RESUMO
PURPOSE: Iatrogenic ureteral injury (IUI) can complicate minimally invasive and open abdominopelvic surgery. The incidence of IUI is low and dependent on the type of surgery (< 10 %), but it is associated with high morbidity. Therefore, intraoperative visualization of the ureter is critical to reduce the incidence of IUI, and some methodologies for ureter visualization have been developed. Amongst these, near-infrared fluorescence (NIRF) visualization is thought to bring an advantage with real-time retroperitoneal visualization through the retroperitoneum. We investigated an indocyanine green (ICG) derivative, ASP5354, which emits NIRF at 820 nm when exposed to near-infrared light at a wavelength of 780 nm, in a rodent and porcine model. PROCEDURES: Wistar rats and Göttingen minipigs under anesthesia were laparotomized and then administered ASP5354 chloride intravenously at dose of 0.03 and 0.3 mg/kg for rats and 0.001 and 0.01 mg/kg for minipigs, respectively. Videos of the abdominal cavity in minipigs were taken using a near-infrared fluorescent camera (pde-neo) and assessed visually by three independent clinicians. Toxicological evaluation was demonstrated with cynomolgus monkeys. RESULTS: The proportion of animals whose ureters were visible up to 3 h after administration of ASP5354 chloride were 33 % at 0.001 mg/kg and 100 % at 0.01 mg/kg, respectively. In a toxicological study in cynomolgus monkeys, ASP5354 chloride demonstrated no significant toxicity, suggesting that 0.01 mg/kg provides an optimal dose when used clinically and could allow for ureter visualization during routine surgical procedures. CONCLUSIONS: The dose of 0.01 mg/kg provided an optimal dose for ureter visualization up to 3 h after administration. ASP5354 shows promise for ureter visualization during abdominopelvic surgery, which may potentially lower the risk of IUI.
Assuntos
Laparoscopia , Ureter , Suínos , Animais , Ratos , Ureter/diagnóstico por imagem , Ureter/lesões , Laparoscopia/métodos , Corantes Fluorescentes , Porco Miniatura , Cloretos , Macaca fascicularis , Ratos Wistar , Verde de Indocianina , Imagem Óptica/métodosRESUMO
Intraoperative ureter identification helps reduce the risk of ureteral injury. Currently, no suitable agents for real-time ureter visualization are approved. ASP5354 (TK-1) is a novel indocyanine green derivative. In this first-in-human phase 1, double-blind, sequential ascending-dose study, urethral catheters were placed in 6 healthy volunteers who were randomized to single-dose, intravenous ASP5354 0.1 mg (n = 4) or placebo (n = 2). Sequential dose escalations to 0.5-, 2-, 8-, and 24-mg ASP5354 in new cohorts were contingent upon Dose-Escalation Committee approval after review of pharmacokinetic (PK) and safety data. Blood and urine samples were collected over 24 hours following dose administration. Objectives were to assess the safety/tolerability and PK of ASP5354. Treatment-emergent adverse events (TEAEs) were reported in 3 (15%) and 2 (20%) participants in the ASP5354 and placebo groups, respectively. In the former, there were 6 TEAEs (5/6 grade 1-2). One ASP5354 participant experienced grade 3 pyelonephritis, attributed to the catheter. No TEAEs were related to ASP5354. Mean plasma terminal elimination half-life ranged from 2.1 to 3.6 hours, with near complete urinary excretion of unchanged ASP5354 within 24 hours after administration. Linear and dose-proportional PK were observed. These results support further evaluation of ASP5354 at doses up to 24 mg for intraoperative near-infrared fluorescence ureter visualization.
Assuntos
Voluntários Saudáveis , Adulto , Área Sob a Curva , Método Duplo-Cego , HumanosRESUMO
We evaluated 3D pseudo-continuous arterial spin labeling (pCASL) using turbo spin echo with a pseudo-steady-state (PSS) readout in comparison with the other major readout methods of 3D spiral and 2D echo-planar imaging (EPI). 3D-PSS produced cerebral blood flow (CBF) values well correlated to those of the 3D spiral readout. By visual evaluation, the image quality of 3D-PSS pCASL was superior to that of 2D-EPI. The 3D-PSS technique was suggested useful as pCASL readout.
Assuntos
Artérias/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Imagem Ecoplanar/métodos , Imageamento Tridimensional/métodos , Neuroimagem/métodos , Marcadores de Spin , Adulto , Encéfalo/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Razão Sinal-RuídoRESUMO
PURPOSE: Noncontrast 4D-MR-angiography (MRA) using arterial spin labeling (ASL) is beneficial because high spatial and temporal resolution can be achieved. However, ASL requires acquisition of labeled and control images for each phase. The purpose of this study is to present a new accelerated 4D-MRA approach that requires only a single control acquisition, achieving similar image quality in approximately half the scan time. METHODS: In a multi-phase Look-Locker sequence, the first phase was used as the control image and the labeling pulse was applied before the second phase. By acquiring the control and labeled images within a single Look-Locker cycle, 4D-MRA was generated in nearly half the scan time of conventional ASL. However, this approach potentially could be more sensitive to off-resonance and magnetization transfer (MT) effects. To counter this, careful optimizations of the labeling pulse were performed by Bloch simulations. In in-vivo studies arterial visualization was compared between the new and conventional ASL approaches. RESULTS: Optimization of the labeling pulse successfully minimized off-resonance effects. Qualitative assessment showed that residual MT effects did not degrade visualization of the peripheral arteries. CONCLUSION: This study demonstrated that the proposed approach achieved similar image quality as conventional ASL-MRA approaches in just over half the scan time. Magn Reson Med 79:224-233, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Assuntos
Angiografia/métodos , Interpretação de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética/métodos , Aceleração , Adulto , Angiografia Digital , Artérias , Simulação por Computador , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Ondas de Rádio , Marcadores de Spin , Fatores de Tempo , Adulto JovemRESUMO
A proportion of angiotensin II type 1 receptor blockers (ARBs) improves glucose dyshomeostasis and insulin resistance in a clinical setting. Of these ARBs, telmisartan has the unique property of being a partial agonist for peroxisome proliferator-activated receptor γ (PPARγ). However, the detailed mechanism of how telmisartan acts on PPARγ and exerts its insulin-sensitizing effect is poorly understood. In this context, we investigated the agonistic activity of a variety of clinically available ARBs on PPARγ using isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) system. Based on physicochemical data, we then reevaluated the metabolically beneficial effects of telmisartan in cultured murine adipocytes. ITC and SPR assays demonstrated that telmisartan exhibited the highest affinity of the ARBs tested. Distribution coefficient and parallel artificial membrane permeability assays were used to assess lipophilicity and cell permeability, for which telmisartan exhibited the highest levels of both. We next examined the effect of each ARB on insulin-mediated glucose metabolism in 3T3-L1 preadipocytes. To investigate the impact on adipogenesis, 3T3-L1 preadipocytes were differentiated with each ARB in addition to standard inducers of differentiation for adipogenesis. Telmisartan dose-dependently facilitated adipogenesis and markedly augmented the mRNA expression of adipocyte fatty acid-binding protein (aP2), accompanied by an increase in the uptake of 2-deoxyglucose and protein expression of glucose transporter 4 (GLUT4). In contrast, other ARBs showed only marginal effects in these experiments. In accordance with its highest affinity of binding for PPARγ as well as the highest cell permeability, telmisartan superbly activates PPARγ among the ARBs tested, thereby providing a fresh avenue for treating hypertensive patients with metabolic derangement.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Benzimidazóis/farmacologia , Benzoatos/farmacologia , PPAR gama/agonistas , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Animais , Benzimidazóis/química , Benzoatos/química , Calorimetria , Diferenciação Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular , Relação Dose-Resposta a Droga , Agonismo Parcial de Drogas , Membranas Artificiais , Camundongos , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Ressonância de Plasmônio de Superfície , TelmisartanRESUMO
RecQ-mediated genome instability 1 (RMI1) has been identified as a novel energy homeostasis-related molecule. While recent studies have suggested that change in RMI1 expression levels in adipose tissue may affect the body's energy balance, no reports have identified the mechanism behind this expression regulation. In the present study, we found that RMI1 expression increased on differentiation of 3T3-L1 fibroblasts to adipocytes. In addition, glucose stimulation induced RMI1 expression to approximately eight times the baseline level. Further, knockdown of either E2F5 or E2F8 mRNA using siRNA suppressed this glucose-induced up-regulation of RMI1 expression. These results suggest that RMI1 expression may be regulated by glucose, at least in part, via E2F expression.
Assuntos
Tecido Adiposo/metabolismo , Proteínas de Transporte/metabolismo , Fatores de Transcrição E2F/metabolismo , Glucose/farmacologia , Proteínas Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Animais , Diferenciação Celular/fisiologia , Proteínas de Ligação a DNA , Fatores de Transcrição E2F/efeitos dos fármacos , Fatores de Transcrição E2F/genética , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Camundongos , Modelos Animais , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologiaRESUMO
The escalating prevalence of obesity is one of the most pressing health concerns of the modern era, yet existing medicines to combat this global pandemic are disappointingly limited in terms of safety and effectiveness. The inadequacy of currently available therapies for obesity has made new drug development crucial. In the past several decades, however, major progress has been achieved in understanding adipocyte hyperplasia associated with the pathogenesis of obesity, and consequently new potential targets for the medical treatment of obesity have been identified. We primarily review recent progress in the regulation of adipocyte hyperplasia as a novel emerging nontraditional approach. In this minireview, we focus on recQ-mediated genome instability 1 (RMI1), a recently identified novel molecular target for obesity treatment. RMI1-deficient mice have been found to be resistant to high-fat diet- and genetics-related obesity. Expression of this protein is regulated by E2F transcription factors, and recent studies have suggested that RMI1 plays an important role in the control of energy homeostasis during the development of obesity, with a mode of action based on the regulation of adipocyte hyperplasia.
Assuntos
Adipócitos/metabolismo , Proteínas de Transporte/metabolismo , Proteínas Nucleares/metabolismo , Obesidade/metabolismo , Animais , Ciclo Celular , Humanos , Hiperplasia/metabolismo , Obesidade/tratamento farmacológico , Obesidade/patologiaAssuntos
Anticorpos Antinucleares/sangue , Antígenos Nucleares/imunologia , Proteínas de Ligação a DNA/imunologia , Polimiosite/complicações , Polimiosite/diagnóstico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Técnica Indireta de Fluorescência para Anticorpo/métodos , Humanos , Immunoblotting/métodos , Imunodifusão/métodos , Imunoprecipitação/métodos , Autoantígeno Ku , Manejo de EspécimesRESUMO
IMPORTANCE OF THE FIELD: Inositol polyphosphate 5-phosphatase (SHIP2) is an important negative regulator of intracellular phosphatidylinositol phosphate, a key second messenger of various intracellular signaling pathways. The functional upregulation of SHIP2 results in signaling blockade, leading to related disorders. AREAS COVERED IN THIS REVIEW: We first summarize the role of SHIP2 in the regulation of insulin signaling and type 2 diabetes, including remarkable advances in pharmacological approaches. In addition, this review highlights new findings regarding the involvement of SHIP2 in a number of diseases, including cancer, neurodegenerative diseases, and atherosclerosis. WHAT THE READER WILL GAIN: Recently identified small-molecule inhibitors of SHIP2 phosphatase activity emphasize the potential therapeutic value of SHIP2. In addition, currently available evidence demonstrates the importance of the scaffolding-type protein function of SHIP2. Understanding this interesting function will help clarify the complicated involvement of SHIP2 in various disorders. TAKE HOME MESSAGE: Recent studies have demonstrated that SHIP2 is a promising therapeutic target for not only type 2 diabetes, but also cancer, neurodegenerative diseases, and atherosclerosis. Targeting SHIP2 through specific small-molecule inhibitors will have beneficial effects on these diseases.
Assuntos
Fosfatos de Fosfatidilinositol/fisiologia , Monoéster Fosfórico Hidrolases/fisiologia , Regulação para Cima , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/fisiopatologia , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/fisiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Insulina/agonistas , Insulina/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/fisiopatologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Fosfatos de Fosfatidilinositol/agonistas , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/química , Estrutura Terciária de Proteína , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Lipid phosphatase SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) plays an important role in the regulation of insulin signaling. In this report, we identified AS1938909, a novel small-molecule SHIP2 inhibitor. AS1938909 showed potent inhibition of SHIP2 (Ki=0.44 microuM) and significant selectivity over other related phosphatases. Further, AS1938909 increased Akt phosphorylation, glucose consumption, and glucose uptake in L6 myotubes. Treatment of L6 myotubes with SHIP2 inhibitors for 48 h significantly induced expression of GLUT1 mRNA, but not that of GLUT4. These results suggest that pharmacological inhibition of SHIP2 activates glucose metabolism due, at least in part, to up-regulation of GLUT1 gene expression.
Assuntos
Inibidores Enzimáticos/farmacologia , Transportador de Glucose Tipo 1/genética , Glucose/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Regulação para Cima/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Camundongos , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RatosRESUMO
The aim of this study is to discover and characterize novel energy homeostasis-related molecules. We screened stock mouse embryonic stem cells established using the exchangeable gene trap method, and examined the effects of deficiency of the target gene on diet and genetic-induced obesity. The mutant strain 0283, which has an insertion at the recQ-mediated genome instability 1 (RMI1) locus, possesses a number of striking features that allow it to resist metabolic abnormalities. Reduced RMI1 expression, lower fasting-blood glucose and a reduced body weight (normal diet) were observed in the mutant mice. When fed a high-fat diet, the mutant mice were resistant to obesity, and also showed improved glucose intolerance and reduced abdominal fat tissue mass and food intake. In addition, the mutants were also resistant to obesity induced by the lethal yellow agouti (A(y)) gene. Endogenous RMI1 genes were found to be up-regulated in the liver and adipose tissue of KK-A(y) mice. RMI1 is a component of the Bloom's syndrome gene helicase complex that maintains genome integrity and activates cell-cycle checkpoint machinery. Interestingly, diet-induced expression of E2F8 mRNA, which is an important cell cycle-related molecule, was suppressed in the mutant mice. These results suggest that the regulation of energy balance by RMI1 is attributable to the regulation of food intake and E2F8 expression in adipose tissue. Taken together, these findings demonstrate that RMI1 is a novel molecule that regulates energy homeostasis.
Assuntos
Metabolismo Energético/genética , Obesidade/genética , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Dieta/efeitos adversos , Ingestão de Alimentos/fisiologia , Homeostase/genética , Camundongos , Obesidade/prevenção & controle , Proteínas Repressoras/genética , Regulação para CimaRESUMO
We have developed a sequence for abdominal examination that fat suppressed 3D-T1W by a linear filling order using an adiabatic pulse for frequency selective fat suppression. We simulated the change in fat signal using a linear method and checked the starting point of data filling for the null point using a phantom of different T1 values. We then checked the contrast between the fat signal and liver. After checking by using simulation, a clinical evaluation was done. The change in fat signal was mostly the same after the fourth shot, and we were able to estimate the null point of the fat signal by the following parameters: TR, FA, TFE factor, and shot interval. Consequently, we could control the starting point of data filling in k-space for fat suppression. The contrast between fat and liver was improved because noise was reduced by the linear method. The sequence developed with the linear filling order using frequency selective fat suppression pulse proved to be useful.
Assuntos
Imageamento por Ressonância Magnética/métodos , Gorduras , Humanos , Imageamento Tridimensional , Modelos Teóricos , Imagens de FantasmasRESUMO
More than 50 years have passed since glucocorticoid (GC) therapy was introduced into the treatment of rheumatoid arthritis (RA) . Although the effect of GC monotherapy on RA is limited to short-term and long-term GC treatment carries the risks of adverse effects and rebound phenomenon after the discontinuation, disease-modifying action of GC have been recently reported when used in combination with DMARDs. One of the important side effects associated with GC therapy is osteoporosis, and Japanese guidelines on the management and treatment of glucocorticoid -induced osteoporosis have been published recently. Further studies are necessary to elucidate long-term benefit-risk ratio of low-dose GC therapy on RA.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Medição de Risco , Antirreumáticos/administração & dosagem , Difosfonatos/uso terapêutico , Quimioterapia Combinada , Medicina Baseada em Evidências , Humanos , Guias de Prática Clínica como AssuntoRESUMO
To elucidate the clinical and histopathological features associated with autoantibodies to the signal recognition particle (SRP), we have studied 23 Japanese patients with this specificity among 3,500 patients with polymyositis/dermatomyositis and other connective tissue diseases. Anti-SRP antibodies were determined based on analysis of RNA and protein components by immunoprecipitation assays. The pathological analysis was performed by using special stainings including alkaline phosphatase, myosin ATPase, and modified Gomori trichrome stainings. Twenty-one (92%) of these 23 patients had myositis, 8 of whom (38%) required cytotoxic agents or intravenous immunoglobulin therapy in addition to corticosteroid therapy. Four patients (16%) had rheumatoid arthritis, two of whom had no features of myositis. Muscle biopsy specimens of 11 patients were examined histologically in detail. All 11 had muscle fiber necrosis and/or regeneration, but only one had infiltration of inflammatory cells. Six of the 11 (55%) patients showed type I fiber predominance by ATPase staining, while eight control myositis patients without anti-SRP antibodies did not. There was no correlation of other neurogenic features in histology with the presence of anti-SRP antibodies. These studies suggest that anti-SRP autoantibodies are most likely to be related to myopathies that are resistant to corticosteroid therapy and without inflammation histopathologically.
Assuntos
Autoanticorpos/sangue , Doenças Musculares/diagnóstico , Partícula de Reconhecimento de Sinal/imunologia , Adolescente , Adulto , Povo Asiático , Autoanticorpos/isolamento & purificação , Dermatomiosite/diagnóstico , Dermatomiosite/patologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Doenças Musculares/patologia , Polimiosite/diagnóstico , Polimiosite/patologiaRESUMO
While the brain does not utilize fatty acids as a primary energy source, recent evidence shows that intermediates of fatty acid metabolism serve as hypothalamic sensors of energy status. Increased hypothalamic malonyl-CoA, an intermediate in fatty acid synthesis, is indicative of energy surplus and leads to the suppression of food intake and increased energy expenditure. Malonyl-CoA functions as an inhibitor of carnitine palmitoyl-transferase 1 (CPT1), a mitochondrial outer membrane enzyme that initiates translocation of fatty acids into mitochondria for oxidation. The mammalian brain expresses a unique homologous CPT1, CPT1c, that binds malonyl-CoA tightly but does not support fatty acid oxidation in vivo, in hypothalamic explants or in heterologous cell culture systems. CPT1c knockout (KO) mice under fasted or refed conditions do not exhibit an altered CNS transcriptome of genes known to be involved in fatty acid metabolism. CPT1c KO mice exhibit normal levels of metabolites and of hypothalamic malonyl-CoA and fatty acyl-CoA levels either in the fasted or refed states. However, CPT1c KO mice exhibit decreased food intake and lower body weight than wild-type littermates. In contrast, CPT1c KO mice gain excessive body weight and body fat when fed a high-fat diet while maintaining lower or equivalent food intake. Heterozygous mice display an intermediate phenotype. These findings provide further evidence that CPT1c plays a role in maintaining energy homeostasis, but not through altered fatty acid oxidation.
Assuntos
Peso Corporal/fisiologia , Encéfalo/metabolismo , Carnitina O-Palmitoiltransferase/fisiologia , Ingestão de Alimentos/fisiologia , Ácidos Graxos/metabolismo , Animais , Peso Corporal/genética , Encéfalo/enzimologia , Células CHO , Células COS , Carnitina O-Palmitoiltransferase/genética , Sistema Nervoso Central/enzimologia , Sistema Nervoso Central/metabolismo , Chlorocebus aethiops , Cricetinae , Cricetulus , Ingestão de Alimentos/genética , Ácidos Graxos/genética , Feminino , Isoenzimas/genética , Isoenzimas/fisiologia , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Knockout , OxirreduçãoRESUMO
OBJECTIVE: To determine the efficacy and safety of intermittent cyclical etidronate therapy of up to 7 years for corticosteroid-induced osteoporosis. METHODS: One hundred two Japanese patients who originally participated in a 3-year prospective randomized study were enrolled into an open-label followup study. All patients had received > 7.5 mg of prednisolone daily for at least 90 days before entry into the original study and were randomly assigned to 2 treatment arms: E, those receiving etidronate disodium (200 mg per day) for 2 weeks together with 3.0 g of calcium lactate and 0.75 microg of alphacalcidol daily; and C, controls receiving only the latter. Endpoints included changes from baseline in bone mineral density (BMD) of the lumbar spine and the rate of new vertebral fractures. RESULTS: The mean (+/- SD) lumbar spine BMD had increased by 5.9% +/- 8.8% (p = 0.00007) and 2.2% +/- 5.8% (p = 0.013) from baseline after 7 years in groups E and C, respectively. This improvement in BMD in group E was significantly better than in group C (p = 0.02). The frequency of new vertebral fractures was lower in group E, resulting in reduction of the risk of such new fractures by 67% at year 7 (odds ratio 3.000; 95% confidence interval, 0.604 14.90; p = 0.18). There were no severe adverse events in group E during our study. CONCLUSION: Our results indicate that longterm (up to 7 years) intermittent cyclical etidronate therapy is safe and effective for prevention and treatment of corticosteroid-induced osteoporosis in patients with connective tissue diseases.
Assuntos
Corticosteroides/efeitos adversos , Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Doenças do Tecido Conjuntivo/tratamento farmacológico , Ácido Etidrônico/administração & dosagem , Osteoporose/prevenção & controle , Adulto , Conservadores da Densidade Óssea/efeitos adversos , Esquema de Medicação , Ácido Etidrônico/efeitos adversos , Feminino , Seguimentos , Humanos , Japão , Vértebras Lombares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , TempoRESUMO
Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and autoimmune diabetes are characterized by the production of autoantibodies that serve as useful diagnostic markers, surrogate markers, and prognostic factors. We devised an in vitro system to detect these clinically pivotal autoantibodies using a photoimmobilized autoantigen microarray. Photoimmobilization was useful for preparing the autoantigen microarray, where autoantigens are covalently immobilized on a plate, because it does not require specific functional groups of the autoantigens and any organic material can be immobilized by a radical reaction induced by photoirradiation. Here, we prepared the microarray using a very convenient method. Aqueous solutions of each autoantigen were mixed with a polymer of poly(ethylene glycol) methacrylate and a photoreactive crosslinker, and the mixtures were microspotted on a plate and dried in air. Finally, the plate was irradiated with an ultraviolet lamp to obtain immobilization. In the assay, patient serum was added to the microarray plate. Antigen-specific IgG adsorbed on the microspotted autoantigen was detected by peroxidase-conjugated anti-IgG antibody. The chemical luminescence intensities of the substrate decomposed by the peroxidase were detected with a sensitive CCD camera. All autoantigens were immobilized stably by this method and used to screen antigen-specific IgG. In addition, the plate was covered with a polydimethylsiloxane sheet containing microchannels and automated measurement was carried out.