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A plant, Priva cordifolia mediated silver nanoparticle was prepared and characterized by UV-Vis spectroscopy, fourier-transform infrared spectroscopy (FT-IR), energy dispersive X-ray (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD) analysis. The minimum inhibitory concentration of the synthesized nanoparticle against Staphylococcus aureus was found to be 100⯱â¯0.80⯵g/mL with 9.38⯱â¯0.04â¯mm zone of inhibition. The bactericidal activity was shown primarily due to membrane damage evident from SEM, atomic force microscopy (AFM), potassium efflux, cellular material leakage, and bio-electrochemical changes in electron transport chain data. It was also of interest to find PC@AgNPs interfering with biofilm formation by S.aureus, assessed qualitatively by SEM, confocal laser scanning microscopy (CLSM) and quantitatively by dye staining method. The bio-compatibility of PC@AgNPs was established by anti-coagulant, thrombolytic, partial thromboplastin time, thrombin-like activity and fibrinolytic activity that suggested its good maintenance of hemostatic conditions. PC@AgNPs also prevented the coagulation of rabbit plasma which as per the standard drug Dabigatran reaction was indicative of the down-regulation of virulence Coa gene expression.
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Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Anticoagulantes/farmacologia , Biofilmes/efeitos dos fármacos , Ácidos Graxos/análise , Fibrinolíticos/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Química Verde , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Extratos Vegetais/química , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
In this work, we reported the successful synthesis of novel Ag/TiO2 /CuFe2 O4 ternary nanocomposite by hydrothermal technique by using TiO2 /CuFe2 O4 binary nanocomposite precursor that was also prepared by hydrothermal treatment by using TiO2 nanoparticles and CuFe2 O4 nanoparticles synthesized via sol-gel method. The synthesized nanomaterials were accessed for their morphological, structural, and optical properties. X-ray diffraction (XRD) study reveals the formation of pure Ag/TiO2 /CuFe2 O4 ternary nanocomposite in which the Ag, TiO2 , and CuFe2 O4 are in anatase, spinal, and cubic crystal phases, respectively. Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analyses of Ag/TiO2 /CuFe2 O4 ternary nanocomposite indicated granule-shaped morphology with bright spots of silver. The existence of Ti, O, Cu, Fe, and Ag without any other elements in the energy-dispersive X-ray spectroscopy (EDS) spectra of the prepared ternary nanocomposite depict its purity and its polycrystalline nature was confirmed by its selected area electron diffraction (SAED) pattern. The ternary nanocomposite was utilized for the methylene blue dye degradation with an optimum dose of 1.00 g/100 ml under ultraviolet (UV) light; the enhanced photocatalytic activity of the composite is attributed mainly due to the appreciable magnitudinal difference of positive charge of the valence band and negative charge of the conduction band of TiO2 and CuFe2 O4 ; meanwhile, the interfacially placed Ag acts as a sink for the elections. Also, the ternary nanocomposite showed satisfactory antibacterial activities. PRACTITIONER POINTS: The prepared ternary nanocomposite showed effective results in dye degradation and satisfactory antibacterial property. The concentration of methylene dye has decreased considerably in every degradation process which was accessed through UV-vis studies. The highest degradation by using the ternary nanocomposite archived at pH = 6 Appreciable antibacterial activity was achieved against a few Gram-positive strains and Gram-negative strains of bacteria. This research activity can open a broad area of research towards textile dye degradation and antibacterial studies.
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Azul de Metileno , Nanocompostos , Antibacterianos/química , Antibacterianos/farmacologia , Catálise , Azul de Metileno/química , Nanocompostos/química , Titânio/química , Titânio/farmacologiaRESUMO
OBJECTIVE: To systematically review the literature focusing on obstetric and perinatal outcomes in women with previous or current eating disorders (EDs) and on the consequences of maternal EDs for the offspring. METHODS: The study was performed following the systematic review and meta-analysis (PRISMA) statement. PubMed, SciELO, and Cochrane databases were searched for non-interventional studies published in English or Portuguese from January 1980 to December 2020. Risk of bias was assessed using the Methods guide for effectiveness and comparative effectiveness reviews (American Agency for Healthcare Research and Quality). RESULTS: The search yielded 441 records, and 30 articles were included. The psychiatric outcome associated with EDs in women was mainly perinatal depression. The most prevalent obstetric outcomes observed in women with EDs were vomiting, hyperemesis, bleeding, and anemia. Most studies found maternal anorexia nervosa and bulimia nervosa to be associated with low birth weight and slow fetal growth. Women with binge EDs delivered children with increased birth weight. Of the 30 studies included, methodological quality was good in seven, fair in eight, and poor in 15 studies. CONCLUSION: A considerable body of evidence was reviewed to assess obstetric and perinatal outcomes in EDs. Acute and lifetime EDs, especially if severe, correlated with poor perinatal, obstetric, and neonatal outcomes. Obstetricians and general practitioners should be vigilant and screen for EDs during pregnancy.
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Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Criança , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , GravidezRESUMO
Biomaterial research has improved the delivery and efficacy of drugs over a wide range of pharmaceutical applications. The objective of this study was to synthesize benzodioxane coupled piperazine decorated chitosan silver nanoparticle (Bcp*C@AgNPs) against methicillin-resistant Staphylococcus aureus (MRSA) and to assess the nanoparticle as an effective candidate for antibacterial and anti-biofilm care. Antibacterial activity of the compound was examined and minimum inhibitory concentration (MIC) was observed at (10.21 ± 0.03 ZOI) a concentration of 200 µg/mL. The Bcp*C@AgNPs interferes with surface adherence of MRSA, suggesting an anti-biofilm distinctive property that is verified for the first time by confocal laser microscopic studies. By ADMET studies the absorption, distribution, metabolism, excretion and toxicity of the compound was examined. The interaction solidity and the stability of the compound when surrounded by water molecules were analyzed by docking and dynamic simulation analysis. The myoblast cell line (L6) was considered for toxicity study and was observed that the compound exhibited less toxic effect. This current research highlights the biocidal efficiency of Bcp*C@AgNPs with their bactericidal and anti-biofilm properties over potential interesting clinical trial targets in future.
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Biofilmes/efeitos dos fármacos , Quitosana/síntese química , Dioxanos/farmacologia , Nanopartículas Metálicas/química , Staphylococcus aureus Resistente à Meticilina/fisiologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Piperazina/farmacologia , Prata/farmacologia , Animais , Anti-Infecciosos/farmacologia , Linhagem Celular , Quitosana/química , Fluorescência , Ligantes , Nanopartículas Metálicas/ultraestrutura , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/ultraestrutura , Testes de Sensibilidade Microbiana , Piperazina/química , Plâncton/efeitos dos fármacos , Ratos , Testes de ToxicidadeRESUMO
OBJECTIVE: This study translated, culturally adapted, and validated a Brazilian Portuguese version (SCOFF-BR) of the Sick, Control, One Stone, Fat, Food Questionnaire (SCOFF) to screen eating disorders in young adults. METHODS: This study used back-translation to culturally adapt the questionnaire according to International Society of Pharmacoeconomics and Outcome Research principles. The SCOFF-BR validation process involved a sample of men and women aged 18-32 years from a university community. After the participants completed the SCOFF-BR questionnaire, pre-trained researchers interviewed them with the Mini International Neuropsychiatric Interview (MINI). The presence of eating disorders was determined according to DSM-5 criteria. RESULTS: Of the 361 subjects, 9.7% had an eating disorder (2.2% anorexia nervosa, 5% bulimia nervosa, and 2.5% binge-eating disorder). Using a cutoff point of two positive responses, we obtained a sensitivity of 80% and a specificity of 71.5%, with an accuracy of 72.3%. The positive and negative predictive values were 23.1% and 97.1%, respectively. CONCLUSION: This study demonstrated that the Brazilian version of the SCOFF questionnaire presents satisfactory accuracy and reliability to screen eating disorders among young adults in the Brazilian university community.
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Transtornos da Alimentação e da Ingestão de Alimentos , Universidades , Brasil , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
Marine invertebrates produce different kinds of sulfated polysaccharides. These glycans play essential roles in several biological processes and the study of these molecules is promising in a variety of fields. In the following sections, we describe the materials and methods used for the extraction, purification, and characterization of marine invertebrate-derived glycosaminoglycans.
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Glicosaminoglicanos/química , Sulfatos/química , Animais , Organismos Aquáticos/química , Precipitação Química , Cromatografia por Troca Iônica/métodos , Dissecação/métodos , Eletroforese em Gel de Ágar/métodos , Glicosaminoglicanos/isolamento & purificação , Invertebrados/química , Espectroscopia de Ressonância Magnética/métodos , Proteólise , Sulfatos/isolamento & purificaçãoRESUMO
OBJECTIVES: Walking and postural balance are extremely important to obtain food and to work. Both are critical for quality of life and ability to survive. While walking reflects musculoskeletal and cardiopulmonary systems, postural balance depends on body size, muscle tone, visual, vestibular and nervous systems. Since GH and IGF-I act on all these systems, we decided to study those parameters in a cohort of individuals with severe short stature due to untreated isolated GH deficiency (IGHD) caused by a mutation in the GHRH receptor gene. These IGHD subjects, despite reduction in muscle mass, are very active and have normal longevity. METHODS: In a cross-sectional study, we assessed walking (by a 6-min walk test), postural balance (by force platform) and fall risk (by the 'Timed Up and Go' test) in 31 IGHD and 40 matched health controls. RESULTS: The percentage of the walked distance measured in relation to the predicted one was similar in groups, but higher in IGHD, when corrected by the leg length. Absolute postural balance data showed similar velocity of unipodal support in the two groups, and better values, with open and closed eyes and unipodal support, in IGHD, but these differences became non-significant when corrected for height and lower-limb length. The time in 'Timed Up and Go' test was higher in IGHD cohort, but still below the cut-off value for fall risk. CONCLUSION: IGHD subjects exhibit satisfactory walking and postural balance, without increase in fall risk.
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PURPOSE: While growth hormone (GH) and the insulin-like growth factor type I (IGF-I) are known to exert synergistic actions on muscle anabolism, the consequences of prolonged GH deficiency (GHD) on muscle function have not been well defined. We have previously described a large cohort of subjects with isolated GHD (IGHD) caused by a mutation in the GH-releasing hormone receptor gene, with low serum levels of GH and IGF-I. The aim of this study was to assess muscular function in these IGHD subjects. METHODS: A total of 31 GH-naïve IGHD (16 males) and 40 control (20 males) subjects, matched by age and degree of daily physical activity, were enrolled. Fat free mass was measured by bioelectrical impedance; muscle strength by dynamometry of handgrip, trunk extension, and knee extension; myoelectric activity and muscle fatigue by fractal dimension; conduction velocity in vastus medialis, rectus femoris, and vastus lateralis muscles by surface electromyography. RESULTS: The IGHD group showed higher knee extension strength both when corrected for weight and fat free mass, and higher handgrip and trunk extension strength corrected by fat free mass. They also exhibit higher conduction velocity of the muscles vastus medialis, rectus femoris, and vastus lateralis, but lower free fat mass and myoelectric activity of the vastus medialis, rectus femoris and vastus lateralis. There were no differences between the two groups in fractal dimension in all studied muscles. CONCLUSION: Individuals with untreated IGHD have better muscle strength parameters adjusted for weight and fat free mass than controls. They also exhibit greater peripheral resistance to fatigue, demonstrating satisfactory muscle function.
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Nanismo Hipofisário/fisiopatologia , Músculo Esquelético/fisiopatologia , Adulto , Idoso , Composição Corporal , Brasil , Estudos de Coortes , Nanismo Hipofisário/genética , Impedância Elétrica , Eletromiografia , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Fadiga Muscular , Força Muscular , Dinamômetro de Força Muscular , Receptores da Somatotropina/genéticaRESUMO
Nanoparticles (NPs) are currently being investigated along with the use of biodegradable polymer containing active agents in many areas of medicine for targeted applications. The present study was aimed to synthesize novel compound Benzodioxane midst piperazine (BP) and characterization of a BP decorated chitosan silver nanoparticles (BP*C@AgNPs) and shown effective against hazardous pathogens, and also having anti-inflammatory property. It was further evaluated for molecular docking proofs, and toxicity. The BP*C@AgNPs had spherical shape with size of 36.6nm with wide biocidal activity against hazardous Gram-positive and Gram-negative bacteria with excellent inhibition at 100µg/mL for S. aureus (10.08±0.05mm ZOI), and E. coli (10.03±0.04mm ZOI) compared to antibiotic Streptomycin. The anti-inflammatory activity exhibited IC50 value of 71.61±1.05µg/mL for BP*C@AgNPs compared to indomethacin (IC50=40.15±1.21µg/mL). Also, the docking study of BP showed excellent score for COX1 and DNA gyrase. This in silico study confirmed the achieved efficacy of BP, with less toxicity against normal PMBCs in vitro and in vivo studies. This study concludes that, the novel synthesized BP*C@AgNPs had excellent biocidal property and as anti-inflammatory candidate revealed by docking studies, it confirms BP*C@AgNPs for first-class therapeutic applications in the area of medicinal nanotechnology for the coming days.
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Anti-Infecciosos/química , Anti-Inflamatórios/química , Quitosana , Nanopartículas Metálicas/química , Piperazinas/química , Prata , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/ultraestrutura , Quitosana/química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Testes de Sensibilidade Microbiana , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estresse Oxidativo/efeitos dos fármacos , Piperazina , Prata/química , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Difração de Raios XRESUMO
BACKGROUND: Histone deacetylase inhibitors (HDACi) are promising anti-cancer drugs that could also be employed for urothelial carcinoma (UC) therapy. It is unclear, however, whether inhibition of all 11 zinc-dependent HDACs or of individual enzymes is more efficacious and specific. Here, we investigated the novel HDACi 19i (LMK235) with presumed preferential activity against class IIA HDAC4/5 in comparison to the pan-HDACi vorinostat (SAHA) and the HDAC4-specific HDACi TMP269 in UC cell lines with basal expression of HDAC4 and characterized two HDAC4-overexpressing UC cell lines. METHODS: Cytotoxic concentrations 50% (CC50s) for HDACi were determined by MTT assay and high-content analysis-based fluorescent live/dead assay in UC cell lines with different expression of HDAC4 and as well as in normal urothelial cell cultures, HBLAK and HEK-293 cell lines. Effects of HDACis were analyzed by flow cytometry; molecular changes were followed by qRT-PCR and Western blots. UC lines overexpressing HDAC4 were established by lentiviral transduction. Inhibitor activity profiles of HDACi were obtained by current state in vitro assays, and docking analysis was performed using an updated crystal structure of HDAC4. RESULTS: In UC cell lines, 19i CC50s ranged around 1 µM; control lines were similarly or less sensitive. Like SAHA, 19i increased the G2/M-fraction, disturbed mitosis, and elicited apoptosis or in some cells senescence. Thymidylate synthase expression was diminished, and p21CIP1 was induced; global histone acetylation and α-tubulin acetylation also increased. In most cell lines, 19i as well as SAHA induced HDAC5 and HDAC4 mRNAs while rather repressing HDAC7. UC cell lines overexpressing HDAC4 were not significantly less sensitive to 19i. Reevaluation of the in vitro HDAC isoenzyme activity inhibition profile of 19i and its docking to HDAC4 using current assays suggested rather low activity against class IIA HDACs. The specific class IIA HDAC inhibitor TMP269 impeded proliferation of UC cell lines only at concentrations > 10 µM. CONCLUSIONS: Anti-neoplastic effects of 19i on UC cells appear to be exerted by targeting class I HDACs. In fact, HDAC4 may rather impede UC growth. Our results suggest that targeting of class IIA HDACs 4/5 may not be optimal for UC therapy. Moreover, our investigation provides further evidence for cross-regulation of class IIA HDACs by class I HDACs.
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Carcinoma de Células de Transição/genética , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/genética , Neoplasias da Bexiga Urinária/genética , Vorinostat/farmacologia , Carcinoma de Células de Transição/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Metilação de DNA , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Inibidores de Histona Desacetilases/química , Histona Desacetilases/química , Humanos , Simulação de Acoplamento Molecular , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vorinostat/químicaRESUMO
INTRODUCTION: Recently, a novel purely synthetic topical haemostatic agent (PuraStat®) has been proposed in surgery based on the self-assembling tendency of some repeating peptide sequences. This transparent, ready to use hydrogel appears suitable for use in FEES with low rates of post-operative re-bleeding and adhesion formation.A first series of 60 patients experiencing endonasal powered turbinoplasty across various hospitals in Sydney using PuraStat® was observed for postoperative re-bleeding and adhesion formation. DISCUSSION: In all 60 patients, no post-operative re-bleeding was observed, while healing went well in absence of adhesion formation. Effective haemostasis with PuraStat® is well documented in other surgical fields, but its use in FEES and adhesion prevention is relatively novel. CONCLUSION: Synthetic self-assembling peptides appear to be indicated in this area. Further studies are needed to confirm their potential for adhesion prevention.
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We describe the use of peripheral veno-venous extracorporeal membrane oxygenation (VV ECMO) and high-flow nasal oxygen as procedural support in a patient undergoing debulking of a malignant tumour of the lower airway. Due to the significant risk of complete airway obstruction upon induction of anaesthesia, ECMO was established while the patient was awake, and was maintained without systemic anticoagulation to minimise the risk of intraoperative bleeding. This case illustrates that ECMO support with high-flow nasal oxygen can be considered as part of the algorithm for airway management during surgery for subtotal lower airway obstruction, as it may be the only viable option for maintaining adequate gas exchange.
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Obstrução das Vias Respiratórias/cirurgia , Oxigenação por Membrana Extracorpórea/métodos , Oxigênio/administração & dosagem , Neoplasias da Traqueia/cirurgia , Idoso , Manuseio das Vias Aéreas/métodos , Obstrução das Vias Respiratórias/etiologia , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Melanoma/patologia , Melanoma/cirurgia , Troca Gasosa Pulmonar , Neoplasias da Traqueia/patologia , Neoplasias da Traqueia/secundárioRESUMO
Staphylococcus aureus is a commonly found pathogen that can cause food-spoilage and life threatening infections. However, the potential molecular effects of natural active thymol molecules and chitosan silver nanoparticles (C@AgNPs) in bacteria remain unclear. This gap in the literature has prompted us to study the effects of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) against biofilm associated proteins in methicillin-resistant S. aureus (Bap-MRSA) 090 and also their toxicity, anti-cancer activity, and validation of their in silico molecular docking. The results showed excellent antibacterial activity of T-C@AgNPs against Bap-MRSA 090, having a minimum inhibitory concentration of 100 µg mL-1 and a 10.08 ± 0.06 mm zone of inhibition (ZOI). The cyclic voltammogram (CV) analysis clearly showed pore forming of T-C@AgNPs at 300 µg mL-1 concentration, and evidence of the interruption of the electron transport chain was clearly seen. The 200 µg mL-1 concentration exhibited a 52.60 ± 0.25% anti-biofilm property by T-C@AgNPs against Bap-MRSA 090. The T-C@AgNPs showed no toxicity to peripheral blood mononuclear cells (PBMC) (IC50 = 221 ± 0.71 µg mL-1) compared to the control, and anti-cancer activity against human triple negative breast cancer cell line (MDA-MB-231) (IC50 110 ± 1.0 µg mL-1) compared to the standard drug Doxorubicin (IC50 = 19 ± 1.0). The excellent properties of T-C@AgNPs were validated by in silico molecular docking studies and showed best match scoring to target proteins compared to standards. These excellent properties of T-C@AgNPs highlight for the first time its pharmacology and potential in medicinal drug development applications for future research.
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Objective: To systematically review the literature focusing on obstetric and perinatal outcomes in women with previous or current eating disorders (EDs) and on the consequences of maternal EDs for the offspring. Methods: The study was performed following the systematic review and meta-analysis (PRISMA) statement. PubMed, SciELO, and Cochrane databases were searched for non-interventional studies published in English or Portuguese from January 1980 to December 2020. Risk of bias was assessed using the Methods guide for effectiveness and comparative effectiveness reviews (American Agency for Healthcare Research and Quality). Results: The search yielded 441 records, and 30 articles were included. The psychiatric outcome associated with EDs in women was mainly perinatal depression. The most prevalent obstetric outcomes observed in women with EDs were vomiting, hyperemesis, bleeding, and anemia. Most studies found maternal anorexia nervosa and bulimia nervosa to be associated with low birth weight and slow fetal growth. Women with binge EDs delivered children with increased birth weight. Of the 30 studies included, methodological quality was good in seven, fair in eight, and poor in 15 studies. Conclusion: A considerable body of evidence was reviewed to assess obstetric and perinatal outcomes in EDs. Acute and lifetime EDs, especially if severe, correlated with poor perinatal, obstetric, and neonatal outcomes. Obstetricians and general practitioners should be vigilant and screen for EDs during pregnancy.
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APOBEC4 (A4) is a member of the AID/APOBEC family of cytidine deaminases. In this study we found a high mRNA expression of A4 in human testis. In contrast, there were only low levels of A4 mRNA detectable in 293T, HeLa, Jurkat or A3.01 cells. Ectopic expression of A4 in HeLa cells resulted in mostly cytoplasmic localization of the protein. To test whether A4 has antiviral activity similar to that of proteins of the APOBEC3 (A3) subfamily, A4 was co-expressed in 293T cells with wild type HIV-1 and HIV-1 luciferase reporter viruses. We found that A4 did not inhibit the replication of HIV-1 but instead enhanced the production of HIV-1 in a dose-dependent manner and seemed to act on the viral LTR. A4 did not show detectable cytidine deamination activity in vitro and weakly interacted with single-stranded DNA. The presence of A4 in virus producer cells enhanced HIV-1 replication by transiently transfected A4 or stably expressed A4 in HIV-susceptible cells. APOBEC4 was capable of similarly enhancing transcription from a broad spectrum of promoters, regardless of whether they were viral or mammalian. We hypothesize that A4 may have a natural role in modulating host promoters or endogenous LTR promoters.
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Citidina Desaminase/fisiologia , HIV-1/fisiologia , Replicação Viral/fisiologia , Linhagem Celular , Citidina/metabolismo , Citidina Desaminase/metabolismo , Desaminação , Repetição Terminal Longa de HIV , Humanos , Masculino , Regiões Promotoras Genéticas , Testículo/metabolismoRESUMO
The protease ADAM17 (a disintegrin and metalloproteinase 17) catalyzes the shedding of various transmembrane proteins from the surface of cells, including tumor necrosis factor (TNF) and its receptors. Liberation of TNF receptors (TNFRs) from cell surfaces can dampen the cellular response to TNF, a cytokine that is critical in the innate immune response and promotes programmed cell death but can also promote sepsis. Catalytically inactive members of the rhomboid family of proteases, iRhom1 and iRhom2, mediate the intracellular transport and maturation of ADAM17. Using a genetic screen, we found that the presence of either iRhom1 or iRhom2 lacking part of their extended amino-terminal cytoplasmic domain (herein referred to as ΔN) increases ADAM17 activity, TNFR shedding, and resistance to TNF-induced cell death in fibrosarcoma cells. Inhibitors of ADAM17, but not of other ADAM family members, prevented the effects of iRhom-ΔN expression. iRhom1 and iRhom2 were functionally redundant, suggesting a conserved role for the iRhom amino termini. Cells from patients with a dominantly inherited cancer susceptibility syndrome called tylosis with esophageal cancer (TOC) have amino-terminal mutations in iRhom2. Keratinocytes from TOC patients exhibited increased TNFR1 shedding compared with cells from healthy donors. Our results explain how loss of the amino terminus in iRhom1 and iRhom2 impairs TNF signaling, despite enhancing ADAM17 activity, and may explain how mutations in the amino-terminal region contribute to the cancer predisposition syndrome TOC.
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Proteínas ADAM/metabolismo , Neoplasias Esofágicas , Fibrossarcoma , Predisposição Genética para Doença , Ceratodermia Palmar e Plantar , Mutação , Proteínas de Neoplasias , Receptores do Fator de Necrose Tumoral/metabolismo , Proteínas ADAM/genética , Proteína ADAM17 , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Fibrossarcoma/genética , Fibrossarcoma/metabolismo , Fibrossarcoma/patologia , Humanos , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/metabolismo , Ceratodermia Palmar e Plantar/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estrutura Terciária de Proteína , Receptores do Fator de Necrose Tumoral/genéticaRESUMO
Noninvasive monitoring of cardiac output can greatly facilitate the clinical assessment and management of neonates with cardiovascular compromise. To assess normal values of cardiac output in neonates, mean blood flow velocity was measured in the ascending aorta from a suprasternal approach using a range-gated, pulsed Doppler velocity meter, and aortic root diameter was determined from an M-mode echocardiogram. These techniques were combined, and cardiac output was evaluated in 59 healthy premature and 62 term newborn infants during the first week of life. Birth weights ranged from 780 g to 4,740 g and gestational age from 27 to 42 weeks. Cardiac output values increased linearly with advancing birth weight (r = +.94, P less than 0.001) and gestational age (r = +.95, P less than .001). Mean cardiac output values (+/- SD) per kilogram of body weight were 249 +/- 34 mL/min/kg and decreased with advancing birth weight: less than 1,500 g = 265 +/- 32 mL/min/kg; 1,500 to 2,500 g = 253 +/- 34 mL/min/kg; and greater than 2,500 g = 241 +/- 33 mL/min/kg. For clinical use, 325 mL/min/kg and 200 mL/min/kg can be used as upper and lower limits of normal, respectively. Doppler cardiac output estimates compared favorably with studies using invasive techniques.
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Débito Cardíaco , Recém-Nascido , Recém-Nascido Prematuro , Peso ao Nascer , Velocidade do Fluxo Sanguíneo , Ecocardiografia , Idade Gestacional , Humanos , Valores de Referência , ReologiaRESUMO
Neurologic deterioration observed following head injury is recognized as having a deleterious effect on outcome. The present study examines this occurrence in detail to determine the frequency of these episodes, their antecedent events and causal relationships in order to identify patients who are at risk. Data was collected prospectively from a consecutive series of 427 patients entered into the international trial of the NMDA receptor antagonist Selfotel. Using a definition of neurologic worsening based upon objective criteria, 117 patients were identified who suffered 164 episodes of deterioration. The occurrence of a single episode of neurologic worsening increased mortality by more than five-fold and reduced favorable outcomes (good or moderate on the Glasgow Outcome Scale), by more than 50%. Increased intracranial volume resulting in intracranial hypertension was the single most frequent cause of neurologic worsening. This serves to emphasize the importance of more adequate treatments of intracranial hypertension in improving the outcome of patients with severe head injury.
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Traumatismos Craniocerebrais/etiologia , Traumatismos Craniocerebrais/fisiopatologia , Sistema Nervoso/fisiopatologia , Adolescente , Adulto , Idoso , Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/mortalidade , Progressão da Doença , Método Duplo-Cego , Feminino , Escala de Coma de Glasgow , Humanos , Pressão Intracraniana , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Wound care is constantly evolving with the advances in medicine. Search for the ideal dressing material still continues as wound care professionals are faced with several challenges. Due to the emergence of multi-resistant organisms and a decrease in newer antibiotics, wound care professionals have revisited the ancient healing methods by using traditional and alternative medicine in wound management. People's perception towards traditional medicine has also changed and is very encouraging. The concept of moist wound healing has been well accepted and traditional medicine has also incorporated this method to fasten the healing process. Several studies using herbal and traditional medicine from different continents have been documented in wound care management. Honey has been used extensively in wound care practice with excellent results. Recent scientific evidences and clinical trials conducted using traditional and alternative medicine in wound therapy holds good promise in the future.