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Genomics ; 112(3): 2489-2498, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32027956


The acquisition of UCP1-mediated non-shivering thermogenesis (NST) was an important event during the evolution of mammals. Here, we assessed the thermogenic neofunctionalization that occurred in the mammalian UCP1, by performing detailed comparative evolutionary genomics analyses (including phylogenetic and selection analyses) of the UCP family members across all major vertebrate classes. Heterogeneously distributed positive selection signatures were found in several UCPs, being preferably located in the mitochondrial matrix domains. Additionally, comparisons with non-mammalian orthologs showed increased evolutionary rates of the mammalian UCP1, not observable in the phylogenetically related UCP2 and UCP3 paralogs. Also, parallel signatures of episodic positive selection (ω > 1) were found in the ancestral branches of both Glires (rodents and lagomorphs) and Afroinsectivores (afrosoricids and macroscelids), underlining the importance of the UCP1 thermogenic activity in these mammalian groups. Finally, we hypothesize that the independent positive selection events that occurred in these two lineages resulted in two UCP1-mediated NST approaches, namely the cold acute response in the Glires and the reproduction success enhancement in the Afroinsectivores.

Life Sci ; 234: 116738, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398418


AIMS: Oxidative stress has been linked to the development and progression of diabetic nephropathy (DN). The present study evaluated whether the dipeptidyl peptidase-4 inhibitor sitagliptin attenuates glomerular lesions and oxidative stress evoked by chronic hyperglycemia, by a mechanism independent of insulin secretion and glycemia normalization. MAIN METHODS: A rat model of DN caused by streptozotocin injection was established and the effects of sitagliptin (5 mg/kg/day) were evaluated after two weeks of treatment. KEY FINDINGS: Sitagliptin treatment did not change body weight, glycemic and lipid profiles. However, histopathological observation revealed that sitagliptin attenuates diabetes-induced glomerular lesions on diabetic rats. Sitagliptin also ameliorated the increase in DPP-4 content and promoted the stabilization of GLP-1 in the diabetic kidney. Furthermore, sitagliptin treatment significantly attenuated the increase of free-radical formation and the decrease of antioxidant defenses, attenuating therefore the oxidative stress in the kidneys of diabetic animals. SIGNIFICANCE: The results suggest that sitagliptin treatment alleviates kidney oxidative stress in type 1 diabetic rats, which could play a key role in reducing the progression of DN.

Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfato de Sitagliptina/uso terapêutico , Animais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Masculino , Ratos , Ratos Wistar , Fosfato de Sitagliptina/farmacologia
Trends Cell Biol ; 29(10): 835-847, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31358412


Connexin43 (Cx43) is commonly associated with direct cell-cell communication through gap junctions (GJs). However, recent groundbreaking studies have challenged this dogma, implicating Cx43 in other biological processes, such as transcription, metabolism, autophagy, and ion channel trafficking. How Cx43 participates in these processes remains largely unknown, although its high turnover rate, capacity to bind to myriad proteins, and the discovery of truncated isoforms of Cx43, ascribe to this protein unanticipated roles in chief processes that require fine-tuned regulation. Accordingly, Cx43 can be regarded as a central integrative hub to which diverse cues converge to be processed in a concerted manner. In this review, we examine the noncanonical roles of Cx43 and discuss the implications of these functions in human diseases and future therapeutic strategies.

Comput Biol Chem ; 83: 107089, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31323386


Fluorescent proteins have been applied in a wide variety of fields ranging from basic science to industrial applications. Apart from the naturally occurring fluorescent proteins, there is a growing interest in genetically modified variants that emit light in a specific wavelength. Genetically modifying a protein is not an easy task, especially because the exchange of one residue by other has to achieve the desired property while maintaining protein stability. To help in the choice of residue exchange, computational methods are applied to predict function and stability of proteins. In this work we have prepared a dataset composed by 109 fluorescent proteins and tested four classical supervised classification algorithms: artificial neural networks (ANNs), decision trees (DTs), support vector machines (SVMs) and random forests (RFs). This is the first time that algorithms are compared in this task. Results of comparing the algorithm's performance shows that DT, SVM and RF were significantly better than ANNs, and RF was the best method in all the scenarios. However, the interpretability of DTs is highly relevant and can provide important clues about the mechanisms involved in protein color emission. The results are promising and indicate that the use of in silico methods can greatly reduce the time and cost of the in vitro experiments.

Algoritmos , Cor , Proteínas Luminescentes/química , Árvores de Decisões , Proteínas Luminescentes/metabolismo , Estabilidade Proteica , Máquina de Vetores de Suporte
Lifestyle Genom ; 12(1-6): 1-9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31352438


BACKGROUND/AIMS: Metabolic syndrome (MetS) comprises a cluster of physiological and anthropometric abnormalities. MetS has been linked to lactose intolerance (LI). The aim of this study was to compare the sensitivity and specificity to detect LI using 2 different tests: (1) a genetic test and (2) an oral lactose tolerance test (OLTT). METHODS: Two hundred and fifty-four MetS patients, ≥20 years of age, of both genders, were recruited for this comparative study. Nine single nucleotide polymorphisms (SNPs) were selected for genetic investigation: rs182549and rs4988235(both considered "gold standard"); rs56064699; rs148142676; rs562211644; rs59533246; rs3754689; rs2278544,and rs10552864(as potential novel SNPs). Sensitivity and specificity, as well as positive and negative predictive values, were calculated for each genotype using WINPEPI version 11.65. Differences between positive and negative OLTT groups were considered statistically significant when p ≤ 0.05. RESULTS: Among the selected SNPs, only rs182549(p < 0.001) and rs4988235(p < 0.001) gave similar results compared to an OLTT. The sensitivity of both SNPs to detect LI was 87 and 86%, and specificity was 83 and 82.5%, respectively. CONCLUSION: Genetic tests using rs182549and rs4988235SNPs showed high agreement with OLTT. These genetic tests may be a good option to replace OLTT in MetS patients.

Pesqui. prát. psicossociais ; 14(2): 1-12, abr.-jun. 2019.
Artigo em Português | LILACS-Express | ID: biblio-1012730


A partir de narrativas de cenas cotidianas e fragmentos de casos clínicos, discutimos as implicações da permeabilidade entre um Centro de Atenção Psicossocial III (Caps) e o território para a estruturação do cuidado, salientando aspectos que favorecem ou dificultam seu funcionamento como um serviço aberto. Verificamos que, apesar de algumas contradições, ocorre uma ruptura com a noção de fechamento no que concerne à espacialidade, à organização do trabalho e à produção das relações de cuidado. Nesse contexto, a interlocução com territórios marcados por precariedades materiais e violências estruturais interrogam a instituição, seus supostos saberes sobre a loucura e suas formas de tratamento e convidam os trabalhadores a sair de seus muros, buscando construir com os usuários saídas sempre singulares para o que os aflige em seus enlaçamentos com o mundo.

From the narratives of daily scenes and fragments of clinical cases, we discuss the implications of permeability between a Psychosocial Care Center III (Caps) and the territory for structuring care, highlighting aspects that favor or hinder its functioning as an open service. We find that, despite some contradictions, there is a rupture with the notion of closure regarding spatiality, the organization of work and the production of care relations. In this context, the interlocution with territories marked by material precarities and structural violence question the institution, its supposed knowledge about madness and its forms of treatment and invite workers to leave their walls, seeking to build with the users always unique outputs for what afflicts them in their entanglements with the world.

A partir de narrativas de escenas cotidianas y fragmentos de casos clínicos, discutimos las implicaciones de la permeabilidad entre un Centro de Atención Psicosocial III (Caps) y el territorio para la estructuración del cuidado, destacando aspectos que favorecen o dificultan su funcionamiento como un servicio abierto. Verificamos que, a pesar de algunas contradicciones, ocurre una ruptura con la noción de cierre en lo que concierne a la espacialidad, a la organización del trabajo ya la producción de las relaciones de cuidado. En este contexto, la interlocución con territorios marcados por precariedades materiales y violencias estructurales interroga a la institución, sus supuestos saberes sobre la locura y sus formas de tratamiento e invita a los trabajadores a salir de sus muros, buscando construir con los usuarios salidas siempre singulares para lo que los aflige en sus enlazados con el mundo.

PLoS One ; 14(5): e0217391, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31120961


The study aimed to evaluate the histopathological characteristics of renal lesions in chronically infected sheep and with low titers of anti-Leptospira antibodies from a slaughterhouse. In the serological analysis, 24.74% (48/194) presented seroreactivity with a titer equal to or greater than 100. Among these seroreactive sheep, titers of 100 were predominant (58.33%, 28/48), with the highest titer being 1,600 (2.08%, 1/48). Serogroup Sejroe (sv. Hardjo) was the most frequent at 35.42% (17/48). Leptospiral DNA was verified in 4.12% (8/194) of the kidney samples tested, and no urine sample was positive. All the samples corresponded to the pathogenic species L. interrogans. The eight amplicons with 202-nucleotides were identical with two mismatches (presented 100% of identity) using the PCR targeting to secY gene. Histological sections of PCR-positive kidneys were submitted to direct detection by the anti-LipL32 immunohistochemistry (IHC) technique. The Leptospira spp. antigen was evident in 62.5% (5/8) of the kidneys. Positive staining was observed in the cytoplasm of tubular cells and in the form of brownish aggregates that adhered to tubular epithelial cells and projected into the lumen. Inflammatory lymphoplasmacytic infiltrate, ranging from mild to moderate, with multifocal distribution, was the predominant finding in seroreactive animals (33.33%, 16/48). The demonstration of the leptospiral antigen lining the renal tubules through IHC of naturally infected sheep confirmed by PCR characterizes renal colonization in a species with the presence of histological changes compatible with leptospirosis.

Leptospira interrogans , Leptospirose/veterinária , Doenças dos Ovinos/microbiologia , Carneiro Doméstico/microbiologia , Matadouros , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Infecções Assintomáticas , Brasil , Doença Crônica , DNA Bacteriano/genética , Reservatórios de Doenças/microbiologia , Reservatórios de Doenças/veterinária , Rim/microbiologia , Rim/patologia , Leptospira interrogans/genética , Leptospira interrogans/imunologia , Leptospira interrogans/patogenicidade , Leptospirose/microbiologia , Leptospirose/patologia , Sorogrupo , Ovinos , Doenças dos Ovinos/patologia
BMC Med Genet ; 20(1): 64, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035956


BACKGROUND: GATA2 is a transcription factor that is a critical regulator of gene expression in hematopoietic cells. GATA2 deficiency presents with multi-lineage cytopenia, mycobacterial, fungal and viral infections. Patients with GATA2 mutation have a high risk of developing myelodysplastic syndrome or acute myeloid leukemia. CASE PRESENTATION: We described a 43 years-old white male with 20-year follow-up of autoimmune and thrombotic phenomena, hypothyroidism, disseminated refractory Mycobacterium kansasii infection and MonoMAC syndrome. GATA2 c.1061 C > T; p.T354 M mutation was identified after he progressed from myelodysplastic pancytopenia to refractory anemia with excess blasts type II. His relatives were also investigated and he underwent unsuccessful haematopoietic stem cell transplantation. We discuss the clinical features, genetic diagnosis and treatment of this immunodeficiency disorder. CONCLUSIONS: This case illustrates the challenge how a multidisciplinary disease should be handle. Once usual causes of immunodeficiency were excluded, clinicians should considerGATA2 deficiency in patients with myelodysplasia and long-standing Mycobacterium kansasii infection.

Deficiência de GATA2/genética , Fator de Transcrição GATA2/genética , Mutação , Infecções por Micobactéria não Tuberculosa/genética , Infecções por Micobactéria não Tuberculosa/microbiologia , Mycobacterium kansasii/isolamento & purificação , Síndromes Mielodisplásicas/genética , Adulto , Antibacterianos/uso terapêutico , Humanos , Masculino , Infecções por Micobactéria não Tuberculosa/complicações , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico
Curr Top Med Chem ; 19(11): 914-926, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31072293


BACKGROUND: PIM-1 is a kinase which has been related to the oncogenic processes like cell survival, proliferation, and multidrug resistance (MDR). This kinase is known for its ability to phosphorylate the main extrusion pump (ABCB1) related to the MDR phenotype. OBJECTIVE: In the present work, we tested a new mechanistic insight on the AZD1208 (PIM-1 specific inhibitor) under interaction with chemotherapy agents such as Daunorubicin (DNR) and Vincristine (VCR). MATERIALS AND METHODS: In order to verify a potential cytotoxic effect based on pharmacological synergism, two MDR cell lines were used: Lucena (resistant to VCR) and FEPS (resistant to DNR), both derived from the K562 non-MDR cell line, by MTT analyses. The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123. Furthermore, we performed a molecular docking simulation to delve into the molecular mechanism of PIM-1 alone, and combined with chemotherapeutic agents (VCR and DNR). RESULTS: Our in vitro results have shown that AZD1208 alone decreases cell viability of MDR cells. However, co-exposure of AZD1208 and DNR or VCR reverses this effect. When we analyzed the ABCB1 activity AZD1208 alone was not able to affect the pump extrusion. Differently, co-exposure of AZD1208 and DNR or VCR impaired ABCB1 activity, which could be explained by compensatory expression of abcb1 or other extrusion pumps not analyzed here. Docking analysis showed that AZD1208 is capable of performing hydrophobic interactions with PIM-1 ATP- binding-site residues with stronger interaction-based negative free energy (FEB, kcal/mol) than the ATP itself, mimicking an ATP-competitive inhibitory pattern of interaction. On the same way, VCR and DNR may theoretically interact at the same biophysical environment of AZD1208 and also compete with ATP by the PIM-1 active site. These evidences suggest that AZD1208 may induce pharmacodynamic interaction with VCR and DNR, weakening its cytotoxic potential in the ATP-binding site from PIM-1 observed in the in vitro experiments. CONCLUSION: Finally, the current results could have a pre-clinical relevance potential in the rational polypharmacology strategies to prevent multiple-drugs resistance in human leukemia cancer therapy.

Compostos de Bifenilo/farmacologia , Resistência a Múltiplos Medicamentos , Leucemia Eritroblástica Aguda/tratamento farmacológico , Leucemia Eritroblástica Aguda/enzimologia , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Tiazolidinas/farmacologia , Compostos de Bifenilo/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia Eritroblástica Aguda/patologia , Conformação Molecular , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Tiazolidinas/química , Células Tumorais Cultivadas
Rev. biol. trop ; 67(1): 1-10, Jan.-Mar. 2019. graf
Artigo em Inglês | LILACS-Express | ID: biblio-1041889


Abstract Phyllomedusa azurea is a frog species well distributed geographically in South America, including Brazilian biomes as Pantanal and Cerrado. Compared with other anurans from the Phyllomedusinae family, there are few reports on the bioactive potential of skin-derived molecules from this species. In this perspective, the aim of the present study was to evaluate the in vitro antibacterial activity of skin secretion of P. azurea by detection of Minimum Inhibitory Concentration (MIC) of the growth of bacterial indicator strains and to determine if occurs a changing in the bacterial cell envelope permeability. The MIC determination was carried out by the microdilution plate method. The absorbance was measured and analyzed statistically using the t-test to compare two groups (0.05 % of significance). The impact of the crude extract on cell envelope permeability of Staphylococcus aureus ATCC 25923 was conducted by the crystal violet assay, and the absorbance was measured spectrophotometry followed by the calculation of the crystal violet uptake percentage. The specific MIC for S. aureus ATCC 25923 and Escherichia coli ATCC 25922 was 31.25 µg/mL, while for Bacillus subtilis ATCC 6633 was 125 µg/mL and Pseudomonas aeruginosa ATCC 27853 was 250 µg/mL. The treatment with crescent concentrations of frog skin secretion increased the crystal violet uptake by S. aureus ATCC 25923 cells, suggesting an action on the cell plasma membrane. The results demonstrated that the skin secretion of P. azurea presents antibacterial activity and merit further investigations to characterize the bioactive molecules.

Resumen P. azurea es una especie de rana bien distribuida geográficamente en América del Sur, que incluye biomas brasileños como Pantanal y Cerrado. En comparación con otros anuros de Phyllomedusinae, existen pocos informes sobre el potencial bioactivo de las moléculas derivadas de la piel de esta especie. En esta perspectiva, el objetivo del presente estudio fue evaluar la actividad antibacteriana in vitro de la secreción de la piel de P. azurea mediante la detección de la Concentración Inhibitoria Mínima (CIM) del crecimiento de cepas indicadoras bacterianas y determinar si ocurre un cambio en la permeabilidad de la envoltura celular bacteriana. La determinación de MIC se llevó a cabo mediante el método de la placa de microdilución. La absorbancia se midió y se analizó estadísticamente mediante la prueba t para comparar dos grupos (0.05 de significancia). El impacto del extracto crudo sobre la permeabilidad de la envoltura celular de Staphylococcus aureus ATCC 25923 se realizó mediante el ensayo de cristal violeta, y se midió la absorbancia mediante espectrofotometría seguida del cálculo del porcentaje de absorción de violeta cristal. La CIM específica para S. aureus ATCC 25923 y Escherichia coli ATCC 25922 fue 31.25 μg / ml, mientras que para Bacillus subtilis ATCC 6633 de 125 μg / ml y Pseudomonas aeruginosa ATCC 27853 de 250 μg / ml. El tratamiento con concentraciones crecientes de secreción de piel de rana aumentó la absorción de violeta cristal por las células de S. aureus ATCC 25923, sugiriendo una acción sobre la membrana plasmática de la célula. Los resultados demostraron que la secreción de la piel de P. azurea presenta actividad antibacteriana y amerita más investigaciones para caracterizar las moléculas bioactivas.

Environ Sci Pollut Res Int ; 26(8): 8280-8288, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30706268


Triphenyltin (TPT) is an organotin compound (OT), primarily used in agriculture and in the composition of antifouling paints for ships worldwide. Studies have showed its effects as an endocrine disrupter in several organisms by preventing enzymatic expression and causing reproductive toxicity. This study aimed to evaluate the effects of exposure to TPT, via breastfeeding, on reproductive physiology in the Calomys laucha species. The experimental design was compound of five groups, two controls and three with different doses of TPT. Moreover, females were exposed by gavage to the TPT for 20 days, from the 1st day postpartum to the 21st postnatal day (PND). Then, the pups were euthanized and the kinetics, organelles, and biochemistry of the sperm were evaluated. The results presented a reduction in total motility in the groups exposed to TPT. Regarding cellular organelles analysis, a loss in membrane integrity was evidenced; the functionality of mitochondria showed diminution followed by increased acrosome reaction. In conclusion, the TPT causes alteration of the reproductive parameters, decreasing the activity and sperm quality in individuals exposed in the breastfeeding phase.

Arvicolinae/fisiologia , Compostos Orgânicos de Estanho/toxicidade , Espermatozoides/efeitos dos fármacos , Animais , Ecotoxicologia/métodos , Disruptores Endócrinos/toxicidade , Feminino , Lactação , Masculino , Reprodução/efeitos dos fármacos , Espermatozoides/patologia
Toxicology ; 411: 81-92, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30339824


In the present study, the molecular docking mechanism based on pharmacodynamic interactions between the ligands AZD1208 and recognized chemotherapy agents (Vincristine and Daunorubicin) with human ATP-binding cassette (ABC) transporters (ABCB1) was investigated. For the first time, were combined an in silico approaches like molecular docking and ab initio computational simulation based on Density Functional Theory (DFT) to explain the drug-drug interaction mechanism of aforementioned chemotherapy ligands with the transmembrane ligand extrusion binding domains (TMDs) of ABCB1. In this regard, the theoretical pharmacodynamic interactions were characterized by using the Gibbs free energy (FEB, kcal/mol) from the best ABCB1-ligand docking complexes. The molecular docking results pointing that for the three chemotherapy ABCB1-ligand complexes are mainly based in non-covalent hydrophobic and hydrogen-bond interactions showing a similar toxicodynamic behavior in terms of strength of interaction (FEB, kcal/mol) and very close free binding energies when compared with the FEB-values of the ABCB1 specific-inhibitor (Rhodamine B) = -6.0 kcal/mol used as theoretical docking control to compare with FEB (AZD1208-ABCB1) ∼ FEB (Vincristine-ABCB1) ∼ FEB (Daunorubicin-ABCB1) -6.2 kcal/mol as average. Ramachandran plot suggests that the 3D-crystallographic structure from ABCB1 transporter can be efficiently-modeled with conformationally-favored Psi versus Phi dihedral angles for all key TMDs-residues. Though, the results of DFT-simulation corroborate the existence of drug-drug interaction between (AZD1208/Vincristine) > (AZD1208/Daunorubicin). These theoretical pieces of evidence have preclinical relevance potential in the design of the new drugs to understand the polypharmacology influence in the molecular mechanism of multiple-drugs resistance, contributing with a higher success in chemotherapy and prognosis of cancer patients.

Antibióticos Antineoplásicos/toxicidade , Antineoplásicos Fitogênicos/toxicidade , Compostos de Bifenilo/toxicidade , Daunorrubicina/toxicidade , Inibidores de Proteínas Quinases/toxicidade , Transporte Proteico/efeitos dos fármacos , Tiazolidinas/toxicidade , Vincristina/toxicidade , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/efeitos dos fármacos , Sítios de Ligação/efeitos dos fármacos , Linhagem Celular Tumoral , Teoria da Densidade Funcional , Interações de Medicamentos , Humanos , Ligantes , Conformação Molecular , Simulação de Acoplamento Molecular
Genomics ; 111(6): 1720-1727, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30508561


The Harderian gland is a cephalic structure, widely distributed among vertebrates. In snakes, the Harderian gland is anatomically connected to the vomeronasal organ via the nasolacrimal duct, and in some species can be larger than the eyes. The function of the Harderian gland remains elusive, but it has been proposed to play a role in the production of saliva, pheromones, thermoregulatory lipids and growth factors, among others. Here, we have profiled the transcriptomes of the Harderian glands of three non-front-fanged colubroid snakes from Cuba: Caraiba andreae (Cuban Lesser Racer); Cubophis cantherigerus (Cuban Racer); and Tretanorhinus variabilis (Caribbean Water Snake), using Illumina HiSeq2000 100 bp paired-end. In addition to ribosomal and non-characterized proteins, the most abundant transcripts encode putative transport/binding, lipocalin/lipocalin-like, and bactericidal/permeability-increasing-like proteins. Transcripts coding for putative canonical toxins described in venomous snakes were also identified. This transcriptional profile suggests a more complex function than previously recognized for this enigmatic organ.

Rev. bras. parasitol. vet ; 27(4): 562-569, Oct.-Dec. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-977926


Abstract Infection by the acantocephalan Neoechinorhynchus buttnerae is considered one of most important concerns for tambaqui fish (Colossoma macropomum ) production. Treatment strategies have been the focus of several in vivo studies; however, few studies have been undertaken on in vitro protocols for parasite maintenance. The aim of the present study was to develop the best in vitro culture condition for N. buttnerae to ensure its survival and adaptation out of the host to allow for the testing of substances to be used to control the parasite. To achieve this, parasites were collected from naturally infected fish and distributed in 6-well culture plates under the following treatments in triplicate: 0.9% NaCl, sterile tank water, L-15 Leibovitz culture medium, L-15 Leibovitz + agar 2% culture medium, RPMI 1640 culture medium, and RPMI 1640 + agar 2% culture medium. The plates containing the parasites were maintained at 24 °C, 28 °C, and 32 °C. The RPMI 1640 + agar 2% culture medium showed the best survival of 24 days at 24 °C. No body alterations such as swollen parasites, body deformation, dehydration and hardening were observed in the RPMI 1640 + 2% culture medium.

Resumo A infecção pelo acantocéfalo Neoechinorhynchus buttnerae é considerada uma das preocupações mais importantes para produção de tambaqui (Colossoma macropomum). Estratégias de tratamento têm sido o foco de vários estudos in vivo ; entretanto, poucos estudos foram realizados em protocolos in vitro para manutenção do parasito. O objetivo deste estudo foi desenvolver a melhor condição de cultura in vitro para N. buttnerae para garantir sua sobrevivência e adaptação fora do hospedeiro, a ser utilizado para teste com substâncias no controle do parasito. Para isso, os parasitos foram coletados de peixes naturalmente infectados e distribuídos em placas de cultura de 6 poços sob os seguintes tratamentos em triplicata: 0.9% NaCl, água estéril do tanque, meio de cultura L-15 Leibovitz, meio de cultura L-15 Leibovitz + ágar 2%, meio de cultura RPMI 1640, e meio de cultura RPMI 1640 + ágar 2%. As placas contendo os parasitos foram mantidos a 24 °C, 28 °C, e 32 °C. O meio de cultura RPMI 1640 + ágar 2% apresentou a melhor sobrevivência de 24 dias a 24 °C. Nenhuma alteração corporal tais como inchaço dos parasitos, deformação corporal, desidratação e endurecimento foram observados no meio de cultura RPMI 1640 + ágar 2%.

Rev Bras Parasitol Vet ; 27(4): 562-569, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30462824


Infection by the acantocephalan Neoechinorhynchus buttnerae is considered one of most important concerns for tambaqui fish (Colossoma macropomum ) production. Treatment strategies have been the focus of several in vivo studies; however, few studies have been undertaken on in vitro protocols for parasite maintenance. The aim of the present study was to develop the best in vitro culture condition for N. buttnerae to ensure its survival and adaptation out of the host to allow for the testing of substances to be used to control the parasite. To achieve this, parasites were collected from naturally infected fish and distributed in 6-well culture plates under the following treatments in triplicate: 0.9% NaCl, sterile tank water, L-15 Leibovitz culture medium, L-15 Leibovitz + agar 2% culture medium, RPMI 1640 culture medium, and RPMI 1640 + agar 2% culture medium. The plates containing the parasites were maintained at 24 °C, 28 °C, and 32 °C. The RPMI 1640 + agar 2% culture medium showed the best survival of 24 days at 24 °C. No body alterations such as swollen parasites, body deformation, dehydration and hardening were observed in the RPMI 1640 + 2% culture medium.

Acantocéfalos/crescimento & desenvolvimento , Temperatura Ambiente , Animais , Caraciformes/parasitologia , Meios de Cultura
Pharmaceuticals (Basel) ; 11(2)2018 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-29734752


The potential neurotoxic effects of anticancer drugs, like doxorubicin (DOX) and mitoxantrone (MTX; also used in multiple sclerosis), are presently important reasons for concern, following epidemiological data indicating that cancer survivors submitted to chemotherapy may suffer cognitive deficits. We evaluated the in vitro neurotoxicity of two commonly used chemotherapeutic drugs, DOX and MTX, and study their underlying mechanisms in the SH-SY5Y human neuronal cell model. Undifferentiated human SH-SY5Y cells were exposed to DOX or MTX (0.13, 0.2 and 0.5 μM) for 48 h and two cytotoxicity assays were performed, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction and the neutral red (NR) incorporation assays. Phase contrast microphotographs, Hoechst, and acridine orange/ethidium bromide stains were performed. Mitochondrial membrane potential was also assessed. Moreover, putative protective drugs, namely the antioxidants N-acetyl-l-cysteine (NAC; 1 mM) and 100 μM tiron, the inhibitor of caspase-3/7, Ac-DEVD-CHO (100 μM), and a protein synthesis inhibitor, cycloheximide (CHX; 10 nM), were tested to prevent DOX- or MTX-induced toxicity. The MTT reduction assay was also done in differentiated SH-SY5Y cells following exposure to 0.2 μM DOX or MTX. MTX was more toxic than DOX in both cytotoxicity assays and according to the morphological analyses. MTX also evoked a higher number of apoptotic nuclei than DOX. Both drugs, at the 0.13 μM concentration, caused mitochondrial membrane potential depolarization after a 48-h exposure. Regarding the putative neuroprotectors, 1 mM NAC was not able to prevent the cytotoxicity caused by either drug. Notwithstanding, 100 μM tiron was capable of partially reverting MTX-induced cytotoxicity in the NR uptake assay. One hundred μM Ac-DEVD-CHO and 10 nM cycloheximide (CHX) also partially prevented the toxicity induced by DOX in the NR uptake assay. MTX was more toxic than DOX in differentiated SH-SY5Y cells, while MTX had similar toxicity in differentiated and undifferentiated SH-SY5Y cells. In fact, MTX was the most neurotoxic drug tested and the mechanisms involved seem dissimilar among drugs. Thus, its toxicity mechanisms need to be further investigated as to determine the putative neurotoxicity for multiple sclerosis and cancer patients.

Bioinform Biol Insights ; 12: 1177932218755337, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29780242


Caseous lymphadenitis (CLA) is a disease caused by Corynebacterium pseudotuberculosis bacteria that affects sheep and goats. The absence of a serologic diagnose is a factor that contributes for the disease dissemination, and due to the formation of granuloma, the treatment is very expensive. Therefore, prophylaxis is the approach with best cost-benefit relation; however, it still lacks an effective vaccine. In this sense, this work seeks to apply bioinformatic tools to design an effective vaccine against CLA, using CP40 protein as standard for the design of immunodominant epitopes, from which a total of 6 sequences were obtained, varying from 10 to 16 amino acid residues. The evaluation of different properties of the vaccines showed that the vaccine is a potent and nonallergenic antigen remaining stable in a wide range of temperatures. The initial tertiary structure of the vaccine was then predicted and a model selected. Later, the process of CP40 protein and TLR2 receptor binding was performed, presenting interaction with this receptor, which plays an important role in the activation of the immune response.

Artigo em Inglês | MEDLINE | ID: mdl-29530717


The brain is a highly demanding organ in terms of energy requirements, and precise regulatory mechanisms must operate to ensure adequate energy delivery to maintain normal neuronal activity. Of the energy-promoting substrates present in the circulation, glucose is preferred by the brain, and as with all other substrates, its utilization depends on the presence of humoral factors such as hormones including growth hormone (GH). Glucose enters the cells though specific transport proteins. Among all transporter families and subtypes described to date, the most studied ones are the glucose transporters (GLUTs). The aim of this study is to determine a possible relationship between GH and GLUTs. Therefore, we evaluated the effect of GH-transgenesis and recombinant GH injections upon GLUT expression in the brain of male zebrafish. Overall, the results demonstrated that increasing the GH concentrations above the normal level, via transgenesis or injection, in the fish may impair energy uptake by the brain. This appeared to occur through downregulation of most of the analyzed GLUTs.

Perfilação da Expressão Gênica , Glucose/metabolismo , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Transporte Biológico , Encéfalo/metabolismo , Metabolismo Energético , Hormônio do Crescimento/genética , Masculino , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
Fish Physiol Biochem ; 44(2): 465-474, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29423894


Dietary supplements are commonly used by animals and humans and play key roles in diverse systems, such as the immune and reproductive systems, and in metabolism. Essential oils (EOs), which are natural substances, have potential for use in food supplementation; however, their effects on organisms remain to be elucidated. Here, we examine the effects of dietary Aloysia triphylla EO supplementation on zebrafish behavior, metabolism, stress response, and growth performance. We show that fish fed diets containing A. triphylla EO presented an anxiolytic response, with reduced exploratory activity and oxygen consumption; no changes were observed in neuroendocrine stress axis functioning and growth was not impaired. Taken together, these results suggest that the A. triphylla EO supplementation is a strong candidate for use in feed, since it ensures fish welfare (anxiolytic behavior) with decreased oxygen consumption. This makes it suitable for use in high-density production systems without causing damage to the neuroendocrine stress axis and without growth performance being impaired.

Comportamento Animal/efeitos dos fármacos , Suplementos Nutricionais , Óleos Vegetais/administração & dosagem , Verbenaceae/química , Peixe-Zebra/fisiologia , Animais , Consumo de Oxigênio/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento
Nutr. clín. diet. hosp ; 38(2): 122-127, 2018. tab
Artigo em Português | IBECS | ID: ibc-175489


Introdução: A diarreia é considerada uma das complicações mais frequentes em pacientes de unidade de terapia intensiva (UTI). A variação dos dados sobre sua incidência pode ser resultado da inconsistência das definições adotadas. As causas são complexas e multifatoriais, mas vários fatores contribuintes são descritos. Objetivos: Determinar a incidência e fatores associados à diarreia nos pacientes internados em uma UTI de um hospital público. Métodos: Trata-se de um estudo analítico tipo coorte prospectivo, cuja população foi composta por 103 pacientes adultos (≥ 18 anos) em uso de terapia nutricional enteral exclusiva internados em UTI adulta clínica em hospital público de urgência. A ocorrência da diarreia foi definida como a presença de 3 ou mais evacuações líquidas ou pastosas em 24 horas e os possíveis fatores associados foram: terapia nutricional, presença de febre, infecção, hipoalbuminemia, medicamentos em uso. A análise estatística descritiva e cálculo do risco relativo foram realizados utilizando o programa Epiinfo (R) versão 7. Para comparações entre os grupos utilizouse o teste t de Student e o teste qui quadrado ou exato de Fischer, quando apropriado, com nível de significância estatística estabelecido em P <0,05. Resultados: Do total de 103 pacientes, 46,6% (48) apresentaram diarreia com duração média de 1,3 dias (±2,1). O grupo com diarreia teve um tempo de permanência maior do que os pacientes sem diarreia - 37 x 20,3 dias (p=0,002). Os fatores de risco que estiveram associados com o desenvolvimento de diarreia foram: presença de febre (RR=1,96), presença de hipoalbuminemia (RR=1,54), uso de procinético (RR=1,86), uso de carbapenêmicos (RR=1,71) e glicopeptídeos (RR=2,1). Conclusão: A incidência de diarreia nos pacientes em uso de terapia nutricional na unidade pesquisada foi alta, mas semelhante a outros dados reportados na literatura

Introduction: Diarrhea is considered one of the most frequent complications in intensive care unit (ICU) patients. The variation of the data on its incidence may be a result of the inconsistency of the definitions adopted. The causes are complex and multifactorial, but several contributing factors are described. Objectives: To determine the incidence and factors associated with diarrhea in patients admitted to an ICU of a public hospital. Methods: This is a prospective cohort-type study, whose population was composed of 103 adult patients (≥ 18 years old) using exclusive enteral nutritional therapy hospitalized in a clinical adult ICU at a public emergency hospital. The occurrence of diarrhea was defined as the presence of 3 or more liquid or pasty stools in 24 hours and the possible associated factors were: nutritional therapy, presence of fever, infection, hypoalbuminemia, medications in use. Descriptive statistical analysis and relative risk calculation were performed using the Epi-info(R) version 7 program. For comparisons between the groups, Student's t-test and chi-square or Fischer's exact test were used, where appropriate, with level of statistical significance established at P <0.05. Results: Out of 103 patients, 46.6% (48) presented diarrhea with a mean duration of 1.3 days (± 2.1). The group with diarrhea had a longer residence time than patients without diarrhea - 37 x 20.3 days (p = 0.002). Risk factors associated with diarrhea were: presence of fever (RR = 1.96), presence of hypoalbuminemia (RR = 1.54), prokinetic use (RR = 1.86), use of carbapenems (RR = 1.71) and glycopeptides (RR = 2.1). Conclusion: The incidence of diarrhea in patients using nutritional therapy in the unit studied was high, but similar to other data reported in the literature

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Humanos , Diarreia/epidemiologia , Terapia Nutricional , Nutrição Enteral , Gastroenteropatias/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Fatores de Risco , Estudos de Coortes , Estudos Prospectivos , Hospitalização/estatística & dados numéricos , Diarreia/etiologia , Antibacterianos/efeitos adversos