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1.
Cell ; 167(4): 897-914, 2016 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-27814520

RESUMO

The dentate gyrus of the mammalian hippocampus continuously generates new neurons during adulthood. These adult-born neurons become functionally active and are thought to contribute to learning and memory, especially during their maturation phase, when they have extraordinary plasticity. In this Review, we discuss the molecular machinery involved in the generation of new neurons from a pool of adult neural stem cells and their integration into functional hippocampal circuits. We also summarize the potential functions of these newborn neurons in the adult brain, their contribution to behavior, and their relevance to disease.


Assuntos
Células-Tronco Adultas/citologia , Hipocampo/citologia , Hipocampo/fisiologia , Células-Tronco Neurais/citologia , Neurogênese , Células-Tronco Adultas/metabolismo , Animais , Humanos , Transtornos Mentais/patologia , Transtornos Mentais/fisiopatologia , Células-Tronco Neurais/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia
2.
Proc Natl Acad Sci U S A ; 119(32): e2201151119, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35930664

RESUMO

Epilepsy is a devastating brain disorder for which effective treatments are very limited. There is growing interest in early intervention, which requires a better mechanistic understanding of the early stages of this disorder. While diverse brain insults can lead to epileptic activity, a common cellular mechanism relies on uncontrolled recurrent excitatory activity. In the dentate gyrus, excitatory mossy cells (MCs) project extensively onto granule cells (GCs) throughout the hippocampus, thus establishing a recurrent MC-GC-MC excitatory loop. MCs are implicated in temporal lobe epilepsy, a common form of epilepsy, but their role during initial seizures (i.e., before the characteristic MC loss that occurs in late stages) is unclear. Here, we show that initial seizures acutely induced with an intraperitoneal kainic acid (KA) injection in adult mice, a well-established model that leads to experimental epilepsy, not only increased MC and GC activity in vivo but also triggered a brain-derived neurotrophic factor (BDNF)-dependent long-term potentiation (LTP) at MC-GC excitatory synapses. Moreover, in vivo induction of MC-GC LTP using MC-selective optogenetic stimulation worsened KA-induced seizures. Conversely, Bdnf genetic removal from GCs, which abolishes LTP, and selective MC silencing were both anticonvulsant. Thus, initial seizures are associated with MC-GC synaptic strengthening, which may promote later epileptic activity. Our findings reveal a potential mechanism of epileptogenesis that may help in developing therapeutic strategies for early intervention.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Epilepsia , Potenciação de Longa Duração , Fibras Musgosas Hipocampais , Convulsões , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/fisiopatologia , Ácido Caínico/farmacologia , Camundongos , Fibras Musgosas Hipocampais/efeitos dos fármacos , Fibras Musgosas Hipocampais/fisiopatologia , Convulsões/induzido quimicamente , Convulsões/fisiopatologia
3.
J Dairy Sci ; 106(12): 9276-9286, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37641286

RESUMO

The objective of this observational study was to describe variations in partial direct costs of clinical mastitis (CM) treatments among 37 dairy herds using data obtained from herd management records. Animal health and drug purchase records were retrospectively collected from 37 Wisconsin dairy herds for a period of 1 yr. Each farm was visited to verify case definitions, recording accuracy, and detection criteria of CM cases. Descriptive statistics were used to summarize cost of drugs and milk discard. Differences in costs among protocols, intramammary (IMM) products, parities, days in milk, and recurrence were analyzed using ANOVA. Of 20,625 cases of CM, 31% did not receive antimicrobial treatment. The average cost of drugs and milk discard (including cases that were not treated) was $192.36 ± 8.90 (mean ± SE) per case and ranged among farms from $118.13 to $337.25. For CM cases treated only with IMM antimicrobials, milk discard accounted for 87% of total costs and was highly influenced by duration of therapy. Differences in costs were observed among parities, recurrence, and stage of lactation at case detection. Eight different treatment protocols were observed, but 64% of cases were treated using only IMM antimicrobials. Treatment costs varied among protocols; however, cases treated using both IMM and injectable antimicrobials as well as supportive therapy had the greatest costs as they were also treated for the longest duration. Ceftiofur was used for 82% of cases that received IMM antimicrobials while ampicillin was used for 51% of cases treated using injectable antimicrobials. With the exception of ceftiofur and pirlimycin IMM products, many IMM products were given for durations that exceeded the maximum labeled duration. For cases treated using only IMM therapy, as compared with observed costs, we estimated that partial direct costs could be reduced by $65.20 per case if the minimum labeled durations were used. Overall, partial direct costs per case varied among herds, cow factors, and treatment protocols and were highly influenced by the duration of therapy.


Assuntos
Anti-Infecciosos , Doenças dos Bovinos , Mastite Bovina , Bovinos , Feminino , Animais , Fazendas , Wisconsin , Estudos Retrospectivos , Mastite Bovina/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Lactação , Leite , Antibacterianos/uso terapêutico , Indústria de Laticínios/métodos , Doenças dos Bovinos/tratamento farmacológico
4.
Public Health ; 220: 148-154, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37320945

RESUMO

OBJECTIVES: The study investigated the longitudinal association between physical activity and the risk of long COVID in patients who recovered from COVID-19 infection. STUDY DESIGN: We analyzed longitudinal data of the Prospective Study About Mental and Physical Health cohort, a prospective cohort study with adults living in Southern Brazil. METHODS: Participants responded to an online, self-administered questionnaire in June 2020 (wave 1) and June 2022 (wave 4). Only participants who self-reported a positive test for COVID-19 were included. Physical activity was assessed before (wave 1, retrospectively) and during the pandemic (wave 1). Long COVID was assessed in wave 4 and defined as any post-COVID-19 symptoms that persisted for at least 3 months after infection. RESULTS: A total of 237 participants (75.1% women; mean age [standard deviation]: 37.1 [12.3]) were included in this study. The prevalence of physical inactivity in baseline was 71.7%, whereas 76.4% were classified with long COVID in wave 4. In the multivariate analysis, physical activity during the pandemic was associated with a reduced likelihood of long COVID (prevalence ratio [PR]: 0.83; 95% confidence interval [CI]: 0.69-0.99) and a reduced duration of long COVID symptoms (odds ratio: 0.44; 95% CI: 0.26-0.75). Participants who remained physically active from before to during the pandemic were less likely to report long COVID (PR: 0.74; 95% CI: 0.58-0.95), fatigue (PR: 0.49; 95% CI: 0.32-0.76), neurological complications (PR: 0.47; 95% CI: 0.27-0.80), cough (PR: 0.40; 95% CI: 0.22-0.71), and loss of sense of smell or taste (PR: 0.43; 95% CI: 0.21-0.87) as symptom-specific long COVID. CONCLUSION: Physical activity practice was associated with reduced risk of long COVID in adults.


Assuntos
COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Adulto , Feminino , Masculino , COVID-19/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Exercício Físico
5.
Trop Anim Health Prod ; 55(5): 314, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37736780

RESUMO

Although it is considered an economically relevant and prevalent disease, little information is available on the epidemiology and risk factors of porcine proliferative enteropathy (PPE) in commercial pigs, and no publication is available on subsistence pig farming. The objectives of this study were to estimate the seroprevalence of L. intracellularis and identify associated risk factors in backyard pigs in the 12 mesoregions of the state of Minas Gerais, Brazil. Blood from pigs between 2 months and 6 years of age were sampled; an epidemiological questionnaire was applied to 288 properties investigated in 2016. Serum samples were tested for the presence of anti-L. intracellularis antibodies using an immunoperoxidase monolayer assay. The seroprevalence of L. intracellularis was 97.7% (CI 95%: 96.7-98.4), and there was no statistical difference among the prevalence of the sampled mesoregions. Only 3 of the 12 risk factors were significant when samples were analyzed from strongly seropositive animals (≥ 1:120) in a Poisson multivariate regression model. There was an interaction between properties in peri-urban areas and extensive production systems. This interaction demonstrated an increase in prevalence rates by 3.7 times (95%CI: 2.4-5.8). Properties close to dumps demonstrated an increase in prevalence rates by 2.2 times (95%CI: 0.99-4.8). In conclusion, anti-L. intracellularis antibodies were widely dispersed in subsistence pig farming's in Minas Gerais, indicating a wide circulation of the agent in this type of production system. The interactions of animals raised close to peri-urban areas, extensively, and close to landfills are risk factors for spread of PPE.


Assuntos
Lawsonia (Bactéria) , Animais , Suínos , Brasil/epidemiologia , Estudos Soroepidemiológicos , Agricultura , Fatores de Risco
6.
J Neurosci ; 41(13): 2899-2910, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33637561

RESUMO

The addition of new neurons to existing neural circuits in the adult brain remains of great interest to neurobiology because of its therapeutic implications. The premier model for studying this process has been the hippocampal dentate gyrus in mice, where new neurons are added to mature circuits during adulthood. Notably, external factors such as an enriched environment (EE) and exercise markedly increase hippocampal neurogenesis. Here, we demonstrate that EE acts by increasing fibroblast growth factor receptor (FGFR) function autonomously within neurogenic cells to expand their numbers in adult male and female mice. FGFRs activated by EE signal through their mediators, FGFR substrate (FRS), to induce stem cell proliferation, and through FRS and phospholipase Cγ to increase the number of adult-born neurons, providing a mechanism for how EE promotes adult neurogenesis.SIGNIFICANCE STATEMENT How the environment we live in affects cognition remains poorly understood. In the current study, we explore the mechanism underlying the effects of an enriched environment on the production of new neurons in the adult hippocampal dentate gyrus, a brain area integral in forming new memories. A mechanism is provided for how neural precursor cells in the adult mammalian dentate gyrus respond to an enriched environment to increase their neurogenic output. Namely, an enriched environment acts on stem and progenitor cells by activating fibroblast growth factor receptor signaling through phospholipase Cγ and FGF receptor substrate proteins to expand the pool of precursor cells.


Assuntos
Meio Ambiente , Hipocampo/citologia , Hipocampo/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Fatores Etários , Animais , Feminino , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Receptores de Fatores de Crescimento de Fibroblastos/genética
7.
Fish Shellfish Immunol ; 83: 348-358, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30227256

RESUMO

This study aimed to evaluate the protective effects of four autochthonous bacteria isolated from juvenile sole (Solea senegalensis) intestine as dietary probiotic supplement against bacterial pathogen infection and handling/transport stressors. Growth performance and immune responses were evaluated after 85 days of feeding trial. Sole (IBW = 16.07 ±â€¯0.11 g) were fed six experimental diets, a control diet (CTRL, without the dietary probiotic supplementation), and five diets supplemented with probiotic bacteria: PB1 (Shewanella hafniensis), PB2 (Enterococcus raffinosus), PB3 (Shewanella hafniensis + Arthrobacter soli), PB4 (Pseudomonas protegens + Arthrobacter soli) and PB5 (Shewanella hafniensis + Arthrobacter soli + Enterococcus raffinosus). All bacteria were selected based on their in vitro antimicrobial activity. After the growth trial, fish were submitted to a stress factor (transport) and then each dietary group was divided in two additional groups: non-infected (placebo) and infected with Photobacterium damselae subsp. piscicida. Immune and antioxidant responses were evaluated at day 10 post-infection. In infection trial A, fish were infected on the same day of transport, whereas in trial B fish were infected after a 7-day recovery from the transport stress. At the end of the feeding trial, fish fed with PB2 and PB4 showed lower final body weight when compared with the other dietary groups. Respiratory burst activity and nitric oxide production were not affected by probiotic supplementation. Fish fed with PB5 presented lower peroxidase activity compared to CTRL. Lysozyme and alternative complement pathway activity (ACH50) showed no significant differences between treatments. The innate immune responses were significantly affected after handling stress and bacterial infection. In trial A, the ACH50 levels of infected fish were significantly lower than the placebo groups. On the other hand, in trial B fish infected with Pdp demonstrated higher ACH50 levels when compared to placebos. Peroxidase levels were strongly modulated by bacterial infection and handling stress. In trials A and B, infection had a clear downgrade effect in peroxidase levels. Lipid peroxidation, catalase, glutathione S-transferase and glutathione reductase were altered by both bacterial infection and transport. Overall, dietary probiotic supplementation did not influence growth performance of sole. The immune and oxidative defenses of sole responded differently to infection depending on the probiotic and the synergy between pathogen infection and transport.


Assuntos
Doenças dos Peixes/imunologia , Linguados/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Photobacterium , Probióticos/farmacologia , Estresse Fisiológico/imunologia , Animais , Dieta/veterinária , Linguados/crescimento & desenvolvimento , Infecções por Bactérias Gram-Negativas/veterinária
8.
J Dairy Sci ; 101(10): 9406-9418, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30031577

RESUMO

Determination of antimicrobial susceptibility (AMS) of Escherichia coli causing clinical mastitis (CM) according to the phylogenetic groups and its association with descriptors at the cow and herd level may help improve specific strategies for treatment and control of this pathogen in dairy herds. The aims of the present study were to (a) determine the frequency of phylogenetic groups of E. coli isolated from CM in dairy cows, and its association with cow-level descriptors (parity, lactation stage, CM severity, and affected quarter position), housing system, and season; and (b) determine and compare AMS among E. coli phylogenetic groups. A quadruplex PCR method was used to classify E. coli isolates into 1 of the 7 phylogenetic groups. Minimal inhibitory concentrations were determined for 10 antimicrobials, and survival analysis was performed to evaluate the AMS differences among E. coli phylogroups. Most E. coli isolates belonged to phylogroups A (52%) and B1 (38%). None of the cow- and herd-level descriptors were associated with the E. coli phylogenetic groups. Overall, E. coli isolates were mostly susceptible to ceftiofur (96.8%), sulfadimethoxine (75.5%), and cephalothin (74.5%). Based on the survival analysis, differences in AMS between phylogenetic groups of E. coli was observed only for cephalothin, in which strains of phylogroup A were inhibited at lower minimum inhibitory concentration than strains of phylogroup B1. Results of this study indicated low susceptibility of E. coli isolates identified from CM to most antimicrobials. In addition, differences in AMS can occur among E. coli phylogenetic groups, although they may be uncommon as they were limited to only one antimicrobial (i.e., cephalothin).


Assuntos
Antibacterianos/uso terapêutico , Infecções por Escherichia coli/veterinária , Escherichia coli/efeitos dos fármacos , Mastite Bovina/microbiologia , Testes de Sensibilidade Microbiana/veterinária , Animais , Bovinos , Escherichia coli/classificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Feminino , Mastite Bovina/tratamento farmacológico , Filogenia , Gravidez
9.
J Dairy Sci ; 101(11): 10116-10125, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30146281

RESUMO

The emergence of antimicrobial resistance to commonly used antibiotics has necessitated the development of new antimicrobial products. Crude extracts produced by actinomycetes contain antimicrobial metabolites that can inhibit bacterial growth. The objective of our study was to evaluate the antimicrobial activity of crude extracts (Caat1-54 and CaatP5-8) produced by actinomycetes against isolates of Staphylococcus aureus, Staphylococcus chromogenes, Streptococcus dysgalactiae, and Streptococcus uberis, which were obtained from the milk of cows affected by mastitis in 23 dairy herds. Twenty isolates of each bacterial species were used to define minimum inhibitory concentrations (MIC) of both crude extracts and ceftiofur (positive control). The MIC50 and MIC90 were defined at the concentration required to inhibit the growth of 50 and 90% of bacterial isolates tested, respectively. The MIC results were evaluated by survival analysis. Staphylococcus aureus isolates presented MIC90 of Caat 1-54 ≥6.25 µg/mL, ceftiofur ≥12.5 µg/mL, and Caat P5-8 ≥100 µg/mL. Streptococcus uberis presented MIC90 of ceftiofur ≥0.39 µg/mL, Caat 1-54 ≥50 µg/mL, and Caat P5-8 ≥100 µg/mL. Staphylococcus chromogenes isolated from subclinical mastitis presented MIC90 of Caat 1-54 ≥0.78 µg/mL and ceftiofur and Caat P5-8 of ≥6.25 and ≥100 µg/mL, respectively. Streptococcus dysgalactiae isolated from clinical mastitis presented similar MIC90 values between antimicrobials tested (ceftiofur, Caat 1-54, and Caat P-58), but these values (≥100 µg/mL) were higher than the values obtained from other pathogens evaluated in the present study. Our results indicate that Caat 1-54 and Caat P5-8 crude extracts present in vitro antimicrobial activity against isolates of Staph. aureus, Staph. chromogenes, Strep. dysgalactiae, and Strep. uberis isolated from clinical and subclinical mastitis.


Assuntos
Actinobacteria/química , Anti-Infecciosos/farmacologia , Misturas Complexas/farmacologia , Mastite Bovina/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Infecções Estreptocócicas/veterinária , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Bovinos , Cefalosporinas/química , Cefalosporinas/isolamento & purificação , Cefalosporinas/farmacologia , Misturas Complexas/química , Misturas Complexas/isolamento & purificação , Feminino , Mastite Bovina/microbiologia , Testes de Sensibilidade Microbiana/veterinária , Leite/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus/efeitos dos fármacos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus/efeitos dos fármacos
10.
Zygote ; 26(6): 465-470, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30767819

RESUMO

SummaryThe present study aimed to investigate the effect of quercetin as an alternative antioxidant to cysteamine on in vitro maturation. Oocytes were collected from goat ovaries, destined for in vitro maturation and distributed into three groups: CIS group, oocytes were immersed in MIV base medium; in Groups Q4 and Q8, oocytes were immersed in the medium of the CIS group, adding 4 µM or 8 µM of quercetin, respectively, and cultured for 24 h at 38.5°C with 5% CO2. The CIS and Q4 groups presented the same percentage of expanded cumulus cells, but the per cent in the Q8 group was significantly lower than that of the other groups (P<0.05). The oocyte retraction rate in the Q8 group was higher (P<0.05) than in the CIS and Q4 groups. Treatment with 8 µM of quercetin presented a lower proportion of expanded oocytes than the CIS group and 4 µM of quercetin (P<0.05). The percentage of MII oocytes was higher in the Q4 group than in the CIS group (P<0.05), but the percentages in the CIS and Q8 groups were similar. The rate of apoptosis was higher in the CIS group than in the other groups (P<0.05). In addition, oocytes matured with 4 µM quercetin showed higher mitochondrial activity than matured oocytes in the CIS and Q8 groups (P<0.05). In conclusion, 4 µM of quercetin can be used as an alternative to cysteamine in the in vitro maturation of goat oocytes.


Assuntos
Técnicas de Maturação in Vitro de Oócitos/métodos , Mitocôndrias/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Quercetina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Cromatina/efeitos dos fármacos , Cromatina/ultraestrutura , Células do Cúmulo , Fragmentação do DNA/efeitos dos fármacos , Glutationa/metabolismo , Cabras , Mitocôndrias/metabolismo , Quercetina/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo
12.
Int J Cosmet Sci ; 40(4): 408-419, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30047992

RESUMO

OBJECTIVE: Human hair is an element with unquestionable relevance in society both for women and men. Therefore, it is of great importance to develop new cosmetic products for hair care capable to restore and improve hair's characteristics. Here, we explore the potential of keratin-based particles in the protection and recovery of hair mechanical properties and thermal stability. METHODS: Keratin-based particles were obtained by high pressure homogenization (HPH) using keratin and silk fibroin. The particles were characterized regarding size, superficial charge and polydispersity index. Their safety to cells was assessed using human skin keratinocytes. Virgin and overbleached Asian hair were treated with eight keratin-based formulations. The effect of particles on hair's mechanical properties was evaluated in terms of stiffness and tensile strength. The impact of treatments in hair thermal performance was studied using differential scanning calorimetry (DSC). RESULTS: Keratin-based particles were capable to recover and/or improve the mechanical properties of virgin and overbleached hair. Virgin hair treated with K80 SF20 P particles presented an improvement in the mechanical properties of around 40%. An increase in keratin α-helix denaturation enthalpy and in surface smoothness for both types of hair was also verified after treatment. These particles demonstrated stability over time and proved to be safe when tested in human keratinocytes. CONCLUSION: The keratin-based particles here presented have the potential to be incorporated in the development of new and effective hair care cosmetic formulations.


Assuntos
Preparações para Cabelo , Cabelo/efeitos dos fármacos , Queratinas/administração & dosagem , Povo Asiático , Varredura Diferencial de Calorimetria , Linhagem Celular , Feminino , Humanos , Queratinócitos/efeitos dos fármacos , Queratinas/química , Queratinas/farmacologia , Masculino , Microscopia Eletrônica de Transmissão e Varredura , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier , Resistência à Tração
13.
Neural Comput ; 29(1): 50-93, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27870612

RESUMO

Our understanding of neural population coding has been limited by a lack of analysis methods to characterize spiking data from large populations. The biggest challenge comes from the fact that the number of possible network activity patterns scales exponentially with the number of neurons recorded ([Formula: see text]). Here we introduce a new statistical method for characterizing neural population activity that requires semi-independent fitting of only as many parameters as the square of the number of neurons, requiring drastically smaller data sets and minimal computation time. The model works by matching the population rate (the number of neurons synchronously active) and the probability that each individual neuron fires given the population rate. We found that this model can accurately fit synthetic data from up to 1000 neurons. We also found that the model could rapidly decode visual stimuli from neural population data from macaque primary visual cortex about 65 ms after stimulus onset. Finally, we used the model to estimate the entropy of neural population activity in developing mouse somatosensory cortex and, surprisingly, found that it first increases, and then decreases during development. This statistical model opens new options for interrogating neural population data and can bolster the use of modern large-scale in vivo Ca[Formula: see text] and voltage imaging tools.


Assuntos
Potenciais de Ação/fisiologia , Modelos Neurológicos , Modelos Estatísticos , Neurônios/fisiologia , Animais , Cálcio/metabolismo , Entropia , Macaca , Estimulação Luminosa , Córtex Visual/citologia , Imagens com Corantes Sensíveis à Voltagem
14.
Phys Chem Chem Phys ; 19(2): 1335-1341, 2017 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-27973632

RESUMO

This study provides a comprehensive insight into the effects of controlled off-stoichiometry on the structural and multiferroic properties of the hexagonal manganite LuMn1-xO3+δ (x = 0.02; δ ∼ 0), supported by neutron powder diffraction measurements confirming single phase P63cm symmetry and evidencing a relevant ferromagnetic component, below TN ∼ 90 K, which breaks the archetypal geometrically frustrated antiferromagnetic state typically ascribed to LuMnO3. The perturbations in the triangular disposition of spins prompt an additional electric polarization contribution and a clear enhancement of the magnetoelectric coupling which are in good agreement with the results of first principles calculations. In addition, Raman spectroscopy, dielectric permittivity, pyroelectric current and magnetic measurements as a function of temperature point out the precursor effects of the magnetic phase transitions involving a strong coupling between spins, lattice and electric order, even above the Néel temperature.

15.
J Eur Acad Dermatol Venereol ; 31(3): 507-517, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27768242

RESUMO

BACKGROUND: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis. OBJECTIVE: Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). METHODS: Two hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for apremilast vs. etanercept comparisons. RESULTS: At Week 16, PASI-75 achievement was greater with apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept (P < 0.0001 vs. placebo). PASI-75 response was maintained in 47.3% (apremilast/apremilast), 49.4% (etanercept/apremilast) and 47.9% (placebo/apremilast) of patients at Week 52. Most common adverse events (≥5%) with apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with apremilast. CONCLUSION: Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of apremilast. Switching from etanercept to apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with apremilast through Week 52.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Etanercepte/uso terapêutico , Psoríase/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Diarreia/induzido quimicamente , Método Duplo-Cego , Etanercepte/efeitos adversos , Feminino , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringite/induzido quimicamente , Náusea/induzido quimicamente , Dor/etiologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Prurido/etiologia , Psoríase/complicações , Infecções Respiratórias/induzido quimicamente , Índice de Gravidade de Doença , Avaliação de Sintomas , Cefaleia do Tipo Tensional/induzido quimicamente , Talidomida/efeitos adversos , Talidomida/uso terapêutico
16.
J Clin Pharm Ther ; 42(2): 239-243, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27859438

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. MAIN ISSUES: The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. WHAT IS NEW AND CONCLUSION: The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Farmacêuticos , Serviço de Farmácia Hospitalar , Humanos
17.
J Dairy Sci ; 100(7): 5701-5708, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28478008

RESUMO

The aim of the present study was to evaluate the effect of different sources of Saccharomyces cerevisiae (SC) biomass (20.0 g/d) obtained from sugarcane (cell wall, CW; dried yeast, DY; autolyzed yeast, AY) and the beer industry (partially dehydrated brewery yeast, BY) on milk production, fat and protein percentages, and aflatoxin M1 (AFM1) excretion in milk from dairy cows receiving 480 µg aflatoxin B1 (AFB1) per day. A completely randomized design was used with 2 lactating cows assigned to each of 10 dietary treatments, as follows: negative controls (no AFB1 or SC-based biomass), positive controls (AFB1 alone), DY alone, DY + AFB1, BY alone, BY + AFB1, CW alone, CW + AFB1, AY alone, and AY + AFB1. The cows in the aflatoxin treatment group received AFB1 from d 1 to 6, while the SC biomass was administered with the AFB1 bolus from d 4 to 6. Aflatoxin B1 or SC-based products did not affect milk production or milk composition during the experimental period. Aflatoxin M1 was detected in the milk from all aflatoxin treatment group cows, reaching maximum levels at d 3 and varying from 0.52 ± 0.03 to 1.00 ± 0.04 µg/L. At end of the treatment period, CW, AY, DY, and BY removed 78%, 89%, 45%, and 50% of AFM1 from the milk, respectively, based on the highest level found on d 3. Results indicate a potential application of industrial fermentation by-products, especially CW and AY, as a feed additive in the diets of dairy cows to reduce the excretion of AFM1 in milk.


Assuntos
Aflatoxina B1/administração & dosagem , Aflatoxina M1/metabolismo , Biomassa , Proteínas do Leite/metabolismo , Leite/química , Leite/metabolismo , Saccharomyces cerevisiae , Ração Animal , Animais , Bovinos , Feminino , Aditivos Alimentares/administração & dosagem , Lactação , Saccharum , Fermento Seco
18.
Genet Mol Res ; 16(1)2017 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-28362991

RESUMO

Ocimum gratissimum L. or clove basil, belongs to the Lamiaceae family, has various desirable uses and applications. Beyond its aromatic, seasoning, and medicinal applications, this plant also has antimicrobial activity. This study was aimed at assessing the antifungal activity, yield, and composition of the essential oil (EO) of O. gratissimum. The species was cultivated in garden beds with dystrophic red latosol soil type containing high organic-matter content. The EO was obtained by hydrodistillation of dried leaves in a modified Clevenger apparatus, followed by determination of its content. Chemical characterization was carried out by gas chromatography-mass spectrometry (GC-MS). Microbial activity was assessed using the broth microdilution method, by determining the minimum inhibitory concentration (MIC), in order to compare the antimicrobial effect of EO in 10 isolates-Fusarium oxysporum f. sp tracheiphilum (CMM-0033), F. oxysporum f. sp. cubense (CMM-0813 and CMM-2819), F. oxysporum f. sp lycopersici (CMM-1104), F. solani (CMM-3828), Rhizoctonia solani (CMM-3274), and Macrophomina phaseolina (CMM-2715, CMM-3875, CMM-3615, and CMM-3650). The EO was a highly effective inhibitor of the studied phytopathogenic fungi, with MICs varying from 31.25 to 125 µg/mL. F. oxysporum f. sp lycopersici and R. solani were the most sensitive; both were inhibited at an MIC of 31.25 µg/mL. The EO content in the plant extract was 0.18%. Thirty chemical compounds were detected via GC-MS, with linalool (32.9%) being the major compound followed by 1,8-cineole (21.9%), both oxygenated monoterpenes. It can be concluded that clove basil EO is a highly effective antifungal agent, and therefore, a potential alternative for the control of plant pathogenic diseases.


Assuntos
Ascomicetos/efeitos dos fármacos , Fungos Mitospóricos/efeitos dos fármacos , Ocimum/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Ascomicetos/classificação , Fusarium/classificação , Fusarium/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Fungos Mitospóricos/classificação , Folhas de Planta/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Rhizoctonia/efeitos dos fármacos
19.
Genet Mol Res ; 16(2)2017 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-28407186

RESUMO

Brunfelsia genus is traditionally utilized in popular medicine due to its antibacterial and antifungal properties to name but a few. However, studies on the antimicrobial activity of Brunfelsia uniflora flower oleoresin have not been found yet. This study aimed to evaluate the chemical composition and antimicrobial activity of B. uniflora flower oleoresin obtained by supercritical carbon dioxide. Oleoresin from the plant dried flowers was obtained by carbon dioxide, and the chemical composition was analyzed by gas chromatographic-mass spectrometry. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) of this oleoresin for seven bacteria and eight fungi were determined using 96-well microtiter plates. The oleoresin MBC for Bacillus cereus, Enterobacter cloacae, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella enterica, and Staphylococcus aureus ranged from 0.01 to 0.08 mg/mL, whereas the controls streptomycin and ampicillin varied from 0.1 and 0.5 mg/mL. The oleoresin MFC for Aspergillus fumigatus, Aspergillus niger, Aspergillus ochraceus, Aspergillus versicolor, Penicillium funiculosum, Penicillium ochrochloron, Penicillium verrucosum var. cyclopium, and Trichoderma viride varied from 0.01 to 0.08 mg/mL, whereas the controls bifonazole and ketoconazole ranged from 0.2 to 3.5 mg/mL. The oleoresin obtained by supercritical carbon dioxide presented bacteriostatic, bactericidal, fungistatic, and fungicidal activities that were higher than the positive controls streptomycin, ampicillin, bifonazole, and ketoconazole. The high antimicrobial activity was related to the high content of (E, E)-geranyllinalool that composes 21.0% of the oleoresin and a possible synergic action with fatty acid esters that made up 50.5% of the oleoresin. The oleoresin antimicrobial activity against common multiresistant bacteria in severe infectious processes as P. aeruginosa or against toxin-producing fungi such as P. ochrochloron or fungi that are difficult to control such as T. viride suggests the development of promising applications of this product in the food, farming, livestock, and pharmaceutical industry.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Extratos Vegetais/farmacologia , Solanaceae/química , Antibacterianos/química , Antifúngicos/química , Dióxido de Carbono/química , Flores/química , Extratos Vegetais/química
20.
Genet Mol Res ; 16(3)2017 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28829897

RESUMO

In this study, the temperature and pressure of supercritical CO2 extraction were evaluated to obtain oleoresin of Brunfelsia uniflora leaves and flowers. The oleoresin compounds were identified by gas chromatography-mass spectrometry. The antioxidant activity was evaluated by three different methods. The highest oleoresin yields were 3.32% at 40°C and 200 bar for the leaves, and 1.03% at 60°C and 200 bar for the flowers. The main extracted compounds from leaves were phytol varying from 11.95 to 36.42% and α-tocopherol from 15.53 to 43.10%, and from flowers were geranyl linalool from 11.05 to 21.42% and α-amyrin from 9.66 to 22.12%. Oleoresin obtained at 60°C and 150 bar from leaves presented high antioxidant activity by DPPH (IC50 1.90 mg/mL) and by FRAP (1.8 µmol Fe2+/mg). ß-carotene/linoleic acid co-oxidation oleoresin from leaves at 0.25 mg/mL presented higher antioxidant activity than Trolox. The total phenolic content of the oleoresin from leaves ranged from 66.20 to 83.33 µg/mg and from flowers it was just up to 12.46 µg/mg. The extraction conditions affected yield, chemical composition, and antioxidant activity of oleoresin from leaves and flowers. This is the first report on the antioxidant activity of B. uniflora oleoresin from leaves and flowers and provides subsidies for potential applications in chemical, pharmaceutical, and food industries.


Assuntos
Antioxidantes/química , Extratos Vegetais/química , Solanaceae/química , Monoterpenos Acíclicos , Antioxidantes/farmacologia , Diterpenos/análise , Flores/química , Ácido Linoleico/análise , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/análise , Fitol/análise , Extratos Vegetais/farmacologia , Folhas de Planta/química , Tocoferóis/análise , beta Caroteno/análise
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