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1.
Artigo em Inglês | MEDLINE | ID: mdl-31939047

RESUMO

In the past, researchers have attempted to model trabecular bone using computational techniques. However, only a few of these models are visually similar, but not representative of the microstructural characteristics of real trabecular bones. In this study, we hypothesized that probabilistic modeling approaches could be used to generate representative digital models that capture the microstructural features of real trabecular bones. To test this hypothesis, we proposed a novel mathematical framework to build the digital models and compared the digital models to real bone specimens. First, an initial three-dimensional cellular structure was generated using Voronoi tessellation, with the faces and edges of the Voronoi cells considered as a pool of potential trabecular plates and rods, respectively. Then, inverse Monte Carlo simulations were performed to select, delete, or reassign plates and rods until the underlying size, orientation, and spatial distributions of the plates and rods converged to the target distributions obtained from real trabecular bone microstructures. Next, digital graphics techniques were used to define the thickness of trabecular plates and the diameter of trabecular rods, followed by writing the model into a Standard Tessellation Language file and then smoothing the model surfaces for a more natural appearance. To verify the efficacy of the digital model in capturing the microstructural features of real trabecular bones, forty-six digital models with a large variation in microstructural features were generated based on the target distributions obtained from trabecular bone specimens of twelve human cadaveric femurs. Then, the histomorphological parameters of the digital models were compared with those of the real trabecular bone specimens. The results indicate that the digital models are capable of capturing major microstructural features of the trabecular bone samples, thus proving the hypothesis that the proposed probabilistic modeling approach could render real trabecular bone microstructures.

2.
Acta Biomater ; 102: 326-340, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31805408

RESUMO

Articular cartilage defects are a common source of joint pain and dysfunction. We hypothesized that sustained low-dose dexamethasone (DEX) delivery via an acellular osteochondral implant would have a dual pro-anabolic and anti-catabolic effect, both supporting the functional integrity of adjacent graft and host tissue while also attenuating inflammation caused by iatrogenic injury. An acellular agarose hydrogel carrier with embedded DEX-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres (DLMS) was developed to provide sustained release for at least 99 days. The DLMS implant was first evaluated in an in vitro pro-inflammatory model of cartilage degradation. The implant was chondroprotective, as indicated by maintenance of Young's modulus (EY) (p = 0.92) and GAG content (p = 1.0) in the presence of interleukin-1ß insult. In a subsequent preliminary in vivo experiment, an osteochondral autograft transfer was performed using a pre-clinical canine model. DLMS implants were press-fit into the autograft donor site and compared to intra-articular DEX injection (INJ) or no DEX (CTL). Functional scores for DLMS animals returned to baseline (p = 0.39), whereas CTL and INJ remained significantly worse at 6 months (p < 0.05). DLMS knees were significantly more likely to have improved OARSI scores for proteoglycan, chondrocyte, and collagen pathology (p < 0.05). However, no significant improvements in synovial fluid cytokine content were observed. In conclusion, utilizing a targeted DLMS implant, we observed in vitro chondroprotection in the presence of IL-1-induced degradation and improved in vivo functional outcomes. These improved outcomes were correlated with superior histological scores but not necessarily a dampened inflammatory response, suggesting a primarily pro-anabolic effect. STATEMENT OF SIGNIFICANCE: Articular cartilage defects are a common source of joint pain and dysfunction. Effective treatment of these injuries may prevent the progression of osteoarthritis and reduce the need for total joint replacement. Dexamethasone, a potent glucocorticoid with concomitant anti-catabolic and pro-anabolic effects on cartilage, may serve as an adjuvant for a variety of repair strategies. Utilizing a dexamethasone-loaded osteochondral implant with controlled release characteristics, we demonstrated in vitro chondroprotection in the presence of IL-1-induced degradation and improved in vivo functional outcomes following osteochondral repair. These improved outcomes were correlated with superior histological cartilage scores and minimal-to-no comorbidity, which is a risk with high dose dexamethasone injections. Using this model of cartilage restoration, we have for the first time shown the application of targeted, low-dose dexamethasone for improved healing in a preclinical model of focal defect repair.

3.
Chemosphere ; 244: 125494, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31812767

RESUMO

Puberty is a crucial developmental period for structural modifications of brain and activation of the neural circuits underlying sex differences in social behavior. It is possible that pubertal exposure to bisphenol-A (BPA), a common EED with a weak estrogenic activity, influences social behavior. After being exposed to BPA at 0.04, 0.4, 4 mg kg-1 for 18 days, the 7-week-old male mice were tested with social play and three-chamber. The results showed that pubertal BPA exposure decreased social play between adolescent males and sociability of adolescent males. Further, pubertal BPA exposure reduced sociability and inhibited social novel preferences of adult males. BPA inhibited social interactions with opposite sex but improved socio-sexual exploration and the low-intensity mating behavior (mounting) with same sex in adult males. In residential-intruder test, BPA-exposed adult males showed a decrease in aggressiveness and an enhancement in prosocial behavior with intruder. Western blot analysis showed that BPA (especially at 4 mg/kg/d) down-regulated the levels of AR in the amygdala and the striatum but up-regulated the levels of DR1 and DAT proteins in the striatum of adult males. BPA at 4 mg kg-1 decreased the levels of T in the serum and the brain. These results suggest that pubertal BPA exposure affects social play and sociability of adolescent males and even results in long-term effects on social behavior of adult males. BPA-induced down-regulations of the levels of AR in the amygdala and the striatum and up-regulation of the levels of DR1 and DAT in the striatum may be involved.

4.
Spinal Cord ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664187

RESUMO

STUDY DESIGN: Animal study. OBJECTIVE: This study examined how soon after spinal cord injury (SCI) bone loss occurs, and investigated the underlying molecular mechanism. METHODS: Eight-week-old male Wistar rats underwent complete transection of the thoracic spinal cord at T3-4 or sham operation (n = 10-12 per group). Blood, hindlimb bone samples, and bone marrows were collected at 2 and 7 days after SCI. RESULTS: The neurologically motor-complete SCI causes loss of bone mass and deterioration of trabecular bone microstructure as early as 2 days after injury; these skeletal defects become more evident at 7 days. These changes are associated with a dramatic increase in levels of bone resorption maker CTX in blood. Alternations of gene expression in hindlimb bone tissues and bone marrow cells at the first week after SCI were examined. Gene expressions responsible for both bone resorption and formation are increased at 2 days post-SCI, and the associated bone loss and bone deterioration are likely the result of higher levels of osteoclastic resorption over osteoblastic formation, as may be extrapolated from findings at molecular levels. CONCLUSIONS: Rapid bone loss occurs as early as 2 days after motor-complete SCI and interventions for inhibiting bone resorption and prompting bone formation should start as soon as possible after the injury to prevent bone loss.

5.
J Biomech Eng ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260520

RESUMO

High-resolution peripheral quantitative computed tomography (HRpQCT) is a promising imaging modality that provides in vivo three-dimensional assessment of bone microstructure by scanning fixed regions of the distal radius and tibia. However, how microstructural parameters and mechanical analysis based on these segment scans correlate to whole distal radius and tibia mechanics is not well-characterized. On 26 sets of cadaveric radius and tibia, HRpQCT scans were performed on the standard scan segment, a segment distal to the standard segment, and a segment proximal to the standard segment. Whole distal bone stiffness was determined through mechanical testing. Segment bone stiffness was estimated using linear finite element (FE) analysis based on segment scans. Standard morphological and Individual Trabecula Segmentation (ITS) analyses were used estimate microstructural properties. Significant variations in microstructural parameters were observed among segments at both sites. Correlation to whole distal bone stiffness was moderate for microstructural parameters at the standard segment, but correlation was significantly increased for FE-predicted segment bone stiffness based on standard segment scans. Similar correlation strengths were found between FE-predicted segment bone stiffness and whole distal bone stiffness. Additionally, microstructural parameters at the distal segment had higher correlation to whole distal bone stiffness than at standard or proximal segments. Our results suggest that FE-predicted segment stiffness is a better predictor of whole distal bone stiffness for clinical HRpQCT analysis, and that microstructural parameters at the distal segment is more highly correlated with whole distal bone stiffness than at the standard or proximal segments.

6.
Arch Osteoporos ; 14(1): 70, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31250235

RESUMO

Significant correlations for bone mineral density and bone microstructure between spinal and non-spinal skeletal sites (distal radius and proximal femur) in adolescent idiopathic scoliosis (AIS) patients were observed, indicating that proximal femoral DXA and distal radial HR-pQCT could provide valid clinical assessments in patients with AIS. PURPOSE: Low bone mass is an important feature of adolescent idiopathic scoliosis (AIS), which is a complex 3D spinal deformity that affects girls during puberty. However, no clinical imaging modality is suitable for regular monitoring on their spinal bone qualities in rapid growth period. Therefore, we investigated whether bone mineral density (BMD) and bone microstructure at non-spinal sites correlated with BMD and mechanical property in the spine in AIS patients. METHODS: Thirty-two AIS girls (16.7 ± 3.5 years old with mean Cobb angle of 67 ± 11°) who underwent pre-operative spine CT examination for navigation surgery were recruited. Volumetric BMD (vBMD) of lumbar spine (LS) was measured by quantitative computed tomography (QCT), vBMD and bone microstructure of distal radius (DR) by high-resolution peripheral QCT (HR-pQCT) and areal BMDs of total hip (TH) and femoral necks (FN) by dual-energy X-ray absorptiometry (DXA). Biomechanical properties of the DR and LS were estimated by finite element analysis (FEA). Pearson correlation was performed to study the correlation between bone parameters at these three sites. RESULTS: LS vBMD correlated significantly with both FN and TH aBMD (R = 0.663-0.725, both p < 0.01) and with DR microstructural parameters (R = 0.380-0.576, all p < 0.05). Mechanical properties of LS and DR were also correlated (R = 0.398, p = 0.039). CONCLUSIONS: Bone measurement at proximal femur and distal radius could provide an additional predictive power in estimating the bone changes at spine, which is the primary site of deformity in AIS patients. Our result indicated that DXA and HR-pQCT could provide a valid surrogate for spine bone measurements in AIS patients.

7.
Mol Cell Endocrinol ; 485: 35-43, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30707916

RESUMO

Intracellular Ca2+ signaling plays an essential role in synaptic plasticity. This study examined the effect of BPA on concentration of intracellular Ca2+ ([Ca2+]i) by measuring fluorescence intensity of Ca2+ in hippocampal neurons in vitro. The results showed that BPA for 30 min exerted dose-dependently dual effects on glutamate-elevated [Ca2+]i: BPA at 1-10 µM suppressed but at 1-100 nM enhanced glutamate-raised [Ca2+]i. BPA-potentiated [Ca2+]i was blocked by the antagonist of NMDA receptor and was eliminated by an estrogen-related receptor gamma (ERRγ) antagonist rather than an AR antagonist. Both inhibitors of MAPK/ERKs and MAPK/p38 blocked BPA-enhanced [Ca2+]i. Co-treatment of BPA with 17ß-E2 or DHT eliminated the enhancement of 17ß-E2, DHT, and BPA in glutamate-elevated [Ca2+]i. These results suggest that BPA at nanomole level rapidly enhances Ca2+ influx through NMDA receptor by ERRγ-mediated MAPK/ERKs and MAPK/p38 signaling pathways. However, BPA antagonizes both estrogen and androgen enhancing NMDA receptor-mediated Ca2+ influx in hippocampal neurons.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Sinalização do Cálcio/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Hipocampo/citologia , Fenóis/efeitos adversos , Animais , Compostos Benzidrílicos/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fenóis/farmacologia , Ratos , Ratos Sprague-Dawley , Análise de Célula Única
8.
J Biomech Eng ; 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30703208

RESUMO

The high-resolution peripheral quantitative computed tomography (HRpQCT) provides unprecedented visualization of bone microstructure and the basis for constructing patient-specific micro-finite element (µFE) models. Based on HRpQCT images, we have developed a plate rod µFE (PRµFE) method for whole bone segments using individual trabecula segmentation (ITS) and an adaptive cortical meshing technique. In contrast to the conventional voxel approach, the complex microarchitecture of the trabecular compartment is simplified into shell and beam elements based on the trabecular plate-and-rod configuration. Compared to voxel-based µFE models of µCT and mechanical testing, nonlinear analyses of stiffness and yield strength using the HRpQCT-based PRµFE models demonstrated high correlation and accuracy, indicating that the combination of segmented trabecular plate-rod morphology and adjusted cortical mesh adequately captures mechanics of the whole bone segment. Meanwhile, the PRµFE approach reduced model size by nearly 300-fold and shortened computation time for nonlinear analysis from days to within hours, permitting broader clinical application of HRpQCT-based nonlinear µFE modeling. Furthermore, the presented approach was tested using a subset of radius and tibia HRpQCT scans of patients with prior vertebral fracture from a previous study. Results indicated that yield strength for radius and tibia predicted by the PRµFE model was effective in discriminating vertebral fracture subjects from non-fractured controls. In conclusion, the PR µFE model of HRpQCT images accurately predicted mechanics for whole bone segments and can serve as a valuable clinical tool to evaluate musculoskeletal diseases.

9.
J Bone Miner Res ; 33(9): 1665-1675, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29750829

RESUMO

Type 2 diabetes (T2D) patients have an increased fracture risk, which may be partly explained by compromised bone microarchitecture within the cortical bone compartment. Data on trabecular bone parameters in T2D are contradictory. By high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular microarchitecture is preserved, yet larger trabecular holes are detected in T2D by MRI and DXA-based trabecular bone scores are abnormal. To determine if there are differences in trabecular microstructure, connectivity, and alignment in postmenopausal women with T2D as compared with controls, we performed an individual trabecula segmentation (ITS) analysis on HR-pQCT scans of the distal radius and tibia in 92 women with (n = 42) and without (n = 50) T2D. Unadjusted analyses showed that T2D subjects had greater total trabecular bone volume, trabecular plate volume fraction, plate number density, plate junction density, and axial alignment at the radius and tibia, and increased plate tissue fraction, but decreased rod tissue fraction and rod length at the radius (p < 0.05 for all). After adjustments for clinical covariates, plate number density and plate junction density remained higher at the radius and tibia, whereas total trabecular bone volume was increased and trabecular rod length was decreased at the radius. These differences remained significant after adjustment for hip BMD and trabecular volumetric bone density. Notably, the increased plate-like ITS qualities were seen in those with T2D duration of <10 years, whereas ITS parameters in subjects with T2D duration ≥10 years did not differ from those of control subjects. In conclusion, postmenopausal women with early T2D had a greater plate-like and less rod-like trabecular network. This early advantage in trabecular plate quality does not explain the well-established increased fracture risk in these patients and does not persist in the later stage of T2D. © 2018 American Society for Bone and Mineral Research.


Assuntos
Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Diabetes Mellitus Tipo 2/patologia , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Absorciometria de Fóton , Fenômenos Biomecânicos , Densidade Óssea , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/patologia , Tíbia/diagnóstico por imagem , Tíbia/patologia , Fatores de Tempo
10.
Horm Behav ; 102: 129-138, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29778459

RESUMO

Bisphenol-A (BPA) is a well-known environmental endocrine disruptor. Developmental exposure to BPA affected a variety of behaviors in multiple model organisms. Our recent study found that exposure to BPA during adulthood aggravated anxiety- and depression-like states in male mice but not in females. In this study, 11-w-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5 mg/kg), TP and BPA (0.04, 0.4, or 4 mg/kg), or vehicle for 45 days. BPA (0.4 or 4 mg/kg) did not affect the elevated plus maze task of GDX mice but shortened the time on open arms and decreased the frequency of head dips of sham and TP-GDX mice. In forced swim task, BPA prolonged the total time of immobility of both sham and TP-GDX mice but not GDX mice. In addition, BPA reduced the levels of T in the serum and the brain of sham and TP-GDX mice. Western blot analysis further showed that BPA reduced the levels of androgen receptor (AR) and GABA(A)α2 receptor of the hippocampus and the amygdala in sham and inhibited the rescue of TP in these proteins levels of GDX mice. Meanwhile, BPA decreased the level of phospho-ERK1/2 in these two brain regions of sham and TP-GDX mice. These results suggest that long-term exposure to BPA inhibited TP-improved anxiety- and depression-like behaviors in GDX male mice. The down-regulated levels of GABA(A)α2 receptor and AR and an inhibited activity of ERK1/2 pathway in the hippocampus and the amygdala may be involved in these process.


Assuntos
Ansiedade/prevenção & controle , Compostos Benzidrílicos/farmacologia , Depressão/prevenção & controle , Disruptores Endócrinos/farmacologia , Fenóis/farmacologia , Testosterona/farmacologia , Animais , Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Depressão/induzido quimicamente , Antagonismo de Drogas , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Orquiectomia , Testosterona/sangue
11.
Bone ; 111: 59-70, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29534998

RESUMO

Understanding the relationship between the microstructure and mechanical function of trabecular bone is critical for prediction and prevention of bone fragility fractures. However, a detailed understanding of the structural design of trabecular microarchitecture is still missing. This study hypothesized that there exists a commonality in the underlying probabilistic distributions of microstructural features of trabecular bones, whereas the microstructural differences among individuals are primarily describe by a set of scalar parameters. To test the hypothesis, twenty-three trabecular bone specimens were obtained from two anatomic locations (i.e., femoral neck and vertebral body) and a diverse group of seventeen donors of different age and sex. The number, size, spatial location, and orientation of individual plates and rods in the trabecular bone specimens were determined via volumetric decomposition of 3D µCT images using the Individual Trabecula Segmentation (ITS) technique. Then, m/n bootstrap Kolmogorov-Smirnov tests were performed to compare the normalized distributions of size, orientation, and spatial arrangement of trabecular plates and rods in the specimens. The results showed that 100% of the twenty-three normalized distributions of each microstructural feature were statistically equivalent irrespective of individual differences among the bone specimens, except the distributions of rod spatial arrangement (<100%). On the other hand, nonparametric Mann-Whitney U tests showed that a set of scalar parameters (i.e., the number, average size, and average nearest neighbor distance of trabecular plates and rods) were statistically different among the individual specimens (p<0.05). Due to the commonality of the underlying distributions, the individual differences in the trabecular microstructure among the specimens seemed to be reflected primarily by changes in the scalar parameters. The above results strongly support the hypothesis of this study and may shed more light on understanding the natural design of trabecular bone microstructures.


Assuntos
Osso Esponjoso/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Feminino , Colo do Fêmur/ultraestrutura , Fraturas Ósseas/diagnóstico , Voluntários Saudáveis , Humanos , Imagem Tridimensional , Vértebras Lombares/ultraestrutura , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Microtomografia por Raio-X
12.
J Bone Miner Res ; 33(2): 316-327, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29044705

RESUMO

Developing effective treatment for osteoarthritis (OA), a prevalent and disabling disease, has remained a challenge, primarily because of limited understanding of its pathogenesis and late diagnosis. In the subchondral bone, rapid bone loss after traumatic injuries and bone sclerosis at the advanced stage of OA are well-recognized hallmarks of the disease. Recent studies have further demonstrated the crucial contribution of subchondral bone in the development of OA. However, the microstructural basis of these bone changes has not been examined thoroughly, and the paradox of how abnormal resorption can eventually lead to bone sclerosis remains unanswered. By applying a novel microstructural analysis technique, individual trabecula segmentation (ITS), to micro-computed tomography (µCT) images of human OA knees, we have identified a drastic loss of rod-like trabeculae and thickening of plate-like trabeculae that persisted in all regions of the tibial plateau, underneath both severely damaged and still intact cartilage. The simultaneous reduction in trabecular rods and thickening of trabecular plates provide important insights to the dynamic and paradoxical subchondral bone changes observed in OA. Furthermore, using an established guinea pig model of spontaneous OA, we discovered similar trabecular rod loss and plate thickening that preceded cartilage degradation. Thus, our study suggests that rod-and-plate microstructural changes in the subchondral trabecular bone may play an important role in the development of OA and that advanced microstructural analysis techniques such as ITS are necessary in detecting these early but subtle changes. With emerging high-resolution skeletal imaging modalities such as the high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular rod loss identified by ITS could potentially be used as a marker in assessing the progression of OA in future longitudinal studies or clinical diagnosis. © 2017 American Society for Bone and Mineral Research.


Assuntos
Reabsorção Óssea/patologia , Osso Esponjoso/patologia , Osteoartrite do Joelho/patologia , Idoso , Animais , Reabsorção Óssea/diagnóstico por imagem , Osso Esponjoso/diagnóstico por imagem , Cartilagem/patologia , Feminino , Cobaias , Humanos , Masculino , Modelos Biológicos , Osteoartrite do Joelho/diagnóstico por imagem , Microtomografia por Raio-X
13.
Chemosphere ; 195: 567-575, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29278848

RESUMO

Bisphenol A (BPA), a common environmental endocrine disruptor, modulates estrogenic, antiestrogenic, and antiandrogenic effects throughout the lifespan. Recent studies found more obvious adverse effect of BPA on some neurobehavior in males than that in females. In this study, BPA at 10-100 nM rapidly increased the densities of the dendrite spine and synapse in cultured hippocampal neurons of rats in vitro within 1 h. Co-treatment of BPA (100 nM) with dihydrotestosterone (DHT, 10 nM) or with 17ß-E2 (10 nM) completely eliminated the promotion of DHT or 17ß-E2 in the densities of the dendritic spine and synapse. Pretreatment of estrogen receptors (ERs) antagonist ICI182,780 but not of androgen receptors (ARs) antagonist flutamide (Flu) for 30min completely blocked BPA-enhanced densities of the dendritic spine and synapse. Pretreatment of flutamide for 30min before BPA and DHT completely rescued BPA-enhanced densities of the dendritic spine and synapse. Furthermore, pretreatment of ERK1/2 inhibitor U0126 or p38 inhibitor SB203580 entirely eliminated BPA-induced increases in the densities of the dendritic spine and synapse. Meanwhile, BPA (100 nM) enhanced long-term potentiation (LTP) induction of dentate gyrus in hippocampal slices of younger male rats, which was not blocked by co-incubation of flutamide but was inhibited by pretreatment of an P38 inhibitor SB203580. Co-application of BPA with DHT inhibited DHT-suppressed LTP. These results are the first demonstrating the antagonism of BPA to the rapid modification of DHT in synaptic plasticity. However, BPA alone rapidly promotes spinogenesis and synaptic activity through ER instead of AR, and both ERKs and p38 signaling pathways are involved in these processes.


Assuntos
Compostos Benzidrílicos/farmacologia , Espinhas Dendríticas/efeitos dos fármacos , Di-Hidrotestosterona/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fenóis/farmacologia , Animais , Disruptores Endócrinos/farmacologia , Feminino , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Ratos , Receptores Androgênicos/metabolismo , Receptores Estrogênicos/metabolismo , Sinapses/efeitos dos fármacos
14.
Bone ; 107: 181-187, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29154969

RESUMO

Individuals with cystic fibrosis (CF) have lower bone mineral density (BMD) by DXA and are at higher risk of fracture than healthy controls. However, the 2-dimensional measurement of areal BMD (aBMD) provided by DXA is influenced by bone size and the true extent of the bone deficit is unclear. Our objective was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) and individual trabecula segmentation (ITS) analysis to compare volumetric BMD (vBMD), microarchitecture and estimated strength at the distal radius and tibia in 26 young adults with CF and 26 controls matched for age, gender, and race. To assess the effect of limb length and minimize the confounding effects of size on HR-pQCT outcomes, we scanned participants at both the standard fixed HR-pQCT measurement sites and at a subject-specific relative site that varied according to limb length. CF participants did not differ significantly in age, height, weight, or BMI from controls. Ulnar and tibial lengths were 9mm shorter in CF patients, though differences were not significant. CF patients had significantly lower BMI-adjusted aBMD by DXA at the lumbar spine (8.9%, p<0.01), total hip (11.5%, p<0.01) and femoral neck (14.5%, p<0.01), but not at the forearm. At the fixed radius site, thickness of trabecular plates and torsional stiffness were significantly lower in CF participants than controls. At the relative radius site, only torsional stiffness was significantly lower in CF participants. At the tibia, total, trabecular and cortical vBMD were significantly lower at both fixed and relative sites in CF participants, with fewer, more widely-spaced trabecular plates, lower trabecular connectivity, and lower axial and torsional stiffness. Our results confirm that aBMD is lower at the spine and hip in young adults with CF, independent of BMI and body size. We also conclude that vBMD and stiffness are lower at the weight-bearing tibia. The pathogenesis of these differences in bone density and strength at the tibia appear to be related to trabecular drop-out and reduced trabecular connectivity and to be independent of differences in limb length, as assessed by scanning participants at both standard and relative sites. We concluded that significant deficits in bone structure and strength persist in young adults with CF, despite advances in care that permit them to attain relatively normal height and weight.


Assuntos
Osso e Ossos/patologia , Fibrose Cística/complicações , Fibrose Cística/patologia , Adulto , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiopatologia , Feminino , Humanos , Masculino , Rádio (Anatomia) , Coluna Vertebral , Tíbia , Tomografia Computadorizada por Raios X
16.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(4): 2423-4, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26057009

RESUMO

The mitochondrial genome of the little brown bat, Myotis lucifugus (Chiroptera: Vespertilionidae), is a circular molecule of 17,038 bp in length, containing 22 transfer RNAs genes, 13 protein-coding genes, two ribosomal RNAs, and one D-loop region. The A + T content of the overall base composition of the H-strand is 63.2% with individual nucleotides comprising T 29.8%, C 23.4%, A 33.3%, and G 13.5%. In BI and ML trees, we found M. lucifugus is a sister clade to M. brandtii, Myotis is a sister clade to Murina, and Pipistrellus is a sister clade to (Chalinolobus + (Eptesicus + Vespertilio)) (1.00 in BI, >100% in ML). The monophyly of Myotis, Murina, and Plecotus is well supported (1.00 in BI, 100% in ML).


Assuntos
Quirópteros/classificação , Quirópteros/genética , Genoma Mitocondrial , Animais , Composição de Bases , Genes Mitocondriais , Tamanho do Genoma , Fases de Leitura Aberta , Filogenia , Análise de Sequência de DNA , Sequenciamento Completo do Genoma
17.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(4): 2608-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26024127

RESUMO

The complete mitochondrial genome of the thirteen-lined ground squirrel, Ictidomys tridecemlineatus (Rodentia: Sciuridae) was sequenced to analyze the gene arrangement. It is a circular molecule of 16,458 bp in length including 37 genes typically found in other squirrels. The AT content of the overall base composition is 63.7% and the length of the control region is 1016 bp with 63.0% AT content. In BI and ML phylogenetic trees, I. tridecemlineatus is a sister clade to the genus Cynomys, and Tamias sibiricus is a sister clade to (Marmota himalayana + (I. tridecemlineatus + (C. leucurus + C. ludovicianus))). Ratufinae is well supported as the basal clade of Sciuridae. The monophyly of the family Sciuridae and its subfamilies Callosciurinae, Xerinae and Sciurinae are well supported.


Assuntos
Genoma Mitocondrial/genética , Sciuridae/genética , Animais , Composição de Bases/genética , Filogenia , Sciuridae/classificação , Análise de Sequência de DNA
18.
Forensic Sci Int ; 253: 112-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26115227

RESUMO

Carbon monoxide (CO) poisoning is a common cause of death globally, and case reports and empirical studies on CO poisoning are widely examined. However, to the authors' knowledge, CO poisoning deaths in the mainland China are scarcely studied. Therefore, this study aims to explore the incidence trend of CO poisoning deaths that occurred in Wuhan - a mega city in Central China - for a six-year period (2009-2014). This arguably is the first comprehensive study to provide an overall analysis of CO poisoning deaths that sampled the mainland Chinese population. Using the data provided by the legal physicians who are employed in nine districts of Wuhan, a total of 131 cases of CO poisoning that resulted in the death of 156 victims are collected. Out of the total, 76 cases (97 deaths) are classified as accidents, 49 cases (51 deaths) are suicides, three cases (four deaths) are homicides, one case (three deaths) is homicide-suicide, and one case (one death) is classified as undetermined. Male victims are found to be the dominant sex group (53.5%; N=83); with a mean age of 44.9 years, while female victims averagely aged 46.1 years. The highest death occurring month is in January, and followed by February and December. Coal or charcoal burning is found to be the major cause of suicide CO poisoning death (66.7%), while fire accident is the major cause of accidental CO poisoning death (60.8%) in Wuhan during the six-year period.


Assuntos
Intoxicação por Monóxido de Carbono/mortalidade , População Urbana , Acidentes/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Carboxihemoglobina/análise , Criança , Pré-Escolar , China/epidemiologia , Feminino , Patologia Legal , Homicídio/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Suicídio/estatística & dados numéricos , Adulto Jovem
19.
Horm Behav ; 71: 41-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25870019

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disrupter. Currently, little is known about neurodevelopmental toxicity of DEHP in wildlife and humans. The present study investigated the effects of DEHP, focusing on the changes in the behavior of offspring mice at the ages of 6 and 12w, respectively, following utero and lactational exposure to DEHP (10, 50, and 200mg/kg/d) from gestation day 7 through postnatal day 21. The results of open field tasks showed that DEHP increased the grooming of males at age 6w and females at age 12w but decreased the frequency of rearing of 6-w-old females and the number of grid crossings of 12-w-old females. In the Morris water maze task, 50 and 200mg/kg/d DEHP significantly prolonged the time of searching the hidden platform in water maze and reduced the time staying in the target quadrant during a probe trial of 6-w-old male mice, but not of 6-w-old females nor 12-w-old mice of both sexes, suggesting an impaired spatial learning and memory among younger males after perinatal exposure to DEHP. Western blot analyses further showed that DEHP at 50 and 200mg/kg/d decreased the levels of the N-methyl-d-aspartic acid (NMDA) receptor subunits NR1 and NR2B in the hippocampus of 6-w-old males. These results suggest that uterine and lactational exposure to low doses of DEHP sex-specifically impacted behaviors, including locomotion activity and spatial memory, via the concomitant inhibition of the NMDA receptor of the hippocampus in offspring mice.


Assuntos
Dietilexilftalato/farmacologia , Disruptores Endócrinos/farmacologia , Hipocampo/metabolismo , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Lactação , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Receptores de N-Metil-D-Aspartato/metabolismo
20.
Biophys J ; 108(2): 431-7, 2015 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-25606690

RESUMO

Reattachment and healing of tendon to bone poses a persistent clinical challenge and often results in poor outcomes, in part because the mechanisms that imbue the uninjured tendon-to-bone attachment with toughness are not known. One feature of typical tendon-to-bone surgical repairs is direct attachment of tendon to smooth bone. The native tendon-to-bone attachment, however, presents a rough mineralized interface that might serve an important role in stress transfer between tendon and bone. In this study, we examined the effects of interfacial roughness and interdigital stochasticity on the strength and toughness of a bimaterial interface. Closed form linear approximations of the amplification of stresses at the rough interface were derived and applied in a two-dimensional unit-cell model. Results demonstrated that roughness may serve to increase the toughness of the tendon-to-bone insertion site at the expense of its strength. Results further suggested that the natural tendon-to-bone attachment presents roughness for which the gain in toughness outweighs the loss in strength. More generally, our results suggest a pathway for stochasticity to improve surgical reattachment strategies and structural engineering attachments.


Assuntos
Úmero/fisiologia , Modelos Biológicos , Manguito Rotador/fisiologia , Animais , Fenômenos Biomecânicos , Úmero/química , Úmero/ultraestrutura , Camundongos , Minerais/química , Proteínas/química , Manguito Rotador/química , Manguito Rotador/ultraestrutura , Processos Estocásticos
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