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1.
J Pharm Sci ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32173323

RESUMO

Epithelial-mesenchymal transition (EMT) plays a role in not only cancer metastasis, but also drug resistance, which is associated with increased levels of efflux transporters such as P-glycoprotein (P-gp). Here, we examined whether P-gp activation during Snail-induced EMT of lung cancer cells is mediated by ezrin, radixin and moesin (ERM), which regulate transporter localization. HCC827 lung cancer cells overexpressing the transcription factor Snail showed increased Rhodamine123 efflux and increased paclitaxel resistance, reflecting increased P-gp activity. Concomitantly, the expression level of moesin, but not ezrin or radixin, was significantly increased. The increase of P-gp activity was suppressed by knockdown of moesin. Thus, the increase of P-gp activity associated with Snail-induced EMT may be mediated mainly by moesin in HCC827 cells. On the other hand, the Snail mRNA expression level was correlated with the expression level of each ERM in four non-small-cell lung cancer cell lines (HCC827, A549, H441, H1975) and in tumor tissues, but not normal tissues, of lung cancer patients. These results suggest that P-gp activation during EMT is at least partially due to increased expression of moesin. Co-administration of moesin inhibitors with anticancer drugs might block P-gp-mediated drug efflux organ-specifically, improving treatment efficacy and minimizing side effects on other organs.

2.
J Immunol ; 204(6): 1641-1649, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32005755

RESUMO

Mouse mast cell proteases (mMCP)-1 and -2 are specifically expressed in mucosal mast cells (MCs). However, the transcriptional regulation mechanism of the Mcpt1 and Mcpt2 genes induced in mucosal MCs is largely unknown. In the current study, we found that TGF-ß stimulation drastically induced upregulation of Mcpt1 and Mcpt2 mRNA in mouse bone marrow-derived MCs (BMMCs). TGF-ß-induced expression of Mcpt1 and Mcpt2 was markedly suppressed by transfection with small interfering RNA targeting Smad2 or Smad4 and moderately reduced by Smad3 small interfering RNA. We next examined the roles of the hematopoietic cell-specific transcription factors GATA1 and GATA2 in the expression of Mcpt1 and Mcpt2 and demonstrated that knockdown of GATA1 and GATA2 reduced the mRNA levels of Mcpt1 and Mcpt2 in BMMCs. The recruitment of GATA2 and acetylation of histone H4 of the highly conserved GATA-Smad motifs, which were localized in the distal regions of the Mcpt1 and Mcpt2 genes, were markedly increased by TGF-ß stimulation, whereas the level of GATA2 binding to the proximal GATA motif was not affected by TGF-ß. A reporter assay showed that TGF-ß stimulation upregulated GATA2-mediated transactivation activity in a GATA-Smad motif-dependent manner. We also observed that GATA2 and Smad4 interacted in TGF-ß-stimulated BMMCs via immunoprecipitation and Western blotting analysis. Taken together, these results demonstrate that TGF-ß induced mMCP-1 and -2 expression by accelerating the recruitment of GATA2 to the proximal regions of the Mcpt1 and Mcpt2 genes in mucosal MCs.

3.
Sci Rep ; 10(1): 977, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969665

RESUMO

As a clinical manifestations of diabetic retinopathy (DR), pericytes (PCs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic acid (UDCA) in PC depletion mice by injection of an antibody against platelet-derived growth factor reception-ß (PDGFR-ß clone APB5). To assess the integrity of the retinal vessels, their density, diameters, vessel branching points, and number of acellular capillaries were evaluated. While all types of retinal vessels became enlarged in APB5-induced mice, treatment with UDCA rescued the vasculature; the vessel density, diameter of the veins and capillaries, and vessel branching points were significantly lower in mice treated with UDCA. Although APB5-induced mice displayed progressive exacerbation of retinal edema, whole retinal thickness upon treatment with UDCA was significantly decreased. Additionally, UDCA reduced the expression of F4/80+ macrophages in the APB5-induced retina according to immunofluorescent labeling. UDCA also reduced the increased expression of angiogenic factors and inflammatory mediators (vascular endothelial growth factor, intercellular adhesion molecule-1, and monocyte chemotactic protein-1). These findings suggest that UDCA can be used to prevent the progression of and treat DR.

4.
J Comput Assist Tomogr ; 44(1): 32-36, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939879

RESUMO

OBJECTIVE: To evaluate the effect of ultra high-resolution computed tomography (UHRCT) and model-based iterative reconstruction (MBIR) on the detectability of simulated submillimeter artery. METHODS: A small vessel phantom ranging from 0.4 to 2.0 mm in diameter and edge phantoms of low to high attenuation values were scanned by UHRCT (super-high-resolution mode and normal-resolution-mode) and conventional CT, and data were reconstructed by MBIR and filtered back projection (FBP). Vessel detectability was assessed subjectively and the effective size at which 50% of response was achieved (ES50 [mm]) was calculated. Modulation transfer function (MTF) was calculated by an edge spread function method. RESULTS: ES50 of super high-resolution mode (0.36 mm for MBIR and 0.50 mm for FBP) was significantly smaller than those of normal-resolution mode (P < 0.01). In the MTF analysis, the MTF of MBIR improved as the edge phantom attenuation increased, whereas that of FBP was stable. CONCLUSIONS: Both UHRCT and MBIR are effective for the detectability of simulated submillimeter artery.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Vasos Coronários/diagnóstico por imagem , Algoritmos , Humanos , Imagens de Fantasmas , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador
5.
Gynecol Oncol ; 156(3): 629-635, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926638

RESUMO

PURPOSE: The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) to prevent nausea and vomiting in carboplatin (CBDCA) combination therapy for patients with gynecological cancer. METHODS: We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper on days 1-4) combined with NK1RA, 5-HT3RA, and DEX. The primary end point was complete response (CR; no emesis and rescue therapy) during overall phase (120 h after the start of carboplatin administration). RESULTS: Between May 2018 and June 2019, 60 patients were enrolled from 3 institutions in Japan. A total of 57 patients who met the criteria were included in the efficacy and safety analysis. The CR rate for the overall phase was 78.9%. Acute (0-24 h) and delayed phases (24-120 h) were 96.5% and 80.7%, respectively. Somnolence was observed in 73.7% patients. However, somnolence of grade 2 or higher was observed in only 3.5% of cases. There were no grade 3 or 4 toxicities associated with OLZ. CONCLUSIONS: Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy.

6.
Eur Arch Otorhinolaryngol ; 276(11): 3159-3164, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31485732

RESUMO

PURPOSE: Ultra-high-resolution computed tomography (UHRCT) is an emerging imaging technology that is able to achieve simultaneous 160 slices with super-thin 0.25 mm thickness. The purpose of this study was to assess the feasibility of UHRCT to visualize laryngeal structure and kinetics. METHODS: Three normal volunteers and three patients with unilateral vocal fold paralysis (UVFP) were incorporated in this case series. First, images were taken under five conditions in normal volunteers. Five tasks consisted of (1) air inspiration through the nose (IN), (2) breath holding (BH), (3) sustained vowel /i:/ phonation (IP), (4) humming phonation (HP), and (5) forced glottic closure during exhalation (FC). Three-dimensional CT images of arytenoid and cricoid cartilages, as well as virtual laryngoscopic images, were reconstructed using UHRCT data. Reconstructed images were compared among five conditions to assess the best tasks to picture laryngeal kinetics. Second, pre- and post-phonosurgical images were examined in UVFP patients to evaluate potential role of UHRCT to assess laryngeal pathology in hoarse patients. RESULTS: Among the five conditions, IN and IP conditions were considered suitable to visualize laryngeal structure at rest and during phonation, respectively. Kinetic abnormalities including asymmetric motion of arytenoid cartilages were elucidated in UVFP patients, and virtual endoscopy visualized the clinically invisible posterior three-dimensional glottic chinks. Furthermore, UHRCT was useful to understand changes in laryngeal structure achieved by phonosurgery. CONCLUSIONS: UHRCT is an emerging imaging technology that can be used for minimally invasive visualization and assessment of laryngeal structure and kinetics. Future studies to assess more number of patients with laryngeal dysfunction are warranted.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imagem Tridimensional/métodos , Laringe , Tomografia Computadorizada Multidetectores/métodos , Paralisia das Pregas Vocais , Adulto , Cartilagem Aritenoide/diagnóstico por imagem , Feminino , Humanos , Cinética , Laringoplastia/métodos , Laringoscopia/métodos , Laringe/diagnóstico por imagem , Laringe/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fonação/fisiologia , Reprodutibilidade dos Testes , Paralisia das Pregas Vocais/diagnóstico , Paralisia das Pregas Vocais/fisiopatologia , Paralisia das Pregas Vocais/cirurgia
7.
Biocontrol Sci ; 23(3): 133-138, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30249963

RESUMO

The thermotolerant yeast Kluyveromyces marxianus, growing at high temperature (45℃) , showed stronger survival under heat shock at 50℃ than the brewing yeast Saccharomyces cerevisiae, which was unable to grow at 45℃. The survival rate of K. marxianus decreased to 10% during heat shock at 50℃ for 20 min, and to less than 0.01% at 60℃ for 20 min. Cells with damaged cellular membranes were infrequently observed at 50℃ and had decreased significantly from heat shock at 60℃. The metabolic activity of K. marxianus was retained at 50℃, whereas that of S. cerevisiae was not. The trehalose content of K. marxianus was approximately two times that of S. cerevisiae. These results suggest that K. marxianus protects itself from heat shock-induced damage through the use of trehalose (a protective molecule in S. cerevisiae) as well as other different factors.


Assuntos
Kluyveromyces/fisiologia , Termotolerância/fisiologia , Trealose/metabolismo , Membrana Celular/química , Resposta ao Choque Térmico , Temperatura Alta , Kluyveromyces/química , Viabilidade Microbiana , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/fisiologia , Especificidade da Espécie
8.
Int J Clin Oncol ; 23(2): 382-388, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29039073

RESUMO

PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). METHODS: A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥ 50 mg/m2). Patients were randomly assigned either olanzapine 10 or 5 mg orally on days 1-4, combined with standard antiemetic treatment. The primary endpoint was a complete response (CR; no emesis and no use of rescue medications) in the delayed phase (24-120 h after the start of cisplatin treatment). RESULTS: 153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3-83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2-90.7, P < 0.001) in the 5 mg group (P value for H 0: complete response rate ≤ 65%). The most common adverse event was somnolence, which had an incidence of 53.3 and 45.5% in the 10 and 5 mg olanzapine groups, respectively. CONCLUSIONS: Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates. CLINICAL TRIAL INFORMATION: UMIN000014214.


Assuntos
Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Benzodiazepinas/administração & dosagem , Vômito/prevenção & controle , Adulto , Idoso , Antieméticos/uso terapêutico , Aprepitanto , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Cisplatino/efeitos adversos , Dexametasona/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Isoquinolinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Neoplasias/tratamento farmacológico , Olanzapina , Palonossetrom , Quinuclidinas/uso terapêutico , Resultado do Tratamento , Vômito/induzido quimicamente
9.
Br J Ophthalmol ; 102(4): 525-530, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28765147

RESUMO

BACKGROUND/AIMS: To investigate the relationship between gaze tracking (GT) results and ocular surface condition in glaucoma. METHOD: The Humphrey 24-2 visual field (VF) was measured in 34 eyes of 30 patients with open-angle glaucoma without VF damage. Tear break-up time, Schirmer's test, tear meniscus volume (TMV) and presence of superficial punctate keratopathy (SPK) were also measured in order to describe the condition of the ocular surface. Various GT parameters were calculated: the average frequency of eye movements per stimulus between 1° and 2° (move1-2), the average frequency of eye movements per stimulus between 3° and 5° (move3-5), the average frequency of eye movements per stimulus more than 6° (move≥6), the average tracking failure frequency per stimulus (TFF) and the average blinking frequency. The relationship between GT parameters, reliability indices and ocular surface measurements was investigated using linear mixed modelling. RESULTS: SPK was positively associated with high rates of move3-5 (coefficient=0.12 for SPK+, p=0.003) and move≥6 (coefficient=0.052 for SPK+, p=0.023). High TMV was significantly related to TFF (coefficient=0.37, p=0.023). Fixation losses, false-positives and false-negatives were not significantly associated with any GT parameters or ocular surface measurements. CONCLUSION: SPK is associated with increased frequency of eye movements (move3-5 and move≥6). In addition, large TMV is associated with increased rate of TFF. Careful attention should be paid when interpreting GT parameters in patients with SPK or a large TMV.


Assuntos
Córnea/patologia , Movimentos Oculares/fisiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Campos Visuais/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Medições dos Movimentos Oculares , Feminino , Fixação Ocular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Lágrimas/metabolismo
10.
Ocul Immunol Inflamm ; 26(5): 779-782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28282736

RESUMO

PURPOSE: We report three cases of ocular inflammation and polymyalgia rheumatica without concomitant giant-cell arteritis. METHODS: Report of three cases. RESULTS: Polymyalgia rheumatica onset was at a mean age of 66.7 years, and ocular inflammation, which developed 7-21 months later, was bilateral in all patients. Ocular inflammation presented as episcleritis, scleritis, or anterior uveitis, and it emerged during the tapering of low-dose prednisolone prescribed for polymyalgia rheumatica in all patients. Recurrence of ocular inflammation was observed in two patients. CONCLUSIONS: Ocular inflammation associated with polymyalgia rheumatica was often bilateral and occurred during steroid tapering. Although this presentation is relatively uncommon, polymyalgia rheumatica should be considered in the differential diagnosis of older patients presenting with ocular inflammation, especially those with proximal myalgia and elevated inflammatory markers.


Assuntos
Fluormetolona/administração & dosagem , Polimialgia Reumática/complicações , Prednisolona/administração & dosagem , Esclerite/etiologia , Uveíte Anterior/etiologia , Administração Oral , Idoso , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Arterite de Células Gigantes , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Esclerite/diagnóstico , Esclerite/tratamento farmacológico , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico
11.
J Arrhythm ; 33(4): 318-323, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28765763

RESUMO

BACKGROUND: When performing catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT), it can be difficult to maintain a safe distance from the His recording site to avoid AV block in patients with a short distance between this recording site to the coronary sinus (CS) ostium (small triangle of Koch [TOK]). In this study, we sought to identify parameters predicting small TOK and test these parameters in patients undergoing AVNRT catheter ablation. METHODS: Twenty-eight patients who underwent catheter ablation of atrial fibrillation using a three-dimensional (3D) electroanatomical mapping system (EAM) with computed tomography (CT) merge (23 males; mean age, 65.8±12.1 years) were included. The shortest distance between the CS ostium and His recording sites (His-CSd) was measured on the EAM. Aortic (Ao) unfolding in chest X-ray scan, Ao angle to the LV, Ao length, Ao to the right ventricular distance, size of the Valsalva in the CT scan, and parameters of echocardiogram were evaluated. The identified parameters were subsequently tested as predictors for small TOK in patients undergoing AVNRT ablation. RESULTS: The size of TOK was associated with Ao length (r = -0.70, p<0.01), left ventricular end-systolic dimension (LVDs) (r = -0.51, p<0.01), and Ao unfolding. In patients with AVNRT, only Ao unfolding predicted a smaller TOK. CONCLUSIONS: Small TOK was associated with longer Ao, larger LVDs, and Ao unfolding. Of these, Ao unfolding was associated with smaller TOK in patients with AVNRT.

12.
Dalton Trans ; 46(1): 44-48, 2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27918046

RESUMO

The first tellurocarbonyl complex with a half-sandwich structure [CpRuCl(CTe)(H2IMes)] was synthesized by a ligand substitution reaction. The practically complete series of the CpCE complexes [CpRuCl(CE)(H2IMes)] (E = O, S, Se, Te) were systematically explored. The tellurium atom in the CTe complex could be smoothly replaced with lighter chalcogen atoms.

13.
ChemSusChem ; 9(13): 1680-8, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27226396

RESUMO

Rh-MoOx /SiO2 (Mo/Rh=0.13) is an effective catalyst for the hydrogenolysis of 1,4-anhydroerythritol (1,4-AHERY) and provides 2-BuOH in high yield of 51 %. This is the first report of the production of 2-BuOH from 1,4-AHERY by hydrogenolysis. 1,4-AHERY was more suitable as a starting material than erythritol because the 2-BuOH yield from erythritol was low (34 %). Based on the kinetics and comparison of reactivities of the related compounds using Rh-MoOx /SiO2 and Rh/SiO2 catalysts, the modification of Rh/SiO2 with MoOx leads to the high activity and high selectivity to 2-BuOH because of the generation of reactive hydride species and the strong adsorption of 1,4-AHERY on MoOx species. The reaction proceeds by main two routes, (I) the combination of single C-O hydrogenolysis with the desorption of intermediates, a usual route in hydrogenolysis, and (II) multiple C-O hydrogenolysis without the desorption of intermediates from the active site, and the reaction mechanism for Route (II) is proposed.


Assuntos
Butanóis/química , Butanóis/síntese química , Eritritol/análogos & derivados , Molibdênio/química , Óxidos/química , Ródio/química , Dióxido de Silício/química , Técnicas de Química Sintética , Eritritol/química , Hidrogênio/química , Cinética
14.
Nucl Med Biol ; 43(1): 101-107, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26602328

RESUMO

Phosphatidylinositol 3-kinase (PI3K) activity and protein expression levels are often increased in tumor regions. Since PI3K plays a crucial role in regulating cell growth and proliferation, inhibiting PI3K-dependent pathways could be a promising approach for cancer treatment. In clinical practice, however, evaluation of PI3K expression levels is limited to immunohistochemistry of patient samples, which requires invasive biopsies. Here we report the synthesis of three candidate compounds, FMTA-1, 2 and 3, and evaluate their capacity to detect PI3K expression levels with positron emission tomography (PET). Among the three candidates, FMTA-2 showed a lower IC50 value for PI3K. (18)F Radiolabeling of FMTA-2 to produce [(18)F]FMTA-2 was accomplished and its capacity for detecting PI3K expression levels was evaluated in vitro and in vivo. Cell uptake of [(18)F]FMTA-2 correlated well with cellular PI3K expression levels, and was suppressed by the ATP-competitive PI3K inhibitor ZSTK474. In an in vivo experiment using tumor-transplanted model mice, a higher signal-to-noise ratio (S/N) was seen with [(18)F]FMTA-2 in animals transplanted with DMS114 cells (expressing high PI3K levels) relative to DU145 cells (expressing low PI3K levels). However, in vivo pharmacokinetics of [(18)F]FMTA-2 was undesirable and the absolute amount of this compound that accumulated at the tumor region was low. To the best of our knowledge, this study represents the first trial of a PET tracer for detecting PI3K. Although further improvement of the probe is required prior to clinical application, these results should encourage future work.


Assuntos
Descoberta de Drogas , Radioisótopos de Flúor , Fosfatidilinositol 3-Quinases/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Triazinas/metabolismo , Animais , Transporte Biológico , Linhagem Celular Tumoral , Masculino , Camundongos , Radioquímica , Triazinas/síntese química , Triazinas/química
15.
Allergy Asthma Proc ; 34(4): 362-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23883601

RESUMO

Some patients with infantile atopic dermatitis (AD) achieve remission around 1 year old, but in others it persists. The difference between them is unclear. We performed a birth cohort study to find the markers predicting the outcome of infantile AD. We followed up a cohort (n = 314) from birth to 14 months of age, and cord blood was taken from the participants. Some of them (n = 144) had a physical examination and a blood test at 6 and 14 months of age. The subjects who had AD at 6 months (n = 34) were divided into two groups, named the transient group (those who had no AD at 14 months of age; n = 16) and the persistent group (those who still had AD at 14 months of age; n = 18). Then, laboratory data were compared between these two groups. Percentage of CD8 in cord blood lymphocytes and total IgE at 6 months of age in the persistent group was significantly higher than those of the transient group. The area under the curves of a receiver operating characteristic analysis were 0.792 (p = 0.007) and 0.722 (p = 0.027). In the persistent group, total IgE, percentages of T-helper (Th) 2 and phytohemagglutinin-induced IL-4 production from peripheral blood mononuclear cells at 14 months of age were also significantly higher than those of the transient group. Thus Th2 polarization in the persistent group was confirmed. In clinical use, total IgE at 6 months of age is the most useful predictive marker to know the outcome of infantile AD. The clinical trial registration ID is UMIN000002926.


Assuntos
Dermatite Atópica/sangue , Dermatite Atópica/diagnóstico , Imunoglobulina E/sangue , Células Cultivadas , Estudos de Coortes , Citocinas/imunologia , Dermatite Atópica/imunologia , Feminino , Sangue Fetal/imunologia , Humanos , Lactente , Recém-Nascido , Leucócitos Mononucleares/imunologia , Ativação Linfocitária , Masculino , Valor Preditivo dos Testes , Células Th2/imunologia , Fatores de Tempo
16.
Clin Biomech (Bristol, Avon) ; 28(6): 642-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23725792

RESUMO

BACKGROUND: Dynamic alignment of "knee-in & toe-out" is a risk factor for anterior cruciate ligament injury and is possibly influenced by static knee alignment, range of tibial rotation and tibial plateau geometry. METHODS: Twenty-eight healthy women were classified into valgus, neutral and varus groups based on static alignment of their knees. A 3-dimensional motion analysis was carried out for a single limb drop landing. The range of tibial rotation and posterior tibial slope angle was measured by MRI. Comparison among the 3 groups and correlation between the angles was analyzed during motion. FINDINGS: The differences between the medial and lateral posterior tibial slope angles were greater (P=0.019), also range of internal tibial rotation for the valgus group (P=0.017) and, for the varus group, the "knee-in" angle (P=0.048). The "knee-in" angle correlated significantly with the tibial rotation angle (R=-0.39, P=0.038), and the range of tibial rotation correlated with the variations between the medial and lateral posterior tibial slope angles (R=0.90, P=0.003). INTERPRETATION: The range of tibial rotation, posterior tibial slope and "knee-in" angle varied according to whether the knee was in valgus or varus with the range of tibial rotation dependent on the posterior tibial slope angle. The greater the "knee-in" angle became, the smaller the internal tibial rotation was, acting in a kinetic chain. The results suggest that static alignment of the knee may be utilized as a predictor for potential problems that occur during motion.


Assuntos
Articulação do Joelho/anatomia & histologia , Articulação do Joelho/fisiologia , Amplitude de Movimento Articular/fisiologia , Suporte de Carga/fisiologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Imagem Tridimensional , Imagem por Ressonância Magnética , Movimento/fisiologia , Valores de Referência , Rotação , Esportes/fisiologia , Tíbia/anatomia & histologia , Tíbia/fisiologia , Adulto Jovem
17.
Bioorg Med Chem Lett ; 23(6): 1617-21, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23414800

RESUMO

A series of novel 5-trans-hydroxyadamantan-2-yl-5,6,7,8-tetrahydropyrazolo[4,3-c]azepin-4(1H)-ones that inhibit 11beta-hydroxysteroid dehydrogenase type 1 are described. We discovered these 7-membered cyclic amide derivatives by introducing a distinctive linker through pharmacophore analysis of known ligands included in X-ray co-crystal structures. Further optimization using docking studies led to highly potent inhibitors 15b and 27, which furthermore showed the potent efficacy in in vivo studies.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Amidas/química , Inibidores Enzimáticos/química , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Amidas/síntese química , Amidas/metabolismo , Animais , Sítios de Ligação , Cristalografia por Raios X , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Simulação de Acoplamento Molecular , Ligação Proteica , Estrutura Terciária de Proteína , Estereoisomerismo , Relação Estrutura-Atividade
18.
Anal Biochem ; 419(2): 241-9, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21907698

RESUMO

Screening for prostate cancer remains unsatisfactory. Recent studies have examined the cancer diagnostic/prognostic values of various acute phase proteins, such as haptoglobin. We describe here a novel method of surface plasmon resonance (SPR) based on multi-sequential analysis with SNA-1, AAL, and PHA-L(4) lectin, to estimate the glycosylation status of haptoglobin in sera of patients with prostate cancer (n=15), benign prostate disease (BPD) including benign prostatic hypertrophy (n=20), and normal subjects (n=11). The SPR-based analysis involves the use of anti-haptoglobin as ligand and dilution of the analyte to 1400-fold and filtration, followed by detection of the sugar chain by lectin solution. The normalized RU of lectin to haptoglobin represents the binding amount of lectin divided by that of haptoglobin. The normalized RU by SNA-1 of the prostate cancer group was significantly higher than those of the control and BPD group. SNA-1 detected NeuAcα2,6 in a biantennary sugar chain, whose content was the highest among the major glycoproteins in serum. Serum samples diluted about 7000-fold were subjected to microanalysis at 10 ng/µl and 10 µl/min for 4 min. The combination of SNA-1 and haptoglobin by SPR multi-sequential analysis offered the most accurate diagnosis of prostate cancer without any modification of serum glycoproteins.


Assuntos
Haptoglobinas/análise , Lectinas/análise , Hiperplasia Prostática/sangue , Neoplasias da Próstata/sangue , Ressonância de Plasmônio de Superfície/métodos , Western Blotting , Calibragem , Metabolismo dos Carboidratos , Estudos de Casos e Controles , Humanos , Masculino , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Ligação Proteica , Curva ROC
19.
J Child Neurol ; 24(8): 1010-2, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19666885

RESUMO

Spinal muscular atrophy is an entity of neurodegenerative disorders at the anterior horn neuron of the spinal cord caused by telomeric survival motor neuron gene abnormality. There is no definitive treatment for spinal muscular atrophy, but recent reports have indicated the efficacy of intravenous injection, but not oral administration, of thyrotropin-releasing hormone (TRH). We treated an 18-year-old male patient with spinal muscular atrophy type III by oral administration of the thyrotropin-releasing hormone analogue, taltireline hydrate. His muscle strength increased significantly after the therapy, and he showed no clinical or laboratory identifiable adverse effects, including thyroid-stimulating hormone suppression that had been observed with intravenous thyrotropin-releasing hormone therapy. Oral administration of this thyrotropin-releasing hormone analogue should be noted as a promising therapy for spinal muscular atrophy.


Assuntos
Atrofias Musculares Espinais da Infância/tratamento farmacológico , Hormônio Liberador de Tireotropina/análogos & derivados , Administração Oral , Adolescente , Humanos , Masculino , Força Muscular/efeitos dos fármacos , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/uso terapêutico , Resultado do Tratamento
20.
Allergol Int ; 57(4): 331-8, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18690006

RESUMO

BACKGROUND: The differentiation of Th1 and Th2 is strictly regulated by humoral and cellular factors. The imbalance between Th1 and Th2 is considered to be the pathogenesis of allergic and autoimmune disorders. It is important to elucidate the effect of environmental factors, such as temperature, on the expression of cytokines of Th1 and Th2. METHODS: We investigated the expression of IFN-gamma, IL-4, IL-5, IL-10 and IL-12 from LPS- or PHA-stimulated PBMCs at 30 degrees C or 37 degrees C using ELISA and Real-time PCR. We measured the change of NF-kappaB activity at 30 degrees C or 37 degrees C with LPS stimulation using the reporter gene assay. RESULTS: IFN-gamma production from LPS-stimulated PBMCs at 30 degrees C was up-regulated compared with 37 degrees C. IL-5 and IL-10 production from PHA-stimulated PBMCs at 30 degrees C were down-regulated compared with 37 degrees C. This augmented IFN-gamma production was caused by the up-regulation of IL-12 production from CD14+ blood monocytes. Both IL-12 mRNA and IL12 protein at 30 degrees C were up-regulated compared with 37 degrees C. NF-kappaB, the key molecule for the expression of IL-12, was also augmented at 30 degrees C compared with 37 degrees C. CONCLUSIONS: Hypothermia up-regulated the expression of IL-12 and IFN-gamma due to the augmented NF-kappaB activity. It is suggested that hypothermia modifies the pattern of cytokine gene expression.


Assuntos
Hipotermia/metabolismo , Interferon gama/metabolismo , Interleucina-12/metabolismo , Monócitos/metabolismo , NF-kappa B/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Temperatura Baixa , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Genes Reporter , Humanos , Hipotermia/patologia , Receptores de Lipopolissacarídeos , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Monócitos/patologia , NF-kappa B/genética , NF-kappa B/imunologia , Fito-Hemaglutininas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Células Th1/imunologia , Células Th2/imunologia , Receptores Toll-Like/imunologia , Transfecção
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