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1.
JMIR Mhealth Uhealth ; 8(6): e17557, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32496203

RESUMO

BACKGROUND: Emergency department (ED) patients have high rates of risky alcohol use, and an ED visit offers an opportunity to intervene. ED-based screening, brief intervention, and referral to treatment (SBIRT) reduces alcohol use and health care costs. Mobile health (mHealth) interventions may expand the impact of SBIRTs but are understudied in low-resource ED populations. OBJECTIVE: The objective of this study was to assess the feasibility of and patient satisfaction with a text-based mHealth extension of an ED screening program to reduce risky alcohol use in low-income, urban patients. METHODS: Research assistants screened a convenience sample of ED patients in person for risky alcohol use via the Alcohol Use Disorders Identification Test (AUDIT). Patients who reported AUDIT scores ≥8 and <20 were informed of their AUDIT score and risk. RAs invited patients with SMS text message-capable phones to receive mROAD (mobilizing to Reduce Overuse of Alcohol in the ED), an SMS text message-based extension of the ED screening program. mROAD is a 7-day program of twice-daily SMS text messages based on the National Institutes of Health's Rethinking Drinking campaign. Participants were allocated to a control group (daily sham text messages without specific guidance on behaviors, such as "Thanks for taking part!") or to the mROAD intervention group. Patients were interviewed at 30 days to assess acceptability, satisfaction, and changes in drinking behavior. Satisfaction was examined descriptively. Pre and post measurements of drinking behaviors and motivation were compared, as were differences in change scores between the intervention arms. RESULTS: Of 1028 patients screened, 95 (9.2%) exhibited risky alcohol use based on AUDIT, and 23/95 (24%) of those patients did not own an SMS text messaging-capable phone; this left 72/95 (76%) eligible patients. Among eligible participants, 48/72 (67%) agreed to enroll; 31/48 (65%) achieved follow-up (18/24 (75%) in the intervention group and 13/24 (55%) in the control group). Participants who completed follow-up reported high satisfaction. Changes in behavior were similar between the arms. Overall, the number of drinking days reported in the prior 30 days decreased by 5.0 (95% CI 1.7-8.3; P=.004), and the number of heavy drinking days decreased by 4.1 (95% CI 1.0 to 7.15, P=.01). Patients reported an 11-point increase (95% CI 2.6-20, P=.01, 10% overall increase) in motivation to change alcohol use via the Change Questionnaire. The were no statistical differences in drinking days, heavy drinking days, or motivation to change between the arms. CONCLUSIONS: The mROAD trial was feasible. Over three-quarters of ED patients with risky alcohol use owned a text message-capable phone, and two-thirds of these patients were willing to participate; only 1 patient opted out of the intervention. Although 35% of patients were lost to follow-up at 30 days, those patients who did follow up had favorable impressions of the program; more than 90% reported that SMS text messages were a "good way to teach," and 89% of intervention arm participants enjoyed the program and found that the messages were motivating. Both the mROAD and sham message groups showed promising changes in alcohol use and motivation to change. mROAD is a feasible intervention that may reduce rates of risky alcohol use in ED patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02158949; https://clinicaltrials.gov/ct2/show/NCT02158949.

2.
J Immigr Minor Health ; 22(3): 439-447, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31898078

RESUMO

Many ED patients have limited English proficiency (LEP). Under Title VI of the 1964 Civil Rights Act, LEP patients are entitled to language assistance, however, multiple studies demonstrate that language assistance is underutilized. We aimed to characterize the knowledge, practice patterns, and preferences of ED providers and staff regarding language assistance for LEP patients. We performed a self-administered, anonymous questionnaire in an urban, public ED where most patients have LEP. Subjects included all ED providers and staff with substantial patient contact. We recorded ED role, knowledge of language assistance policy, prior training on working with interpreters, non-English language skills and bilingual certification. Outcomes included frequency of and comfort level with respondent's own non-English language (NEL) use in the ED, and the preferred and most frequently used modalities of language assistance. Of the 354 total ED employees, 261 were approached and 259 agreed to participate, which represents a 73% response rate (259/354). Respondents were 37% MD/NPs, 34% RNs and 29% other ED staff. Only 50/259 (19%) had prior training on working with interpreters. 171/257 (67%) were "unsure" if the hospital had a policy on language assistance. The most frequent modalities accessed for spoken language assistance were "Other ED staff" 106/259 (41%) or "ad hoc interpreter" 62/259 (24%). Although 227/274 (83%) use a non-English language with patients regularly, comfort levels in using their NEL for clinical care were variable. Most ED providers and staff had little training in the use of language assistance and were unaware of hospital policy. Use of NEL skills by providers for clinical care is common. Dissemination of best practices for the provision of language assistance and the clinical use of NEL skills has the potential to improve communication with LEP patients.

3.
Top Curr Chem (Cham) ; 378(1): 15, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31938922

RESUMO

Nowadays, biomaterials have become a crucial element in numerous biomedical, preclinical, and clinical applications. The use of nanoparticles entails a great potential in these fields mainly because of the high ratio of surface atoms that modify the physicochemical properties and increases the chemical reactivity. Among them, carbon nanotubes (CNTs) have emerged as a powerful tool to improve biomedical approaches in the management of numerous diseases. CNTs have an excellent ability to penetrate cell membranes, and the sp2 hybridization of all carbons enables their functionalization with almost every biomolecule or compound, allowing them to target cells and deliver drugs under the appropriate environmental stimuli. Besides, in the new promising field of artificial biomaterial generation, nanotubes are studied as the load in nanocomposite materials, improving their mechanical and electrical properties, or even for direct use as scaffolds in body tissue manufacturing. Nevertheless, despite their beneficial contributions, some major concerns need to be solved to boost the clinical development of CNTs, including poor solubility in water, low biodegradability and dispersivity, and toxicity problems associated with CNTs' interaction with biomolecules in tissues and organs, including the possible effects in the proteome and genome. This review performs a wide literature analysis to present the main and latest advances in the optimal design and characterization of carbon nanotubes with biomedical applications, and their capacities in different areas of preclinical research.


Assuntos
Nanomedicina/métodos , Nanotecnologia/métodos , Nanotubos de Carbono/análise , Animais , Humanos , Modelos Moleculares , Nanotubos de Carbono/toxicidade , Nanotubos de Carbono/ultraestrutura
4.
Artigo em Inglês | MEDLINE | ID: mdl-31642207

RESUMO

Due to their ability to effectively downregulate the expression of target genes, small interfering RNA (siRNA) have emerged as promising candidates for precision medicine in cancer. Although some siRNA-based treatments have advanced to clinical trials, challenges such as poor stability during circulation, and less than optimal pharmacokinetics and biodistribution of siRNA in vivo present barriers to the systemic delivery of siRNA. In recent years, theranostic nanomedicine integrating siRNA delivery has attracted significant attention for precision medicine. Theranostic nanomedicine takes advantage of the high capacity of nanoplatforms to ferry cargo with imaging and therapeutic capabilities. These theranostic nanoplatforms have the potential to play a major role in gene specific treatments. Here we have reviewed recent advances in the use of theranostic nanoplatforms to deliver siRNA, and discussed the opportunities as well as challenges associated with this exciting technology. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

5.
Mater Sci Eng C Mater Biol Appl ; 106: 110173, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753390

RESUMO

Bone substitutes based on calcium phosphates can be classified in two major groups: ceramics and cements. Both are biomaterials with excellent biocompatibility that have been studied as local delivery systems for drugs. This study aims to evaluate drug-release kinetics in silicon beta-tricalcium phosphate ceramics (Si-ß-TCP) and in silicon calcium phosphate cements (Si-CPCs). We want to investigate if the differences in composition and in structure of the Si-ß-TCP and the Si-CPC may influence for drug loading and in its release kinetics from the biomaterial. The results obtained indicate that all drug-loaded materials were efficient to tailor drug release kinetics and inhibited the growth of Staphylococcus aureus. The cements prepared with high concentrations of silicon (80% Si-CPC) present zero-order release kinetics, independent of the drug concentration loaded. Si-ß-TCP and Si-CPC offer a simple technology that could serve to personalize the delivery of bioactive molecules according to each patient's needs in the treatment of bone conditions, not only limited to prophylaxis, but also for the treatment of bone infection.


Assuntos
Antibacterianos/química , Fosfatos de Cálcio/química , Cerâmica/química , Silício/química , Materiais Biocompatíveis/química , Humanos , Cinética , Teste de Materiais , Engenharia Tecidual
6.
PLoS One ; 14(10): e0222837, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31665147

RESUMO

Statements about building walls, deportation and denying services to undocumented immigrants made during President Trump's presidential campaign and presidency may induce fear in Latino populations and create barriers to their health care access. To assess how these statements relate to undocumented Latino immigrants' (UDLI) and Latino legal residents/citizens' (LLRC) perceptions of safety and their presentations for emergency care, we conducted surveys of adult patients at three county emergency departments (EDs) in California from June 2017 to December 2018. Of 1,684 patients approached, 1,337 (79.4%) agreed to participate: 34.3% UDLI, 36.9% LLRC, and 29.8% non-Latino legal residents/citizens (NLRC). The vast majority of UDLI (95%), LLRC (94%) and NLRC (85%) had heard statements about immigrants. Most UDLI (89%), LLRC (88%) and NLRC (87%) either thought that these measures were being enacted now or will be enacted in the future. Most UDLI and half of LLRC reported that these statements made them feel unsafe living in the US, 75% (95% CI 70-80%) and 51% (95% CI 47-56%), respectively. More UDLI reported that these statements made them afraid to come to the ED (24%, 95% CI 20-28%) vs LLRC (4.4%, 95% CI 3-7%) and NLRC (3.5%, 95% CI 2-6%); 55% of UDLI with this fear stated it caused them to delay coming to the ED (median delay 2-3 days). The vast majority of patients in our California EDs have heard statements during the 2016 presidential campaign or from President Trump about measures against undocumented immigrants, which have induced worry and safety concerns in both UDLI and LLRC patients. Exposure to these statements was also associated with fear of accessing emergency care in some UDLIs. Given California's sanctuary state status, these safety concerns and ED access fears may be greater in a nationwide population of Latinos.


Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Emigrantes e Imigrantes/estatística & dados numéricos , Imigrantes Indocumentados , Adulto , California/epidemiologia , Tratamento de Emergência , Medo/psicologia , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Masculino , Estados Unidos/epidemiologia
7.
Front Cardiovasc Med ; 6: 126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552270

RESUMO

Platelet concentrates (PCs) are biological autologous products derived from the patient's whole blood and consist mainly of supraphysiologic concentration of platelets and growth factors (GFs). These GFs have anti-inflammatory and healing enhancing properties. Overall, PCs seem to enhance bone and soft tissue healing in alveolar ridge augmentation, periodontal surgery, socket preservation, implant surgery, endodontic regeneration, sinus augmentation, bisphosphonate related osteonecrosis of the jaw (BRONJ), osteoradionecrosis, closure of oroantral communication (OAC), and oral ulcers. On the other hand, no effect was reported for gingival recession and guided tissue regeneration (GTR) procedures. Also, PCs could reduce pain and inflammatory complications in temporomandibular disorders (TMDs), oral ulcers, and extraction sockets. However, these effects have been clinically inconsistent across the literature. Differences in study designs and types of PCs used with variable concentration of platelets, GFs, and leucocytes, as well as different application forms and techniques could explain these contradictory results. This study aims to review the clinical applications of PCs in oral and craniofacial tissue regeneration and the role of their molecular components in tissue healing.

8.
Materials (Basel) ; 12(11)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163572

RESUMO

The optical behavior exhibited by bimetallic nanoparticles was analyzed by the influence of ultrasonic and nonlinear optical waves in propagation through the samples contained in an ethanol suspension. The Au-Pt nanoparticles were prepared by a sol-gel method. Optical characterization recorded by UV-vis spectrophotometer shows two absorption peaks correlated to the synergistic effects of the bimetallic alloy. The structure and nanocrystalline nature of the samples were confirmed by Scanning Transmission Electron Microscopy with X-ray energy dispersive spectroscopy evaluations. The absorption of light associated with Surface Plasmon Resonance phenomena in the samples was modified by the dynamic influence of ultrasonic effects during the propagation of optical signals promoting nonlinear absorption and nonlinear refraction. The third-order nonlinear optical response of the nanoparticles dispersed in the ethanol-based fluid was explored by nanosecond pulses at 532 nm. The propagation of high-frequency sound waves through a nanofluid generates a destabilization in the distribution of the nanoparticles, avoiding possible agglomerations. Besides, the influence of mechanical perturbation, the container plays a major role in the resonance and attenuation effects. Ultrasound interactions together to nonlinear optical phenomena in nanofluids is a promising alternative field for a wide of applications for modulating quantum signals, sensors and acousto-optic devices.

9.
Med. oral patol. oral cir. bucal (Internet) ; 24(3): e326-e338, mayo 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-185641

RESUMO

Background: Tyrosine kinase receptor family is involved in tumor growth, pathological angiogenesis and the progression (metastasis) of cancer. Sunitinib (Sutent(R)) inhibits members of the tyrosine kinase receptor family affecting the induction of angiogenesis and tumor progression. It is not clear if sunitinib increases the risk of osteonecrosis of the jaws (ONJ). The aim of this study was to carry out a systematic review about ONJ related to sunitinib, describing existing cases and possible associated risk factors. Material and Methods: The PubMed/MEDLINE and Cochrane Library databases were searched without date restriction up to September 2018. We included prospective and retrospective observational studies, cross-sectional studies, clinical cases and series of cases, involving only human subjects. The methodological quality of the studies was assessed using The Joanna Briggs Institute (JBI) and Newcastle-Ottawa tools. Results: A total of 13 studies fulfilled our inclusion criteria of which 7 were clinical cases, 5 case series and a retrospective study. All the articles were published between 2009 and 2018. Of the 102 patients treated with sunitinib analyzed in this study, 58 developed ONJ, being or having been treated with sunitinib and bisphosphonates or exclusively with sunitinib. Conclusions: In this systematic review, we found an increase of ONJ in patients who are medicated with other drugs different than bisphosphonates and denosumab. It is necessary that dentists, oral and maxillofacial surgeons as well as oncologists know the risk of ONJ that these antiresorptive drugs could have. There is a need to continue researching in this field with the aim of an increasing knowledge in this area and creating an adequate protocol of action for this population


No disponible


Assuntos
Humanos , Conservadores da Densidade Óssea , Osteonecrose , Estudos Transversais , Difosfonatos , Estudos Prospectivos , Estudos Retrospectivos , Sunitinibe
10.
Cancer Metastasis Rev ; 38(1-2): 51-64, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30840168

RESUMO

Hypoxia in cancers has evoked significant interest since 1955 when Thomlinson and Gray postulated the presence of hypoxia in human lung cancers, based on the observation of necrosis occurring at the diffusion limit of oxygen from the nearest blood vessel, and identified the implication of these observations for radiation therapy. Coupled with discoveries in 1953 by Gray and others that anoxic cells were resistant to radiation damage, these observations have led to an entire field of research focused on exploiting oxygenation and hypoxia to improve the outcome of radiation therapy. Almost 65 years later, tumor heterogeneity of nearly every parameter measured including tumor oxygenation, and the dynamic landscape of cancers and their microenvironments are clearly evident, providing a strong rationale for cancer personalized medicine. Since hypoxia is a major cause of extracellular acidosis in tumors, here, we have focused on the applications of imaging to understand the effects of hypoxia in tumors and to target hypoxia in theranostic strategies. Molecular and functional imaging have critically important roles to play in personalized medicine through the detection of hypoxia, both spatially and temporally, and by providing new understanding of the role of hypoxia in cancer aggressiveness. With the discovery of the hypoxia-inducible factor (HIF), the intervening years have also seen significant progress in understanding the transcriptional regulation of hypoxia-induced genes. These advances have provided the ability to silence HIF and understand the associated molecular and functional consequences to expand our understanding of hypoxia and its role in cancer aggressiveness. Most recently, the development of hypoxia-based theranostic strategies that combine detection and therapy are further establishing imaging-based treatment strategies for precision medicine of cancer.


Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Hipóxia Tumoral/fisiologia , Animais , Humanos , Imagem por Ressonância Magnética , Metástase Neoplásica , Neoplasias/irrigação sanguínea , Tomografia por Emissão de Pósitrons
11.
Microsc Res Tech ; 82(5): 507-516, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30597696

RESUMO

Spruce wood (picea abis) has been widely used as structural element, from buildings to musical instruments, due to its outstanding mechanical performances. The main stem transverse section exhibits growth rings formed by periodic fringes patterns, which are constituted by lamellae-tracheid arrangements. In order to improve the understanding of each wood microstructure role, the morphology and crystallinity of earlywood and latewood fibers were examined mainly using scanning electron microscopy, atomic force microscopy, and X-ray difracction. Moreover, measurements of effective elastic modulus and hardness were obtained by nanoindentation tests using a Berkovich indenter in order to confirmed increase in compactness of the wood microstructures. The results indicate that variations in mechanical properties values can be associated with well defined microstructural performances for each characteristic fiber type, where those that belong to latewood fiber showed the most improved behaviors. A finite element simulation of a lamellar-tracheids arrangement was carried out in order to clarify its stiffness and elastic deformation capabilities, as relevant factors contributing to the successful adaptation of picea abis colonies to harsh conditions habitats as well as for its construction applications of string instruments.


Assuntos
Microscopia de Força Atômica , Picea/ultraestrutura , Madeira/ultraestrutura , Fenômenos Biomecânicos , Análise de Elementos Finitos , Microscopia Eletrônica de Varredura , Difração de Raios X
12.
NMR Biomed ; 32(10): e4053, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30693605

RESUMO

Because of the spatial and temporal heterogeneities of cancers, technologies to investigate cancer cells and the consequences of their interactions with abnormal physiological environments, such as hypoxia and acidic extracellular pH, with stromal cells, and with the extracellular matrix, under controlled conditions, are valuable to gain insights into the functioning of cancers. These insights can lead to an understanding of why cancers invade and metastasize, and identify effective treatment strategies. Here we have provided an overview of the applications of MRI/MRS/MRSI to investigate intact perfused cancer cells, their metabolism and invasion, and their interactions with stromal cells and the extracellular matrix.


Assuntos
Comunicação Celular , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Neoplasias/metabolismo , Neoplasias/patologia , Perfusão , Humanos , Invasividade Neoplásica , Células Estromais/patologia
13.
Magn Reson Imaging ; 58: 67-75, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30660705

RESUMO

INTRODUCTION: Functional magnetic resonance imaging (fMRI) is one of the most highly regarded techniques in the neuroimaging field. This technique is based on vascular responses to neuronal activation and is extensively used in clinical and animal research studies. In preclinical settings, fMRI is usually applied to anesthetized animals. However, anesthetics cause alterations, e.g. hypothermia, in the physiology of the animals and this has the potential to disrupt fMRI signals. The current temperature control method involves a technician, as well as monitoring the acquisition MRI sequences, also controlling the temperature of the animal; this is inefficient. METHODS: In order to avoid hypothermia in anesthetized rodents an Open-Source automatic temperature control device is presented. It takes signals from an intrarectal temperature sensor, as well as signals from a thermal bath, which warms up the body of the animal under study, in order to determine the mathematical model of the thermal response of the animal. RESULTS: A Proportional-Integral-Derivative (PID) algorithm, which was discretized in an Arduino microcontroller, was developed to automatically keep stable the body temperature of the animal under study. The PID algorithm has been shown to be accurate in preserving the body temperature of the animal. CONCLUSION: This work presents the TherMouseDuino. It is an Open-Source automatic temperature control system and reduces temperature fluctuations, thus providing robust conditions in which to perform fMRI experiments. Furthermore, our device frees up the technician to focus solely on monitoring the MRI sequences.


Assuntos
Desenho de Equipamento , Hipotermia Induzida , Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/métodos , Algoritmos , Animais , Temperatura Corporal , Computadores , Temperatura Alta , Camundongos , Modelos Teóricos , Neuroimagem/instrumentação , Neuroimagem/métodos , Neurônios
14.
Br J Cancer ; 119(5): 622-630, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30206370

RESUMO

BACKGROUND: Tumour carbonic anhydrase IX (CAIX), a hypoxia-inducible tumour-associated cell surface enzyme, is thought to acidify the tumour microenvironment by hydrating CO2 to form protons and bicarbonate, but there is no definitive evidence for this in solid tumours in vivo. METHODS: We used 1H magnetic resonance spectroscopic imaging (MRSI) of the extracellular pH probe imidazolyl succinic acid (ISUCA) to measure and spatially map extracellular pH in HCT116 tumours transfected to express CAIX and empty vector controls in SCID mice. We also measured intracellular pH in situ with 31P MRS and measured lactate in freeze-clamped tumours. RESULTS: CAIX-expressing tumours had 0.15 pH-unit lower median extracellular pH than control tumours (pH 6.71 tumour vs pH 6.86 control, P = 0.01). Importantly, CAIX expression imposed an upper limit for tumour extracellular pH at 6.93. Despite the increased lactate concentration in CAIX-expressing tumours, 31P MRS showed no difference in intracellular pH, suggesting that CAIX acidifies only the tumour extracellular space. CONCLUSIONS: CAIX acidifies the tumour microenvironment, and also provides an extracellular pH control mechanism. We propose that CAIX thus acts as an extracellular pH-stat, maintaining an acidic tumour extracellular pH that is tolerated by cancer cells and favours invasion and metastasis.


Assuntos
Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Anidrase Carbônica IX/genética , Anidrase Carbônica IX/metabolismo , Neoplasias Colorretais/patologia , Ácido Láctico/análise , Animais , Hipóxia Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Células HCT116 , Humanos , Imidazóis/química , Camundongos , Transplante de Neoplasias , Espectroscopia de Prótons por Ressonância Magnética , Microambiente Tumoral
15.
Front Neuroanat ; 12: 31, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755326

RESUMO

Thyroid hormone deficiency at early postnatal ages affects the cytoarchitecture and function of neocortical and telencephalic limbic areas, leading to impaired associative memory and in a wide spectrum of neurological and mental diseases. Neocortical areas project interhemispheric axons mostly through the corpus callosum and to a lesser extent through the anterior commissure (AC), while limbic areas mostly project through the AC and hippocampal commissures. Functional magnetic resonance data from children with late diagnosed congenital hypothyroidism and abnormal verbal memory processing, suggest altered ipsilateral and contralateral telencephalic connections. Gestational hypothyroidism affects AC development but the possible effect of transient and chronic postnatal hypothyroidism, as occurs in late diagnosed neonates with congenital hypothyroidism and in children growing up in iodine deficient areas, still remains unknown. We studied AC development using in vivo magnetic resonance imaging and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated rats were studied. One group was MMI-treated from postnatal day (P) 0 to P21; some of these rats were also treated with L-thyroxine (T4) from P15 to P21, as a model for early transient hypothyroidism. Other rats were MMI-treated from P0 to P150 and from embryonic day (E) 10 to P170, as a chronic hypothyroidism group. The results were compared with age paired control rats. The normalized T2 signal using magnetic resonance image was higher in MMI-treated rats and correlated with the number and percentage of myelinated axons. Using electron microscopy, we observed decreased myelinated axon number and density in transient and chronic hypothyroid rats at P150, unmyelinated axon number increased slightly in chronic hypothyroid rats. In MMI-treated rats, the myelinated axon g-ratio and conduction velocity was similar to control rats, but with a decrease in conduction delays. These data show that early postnatal transient and chronic hypothyroidism alters AC maturation that may affect the transfer of information through the AC. The alterations cannot be recovered after delayed T4-treatment. Our data support the neurocognitive delay found in late T4-treated children with congenital hypothyroidism.

16.
Nanoscale ; 10(14): 6349-6360, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29560985

RESUMO

The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T1-T2 dual-mode relaxivity requires the accurate assembly of T1 and T2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)4[Fe(CN)6] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)4[Fe(CN)6]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T1- and T2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.

17.
Food Chem Toxicol ; 115: 20-25, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29501275

RESUMO

The impact of bisphenol A (BPA) on the prostate gland has taken center stage, with a special focus placed on understanding how BPA affects prostate physiopathology. In this study, we evaluated the ability of lower doses of BPA to induce alterations in 5α-R isozymes and aromatase, in the prostate of juvenile rats exposed during developmental stage. Gestating Wistar rats were treated s.c with either vehicle or BPA (2.4 and 10 µg/kg b.w./day) from gestational day 12 to parturition. Then, male pups were s.c treated from postnatal day 1 through day 21, when they were euthanized and qRT-PCR, western blot and hormone levels determination were performed. We found that BPA at dose of 2.4 and 10 µg/kg b.w./day significantly decreased the mRNA and protein levels of 5α-R2. However, neither 5α-R1 nor 5α-R3 was affected by this exposure. BPA at dose of 10 µg/kg b.w./day significantly increased the mRNA and protein levels of aromatase. BPA also decreased plasma levels of both testosterone and dihydrotestosterone and increased estradiol. These data lend support that low-dose BPA during fetal and neonatal prostate development interfere with in situ estrogen and androgen production in the prostate gland of juvenile rats through the enzymes aromatase and 5α-Reductase.


Assuntos
Aromatase/metabolismo , Compostos Benzidrílicos/toxicidade , Colestenona 5 alfa-Redutase/metabolismo , Fenóis/toxicidade , Próstata/efeitos dos fármacos , Próstata/enzimologia , Androgênios/metabolismo , Animais , Aromatase/genética , Colestenona 5 alfa-Redutase/genética , Feminino , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Exposição Materna/efeitos adversos , Próstata/crescimento & desenvolvimento , Ratos , Ratos Wistar , Testosterona/metabolismo
18.
Methods Mol Biol ; 1718: 117-134, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29341006

RESUMO

Since its discovery in the early 90s, BOLD signal-based functional Magnetic Resonance Imaging (fMRI) has become a fundamental technique for the study of brain activity in basic and clinical research. Functional MRI signals provide an indirect but robust and quantitative readout of brain activity through the tight coupling between cerebral blood flow and neuronal activation, the so-called neurovascular coupling. Combined with experimental techniques only available in animal models, such as intracerebral micro-stimulation, optogenetics or pharmacogenetics, provides a powerful framework to investigate the impact of specific circuit manipulations on overall brain dynamics. The purpose of this chapter is to provide a comprehensive protocol to measure brain activity using fMRI with intracerebral electric micro-stimulation in murine models. Preclinical research (especially in rodents) opens the door to very sophisticated and informative experiments, but at the same time imposes important constrains (i.e., anesthetics, translatability), some of which will be addressed here.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Estimulação Elétrica , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Neurônios/fisiologia , Animais , Circulação Cerebrovascular , Neuroimagem Funcional , Acoplamento Neurovascular , Oxigênio/metabolismo , Roedores
19.
Methods Mol Biol ; 1718: 297-313, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29341016

RESUMO

Oxygen monitoring is a topic of exhaustive research due to its central role in many biological processes, from energy metabolism to gene regulation. The ability to monitor in vivo the physiological distribution and the dynamics of oxygen from subcellular to macroscopic levels is a prerequisite to better understand the mechanisms associated with both normal and disease states (cancer, neurodegeneration, stroke, etc.). This chapter focuses on magnetic resonance imaging (MRI) based techniques to assess oxygenation in vivo. The first methodology uses injected fluorinated agents to provide quantitative pO2 measurements with high precision and suitable spatial and temporal resolution for many applications. The second method exploits changes in endogenous contrasts, i.e., deoxyhemoglobin and oxygen molecules through measurements of T 2* and T 1, in response to an intervention to qualitatively evaluate hypoxia and its potential modulation.


Assuntos
Hemoglobinas/metabolismo , Hipóxia/fisiopatologia , Imagem por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Monitorização Fisiológica , Oxigênio/metabolismo , Animais , Humanos
20.
Brain ; 141(2): 365-376, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29253101

RESUMO

Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. Bacterial artificial chromosome (BAC) transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human pain-insensitive phenotype are therefore potential novel targets for the development of new analgesic drugs.awx326media15680039660001.


Assuntos
Insensibilidade Congênita à Dor/genética , Limiar da Dor/fisiologia , Dor/fisiopatologia , Mutação Puntual/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Adolescente , Adulto , Idoso , Animais , Cálcio/metabolismo , Capsaicina/efeitos adversos , Modelos Animais de Doenças , Feminino , Gânglios Espinais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Hiperalgesia/patologia , Hiperalgesia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Dor/induzido quimicamente , Insensibilidade Congênita à Dor/patologia , Insensibilidade Congênita à Dor/fisiopatologia , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/fisiologia , Pele/patologia , Adulto Jovem
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