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1.
Pain ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985168

RESUMEN

ABSTRACT: Neuropathic pain is one of the most challenging types of pain to diagnose and treat, a problem exacerbated by the lack of a quantitative biomarker. Recently, several clinical and preclinical studies have shown that neuropathic pain induces cerebral hemodynamic changes as a result of neuroplasticity in the brain. Our hypothesis in this study is that neuropathic pain leads to cerebral hemodynamic changes over postoperative time in a spinal nerve ligation (SNL) rat model, which has not been longitudinally explored previously. Furthermore, by identifying multiple regional hemodynamic features that are the most distinct between SNL and sham groups, where the sham group underwent only an incision without SNL, it may be possible to classify the SNL group regardless of when the onset of pain occurs. We investigate cerebral hemodynamic changes using dynamic susceptibility contrast magnetic resonance imaging in a rat model up to 28 days after ligating L5/L6 spinal nerves. We trained a linear support vector machine with relative cerebral blood volume data from different brain regions and found that the prediction model trained on the nucleus accumbens, motor cortex, pretectal area, and thalamus classified the SNL group and sham group at a 79.27% balanced accuracy, regardless of when the onset of pain occurred (SNL/sham: 60/45 data points). From the use of the SNL model without prior knowledge of the onset time of pain, the current findings highlight the potential of relative cerebral blood volume in the 4 highlighted brain regions as a biomarker for neuropathic pain.

2.
Magn Reson Imaging ; 103: 75-83, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37451521

RESUMEN

Ex vivo ratiometric measurements of short- and long-T2 components using the multiple spin echo sequence of MRI are often employed to evaluate alterations in myelin content in the white matter (WM) of the brain. However, the relationship between absolute MRI-T2 values (long-T2 component) and myelin volumetric information in aged ex vivo rodent WM appears to be influenced by factors such as animal species, field strength, and fixation durations/washing. Here, multiple spin echo sequence-based MRI-R2 (the reciprocal of T2) values were measured in the corpus callosum (CC) region in the post-mortem rat brains (n = 9) of different age groups with common fixation techniques without washing at 7 T. Transmission electron microscopy (TEM)-based quantification of myelin volume fraction (MVF) and corresponding Monte-Carlo simulation to estimate relaxation rates (R2,IE) due to diffusion in the presence of inhomogeneous magnetic field perturbation in intra- and extra-cellular (IE) spaces were respectively performed. To determine whether the short-T2 components originating from myelin water were mixed with long-T2 components from IE water or were undetectable, the MVF values obtained from TEM results were respectively compared with MRI-R2 and R2,IE values. A significant correlation (Pearson's correlation coefficient r = 0.8763; p < 0.01) of average MRI-R2 and MVF values was observed. Estimated R2,IE values from Monte-Carlo simulations in IE water signals were also positively correlated (r = 0.8281; p < 0.01) with MVF values. However, the magnitudes of R2,IE values were much smaller than those observed for MRI-R2 values, indicating that changes in R2 related MVF are likely dominated by myelin water components. Such comparisons between independent parameters from MRI, TEM, and simulations support the suggestion that myelin water signals were indistinguishably mixed to exhibit mono-exponential T2 relaxation, and multiple spin echo sequence-based MRI-R2 values in aging ex vivo rat CC without prolonged washing still reflect the volumetric information of myelin, likely due to enhanced water exchange across the myelin.


Asunto(s)
Cuerpo Calloso , Vaina de Mielina , Ratas , Animales , Cuerpo Calloso/diagnóstico por imagen , Encéfalo , Imagen por Resonancia Magnética , Agua , Envejecimiento
3.
Opt Lett ; 48(7): 1798-1801, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37221769

RESUMEN

In this Letter, we propose a generalized optical signal-to-noise ratio (GOSNR) monitoring scheme using a convolutional neural network trained on constellation density features acquired from a back-to-back setup and demonstrate accurate GOSNR estimations for links having different nonlinearities. The experiments were carried over dense wavelength division multiplexing links configured on 32-Gbaud polarization division multiplexed 16-quadrature amplitude modulation (QAM) and demonstrated that the GOSNRs are estimated within 0.1 dB mean absolute error with maximum estimation errors below 0.5 dB on metro class links. The proposed technique does not require any information about the noise floor in the conventional spectrum-based means and therefore is readily deployable for real-time monitoring.

4.
J Craniofac Surg ; 34(3): e246-e247, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36730881

RESUMEN

The sphenoid bone is a complex structure in terms of its embryological origin. At birth, the sphenoid sinus is nonpneumatized. Arrested pneumatization of the sphenoid sinus is considered a normal anatomic variant but may be mistaken for disease in imaging studies. We report 2 cases of arrested pneumatization of the sphenoid sinus, a normal variant commonly misdiagnosed as a serious disease of the skull base. A 29-year-old man with a complaint of dizziness visited a local clinic for assessment. Computed tomography (CT) of the paranasal sinuses (PNS) showed a noneroding, nonexpansile, and nonhomogenous lesion in the sphenoid bone. Magnetic resonance imaging (MRI) of the brain revealed a high-signal lesion on both T1-weighted and T2-weighted images. Given these typical findings in the CT of PNS and MRI of the brain, the lesion was diagnosed as arrested pneumatization of the sphenoid sinus. In the second case, a 60-year-old woman with a complaint of headache visited a local clinic for assessment. CT of PNS showed a fibro-osseous lesion (with features of sclerosis and osteolysis) in the skull base. Brain MRI revealed a low-signal lesion on a T1-weighted image containing a high-signal intensity around the sphenoid bone, thereby suggesting internal fat contents. A precise interpretation of CT of PNS and brain MRI is essential to distinguish arrested pneumatization of the sphenoid sinus and to help establish a differential diagnosis and avoid needless biopsy.


Asunto(s)
Paro Cardíaco , Senos Paranasales , Masculino , Recién Nacido , Femenino , Humanos , Persona de Mediana Edad , Adulto , Seno Esfenoidal/diagnóstico por imagen , Seno Esfenoidal/patología , Tomografía Computarizada por Rayos X/métodos , Base del Cráneo , Imagen por Resonancia Magnética , Hueso Esfenoides
5.
Int J Mol Sci ; 23(24)2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-36555310

RESUMEN

Blood-based biomarkers are needed for the early diagnosis of Alzheimer's disease (AD). We analyzed longitudinal human plasma samples from AD and control cases to identify biomarkers for the early diagnosis of AD. Plasma samples were grouped based on clinical diagnosis at the time of collection: AD, mild cognitive impairment (MCI), and pre-symptomatic (preMCI). Samples were analyzed by ELISA using a panel of reagents against nine different AD-related amyloid-ß (Aß), tau, or TDP-43 variants. Receiver operating characteristic (ROC) curves of different biomarker panels for different diagnostic sample groups were determined. Analysis of all of the samples gave a sensitivity of 92% and specificity of 76% for the diagnosis of AD. Early-stage diagnosis of AD, utilizing only the preMCI and MCI samples, identified 88% of AD cases. Using sex-biased biomarker panels, early diagnosis of AD cases improved to 96%. Using the sex-biased panels, we also identified 6 of the 25 control group cases as being at high risk of AD, which is consistent with what is expected given the advanced age of the control cases. Specific AD-associated protein variants are effective blood-based biomarkers for the early diagnosis of AD. Notably, significant differences were observed in biomarker profiles for the early detection of male and female AD cases.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Masculino , Femenino , Humanos , Proteínas tau , Péptidos beta-Amiloides , Disfunción Cognitiva/diagnóstico , Diagnóstico Precoz , Pruebas Hematológicas , Biomarcadores , Fragmentos de Péptidos
6.
J Control Release ; 352: 685-699, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36328077

RESUMEN

Three-dimensional printing enables precise and on-demand manufacture of customizable drug delivery systems to advance healthcare toward the goal of personalized medicine. However, major challenges remain in realizing personalized drug delivery that fits a patient-specific drug dosing schedule using local drug delivery systems. In this study, a user-designed device is developed as implantable therapeutics that can realize personalized drug release kinetics by programming the inner structural design on the microscale. The drug release kinetics required for various treatments, including dose-dense therapy and combination therapy, can be implemented by controlling the dosage and combination of drugs along with the rate, duration, initiation time, and time interval of drug release according to the device layer design. After implantation of the capsular device in mice, the in vitro-in vivo and pharmacokinetic evaluation of the device is performed, and the therapeutic effect of the developed device is achieved through the local release of doxorubicin. The developed user-designed device provides a novel platform for developing next-generation drug delivery systems for personalized and localized therapy.


Asunto(s)
Sistemas de Liberación de Medicamentos , Impresión Tridimensional , Ratones , Animales , Liberación de Fármacos , Preparaciones Farmacéuticas , Medicina de Precisión
7.
Aging Cell ; 21(9): e13694, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35984750

RESUMEN

Progressive iron accumulation in the substantia nigra in the aged human brain is a major risk factor for Parkinson's disease and other neurodegenerative diseases. Heavy metals, such as iron, produce reactive oxygen species and consequently oxidative stress in cells. It is unclear, however, how neurons in the substantia nigra are protected against the age-related, excessive accumulation of iron. In this study, we examined the cellular response of the substantia nigra against age-related iron accumulation in rats of different ages. Magnetic resonance imaging confirmed the presence of iron in 6-month-old rats; in 15-month-old rats, iron accumulation significantly increased, particularly in the midbrain. Transcriptome analysis of the region, in which iron deposition was observed, revealed an increase in stress response genes in older animals. To identify the genes related to the cellular response to iron, independent of neurodevelopment, we exposed the neuroblastoma cell line SH-SY5Y to a similar quantity of iron and then analyzed their transcriptomic responses. Among various stress response pathways altered by iron overloading in the rat brain and SH-SY5Y cells, the genes associated with topologically incorrect protein responses were significantly upregulated. Knockdown of HERPUD1 and CLU in this pathway increased susceptibility to iron-induced cellular stress, thus demonstrating their roles in preventing iron overload-induced toxicity. The current study details the neuronal response to excessive iron accumulation, which is associated with age-related neurodegenerative diseases.


Asunto(s)
Neuroblastoma , Enfermedad de Parkinson , Anciano , Animales , Neuronas Dopaminérgicas/metabolismo , Humanos , Lactante , Hierro/metabolismo , Neuroblastoma/patología , Enfermedad de Parkinson/metabolismo , Ratas , Sustancia Negra/metabolismo
8.
Opt Express ; 30(2): 2693-2710, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35209404

RESUMEN

We demonstrate accurate estimation of generalized optical signal to noise ratio (GOSNR) for wavelength division multiplexed fiber communication systems using an experimentally trained multi-tasking convolutional neural network while simultaneously estimating linear and nonlinear noise contributions. Using dual-polarized 32-GBaud 16QAM DWDM links we extract learnable features from constellation density matrices and accurately estimate GOSNR while simultaneously estimating linear and nonlinear contributions. Estimation of the OSNRASE, OSNRNL and GOSNR are demonstrated with < 0.5 dB mean absolute error. We also assess the universality of our model within the regime of metro networks by cross-training with data from such links comprised of different fiber types. We demonstrate a path to a practical universal training method that includes additional link parameters. The methods do not require contiguous high-speed sampling, additional hardware nor transmission of special symbols or patterns and are readily implemented in deployed systems.

9.
NMR Biomed ; 35(3): e4645, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34739153

RESUMEN

In studies of the white matter (WM) in aging brains, both quantitative susceptibility mapping (QSM) and direct R1 measurement offer potentially useful ex vivo MRI tools that allow volumetric characterization of myelin content changes. Despite the technical importance of such MRI methods in numerous age-related diseases, the supposed linear relationship between the estimates of either the QSM or R1 method and age-affected myelin contents has not been validated. In this study, the absolute myelin volume fraction (MVF) was determined by transmission electron microscopy (TEM) as a gold standard measure for comparison with the values obtained by the aforementioned MR methods. To theoretically evaluate and understand the MR signal characteristics, QSM simulations were performed using the finite perturber method (FPM). Specifically, the simulation geometry modeling was based on TEM-derived structures aligned orthogonally to the main magnetic field, the construct of which was used to estimate the magnetic field shift (ΔB) changes arising from the conjectured myelin structures. Experimentally, ex vivo corpus callosum (CC) samples from rat brains obtained at 6 weeks (n = 3), 4 months (n = 3), and 20 months (n = 3) after birth were used to establish the relationship between changes quantified by either QSM or R1 with the absolute MVF by TEM. From the ex vivo brain samples, the scatterplot of mean MVF versus R1 was fitted to a linear equation, where R1mean = 0.7948 × MVFmean + 0.8118 (Pearson's correlation coefficient r = 0.9138; p < 0.01), while the scatterplot of mean MVF versus MRI-derived magnetic susceptibility (χ) was also fitted to a line where χmeasured,mean = -0.1218 × MVFmean - 0.006345 (r = -0.8435; p < 0.01). As a result of the FPM-based QSM simulations, a linearly proportional relationship between the simulated magnetic susceptibility, χsimulated,mean , and MVF (r = -0.9648; p < 0.01) was established. Such a statistically significant linear correlation between MRI-derived values by the QSM (or R1 ) method and MVF demonstrated that variable myelin contents in the WM (i.e., CC) can be quantified across multiple stages of aging. These findings further support that both techniques based on QSM and R1 provide an efficient means of studying the brain-aging process with accurate volumetric quantification of the myelin content in WM.


Asunto(s)
Envejecimiento/fisiología , Mapeo Encefálico/métodos , Cuerpo Calloso/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Vaina de Mielina/fisiología , Animales , Cuerpo Calloso/fisiología , Femenino , Microscopía Electrónica de Transmisión , Vaina de Mielina/ultraestructura , Ratas , Ratas Sprague-Dawley
10.
J Audiol Otol ; 26(1): 50-54, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34167183

RESUMEN

We report a case of a pseudoaneurysm secondary to skull base osteomyelitis (SBO) in an 82-year-old female. The patient was hospitalized with an acute episode of bleeding from the right ear, which persisted despite packing placed in the ear. We suspected bleeding from the internal carotid artery (ICA) and performed angiography, which revealed a pseudoaneurysm that presumably developed secondary to invasion of the wall of the petrous segment of the right ICA, and the patient underwent emergency coil embolization. Bleeding from the ear recurred a week later, and we performed repeat angiography, followed by embolization and deployment of multiple stents at the site of the pseudoaneurysm, which controlled the bleeding. Clinicians should be mindful of a pseudoaneurysm as a rare complication of SBO, following the spread of infection to adjacent soft tissues or vessels. A pseudoaneurysm should be considered in the differential diagnosis in patients with recurrent epistaxis or bleeding from the ears in addition to cranial nerve symptoms, and this condition warrants urgent evaluation.

11.
NMR Biomed ; 34(10): e4570, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34132432

RESUMEN

Pharmacokinetic K2 mapping from dynamic susceptibility contrast (DSC)-MRI can be a sensitive technique for evaluating the vascular permeability of the subtly damaged blood-brain barrier (BBB) in ischemic regions. However, the K2 values of ischemic lesions depend upon the selection of the intact BBB reference region. As previous observations suggest that the ΔR2* curve of pre-loaded DSC-MRI is not significantly affected by the extravasation of contrast agent, dual DSC-MRI acquisitions can be performed to derive the BBB leakage index from the voxel-wise reference input function for ischemic regions. This study aims to demonstrate the robustness of such model-free leakage index estimation in ischemic brains. By configuring the relationship between dual ΔR2* curves of the intact contralateral brain, the deviation of the measured ΔR2* curve from the unloaded DSC-MRI with respect to the non-deviated ΔR2* curve in the pre-loaded DSC-MRI can be quantified as the BBB leakage index. Such model-free leakage index values from rats with transient middle carotid artery occlusion (tMCAO) (n = 17) and normal controls (n = 3) were evaluated and compared with conventional K2 values with multiple reference regions. Inter-subject leakage index values were also compared with the corresponding ΔT1 map. Evans-blue-stained images were used to validate the leakage index. For the tMCAO group, leakage index values correlated well with ΔT1 (Pearson's r = 0.828). The hyperintense area on the leakage index map matched well with the corresponding Evans-blue-stained area (Dice correlation = 0.626). The slopes of the scatter-plot from the leakage index (0.97-1.00) were observed to be more robust against changes in the reference region than those from conventional K2 values (0.94-1.07). In a subtly damaged BBB tMCAO model, model-free evaluation of vascular permeability using dual DSC-MRIs would provide a consistent measure of inter-subject vascular permeability.


Asunto(s)
Barrera Hematoencefálica/diagnóstico por imagen , Barrera Hematoencefálica/patología , Medios de Contraste/química , Imagen por Resonancia Magnética , Modelos Biológicos , Animales , Femenino , Ratas Sprague-Dawley
12.
Neurobiol Dis ; 155: 105388, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33962010

RESUMEN

Human immunodeficiency virus-1 (HIV-1) has been shown to cross the blood-brain barrier and cause HIV-associated neurocognitive disorders (HAND) through a process that may involve direct or indirect interactions with the central nervous system (CNS) cells and alterations of amyloid ß (Aß) homeostasis. The present study focused on the mechanisms of HIV-1 infecting human neural progenitor cells (hNPCs) and affecting NPC intercellular communications with human brain endothelial cells (HBMEC). Despite the lack of the CD4 receptor, hNPCs were effectively infected by HIV-1 via a mechanism involving the chemokine receptors, CXCR4 and CCR5. HIV-1 infection increased expression of connexin-43 (Cx43), phosphorylated Cx43 (pCx43), and pannexin 2 (Panx2) protein levels in hNPCs, suggesting alterations in gap-junction (GJ) and pannexin channel communication. Indeed, a functional GJ assay indicated an increase in communication between HIV-infected hNPCs and non-infected HBMEC. We next analyzed the impact of HBMEC-derived extracellular vesicles (EVs) and EVs carrying Aß (EV-Aß) on the expression of Cx43, pCx43, and Panx2 in HIV-1 infected and non-infected hNPCs. Exposure to EV-Aß resulted in significant reduction of Cx43 and pCx43 protein expression in non-infected hNPCs when compared to EV controls. Interestingly, EV-Aß treatment significantly increased levels of Cx43, pCx43, and Panx2 in HIV-1-infected hNPCs when compared to non-infected controls. These results were confirmed in a GJ functional assay and an ATP release assay, which is an indicator of connexin hemichannel and/or pannexin channel functions. Overall, the current study demonstrates the importance of hNPCs in HIV-1 infection and indicates that intercellular communications between infected hNPCs and HBMEC can be effectively modulated by EVs carrying Aß as their cargo.


Asunto(s)
Comunicación Celular/fisiología , Vesículas Extracelulares/metabolismo , Uniones Comunicantes/metabolismo , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Células-Madre Neurales/metabolismo , Péptidos beta-Amiloides/metabolismo , Línea Celular , Células Cultivadas , Endotelio Vascular/metabolismo , Endotelio Vascular/virología , Vesículas Extracelulares/virología , Uniones Comunicantes/virología , Humanos , Células-Madre Neurales/virología
13.
Eur Arch Otorhinolaryngol ; 278(8): 2817-2822, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32960351

RESUMEN

PURPOSE: Skull base osteomyelitis (SBO) is an uncommon and a potentially life-threatening condition if not promptly recognized and properly treated. The aim of our study was to present a 32-case series of patients diagnosed with SBO at a single center. METHODS: In this retrospective study, we reviewed the data of patients diagnosed with otogenic SBO between January 2011 and January 2020. 32 patients were enrolled in the study. SBO diagnosis was based on a combination of symptoms and physical examination, bone scan, brain magnetic resonance imaging, and pathologic examination findings. The following clinical data were collected during the follow-up period: types of antibiotics used, duration of antibiotic treatment, C-reactive protein level, presence of disease control, duration from the onset of symptoms to diagnosis, and patient survival. RESULTS: The mean follow-up period was 11 (1-110) months. The mean duration of antibiotic treatment was 115 (19-223) days. The mean C-reactive protein levels at the time of diagnosis and at the endpoint of follow-up were 3.05 (0.56-18.31) and 0.21 (0.03-33.61) mg/dL, respectively (P < 0.001). Disease control rate was 34.9% at 1-year and 83.7% at 5-year follow-up. Patient survival rate was 90.6% at 1- and 3-year follow-ups. At the endpoint of follow-up, three patients died. The mean durations from the onset of symptoms to diagnosis were 50 (5-360) and 90 (30-480) days in patients with the controlled disease and in those with the uncontrolled disease, respectively, at the endpoint of follow-up (P = 0.043). CONCLUSION: Comprehensive assessment and aggressive treatment of patients exhibiting symptoms suggestive of SBO would help in the rapid diagnosis of otogenic SBO, resulting in an improvement in prognosis.


Asunto(s)
Osteomielitis , Base del Cráneo , Antibacterianos/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Osteomielitis/diagnóstico , Osteomielitis/terapia , Estudios Retrospectivos , Base del Cráneo/diagnóstico por imagen
14.
Opt Express ; 28(21): 32087-32104, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33115171

RESUMEN

We experimentally demonstrate accurate modulation format identification, optical signal to noise ratio (OSNR) estimation, and bit error ratio (BER) estimation of optical signals for wavelength division multiplexed optical communication systems using convolutional neural networks (CNN). We assess the benefits and challenges of extracting information at two distinct points within the demodulation process: immediately after timing recovery and immediately prior to symbol unmapping. For the former, we use 3D Stokes-space based signal representations. For the latter, we use conventional I-Q constellation images created using demodulated symbols. We demonstrate these methods on simulated and experimental dual-polarized waveforms for 32-GBaud QPSK, 8QAM, 16QAM, and 32QAM. Our results show that CNN extracts distinct and learnable features at both the early stage of demodulation where the information can be used to optimize subsequent stages and near the end of demodulation where the constellation images are readily available. Modulation format identification is demonstrated with >99.8% accuracy, OSNR estimation with <0.5 dB average discrepancy and BER estimation with percentage error of <25%.

15.
Front Cell Dev Biol ; 8: 618796, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33511129

RESUMEN

Background: Cardiovascular complications are the leading cause of mortality in patients with chronic kidney disease (CKD). Uremic vasculopathy plays a crucial role in facilitating the progression of cardiovascular complications in advanced CKD. However, the improvement of conventional research methods could provide further insights into CKD. Objectives: In this study, we aimed to develop a novel model of uremic vasculopathy as a potential drug screening system. Methods and Results: The effects of uremic serum and different combinations of uremic toxins on induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) of a normal control and a CKD patient were investigated using several functional assays. We found that a mixture of uremic toxins composed of high urea, creatinine, uric acid, and indoxyl sulfate exerted deleterious effects on normal control iPSC-ECs that were comparable to uremic serum by increasing reactive oxygen species and apoptosis, as well as suppression of tube formation. Additional characterization revealed a potential involvement of dysregulated TGF-ß signaling as treatment with either losartan or TGF-ß inhibitors led to the attenuation of adverse effects induced by uremic toxins. Importantly, impaired wound healing potential seen in CKD patient-specific iPSC-ECs was rescued by treatment with losartan and TGF-ß inhibitors. Conclusion: Our study demonstrated that simplified uremic toxin mixtures can simulate the uremic micromilieu reproducibly and CKD patient-specific iPSC-ECs can potentially recapitulate susceptibility to uremic vasculopathy. This novel model of uremic vasculopathy may provide a new research tool as a drug screening system.

16.
Brain ; 142(3): 502-511, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30668645

RESUMEN

Pericytes are multifunctional cells wrapped around endothelial cells via cytoplasmic processes that extend along the abluminal surface of the endothelium. The interactions between endothelial cells and pericytes of the blood-brain barrier are necessary for proper formation, development, stabilization, and maintenance of the blood-brain barrier. Blood-brain barrier pericytes regulate paracellular flow between cells, transendothelial fluid transport, maintain optimal chemical composition of the surrounding microenvironment, and protect endothelial cells from potential harmful substances. Thus, dysfunction or loss of blood-brain barrier pericytes is an important factor in the pathogenesis of several diseases that are associated with microvascular instability. Importantly, recent research indicates that blood-brain barrier pericytes can be a target of HIV-1 infection able to support productive HIV-1 replication. In addition, blood-brain barrier pericytes are prone to establish a latent infection, which can be reactivated by a mixture of histone deacetylase inhibitors in combination with TNF. HIV-1 infection of blood-brain barrier pericytes has been confirmed in a mouse model of HIV-1 infection and in human post-mortem samples of HIV-1-infected brains. Overall, recent evidence indicates that blood-brain barrier pericytes can be a previously unrecognized HIV-1 target and reservoir in the brain.


Asunto(s)
Barrera Hematoencefálica/patología , Pericitos/metabolismo , Pericitos/virología , Animales , Transporte Biológico , Encéfalo/patología , Células Endoteliales/patología , Infecciones por VIH/metabolismo , VIH-1/patogenicidad , Humanos , Ratones , Pericitos/fisiología
17.
Hip Pelvis ; 30(2): 109-114, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29896460

RESUMEN

The long-term use of adefovir and tenofovir-antiviral medications commonly used to treat chronic hepatitis B-can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemic osteomalacia. However, there have been few reports about pathological fractures requiring surgical stabilization in cases of antiviral drug-induced hypophosphatemic osteomalacia. We present the case of a 51-year-old man who sustained bilateral pathological hip fractures associated with antiviral drug-induced hypophosphatemic osteomalacia. To treat a lamivudine-resistant hepatitis-B viral infection, the patient received adefovir for 7 years followed by tenofovir for the subsequent 3 years. He had suffered from polyarthralgia and generalized weakness for 2 years prior to presentation at our clinic. Misdiagnosis and inadequate management of his condition accelerated weakness of the bone matrix and ultimately induced pathological fractures. The patient was managed via cementless total hip arthroplasty on the left hip and internal fixation on the right hip. This case highlights that orthopaedic surgeons should consider the possibility of hypophosphatemic osteomalacia if patients receiving antiviral drugs complain of polyarthralgia and generalized weakness.

18.
Ann Biomed Eng ; 46(6): 877-887, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29500566

RESUMEN

To analyze complex inflammatory responses in an in vitro system, we constructed a new 3D in vitro brain tissue model that exhibits in vivo-like tissue responses (e.g. immune cell phenotypes, and molecular response) to inflammatory stimuli. Finite element modeling of oxygen diffusion and cellular oxygen consumption predicted the oxygen profile within 3D structures, consisting of Type I collagen hydrogel embedded with murine microglia. Viability and cytotoxicity analyses supported the mathematical analysis, determining optimal cell growth conditions for 3D construct development. Real-time RT-PCR and ELISA demonstrated significant up-regulation of pro-inflammatory mediators, such as TNF-α, MCP-1, IL-6 and IL-1ß, in lipopolysaccharide (LPS)-stimulated in vitro cell culture (2D and 3D) and in vivo mouse model systems. Interestingly, levels of inflammatory responses from the in vitro 3D model system were more similar to in vivo than in vitro 2D. Additionally, in situ dihydroethidium (DHE) assay and immunofluorescence staining revealed that levels of LPS-stimulated reactive oxygen species (ROS) generation and microglial activation from in vitro 3D model system were closer to in vivo than in vitro 2D. These results demonstrated that an in vitro 3D model provides more physiologically relevant pro-oxidative and pro-inflammatory environments in brain than an in vitro 2D model.


Asunto(s)
Colágeno Tipo I/química , Hidrogeles/química , Microglía/metabolismo , Modelos Biológicos , Estrés Oxidativo , Animales , Técnicas de Cultivo de Célula , Línea Celular , Citocinas/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/toxicidad , Ratones , Microglía/patología , Ratas
19.
Acta Orthop Traumatol Turc ; 52(2): 162-165, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28615116

RESUMEN

Synovial chondromatosis commonly occurs in the anterior compartment of the knee joint, predominantly in middle-aged men. It is relatively unusual in female children and is rarely encountered in the synovium beneath the meniscus. The present report describes a rare case of synovial chondromatosis that developed in the synovium just inferior to both menisci of the right knee in a 10-year-old girl. At this unusual age and location, there is a greater probability of missed diagnosis, due to the lack of definite informative incidence, and difficulty in finding the lesions during arthroscopic examinations. In the present case, multiple loose bodies were hidden by the meniscus, and thus, there were no structural abnormalities in the initial arthroscopic views before probing the meniscus. After careful inspection, we found numerous cartilaginous loose bodies and removed them as much as possible with arthroscopy.


Asunto(s)
Artroscopía/métodos , Condromatosis Sinovial , Cuerpos Libres Articulares/diagnóstico por imagen , Articulación de la Rodilla , Niño , Condromatosis Sinovial/patología , Condromatosis Sinovial/fisiopatología , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Femenino , Humanos , Articulación de la Rodilla/patología , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Examen Físico/métodos , Membrana Sinovial/patología
20.
J Orthop Sci ; 23(1): 97-104, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29092756

RESUMEN

BACKGROUND: Management of a displaced comminuted patellar fractures is challenging, and various surgical fixation methods have been suggested. However, issues of loss of reduction and breakage of fixatives have not yet been resolved. In the current study, we describe a new technique for exposure and stabilization of comminuted patellar fractures and evaluate the clinical and radiologic outcomes of this new treatment. MATERIALS AND METHODS: Thirteen patellar fractures with articular comminution, which were treated by headless compression screws with additional separate vertical wiring were enrolled in this study. Loose articular fragments were fixed with headless compression screws under direct visual reduction of the articular surface, which was facilitated by the superior everting of the patella. Radiographs of the knee were obtained at routine follow-up to assess fracture healing and widening of articular step-off. Clinical outcomes including range of motion, quadriceps circumference, visual analog scale (VAS) related pain score, Lysholm, and Bostman grading scales were measured at the last follow-up. RESULTS: All the fractures healed at a mean of 15 weeks. No patient had loss of reduction, evidence of implant migration, or metallic failure. Articular step-off larger than 2 mm was not seen in any of the cases. The average range of motion arc was 134.2° (range, 120°-145°), and the mean Lysholm and Bostman scores were 94.4 (range, 84-100 points) and 28.7 (range, 25-30 points), respectively. Thigh muscle wasting was observed in four patients (33.3%), but no patient had >1.5 cm difference in thigh circumference girth between the injured and uninjured lower limbs. The average VAS-related pain score was 0.4. CONCLUSIONS: Articular fixations with headless compression screws under direct visual reduction of the articular surface resulted in good clinical outcomes and were considered clinically effective for comminuted patellar fractures.


Asunto(s)
Fijación Interna de Fracturas/instrumentación , Fracturas Conminutas/cirugía , Imagenología Tridimensional , Traumatismos de la Rodilla/cirugía , Rótula/cirugía , Adulto , Anciano , Tornillos Óseos , Hilos Ortopédicos , Estudios de Cohortes , Femenino , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/rehabilitación , Curación de Fractura/fisiología , Fracturas Conminutas/diagnóstico por imagen , Humanos , Puntaje de Gravedad del Traumatismo , Traumatismos de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Rótula/diagnóstico por imagen , Rótula/lesiones , Cuidados Posoperatorios/métodos , Pronóstico , Rango del Movimiento Articular/fisiología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Adulto Joven
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