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1.
BMC Med Educ ; 22(1): 579, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902953

RESUMO

BACKGROUND: The use of head mounted display (HMD)-based immersive virtual reality (VR) coaching systems (HMD-VRC) is expected to be effective for skill acquisition in radiography. The usefulness of HMD-VRC has been reported in many previous studies. However, previous studies have evaluated the effectiveness of HMD-VRC only through questionnaires. HMD-VRC has difficulties in palpation and patient interaction compared to real-world training. It is expected that these issues will have an impact on proficiency. The purpose of this study is to determine the impact of VR constraints in HMD-VRC, especially palpation and patient interaction, on radiographic skills proficiency in a real-world setting. METHODS: First-year students (n = 30) at a training school for radiology technologists in Japan were randomly divided into two groups, one using HMD-VRC (HMD-VRC group) and the other practicing with conventional physical equipment (RP group) and trained for approximately one hour. The teachers then evaluated the students for proficiency using a rubric method. RESULTS: In this study, it was found that some skills in the HMD-VRC group were equivalent to those of the RP group and some were significantly lower than those of the RP group. There was a significant decrease in proficiency in skills related to palpation and patient interaction. CONCLUSIONS: This study suggests that HMD-VRC can be less effective than real-world training in radiographic techniques, which require palpation and patient interaction. For effective training, it is important to objectively evaluate proficiency in the real world, even for HMD-VRC with new technologies, such as haptic presentation and VR patient interaction. TRIAL REGISTRATION: The study was conducted with the approval of the Ethics Committee of International University of Health and Welfare (Approval No.21-Im-035, Registration date: September 28, 2021).


Assuntos
Radiografia , Radiologia , Realidade Virtual , Avaliação Educacional/métodos , Humanos , Radiologia/educação , Óculos Inteligentes
2.
Pain Pract ; 16(2): 175-82, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26452158

RESUMO

Nerve growth factor (NGF) was first discovered approximately 60 years ago by Rita Levi-Montalcini as a protein that induces the growth of nerves. It is now known that NGF is also associated with Alzheimer's disease and intractable pain, and hence, it, along with its high-affinity receptor, tropomyosin receptor kinase (Trk) A, is considered to be 1 of the new targets for therapies being developed to treat these diseases. Anti-NGF antibody and TrkA inhibitors are known drugs that suppress NGF/TrkA signaling, and many drugs of these classes have been developed thus far. Interestingly, local anesthetics also possess TrkA inhibitory effects. This manuscript describes the development of an analgesic that suppresses NGF/TrkA signaling, which is anticipated to be 1 of the new methods to treat intractable pain.


Assuntos
Analgésicos/farmacologia , Fator de Crescimento Neural/metabolismo , Dor/tratamento farmacológico , Receptor trkA/metabolismo , Transdução de Sinais/fisiologia , Animais , Humanos , Dor/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Surg Endosc ; 27(6): 2193-200, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23344506

RESUMO

BACKGROUND: When comparing a single-stroke dissection maneuver among surgeons with differing experience levels, there are major differences in the force applied to the instrument tip. It is difficult to explain to surgeons in training the appropriate force and for the surgeons to ascertain the force intuitively. We quantified the force pattern during single-stroke laparoscopic dissection maneuvers to reveal the factors related to expertise. METHODS: We recorded the force pattern of a single maneuver and measured the magnitude of vertical (VF) and horizontal forces (HF) on the instrument tip using a box trainer (ex vivo). We compared VF and HF among surgeons: experts (n = 10), intermediates (n = 10), and novices (n = 10). The dissection time of a single stroke (T), magnitude of the VF and HF, and the timing of the peak vertical force (TPV) and horizontal force (TPH) were evaluated as performance parameters. RESULTS: The dissection time of a single stroke (T) was shortest in the expert group (p < 0.05). The average maximum magnitude of VF and HF was smallest in the expert group. TPV occurred significantly earlier than TPH in all three groups (p < 0.05). TPV in the expert group occurred earlier than in the intermediate and novice groups (p < 0.05). With increasing experience, TPV occurred earlier. CONCLUSIONS: Expert surgeons apply the most efficient vertical forces to make an initial dissection point and then change to the horizontal direction to separate surrounding tissues from the target organ. Measuring instrument tip force could help in understanding and improving the safety margin in laparoscopic surgical dissection.


Assuntos
Competência Clínica/normas , Dissecação/normas , Laparoscopia/normas , Desempenho Psicomotor/fisiologia , Adulto , Fenômenos Biomecânicos , Dissecação/instrumentação , Desenho de Equipamento , Feminino , Humanos , Laparoscopia/instrumentação , Masculino , Pessoa de Meia-Idade
4.
IEEE Trans Haptics ; 16(4): 770-784, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37843996

RESUMO

Thermal sensation is crucial to enhancing our comprehension of the world and enhancing our ability to interact with it. Therefore, the development of thermal sensation presentation technologies holds significant potential, providing a novel method of interaction. Traditional technologies often leave residual heat in the system or the skin, affecting subsequent presentations. Our study focuses on presenting thermal sensations with low residual heat, especially cold sensations. To mitigate the impact of residual heat in the presentation system, we opted for a non-contact method, and to address the influence of residual heat on the skin, we present thermal sensations without significantly altering skin temperature. Specifically, we integrated two highly responsive and independent heat transfer mechanisms: convection via cold air and radiation via visible light, providing non-contact thermal stimuli. By rapidly alternating between perceptible decreases and imperceptible increases in temperature on the same skin area, we maintained near-constant skin temperature while presenting continuous cold sensations. In our experiments involving 15 participants, we observed that when the cooling rate was -0.2 to -0.24 °C/s and the cooling time ratio was 30 to 50%, more than 86.67% of the participants perceived only persistent cold without any warmth.


Assuntos
Temperatura Alta , Percepção do Tato , Humanos , Sensação Térmica , Pele , Temperatura Cutânea , Temperatura Baixa , Sensação
5.
Front Neurosci ; 17: 1278584, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148942

RESUMO

Introduction: Assessment of human gait posture can be clinically effective in diagnosing human gait deformities early in life. Currently, two methods-static and dynamic-are used to diagnose adult spinal deformity (ASD) and other spinal disorders. Full-spine lateral standing radiographs are used in the standard static method. However, this is a static assessment of joints in the standing position and does not include information on joint changes when the patient walks. Careful observation of long-distance walking can provide a dynamic assessment that reveals an uncompensated posture; however, this increases the workload of medical practitioners. A three-dimensional (3D) motion system is proposed for the dynamic method. Although the motion system successfully detected dynamic posture changes, access to the facilities was limited. Therefore, a diagnostic approach that is facility-independent, has low practice flow, and does not involve patient contact is required. Methods: We focused on a video-based method to classify patients with spinal disorders either as ASD, or other forms of ASD. To achieve this goal, we present a video-based two-stage machine-learning method. In the first stage, deep learning methods are used to locate the patient and extract the area where the patient is located. In the second stage, a 3D CNN (convolutional neural network) device is used to capture spatial and temporal information (dynamic motion) from the extracted frames. Disease classification is performed by discerning posture and gait from the extracted frames. Model performance was assessed using the mean accuracy, F1 score, and area under the receiver operating characteristic curve (AUROC), with five-fold cross-validation. We also compared the final results with professional observations. Results: Our experiments were conducted using a gait video dataset comprising 81 patients. The experimental results indicated that our method is effective for classifying ASD and other spinal disorders. The proposed method achieved a mean accuracy of 0.7553, an F1 score of 0.7063, and an AUROC score of 0.7864. Additionally, ablation experiments indicated the importance of the first stage (detection stage) and transfer learning of our proposed method. Discussion: The observations from the two doctors were compared using the proposed method. The mean accuracies observed by the two doctors were 0.4815 and 0.5247, with AUROC scores of 0.5185 and 0.5463, respectively. We proved that the proposed method can achieve accurate and reliable medical testing results compared with doctors' observations using videos of 1 s duration. All our code, models, and results are available at https://github.com/ChenKaiXuSan/Walk_Video_PyTorch. The proposed framework provides a potential video-based method for improving the clinical diagnosis for ASD and non-ASD. This framework might, in turn, benefit both patients and clinicians to treat the disease quickly and directly and further reduce facility dependency and data-driven systems.

6.
J Anesth ; 26(4): 545-51, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22618952

RESUMO

PURPOSE: Tropomyosin receptor kinase (Trk) A, a high-affinity receptor of nerve growth factor, is a therapeutic target for both noxious and neuropathic pain. The present study examined the effects of an inhibitory peptide of Trk activity (IPTRK) 3 that inhibits TrkA activity on cancer-induced pain in a mouse melanoma model. METHODS: The hind paws of mice were inoculated with B16-F1 mouse melanoma cells on day 0. We administered IPTRK3 (20 mg/kg i.p.) repetitively on days 5, 6, 7, 8, and 9, and evaluated pain-related behaviors on days 0, 5, 10, 15, and 20 after tumor inoculation. RESULTS: Following inoculation, mice demonstrated mechanical allodynia and thermal hyperalgesia with an increased number of flinches, and paw volume increased gradually. However, an intraperitoneal injection of IPTRK3 significantly inhibited mechanical allodynia on day 15 and suppressed the number of flinches on day 20. The increased paw volume was significantly suppressed on day 20 after tumor inoculation. IPTRK3, however, showed no significant effect on thermal hyperalgesia. CONCLUSIONS: These results suggest that TrkA inhibitory peptide likely suppress melanoma-induced pain with concomitant reduction in the increased paw volume in a mouse skin cancer pain model.


Assuntos
Melanoma Experimental/complicações , Dor Intratável/tratamento farmacológico , Receptor trkA/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Proliferação de Células/efeitos dos fármacos , Pé/patologia , Imuno-Histoquímica , Injeções Intraperitoneais , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Fator de Crescimento Neural/farmacologia , Dor Intratável/etiologia , Dor Intratável/psicologia , Fosforilação , Receptor trkA/metabolismo , Receptor trkA/farmacologia
7.
IEEE Trans Haptics ; 15(3): 592-602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35776813

RESUMO

Cold sensations of varying intensities are perceived when human skin is subject to diverse environments. The accurate presentation of temperature changes is important to elicit immersive sensations in applications such as virtual reality. In this article, we developed a method to elicit intensity-adjustable non-contact cold sensations based on the vortex effect. We applied this effect to generate cold air at approximately 0 °C and varied the skin temperature over a wide range. The perception of different temperatures can be elicited by adjusting the volume flow rate of the cold air. Additionally, we introduced a cooling model to relate the changes in skin temperature to various parameters such as the cold air volume flow rate and distance from the cold air outlet to the skin. For validation, we conducted measurement experiments and found that our model can estimate the change in skin temperature with a root mean-square error of 0.16 °C. Furthermore, we evaluated the performance of a prototype in psychophysical cold discrimination experiments based on the discrimination threshold. Thus, cold sensations of varying intensities can be generated by varying the parameters. These cold sensations can be combined with images, sounds, and other stimuli to create an immersive and realistic artificial environment.


Assuntos
Temperatura Baixa , Temperatura Cutânea , Temperatura Alta , Humanos , Sensação , Pele
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 3487-3491, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34891991

RESUMO

Surgical navigation for understanding the internal structure of an organ is being actively studied, and it is necessary to estimate the incision trajectory to update the structure information dynamically. In this study, we focused on the fact that the region incised by the electric knife becomes high in temperature. Thus, we propose an estimation method of incision trajectory by restoring thermal source from diffused thermal images using a ConvLSTM and connecting the restored thermal sources. We first verified the possibility of thermal source restoration, and confirmed that the method enabled to restore the thermal source with high PSNR equivalent to 42.61. Next, we verified the accuracy of the incision trajectory from proposed method by comparing with the traditional method. The results suggested a better performance compared with the traditional method.


Assuntos
Equipamentos Cirúrgicos , Temperatura , Eletricidade
9.
J Pharmacol Sci ; 114(1): 79-84, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20710118

RESUMO

Nerve growth factor (NGF) and its high-affinity receptor, TrkA, are one of the targets in the production of new drugs for the treatment of neuropathic pain. NGF contributes to both the initiation and maintenance of sensory abnormalities after peripheral nerve injury. This study examined the effects of IPTRK3, a new synthetic cell-penetrating peptide that antagonizes TrkA function, on neuropathic pain in mice. Partial sciatic nerve ligation (PSNL) was used to generate neuropathic pain, and we injected IPTRK3 (2 or 10 mg/kg) intraperitoneally on day 7 after PSNL. Effects of the peptide on hyperalgesia, allodynia, and expression of Fos in the spinal cord were examined. Single administration of the peptide on day 7 significantly suppressed both thermal hyperalgesia and mechanical allodynia. Gentle touch stimuli-evoked Fos expression in the lumbar spinal cord was also significantly reduced. Intraperitoneal injection of a cell-penetrating peptide antagonizing TrkA function appears effective for treatment of neuropathic pain in a mouse pain model.


Assuntos
Peptídeos Penetradores de Células/uso terapêutico , Neuralgia/prevenção & controle , Medição da Dor/efeitos dos fármacos , Receptor trkA/antagonistas & inibidores , Receptor trkA/fisiologia , Animais , Peptídeos Penetradores de Células/síntese química , Peptídeos Penetradores de Células/farmacologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Masculino , Camundongos , Neuralgia/metabolismo , Neuralgia/patologia , Proteínas Oncogênicas v-fos/biossíntese , Medição da Dor/métodos
10.
J Pept Sci ; 16(4): 165-70, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20196122

RESUMO

The synthetic peptide fragment (LC5: LRCRNEKKRHRAVRLIFTI) inhibits human immunodeficiency virus type 1 (HIV-1) infection of MT-4 cells. In this study, the solution structure of LC5 in SDS micelles was elucidated by using the standard (1)H two-dimensional NMR spectroscopic method along with circular dichroism and fluorescence quenching. The peptide adopts a helical structure in the C-terminal region (residues 13-16), whereas the N-terminal part remains unstructured. The importance of Phe17 in maintaining the structure of LC5 was demonstrated by replacing Phe17 with Ala, which resulted in the dramatic conformational change of LC5. The solution structure of LC5 elucidated in the present work provides a basis for further study of the mechanism of the inhibition of HIV-1 infection.


Assuntos
Fármacos Anti-HIV/química , HIV-1/efeitos dos fármacos , Fragmentos de Peptídeos/química , Receptores CCR5/química , Sequência de Aminoácidos , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Dicroísmo Circular , Humanos , Espectroscopia de Ressonância Magnética/métodos , Dados de Sequência Molecular , Fragmentos de Peptídeos/farmacologia , Estrutura Secundária de Proteína , Espectrometria de Fluorescência
11.
J Pept Sci ; 15(5): 327-36, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19206072

RESUMO

In an attempt to develop non-ATP-competitive inhibitors of the autophosphorylation of IR, the effects of the synthetic peptides, Ac-DIY(1158)ET-NH(2) and Ac-DY(1162)Y(1163)RK-NH(2), on the phosphorylation of IR were studied in vitro. The peptides were derived from the amino-acid sequence in the activation loop of IR. They inhibited the autophosphorylation of IR to 20.5 and 40.7%, respectively, at 4000 microM. The Asp/Asn- and Glu/Gln-substituted peptides, Ac-NIYQT-NH(2) and Ac-NYYRK-NH(2), more potently inhibited the autophosphorylation than did the corresponding parent peptides. The inhibitory potencies of the substituted peptides were decreased with increasing concentrations of ATP, indicating that these peptides employ an ATP-competitive mechanism in inhibiting the autophosphorylation of IR. In contrast, those of the parent peptides were not affected. Mass spectrometry showed that the parent peptides were phosphorylated by IR, suggesting that they interact with the catalytic loop. Moreover, docking simulations predicted that the substituted peptides would interact with the ATP-binding region of IR, whereas their parent peptides would interact with the catalytic loop of IR. Thus, Ac-DIYET-NH(2) and Ac-DYYRK-NH(2) are expected to be non-ATP-competitive inhibitors. These peptides could contribute to the development of a drug employing a novel mechanism.


Assuntos
Trifosfato de Adenosina/metabolismo , Oligopeptídeos/farmacologia , Fosforilação/efeitos dos fármacos , Receptor de Insulina/metabolismo , Animais , Humanos , Espectrometria de Massas , Oligopeptídeos/síntese química , Oligopeptídeos/química , Ratos
12.
Stud Health Technol Inform ; 132: 230-2, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18391292

RESUMO

In surgery, many kinds of manipulations are conducted using multiple fingers and instruments. The aim of this study is to investigate required haptic rate for multi-finger manipulation and instrumental manipulation. This paper investigated required haptic rate for multi-finger haptic interaction with haptic device and soft tissue deformation. Results of experiment clarified the fact that there is difference of threshold of haptic rate between the number of manipulating fingers.


Assuntos
Dedos , Instrumentos Cirúrgicos , Tato , Interface Usuário-Computador , Simulação por Computador , Humanos , Japão
13.
Stud Health Technol Inform ; 132: 411-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18391332

RESUMO

Many VR technology based training systems use expert's motion data as the training aid, but would not provide any short-cut to teaching medical skills that do not depend on exact motions. Earlier we presented Annotated Simulation Records (ASRs), which can be used to encapsulate experts' insight on psychomotor skills. Annotations made to behavioural parameters in training simulators enable asynchronous teaching instead of just motion training in a proactive way to the learner. We evaluated ASRs for asynchronous teaching of Digital Rectal Examination (DRE) with 3 urologists and 8 medical students. The ASRs were found more effective than motion-based training with verbal feedback.


Assuntos
Exame Retal Digital , Desempenho Psicomotor , Ensino , Interface Usuário-Computador , Competência Clínica , Simulação por Computador , Educação Médica , Humanos , Japão
14.
IEEE Trans Haptics ; 11(2): 204-211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29911979

RESUMO

In this study, we present a system that performs natural-touch-based elasticity estimation for an object by using a depth camera. To estimate elasticity, which is defined as an object's Young's modulus, a strain-stress curve is obtained from fingernail images during haptic palpation. From a color image, the proposed system detects a fingernail and extracts 10 feature values related to the contact force; then, it estimates the force using a multiple regression model. Deformation of the object was estimated from the finger's three-dimensional position obtained from both color and depth images. Then, a strain-stress curve was determined using the force and deformation data. Evaluation experiments were designed to obtain the strain-stress curves of five objects from 10 participants; then, the estimation performance was investigated. The results show that the reliable range of sensing was within Young's modulus values of 0.12-5.6 MPa and the precision of the measurement was 55 percent of the estimated elasticity.


Assuntos
Fenômenos Biomecânicos/fisiologia , Técnicas de Imagem por Elasticidade/métodos , Elasticidade , Dedos/fisiologia , Percepção do Tato/fisiologia , Adulto , Técnicas de Imagem por Elasticidade/instrumentação , Humanos , Masculino , Adulto Jovem
15.
IEEE Trans Vis Comput Graph ; 24(4): 1506-1514, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29543168

RESUMO

Most existing locomotion devices that represent the sensation of walking target a user who is actually performing a walking motion. Here, we attempted to represent the walking sensation, especially a kinesthetic sensation and advancing feeling (the sense of moving forward) while the user remains seated. To represent the walking sensation using a relatively simple device, we focused on the force rendering and its evaluation of the longitudinal friction force applied on the sole during walking. Based on the measurement of the friction force applied on the sole during actual walking, we developed a novel friction force display that can present the friction force without the influence of body weight. Using performance evaluation testing, we found that the proposed method can stably and rapidly display friction force. Also, we developed a virtual reality (VR) walk-through system that is able to present the friction force through the proposed device according to the avatar's walking motion in a virtual world. By evaluating the realism, we found that the proposed device can represent a more realistic advancing feeling than vibration feedback.


Assuntos
Fricção/fisiologia , Interface Usuário-Computador , Realidade Virtual , Caminhada/fisiologia , Adulto , Desenho de Equipamento , Humanos , Cinestesia/fisiologia , Postura Sentada , Adulto Jovem
16.
IEEE Trans Biomed Circuits Syst ; 12(5): 1155-1164, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29994404

RESUMO

This study proposed a novel sensing method of 3-D contact force at a fingertip by using a photoplethysmogram (PPG) device on the proximal part of a finger. The proposed system detects nonpulsatile and pulsatile components of PPG signals from both sides of the proximal part, extracts 16 feature values related to the contact force, and estimates the 3-D force by using a multiple linear regression model. In the validation experiments, the participants wore a PPG device at the proximal parts of their index fingers and applied a contact force at the fingertips for the 11 types of touch actions. The results indicated that satisfactory agreements are observed between the system outputs and the reference forces by the calibrated force sensor. Moreover, the results revealed that the most effective number of feature values corresponded to six for the higher reproducible sensing. Although the development of the effective calibration method is expected to increase robustness, we realized that the proposed method can potentially be used for a 3-D input user interface.


Assuntos
Dedos/fisiologia , Hemodinâmica , Fotopletismografia/métodos , Adulto , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Fotopletismografia/instrumentação , Dispositivos Eletrônicos Vestíveis , Adulto Jovem
17.
Biophys J ; 93(11): 3900-6, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17704174

RESUMO

The effect of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in mixed membranes with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) on interaction with a class A amphipathic peptide, Ac-DWLKAFYDKVAEKLKEAF-NH(2) (Ac-18A-NH(2)), was investigated. The fluorescence lifetime of 2-(9-anthroyloxy)stearic acid and (2)H NMR spectra were used to evaluate the penetration of water molecules into the membrane interface and the order of lipid acyl chains, respectively. The results demonstrated that DOPE in the mixed membranes decreased the fluorescence lifetime and increased the acyl-chain order, and that Ac-18A-NH(2) affected them more for membranes with higher DOPE fractions. The partition coefficient (K(p)) of the peptide to the mixed membranes was increased with the increase in the DOPE mole fractions. From the temperature dependence of the K(p) values, the binding of Ac-18A-NH(2) to POPC/DOPE mixed membranes was found to be entropy-driven. The formation of an alpha-helix at the membrane's surface is supposed to induce positive curvature strain, which decreases the headgroup hydration and acyl-chain order of lipids. Thus, the binding of Ac-18A-NH(2) to membranes is entropically more favorable at higher DOPE fractions since the peptide's insertion into the membrane can decrease the order parameter and unfavorable headgroup hydration, which explains the enhanced peptide binding.


Assuntos
Bicamadas Lipídicas/química , Peptídeos/química , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Tensoativos/química , Sítios de Ligação , Misturas Complexas/química , Ligação Proteica
18.
Nucl Med Biol ; 34(5): 503-10, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17591550

RESUMO

Since elevated levels of gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are associated with a poor prognosis in cancer patients, these enzymes are potential targets for tumor imaging. In the present study, a cyclic decapeptide, cCTTHWGFTLC (CTT), was selected as a mother compound because of its selective inhibitory activity toward gelatinases. For imaging gelatinase activity in tumors, we designed a CTT-based radiopharmaceutical taking into consideration that (1) the HWGF motif of the peptide is important for the activity, (2) hydrophilic radiolabeled peptides show low-level accumulation in the liver and (3) an increase in the negative charge of radiolabeled peptides is effective in reducing renal accumulation. Thus, a highly hydrophilic and negatively charged radiolabel, indiun-111-diethylenetriaminepentaacetic acid ((111)In-DTPA), was attached to an N-terminal residue distant from the HWGF motif ((111)In-DTPA-CTT). In MMP-2 inhibition assays, In-DTPA-CTT significantly inhibited the proteolytic activity in a concentration-dependent fashion. When injected into normal mice, (111)In-DTPA-CTT showed low levels of radioactivity in the liver and kidney. A comparison of the pharmacokinetic characteristics of (111)In-DTPA-CTT with those of other CTT derivatives having different physicochemical properties revealed that the increase in hydrophilicity and negative charge caused by the conjugation of (111)In-DTPA reduced levels of radioactivity in the liver and kidney. In tumor-bearing mice, a significant correlation was observed between the accumulation in the tumor as well as tumor-to-blood ratio of (111)In-DTPA-CTT and gelatinase activity. These findings support the validity of the chemical design of (111)In-DTPA-CTT for reducing accumulation in nontarget tissues and maintaining the inhibitory activity of the mother compound. Furthermore, (111)In-DTPA-CTT derivatives would be potential radiopharmaceuticals for the imaging of gelatinase activity in metastatic tumors in vivo.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/enzimologia , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Ácido Pentético/análogos & derivados , Peptídeos Cíclicos/farmacocinética , Animais , Linhagem Celular Tumoral , Desenho de Fármacos , Ativação Enzimática , Humanos , Marcação por Isótopo/métodos , Taxa de Depuração Metabólica , Camundongos , Especificidade de Órgãos , Ácido Pentético/química , Ácido Pentético/farmacocinética , Peptídeos Cíclicos/química , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
19.
Stud Health Technol Inform ; 125: 238-40, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17377275

RESUMO

This study aims to provide physics-based force feedback system on distributed system for simulating invasive operation such as ablation. conventional PC-based VR surgical simulators with haptic interaction are hard to provide sufficient computational resources for the simulation of physics-based soft tissue fracture. For proper presentation of force feedback as real operations, physics-based simulation is inevitable. At the same time finite element method requires huge computational complexites. In this paper, the authors propose server-side speculative operation method on application layer for hiding the calculation latencies. The proposed method would achieve the response acceleration without the decomposition of conventional simulation process. The theoritical estimates of speculation parameters are mentioned.


Assuntos
Ablação por Cateter , Simulação por Computador , Retroalimentação , Tato , Interface Usuário-Computador , Análise de Elementos Finitos , Humanos , Japão
20.
Stud Health Technol Inform ; 125: 244-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17377277

RESUMO

Exclusion is a surgical manipulation of pushing aside organ in open surgery. Recently, training opportunity of surgeon is decreasing due to animal protection and patient's rights. In this study, we propose an organ exclusion training simulator with multi-finger haptic device and stress visualization. The method was applied to a medical application of exclusion which is an important manipulation to make a hidden tissue visible or to enlarge workspace. The system equips FEM-based soft tissue deformation and multi-finger haptic device. Real-time simulation was achieved with a prototype system. Experimental results of training trial suggested the effectiveness of the system and stress visualization for exclusion training. Results of subjective evaluation by surgeons were highly positive as to realism of manipulation and usefulness of the simulator.


Assuntos
Simulação por Computador , Dedos , Procedimentos Cirúrgicos Operatórios , Tato , Humanos , Japão , Estresse Mecânico , Interface Usuário-Computador
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