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1.
Proc Natl Acad Sci U S A ; 118(34)2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34417304

RESUMO

Despite widespread yearly vaccination, influenza leads to significant morbidity and mortality across the globe. To make a more broadly protective influenza vaccine, it may be necessary to elicit antibodies that can activate effector functions in immune cells, such as antibody-dependent cellular cytotoxicity (ADCC). There is growing evidence supporting the necessity for ADCC in protection against influenza and herpes simplex virus (HSV), among other infectious diseases. An HSV-2 strain lacking the essential glycoprotein D (gD), was used to create ΔgD-2, which is a highly protective vaccine against lethal HSV-1 and HSV-2 infection in mice. It also elicits high levels of IgG2c antibodies that bind FcγRIV, a receptor that activates ADCC. To make an ADCC-eliciting influenza vaccine, we cloned the hemagglutinin (HA) gene from an H1N1 influenza A strain into the ΔgD-2 HSV vector. Vaccination with ΔgD-2::HAPR8 was protective against homologous influenza challenge and elicited an antibody response against HA that inhibits hemagglutination (HAI+), is predominantly IgG2c, strongly activates FcγRIV, and protects against influenza challenge following passive immunization of naïve mice. Prior exposure of mice to HSV-1, HSV-2, or a replication-defective HSV-2 vaccine (dl5-29) does not reduce protection against influenza by ΔgD-2::HAPR8 This vaccine also continues to elicit protection against both HSV-1 and HSV-2, including high levels of IgG2c antibodies against HSV-2. Mice lacking the interferon-α/ß receptor and mice lacking the interferon-γ receptor were also protected against influenza challenge by ΔgD-2::HAPR8 Our results suggest that ΔgD-2 can be used as a vaccine vector against other pathogens, while also eliciting protective anti-HSV immunity.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Herpes Simples/imunologia , Vacinas contra Influenza/administração & dosagem , Infecções por Orthomyxoviridae/prevenção & controle , Orthomyxoviridae/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Herpes Simples/prevenção & controle , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/fisiologia , Vacinas contra Influenza/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/imunologia
2.
Molecules ; 27(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36500534

RESUMO

Mosquitoes can be vectors of pathogens and transmit diseases to both animals and humans. Species of the genus Culex are part of the cycle of neglected diseases, especially Culex quinquefasciatus, which is an anthropophilic vector of lymphatic filariasis. Natural products can be an alternative to synthetic insecticides for vector control; however, the main issue is the poor water availability of some compounds from plant origin. In this context, nanoemulsions are kinetic stable delivery systems of great interest for lipophilic substances. The objective of this study was to investigate the larvicidal activity of the Hyptis suaveolens essential oil nanoemulsion on Cx. quinquefasciatus. The essential oil showed a predominance of monoterpenes with retention time (RT) lower than 15 min. The average size diameter of the emulsions (sorbitan monooleate/polysorbate 20) was ≤ 200 nm. The nanoemulsion showed high larvicidal activity in concentrations of 250 and 125 ppm. CL50 values were 102.41 (77.5253−149.14) ppm and 70.8105 (44.5282−109.811) ppm after 24 and 48 h, respectively. The mortality rate in the surfactant control was lower than 9%. Scanning micrograph images showed changes in the larvae's integument. This study achieved an active nanoemulsion on Cx. quinquefasciatus through a low-energy-input technique and without using potentially toxic organic solvents. Therefore, it expands the scope of possible applications of H. suaveolens essential oil in the production of high-added-value nanosystems for tropical disease vector control.


Assuntos
Aedes , Culex , Culicidae , Inseticidas , Lamiaceae , Óleos Voláteis , Humanos , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/análise , Larva , Mosquitos Vetores , Inseticidas/química , Extratos Vegetais/química , Folhas de Planta/química
3.
Hematol Oncol ; 37(5): 564-568, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31475375

RESUMO

Patients with follicular lymphoma (FL) refractory to front-line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high-risk FL. Twenty-five patients with FL refractory to front-line ICT and 10 non-refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three-year progression-free survival (PFS) and OS probabilities were 25% (95% CI, 13%-41%) and 53% (34%-69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0-3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non-refractory). In conclusion, in this study, patients with high-risk follicular lymphoma were genetically heterogeneous.


Assuntos
Biomarcadores Tumorais/genética , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Idoso , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Estimativa de Kaplan-Meier , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mutação , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
5.
Inflammopharmacology ; 26(4): 1057-1080, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29404883

RESUMO

The essential oil from Rosmarinus officinalis L. (OERO) has bioactive compounds with anti-inflammatory activity. The objective of this study was to evaluate the anti-inflammatory potency of nanoemulsions containing essential oil of Rosmarinus officinalis L. (NOERO, NECHA, NECULT, and NECOM) in vitro and in vivo. This study was accomplished in a quantitative format through tests with diphenyl picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cellular antioxidant activity (CCA), determination of nitric oxide production, cellular viability and anti-inflammatory activity in zebrafish. OERO's were submitted to the analysis-coupled gas chromatography-mass spectrometry (GC-MS), which highlighted 1,8-cineol and camphor as major compounds. NOEROs were obtained by a low-energy method and presenting the medium size smaller than 200 nm. The efficiency of encapsulation by spectrometry and gas chromatographic analysis was 67.61 and 75.38%, respectively. In the CCA assay, all of the samples presented percentage values of inhibition similar to the quercetin pattern, indicating antioxidant activity. In the test for determination of NO·, all of the samples inhibited the production of NO· when compared to LPS, and NOEROS were more effective than OEROS to 5 µg/mL. In the cell viability assay, the cells remained viable after contact with the samples, demonstrating an absence of cytotoxicity. This study showed that all nanoemulsions (NECHA, NECULT, and NECOM) showed no toxicity to macrophages, besides demonstrating antioxidant activity and potentiation of the essential oil effect in the proliferation of viable fibroblasts. Nanoemulsions has also shown the ability to potentiate the anti-inflammatory action of essential oils by exerting immunomodulatory activity by inhibiting the production of the pro-inflammatory mediator nitric oxide. The results obtained with NECHA in zebrafish confirm the hypothesis that prominent terpenic compounds, alpha-pinene, 1,8-cineole, and camphor, became more available at the target sites, inhibiting the inflammatory process in this animal species.


Assuntos
Anti-Inflamatórios/farmacologia , Nanopartículas , Óleos Voláteis/farmacologia , Rosmarinus/química , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Emulsões , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Óleos Voláteis/administração & dosagem , Óleos Voláteis/isolamento & purificação , Tamanho da Partícula , Peixe-Zebra
6.
J Nanobiotechnology ; 15(1): 2, 2017 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-28049483

RESUMO

BACKGROUND: Preparation of nanoformulations using natural products as bioactive substances is considered very promising for innovative larvicidal agents. On this context, oil in water nanoemulsions develop a main role, since they satisfactorily disperse poor-water soluble substances, such as herbal oils, in aqueous media. Pterodon emarginatus, popularly known as sucupira, has a promising bioactive oleoresin. However, to our knowledge, no previous studies were carried out to evaluate its potential against Culex quinquefasciatus, the main vector of the tropical neglected disease called lymphatic filariasis or elephantiasis. Thus, we aimed to investigate influence of different pairs of surfactants in nanoemulsion formation and investigate if a sucupira oleoresin-based nanoemulsion has promising larvicidal activity against this C. quinquefasciatus. We also evaluated morphological alteration, possible mechanism of insecticidal action and ecotoxicity of the nanoemulsion against a non-target organism. RESULTS: Among the different pairs of surfactants that were tested, nanoemulsions obtained with polysorbate 80/sorbitan monooleate and polysorbate 80/sorbitan trioleate presented smallest mean droplet size just afterwards preparation, respectively 151.0 ± 2.252 and 160.7 ± 1.493 nm. They presented high negative zeta potential values, low polydispersity index (<0.300) and did not present great alteration in mean droplet size and polydispersity index after 1 day of preparation. Overall, nanoemulsion prepared with polysorbate 80/sorbitan monooleate was considered more stable and was chosen for biological assays. It presented low LC50 value against larvae (34.75; 7.31-51.86 mg/L) after 48 h of treatment and some morphological alteration was observed. The nanoemulsion did not inhibit acetylcholinesterase of C. quinquefasciatus larvae. It was not toxic to green algae Chlorella vulgaris at low concentration (25 mg/L). CONCLUSIONS: Our results suggest that optimal nanoemulsions may be prepared with different surfactants using a low cost and low energy simple method. Moreover, this prototype proved to be effective against C. quinquefasciatus, being considered an ecofriendly novel nanoproduct that can be useful in integrated control programs of vector control.


Assuntos
Culicidae/efeitos dos fármacos , Emulsões/toxicidade , Fabaceae/química , Controle de Insetos , Inseticidas/toxicidade , Extratos Vegetais/toxicidade , Animais , Chlorella vulgaris/efeitos dos fármacos , Chlorella vulgaris/fisiologia , Culicidae/fisiologia , Emulsões/química , Feminino , Inseticidas/química , Larva/efeitos dos fármacos , Larva/fisiologia , Extratos Vegetais/química
7.
J Food Sci Technol ; 53(9): 3465-3476, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27777452

RESUMO

Phenolic compounds are phytochemicals with high health-promoting properties. Carrot is a vegetable highly worldwide consumed although its phenolic content is low compared to other plant products. The aim of this work was to evaluate changes in phenolic compounds in carrots caused by abiotic stresses. The phenylalanine ammonia-lyase (PAL) activity, phenolic compounds and total antioxidant capacity (TAC) changes during storage up to 72 h at 15 °C after wounding (shredding), 9 kJ UV-C m-2 pretreatment and hyperoxia (80 kPa) conditions of carrots were studied. Shredding and hyperoxia storage induced the highest phenolic compounds and TAC enhancements. Accumulation of phenolic compounds in shredded carrots could be structured in the following phases: 1st phase (<24 h): unchanged phenolic compounds levels with minimum PAL activity; 2nd phase (24-48 h): moderate phenolic increases (≈600-700 mg CAE kg-1 accumulated in 24 h) concurring with the greatest increase of PAL activity; 3nd phase (48-72 h): high phenolic increases (≈1600-2700 mg CAE kg-1, accumulated in 24 h) while a moderate increment of PAL activity was registered. Although UV-C pretreatment of shreds reduced phenolic accumulation, 600 % increments were still registered in those samples stored under hyperoxia conditions for 72 h. However, the contents of chlorogenic acid at 72 h were 1.4-fold higher in irradiated shreds under hyperoxia compared to the same samples under air conditions.

8.
Br J Nurs ; 24(21): 1080-2, 1084, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26618679

RESUMO

Globalisation in the academic context provides the opportunity for sharing knowledge and innovations between institutions in different countries, through the creation of study abroad and academic mobility programmes. For nursing students, studying abroad facilitates the development of cultural sensitivity so that they may care appropriately for an increasingly multicultural patient population in their own countries. This article describes a Brazilian 'study abroad' student nurse's experience of studying a 'communication and therapeutic relationships' module in an Irish university. Johns' model of structured reflection was used to frame, describe and reflect on the experience. This reflection informs 'study abroad' students and their universities about the student experience through a personal account of one such student.


Assuntos
Atitude do Pessoal de Saúde , Comunicação , Intercâmbio Educacional Internacional , Estudantes de Enfermagem/psicologia , Brasil/etnologia , Currículo , Bacharelado em Enfermagem , Humanos , Relações Interpessoais , Irlanda
9.
J Neurol Surg Rep ; 85(2): e29-e38, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38596232

RESUMO

Background Spinal epidural abscess is a rare but serious condition that can cause spinal cord compression and neurological deficits. Case Description and Methods The article reports a case of a 31-year-old patient who presented with an infectious cellulitis in the left hand, which progressed to a spinal epidural abscess. The diagnosis was confirmed by clinical examination and magnetic resonance imaging. Treatment involved laminectomy, after which the patient had complete recovery of neurological deficits. This article is a case report with a literature review. Patient data and images were collected by the researchers who participated in the patient's care. The literature was reviewed by one of the researchers based on the search for articles in the PubMed database. For the research, the following keywords were inserted: "Spinal epidural empyema," "Spinal epidural abscess." Conclusion Spinal epidural abscess is often underdiagnosed, which can lead to delays in treatment and serious complications. The relationship between cellulitis and spinal epidural abscess may be related to the spread of infection through the lymphatic or blood system.

10.
Beilstein J Nanotechnol ; 15: 104-114, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38264062

RESUMO

Plant-based insecticides offer advantages such as negligible residual effects, reduced risks to both humans and the environment, and immunity to resistance issues that plague conventional chemicals. However, the practical use of monoterpenes in insect control has been hampered by challenges including their poor solubility and stability in aqueous environments. In recent years, the application of nanotechnology-based formulations, specifically nanoemulsions, has emerged as a prospective strategy to surmount these obstacles. In this study, we developed and characterized nanoemulsions based on cymene and myrcene and assessed their toxicity both in vitro using human keratinocytes (HaCAT) cells and in an in vivo model involving Galleria mellonella larvae. Additionally, we investigated the insecticidal efficacy of monoterpenes against the mosquito Aedes aegypti, the primary dengue vector, via larval bioassay. Employing a low-energy approach, we successfully generated nanoemulsions. The cymene-based nanoemulsion exhibited a hydrodynamic diameter of approximately 98 nm and a zeta potential of -25 mV. The myrcene-based nanoemulsion displayed a hydrodynamic diameter of 118 nm and a zeta potential of -20 mV. Notably, both nanoemulsions demonstrated stability over 60 days, accompanied by controlled release properties and low toxicity towards HaCAT cells and Galleria mellonella larvae. Moreover, the nanoemulsions exhibited significant lethality against third-instar Aedes aegypti larvae at a concentration of 50 mg/L. In conclusion, the utilization of nanoemulsions encapsulating cymene and myrcene presents a promising avenue for overcoming the limitations associated with poor solubility and stability of monoterpenes. This study sheds light on the potential of the nanoemulsions as effective and environmentally friendly insecticides in the ongoing battle against mosquito-borne diseases.

11.
Viruses ; 16(2)2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38400068

RESUMO

Bluetongue Virus (BTV) and Epizootic Hemorrhagic Disease Virus (EHDV) are Orbiviruses primarily transmitted by their biological vector, Culicoides spp. Latreille, 1809 (Diptera: Ceratopogonidae). These viruses can infect a diverse range of vertebrate hosts, leading to disease outbreaks in domestic and wild ruminants worldwide. This study, conducted at the Belo Horizonte Municipal Parks and Zoobotany Foundation (FPMZB-BH), Minas Gerais, Brazil, focused on Orbivirus and its vectors. Collections of Culicoides spp. were carried out at the FPMZB-BH from 9 December 2021 to 18 November 2022. A higher prevalence of these insects was observed during the summer months, especially in February. Factors such as elevated temperatures, high humidity, fecal accumulation, and proximity to large animals, like camels and elephants, were associated with increased Culicoides capture. Among the identified Culicoides spp. species, Culicoides insignis Lutz, 1913, constituted 75%, and Culicoides pusillus Lutz, 1913, 6% of the collected midges, both described as competent vectors for Orbivirus transmission. Additionally, a previously unreported species in Minas Gerais, Culicoides debilipalpis Lutz, 1913, was identified, also suspected of being a transmitter of these Orbiviruses. The feeding preferences of some Culicoides species were analyzed, revealing that C. insignis feeds on deer, Red deer (Cervus elaphus) and European fallow deer (Dama dama). Different Culicoides spp. were also identified feeding on humans, raising concerns about the potential transmission of arboviruses at the site. In parallel, 72 serum samples from 14 susceptible species, including various Cervids, collected between 2012 and 2022 from the FPMZB-BH serum bank, underwent Agar Gel Immunodiffusion (AGID) testing for BTV and EHDV. The results showed 75% seropositivity for BTV and 19% for EHDV. Post-testing analysis revealed variations in antibody presence against BTV in a tapir and a fallow deer and against EHDV in a gemsbok across different years. These studies confirm the presence of BTV and EHDV vectors, along with potential virus circulation in the zoo. Consequently, implementing control measures is essential to prevent susceptible species from becoming infected and developing clinical diseases.


Assuntos
Antílopes , Vírus Bluetongue , Ceratopogonidae , Cervos , Vírus da Doença Hemorrágica Epizoótica , Orbivirus , Humanos , Animais , Vírus Bluetongue/genética , Brasil/epidemiologia , Insetos Vetores , Orbivirus/genética
12.
Surg Neurol Int ; 15: 94, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628535

RESUMO

Background: The Klippel-Feil syndrome (KFS) is a rare congenital anomaly characterized by the fusion of cervical vertebrae, which may be associated with other malformations, such as dermoid tumors and teratoma. Some theories explain the embryology of these associations. Another condition that may be present is the dermal sinus (DS), communication between intracranial tumors and the subcutaneous tissue, and predisposing infections. This case report aims to describe an association between these three pathologies as well as correlate them from the literature. This report was based on medical records retrospectively reviewed associated with the systematic bibliographical consultation using indexed databases based on inclusion and exclusion methods. Case Description: An adult male patient, 24 years old, was admitted to our service, presenting fever and meningeal irritation as initial symptoms. In the patient's clinical history, he was diagnosed with an occipital DS in his childhood, which was previously instructed to be operated on by another neurosurgical team, but the patient chose not to perform the procedure. The magnetic resonance imaging investigation showed a DS associated with a cerebellar infected mass with 2 cm on its main diameter. The patient was treated with preoperative antibiotic therapy and underwent gross total surgical resection of the tumor as well as DS correction, confirmed in the histopathological examination as a teratoma. After surgery, further computed tomography scan analysis showed the presence of cervical vertebrae fusion, compatible with KFS diagnosis. Conclusion: The association between KFS, cerebellar teratoma, and DS has not yet been described in the literature, with only the association of the first two being extremely rare.

13.
Pathogens ; 13(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38251354

RESUMO

The reintroduction of captive animals to the wild helps restore endangered species, but it risks pathogen transmission, harming wild populations. Such transmission can impact the genetic diversity and long-term viability of these populations. This study assessed parasite diversity and load in captive Pecari tajacu, a species native to the Americas and culturally significant to Brazilian indigenous culture, prior to reintroduction. Samples from 24 peccaries were analyzed for ectoparasites, hemopathogens, and stool parasites with direct and molecular analysis. Findings showed that various parasites were present. Two peccaries (8.3%) were infested by the adult tick Amblyomma sculptum. Six (25.0%) tested positive for Trypanosoma evansi, four (16.7%) for hemobacteria of the family Anaplasmataceae, twelve (50.0%) for hemotropic Mycoplasma, and seven (29.2%) for Leishmania braziliensis. Stool samples indicated multiple parasites, with sixteen (66.7%) peccaries infected by Strongylida order parasites, Spiruridae in three (12.5%), and Ascaris suum in one (4.2%) animal. Cysts of Balantidium sp. were found in twenty (83.3%), Entamoeba polecki in five (20.8%), and Iodamoeba bütschlii in two (8.3%) peccaries. To our current knowledge, this is the first global report of Leishmania braziliensis, Iodamoeba bütschlii, and Entamoeba polecki in P. tajacu, irrespective of the environment, including both captivity and wild conditions. Some of these parasites are common in domestic animals, and others are zoonotic, indicating potential interspecies pathogen transmission.

14.
Inflammation ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904872

RESUMO

Platelet-rich plasma (PRP) is a biological blood-derived therapeutic obtained from whole blood that contains higher levels of platelets. PRP has been primarily used to mitigate joint degeneration and chronic pain in osteoarthritis (OA). This clinical applicability is based mechanistically on the release of several proteins by platelets that can restore joint homeostasis. Platelets are the primary source of brain-derived neurotrophic factor (BDNF) outside the central nervous system. Interestingly, BDNF and PRP share key biological activities with clinical applicability for OA management, such as anti-inflammatory, anti-apoptotic, and antioxidant. However, the role of BDNF in PRP therapeutic activities is still unknown. Thus, this work aimed to investigate the implications of BDNF in therapeutic outcomes provided by PRP therapy in vitro and in-vivo, using the MIA-OA animal model in male Wistar rats. Initially, the PRP was characterized, obtaining a leukocyte-poor-platelet-rich plasma (LP-PRP). Our assays indicated that platelets activated by Calcium release BDNF, and suppression of M1 macrophage polarization induced by LP-PRP depends on BDNF full-length receptor, Tropomyosin Kinase-B (TrkB). OA animals were given LP-PRP intra-articular and showed functional recovery in gait, joint pain, inflammation, and tissue damage caused by MIA. Immunohistochemistry for activating transcriptional factor-3 (ATF-3) on L4/L5 dorsal root ganglia showed the LP-PRP decreased the nerve injury induced by MIA. All these LP-PRP therapeutic activities were reversed in the presence of TrkB receptor antagonist. Our results suggest that the therapeutic effects of LP-PRP in alleviating OA symptoms in rats depend on BDNF/TrkB activity.

15.
J Virol ; 86(1): 143-55, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22013059

RESUMO

Adeno-associated virus type 2 (AAV2) is a human parvovirus that relies on a helper virus for efficient replication. Herpes simplex virus 1 (HSV-1) supplies helper functions and changes the environment of the cell to promote AAV2 replication. In this study, we examined the accumulation of cellular replication and repair proteins at viral replication compartments (RCs) and the influence of replicating AAV2 on HSV-1-induced DNA damage responses (DDR). We observed that the ATM kinase was activated in cells coinfected with AAV2 and HSV-1. We also found that phosphorylated ATR kinase and its cofactor ATR-interacting protein were recruited into AAV2 RCs, but ATR signaling was not activated. DNA-PKcs, another main kinase in the DDR, was degraded during HSV-1 infection in an ICP0-dependent manner, and this degradation was markedly delayed during AAV2 coinfection. Furthermore, we detected phosphorylation of DNA-PKcs during AAV2 but not HSV-1 replication. The AAV2-mediated delay in DNA-PKcs degradation affected signaling through downstream substrates. Overall, our results demonstrate that coinfection with HSV-1 and AAV2 provokes a cellular DDR which is distinct from that induced by HSV-1 alone.


Assuntos
Coinfecção/genética , Dano ao DNA , Dependovirus/fisiologia , Herpes Simples/genética , Herpesvirus Humano 1/fisiologia , Infecções por Parvoviridae/genética , Animais , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Coinfecção/enzimologia , Coinfecção/virologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dependovirus/genética , Herpes Simples/enzimologia , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Interações Hospedeiro-Patógeno , Humanos , Infecções por Parvoviridae/enzimologia , Infecções por Parvoviridae/virologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Replicação Viral
16.
BMC Infect Dis ; 13: 254, 2013 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-23725365

RESUMO

BACKGROUND: Maternal dengue antibodies are considered to play a significant role in dengue pathogenesis among infants. Determining the transplacental specific antibody transfer is invaluable for establishing the optimal vaccination age among infants in endemic regions. METHODS: We conducted a cross-sectional study among pairs of maternal and corresponding umbilical cord blood samples in public hospitals. The prevalence and incidence of dengue infection were determined in 505 pairs of pregnant women and neonates during a large outbreak (2009-2010) in central Brazil. The women were interviewed at late pregnancy to assess current or past symptoms of dengue. All parturients and their neonates were screened using Dengue IgG Indirect ELISA (Panbio) to assess previous dengue exposure. A semi-quantitative measurement of the IgG antibody expressed by the index ratio was calculated using optical density (OD) values according to the manufacturer's instructions. The studied population of parturients and their offspring was also screened for recent dengue infection by the Dengue IgM-capture ELISA (Panbio). Those participants with history of fever and two or more symptoms of dengue at least 10 days before the delivery were also tested for the dengue NS1 antigen using the Dengue Early ELISA (Panbio) and RT-PCR. RESULTS: The mean maternal age was 25.8 (SD = 6.4), and 83.6% of deliveries were between 37 and 41 weeks. Approximately half of the 505 women and neonates were IgG-seropositive, yielding 99.3% co-positive mother-child frequency of antibody transfer (Kappa = 0.96). The incidence of dengue infection was 2.8% (95% CI 1.4-4.4%) among the women considering 14 IgM-positive results and one DENV2 detected by RT-PCR. The dengue NS1 antigen was undetectable in the matched pairs. CONCLUSION: This study provides critical data on the prevalence of transplacental transferred maternal-infant anti-dengue antibodies and incidence of infection. The design of future vaccine trials should consider diverse regional epidemiological scenarios.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Dengue/isolamento & purificação , Dengue/epidemiologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Brasil/epidemiologia , Estudos Transversais , Dengue/imunologia , Dengue/transmissão , Feminino , Sangue Fetal/química , Sangue Fetal/virologia , Humanos , Imunoglobulina G/sangue , Incidência , Recém-Nascido , Placenta/imunologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/imunologia , Prevalência
17.
Clinics (Sao Paulo) ; 78: 100245, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37478629

RESUMO

OBJECTIVE: Investigate the auditory function of the elderly using the middle latency potentials. METHODOLOGY: Group 1 (G1): 20 healthy individuals of both genders, older than 60 years, without hearing loss. Group 2 (G2): 20 healthy individuals of both sexes, older than 60 years, with hearing loss in frequencies from 4 to 8 kHz. Potential recording was performed with unilateral and bilateral stimulation and the Binaural Interaction Component was calculated. RESULTS: Na latency in C3A1 was greater in the stimulation of the right ear in G2 and the amplitude of Na-Pa was greater in the stimulation of the right ear and recording in C3A1 in G1. The latency of the Pa component was higher in the stimulation of the right ear recorded in C4A2. The Pb component in G2 by bilateral stimulation and recorded in C4A2 had higher latency. The first and second negative and positive peaks presented greater amplitude in G1. In C3A1, the 1st negative peak was more negative in G1 and the 2nd positive peak showed greater amplitude in C4A2 in both groups. CONCLUSION: The transmission of auditory information to the primary auditory cortex is impaired with aging, especially in unilateral stimulation, reinforced by losses in elderly people with peripheral hearing loss, such as in the binaural interaction at the cortical and subcortical levels. Thus, the AMLR has shown to be a sensitive examination to investigate neuroauditory disorders in the elderly, especially related to high-frequency hearing loss and primary auditory cortex dysfunctions caused by the aging process.


Assuntos
Córtex Auditivo , Perda Auditiva , Idoso , Humanos , Masculino , Feminino , Potenciais Evocados Auditivos/fisiologia , Audição , Envelhecimento/fisiologia , Orelha , Estimulação Acústica , Córtex Auditivo/fisiologia
18.
Heliyon ; 9(7): e17834, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37501953

RESUMO

The estimative of the leaf area using a nondestructive method is paramount for successive evaluations in the same plant with precision and speed, not requiring high-cost equipment. Thus, the objective of this work was to construct models to estimate leaf area using artificial neural network models (ANN) and regression and to compare which model is the most effective model for predicting leaf area in sesame culture. A total of 11,000 leaves of four sesame cultivars were collected. Then, the length (L) and leaf width (W), and the actual leaf area (LA) were quantified. For the ANN model, the parameters of the length and width of the leaf were used as input variables of the network, with hidden layers and leaf area as the desired output parameter. For the linear regression models, leaf dimensions were considered independent variables, and the actual leaf area was the dependent variable. The criteria for choosing the best models were: the lowest root of the mean squared error (RMSE), mean absolute error (MAE), and absolute mean percentage error (MAPE), and higher coefficients of determination (R2). Among the linear regression models, the equation yˆ=0.515+0.584*LW was considered the most indicated to estimate the leaf area of the sesame. In modeling with ANNs, the best results were found for model 2-3-1, with two input variables (L and W), three hidden variables, and an output variable (LA). The ANN model was more accurate than the regression models, recording the lowest errors and higher R2 in the training phase (RMSE: 0.0040; MAE: 0.0027; MAPE: 0.0587; and R2: 0.9834) and in the test phase (RMSE: 0.0106; MAE: 0.0029; MAPE: 0.0611; and R2: 0.9828). Thus, the ANN method is the most indicated and accurate for predicting the leaf area of the sesame.

19.
Brain Sci ; 13(7)2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37508912

RESUMO

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder caused by pathogenic variants in CYP27A1, leading to a deficiency in sterol 27-hydroxylase. This defect results in the accumulation of cholestanol and bile alcohols in various tissues, including the brain, tendons and peripheral nerves. We conducted this review to evaluate lipid profile abnormalities in patients with CTX. A search was conducted in PubMed, Embase and the Virtual Health Library in January 2023 to evaluate studies reporting the lipid profiles of CTX patients, including the levels of cholestanol, cholesterol and other lipids. Elevated levels of cholestanol were consistently observed. Most patients presented normal or low serum cholesterol levels. A decrease in chenodeoxycholic acid (CDCA) leads to increased synthesis of cholesterol metabolites, such as bile alcohols 23S-pentol and 25-tetrol 3-glucuronide, which may serve as surrogate follow-up markers in patients with CTX. Lipid abnormalities in CTX have clinical implications. Cholestanol deposition in tissues contributes to clinical manifestations, including neurological symptoms and tendon xanthomas. Dyslipidemia and abnormal cholesterol metabolism may also contribute to the increased risk of atherosclerosis and cardiovascular complications observed in some CTX patients.

20.
Environ Sci Pollut Res Int ; 30(20): 57850-57861, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36971943

RESUMO

Methylparaben, chloro-methylparaben, and dichloro-methylparaben were evaluated in Allium cepa at 5, 10, 50, and 100 µg/L and in Eisenia fetida at 10 and 100 µg/L. In A. cepa roots, 100 µg/L methylparaben and 50 and 100 µg/L chlorinated methylparabens reduced cell proliferation, caused cellular changes, and reduced cell viability in meristems, which caused a reduction in root growth. Furthermore, they caused drastic inhibition of catalase, ascorbate peroxidase, and superoxide dismutase; activated guaiacol peroxidase and promoted lipid peroxidation in meristematic root cells. In earthworms, after 14 days exposure to the three compounds, there were no deaths, and catalase, ascorbate peroxidase, and superoxide dismutase were not inhibited. However, guaiacol peroxidase activity and lipid peroxidation were observed in animals exposed to dichloro-methylparaben. Soils with dichloro-methylparaben also caused the escape of earthworms. It is inferred that the recurrent contamination of soils with these methylparabens, with emphasis on chlorinated derivatives, can negatively impact different species that depend directly or indirectly on soil to survive.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Catalase/metabolismo , Cebolas/fisiologia , Oligoquetos/metabolismo , Ascorbato Peroxidases/metabolismo , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo , Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Estresse Oxidativo , Malondialdeído/metabolismo
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