We aimed to analyze the efficacy and safety of arketamine, the
R
(−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD ...received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion to 10.4 after one day, a mean difference of 20.3 points CI 95% 13.6–27.0;
p
< 0.001; dissociation was nearly absent. Arketamine might produce fast-onset and sustained antidepressant effects in humans with favorable safety profile, like previously reported with animals; further controlled-trials are needed.
We verify the effects of different cryoprotectants on the cryopreservation of agouti (Dasyprocta leporina) epididymal sperm. We used 16 pairs of testes–epididymis complexes of sexually mature ...animals. We immediately evaluated epididymal sperm obtained by retrograde flushing for concentration, motility, vigor, viability, osmotic response, and morphology. Samples were extended in a coconut water extender plus 20% egg yolk, containing glycerol, ethylene glycol, dimethylsulfoxide – DMSO, or dimethylformamide. Finally, samples were stored in 0.25 mL straws, frozen in liquid nitrogen, and thawed after one week, being reevaluated and assessed for membrane integrity using fluorescent probes. The higher values for postthawing sperm motility, vigor, and membrane integrity were achieved by the usage of glycerol, when compared to ethylene glycol and dimethylformamide (P < 0.05); however, no differences were found between glycerol and DMSO (P > 0.05). All cryoprotectants provided a similar effect on the preservation of sperm morphology, osmotic response, and viability (P > 0.05). Therefore, here onwards, there was testing of glycerol and DMSO at 3 and 6% concentrations using the same freezing–thawing protocol reported previously. As the main result, DMSO at 6% concentration provided a decrease in sperm parameters, as well as in the chromatin integrity and in the binding capability of sperm. In conclusion, glycerol 3 or 6% and DMSO 3% can be used as alternative cryoprotectants for agouti epididymal sperm cryopreservation.
RESUMO O enriquecimento ambiental é uma ferramenta importante dentro dos sistemas de produção, a fim de promover o bem-estar e favorecer a saúde dos animais. Portanto, o objetivo deste trabalho foi ...avaliar o efeito do enriquecimento ambiental sobre o estresse de suínos na fase de creche. Foram utilizados 32 leitões, alojados em granja experimental, distribuídos em quatro grupos (n= 8): corda, corrente, garrafa PET e controle negativo. Amostras de sangue foram coletadas no início e no final do experimento para contagem de leucócitos circulantes e determinação de antioxidantes não enzimáticos, óxido nítrico, malondialdeído, e de saliva para avaliação do cortisol. Foi aplicado etograma e fez-a ganho médio de peso diário e a conversão alimentar. Os parâmetros avaliados no primeiro dia do experimento não variaram entre os grupos (P>0,05). No último dia do experimento, os valores de neutrófilos e da relação neutrófilo/linfócito foram mais elevados nos leitões do grupo corrente, assim como os valores de cortisol salivar (P<0,05). O ácido úrico apresentou-se mais elevado nos leitões do grupo corrente e o malondialdeído (MDA) nos do grupo garrafa (P< 0,05). Os enriquecimentos ambientais estimularam comportamentos positivos nos leitões, tendo a corda se destacado como o mais atrativo. Por outro lado, a corrente apresentou efeito negativo sobre a fisiologia dos animais, gerando estresse, assim como a garrafa, que induziu a peroxidação lipídica e um menor ganho de peso nos leitões.
ABSTRACT Environmental enrichment is an important tool within production systems to promote welfare and animal health. The aim of this study was to evaluate the effect of enrichment objects on stress of piglets in nursery phase. 32 piglets housed in experimental farm were distributed in 4 groups (n= 8): rope, chain, pet bottle and negative control. Blood samples were collected at the beginning and end of the experiment to count circulating leukocytes and determine non-enzymatic antioxidants, nitric oxide, malondialdehyde, and saliva to evaluate cortisol. At the same time, an etogram and evaluation of mean daily gain and feed conversion were applied. The evaluated parameters on first day of the experiment did not vary between groups (P> 0.05). On the last day, neutrophil and neutrophil /lymphocyte ratios were higher in chain group piglets, as were salivary cortisol values (P< 0.05). Uric acid was higher in chain group and MDA in bottle group (P< 0.05). Environmental enrichment stimulated positive behaviors in piglets, where the rope stood out as the most attractive. On the other hand, chain had a negative effect on animal physiology, generating stress, as well as the bottle that induced lipid peroxidation and a lower weight gain in piglets.
Limitations of the recognition elements in terms of synthesis, cost, availability, and stability have impaired the translation of biosensors into practical use. Inspired by nature to mimic the ...molecular recognition of the anti-SARS-CoV-2 S protein antibody (AbS) by the S protein binding site, we synthesized the peptide sequence of Asn-Asn-Ala-Thr-Asn-COOH (abbreviated as PEP2003) to create COVID-19 screening label-free (LF) biosensors based on a carbon electrode, gold nanoparticles (AuNPs), and electrochemical impedance spectroscopy. The PEP2003 is easily obtained by chemical synthesis, and it can be adsorbed on electrodes while maintaining its ability for AbS recognition, further leading to a sensitivity 3.4-fold higher than the full-length S protein, which is in agreement with the increase in the target-to-receptor size ratio. Peptide-loaded LF devices based on noncovalent immobilization were developed by affording fast and simple analyses, along with a modular functionalization. From studies by molecular docking, the peptide–AbS binding was found to be driven by hydrogen bonds and hydrophobic interactions. Moreover, the peptide is not amenable to denaturation, thus addressing the trade-off between scalability, cost, and robustness. The biosensor preserves 95.1% of the initial signal for 20 days when stored dry at 4 °C. With the aid of two simple equations fitted by machine learning (ML), the method was able to make the COVID-19 screening of 39 biological samples into healthy and infected groups with 100.0% accuracy. By taking advantage of peptide-related merits combined with advances in surface chemistry and ML-aided accuracy, this platform is promising to bring COVID-19 biosensors into mainstream use toward straightforward, fast, and accurate analyses at the point of care, with social and economic impacts being achieved.
This study reports on the synthesis and characterization of cobalt ferrite (CoFe2O4) nanoparticles (NPs) synthesized by chemical co-precipitation in alkaline medium at increasing temperatures in the ...range of 27 °C to 100 °C. High-quality samples in the size range of 5 to 10 nm were produced using very low stirring speed (250 rpm) and moderate alkaline aqueous solution concentration (4.8 mol/L). Three samples were synthesized and characterized by x–ray diffraction (XRD) and room-temperature (RT) magnetization measurements. All samples present superparamagnetic (SPM) behavior at RT and Rietveld refinements confirm the inverse cubic spinel structure (space group Fd-3m (227)) with minor detectable impurity phase. As the synthesis temperature increases, structural parameters such as lattice constant and grain size change monotonically from 8.385 to 8.383 Å and from 5.8 to 7.4 nm, respectively. Likewise, as the synthesis temperature increases the NPs’ magnetic moment and saturation magnetization increases monotonically from 2.6 ×103 to 16×103 μB and from 37 to 66 emu/g, respectively. The RT magnetization (M) versus applied field (H) curves were analyzed by the first-order Langevin function averaged out by a lognormal distribution function of magnetic moments. The excellent curve-fitting of the M versus H data is credited to a reduced particle-particle interaction due to both the SPM behavior and the existence of a surface amorphous shell layer (dead layer), the latter reducing systematically as the synthesis temperature increases.
Many phenolic compounds found in foods and medicinal plants have shown interesting therapeutic potential and have attracted the attention of the pharmaceutical industry as promising pharmacologically ...active compounds in health promotion and disease prevention. Vanillin is a phenolic aldehyde, widely used as a flavoring agent in the food, pharmaceutical, and cosmetics industries. A variety of pharmacological activities has been attributed to this compound and its main metabolites, vanillic acid and vanillyl alcohol, including their anti-inflammatory ability. The relationship of the anti- inflammatory effects of vanillin, vanillic acid, and vanillyl alcohol and their actions on oxidative stress is well established. Considering that the inflammatory process is related to several pathologies, including new diseases with few therapeutic options, and limited efficiency, the search for effective treatment strategies and discovery of new anti-inflammatory agents capable of modulating inflammation becomes necessary. Therefore, in this review, we discuss the therapeutic potential of vanillin and its main metabolites for the treatment of inflammatory diseases and their actions on redox status. In addition, the molecular docking evaluation of vanillin, its metabolites and isoeugenol were carried out into the phospholipase A2 binding site.
This study analyzed IGF-1 protein immunostaining in sheep ovaries, the effect of IGF-1 alone or associated with FSH on the culture of secondary follicles, and the immunostaining of LHR protein in ...antral follicles before and after culture. Ovaries were collected for IGF-1 protein analysis. In experiment 1, secondary follicles were cultured in α-MEM+ (control) or α-MEM+ supplemented with IGF-1 (10, 50 or 100 ng/mL). In experiment 2, follicles were cultured in the same media of experiment 1 plus 750 ng/mL FSH. Moreover, LHR immunostaining was analyzed in fresh antral follicles and after culture in 50 ng/mL IGF-1 + FSH. The IGF-1 protein was immunolocalized in oocytes from all stages of follicle development and in the granulosa cells from secondary and antral follicles. IGF-1 did not influence (P > 0.05) follicular viability and growth (experiment 1). However, in experiment 2, 50 ng/mL IGF-1 + FSH stimulated oocyte growth (P < 0.05) and LHR immunostaining in antral follicles. Control medium, 10 or 50 ng/mL IGF-1 + FSH showed similar levels of reactive oxygen species, glutathione and active mitochondria (P > 0.05). In conclusion, the IGF-1 protein is present in all ovarian follicle stages in sheep. Moreover, the association between 50 ng/mL IGF-1 and FSH has a synergistic effect in vitro, increasing the percentage of fully grown oocytes and the intensity of immunostaining of LHR protein in oocytes and granulosa cells of cultured antral follicles.
•The IGF-1 protein is expressed in all ovarian follicle stages in sheep.•The association between 50 ng/mL IGF-1 and FSH increase the percentage of fully grown oocytes.•The combination between 50 ng/mL IGF-1 + FSH increase the LHR expression protein in antral follicles.
In telecommunications, with the growing demand of data traffic in the networks of third generation (3G), the mobile operators have attempted to focus resources on infrastructure in places where it is ...identified a greater need. The channeling investments have the goal of maintaining quality of service, especially in dense urban areas. In this work, the prediction of time series in WCDMA networks is carried on for the parameters: received power (Rx Power), Received Signal Code Power (RSCP), Energy per chip/Interference (Ec/Io) and throughput at the physical layer. The collection of parameters values was performed on a fully operational network through a drive test in Natal/RN. The model used to predict the time series was the model of Holt exponential smoothing. The objective of the predictions of the series is to check which parameters HSPA network - WCDMA model best adapted Holt.
Candida albicans is the most frequently isolated opportunistic pathogen in the female genital tract, with 92.3% of cases in Brazil associated with vulvovaginal candidiasis (VVC). Linalool is a ...monoterpene compound from plants of the genera Cinnamomum, Coriandrum, Lavandula, and Citrus that has demonstrated a fungicidal effect on strains of Candida spp., but its mechanism of action is still unknown. For this purpose, broth microdilution techniques were applied, as well as molecular docking in a predictive manner for this mechanism. The main results of this study indicated that the C. albicans strains analyzed were resistant to fluconazole and sensitive to linalool at a dose of 256 microg/mL. Furthermore, the increase in the minimum inhibitory concentration (MIC) of linalool in the presence of sorbitol and ergosterol indicated that this molecule possibly affects the cell wall and plasma membrane integrity of C. albicans. Molecular docking of linalool with proteins that are key in the biosynthesis and maintenance of the cell wall and the fungal plasma membrane integrity demonstrated the possibility of linalool interacting with three important enzymes: 1,3-beta-glucan synthase, lanosterol 14alpha- demethylase, and DELTA 14-sterol reductase. In silico analysis showed that this monoterpene has theoretical but significant oral bioavailability, low toxic potential, and high similarity to pharmaceuticals. Therefore, the findings of this study indicated that linalool probably causes damage to the cell wall and plasma membrane of C. albicans, possibly by interaction with important enzymes involved in the biosynthesis of these fungal structures, in addition to presenting low in silico toxic potential. Key words: Linalool; Antifungal resistance; Fluconazole; Vulvovaginal candidiasis; Mechanism of action
This study was conducted to report the richness of endophytic
Penicillium
and
Talaromyces
species isolated from
Tillandsia catimbauensis
, a bromeliad endemic in the Brazilian tropical dry forest ...(Caatinga), to verify their ability to produce the enzyme
l
-asparaginase and to partially optimise the production of biomass and
l
-asparaginase of the best enzyme producer. A total of 184 endophytes were isolated, of which 52 (29%) were identified through morphological and phylogenetic analysis using β-tubulin sequences into nine putative species, four in
Penicillium
and five in
Talaromyces. Talaromyces diversus
and
T
. cf.
cecidicola
were the most frequent taxa. Among the 20 endophytic isolates selected for
l
-asparaginase production, 10 had the potential to produce the enzyme (0.50–2.30 U/g), especially
T
. cf.
cecidicola
URM 7826 (2.30 U/g) and
Penicillium
sp. 4 URM 7827 (1.28 U/g). As
T
. cf.
cecidicola
URM 7826 exhibited significant ability to produce the enzyme, it was selected for the partial optimisation of biomass and
l
-asparaginase production. Results of the 2
3
factorial experimental design showed that the highest dry biomass (0.66 g) was obtained under pH 6.0, inoculum concentration of 1 × 10
8
and 1%
l
-proline. However, the inoculum concentration was found to be statistically significant, the pH was marginally significant and the concentration of
l
-proline was not statistically significant.
l
-Asparaginase production varied between 0.58 and 1.02 U/g and did not reach the optimal point for enzyme production. This study demonstrates that
T. catimbauensis
is colonised by different
Penicillium
and
Talaromyces
species, which are indicated for enzyme production studies.
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