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1.
Int J Food Sci Nutr ; 75(4): 426-435, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38557440

RESUMO

This randomised, placebo-controlled, double-blind, parallel-group study aimed to determine whether encapsulated Ashitaba chalcone (16 mg comprising 10.1 mg 4-hydroxyderricin and 5.9 mg xanthoangelol) could reduce obesity in 17 men and 25 women with a body mass index (BMI) of 25 to < 30. Participants ingested capsules containing either the chalcone or a placebo daily for 12 weeks. The primary endpoint was changes in visceral fat areas determined by computed tomography (CT) at baseline, and at 8 and 12 weeks later. The primary endpoint, abdominal visceral fat area, was significantly reduced in the chalcone, compared with a placebo group 12 weeks after screening (p < 0.05). The secondary endpoint, waist circumference, was significantly decreased in the chalcone, compared with the placebo group at weeks 8 and 12 (p < 0.05 at week 8; p < 0.01 at week 12). Therefore, Ashitaba chalcone has anti-obesity benefits for overweight men and women.


Assuntos
Chalcona , Gordura Intra-Abdominal , Sobrepeso , Circunferência da Cintura , Humanos , Masculino , Feminino , Método Duplo-Cego , Adulto , Pessoa de Meia-Idade , Gordura Intra-Abdominal/efeitos dos fármacos , Chalcona/análogos & derivados , Chalcona/farmacologia , Índice de Massa Corporal , Obesidade , Fármacos Antiobesidade/farmacologia
2.
J Orthop Sci ; 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37863683

RESUMO

BACKGROUND: This study aims to investigate the effect of pre-operative hemoglobin A1c (HbA1c) and pre-operative blood glucose control on the rate of surgical site infection (SSI) after posterior lumbar instrumentation surgery in diabetes mellitus (DM) patients. METHODS: A total of 1046 patients who had undergone posterior lumbar instrumentation surgery were reviewed. Based on pre-operative HbA1c, patients were divided into three groups: non-DM group, low HbA1c group (HbA1c < 7.0 % in DM) and high HbA1c group (≥7.0). As well, based on the status of blood glucose control in DM patients immediately before surgery, patients were divided into two groups: good control group (post-prandial blood glucose [PBG] < 200 mg/dl) and poor control group (≥200). The rate of SSI was compared among these groups. RESULTS: SSI occurred in 1.9 % in non-DM group, 2.4 % in low HbA1c group, and 9.3 % in high HbA1c group. Compared with non-DM group, high HbA1c group had significantly higher rate of SSI (p = 0.001). There was not statistically different between non-DM and low HbA1c groups (p = 0.550). SSI occurred in 2.2 % in good control group, and 10.2 % in poor control group. The rate of SSI was significantly lower in good control group (p = 0.013). CONCLUSION: This study showed that the rate of SSI after posterior lumbar instrumentation surgery tend to be higher in DM patients with high HbA1c. However, the rate might be reduced to the same level as that of non-DM group by lowering PBG to <200 mg/dl immediately before surgery.

3.
Biochem Biophys Res Commun ; 524(3): 723-729, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32035622

RESUMO

Recent research has revealed that glioblastoma (GBM) avoids the immune system via strong expression of indoleamine 2,3-dioxygenase 1 (IDO1). IDO1, an enzyme involved in tryptophan metabolism, is now proposed as a new target in GBM treatment, since several reports have demonstrated that IDO1 expression is related to GBM malignancy. On the other hand, it is well known that glioma stem cells (GSCs) are strongly related to the malignancy of GBM. However, there is as yet no report evaluating the relationship between GSCs and IDO1. We therefore examined the expression levels of IDO1 in GSCs in order to identify a new therapeutic target for GBM based on the immune systems of GSCs. In the present study, we employed human GBM cell lines (U-138MG, U-251MG) and patient-derived GSC model cell lines (0125-GSC, 0222-GSC). GSC model cell lines Rev-U-138MG and Rev-U-251MG were established by culturing U-138MG and U-251MG in serum-free media, while differentiated GBM model cell lines 0125-DGC and 0222-DGC were established by culturing 0125-GSC and 0222-GSC in serum-containing media. The expression levels of stem cell markers (Nanog, Nestin, Oct4 and Sox2) and IDO1 protein and mRNA were determined. Rev-U-138MG and Rev-U-251MG formed spheres and their expression levels of stem cell markers were increased as compared to U-138MG and U-251MG. On the other hand, 0125-DGC and 0222-DGC suffered breakdown of sphere formation, despite the original 0125-GSC and 0222-GSC forming spheres, and their expression levels of the markers were decreased. IDO1 expressions were strongly recognized in Rev-U-138MG, Rev-U-251MG, 0125-GSC and 0222-GSC as compared to U-138MG, U-251MG, 0125-DGC and 0222-DGC. These findings demonstrate that GSCs exhibit treatment resistance with immunosuppression via high expression levels of IDO1, and could represent a novel target for GBM treatment.


Assuntos
Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Glioma/enzimologia , Glioma/patologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Células-Tronco Neoplásicas/enzimologia , Células-Tronco Neoplásicas/patologia , Linhagem Celular Tumoral , Meios de Cultura Livres de Soro , Glioblastoma/patologia , Humanos , Interferon beta/metabolismo
4.
J Cell Physiol ; 234(8): 13510-13524, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30613977

RESUMO

Interferon ß (IFN-ß) is considered a signaling molecule with important therapeutic potential in cancer since IFN-ß-induced gene transcription mediates antiproliferation and cell death induction. Whereas, TNF-related apoptosis inducing ligand/Apo2 ligand (TRAIL/Apo2L) has emerged as a promising anticancer agent because it induces apoptosis specifically in cancer cells. In this study, we elucidated that IFN-ß augments TRAIL-induced apoptosis synergistically using five human malignant melanoma cells. All of these cells were induced apoptosis by TRAIL. Whereas, the response against IFN-ß was different in amelanotic cells (A375 and CRL1579) and melanotic cells (G361, SK-MEL-28, and MeWo). The responsibility of amelanotic cells against IFN-ß was higher than those of melanotic cells. The synergism of IFN-ß and TRAIL were correlated with the responsibilities of the cells against IFN-ß. The synergistic interaction was confirmed by a combination index based on the Chou-Talalay method. The upregulation of apoptosis in amelanotic cells was caused by very low doses of IFN-ß (over 0.1 IU/ml). Both of p53-mediated intrinsic pathway and Fas-related extrinsic pathway were activated by IFN-ß alone and combination with TRAIL. Further, TRAIL death receptors (DR4 and DR5) were upregulated by a low-dose IFN-ß (over 0.1 IU/ml) and the expression was more promoted by the combination with TRAIL. It was clarified that the upregulation of DR5 is associated with the declination of viability.


Assuntos
Interferon beta/administração & dosagem , Melanoma/tratamento farmacológico , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Expressão Gênica/efeitos dos fármacos , Humanos , Melanoma/metabolismo , Melanoma/patologia , Melanoma Amelanótico/tratamento farmacológico , Melanoma Amelanótico/metabolismo , Melanoma Amelanótico/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Proteínas Recombinantes/administração & dosagem
5.
Opt Express ; 26(21): 27748-27756, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30469835

RESUMO

We demonstrate intense emission in the water-window soft x-ray spectral region by controlling the spectral behavior through changing the balance between emissivity and self-absorption in an expanding plasma. The number of photons obtained from a dual laser irradiated target with a 150-ps pre-pulse was maximized at 3.8 × 1014 photons/sr in λ = 2.34 - 4.38 nm at a pulse separation time of 7 - 10 ns. Enhancement of the number of photons is attributed to efficient coupling with the main laser pulse while maintaining a tiny source size.

6.
Opt Lett ; 43(15): 3750-3753, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30067671

RESUMO

The effect of optical thickness in a bismuth water-window soft x-ray source is considered by comparing the emission from laser-produced plasmas of a 7.5% atomic density foam target and a solid-density target. The number of photons recorded in the 4 nm region was comparable for both targets at a plasma-initiating laser pulse duration of 6 ns. From experiments at different pulse durations of 150 ps and 6 ns, self-absorption (opacity) effects were found to be relatively small for bismuth plasmas as compared to those of tin, based on the same emission mechanism and which are used in 13.5 nm sources for extreme ultraviolet lithography.

7.
Opt Lett ; 43(9): 2042-2045, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29714741

RESUMO

We demonstrated the upper limitation to the number of shots, i.e., target lifetime, together with the number of photons emitted in the water-window soft x-ray spectral region from a number of targets used as sources in this spectral region, for multi-shot irradiation at the same position on the target surface. The spectra involved result from unresolved transition arrays originating from n=3-n=4 transitions in medium-Z element plasmas and from n=4-n=4 transitions originating in high-Z plasmas. The output flux was maintained for the highest number of shots in the case of the high melting point element molybdenum, and the total output in the water window was 7.7×1013 photons/sr at a laser power density of 1.2×1014 W/cm2.

8.
Wilderness Environ Med ; 28(4): 327-331, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28927548

RESUMO

A 48-year-old man developed general fatigue, dyspnea, and fever at an altitude of 1562 m from the morning of the first day of a 3-day hike. Despite pharyngeal discomfort and mild general fatigue, he felt that the symptoms were not sufficient to abandon his plan. He usually required 1.5 hours to reach Tokusawa (6.4 km from the starting point at an altitude of 1500 m), but this time he required 2.5 hours and slept briefly upon arrival at Tokusawa due to extreme fatigue and respiratory discomfort. His symptoms became aggravated, so he presented at a mountain clinic with oxygen saturation at 80% and body temperature of 37.6ºC. He was diagnosed with hypoxemia due to pneumonia and/or other disease(s) and was evacuated to a hospital where a chest computed tomography scan revealed ground glass opacity and infiltrative shadows. He was treated for pneumonia, but another doctor discovered during follow-up that the patient had sprayed 300 mL of a waterproofing aerosol on mountain equipment in a nonventilated, enclosed area of his home on the night before starting out on the hike. Therefore, waterproofing spray was considered to have caused pulmonary damage. Self-reporting or appropriate questionnaires are the only means of identifying this type of injury. The differential diagnosis of pulmonary problems in an outdoor setting should include toxic aerosol exposure from waterproofing spray.


Assuntos
Lesão Pulmonar/diagnóstico , Recreação , Aerossóis , Diagnóstico Diferencial , Humanos , Japão , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade
9.
Kyobu Geka ; 70(7): 525-527, 2017 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-28698421

RESUMO

We report a case of 39-year-old man who developed tricuspid valve infective endocarditis with a complication of pulmonary embolism. He was transferred to our institution because of intermittent fever and enlargement of the vegetation of the tricuspid valve in spite of optimal antibiotics treatment. Computed tomography revealed pulmonary embolism, and transesophageal echocardiography showed a large and mobile vegetation (22×10 mm) on the tricuspid valve with moderate regurgitation. In addition, Streptococcus agalactiae was identified in blood cultures. The patient underwent surgical resection of the vegetation followed by tricuspid valve repair including De Vega's annuloplasty. Antibiotic therapy was continued for 4 weeks after surgery, and he was discharged on the 31st postoperative day. No endocarditis nor tricuspid valve dysfunction has re-occurred.


Assuntos
Miocardite/cirurgia , Embolia Pulmonar/complicações , Insuficiência da Valva Tricúspide/cirurgia , Adulto , Antibacterianos/uso terapêutico , Procedimentos Cirúrgicos Cardíacos , Humanos , Masculino , Miocardite/tratamento farmacológico , Miocardite/microbiologia , Streptococcus agalactiae/isolamento & purificação , Insuficiência da Valva Tricúspide/microbiologia
10.
Acta Derm Venereol ; 96(3): 309-13, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26350793

RESUMO

Inter-observer agreement is problematic in the histopathological diagnosis of melanoma and melanocytic naevi, even among expert pathologists. Formaldehyde-induced fluorescence (FIF) has been used for histochemical demonstration of catecholamines, 5-hydroxytryptamine and their immediate precursors. FIF can detect melanogenic activity and may be useful in differentiating malignant melanoma from other melanocytic lesions. The fluorescence of various types of melanocytic lesions has been previously studied quantitatively in formalin-fixed and paraffin-embedded sections. This study compared 2 sets of excitation and emission bands: 450-490 nm excitation/510-560 nm absorption filters (filter unit A) and 480 nm excitation/510< nm absorption filters (filter unit B). Higher FIF was observed with filter unit A than with filter unit B. FIF intensity of central regions was found to be higher than that of the peripheral regions. Mean FIF was significantly higher in malignant melanomas than in naevi. Fluorescence imaging with filter unit A gave better diagnostic performance. In conclusion, quantitative measurement of FIF is a useful marker of malignant potential.


Assuntos
Catecolaminas/análise , Fixadores/química , Formaldeído/química , Melanoma/química , Microscopia de Fluorescência , Nevo Pigmentado/química , Inclusão em Parafina , Neoplasias Cutâneas/química , Fixação de Tecidos/métodos , Biópsia , Diagnóstico Diferencial , Humanos , Melanoma/patologia , Nevo Pigmentado/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Neoplasias Cutâneas/patologia
11.
Biol Pharm Bull ; 37(12): 1872-81, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25451836

RESUMO

Hematopoiesis in the bone marrow (BM) and spleen is controlled by stromal cells. Inflammation promotes myelopoiesis and simultaneously suppresses B lymphopoiesis. However, the role of the reciprocal regulation of myelopoiesis and B lymphopoiesis by stromal cells during inflammation is not fully understood. We investigated inflammation-induced alteration of hematopoietic regulation in lipopolysaccharide (LPS)-treated mice. C57BL/6 female mice were intravenously injected with a single, 5-µg dose of LPS, which induced a rapid decrease in the number of granulocyte-macrophage progenitors (colony-forming unit granulocyte-macrophage; CFU-GM) and B cell progenitors (CFU-preB) in BM. The CFU-GM count rapidly recovered, whereas the recovery of CFU-preB was delayed. LPS induced a marked increase in the number of CFU-GM but not in the number of CFU-preB in spleen. After LPS treatment, gene expression levels of positive regulators of myelopoiesis such as granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in BM and spleen were markedly upregulated whereas levels of positive regulators for B lymphopoiesis such as stromal cell-derived factor (SDF)-1, stem cell factor (SCF), and IL-7 remained unchanged. Meanwhile, the negative regulator of B lymphopoiesis tumor necrosis factor (TNF)-α was markedly up-regulated. The number of CFU-GM in S-phase in BM increased after LPS treatment, whereas the number of CFU-preB in S-phase decreased. These results suggest that LPS-activated stromal cells induce positive-dominant regulation of myelopoiesis and negative-dominant regulation of B lymphopoiesis, which facilitates emergency myelopoiesis during inflammation by suppressing B lymphopoiesis, thereby contributing to the host defense against infection.


Assuntos
Lipopolissacarídeos/toxicidade , Linfopoese/efeitos dos fármacos , Mielopoese/efeitos dos fármacos , Animais , Linfócitos B/citologia , Linfócitos B/metabolismo , Medula Óssea/efeitos dos fármacos , Medula Óssea/fisiologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Progenitoras de Granulócitos e Macrófagos/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Baço/efeitos dos fármacos , Baço/fisiologia
12.
Sleep Med ; 113: 180-187, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042028

RESUMO

OBJECTIVE: The body's glucose concentration is influenced by carbohydrate intake, insulin-induced carbohydrate reduction, and hepatic glycogen breakdown induced by stress hormones. This study investigated the potential of employing glucose fluctuations as a measure of stress by examining the relationship between heart rate variability (HRV) data and glucose levels during sleep in healthy subjects. METHODS: In this cross-sectional study, a chest-worn electrocardiogram (ECG) and continuous glucose monitoring device (CGM) were respectively used to monitor the heart rate intervals and glucose fluctuations of five subjects (two males, three females) during sleep. A time-series correlation analysis was performed on the HRV data extracted from heart rate intervals and the corresponding glucose fluctuation data. RESULTS: The time-series analysis of ECG and CGM data collected from subjects during sleep (n = 25 nights) revealed a moderate negative correlation between glucose levels and HRV, with a cross-correlation coefficient of r = -0.453. CONCLUSION: Similar to HRV, changes in stress levels can be detected by observing glucose fluctuations, particularly during sleep when the impact of food intake can be eliminated. Our findings highlight a significant correlation between glucose levels and HRV, indicating that glucose fluctuations can be used as an indicator of autonomic nervous system activity in an exploratory study.


Assuntos
Automonitorização da Glicemia , Glucose , Masculino , Feminino , Humanos , Frequência Cardíaca/fisiologia , Estudos Transversais , Glicemia , Sono/fisiologia
13.
FEBS J ; 290(22): 5373-5394, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37552474

RESUMO

Premelanosome protein (PMEL), a melanocyte-specific glycoprotein, has an essential role in melanosome maturation, assembling amyloid fibrils for melanin deposition. PMEL undergoes several post-translational modifications, including N- and O-glycosylations, which are associated with proper melanosome development. C-mannosylation is a rare type of protein glycosylation at a tryptophan residue that might regulate the secretion and localization of proteins. PMEL has one putative C-mannosylation site in its core amyloid fragment (CAF); however, there is no report focusing on C-mannosylation of PMEL. To investigate this, we expressed recombinant PMEL in SK-MEL-28 human melanoma cells and purified the protein. Mass spectrometry analyses demonstrated that human PMEL is C-mannosylated at multiple tryptophan residues in its CAF and N-terminal fragment (NTF). In addition to the W153 or W156 residue (CAF), which lies in the consensus sequence for C-mannosylation, the W104 residue (NTF) was C-mannosylated without the consensus sequence. To determine the effects of the modifications, we deleted the PMEL gene by using CRISPR/Cas9 technology and re-expressed wild-type or C-mannosylation-defective mutants of PMEL, in which the C-mannosylated tryptophan was replaced with a phenylalanine residue (WF mutation), in SK-MEL-28 cells. Importantly, fibril-containing melanosomes were significantly decreased in W104F mutant PMEL-re-expressing cells compared with wild-type PMEL, observed using transmission electron microscopy. Furthermore, western blot and immunofluorescence analysis suggested that the W104F mutation may cause mild endoplasmic reticulumretention, possibly associated with early misfolding, and lysosomal misaggregation, thus reducing functional fibril formation. Our results demonstrate that C-mannosylation of PMEL is required for proper melanosome development by regulating PMEL-derived fibril formation.


Assuntos
Amiloide , Triptofano , Humanos , Glicosilação , Triptofano/genética , Triptofano/metabolismo , Amiloide/química , Melanossomas/genética , Melanossomas/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Proteínas Amiloidogênicas/metabolismo , Antígeno gp100 de Melanoma/genética , Antígeno gp100 de Melanoma/química , Antígeno gp100 de Melanoma/metabolismo
14.
Medicine (Baltimore) ; 101(35): e30471, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107519

RESUMO

Early diagnosis of malignant melanoma is critical for effective treatment and reduced patient mortality. However, current clinical and histological variables show limited accuracy in diagnosis. Serum or urine level of 5-S-cysteinyldopa (5-S-CD) is a commonly used melanoma biomarker in Japan owing to its increased sensitivity compared with other melanoma markers. However, its use as a diagnostic marker has shown some limitations. Therefore, here we examined the combination of 5-S-CD with melanoma inhibitory activity, which showed sensitivity in detecting melanoma comparable with that of 5-S-CD, and interleukin-8, a cytokine linked with melanoma progression, in a cohort of Japanese patients with melanoma. Our results revealed that the triple combination of 5-S-CD, melanoma inhibitory activity, and interleukin-8 showed high diagnostic accuracy in detecting melanoma compared with each of the individual factors. Importantly, the triple marker showed specificity and utility in detecting early-stage melanoma. Our results suggest the utility of the triple marker as a diagnostic biomarker for melanoma patients.


Assuntos
Cisteinildopa , Melanoma , Biomarcadores Tumorais , Citocinas , Humanos , Interleucina-8 , Melanoma/patologia , Neoplasias Cutâneas , Melanoma Maligno Cutâneo
15.
Oncol Rep ; 48(6)2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36281939

RESUMO

Patients with glioblastoma frequently suffer epileptic seizures and often require anticonvulsant therapy during the treatment course. The present study investigated four common antiepileptic drugs, perampanel, carbamazepine (CBZ), sodium valproate (VPA) and levetiracetam (LEV), which are expected to have antitumor effects, and determined the most beneficial drug for the treatment of malignant glioma by comparing antitumor effects such as inhibition of cell proliferation and suppression of migration and invasion (using Transwell assays). The inhibition of cell growth was investigated using six malignant glioma cell lines (A­172, AM­38, T98G, U­138MG, U­251MG and YH­13). Significant inhibition of cell proliferation was observed in all six cell lines treated with perampanel, three cell lines treated with CBZ, four cell lines treated with VPA and two cell lines treated with LEV at the therapeutic blood concentration levels for the drugs to be used as antiepileptics. Further antitumor effects in combination with temozolomide were investigated using T98G and U­251MG cell lines, and were confirmed in both cell lines with perampanel and in T98G cells with LEV, but not observed with CBZ and VPA. Cell migration was significantly suppressed in both T98G and U­251MG cell lines with perampanel, but not with CBZ, VPA or LEV. To investigate the mechanisms by which perampanel suppresses the migration of malignant glioma cells, the expression of mRNA related to epithelial­mesenchymal transition following perampanel treatment was analyzed using reverse transcription­quantitative PCR in the T98G and U­251MG cell lines. The expression of Rac1 and RhoA, which constitute the cytoskeleton that enhances cell motility, were reduced in both cell lines. Furthermore, the expression of the mesenchymal marker N­cadherin, which promotes cell migration and infiltration, was decreased, but the expression of the epithelial marker E­cadherin, which strengthens cell­cell adhesion and reduces cell motility, was increased. Furthermore, the expression of matrix metalloproteinase­2, a proteolytic enzyme, was reduced. These effects may reduce cell motility and increase adhesion between cells, suggesting that perampanel treatment suppressed cell migration. In conclusion, the present study suggests that perampanel may be more beneficial in terms of antitumor efficacy than other antiepileptic drugs for the treatment of malignant glioma.


Assuntos
Anticonvulsivantes , Glioma , Humanos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Metaloproteinase 2 da Matriz , Ácido Valproico/farmacologia , Temozolomida , Glioma/tratamento farmacológico , Carbamazepina/uso terapêutico , Caderinas , RNA Mensageiro
16.
Gen Thorac Cardiovasc Surg ; 70(5): 419-429, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34613579

RESUMO

OBJECTIVE: We assessed the clinical effectiveness of coronary artery bypass grafting (CABG) in comparison with that of percutaneous coronary intervention (PCI) in octogenarians with triple-vessel disease (TVD) or left main coronary artery (LMCA) disease. METHODS: From the CREDO-Kyoto registry cohort-2, 527 patients, who were ≥ 80 years of age and underwent the first coronary revascularization for TVD or LMCA disease, were divided into the CABG group (N = 151) and the PCI group (N = 376). RESULTS: The median and interquartile range of patient's age was 82 (81-84) in the CABG group and 83 (81-85) in the PCI group (P = 0.10). Patients > = 85 years of age accounted for 19% and 31% in the CABG and PCI groups, respectively (P = 0.01). The cumulative 5-year incidence of all-cause death was similar between CABG and PCI groups (35.8% vs. 42.9%, log-rank P = 0.18), while CABG showed a lower rate of the composite of cardiac death/MI than PCI (21.7% vs. 33.9%, log-rank P = 0.005). After adjusting for confounders, the lower risk of CABG relative to PCI was significant for all-cause death (HR 0.61, 95% CI 0.43-0.86, P = 0.005), any coronary revascularization (HR 0.25, 95% CI 0.14-0.43, P < 0.001) and the composite of cardiac death/MI (HR 0.52, 95% CI 0.32-0.85, P = 0.009). CONCLUSIONS: CABG compared with PCI was associated with a lower adjusted risk for all-cause death, any coronary revascularization, and a composite of cardiac death/MI in very elderly patients with TVD or LMCA disease. CABG seemed an acceptable option for selected octogenarians with severe coronary artery disease.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Morte , Humanos , Octogenários , Intervenção Coronária Percutânea/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento
17.
Oncol Lett ; 24(6): 421, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36284648

RESUMO

Glioblastoma has a poor prognosis even after multimodal treatment, such as surgery, chemotherapy and radiation therapy. Patients with glioblastoma frequently develop epileptic seizures during the clinical course of the disease and often require antiepileptic drugs. Therefore, agents with both antiepileptic and antitumoral effects may be very useful for glioblastoma treatment. Perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist, is an antiepileptic drug that is widely used for intractable epilepsy. The present study aimed to assess the potential antitumoral effects of perampanel using malignant glioma cell lines. The cell proliferation inhibitory effect was evaluated using six malignant glioma cell lines (A-172, AM-38, T98G, U-138MG, U-251MG and YH-13). A dose-dependent inhibitory effect of perampanel on cell viability was demonstrated; however, the sensitivity of cells to perampanel varied and further antitumoral effects were demonstrated in combination with temozolomide (TMZ) in certain malignant glioma cells. Furthermore, cell cycle distribution and apoptosis induction analyses were performed in T98G and U-251MG cells using a fluorescence activated cell sorter (FACS) and the expression levels of apoptosis-related proteins were evaluated using western blotting. No significant change was demonstrated in the proportions of cells in the G0/G1, S and G2/M phases under 1.0 µM perampanel treatment, whereas induction of apoptosis was demonstrated using FACS at 10 µM perampanel and western blotting at 1.0 µM perampanel in both glioma cell lines. Overexpression of SERPINE1 may be related to poor prognosis in patients with gliomas. The combination of 1.0 µM perampanel and 5.0 µM tiplaxtinin, a SERPINE1 inhibitor, demonstrated further reduced cell viability in perampanel-resistant U-138MG cells, which have high expression levels of SERPINE1. These results indicated that the antitumor effect of perampanel may not be expected for malignant gliomas with higher expression levels of SERPINE1. The findings of the present study suggested that the antiepileptic drug perampanel may also have an antitumor effect through the induction of apoptosis, which is increased when combined with TMZ in certain malignant glioma cells. These findings also suggested that SERPINE1 expression may be involved in perampanel susceptibility. These results may lead to new therapeutic strategies for malignant glioma.

18.
Am J Dermatopathol ; 33(1): 60-4, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21239898

RESUMO

We carried out a histopathologic study of pilomatrixoma, a benign skin tumor, and also examined apoptosis and hair differentiation with the aim to understand the presence of amorphous debris and cyst formation in the tumor. Among 16 cases of pilomatrixoma examined, 11 were at the early regressive stage and 5 were at the late regressive stage according to the classification by Kaddu et al. In the former cases, tumor nests were basically composed of basophilic, transitional, and shadow cells. Cyst formation was evident in all cases and squamoid epithelium was observed in 4 cases at the early regressive stage. Amorphous debris was found in all cases including those at the late regressive stage. Immunohistochemical analysis revealed positive reaction products for ß-catenin and Lef-1 in basophilic and transitional cells, although their distribution differed. Immunoreactivity for ß-catenin was observed in the lower transitional cells, whereas immunoreactivity for Lef-1 was also evident in the upper transitional cells. Positive reactions for hair keratins were found in the cytoplasm of transitional and shadow cells, but not in the amorphous debris. Examination by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method revealed positive reactions in transitional and some shadow cells. These results suggest that in pilomatrixoma, production of hair keratin and induction of apoptosis may occur at the same time, and that unlike the normal hair follicle irregular expression of ß-catenin and Lef-1 results in the appearance of amorphous debris and cyst formation.


Assuntos
Apoptose , Diferenciação Celular , Doenças do Cabelo/patologia , Pilomatrixoma/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Doenças do Cabelo/metabolismo , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Lactente , Recém-Nascido , Queratinas Específicas do Cabelo/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/biossíntese , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pilomatrixoma/metabolismo , Neoplasias Cutâneas/metabolismo , beta Catenina/biossíntese
19.
Pediatr Dermatol ; 28(4): 412-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20738800

RESUMO

We recently encountered a 2-year-old boy with slightly infiltrative brown papules on the face, trunk, and extremities. Stroking of one of the papules produced an urticarial wheal (positive Darier's sign). Histopathologic tests revealed a dense infiltration of mast cells containing numerous granules and showing metachromasia under Toluidine blue staining. Immunohistochemical tests revealed that these cells were positive for CD68 and for c-kit. In addition, dermal dendritic cells that were positive for S100 and CD1a immunostaining were intermingled with the mast cells. We confirmed through electron microscopy that the dermal dendritic cells that were observed adjacent to the infiltration of mast cells had Birbeck granules in their cytoplasm, namely Langerhans cells. However, because of the greater numbers of mast cells than Langerhans cells, and because of the absence of both monomorphic LC proliferation and systemic symptoms of Langerhans cell histiocytosis, the present case favors a diagnosis of cutaneous mastocytosis in a child with Langerhans cell infiltration.


Assuntos
Células de Langerhans/metabolismo , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/metabolismo , Antígenos CD/metabolismo , Antígenos CD1/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Pré-Escolar , Ciproeptadina/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Células de Langerhans/efeitos dos fármacos , Células de Langerhans/patologia , Células de Langerhans/ultraestrutura , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Mastócitos/patologia , Mastocitose Cutânea/tratamento farmacológico , Mastocitose Cutânea/patologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas S100/metabolismo , Resultado do Tratamento
20.
Gen Thorac Cardiovasc Surg ; 69(12): 1580-1584, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34514539

RESUMO

Acquired pulmonary vein (PV) stenosis (PVS) is a complication following cardiac catheter intervention. However, very few cases of PVS after surgical ablation have been reported. We herein report a case of stenosis and occlusion at the left atrium to each pulmonary vein after surgical ablation. A 73-year-old woman who had received aortic valve replacement and pulmonary vein isolation 10 months earlier was diagnosed with congestive heart failure accompanied by pulmonary hypertension. Contrast-enhanced computed tomography revealed stenosis and complete occlusion of the left atrium to all four pulmonary veins. Surgical repair was performed via pericardial patch reconstruction of the left atrium to each PV. Treating multiple PV lesions with involvement of the left atrium wall requires tailored methods. However, there have been few reports concerning such methods of reconstruction. We herein report a method of reconstructing the left atrium and pulmonary veins at the same time.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Estenose de Veia Pulmonar , Idoso , Fibrilação Atrial/cirurgia , Feminino , Átrios do Coração , Humanos , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Estenose de Veia Pulmonar/diagnóstico por imagem , Estenose de Veia Pulmonar/etiologia , Estenose de Veia Pulmonar/cirurgia , Resultado do Tratamento
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