant, raclopride n’a eu aucun effet sur l’expression de TGF-β.En résumé, ces nouvelles données suggèrent que le récepteur D1 joue un rôle prédominant dans la toxicité de la METH.Methamphetamine (METH) is a potent psychostimulant known to cause cognitive abnormalities and neurodegenerative changes in the brains of METH abusers. One approach for developing therapies for METH abuse is to understand the molecular mechanisms of toxicity of the drug. Investigations in our laboratory and elsewhere have shown that single intraperitoneal injections of METH (30-40 mg/kg of body weight) can cause damage to striatal and cortical monoaminergic systems and induce neuronal apoptosis in the striatum of rodents via activation of endoplasmic reticulum (ER) and mitochondrial death pathways. Hence, the purpose of this thesis was to investigate if toxic binge METH injections can cause ER- and mitochondria-induced stress in the rat striatum. Recent studies have suggested that dopamine (DA) D1 and D2 receptors might mediate neuronal apoptosis in the striatum after single toxic METH doses. We therefore hypothesized that signaling through these two types of DA receptors might activate toxic effects of the binge METH regimen. The role of DA D1 or D2 receptors in METH-induced cell death pathways was thus examined by using pharmacological inhibitors of these receptors. In this dissertation, I report that binge METH regimen caused differential changes in immediate early genes (IEGs) that are known to influence synaptic changes in the brain. METH-induced changed in the expression of the IEGs were dependent on DA D1 receptor stimulation. The second study examined the effects of binge METH on the expression of ER stress- and mitochondrial dysfunction-responsive genes. Pretreatment with the DA D1 receptor antagonist, SCH23390, caused complete inhibition of METH-induced ER and mitochondrial stresses whereas the DA D2 receptor antagonist, raclopride, provided only partial blockade. SCH23390 also blocked METH-induced hyperthermia whereas raclopride failed to do so. Interestingly, both antagonists attenuated METH-induced dopaminergic and serotonergic deficits in the striatum. Moreover, SCH23390 but not raclopride blocked METH-induced serotonergic deficits in cortical tissues. I also found that METH treatment induced upregulation of activin βA mRNA, increased TGF-β and phosphorylated Smad2 proteins in the rat striatum. SCH23390 pretreatment completely blocked all these effects whereas raclopride did not block METH-induced increases in TGF-β expression
Perfil dos pacientes colonizados por enterobactérias produtoras de KPC em hospital terciário de Porto Alegre, Brasil
Introdução: Enterobactérias produtoras de carbapenemase do tipo Klebsiella pneumoniae (KPC) são cada vez mais identificadas em pacientes hospitalizados, porém pouco se conhece sobre o perfil e o prognóstico dos pacientes colonizados por elas. Este estudo objetiva avaliar o perfil epidemiológico e a mortalidade total intra-hospitalar dos pacientes colonizados por KPC em um centro de referência. Métodos: Estudo de coorte retrospectivo em adultos colonizados por KPC em internação clínica de novembro/2012 a março/2013 no Hospital Nossa Senhora da Conceição, Porto Alegre (RS). Foram definidos como colonizados pacientes com exame de rastreio (swab) positivo para bactérias produtoras de KPC durante a internação. Resultados: Foram incluídos 75 pacientes, sendo 40 homens, com mediana de 52 anos. O tempo desde o início da internação até a positivação do swab apresentou uma mediana e amplitude interquartil de 18 (9-33) dias, com período de internação de 36 (24-56) dias. Foi identificado uso de cateter central em 93%, sondagem vesical de demora 88%, sondagem nasogástrica/nasoentérica 87%, ventilação mecânica 81% e hemodiálise 40%. Dois terços dos pacientes apresentaram pelo menos um evento infeccioso após a colonização. O escore de Charlson (OR 1,53 por cada ponto; IC95% 1,25-1,97) e diálise prévia (OR 4,35; IC95% 1,39-15,37) foram preditores independentes de mortalidade. Óbito ocorreu em 56% dos pacientes (n=42).Conclusão: Pacientes colonizados por KPC apresentam mortalidade total intra-hospitalar elevada. Comorbidades prévias à colonização foram associadas com mortalidade. O presente estudo não permite definir qual o papel da colonização no desfecho clínico dos pacientes
Osmoregulators in Hymenaea courbaril and Hymenaea stigonocarpa under water stress and rehydration
The objective of this work was to evaluate the effect of different water deficiency and rehydration levels on the concentrations of osmoregulators in two plant species (Hymenaea courbaril and H. Stigonocarpa) in the Amazon. We adopted a 2 × 5 × 5 factorial system, referring to 2 species (H. courbaril and H. stigonocarpa) and 5 stages of hydration and rehydration. The five hydration and rehydration stages were established in: (1) Control treatment E0; (2) Plants with 13 days of stress after incubation—E13; (3) Plants with 26 days of stress E26; (4) The plants that were established after 26 days after incubation and rehydrated for two days (RD2); (5) rehydrated for two days (RD4). The plants that were established after 26 days after incubation and rehydrated for four days. The experiment totaled fifty young plants with five replicates. Biochemical measurements were performed at the beginning of the experiment (E0) at 13 (E13) and 26 (E26) days after the water stress, in which the plants were rehydrated, repeating the analyses after two (RD2) and four (RD4) days. Both species increased the sucrose concentration by 18%, with a decrease of 52% in starch content. The RD4 time presented the highest mean starch concentration (0.19 mmol g−1 of the residue for H. courbaril and 0.27 mmol g−1 of residue for H. stigonocarpa). Increased proline concentrations were recorded for controls until RD2 for both species. For glycine betaine, the highest increases in treatments E26 and RD2 were observed for the H. courbaril species. Our rehydration period was not sufficient for total recovery of pre-stress concentrations of all studied solutes
Increased interregional virus exchange and nucleotide diversity outline the expansion of chikungunya virus in Brazil
Abstract The emergence and reemergence of mosquito-borne diseases in Brazil such as yellow fever, zika, chikungunya, and dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus across the country since its first detection in 2014 in Northeast Brazil. In this work, we carried out on-site training activities in genomic surveillance in partnership with the National Network of Public Health Laboratories that have led to the generation of 422 chikungunya virus genomes from 12 Brazilian states over the past two years (2021–2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersal dynamics of the chikungunya virus East-Central-South-African lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C > T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving the genetic diversity of the chikungunya virus in Brazil
ATLANTIC ANTS: a data set of ants in Atlantic Forests of South America
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