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1.
PLoS Pathog ; 19(7): e1011505, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37428810

RESUMO

Most microbes have developed responses that protect them against stresses relevant to their niches. Some that inhabit reasonably predictable environments have evolved anticipatory responses that protect against impending stresses that are likely to be encountered in their niches-termed "adaptive prediction". Unlike yeasts such as Saccharomyces cerevisiae, Kluyveromyces lactis and Yarrowia lipolytica and other pathogenic Candida species we examined, the major fungal pathogen of humans, Candida albicans, activates an oxidative stress response following exposure to physiological glucose levels before an oxidative stress is even encountered. Why? Using competition assays with isogenic barcoded strains, we show that "glucose-enhanced oxidative stress resistance" phenotype enhances the fitness of C. albicans during neutrophil attack and during systemic infection in mice. This anticipatory response is dependent on glucose signalling rather than glucose metabolism. Our analysis of C. albicans signalling mutants reveals that the phenotype is not dependent on the sugar receptor repressor pathway, but is modulated by the glucose repression pathway and down-regulated by the cyclic AMP-protein kinase A pathway. Changes in catalase or glutathione levels do not correlate with the phenotype, but resistance to hydrogen peroxide is dependent on glucose-enhanced trehalose accumulation. The data suggest that the evolution of this anticipatory response has involved the recruitment of conserved signalling pathways and downstream cellular responses, and that this phenotype protects C. albicans from innate immune killing, thereby promoting the fitness of C. albicans in host niches.


Assuntos
Candida albicans , Glucose , Humanos , Animais , Camundongos , Glucose/metabolismo , Estresse Oxidativo/fisiologia , Neutrófilos , Saccharomyces cerevisiae/metabolismo , Proteínas Fúngicas/metabolismo
2.
Oral Dis ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566281

RESUMO

OBJECTIVE: To characterize the distribution of macrophages, neutrophils, NK cells, and blood vessels in peri-implantitis compared to healthy aged gingiva samples. MATERIALS AND METHODS: This observational study included eight gingival samples from peri-implantitis and eight from periodontally healthy individuals. By immunofluorescence were identified neutrophils, NK cells, macrophages, and their pro-inflammatory or pro-healing phenotypes, and blood vessels. Two ROIs were designated as zone 1, connective tissue closest to the epithelium and zone 2, connective tissue over 200 microns from the rete ridges. Immune cells and vascular structures were quantified and characterized according to their distribution in both zones. RESULTS: Two peri-implantitis zones were characterized by unique macrophage phenotypes and blood vessel architecture. Blood vessels were larger in zone 2 in peri-implantitis. A greater number of NK cells and macrophages were found in peri-implantitis compared to healthy aged samples. A higher presence of pro-inflammatory macrophages was found in zone 1 compared to zone 2. A similar proportion of pro-inflammatory and pro-healing macrophages were found in zone 2. CONCLUSION: A specific distribution for pro-inflammatory macrophages and vascular architecture is observed in peri-implantitis. TNF-α colocalizes with macrophages in the connective tissue near rete ridges. NK cells are more abundant in peri-implantitis than in healthy samples.

3.
Immunity ; 40(1): 105-16, 2014 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-24412610

RESUMO

Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α(+) DEC-205(+) dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α(+) dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses.


Assuntos
Citocinas/metabolismo , Células Dendríticas/imunologia , Células T Matadoras Naturais/imunologia , Animais , Apresentação de Antígeno , Antígenos/imunologia , Antígenos CD/metabolismo , Antígenos CD1d/metabolismo , Antígenos CD8/metabolismo , Comunicação Celular , Galactosilceramidas/imunologia , Regulação da Expressão Gênica/imunologia , Homeostase , Inflamação/imunologia , Lectinas Tipo C/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Antígenos de Histocompatibilidade Menor , Receptores de Superfície Celular/metabolismo
4.
Protein Expr Purif ; 205: 106228, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36587709

RESUMO

In recent years, many biological-based products have been developed, representing a significant fraction of income in the pharmaceutical market. Ion exchange chromatography is an important downstream step for the purification of target recombinant proteins present in clarified cell extracts, together with many other unknown impurities. This work develops a robust approach to model and simulate the purification of untagged heterologous proteins, so that the improved conditions to carry out an ion exchange chromatography are identified in a rational basis prior to the real purification run itself. Purification of the pneumococcal surface protein A (PspA4Pro) was used as a case study. This protein is produced by recombinant Escherichia coli and is a candidate for the manufacture of improved pneumococcal vaccines. The developed method combined experimental and computational procedures. Different anion exchange operating conditions were mapped in order to gather a broad range of representative experimental data. The equilibrium dispersive and the steric mass action equations were used to model and simulate the process. A training strategy to fit the model and separately describe the elution profiles of PspA4Pro and other proteins of the cell extract was applied. Based on the simulation results, a reduced ionic strength was applied for PspA4Pro elution, leading to increases of 14.9% and 11.5% for PspA4Pro recovery and purity, respectively, compared to the original elution profile. These results showed the potential of this method, which could be further applied to improve the performance of ion exchange chromatography in the purification of other target proteins under real process conditions.


Assuntos
Produtos Biológicos , Misturas Complexas , Cromatografia por Troca Iônica/métodos , Proteínas Recombinantes/química , Misturas Complexas/metabolismo , Produtos Biológicos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo
5.
Sensors (Basel) ; 23(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36772599

RESUMO

Arterial stiffness is a major condition related to many cardiovascular diseases. Traditional approaches in the assessment of arterial stiffness supported by machine learning techniques are limited to the pulse wave velocity (PWV) estimation based on pressure signals from the peripheral arteries. Nevertheless, arterial stiffness can be assessed based on the pressure-strain relationship by analyzing its hysteresis loop. In this work, the capacity of deep learning models based on generative adversarial networks (GANs) to transfer pressure signals from the peripheral arterial region to pressure and area signals located in the central arterial region is explored. The studied signals are from a public and validated virtual database. Compared to other works in which the assessment of arterial stiffness was performed via PWV, in the present work the pressure-strain hysteresis loop is reconstructed and evaluated in terms of classical machine learning metrics and clinical parameters. Least-square GAN (LSGAN) and Wasserstein GAN with gradient penalty (WGAN-GP) adversarial losses are compared, yielding better results with LSGAN. LSGAN mean ± standard deviation of error for pressure and area pulse waveforms are 0.8 ± 0.4 mmHg and 0.1 ± 0.1 cm2, respectively. Regarding the pressure-strain elastic modulus, it is achieved a mean absolute percentage error of 6.5 ± 5.1%. GAN-based deep learning models can recover the pressure-strain loop of central arteries while observing pressure signals from peripheral arteries.


Assuntos
Análise de Onda de Pulso , Rigidez Vascular , Pressão Sanguínea/fisiologia , Análise de Onda de Pulso/métodos , Pressão Arterial , Artérias , Determinação da Pressão Arterial/métodos , Rigidez Vascular/fisiologia
6.
Sensors (Basel) ; 23(18)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37765782

RESUMO

The analysis of the external forces of swimming starts has revealed how swimmers propel themselves out of the block, but data should be properly interpreted to fully understand force-generation mechanisms. This study aimed to assess horizontal and vertical forces in the backstroke start based on swimmers' structural and propulsive actions. Firstly, a simulated structural force was estimated by two transient backstroke-start inter-segmental realistic body positions: a maximally tucked position and an extended one (just before the hands-off and the take-off, respectively). Secondly, 10 competitive backstroke swimmers performed four 15 m maximal backstroke starts with the external forces estimated. Thirdly, the simulated structural force was subtracted from raw horizontal and vertical force data, measured between hands-off and take-off instants, resulting in the propulsive forces. The application of the algorithm has evidenced that backstrokers' horizontal and vertical simulated-structural-force components contributed to ~40% of total force during start propulsion (~0.2-0.12 s before the take-off), followed by the propulsive horizontal force increment and a progressive vertical component reduction (~0.05 s) with ~20° take-off angle. Based on these findings, researchers and coaches can better guide swimmers as to the proper mechanical strategies to achieve effectiveness in the backstroke start, and to improve direct transfer of resistance training programs.

7.
Adv Skin Wound Care ; 36(5): 249-258, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37079788

RESUMO

OBJECTIVE: Stage 3 and 4 pressure injuries (PIs) present an enormous societal burden with no clearly defined interventions for surgical reconstruction. The authors sought to assess, via literature review and a reflection/evaluation of their own clinical practice experience (where applicable), the current limitations to the surgical intervention of stage 3 or 4 PIs and propose an algorithm for surgical reconstruction. METHODS: An interprofessional working group convened to review and assess the scientific literature and propose an algorithm for clinical practice. Data compiled from the literature and a comparison of institutional management were used to develop an algorithm for the surgical reconstruction of stage 3 and 4 PIs with adjunctive use of negative-pressure wound therapy and bioscaffolds. RESULTS: Surgical reconstruction of PI has relatively high complication rates. The use of negative-pressure wound therapy as adjunctive therapy is beneficial and widespread, leading to reduced dressing change frequency. The evidence for the use of bioscaffolds both in standard wound care and as an adjunct to surgical reconstruction of PI is limited. The proposed algorithm aims to reduce complications typically seen with this patient cohort and improve patient outcomes from surgical intervention. CONCLUSIONS: The working group has proposed a surgical algorithm for stage 3 and 4 PI reconstruction. The algorithm will be validated and refined through additional clinical research.


Assuntos
Lesões por Esmagamento , Úlcera por Pressão , Humanos , Úlcera por Pressão/cirurgia , Infecção da Ferida Cirúrgica
8.
Clin Microbiol Rev ; 34(2)2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33361143

RESUMO

The immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.


Assuntos
Doenças Transmissíveis , Células T Matadoras Naturais , Citocinas , Humanos , Imunidade Inata
9.
PLoS Pathog ; 16(7): e1008645, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32667960

RESUMO

Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.


Assuntos
Aspergilose , Aspergillus fumigatus/patogenicidade , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/fisiologia , Gliotoxina/biossíntese , Fatores de Transcrição/metabolismo , Animais , Aspergilose/metabolismo , Aspergilose/microbiologia , Aspergillus fumigatus/metabolismo , Camundongos , Estresse Oxidativo/fisiologia , Virulência/fisiologia
10.
Ann Bot ; 129(3): 331-342, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-34888616

RESUMO

BACKGROUND AND AIMS: Balanophoraceae is one of the most bizarre and biologically interesting plant clades. It groups species with peculiar features that offers an opportunity for investigating several aspects of parasite plant development and morphogenesis. We analysed the development and the mature vegetative body of Lathrophytum peckoltii Eichler, focusing on the formation of the host-parasite interface. Additionally, we analysed how this parasitic interaction causes modifications to the anatomy of Paullinia uloptera Radlk and Serjania clematidifolia Cambess host roots. METHODS: Vegetative bodies of the parasite at different developmental stages were collected while infesting the roots of Sapindaceae vines. Non-parasitized host roots were also collected for comparison. Light, epifluorescence, confocal and scanning electron microscopy were used for the analysis. KEY RESULTS: The initial cells of the vegetative axis divide repeatedly, originating a parenchymatous matrix, which occupies the space from the cortex to the vascular cylinder of the host's root. In the peripheral layers of the matrix, located near the xylem of the host's roots, a few cells initiate the process of wall lignification, originating the parasitic bundle. The vascular cambium of the host's root changes the division plane and becomes composed of fusiform initials, forming the vascular bundle. The vegetative axis presents a dermal tissue similar to a phellem, a parenchymatous matrix and a vascular system with different origins. CONCLUSION: The parasite reproduces by endophytic development, in a manner similar to that observed for endoparasites. The strategy of late cell differentiation could aid the parasite in avoiding early detection and triggering of defence responses by the host. This development causes changes to the host root cambial activity, leading to the establishment of direct, vessel to vessel connection between host and parasite. We associate these changes with the cambium modularity and an influx of parasite-derived hormones into the host cambium.


Assuntos
Balanophoraceae , Sapindaceae , Câmbio , Raízes de Plantas , Xilema
11.
Phys Rev Lett ; 126(9): 098101, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33750159

RESUMO

Much evidence seems to suggest the cortex operates near a critical point, yet a single set of exponents defining its universality class has not been found. In fact, when critical exponents are estimated from data, they widely differ across species, individuals of the same species, and even over time, or depending on stimulus. Interestingly, these exponents still approximately hold to a dynamical scaling relation. Here we show that the theory of quasicriticality, an organizing principle for brain dynamics, can account for this paradoxical situation. As external stimuli drive the cortex, quasicriticality predicts a departure from criticality along a Widom line with exponents that decrease in absolute value, while still holding approximately to a dynamical scaling relation. We use simulations and experimental data to confirm these predictions and describe new ones that could be tested soon.


Assuntos
Encéfalo/fisiologia , Modelos Neurológicos , Processos Estocásticos
12.
Magn Reson Chem ; 59(4): 447-453, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33091177

RESUMO

A set of experimental techniques headed by proton fast field-cycling nuclear magnetic resonance (1 HFFC-NMR) were used to analyze the effects of degradation of lubricant oil used in an internal combustion engine (ICE). Its relaxometric, spectroscopic, and rheological properties were evaluated and interpreted in terms of changes in the chemical structure and the involved molecular dynamics. In order to better understand the relaxometric behavior, chemical changes induced by heat were investigated for selected n-alkanes, as model-systems due to their structural simplicity. Fourier transform infrared (FTIR) spectroscopy, viscosity measurements, and foaming were used to contrast NMR relaxometry experiments. Main observed changes associated with oil degradation can be attributed to molecular oxidation, fragmentation, and ramification. As an outstanding feature of this work, we show that the relaxometric analysis can be done without any special treatment of the sample, allowing results in less than 10 min.

13.
Sensors (Basel) ; 21(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808925

RESUMO

Arterial blood pressure (ABP) is an important vital sign from which it can be extracted valuable information about the subject's health. After studying its morphology it is possible to diagnose cardiovascular diseases such as hypertension, so ABP routine control is recommended. The most common method of controlling ABP is the cuff-based method, from which it is obtained only the systolic and diastolic blood pressure (SBP and DBP, respectively). This paper proposes a cuff-free method to estimate the morphology of the average ABP pulse (ABPM¯) through a deep learning model based on a seq2seq architecture with attention mechanism. It only needs raw photoplethysmogram signals (PPG) from the finger and includes the capacity to integrate both categorical and continuous demographic information (DI). The experiments were performed on more than 1100 subjects from the MIMIC database for which their corresponding age and gender were consulted. Without allowing the use of data from the same subjects to train and test, the mean absolute errors (MAE) were 6.57 ± 0.20 and 14.39 ± 0.42 mmHg for DBP and SBP, respectively. For ABPM¯, R correlation coefficient and the MAE were 0.98 ± 0.001 and 8.89 ± 0.10 mmHg. In summary, this methodology is capable of transforming PPG into an ABP pulse, which obtains better results when DI of the subjects is used, potentially useful in times when wireless devices are becoming more popular.


Assuntos
Aprendizado Profundo , Fotopletismografia , Pressão Sanguínea , Determinação da Pressão Arterial , Demografia , Humanos
14.
Int J Mol Sci ; 23(1)2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-35008806

RESUMO

MicroRNA-423 (miR-423) is highly expressed in breast cancer (BC). Previously, our group showed that the SNP rs6505162:C>A located in the pre-miR-423 was significantly associated with increased familial BC risk in patients with a strong family history of BC. Therefore, in this study, we evaluated the functional role of rs6505162 in mammary tumorigenesis in vitro to corroborate the association of this SNP with BC risk. We found that rs6505162:C>A upregulated expression of both mature miR-423 sequences (3p and 5p). Moreover, pre-miR-423-A enhanced proliferation, and promoted cisplatin resistance in BC cell lines. We also showed that pre-miR-423-A expression decreased cisplatin-induced apoptosis, and increased BC cell migration and invasion. We propose that the rs6505162-A allele promotes miR-423 overexpression, and that the rs6505162-A allele induces BC cell proliferation, viability, chemoresistance, migration, and invasion, and decreases cell apoptosis as a consequence. We suggest that rs6505162:C>A is a functional SNP site with potential utility as a marker for early diagnosis, prognosis, and treatment efficacy monitoring in BRCA1/2-negative BC patients, as well as a possible therapeutic target.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Variação Genética , MicroRNAs/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Polimorfismo de Nucleotídeo Único/genética , Regulação para Cima/genética
15.
Cell Physiol Biochem ; 54(6): 1163-1176, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33216475

RESUMO

BACKGROUND/AIMS: Histamine is an important chemical transmitter involved in inflammatory processes, including asthma and other chronic inflammatory diseases. Its inflammatory effects involve mainly the histamine H4 receptor (H4R), whose role in several studies has already been demonstrated. Our group have explored the effects of 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines as antagonists of H4R, and herein the compounds LINS01005 and LINS01007 were studied with more details, considering the different affinity profile on H4R and the anti-inflammatory potential of both compounds. METHODS: We carried out a more focused evaluation of the modulatory effects of LINS01005 and LINS01007 in a murine asthma model. The compounds were given i.p. (1-7 mg/kg) to ovalbumin sensitized BALB/c male mice (12 weeks old) 30 min before the antigen challenging, and after 24 h the cell analysis from the bronchoalveolar lavage fluid (BALF) was performed. The lung tissue was used for evaluation by western blot (COX-2, 5-LO, NF-κB and STAT3 expressions) and histological analysis. RESULTS: Treatment with the more potent H4R antagonist LINS01007 significantly decreased the total cell count and eosinophils in BALF at lower doses when compared to LINS01005. The expression of COX-2, 5-LO, NF-κB and STAT3 in lung tissue was significantly reduced after treatment with LINS01007. Morphophysiological changes such as mucus and collagen production and airway wall thickening were significantly reduced after treatment with LINS01007. CONCLUSION: These results show important down regulatory effect of novel H4R antagonist (LINS01007) on allergic lung inflammation.


Assuntos
Asma , Pulmão , Piperazinas/farmacologia , Receptores Histamínicos H4 , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Asma/patologia , Modelos Animais de Doenças , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Piperazinas/química , Receptores Histamínicos H4/antagonistas & inibidores , Receptores Histamínicos H4/metabolismo , Índice de Gravidade de Doença
16.
Behav Pharmacol ; 31(5): 435-447, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-28863004

RESUMO

Behavioral and neuroendocrine responses following threatening situations promote the release of corticosterone, which is known to modulate trauma-related learning and memory process. However, it remains unknown whether the aversive learning generated by interoceptive fear conditioning is affected by glucocorticoid modulation. Therefore, the present study aimed to investigate the role of dexamethasone suppression in encoding and expression of pentylenetetrazole-induced olfactory fear conditioning (OFC) and in contextual second-order conditioning promoted by the conditioned odor. Adult male Long-Evans rats were treated with dexamethasone 60 min before the encoding or the expression in both OFC and contextual second-order conditioning. Dexamethasone treatment impaired encoding and expression of the OFC, but failed to impair encoding and expression of the contextual second-order conditioning. Altogether, our results show that although OFC and thereafter contextual second-order conditioning may allow the study of traumatic memories, each order of conditioning seems to present specific features related to their pharmacological modulation. These findings highlight the importance of addressing the role of neuromodulatory systems in first-order and second-order conditioning to gain a better understanding of these phenomena and support future therapies related to traumatic memories.


Assuntos
Condicionamento Psicológico/efeitos dos fármacos , Dexametasona/farmacologia , Medo/psicologia , Consolidação da Memória/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Masculino , Pentilenotetrazol , Ratos
17.
BMC Psychiatry ; 20(1): 420, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842985

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) may stem from the formation of aberrant and enduring aversive memories. Some PTSD patients have recreationally used Cannabis, probably aiming at relieving their symptomatology. However, it is still largely unknown whether and how Cannabis or its psychotomimetic compound Δ9-tetrahydrocannabinol (THC) attenuates the aversive/traumatic memory outcomes. Here, we seek to review and discuss the effects of THC on aversive memory extinction and anxiety in healthy humans and PTSD patients. METHODS: Medline, PubMed, Cochrane Library, and Central Register for Controlled Trials databases were searched to identify peer-reviewed published studies and randomized controlled trials in humans published in English between 1974 and July 2020, including those using only THC and THC combined with cannabidiol (CBD). The effect size of the experimental intervention under investigation was calculated. RESULTS: At low doses, THC can enhance the extinction rate and reduce anxiety responses. Both effects involve the activation of cannabinoid type-1 receptors in discrete components of the corticolimbic circuitry, which could couterbalance the low "endocannabinoid tonus" reported in PTSD patients. The advantage of associating CBD with THC to attenuate anxiety while minimizing the potential psychotic or anxiogenic effect produced by high doses of THC has been reported. The effects of THC either alone or combined with CBD on aversive memory reconsolidation, however, are still unknown. CONCLUSIONS: Current evidence from healthy humans and PTSD patients supports the THC value to suppress anxiety and aversive memory expression without producing significant adverse effects if used in low doses or when associated with CBD. Future studies are guaranteed to address open questions related to their dose ratios, administration routes, pharmacokinetic interactions, sex-dependent differences, and prolonged efficacy.


Assuntos
Canabidiol , Dronabinol , Afeto , Ansiedade/tratamento farmacológico , Canabidiol/uso terapêutico , Humanos , Memória
18.
Food Microbiol ; 85: 103280, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31500706

RESUMO

Listeria monocytogenes causes severe diseases in humans, including febrile gastroenteritis and systemic infections that has a high mortality despite antibiotic treatment. This pathogen may cause massive outbreaks associated to the consumption of contaminated food products, which highlight its importance in public health. In the last decade, L. monocytogenes has emerged as a foodborne pathogen of major importance in Chile. A previous work showed that in Chile during 2008 and 2009, L. monocytogenes serotypes 1/2a, 1/2b and 4b were the most frequently identified in food and clinical strains. Here we report the molecular characterization of L. monocytogenes strains isolated from 2008 to 2017 in the country. Our results indicate that serotypes 1/2a, 1/2b and 4b continue to be the most commonly found in food products. In addition, we identify persistent and widespread PFGE subtypes. This study reports ten years of epidemiological surveillance ofL. monocytogenes in Chile.


Assuntos
Monitoramento Epidemiológico , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Listeria monocytogenes/genética , Listeriose/epidemiologia , Chile/epidemiologia , Contagem de Colônia Microbiana , DNA Bacteriano/genética , Surtos de Doenças , Doenças Transmitidas por Alimentos/microbiologia , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Variação Genética , Humanos , Listeria monocytogenes/patogenicidade , Produtos da Carne/microbiologia , Epidemiologia Molecular , Saúde Pública , Sorogrupo , Sorotipagem , Fatores de Virulência/genética
19.
J Infect Dis ; 219(3): 420-428, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30010905

RESUMO

Background: Initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated. Methods: We compared plasma levels of immunoglobulins, C. neoformans glucuronoxylomannan (GXM) capsule-specific and laminarin (Lam)-binding IgM and IgG, and percentages of peripheral blood total and memory B cells between 27 HIV-infected patients with CM who developed C-IRIS and 63 who did not, and evaluated associations of these parameters with risk of C-IRIS. Results: Prior to initiation of ART, plasma IgM, Lam-binding IgM (Lam-IgM), Lam-IgG, and GXM-IgM levels were significantly lower in patients who developed C-IRIS than those who did not. Multivariate analysis revealed significant inverse associations between C-IRIS and IgM (P = .0003), Lam-IgM (P = .0005), Lam-IgG (P = .002), and GXM-IgM (P = .002) independent of age, sex, HIV viral load, CD4+ T-cell count, and cerebrospinal fluid fungal burden. There were no associations between C-IRIS and total or memory B cells. Discussion: Antibody profiles that include plasma IgM, Lam-IgM, Lam-IgG, and/or GXM-IgM may have value in furthering our understanding of C-IRIS pathogenesis and hold promise as candidate biomarkers of C-IRIS risk.


Assuntos
Formação de Anticorpos/imunologia , Criptococose/imunologia , Síndrome Inflamatória da Reconstituição Imune/imunologia , Imunoglobulinas/sangue , Meningite Criptocócica/imunologia , Plasma/imunologia , Antirretrovirais , Linfócitos B , Cryptococcus neoformans/imunologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Análise Multivariada , Polissacarídeos/imunologia
20.
Am J Otolaryngol ; 40(1): 67-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30472135

RESUMO

PURPOSE: Parathyroidectomy can be subtotal or total with an autograft for the treatment of renal hyperparathyroidism. In both cases, it may be extended with bilateral thymectomy and total or partial thyroidectomy. Thymectomy may be recommended in combination with parathyroidectomy in order to prevent mediastinal recurrence. Also, the occurrence of thyroid disease observed in patients with hyperparathyroidism is poorly understood and the incidence of cancer is controversial. The aim of the present study was to report the experience of a single center in the surgical treatment of renal hyperparathyroidism and to analyse the role of thyroid and thymus surgery in association with parathyroidectomy. MATERIALS AND METHODS: We analysed parathyroid surgery data, considering patient demographics, such as age and gender, and surgical procedure data, such as type of hyperparathyroidism, associated thyroid or thymus surgery, surgical duration and mediastinal recurrence. Histopathological results of thyroid and thymus samples were also analysed. RESULTS: Medical records of 109 patients who underwent parathyroidectomy for secondary hyperparathyroidism were reviewed. On average, thymectomy did not have impact on time of parathyroidectomy (p = 0.62) even when thyroidectomy was included (p = 0.91). Intrathymic parathyroids were detected in 7.5% of the thymuses removed and papillary carcinoma was detected in 20,8% of thyroid tissue samples. Two patients showed recurrence of supernumerary intrathymic parathyroids and a single case of mediastinitis was observed. CONCLUSIONS: Parathyroidectomy with thymectomy and/or thyroidectomy has an important role in the treatment of renal hyperparathyroidism since thyroid cancer can frequently occur and require surgery. Thymectomy should be considered to avoid recurrence and a risky re-operation.


Assuntos
Hiperparatireoidismo Secundário/cirurgia , Paratireoidectomia , Insuficiência Renal Crônica/complicações , Timectomia , Tireoidectomia , Adulto , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do Tratamento
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