RESUMO
OBJECTIVES: To evaluate the clinical characteristics of oligometastatic disease (OMD) in metastatic urothelial carcinoma (mUC) with visceral metastases when classified into synchronous and metachronous metastases. METHODS: Of 957 cases of de novo mUC treated between 2008 and 2023, 374 with visceral metastases were analyzed. Cases were classified into OMD with up to three metastatic lesions and polymetastatic disease (PMD), and into synchronous and metachronous metastases. The clinical characteristics and overall survival (OS) for each group were analyzed. RESULTS: Overall, 196 (52.4%) had synchronous metastasis and 178 (47.6%) had metachronous metastasis. Median OS for synchronous metastases was significantly shorter than for metachronous metastases (12.1 months vs. 15.3 months, p = 0.011). Among the synchronous metastases, 48 (24.5%) were OMD and 148 (75.6%) were PMD. There was no significant difference in OS between the OMDs and PMDs (median 14.9 months vs. 11.7 months, p = 0.32), and only decreased albumin level was identified as a significant predictor of poor OS. Among the metachronous metastases, 64 (36.0%) were OMD and 114 (64.0%) were PMD. There was no significant difference in OS between the OMD and PMD (median 21.2 months vs. 15.0 months, p = 0.35), and no significant predictors of poor OS were identified. CONCLUSIONS: For mUC with visceral metastases, the timing of metastasis appearance was associated with prognosis, with synchronous metastases being a poorer prognostic factor compared to metachronous metastases. There was no prognostic difference between OMD and PMD with visceral metastases when classified into synchronous or metachronous metastases.
RESUMO
BACKGROUND: This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. METHODS: This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. RESULTS: During the median follow-up period of 7.3 months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2 g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42 mg/L was a significant prognostic factor for OS (p = 0.001). CONCLUSION: The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.
Assuntos
Anticorpos Monoclonais Humanizados , Humanos , Masculino , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso de 80 Anos ou mais , Resistencia a Medicamentos Antineoplásicos , Adulto , Biomarcadores Tumorais , Antineoplásicos Imunológicos/uso terapêutico , Intervalo Livre de Progressão , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/mortalidade , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , NeutrófilosRESUMO
Chronic fatigue and central fatigue with malaise significantly impair quality of life. Inattention caused by central fatigue is closely related to attention deficit/hyperactivity disorder (ADHD) symptoms, but the neurochemical mechanism of central fatigue remains hypothetical. The serotonin hypothesis of central fatigue was proposed first, serving as the central dogma for the molecular and neural mechanisms of central fatigue, and underpinning many studies. The tryptophan hypothesis was proposed because tryptophan released into the synaptic cleft of neurons in the brain coincides with and responds sensitively to development of fatigue. Tryptophan is highly bioactive, with brain concentrations of 50 to 200 times that of serotonin. The tryptophan-kynurenic acid-synergy hypothesis posits that central fatigue is not monocausal but a synergistic effect between tryptophan itself and its catabolite kynurenic acid. Central fatigue is associated with mental health problems and is a cause of inattention, thereby warranting scrutiny for its relationship with ADHD. Fatigability in ADHD is mediated by tryptophan, in which abnormal enhancement of the tryptophan-kynurenine-kynurenic acid pathway causes an imbalance in monoamine nervous system function. Notably, noradrenergic neuronal dysfunction is associated with the characteristic inattention of ADHD. Neutral amino acids such as branched-chain amino acids (BCAAs) can assist recovery from attentional and cognitive decline caused by central fatigue. Since they are transported by the same L-amino acid transporter as tryptophan, BCAAs compete with tryptophan to inhibit its brain uptake. Controlling central fatigue this way may improve attentional cognitive performance.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Aminoácidos de Cadeia Ramificada/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Cognição , Humanos , Ácido Cinurênico , Qualidade de Vida , Serotonina/metabolismo , Triptofano/metabolismoRESUMO
BACKGROUND/AIM: Guided bone regeneration (GBR) is one of the surgical methods used for vertical ridge augmentation prior to dental implant placements. Titanium meshes have been used for osteogenic space maintenance in GBR sites by clinicians. We aimed to compare the influence of micropores and macropores in a titanium mesh on bone regeneration in a rat calvarial vertical GBR model. MATERIALS AND METHODS: The calvaria of nine rats were exposed, and plastic cylinders were set bilaterally. Eighteen surgical sites were randomly allocated into three groups according to the materials of titanium lid and bone substitutes: microporous titanium lid+deproteinized bovine bone mineral (DBBM), macroporous titanium lid +DBBM, microporous titanium lid+carbonate apatite. Newly generated bone inside the cylinders was evaluated using micro-computed tomography (micro-CT). Furthermore, bone regeneration and angiogenesis were evaluated histologically at 12 weeks. RESULTS: Quantitative volumetric analyses using micro-CT showed a gradual increase in bone volume inside the cylinders in all three groups. Histological observation confirmed vigorous bone regeneration in the microporous groups compared to that in the macroporous group. In the upper part of the cylinders, soft tissue invaded the GBR site by passing through the pores of the macroporous mesh. The blood vessels in the upper part of the cylinders were smaller in the microporous groups than in the macroporous group. There was no difference in bone formation between cylinders filled with DBBM or carbonate apatite. CONCLUSION: Microvasculature penetrates 50-µm diameter micropores and accelerates bone formation inside the cylinder, which was set on rat calvaria. The microporous titanium mesh can facilitate angiogenesis from both the dura mater and periosteal in vertical ridge augmentation. Our data showed superiority of microporous titanium vascular permeability and osteoconductivity, supporting bone growth.
Assuntos
Telas Cirúrgicas , Titânio , Animais , Regeneração Óssea , Bovinos , Porosidade , Ratos , Microtomografia por Raio-XRESUMO
INTRODUCTION: Glycogen synthase kinase-3ß (GSK-3ß) is a serine/threonine kinase and a negative regulator of cardiac hypertrophy. Phosphorylation of GSK-3ß at Ser9 negatively regulates its kinase activity. The role of GSK-3ß in cardiac aging remains poorly understood. AIM: The study aimed to elucidate the role of GSK-3ß Ser9 phosphorylation in mediating cardiac aging and the underlying mechanism. METHODS AND RESULTS: Phosphorylation of GSK-3ß at Ser9 and the levels of ß-catenin and Mcl-1 were increased in the mouse heart during aging, suggesting that GSK-3ß is inactivated during aging in the heart. Age-induced cardiac hypertrophy, fibrosis, left ventricular dysfunction, and increases in cardiomyocyte apoptosis and senescence were all attenuated in constitutively active GSK-3ßS9A knock-in (KI) mice compared to littermate wild type mice. Although autophagy is inhibited in the heart during aging, KI of GSK-3ßS9A reversed the age-associated decline in autophagy in the mouse heart. GSK-3ß directly phosphorylates Ulk1, a regulator of autophagy, at Ser913, thereby stimulating autophagy in cardiomyocytes. Ulk1Ser913A KI mice exhibited decreased autophagic flux and increased senescence in cardiomyocytes. CONCLUSION: Our results suggest that GSK-3ß is inactivated during aging through Ser9 phosphorylation, which in turn plays an important role in mediating cardiac aging. GSK-3ß promotes autophagy through phosphorylation of Ulk1 at Ser913, which in turn prevents aging in the heart.
RESUMO
Previous research has shown that rope jumping improves physical health; however, little is known about its impact on brain-derived monoamine neurotransmitters associated with cognitive regulation. To address these gaps in the literature, the present study compared outcomes between 15 healthy participants (mean age, 23.1 years) after a long-rope jumping exercise and a control condition. Long-rope jumping also requires co-operation between people, attention, spatial cognition, and rhythm sensation. Psychological questionnaires were administered to both conditions, and Stroop task performance and monoamine metabolite levels in the saliva and urine were evaluated. Participants performing the exercise exhibited lower anxiety levels than those in the control condition. Saliva analyses showed higher 3-methoxy-4-hydroxyphenylglycol (a norepinephrine metabolite) levels, and urine analyses revealed higher 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid (a serotonin metabolite) levels in the exercise condition than in the control. Importantly, urinary 5-hydroxyindoleacetic acid level correlated with salivary and urinary 3-methoxy-4-hydroxyphenylglycol levels in the exercise condition. Furthermore, cognitive results revealed higher Stroop performance in the exercise condition than in the control condition; this performance correlated with salivary 3-methoxy-4-hydroxyphenylglycol levels. These results indicate an association between increased 3-methoxy-4-hydroxyphenylglycol and attention in long-rope jumping. We suggest that long-rope jumping predicts central norepinephrinergic activation and related attention maintenance.
RESUMO
BACKGROUND/PURPOSE: Fibroblast growth factor-2 (FGF-2) regulates bone formation. The concept of guided bone regeneration using a resorbable collagen membrane (RCM) is generally accepted in implant dentistry. This study aimed to investigate the bone healing pattern in rat mandibular bone defects in real-time with and without RCM containing FGF-2 (RCM/FGF-2). MATERIALS AND METHODS: Critical-size circular bone defects (4.0â¯mm diameter) were created on both sides of the rat mandibular bone. The defects were randomly divided into the following groups: control, RCM alone, RCM containing low (0.5⯵g) or high (2.0⯵g) concentration of FGF-2. We performed real-time in vivo micro-computerized tomography scans at the baseline and at 2, 4, and 6 weeks, and measured the volume of newly formed bone (NFB), bone mineral density (BMD) of NFB, and the closure percentage of the NFB area. At 6 weeks, the mandibular specimens were assessed histologically and histomorphometrically to evaluate the area of new bone regeneration. RESULTS: Real-time assessment revealed a significant increase in the volume, BMD, and closure percentage of the NFB area in the RCM/FGF-2-treated groups than that in the control and RCM groups. In the H-FGF-2 group, the volume and BMD of NFB exhibited a significant increase at 6 weeks than that at the baseline. Histological evaluation revealed the presence of osteoblasts, osteocytes, and blood vessels within the NFB. CONCLUSION: The real-time in vivo experiment demonstrated that RCM/FGF-2 effectively promoted bone regeneration within the critical-size mandibular defects in rats and verified new bone formation starting in the early postoperative phase.
RESUMO
BACKGROUND: Exercise-based cardiac rehabilitation (CR) improves health-related quality of life and exercise capacity in patients with heart failure (HF). However, CR efficacy in patients with HF who are elderly, frail, or have HF with preserved ejection fraction remains unclear. We examined whether participation in multidisciplinary outpatient CR is associated with long-term survival and rehospitalization in patients with HF, with subgroup analysis by age, sex, comorbidities, frailty, and HF with preserved ejection fraction. METHODS: This multicenter retrospective cohort study was performed in patients hospitalized for acute HF at 15 hospitals in Japan, 2007 to 2016. The primary outcome (composite of all-cause mortality and HF rehospitalization after discharge) and secondary outcomes (all-cause mortality and HF rehospitalization) were analyzed in outpatient CR program participants versus nonparticipants. RESULTS: Of the 3277 patients, 26% (862) participated in outpatient CR. After propensity matching for potential confounders, 1592 patients were included (n=796 pairs), of which 511 had composite outcomes (223 [14%] all-cause deaths and 392 [25%] HF rehospitalizations, median 2.4-year follow-up). Hazard ratios associated with CR participation were 0.77 (95% CI, 0.65-0.92) for composite outcome, 0.67 (95% CI, 0.51-0.87) for all-cause mortality, and 0.82 (95% CI, 0.67-0.99) for HF-related rehospitalization. CR participation was also associated with numerically lower rates of composite outcome in patients with HF with preserved ejection fraction or frail patients. CONCLUSIONS: Outpatient CR participation was associated with substantial prognostic benefit in a large HF cohort regardless of age, sex, comorbidities, frailty, and HF with preserved ejection fraction.
Assuntos
Reabilitação Cardíaca , Insuficiência Cardíaca/reabilitação , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/fisiopatologia , Avaliação Geriátrica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
In a 75-year-old hemodialysis patient, pneumonia manifested with computed tomography (CT) images suggestive of coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) was not detected with repeated polymerase chain reaction (PCR) tests, but serum immunoglobulin G (IgG) and IgM antibodies against SARS-CoV-2 turned positive with two different assay kits. The patient was thus treated as a probable COVID-19 case, and then recovered through the intensive care including ciclesonide, favipiravir, and methyl prednisolone. In PCR-negative cases, the diagnosis of COVID-19 cannot be established at present, but such COVID-19 cases certainly exist. To avoid a delay in treatment of COVID-19, available diagnostic tools should be utilized with careful attention for their limitations.
RESUMO
OBJECTIVES: The aim of this study was to investigate the impact of intensively lowered low-density lipoprotein cholesterol (LDL-C) level on the deferred lesion prognosis after revascularization deferral based on fractional flow reserve (FFR). BACKGROUND: Lowering LDL-C is associated with lower cardiovascular event rate, but its benefit on the deferred lesion prognosis has not been well evaluated. METHODS: This retrospective, single-center, observational study analyzed 192 deferred lesions with FFR value >0.80 in 192 patients with stable coronary artery disease. According to the first follow-up LDL-C level, they were assigned to the LOW group (<70 mg/dL) or the HIGH group (≥70 mg/dL). Deferred lesion failure (DLF) was defined as the composite of deferred lesion revascularization and deferred vessel myocardial infarction. RESULTS: Of all participants, 61 and 131 patients were assigned to the LOW and the HIGH group, respectively. During the median follow-up of 2.8 years, DLF occurred in 1 and 14 patients in the LOW group and the HIGH group (1.6% and 10.7%, log-rank p = .043), respectively. The incidence of any unplanned revascularization was also significantly lower in the LOW group than in the HIGH group (3.3% vs. 14.5%, log-rank p = .032). CONCLUSIONS: The incidence of DLF was significantly lower in the patients with LDL-C < 70 mg/dL than in those with LDL-C ≥ 70 mg/dL at the first follow-up after FFR-based deferral of revascularization.
Assuntos
Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Doença da Artéria Coronariana/terapia , Estenose Coronária/terapia , Dislipidemias/tratamento farmacológico , Revascularização Miocárdica , Idoso , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/etiologia , Estenose Coronária/fisiopatologia , Progressão da Doença , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/diagnóstico , Ezetimiba/uso terapêutico , Feminino , Reserva Fracionada de Fluxo Miocárdico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Tempo para o Tratamento , Resultado do TratamentoRESUMO
The Fawn-Hooded (FH) rat carries a gene mutation that results in a dysfunctional serotoninergic system. However, previous studies have reported differing features between the FH/Wjd and FH/Har strains. We aimed to compare the behavioural and neurobiological features of FH/HamSlc rats with those of Fischer 344 rats. We performed the open field, elevated minus-maze, Y-maze spontaneous alternation, and forced swim tests to investigate behavioural alterations. We also assessed neurobiological characteristics by quantifying monoamines and their related compounds in the prefrontal cortex, hippocampus, and striatum using high-performance liquid chromatography with an electrochemical detection system. FH/HamSlc rats showed hyperactivity and a high impulsivity tendency in the open field and the elevated minus maze test, but no cognitive dysfunction. In addition, the hyperactivity was suppressed immediately after the forced swim test. FH/HamSlc rats showed low dopamine levels, but high dopamine turnover in the striatum. Serotonin and noradrenaline levels were low in the prefrontal cortex and the hippocampus of FH/HamSlc rats, but high serotonin turnover was observed in the prefrontal cortex, hippocampus, and striatum. FH/HamSlc rats show (1) mania-like behavioural characteristics that are different from those of other strains of FH rats; (2) stimulus dependent suppression of hyperactivity similar to the clinical findings that exercise alleviates the symptoms of bipolar disorder; and (3) monoaminergic dysregulation such as monoamine imbalance and hyperturnover that may be associated with mania-related behavioural characteristics. Thus, the FH/HamSlc rat is a new animal model for mania including bipolar disorder.
RESUMO
BACKGROUND: While the evaluation of burr speed was discussed regarding platelet aggregation, the association between platform speed and acute lumen gain of rotational atherectomy remains unknown. METHODS: Through the evaluation of the potential of low-speed rotational atherectomy (LSRA) in in-vitro experiments, minimum lumen diameter (MLD) and minimum lumen area (MLA) after conventional high-speed rotational atherectomy (HSRA group) and those after LSRA following HSRA (LSRA+HSRA group) treated by 1.5 mm burrs were measured by optical frequency domain imaging (OFDI) in 30 consecutive human lesions. RESULTS: The in-vitro experiments demonstrated that MLD and MLA after LSRA+HSRA were significantly larger (MLD: LSRA+HSRA=1.50 ±0.05 mm, HSRA= 1.43 ±0.05 mm, p=0.015; MLA: LSRA+HSRA= 1.90 ±0.17 mm2, HSRA= 1.71±0.11 mm2, and p= 0.037), requiring more crossing attempts (LSRA= 134 ±20 times, HSRA= 72 ±11 times, and p< 0.001). In human studies, there was no significance in reference vessel diameter and lesion length before the procedure between two groups. MLDs after LSRA+HSRA were significantly larger than those in HSRA (LSRA+HSRA= 1.22 ±0.16 mm, HSRA= 1.07 ±0.14 mm, and p= 0.0078), while MLAs after LSRA+HSRA tended to be larger (LSRA+HSRA= 1.79 ±0.51 mm2, HSRA= 1.55 ±0.47 mm2, and p= 0.19). There was no significance in the occurrence of in-hospital complication, including slow flow or no reflow, major dissection, and procedural myocardial infarction, between LSRA+HSRA and HSRA. CONCLUSIONS: LSRA can achieve larger lumen gain compared, whereas HSRA can pass calcified lesions easily. Combination of LSRA and HSRA is a safe and feasible strategy for severely calcified lesions in clinical practice.
Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana , Vasos Coronários , Teste de Materiais/métodos , Intervenção Coronária Percutânea/métodos , Idoso , Aterectomia Coronária/efeitos adversos , Aterectomia Coronária/instrumentação , Aterectomia Coronária/métodos , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Desenho de Equipamento , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Cirurgia Assistida por Computador/métodos , Resultado do Tratamento , Calcificação Vascular/cirurgiaRESUMO
BACKGROUND: The purpose of this study was to clarify the implementation rate of multidisciplinary heart failure (HF) care and cardiac rehabilitation (CR) in Japan, as well as the relationship between implementation rates and characteristics of the facility.MethodsâandâResults:Survey participants were cardiologists who are members of the Japan Heart Failure Society and belonged to 1 of 845 medical institutions that are members of the Japan Heart Failure Society, as of April 2016. A total of 288 institutions (34.1%) returned the questionnaire. The percentages of hospitals implementing multidisciplinary HF care were 78.5% for inpatients and 32.6% for outpatients with HF. Inpatient and outpatient CR for HF had implementation rates of 80.4% and 56.5%, respectively. In addition, very few HF patients (7.3%, 3,741/51,323 patients) received outpatient CR. Both the presence of nurses certified in chronic HF care and registered CR instructors on staff were consistently associated with implementation of multidisciplinary HF care, and Japanese Circulation Society training hospitals, lower number of hospital beds, and presence of registered CR instructors on staff were consistently associated with implementation of CR. CONCLUSIONS: This first nationwide survey demonstrated that the implementation rates of multidisciplinary care and CR for HF, especially for outpatients, are low in Japan. Skilled healthcare professionals are expected to play important roles in the widespread implementation of this type of HF care in Japan.
Assuntos
Assistência Ambulatorial , Reabilitação Cardíaca , Insuficiência Cardíaca/terapia , Hospitais de Ensino , Inquéritos e Questionários , Estudos Transversais , Insuficiência Cardíaca/epidemiologia , JapãoAssuntos
Síndrome do Roubo Coronário-Subclávio/etiologia , Anastomose de Artéria Torácica Interna-Coronária/efeitos adversos , Esforço Físico , Síncope/etiologia , Circulação Coronária , Síndrome do Roubo Coronário-Subclávio/diagnóstico por imagem , Síndrome do Roubo Coronário-Subclávio/fisiopatologia , Síndrome do Roubo Coronário-Subclávio/terapia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Síncope/diagnóstico , Síncope/fisiopatologia , Síncope/prevenção & controle , Resultado do TratamentoRESUMO
The present study was designed to compare the bone augmentation ability of absorbable collagen sponge (ACS) with that of hydroxyapatite/collagen composite (HAP/Col) using a rat calvaria defect model. Bone defects were created artificially on the surface of the calvariae of 10-week-old male Fisher rats, and then cylindral plastic caps filled with ACS or HAP/Col were placed on the defects. This area was designated as the region of interest (ROI) and new bone formation was observed at 0, 4, 8, and 12 weeks after surgery using micro-CT. Histological examinations were performed using sections obtained from 12-week-old rats. Prominent new bone formation was observed in the HAP/Col group relative to the ACS group; onset of new bone augmentation was evident from 4 weeks after surgery in the HAP/Col group and from 8 weeks in the ACS group. Histological examination revealed that the entire area of the cap was filled with newly formed bone intermingled with the HAP/Col composite. Bone mineral density in the HAP/Col group was double that in the ACS group. These results indicate that the use of HAP/Col contributes significantly to new bone augmentation.
Assuntos
Implantes Absorvíveis , Regeneração Óssea/efeitos dos fármacos , Colágeno/farmacologia , Durapatita/farmacologia , Crânio/cirurgia , Animais , Densidade Óssea , Masculino , Ratos , Ratos Endogâmicos F344 , Crânio/diagnóstico por imagem , Microtomografia por Raio-XRESUMO
We used radiological and histological analyses to evaluate the effects of mechanical barrier permeability in a rat model of calvarial guided bone augmentation (GBA). The calvaria of 20 rats were exposed, and one of four types of plastic caps (an occlusive cylindrical plastic cap; a plastic cap with no top; a plastic cap with three holes; and a plastic cap with four holes) was randomly placed on both sides. Newly generated bone in the plastic caps was evaluated with micro-computed tomography (micro-CT) and histological analysis. Micro-CT volumetric analysis and decalcified hematoxylin and eosin-stained sections showed that GBA barrier permeability was inversely associated with the quantity of augmented bone obtained. Masson's trichrome staining showed that collagen in newly generated bony tissue was more mature in plastic caps with three holes than in those with more-permeable or more-occlusive barriers. Bone augmentation was inhibited in specimens exhibiting invasion of soft tissue through penetrating holes, and barrier permeability was associated with the quantity of augmented bone developed. In conclusion, moderate barrier permeability is optimal for development of mature augmented bone.
Assuntos
Regeneração Tecidual Guiada/instrumentação , Plásticos/farmacologia , Crânio/fisiologia , Animais , Desenho de Equipamento , Masculino , Modelos Animais , Permeabilidade , Ratos , Ratos Endogâmicos F344 , Crânio/diagnóstico por imagem , Coloração e Rotulagem , Microtomografia por Raio-XRESUMO
OBJECTIVES: To evaluate the effectiveness of the proximal optimization technique (POT) to prevent longitudinal stent elongation. BACKGROUND: The mechanism of stent elongation, which occurs after post-balloon dilation, is still unclear. METHODS: A total of 103 lesions treated with optical coherence tomography guided coronary intervention between May 2013 and November 2017 were retrospectively analyzed. Lesions were divided according to the circumferential degree of malapposition at the stent edge immediately after deployment into well-apposed group (<180°) and malapposed group (≥180°). Post-dilation was performed from distal to proximal within the stent until August 2016 (non-POT cohort), and POT was applied thereafter (POT cohort). In the POT cohort, post-dilation was done at the proximal portion of the stent with sufficiently large balloon to minimize malapposition followed by distal dilatations. Stent elongation length was defined as the change in stent length from stent deployment to after post-dilatation. RESULTS: In the non-POT cohort, 72 lesions, including 54 lesions in the well-apposed group and 18 in the malapposed group were analyzed. Stent elongation length was significantly longer in the malapposed group than in the well-apposed group (1.51 ± 1.34 mm vs 0.13 ± 0.84 mm, P < 0.01). In the POT cohort, 31 lesions including 21 in the well-apposed group and 10 in the malapposed group were analyzed. Stent elongation length was not significantly different between the groups (-0.09 ± 0.91 mm vs 0.30 ± 0.99 mm, P = 0.29). CONCLUSIONS: Malapposition of the stent edge is responsible for longitudinal stent elongation caused by post-dilatation. POT appeared to effectively prevent longitudinal stent elongation.
Assuntos
Angioplastia Coronária com Balão , Vasos Coronários , Stents/efeitos adversos , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Falha de Prótese , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos , Tomografia de Coerência Óptica/métodosRESUMO
The effect of estrogen deficiency in bone augmentation, and the mechanisms by which estrogen deficiency impedes osteoblast differentiation and collagen matrix production, were examined. Twenty female Jcl:Wistar rats were divided into two groups: ovariectomized rats; and control rats. Guided bone augmentation was performed by positioning plastic caps in the calvarium of all animals at 8 wk after ovariectomy or sham surgery. Micro-computed tomography and histological sections were used to determine the amount of bone augmentation within the plastic caps. At 8 wk, there was statistically significantly less newly formed bone volume in ovariectomized rats. Immunohistological staining revealed the rare alignment of runt-related transcription factor 2-positive osteoblast-like cells and collagen I-positive bundle fibers in ovariectomized rats. In cell culture experiments, pre-osteoblast-like cells, MC3T3-E1, were treated with the estrogen receptor antagonist, fulvestrant. In treated cells, alkaline phosphatase activity remained high, whereas Alizarin Red staining was completely inhibited. Extracellular staining intensity of collagen I was decreased after fulvestrant treatment. Consistent with these observations, gene-expression analysis confirmed that fulvestrant treatment led to weaker expression of mRNA for osteogenic transcription factors and bone matrix protein-related genes. The results demonstrate that estrogen deficiency suppresses osteoblast differentiation and collagen matrix production in bone augmentation.
Assuntos
Regeneração Óssea/fisiologia , Estrogênios/deficiência , Regeneração Tecidual Guiada , Osteoblastos/fisiologia , Animais , Diferenciação Celular , Subunidade alfa 1 de Fator de Ligação ao Core , Feminino , Osteoblastos/citologia , Ovariectomia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Microtomografia por Raio-XRESUMO
AIM: The aim of this study was to assess the acute and mid-term effects of drug-coated balloon (DCB) in terms of the healing process of non-flow-limiting dissections and changes in the neointimal area after DCB treatment using frequency domain optical coherence tomography (FD-OCT). PATIENTS AND METHODS: Thirty-six consecutive patients with in-stent restenosis pretreated with a scoring balloon were evaluated (19 and 17 patients with and without a DCB, respectively). FD-OCT was performed before and after each procedure during percutaneous coronary intervention and at 6 months of follow-up. RESULTS: Clinical characteristics and baseline FD-OCT findings were comparable between the two groups. No patient required stent implantation because of low-pressure DCB-related dissections. In the acute phase, the DCB distributed paclitaxel to the vessel wall without increasing dissections. The DCB did not reduce the neointimal area by itself. At 6 months, more dissections healed in the DCB group (-4.5±2.3 vs. -2.7±1.3, P=0.02). The DCB group showed less change in the neointimal area (-0.04±0.92 vs. 1.06±1.57 mm, P=0.03). CONCLUSION: The low-pressure DCB was not intended to expand the lumen, but instead to attach paclitaxel to the vessel wall by using FD-OCT examination. The DCB reduced the number of dissections and prevented neointimal proliferation during the mid-term follow-up.
Assuntos
Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/terapia , Vasos Coronários/diagnóstico por imagem , Neointima/diagnóstico por imagem , Idoso , Angina Instável/etiologia , Angiografia Coronária , Reestenose Coronária/complicações , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/patologia , Vasos Coronários/patologia , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Neointima/patologia , Paclitaxel/administração & dosagem , Intervenção Coronária Percutânea , Estudos Retrospectivos , Tomografia de Coerência Óptica , Moduladores de Tubulina/administração & dosagemRESUMO
Brain tryptophan and its neuroactive metabolites play key roles in central fatigue. However, previous brain function analysis targets may have included both glia and neurons together. Here, we clarified the fatigue-cognitive circuit of the central-peripheral linkage, including the role of glial-neuronal interaction in cognition. Using a rat model of central fatigue induced by chronic sleep disorder (CFSD), we isolated presynaptic terminals and oligodendrocytes. Results showed that compared to control group, presynaptic levels of tryptophan, kynurenine, and kynurenic acid, but not serotonin, in the CFSD group were higher in the hypothalamus and hippocampus. Moreover, CFSD group had higher oligodendrocytic levels of tryptophan, and impaired spatial cognitive memory accuracy and increased hyperactivity and impulsivity. These findings suggest that dynamic change in glial-neuronal interactions within the hypothalamus-hippocampal circuit causes central fatigue, and increased tryptophan-kynurenic acid pathway activity in this circuit causes reduced cognitive function. Additionally, CFSD group had 1.5 times higher plasma levels of tryptophan and kynurenine. Furthermore, in rats undergoing intraperitoneal administration of kynurenine (100mg/kg) versus vehicle, kynurenine-treated rats showed enhanced production of kynurenic acid in the hippocampus, with suppressed recall of retained spatial cognitive memory. The study revealed that uptake of periphery-derived kynurenine and tryptophan into the brain enhances kynurenic acid production in the brain, and the three factors produce amplification effect involved in the role of central-peripheral linkage in central fatigue, triggering cognitive dysfunction.