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1.
Nature ; 621(7980): 716-722, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37758891

RESUMO

Einstein's general theory of relativity from 19151 remains the most successful description of gravitation. From the 1919 solar eclipse2 to the observation of gravitational waves3, the theory has passed many crucial experimental tests. However, the evolving concepts of dark matter and dark energy illustrate that there is much to be learned about the gravitating content of the universe. Singularities in the general theory of relativity and the lack of a quantum theory of gravity suggest that our picture is incomplete. It is thus prudent to explore gravity in exotic physical systems. Antimatter was unknown to Einstein in 1915. Dirac's theory4 appeared in 1928; the positron was observed5 in 1932. There has since been much speculation about gravity and antimatter. The theoretical consensus is that any laboratory mass must be attracted6 by the Earth, although some authors have considered the cosmological consequences if antimatter should be repelled by matter7-10. In the general theory of relativity, the weak equivalence principle (WEP) requires that all masses react identically to gravity, independent of their internal structure. Here we show that antihydrogen atoms, released from magnetic confinement in the ALPHA-g apparatus, behave in a way consistent with gravitational attraction to the Earth. Repulsive 'antigravity' is ruled out in this case. This experiment paves the way for precision studies of the magnitude of the gravitational acceleration between anti-atoms and the Earth to test the WEP.

2.
Nature ; 568(7752): 368-372, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30996320

RESUMO

Complex topological configurations are fertile ground for exploring emergent phenomena and exotic phases in condensed-matter physics. For example, the recent discovery of polarization vortices and their associated complex-phase coexistence and response under applied electric fields in superlattices of (PbTiO3)n/(SrTiO3)n suggests the presence of a complex, multi-dimensional system capable of interesting physical responses, such as chirality, negative capacitance and large piezo-electric responses1-3. Here, by varying epitaxial constraints, we discover room-temperature polar-skyrmion bubbles in a lead titanate layer confined by strontium titanate layers, which are imaged by atomic-resolution scanning transmission electron microscopy. Phase-field modelling and second-principles calculations reveal that the polar-skyrmion bubbles have a skyrmion number of +1, and resonant soft-X-ray diffraction experiments show circular dichroism, confirming chirality. Such nanometre-scale polar-skyrmion bubbles are the electric analogues of magnetic skyrmions, and could contribute to the advancement of ferroelectrics towards functionalities incorporating emergent chirality and electrically controllable negative capacitance.

3.
Rhinology ; 62(1): 55-62, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37772802

RESUMO

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.


Assuntos
COVID-19 , Coinfecção , Transtornos do Olfato , Humanos , SARS-CoV-2 , COVID-19/complicações , Anosmia/complicações , Anosmia/epidemiologia , Estudos Prospectivos , Pandemias , Coinfecção/complicações , Coinfecção/epidemiologia , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Olfato
4.
Arch Pharm (Weinheim) ; 356(12): e2300294, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37821361

RESUMO

Natural products belonging to different chemical classes have been established as a promising source of novel anticancer drugs. Several low-molecular-weight compounds from the classes of monoterpenes, phenylpropanoids, and flavonoids were shown to possess anticancer activities in previous studies. In this work, over 20 semisynthetic derivatives of molecules belonging to these classes, namely thymol, eugenol, and 6-hydroxyflavanone were synthesized and tested for their cytotoxicity against two human cancer cell lines, namely AGS cells (gastric adenocarcinoma) and A549 cells (human lung carcinoma). An initial screening based on viability assessment was performed to identify the most cytotoxic compounds at 100 µM. The results evidenced that two 6-hydroxyflavanone derivatives were the most cytotoxic among the compounds tested, being selected for further studies. These derivatives displayed enhanced toxicity when compared with their natural counterparts. Moreover, the lactate dehydrogenase (LDH) assay showed that the loss of cell viability was not accompanied by a loss of membrane integrity, thus ruling out a necrotic process. Morphological studies with AGS cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3/7. Furthermore, a viability assay on a noncancer human embryonic lung fibroblast cell line (MRC-5) confirmed that these two derivatives possess selective anticancer activity.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Células A549 , Neoplasias Pulmonares/patologia , Apoptose , Proliferação de Células
5.
Sensors (Basel) ; 23(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37896641

RESUMO

This paper presents the concept of a novel adaptable sensing solution currently being developed under the EU Commission-founded PHOTONGATE project. This concept will allow for the quantification of multiple analytes of the same or different nature (chemicals, metals, bacteria, etc.) in a single test with levels of sensitivity and selectivity at/or over those offered by current solutions. PHOTONGATE relies on two core technologies: a biochemical technology (molecular gates), which will confer the specificity and, therefore, the capability to be adaptable to the analyte of interest, and which, combined with porous substrates, will increase the sensitivity, and a photonic technology based on localized surface plasmonic resonance (LSPR) structures that serve as transducers for light interaction. Both technologies are in the micron range, facilitating the integration of multiple sensors within a small area (mm2). The concept will be developed for its application in health diagnosis and food safety sectors. It is thought of as an easy-to-use modular concept, which will consist of the sensing module, mainly of a microfluidics cartridge that will house the photonic sensor, and a platform for fluidic handling, optical interrogation, and signal processing. The platform will include a new optical concept, which is fully European Union Made, avoiding optical fibers and expensive optical components.


Assuntos
Metais , Ressonância de Plasmônio de Superfície , Metais/química , Óptica e Fotônica , Bactérias , Fibras Ópticas
6.
Int J Mol Sci ; 24(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36769330

RESUMO

The demand for new fluorophores for different biological target imaging is increasing. Benzo[a]phenoxazine derivatives are fluorochromophores that show promising optical properties for bioimaging, namely fluorescent emission at the NIR of the visible region, where biological samples have minimal fluorescence emission. In this study, six new benzo[a]phenoxazinium chlorides possessing sulfonamide groups at 5-amino-positions were synthesized and their optical and biological properties were tested. Compared with previous probes evaluated using fluorescence microscopy, using different S. cerevisiae strains, these probes, with sulfonamide groups, stained the vacuole membrane and/or the perinuclear membrane of the endoplasmic reticulum with great specificity, with some fluorochromophores capable of even staining the plasma membrane. Thus, the addition of a sulfonamide group to the benzo[a]phenoxazinium core increases their specificity and attributes for the fluorescent labeling of cell applications and fractions, highlighting them as quite valid alternatives to commercially available dyes.


Assuntos
Corantes Fluorescentes , Vacúolos , Saccharomyces cerevisiae , Retículo Endoplasmático , Coloração e Rotulagem , Membrana Celular , Imagem Óptica
7.
Molecules ; 28(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37049869

RESUMO

Melanoma is the deadliest type of skin cancer, with about 61,000 deaths annually worldwide. Late diagnosis increases mortality rates due to melanoma's capacity to metastasise rapidly and patients' resistance to the available conventional therapies. Consequently, the interest in natural products as a strategy for drug discovery has been emerging. Propolis, a natural product produced by bees, has several biological properties, including anticancer effects. Propolis from Gerês is one of the most studied Portuguese propolis. Our group has previously demonstrated that an ethanol extract of Gerês propolis collected in 2018 (G18.EE) and its fractions (n-hexane, ethyl acetate, and n-butanol) decrease melanoma cell viability. Out of all the fractions, G18.EE-n-BuOH showed the highest potential as a melanoma pharmacological therapy. Thus, in this work, G18.EE-n-BuOH was fractioned into 17 subfractions whose effect was evaluated in A375 BRAF-mutated melanoma cells. The subfractions with the highest cytotoxic activity were analysed by UPLC-DAD-ESI/MSn in an attempt to understand which phenolic compounds could account for the anti-melanoma activity. The compounds identified are typical of the Gerês propolis, and some of them have already been linked with antitumor effectiveness. These results reaffirm that propolis compounds can be a source of new drugs and the isolation of compounds could allow its use in traditional medicine.


Assuntos
Antineoplásicos , Melanoma , Própole , Neoplasias Cutâneas , Humanos , Própole/farmacologia , Portugal , Melanoma/tratamento farmacológico , Antineoplásicos/farmacologia , Fenóis/farmacologia
8.
Nat Mater ; 20(2): 194-201, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33046856

RESUMO

Topological solitons such as magnetic skyrmions have drawn attention as stable quasi-particle-like objects. The recent discovery of polar vortices and skyrmions in ferroelectric oxide superlattices has opened up new vistas to explore topology, emergent phenomena and approaches for manipulating such features with electric fields. Using macroscopic dielectric measurements, coupled with direct scanning convergent beam electron diffraction imaging on the atomic scale, theoretical phase-field simulations and second-principles calculations, we demonstrate that polar skyrmions in (PbTiO3)n/(SrTiO3)n superlattices are distinguished by a sheath of negative permittivity at the periphery of each skyrmion. This enhances the effective dielectric permittivity compared with the individual SrTiO3 and PbTiO3 layers. Moreover, the response of these topologically protected structures to electric field and temperature shows a reversible phase transition from the skyrmion state to a trivial uniform ferroelectric state, accompanied by large tunability of the dielectric permittivity. Pulsed switching measurements show a time-dependent evolution and recovery of the skyrmion state (and macroscopic dielectric response). The interrelationship between topological and dielectric properties presents an opportunity to simultaneously manipulate both by a single, and easily controlled, stimulus, the applied electric field.

9.
Phys Rev Lett ; 129(2): 024802, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35867433

RESUMO

A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self-modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.

10.
Int J Mol Sci ; 24(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36614056

RESUMO

Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[a]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. In vivo results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Lisossomos , Oxazinas , Animais , Embrião de Galinha , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Lisossomos/metabolismo , Oxazinas/farmacologia
11.
J Environ Manage ; 311: 114895, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35299134

RESUMO

The management of radioactive waste is a worldwide activity based on the guidelines of the International Atomic Energy Agency (IAEA), and all stages of management require scientifically proven methods for possible deployment. The management of radioactive waste is a huge challenge due to the high risk in the collection, gathering, transport, handling, and storage. In this study, a thermal plasma treatment process was evaluated for its efficiency to process solid radioactive waste. Experiments were carried out with the application of stable isotopes of Lead, Iodine, Cobalt, and Cesium. After the thermal plasma treatments, the slag and the residual gas were analyzed to verify the influence of process time and discharge power on the efficiency of the process. The treatment for 25 min and 10 kW was sufficient to reduce the mass by 50% of the slag. When the applied power was increased to 15 kW, an expressive reduction in the treatment time (10 min) was able to promote the same mass reduction. The results indicated that the treatment of radioactive waste by thermal plasma is a promising method to manage and reduce the mass and volume for the final disposal.

12.
Morphologie ; 106(352): 37-42, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33744125

RESUMO

An important accessory anatomical variation, exclusively human, and related to the muscular ventres of the flexor pollicis longus and flexor digitorum profundus is frequently denominated Gantzer. These variations have close relations with the anterior interosseous nerve (AIN), which provides, for many authors, by direct compression, one of the rare neuropathic syndromes. In this work, thirty-four forearms were dissected from the collections of the Medical School of the Federal University of Minas Gerais and the Department of Basic Sciences of the Federal University of Juiz de Fora, with a prevalence of 50% of the 34 forearms studied for the Gantzer muscle. The muscle relationship was mainly with the flexor pollicis longus muscle and only one occurrence related to the flexor digitorum profundus muscle, described as a rare occurrence of unilateral double formation of Gantzer muscle. Bilaterality was observed in 88.23% of the findings and the dominant innervation for this muscle variation occurred in 82.35% by the anterior interosseous nerve (AIN). The type morphological in all forms found was the fusiform, with 10.5cm of total length and an average of 0.3cm in diameter and all related, as origin, in the medial aspect of the coronoid process of the ulna, next to the origin of the flexor digitorum superficialis muscle. Our work largely reflected the findings of most publications and, considering the controversy of the occurrence of a compressive neuropathy, the data were not sufficient, from a strictly anatomical point of view, to confirm or refute the hypothesis.


Assuntos
Antebraço , Músculo Esquelético , Variação Anatômica , Cadáver , Mãos , Humanos
13.
Cell Tissue Res ; 386(1): 173-190, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34296344

RESUMO

The monocyte chemoattractant protein 1 (MCP-1) belongs to the CC chemokine family and acts in the recruitment of C-C motif chemokine receptor 2 (CCR2)-positive immune cell types to inflammation sites. In testis, the MCP-1/CCR2 axis has been associated with the macrophage population's functional regulation, which presents significant functions supporting germ cell development. In this context, herein, we aimed to investigate the role of the chemokine receptor CCR2 in mice testicular environment and its impact on male sperm production. Using adult transgenic mice strain that had the CCR2 gene replaced by a red fluorescent protein gene, we showed a stage-dependent expression of CCR2 in type B spermatogonia and early primary spermatocytes. Several parameters related to sperm production were reduced in the absence of CCR2 protein, such as Sertoli cell efficiency, meiotic index, and overall yield of spermatogenesis. Daily sperm production decreased by almost 40%, and several damages in the seminiferous tubules were observed. Significant reduction in the expression of important genes related to the Sertoli cell function (Cnx43, Vim, Ocln, Spna2) and meiosis initiation (Stra8, Pcna, Prdm9, Msh5) occurred in comparison to controls. Also, the number of macrophages significantly decreased in the absence of CCR2 protein, along with a disturbance in Leydig cell steroidogenic activity. In summary, our results show that the non-activation of the MCP-1/CCR2 axis disturbs the testicular homeostasis, interfering in macrophage population, meiosis initiation, blood-testis barrier function, and androgen synthesis, leading to the malfunction of seminiferous tubules, decreased testosterone levels, defective sperm production, and lower fertility index.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Macrófagos/metabolismo , Receptores de Quimiocinas/metabolismo , Espermatogênese/fisiologia , Testículo/fisiologia , Animais , Feminino , Humanos , Masculino , Camundongos
14.
Phys Rev Lett ; 126(16): 164802, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33961468

RESUMO

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [≥(4.1±0.4) MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2π) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated.

15.
Bioorg Chem ; 115: 105221, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34364053

RESUMO

Three barbiturate squaraine dyes derived from indolenine or benzothiazole, with different barbituric acid derivatives were prepared, characterized and photophysically evaluated by standard spectroscopic methods. As expectable for squaraines, these dyes showed narrow and intense absorption and emission bands in the Vis/NIR region. The interaction of synthesized dyes with bovine and human serum albumins (BSA and HSA) was also evaluated in phosphate buffer (PB). The results revealed that upon the addition of BSA or HSA the complex dye-protein emit more fluorescence, and the emission intensity is directly proportional to the concentration of protein used (0-3.5 µM). The titration tests allowed to calculate the binding constants, in an order of magnitude of 104-106 M, as well as the limits of detection and quantification in the nanomolar tens range. All dyes showed a good response to the interaction with both proteins, but the most pronounced envisioning their use as protein labeling was observed for the squaraine dye derived from the indolenine with a 1,3-dimethylbarbituric acid moiety. The molecular docking studies revealed the existence of a binding between the compounds and four sites on the HSA molecule, where one of these four locations is a new binding site with which this series of dye interacts.


Assuntos
Ciclobutanos/química , Corantes Fluorescentes/química , Simulação de Acoplamento Molecular , Fenóis/química , Soroalbumina Bovina/análise , Albumina Sérica Humana/análise , Animais , Bovinos , Ciclobutanos/síntese química , Corantes Fluorescentes/síntese química , Humanos , Estrutura Molecular , Fenóis/síntese química
16.
Molecules ; 26(21)2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34771025

RESUMO

A series of ß-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against Sf9 insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.


Assuntos
Amino Álcoois/química , Eugenol/química , Inseticidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Inseticidas/síntese química , Inseticidas/química , Modelos Moleculares , Estrutura Molecular , Spodoptera
17.
Bioorg Chem ; 98: 103730, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32199304

RESUMO

Four new benzo[a]phenoxazinium chlorides with combinations of chloride, ethyl ester and methyl as terminals of the amino substituents were synthesized. These compounds were characterized and their optical properties were studied in absolute dry ethanol and water. Their antiproliferative activity was tested against Saccharomyces cerevisiae in a broth microdilution assay, along with an array of 36 other benzo[a]phenoxazinium chlorides. Minimum Inhibitory Concentration (MIC) values between 1.56 and >200 µM were observed. Fluorescence microscopy studies, used to assess the intracellular distribution of the dyes, showed that these benzo[a]phenoxazinium chlorides function as efficient and site specific probes for the detection of the vacuole membrane. The added advantage of some of the compounds, that displayed the lower MIC values, was the simultaneous staining of both the vacuole membrane and the perinuclear membrane of endoplasmic reticulum (ER). Molecular docking studies were performed on the human membrane protein oxidosqualene cyclase (OSC), using the crystal structure available on PDB (code 1W6K). The results showed that these most active compounds accommodated better in the active sites of ER enzyme OSC suggesting this enzyme as a potential target. As a whole, the results demonstrate that the benzo[a]phenoxazinium chlorides are interesting alternatives to the available commercial dyes. Changes in the substituents of these compounds can tailor both their staining specificity and antimicrobial activity.


Assuntos
Antifúngicos/farmacologia , Corantes Fluorescentes/farmacologia , Oxazinas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Leveduras/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Células Cultivadas , Relação Dose-Resposta a Droga , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Testes de Sensibilidade Microbiana , Microscopia de Fluorescência , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxazinas/síntese química , Oxazinas/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Relação Estrutura-Atividade
18.
BMC Pregnancy Childbirth ; 20(1): 117, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075598

RESUMO

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.


Assuntos
Diabetes Gestacional/fisiopatologia , Doenças Musculares/fisiopatologia , Incontinência Urinária/fisiopatologia , Adulto , Brasil , Cesárea , Estudos de Coortes , Feminino , Idade Gestacional , Ganho de Peso na Gestação , Humanos , Idade Materna , Contração Muscular/fisiologia , Força Muscular/fisiologia , Palpação , Diafragma da Pelve/fisiopatologia , Período Pós-Parto , Gravidez , Reto do Abdome/fisiopatologia , Vagina
19.
Lasers Med Sci ; 35(4): 777-788, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31768691

RESUMO

To date, there is no compilation of evidence-based information associating photobiomodulation effect and salivary glands. This systematic review aims to assess photobiomodulation effect of low intensity laser on salivary glands in the presence of systemic diseases. MEDLINE databases were searched in duplicate through December 2018. In vivo studies and clinical trials were included if photobiomodulation was performed in salivary glands of animal (rat or mice) or human in the presence of systemic disease. The methodological quality was assessed in duplicate using the modified Newcastle-Ottawa scale (NOS). Search strategy identified 483 potentially eligible articles, and 449 were included. The Boolean search naturally leads to a high amount of works the majority of which were excluded because the analysis of the title and abstract demonstrated it was not focusing on PBM. Only 34 studies were selected for the full-text analysis, of which 5 were excluded due to non-use of photobiomodulation, 4 due to lack of control group, 2 because they were studies of cell cultures and 1 because they did not have the total of animals used. Thus, 21 papers were included for the critical evaluation of the impact of photobiomodulation on the major salivary glands; the studies used rats (n = 10) and humans (n = 11). Although studies reported an increase in the salivary rate, decrease in pain, and increase in quality of life after the PBM, the lack of standards for the application of light and reporting of the parameters, make it hard to reproduce the results. This topic is still in need for further research.


Assuntos
Terapia com Luz de Baixa Intensidade , Glândulas Salivares/efeitos da radiação , Animais , Ensaios Clínicos como Assunto , Humanos , Camundongos , Dor/radioterapia , Qualidade de Vida , Ratos
20.
Int J Mol Sci ; 21(23)2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33291666

RESUMO

Eugenol, the generic name of 4-allyl-2-methoxyphenol, is the major component of clove essential oil, and has demonstrated relevant biological potential with well-known antimicrobial and antioxidant actions. New O-alkylated eugenol derivatives, bearing a propyl chain with terminals like hydrogen, hydroxyl, ester, chlorine, and carboxylic acid, were synthesized in the present work. These compounds were later subjected to epoxidation conditions to give the corresponding oxiranes. All derivatives were evaluated against their effect upon the viability of insect cell line Sf9 (Spodoptera frugiperda), demonstrating that structural changes elicit marked effects in terms of potency. In addition, the most promising molecules were evaluated for their impact in cell morphology, caspase-like activity, and potential toxicity towards human cells. Some molecules stood out in terms of toxicity towards insect cells, with morphological assessment of treated cells showing chromatin condensation and fragmentation, which are compatible with the occurrence of programmed cell death, later confirmed by evaluation of caspase-like activity. These findings point out the potential use of eugenol derivatives as semisynthetic insecticides from plant natural products.


Assuntos
Eugenol/farmacologia , Inseticidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Caspases/metabolismo , Linhagem Celular , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Eugenol/análogos & derivados , Eugenol/síntese química , Humanos , Inseticidas/síntese química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Parasitária , Células Sf9
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