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1.
Cells ; 10(4)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810533

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension characterized by the presence of fibrotic intraluminal thrombi and causing obliteration of the pulmonary arteries. Although both endothelial cell (EC) dysfunction and inflammation are linked to CTEPH pathogenesis, regulation of the basal inflammatory response of ECs in CTEPH is not fully understood. Therefore, in the present study, we investigated the role of the nuclear factor (NF)-κB pro-inflammatory signaling pathway in ECs in CTEPH under basal conditions. Basal mRNA levels of interleukin (IL)-8, IL-1ß, monocyte chemoattractant protein-1 (MCP-1), C-C motif chemokine ligand 5 (CCL5), and vascular cell adhesion molecule-1 (VCAM-1) were upregulated in CTEPH-ECs compared to the control cells. To assess the involvement of NF-κB signaling in basal inflammatory activation, CTEPH-ECs were incubated with the NF-κB inhibitor Bay 11-7085. The increase in pro-inflammatory cytokines was abolished when cells were incubated with the NF-κB inhibitor. To determine if NF-κB was indeed activated, we stained pulmonary endarterectomy (PEA) specimens from CTEPH patients and ECs isolated from PEA specimens for phospho-NF-κB-P65 and found that especially the vessels within the thrombus and CTEPH-ECs are positive for phospho-NF-κB-P65. In summary, we show that CTEPH-ECs have a pro-inflammatory status under basal conditions, and blocking NF-κB signaling reduces the production of inflammatory factors in CTEPH-ECs. Therefore, our results show that the increased basal pro-inflammatory status of CTEPH-ECs is, at least partially, regulated through activation of NF-κB signaling and potentially contributes to the pathophysiology and progression of CTEPH.

2.
Polymers (Basel) ; 13(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803415

RESUMO

3D printing has exponentially grown in popularity due to the personalization of each printed part it offers, making it extremely beneficial for the very demanding biomedical industry. This technique has been extensively developed and optimized and the advances that now reside in the development of new materials suitable for 3D printing, which may open the door to new applications. Fused deposition modeling (FDM) is the most commonly used 3D printing technique. However, filaments suitable for FDM must meet certain criteria for a successful printing process and thus the optimization of their properties in often necessary. The aim of this work was to prepare a flexible and printable polyurethane filament parting from a biocompatible waterborne polyurethane, which shows potential for biomedical applications. In order to improve filament properties and printability, cellulose nanofibers and graphene were employed to prepare polyurethane based nanocomposites. Prepared nanocomposite filaments showed altered properties which directly impacted their printability. Graphene containing nanocomposites presented sound enough thermal and mechanical properties for a good printing process. Moreover, these filaments were employed in FDM to obtained 3D printed parts, which showed good shape fidelity. Properties exhibited by polyurethane and graphene filaments show potential to be used in biomedical applications.

3.
Antioxidants (Basel) ; 10(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809405

RESUMO

Abdominal aortic aneurysm (AAA) is a common life-threatening condition characterized by exacerbated inflammation and the generation of reactive oxygen species. Pharmacological treatments to slow AAA progression or to prevent its rupture remain a challenge. Targeting phosphodiesterase 4 (PDE4) has been verified as an effective therapeutic strategy for an array of inflammatory conditions; however, no studies have assessed yet PDE4 in AAA. Here, we used angiotensin II (AngII)-infused apolipoprotein E deficient mice to study the involvement of the PDE4 subfamily in aneurysmal disease. PDE4B but not PDE4D was upregulated in inflammatory cells from both experimental and human AAA. The administration of the PDE4 selective inhibitor rolipram (3 mg/kg/day) to AngII-challenged mice (1000 ng/kg bodyweight/min) protected against AAA formation, limiting the progressive increase in the aortic diameter without affecting the blood pressure. The drug strongly attenuated the rise in vascular oxidative stress (superoxide anion) induced by AngII, and decreased the expression of inflammatory markers, as well as the recruitment of macrophages (MAC3+), lymphocytes (CD3+), and neutrophils (ELANE+) into the vessel wall. Rolipram also normalized the vascular MMP2 expression and MMP activity, preserving the elastin integrity and improving the vascular remodelling. These results point to PDE4B as a new therapeutic target for AAA.

4.
ACS Biomater Sci Eng ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826291

RESUMO

Albumin is widely used in pharmaceutical applications to alter the pharmacokinetic profile, improve efficacy, or decrease the toxicity of active compounds. Various drug delivery systems using albumin have been reported, including microparticles. Macroaggregated albumin (MAA) is one of the more common forms of albumin microparticles, which is predominately used for lung perfusion imaging when labeled with radionuclide technetium-99m (99mTc). These microparticles are formed by heat-denaturing albumin in a bulk solution, making it very challenging to control the size and dispersity of the preparations (coefficient of variation, CV, ∼50%). In this work, we developed an integrated microfluidics platform to create more tunable and precise MAA particles, the so-called microfluidic-MAA (M2A2). The microfluidic chips, prepared using off-stoichiometry thiol-ene chemistry, consist of a flow-focusing region followed by an extended and water-heated curing channel (85 °C). M2A2 particles with diameters between 70 and 300 µm with CVs between 10 and 20% were reliably prepared by adjusting the flow rates of the dispersed and continuous phases. To demonstrate the pharmaceutical utility of M2A2, particles were labeled with indium-111 (111In) and their distribution was assessed in healthy mice using nuclear imaging. 111In-M2A2 behaved similarly to 99mTc-MAA, with lung uptake predominately observed early on followed by clearance over time by the reticuloendothelial and renal systems. Our microfluidic chip represents an elegant and controllable method to prepare albumin microparticles for biomedical applications.

5.
J Crohns Colitis ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33860795

RESUMO

BACKGROUND: The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice. AIMS: To evaluate the durability, effectiveness and safety of ustekinumab in UC in real-life. METHODS: Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) >2] were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at week 16. RESULTS: A total of 95 patients were included. At week 16, 53% of patients had response (including 35% of patients in remission). In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at weeks 24 and 52, respectively. Thirty-six percent of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. CONCLUSIONS: Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

8.
Aliment Pharmacol Ther ; 53(9): 1021-1029, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33715177

RESUMO

BACKGROUND: Methotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited. AIM: To assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti-tumour necrosis factor (anti-TNFα) drugs. METHODS: A retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti-TNFα started on methotrexate monotherapy. Short-term effectiveness was assessed at 12-16 weeks based on Harvey-Bradshaw index (HBI): clinical remission as HBI ≤ 3 points and clinical response as HBI drop of ≥ 3 points over baseline. Long-term effectiveness was defined as steroid-free methotrexate persistence from 12 to 16 weeks until maximum follow up. Adverse events were recorded. RESULTS: Data were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti-TNFα agents. Short-term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long-term effectiveness was achieved in 82% and 74% at 12 and 24 months respectively. In the multivariate analysis, non-remission at short term (vs remission) was associated with long-term failure (HR 2.58, 95%CI 1.95-3.68, P = 0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation. CONCLUSIONS: The benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti-TNFα.


Assuntos
Doença de Crohn , Metotrexato , Doença de Crohn/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Metotrexato/efeitos adversos , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa
9.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33545242

RESUMO

INTRODUCTION: Knowing the natural history of ulcerative colitis (UC) is essential to understand the course of the disease, assess the impact of different treatment strategies and identify poor prognostic factors. One of the most significant matters in this regard is the need for surgery. OBJECTIVES: To analyse the Colectomy Incidence Rate (CIR) from diagnosis to end of follow-up (31/12/2017) and identify predictive factors for colectomy. MATERIAL AND METHODS: A retrospective study enrolling patients with a definitive diagnosis (DD) of UC or Unclassified Colitis (UnC) in the 2001-03 Navarra cohort. RESULTS: We enrolled 174 patients with a DD of UC (E2 42.8%; E3 26.6%) and 5 patients with a DD of UnC: 44.1% women, median age 39.2 years (range 7-88) and median follow-up 15.7 years. A total of 8 patients underwent surgery (CIR 3 colectomies/103 patient-years: 3 at initial diagnosis (<1 month), 2 in the first 2 years, 2 at 5 years from diagnosis and 1 at 12 years from diagnosis. All had previously received steroids; 5 had received immunomodulators and 2 had received biologics. In 7 patients (87%), surgery was performed on an emergency basis. The indication was megacolon in 3 (37.5%), severe flare-up in 3 (37.5%) and medical treatment failure in 2 (25%). In 5 cases (62.5%), an ileoanal pouch was made, and in 3 cases, a definitive ileostomy was performed. In the univariate analysis, patients with loss of more than 5 kg at diagnosis and admission at diagnosis had a lower rate of colectomy-free survival. CONCLUSIONS: In our series, colectomy rates are lower than usually reported. Most colectomies were performed in the first 5 years following diagnosis and had an emergency indication.

10.
BMJ Open ; 11(2): e042966, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574150

RESUMO

OBJECTIVES: The objective of this study is to evaluate the impact of the COVID-19 outbreak on mental health and burn-out syndrome in Spanish internists and the factors that could be related to its appearance. DESIGN: We performed an observational, cross-sectional, descriptive study for which we designed a survey that was distributed in May 2020. SETTING: We included internists who worked in Spain during the COVID-19 outbreak. PARTICIPANTS: A total of 1015 internists responded to the survey. Of those 62.9% were women. RESULTS: Of 1015 people, 58.3% presented with high emotional exhaustion, 61.5% had a high level of depersonalisation and 67.6% reported low personal fulfilment. 40.1% presented with the 3 criteria described, and therefore burn-out syndrome.Burn-out syndrome was independently related to the management of patients with SARS-CoV-2 (HR: 2.26; 95% CI 1.15 to 4.45), the lack of availability of personal protective equipment (HR: 1.41; 95% CI 1.05 to 1.91), increased responsibility (HR: 2.13; 95% CI 1.51 to 3.01), not having received financial compensation for overtime work (HR: 0.43; 95% CI 0.31 to 0.62), not having rested after 24-hour shifts (HR: 1.61; 95% CI 1.09 to 2.38), not having had holidays in the previous 6 months (HR: 1.36; 95% CI 1.01 to 1.84), consumption of sleeping pills (HR: 1.83; 95% CI 1.28 to 2.63) and higher alcohol intake (HR: 1.95; 95% CI 1.39 to 2.73). CONCLUSIONS: During the COVID-19 outbreak, 40.1% of Internal Medicine physicians in Spain presented with burn-out syndrome, which was independently related to the assistance of patients with SARS-CoV-2, overworking without any compensation and the fear of being contagious to their relatives. Therefore, it is imperative to initiate programmes to prevent and treat burn-out in front-line physicians during the COVID-19 outbreak.


Assuntos
Esgotamento Profissional/epidemiologia , Médicos/psicologia , Estudos Transversais , Feminino , Humanos , Medicina Interna , Masculino , Pandemias , Espanha/epidemiologia , Inquéritos e Questionários
11.
ACS Appl Mater Interfaces ; 13(9): 10705-10718, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33635046

RESUMO

The validation of metal-phenolic nanoparticles (MPNs) in preclinical imaging studies represents a growing field of interest due to their versatility in forming predesigned structures with unique properties. Before MPNs can be used in medicine, their pharmacokinetics must be optimized so that accumulation in nontargeted organs is prevented and toxicity is minimized. Here, we report the fabrication of MPNs made of a coordination polymer core that combines In(III), Cu(II), and a mixture of the imidazole 1,4-bis(imidazole-1-ylmethyl)-benzene and the catechol 3,4-dihydroxycinnamic acid ligands. Furthermore, a phenolic-based coating was used as an anchoring platform to attach poly(ethylene glycol) (PEG). The resulting MPNs, with effective hydrodynamic diameters of around 120 nm, could be further derivatized with surface-embedded molecules, such as folic acid, to facilitate in vivo targeting and multifunctionality. The prepared MPNs were evaluated for in vitro plasma stability, cytotoxicity, and cell internalization and found to be biocompatible under physiological conditions. First, biomedical evaluations were then performed by intrinsically incorporating trace amounts of the radioactive metals 111In or 64Cu during the MPN synthesis directly into their polymeric matrix. The resulting particles, which had identical physicochemical properties to their nonradioactive counterparts, were used to perform in vivo single-photon emission computed tomography (SPECT) and positron emission tomography (PET) in tumor-bearing mice. The ability to incorporate multiple metals and radiometals into MPNs illustrates the diverse range of functional nanoparticles that can be prepared with this approach and broadens the scope of these nanoconstructs as multimodal preclinical imaging agents.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33525611

RESUMO

The goal of this study is to better understand the relation between the practice of Mindfulness and the sexual activity, sexual satisfaction and erotic fantasies of Spanish-speaking participants. This research focuses on the comparison between people who practice Mindfulness versus naïve people, and explores the practice of Mindfulness and its relation with the following variables about sexuality: body awareness and bodily dissociation, personal sexual satisfaction, partner and relationship-related satisfaction, desire, subjective sexual arousal, genital arousal, orgasm, pain, attitudes towards sexual fantasies and types of sexual fantasies. The sample consisted of 106 selected adults, 32 men and 74 women, who completed six measures on an online survey platform: (a) Mindfulness Attention Awareness Scale (MAAS), (b) Scale of Body Connection (SBC), (c) New Sexual Satisfaction Scale (NSSS), (d) Scale of Sexual Activity in Women (SSA-W) and Men (SSA-M), (e) Hurlbert Index of Sexual Fantasy (HISF), (f) Wilson's Sex Fantasy Questionnaire. In the MAAS, Body Awareness subscale (SBC), NSSS, SSA-W and SSA-M, HISF and intimate fantasies subscale (Wilson's questionnaire), people in the Mindfulness condition showed higher scores and these differences were statistically significant. These results may have relevant implications in the sexuality of clinical and non-clinical samples.


Assuntos
Atenção Plena , Orgasmo , Adulto , Fantasia , Feminino , Humanos , Masculino , Comportamento Sexual , Sexualidade
13.
IUBMB Life ; 73(3): 582-591, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33615665

RESUMO

Stroke is a major cause of death and long-term disability in the adult. Neuronal apoptosis plays an essential role in the pathophysiology of ischemic brain damage and impaired functional recovery after stroke. The tumor suppressor protein p53 regulates key cellular processes, including cell cycle arrest, DNA repair, senescence, and apoptosis. Under cellular stress conditions, p53 undergoes post-translational modifications, which control protein localization, stability, and proapoptotic activity. After stroke, p53 rapidly accumulates in the ischemic brain, where it activates neuronal apoptosis through both transcriptional-dependent and -independent programs. Over the last years, subcellular localization of p53 has emerged as an important regulator of ischemia-induced neuronal apoptosis. Upon an ischemic insult, p53 rapidly translocates to the mitochondria and interacts with B-cell lymphoma-2 family proteins, which activate the mitochondrial apoptotic program, with higher efficacy than through its activity as a transcription factor. Moreover, the identification of a human single nucleotide polymorphism at codon 72 of the Tp53 gene that controls p53 mitochondrial localization and cell susceptibility to apoptosis supports the important role of the p53 mitochondrial program in neuronal survival and functional recovery after stroke. In this article, we review the relevance of mitochondrial and nuclear localization of p53 on neuronal susceptibility to cerebral ischemia and its impact on functional outcome of stroke patients.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33494471

RESUMO

Mindfulness is connected to positive outcomes related to mental health and well-being. However, the psychological mechanisms that account for these relationships are largely unknown. A multiple-step multiple mediator structural equation modeling (SEM) model was tested with mindfulness as the independent variable; purpose in life and behavioral activation as serial mediators; and happiness, anxiety, and depression as outcome measures. Data were obtained from 1267 women. Higher mindfulness was associated with higher levels of happiness and lower anxiety and depression symptoms. The association of mindfulness with the outcome variables could be partially accounted for by purpose in life and behavioral activation. The SEM model explained large proportions of variance in happiness (50%), anxiety (34%), and depression (44%) symptoms. Mindfulness is associated with both a sense of purpose in life and engagement in activities, which are also connected with positive outcomes. Moreover, having purposes in life is linked to higher levels of behavioral activation.

15.
Emerg Infect Dis ; 27(2): 570-573, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33496241

RESUMO

To document the epidemiology, clinical features, and outcomes of murine typhus patients in the Canary Islands (Spain), we analyzed data that were retrospectively collected for 16 years for 221 patients. Murine typhus in the Canary Islands is characterized by a high rate of complications (31.6%), mainly liver, lung, kidney or central nervous system involvement.

16.
PLoS One ; 16(1): e0244139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33406086

RESUMO

Sheep remains constitute the main archaeozoological evidence for the presence of Early Neolithic human groups in the highlands of the Southern Pyrenees but understanding the role of herding activities in the Neolithisation process of this mountain ecosystem calls for the analysis of large and well-dated faunal assemblages. Cova de Els Trocs (Bisaurri, Huesca, Spain), a cave located at 1564 m a.s.l on the southern slopes of the Central Pyrenees, is an excellent case study since it was seasonally occupied throughout the Neolithic (ca. 5312-2913 cal. BC) and more than 4000 caprine remains were recovered inside. The multi-proxy analytical approach here presented has allowed us to offer new data elaborating on vertical mobility practices and herd management dynamics as has not been attempted up until now within Neolithic high-mountain sites in the Iberian Peninsula. For the first time, δ18O and δ13C stable isotope analyses offer direct evidence on both the regular practice of altitudinal movements of sheep flocks and the extended breeding season of sheep. Autumn births are recorded from the second half of the fifth millennium cal. BC onwards. Age-at-death distributions illustrate the progressive decline in caprine perinatal mortality together with the rising survival rate of individuals older than six months of age and the larger frequency of adults. This trend alongside the 'off-season' lambing signal at the implementation of husbandry techniques over time, probably aiming to increase the size of the flocks and their productivity. Palaeoparasitological analyses of sediment samples document also the growing reliance on herding activities of the human groups visiting the Els Trocs cave throughout the Neolithic sequence. In sum, our work provides substantial arguments to conclude that the advanced herding management skills of the Early Neolithic communities arriving in Iberia facilitated the anthropisation process of the subalpine areas of the Central Pyrenees.

17.
ACS Appl Mater Interfaces ; 13(3): 3722-3737, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33439616

RESUMO

Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) loaded with lipoplexes (LPXs) composed of cationic lipid and anionic siRNA (lipid-polymer hybrid nanoparticles, LPNs). Yet, the in vivo efficacy, potential for prolonging the pharmacological effect, disposition, and safety of LPNs after pulmonary administration have not been investigated. In this study, siRNA against enhanced green fluorescent protein (EGFP-siRNA) was either assembled with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to form LPX or co-entrapped with DOTAP in PLGA nanoparticles to form LPNs. The disposition and clearance of LPXs and LPNs in mouse lungs were studied after intratracheal administration by using single-photon emission computed tomography/computed tomography (SPECT/CT) and gamma counting. Fluorescence spectroscopy, Western blot, and confocal laser scanning microscopy were used to evaluate the silencing of the EGFP expression mediated by the LPXs and LPNs after intratracheal administration to transgenic mice expressing the EGFP gene. The in vivo biocompatibility of LPXs and LPNs was investigated by measuring the cytokine level, total cell counts in bronchoalveolar lavage fluid, and observing the lung tissue histology section. The results showed that the silencing of the EGFP expression mediated by LPNs after pulmonary administration was both prolonged and enhanced as compared to LPXs. This may be attributed to the sustained release characteristics of PLGA, and the prolonged retention in the lung tissue of the colloidally more stable LPNs in comparison to LPXs, as indicated by SPECT/CT. The presence of PLGA effectively alleviated the acute inflammatory effect of cationic lipids to the lungs. This study suggests that PLGA-based LPNs may present an effective formulation strategy to mediate sustained gene silencing effects in the lung via pulmonary administration.


Assuntos
Pulmão/metabolismo , Nanopartículas/química , Poliglactina 910/química , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , Células A549 , Animais , Vias de Administração de Medicamentos , Proteínas de Fluorescência Verde/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Interferente Pequeno/genética
18.
Hypertension ; 77(2): 557-570, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33356402

RESUMO

No drug therapy has shown to limit abdominal aortic aneurysm (AAA) growth or rupture, and the understanding of the disease biology is incomplete; whereby, one challenge of vascular medicine is the development of good animal models and therapies for this life-threatening condition. The nuclear receptor NOR-1 (neuron-derived orphan receptor 1) controls biological processes involved in AAA; however, whether it plays a role in this pathology is unknown. Through a gain-of-function approach we assessed the impact of NOR-1 expression on the vascular response to Ang II (angiotensin II). We used 2 mouse models that overexpress human NOR-1 in the vasculature, one of them specifically in vascular smooth muscle cells. NOR-1 transgenesis amplifies the response to Ang II enhancing vascular inflammation (production of proinflammatory cytokines, chemokines, and reactive oxygen species), increasing MMP (matrix metalloproteinase) activity and disturbing elastin integrity, thereby broking the resistance of C57BL/6 mice to Ang II-induced AAA. Genes encoding for proteins critically involved in AAA formation (Il [interleukin]-6, Il-1ß, Cxcl2, [C-X-C motif chemokine ligand 2], Mcp-1 [monocyte chemoattractant protein 1], and Mmp2) were upregulated in aneurysmal tissues. Both animal models show a similar incidence and severity of AAA, suggesting that high expression of NOR-1 in vascular smooth muscle cell is a sufficient condition to strengthen the response to Ang II. These alterations, including AAA formation, were prevented by the MMP inhibitor doxycycline. Microarray analysis identified gene sets that could explain the susceptibility of transgenic animals to Ang II-induced aneurysms, including those related with extracellular matrix remodeling, inflammatory/immune response, sympathetic activity, and vascular smooth muscle cell differentiation. These results involve NOR-1 in AAA and validate mice overexpressing this receptor as useful experimental models.

19.
Arthritis Res Ther ; 22(1): 281, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256854

RESUMO

BACKGROUND: The discovery and development of new medicines requires high-throughput screening of possible therapeutics in a specific model of the disease. Infrared thermal imaging (IRT) is a modern assessment method with extensive clinical and preclinical applications. Employing IRT in longitudinal preclinical setting to monitor arthritis onset, disease activity and therapeutic efficacies requires a standardized framework to provide reproducible quantitative data as a precondition for clinical studies. METHODS: Here, we established the accuracy and reliability of an inexpensive smartphone connected infrared (IR) camera against known temperature objects as well as certified blackbody calibration equipment. An easy to use protocol incorporating contactless image acquisition and computer-assisted data analysis was developed to detect disease-related temperature changes in a collagen-induced arthritis (CIA) mouse model and validated by comparison with two conventional methods, clinical arthritis scoring and paw thickness measurement. We implemented IRT to demonstrate the beneficial therapeutic effect of nanoparticle drug delivery versus free methotrexate (MTX) in vivo. RESULTS: The calibrations revealed high accuracy and reliability of the IR camera for detecting temperature changes in the rheumatoid arthritis animal model. Significant positive correlation was found between temperature changes and paw thickness measurements as the disease progressed. IRT was found to be superior over the conventional techniques specially at early arthritis onset, when it is difficult to observe subclinical signs and measure structural changes. CONCLUSION: IRT proved to be a valid and unbiased method to detect temperature changes and quantify the degree of inflammation in a rapid and reproducible manner in longitudinal preclinical drug efficacy studies.

20.
Psych J ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33271635

RESUMO

Exam is an academic stressor that frequently triggers the affective reaction of anxiety, as well as psychophysiological changes in the autonomic nervous system. Anxiety is a negative affective variable associated with a low level of performance. This study examined the impact of an academic exam on state anxiety (SA) levels and the effects on cardiovascular activity during its performance, as well as its possible influence on the score. The study group was composed of 122 female university students. Cardiovascular responses (heart rate [HR], diastolic blood pressure, and systolic blood pressure) were recorded continuously in three phases (before, during, and after the exam) for each participant. The SA was obtained with the State-Trait Anxiety Inventory (STAI) before the exam. Then, those with extremely low and high SA scores were assigned to the low and high anxiety groups, respectively. The exam score reflected the performance level. The results partially confirmed our hypotheses. The high SA group showed significant fluctuations in cardiovascular activity; in particular, the HRs were higher than in the low SA group during the exam (not in diastolic and systolic pressures, respectively). On the other hand, the high SA group showed lower performance expectations scores than the low SA group, and the level of performance was similar in the two groups. Therefore, the exam confirmed changes in the HR with respect to the SA level, with no significant impact on performance.

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