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1.
Artigo em Inglês | MEDLINE | ID: mdl-32618500

RESUMO

Amygdalin, prunasin, total cyanide and free cyanide concentrations in 12 powdered loquat seeds were investigated. Loquat (Eriobotrya japonica) is a species of flowering plant in the family Rosaceae, and its fruit is quite popular in Japan. Amygdalin and prunasin were measured using LC-MS/MS. Total cyanide was measured by enzymatic treatment, steam distillation and colorimetric quantification using the pyridine-pyrazolone method. Free cyanide was measured without enzymatic treatment. The mean concentrations of amygdalin, prunasin, total cyanide and free cyanide in powdered loquat seeds were 5900, 760, 410 and 44 mg/kg, respectively. The range of each quantitative value was extensive. Seven out of twelve samples were at risk for exceeding the acute reference dose (ARfD) of cyanide.

2.
Foods ; 9(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244617

RESUMO

Consumption of fish is rapidly increasing worldwide. It is important to evaluate fish fillet quality because fish undergoes physical and chemical changes during frozen storage. Fish fillets exhibit formaldehyde (FA) accumulation from the decomposition of trimethylamine N-oxide. FA is a powerful protein denaturant; thus, it is important to avoid FA buildup during fish processing to preserve fish quality, especially texture. To determine where FA accumulates, in order to maintain the quality of fish fillets, we performed matrix-assisted laser desorption/ionization mass spectrometry imaging, aiming to identify muscle-derived peptides, which reflect conditions such as denaturation and/or aggregation. We used frozen sections from which lipophilic molecules were washed out and detected various peptide peaks. Furthermore, we tried to identify indices to represent fish fillet softening by protease treatment. We could detect characteristic peaks owing to FA and protease treatment; the findings were consistent with the results of texture profiles showing fish fillet's real solidity. These molecules might thus serve as effective markers to evaluate fish fillet quality.

3.
Foods ; 8(12)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810360

RESUMO

Food contains various compounds, and there are many methods available to analyze each of these components. However, the large amounts of low-molecular-weight metabolites in food, such as amino acids, organic acids, vitamins, lipids, and toxins, make it difficult to analyze the spatial distribution of these molecules. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging is a two-dimensional ionization technology that allows the detection of small metabolites in tissue sections without requiring purification, extraction, separation, or labeling. The application of MALDI-MS imaging in food analysis improves the visualization of these compounds to identify not only the nutritional content but also the geographical origin of the food. In this review, we provide an overview of some recent applications of MALDI-MS imaging, demonstrating the advantages and prospects of this technology compared to conventional approaches. Further development and enhancement of MALDI-MS imaging is expected to offer great benefits to consumers, researchers, and food producers with respect to breeding improvement, traceability, the development of value-added foods, and improved safety assessments.

4.
J Neurosci ; 39(42): 8376-8385, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31451580

RESUMO

Although dysfunction of the mesolimbic dopaminergic system has been implicated in chronic pain, the underlying mechanisms remain to be elucidated. We hypothesized that increased inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area (VTA) during chronic pain may induce tonic suppression of the mesolimbic dopaminergic system. To test this hypothesis, male Sprague Dawley rats were subjected to spinal nerve ligation to induce neuropathic pain and then spontaneous IPSCs (sIPSCs) were measured in this neuronal pathway. Whole-cell patch-clamp electrophysiology of brain slices containing the dlBNST revealed that the frequency of sIPSCs significantly increased in VTA-projecting dlBNST neurons 4 weeks after surgery. Next, the role of corticotropin-releasing factor (CRF) signaling within the dlBNST in the increased sIPSCs was examined. CRF increased the frequency of sIPSCs in VTA-projecting dlBNST neurons in sham-operated controls, but not in chronic pain rats. By contrast, NBI27914, a CRF type 1 receptor antagonist, decreased the frequency of sIPSCs in VTA-projecting dlBNST neurons in the chronic pain rats, but not in the control animals. In addition, histological analyses revealed the increased expression of CRF mRNA in the dlBNST. Finally, bilateral injections of NBI27914 into the dlBNST of chronic pain rats activated mesolimbic dopaminergic neurons and induced conditioned place preference. Together, these results suggest that the mesolimbic dopaminergic system is tonically suppressed during chronic pain by enhanced CRF signaling within the dlBNST via increased inhibitory inputs to VTA-projecting dlBNST neurons.SIGNIFICANCE STATEMENT The comorbidity of chronic pain and depression has long been recognized. Although dysfunction of the mesolimbic dopaminergic system has been implicated in both chronic pain and depression, the underlying mechanisms remain to be elucidated. Here, we show that the inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area increase during chronic pain. This neuroplastic change is mediated by enhanced corticotropin-releasing factor signaling within the dlBNST that leads to tonic suppression of the mesolimbic dopaminergic system, which may be involved in the depressive mood and anhedonia under the chronic pain condition.

5.
Toxicol Rep ; 6: 692-702, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31372347

RESUMO

Citrus aurantifolia (Christm.) Swingle (syn. C. MEDICA var. ACIDA Brandis) (family: Rutaceae) essential oil is one of the cheapest oils found in local markets. Although, it is generally accepted as non-toxic to vital organs and cells, majority of people are cynical about it usage. Herein, the present study reports the chemical composition and in vivo oral toxicity study of unripe C. aurantifolia essential oil found in Ghana. The toxicity of C. aurantifolia essential oil extract was investigated via oral administration using two methods: The acute toxicity single dose study (SDS) and the repeated dose method. The oil exhibited no acute toxicity but in the sub-chronic studies, the effects was dose and time-dependent. Chemical profile investigation of the oil showed 9 constituent of phytochemicals (Germacrene isomers (61.2%), Pineen (14%), Linalool dimmer (2.9%), Bornane (11%), Citral (2.9%), Anethole (1.5%), Anisole (1.1%), Safrole (0.3%) and Demitol (0.6%)). Histopathological studies revealed conditions such as necrosis, edema and inflammatory reaction in the liver, spleen and kidneys. Marginal upsurge of biochemical parameters above normal and elevated levels of lymphocytes (35.20-46.40 g/dL) demonstrated mild toxicity among the 100 mg/kg and 500 mg/kg dose groups at the sub-chronic stage. Low levels of hemoglobin (13.60 to 12.70 g/dL), MCV (34.20-24.0 fL), MCH (40.20-36.40 g/dL) along with high levels of liver enzymes confirmed the mild toxicity of the oil at sub-chronic stage. These results demonstrate that, despite consideration of lime essential oil as safe, it can have mild hematotoxic, nephrotoxic and hepatotoxic effects.

6.
Eur J Radiol Open ; 6: 192-197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31193717

RESUMO

Objectives: Isolated superior mesenteric arterial dissection (ISMAD) is an uncommon type of arterial dissection and treated with surgery, stenting, or conservative management. This study aimed to evaluate the criteria for conservative therapy for ISMAD patients based on imaging findings. Methods: Eighteen consecutive ISMAD patients without peritoneal irritation at onset were retrospectively studied. The decision to perform stenting was based on the emergence of peritoneal irritation, aneurysm, or mesenteric ischemia. Clinical manifestations, follow-up contrast-enhanced computed tomography (CECT) findings, and patient outcome were evaluated. Results: Most patients (16, 89%) were successfully treated conservatively; two patients (11%) required endovascular stenting because of an aneurysm or ulcer-like projection (ULP) sign. The median duration of fasting and hospital stays was 3 (range, 1-8) and 9 (range, 4-34) days, respectively. On CECT, the median distance from the superior mesenteric artery (SMA) origin to the entry site was 12 mm (range, 5-35 mm), and the median length of dissection was 87.5 mm (range, 20-150 mm). Among 16 patients treated conservatively, serial imaging was obtained in 11 patients (69%), and disappearance of the dissection within 4 months occurred in five patients. Two patients treated with endovascular stent underwent follow-up CECT 1 year after onset, and there were no complications. Conclusions: ISMAD patients without peritoneal irritation can be treated conservatively if there are no signs of an aneurysm, ULP, or mesenteric ischemia. When an aneurysm or ULP sign exists, endovascular stenting was able to preserve SMA blood flow with the improvement of the dissection.

7.
Gan To Kagaku Ryoho ; 46(4): 823-825, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-31164548

RESUMO

A 74-year-old man presented to our hospital with the chief complaint of epigastric pain; upper gastrointestinal endoscopy revealed a 7-cm-sized type 3 gastric cancer in the lesser curvature of the lower part of the stomach. Abdominal contrast computed tomography revealed a tumor embolus in the right gastric vein; the preoperative diagnosis was cT4a(SE) N3aH0P0M0, cStage ⅢC. Because the cancer could spread during surgical manipulation, performing a safe radical resection was difficult; therefore, we decided to initiate chemotherapy. The patient received 3 courses of trastuzumab plus CapeOX, which led to reduction of the primarylesion, peri-gastric lymph node, and right gastric vein tumor embolus. Partial remission was achieved after chemotherapy; therefore, distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction were performed. Histopathological examination did not reveal viable tumor cells in the primarylesion, lymph nodes, or tumor embolus, and the histological effect was Grade 3. Currently, the patient is alive without relapse at 9 months post operation. Advanced gastric cancer accompanied with tumor embolism in the gastric vein is commonly observed in patients with liver metastasis and in those with severely progressed state of cancer; many of these patients have poor prognosis. Preoperative chemotherapymaybe effective in cases in which tumor embolism in the gastric vein is identified through preoperative diagnostic imaging.


Assuntos
Células Neoplásicas Circulantes , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
8.
Lancet Gastroenterol Hepatol ; 4(8): 611-621, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31109808

RESUMO

BACKGROUND: This study aimed to assess the safety and tolerability of the immune checkpoint inhibitor nivolumab, as monotherapy or combined with chemotherapy, in Japanese patients with biliary tract cancer. METHODS: This multicentre, open-label, phase 1 trial was done at four cancer centres in Japan. Eligible patients were aged 20-79 years, had biliary tract adenocarcinoma (intrahepatic bile duct cancer, extrahepatic bile duct cancer, gallbladder cancer, or ampullary cancer), Eastern Cooperative Oncology Group performance status 0 or 1, adequate hepatic, renal, and haematological function, and tumour tissue samples for PD-L1 expression analysis. Patients with unresectable or recurrent biliary tract cancer that was refractory or intolerant to gemcitabine-based treatment regimens received nivolumab monotherapy (240 mg every 2 weeks [monotherapy cohort]). Chemotherapy-naive patients with unresectable or recurrent biliary tract cancer received nivolumab (240 mg every 2 weeks) and cisplatin (25 mg/m2) plus gemcitabine (1000 mg/m2) chemotherapy (combined therapy cohort). The primary objective was to assess tolerability and safety. The primary objective was assessed in the safety population of all patients who had received at least one dose of nivolumab. This study is registered with www.clinicaltrials.jp, number JapicCTI-153098, and follow-up is ongoing. FINDINGS: 30 patients were enrolled into each cohort between Jan 13, 2016, and April 19, 2017. Data cutoff was Aug 31, 2017. In the monotherapy cohort, the most frequently reported treatment-related adverse events were decreased appetite (five [17%]), malaise (four [13%]), and pruritus (four [13%]). Grade 3-4 treatment-related adverse events were reported by three (10%) patients (rash, maculopapular rash, and amylase increase) and treatment-related serious adverse events were reported by one (3%) patient (pleurisy). In the combined therapy cohort, the most frequently reported treatment-related adverse events were neutrophil count decrease (any grade 25 [83%]; grade 3-4 in 23 [77%] patients) and platelet count decrease (any grade 25 [83%] of 30; grade 3-4 in 15 [50%] patients). Six (20%) patients reported 11 treatment-related serious adverse events (platelet count decrease [three patients], febrile neutropenia [two patients], neutrophil count decrease, anaemia, anaphylactic reaction, decreased appetite, pyrexia, and myocarditis [one patient each]). In the monotherapy cohort, median overall survival was 5·2 months (90% CI 4·5-8·7), median progression-free survival was 1·4 months (90% CI 1·4-1·4), and one of 30 patients had an objective response. In the combined therapy cohort, median overall survival was 15·4 months (90% CI 11·8-not estimable), median progression-free survival was 4·2 months (90% CI 2·8-5·6), and 11 of 30 patients had an objective response. INTERPRETATION: Nivolumab had a manageable safety profile and signs of clinical activity in patients with unresectable or recurrent biliary tract cancer. This initial assessment of nivolumab for the treatment of advanced biliary tract cancer provides supportive evidence for future larger randomised studies of nivolumab in this difficult to treat cancer. FUNDING: Ono Pharmaceutical Co Ltd and Bristol-Myers Squibb Inc.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30949128

RESUMO

Docosahexaenoic acid (DHA) is an n-3 fatty acid that is an important structural component of the cell membrane. DHA exerts potent anti-inflammatory effects through G protein-coupled receptor 120 (GPR120), which is a functional receptor for n-3 fatty acids. DHA also regulates osteoclast formation and function. However, no studies have investigated the effect of DHA on inflammation-induced osteoclast formation in vivo. In the present study, we investigated whether DHA influences osteoclast formation, bone resorption and the expression of osteoclast-associated cytokines during lipopolysaccharide (LPS)-induced inflammation in vivo, and then we elucidated the underlying mechanisms by using in vitro experiments. In vitro experiments revealed both receptor activator of NF-kB ligand (RANKL)- and tumor necrosis factor-α (TNF-α)-induced osteoclast formation was inhibited by DHA. Supracalvarial administration of LPS with or without DHA was carried out for 5 days and then the number of osteoclasts, ratio of bone resorption pits and the level of type I collagen C-terminal cross-linked telopeptide were measured. All measurements were significantly lower in LPS+DHA-co-administered mice than LPS-administered mice. However, this DHA-induced inhibition was not observed in LPS-, DHA-, and selective GPR120 antagonist AH7614-co-administered mice. Furthermore, the expression of RANKL and TNF-α mRNAs was lower in the LPS+DHA-co-administered group than in the LPS-administered group in vivo. TNF-α mRNA levels were decreased in macrophages co-treated with LPS+DHA compared with cells treated with LPS in vitro. In contrast, RANKL mRNA expression levels from osteoblasts co-treated with DHA and LPS in vitro were equal to that in cells treated with LPS alone. Finally, the inhibitory effects of DHA on osteoclast formation in vitro were not observed by using osteoclast precursors from GPR120-deficient mice, and inhibition of LPS-induced osteoclast formation and bone resorption by DHA in vivo was not observed in GPR120-deficient mice. These results suggest that DHA inhibits LPS-induced osteoclast formation and bone resorption in vivo via GPR120 by inhibiting LPS-induced TNF-α production in macrophages along with direct inhibition of osteoclast formation.

10.
Biomed Pharmacother ; 109: 242-253, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30396082

RESUMO

OBJECTIVES: Dipeptidyl peptidase 4 (DPP-4) inhibition is a new therapeutic strategy for type 2 diabetic patients. DPP-4 has been reported to enhance inflammation. However, the effect of DPP-4 inhibition on inflammation remains unknown. Lipopolysaccharide (LPS) is a strong inducer of inflammation and osteoclast formation. In this study, we investigated in vivo effects of DPP-4 inhibition on LPS-induced osteoclast formation and bone resorption, as well as in vitro effects of DPP-4 inhibition on RANKL-induced osteoclastogenesis and TNF-α-induced osteoclastogenesis. METHODS: LPS with or without a DPP-4 inhibitor was subcutaneously injected into mouse calvaria for 5 days. Histological sections of calvaria were stained for tartrate-resistant acid phosphatase, and osteoclast numbers were determined. The ratio of calvaria bone resorption was evaluated via microfocal computed tomography reconstruction images. RESULTS: Osteoclast number and bone resorption were significantly lower in mice that underwent LPS and DPP-4 inhibitor co-administration than in those that underwent LPS administration alone. Moreover, RANKL, TNF-α, and M-CSF expression was reduced in the LPS and DPP-4 inhibitor co-administration group. In vitro, there were no direct effects of DPP-4 inhibitor or DPP-4 on RANKL- and TNF-α-induced osteoclastogenesis, or on LPS-induced RANKL expression in stromal cells. Nevertheless, macrophages from LPS and DPP-4 inhibitor co-administered mice exhibited lower TNF-α expression than macrophages from LPS-only mice. Notably, TNF-α expression was not reduced in LPS and DPP-4 inhibitor co-treated macrophages in vitro, compared with macrophages treated with LPS alone.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Lipopolissacarídeos/toxicidade , Osteoclastos/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Técnicas de Cocultura , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Linagliptina/farmacologia , Linagliptina/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Distribuição Aleatória
11.
Conf Proc IEEE Eng Med Biol Soc ; 2018: 5-8, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30440327

RESUMO

It is known that alpha-band rhythm during memory maintenance is enhanced by increasing memory load. This enhancement is generally thought to be caused by active inhibition of task-irrelevant visual inputs. During sequential memory processing, we previously found that alpha-band activity increases from beginning to midterm during memory encoding, and conversely decreases from midterm to ending. In the present study, we conducted two experiments to determine the spatial and functional role of alpha-band rhythm during sequential memory processing. The first experiment showed that alpha-band rhythm increased in the occipital brain region, suggesting that active inhibition of task-irrelevant visual inputs continues from midterm to ending of memory encoding. The second experiment, in which subjects could not anticipate the ending of the sequential presentation of memory items, demonstrated that alpha-band rhythm is suppressed in correspondence with preparation for memory recall. These results indicate that alpha-band rhythm is simultaneously modulated by multiple brain processes in sequential memory encoding.


Assuntos
Ritmo alfa , Memória , Lobo Occipital , Adulto , Ritmo alfa/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico , Feminino , Humanos , Masculino , Memória/fisiologia , Memória de Curto Prazo/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Lobo Occipital/fisiologia , Adulto Jovem
12.
Shokuhin Eiseigaku Zasshi ; 59(4): 174-182, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30158396

RESUMO

Colchicum autumnale is a perennial, toxic plant that originated in Europe and North Africa. Although inedible, it is occasionally consumed accidentally because it resembles the edible Allium victorialis and other related species. This misidentification has led to episodes of food poisoning in Japan. However, determining the causative agent of a food poisoning outbreak by observing the sample visually or analyzing the chemical composition is challenging when dealing with small samples. Therefore, we developed a novel set of PCR primers that anneal to the internal transcribed spacer (ITS) region of C. autumnale ribosomal DNA, designed to detect the presence of C. autumnale in small samples. These primers successfully detected C. autumnale in all samples in which it was present, and did not give a positive PCR band in the 48 other distinct crop species tested, in which it was not present. Further, our method could amplify DNA from samples of C. autumnale that had been heat-treated and digested using artificial gastric fluids. Thus, this PCR strategy is highly specific and can be used to distinguish C. autumnale simply and rapidly from various other crops.


Assuntos
Colchicum/classificação , DNA de Plantas/isolamento & purificação , Doenças Transmitidas por Alimentos/diagnóstico , Primers do DNA , DNA Espaçador Ribossômico/genética , Humanos , Japão , Reação em Cadeia da Polimerase
13.
Kyobu Geka ; 71(6): 430-433, 2018 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-30042242

RESUMO

A 72-year-old woman with a history of surgery for left breast cancer was found to have sigmoid colon cancer and solitary pulmonary tumor of left upper lobe. We diagnosed adenocarcinoma of the unknown origin by a transbronchial biopsy. We performed left upper segmentectomy and sigmoidectomy. Left pulmonary tumor was diagnosed metastatic lung tumor from breast cancer. A right pulmonary tumor was confirmed by chest computed tomography(CT) after sigmoidectomy. It was also considered to be metastasis from breast cancer and treated with vinorelbine ditartrate. Since no effect was observed by chemotherapy, tumor was surgically removed by wedge resection. Right pulmonary tumor was pathologically diagnosed as metastasis from sigmoid colon cancer. In suspicious case of pulmonary metastases from double cancer, the possibility of different lesions from different primary site should be kept in mind.


Assuntos
Adenocarcinoma/secundário , Neoplasias da Mama/patologia , Neoplasias Pulmonares/secundário , Neoplasias Primárias Múltiplas/patologia , Neoplasias do Colo Sigmoide/patologia , Adenocarcinoma/diagnóstico , Idoso , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias do Colo Sigmoide/diagnóstico , Neoplasias do Colo Sigmoide/terapia , Tomografia Computadorizada por Raios X , Vinorelbina/uso terapêutico
14.
Calcif Tissue Int ; 103(4): 431-442, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29845409

RESUMO

C-X-C motif chemokine 12 (CXCL12) belongs to the family of CXC chemokines. Lipopolysaccharide (LPS) induces inflammation-induced osteoclastogenesis and bone resorption, and in recent years, stimulatory effects of CXCL12 on bone resorption have also been reported. In the present study, we investigated the effects of CXCL12 on LPS-induced osteoclastogenesis and bone resorption. LPS was administered with or without CXCL12 onto mouse calvariae by daily subcutaneous injection. Numbers of osteoclasts and bone resorption were significantly elevated in mice co-administered LPS and CXCL12 compared with mice administered LPS alone. Moreover, receptor activator of NF-kB ligand (RANKL) and tumor necrosis factor-α (TNF-α) mRNA levels were higher in mice co-administered LPS and CXCL12 compared with mice administered LPS alone. These in vitro results confirmed a direct stimulatory effect of CXCL12 on RANKL- and TNF-α-induced osteoclastogenesis. Furthermore, TNF-α and RANKL mRNA levels were elevated in macrophages and osteoblasts, respectively, co-treated in vitro with CXCL12 and LPS, in comparison with cells treated with LPS alone. Our results suggest that CXCL12 enhances LPS-induced osteoclastogenesis and bone resorption in vivo through a combination of increasing LPS-induced TNF-α production by macrophages, increasing RANKL production by osteoblasts, and direct enhancement of osteoclastogenesis.


Assuntos
Reabsorção Óssea/metabolismo , Quimiocina CXCL12/metabolismo , Lipopolissacarídeos/toxicidade , Osteogênese/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos
15.
J Immunol Res ; 2018: 5783639, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29725604

RESUMO

Glucagon-like peptide-1 (GLP-1) receptor agonists are an effective treatment approach for type 2 diabetes. Recently, anti-inflammatory effects of GLP-1 receptor agonists have also been reported. Lipopolysaccharide (LPS) induces inflammation and osteoclast formation. In this study, we investigated the effect of exendin-4, a widely used GLP-1 receptor agonist, in LPS-induced osteoclast formation and bone resorption. LPS with or without exendin-4 was administered on mouse calvariae by daily subcutaneous injection. The number of osteoclasts, the ratio of bone resorption pits, and the level of C-terminal cross-linked telopeptide of type I collagen (CTX) were significantly lower in LPS- and exendin-4-coadministered mice than in mice administered with LPS alone. RANKL and TNF-α mRNA expression levels were lower in the exendin-4- and LPS-coadministered group than in the LPS-administered group. Our in vitro results showed no direct effects of exendin-4 on RANKL-induced osteoclast formation, TNF-α-induced osteoclast formation, or LPS-induced RANKL expression in stromal cells. Conversely, TNF-α mRNA expression was inhibited in the exendin-4- and LPS-cotreated macrophages compared with cells treated with LPS alone. These results indicate that the GLP-1 receptor agonist exendin-4 may inhibit LPS-induced osteoclast formation and bone resorption by inhibiting LPS-induced TNF-α production in macrophages.


Assuntos
Anti-Inflamatórios/farmacologia , Reabsorção Óssea/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Macrófagos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Peptídeos/farmacologia , Peçonhas/farmacologia , Animais , Diferenciação Celular , Células Cultivadas , Exenatida , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/imunologia , Fator de Necrose Tumoral alfa/metabolismo
16.
Anal Cell Pathol (Amst) ; 2018: 8047610, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29666781

RESUMO

Lipopolysaccharide (LPS) is an endotoxin and bacterial cell wall component that is capable of inducing inflammation and immunological activity. Muramyl dipeptide (MDP), the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is another inflammation-inducing molecule that is ubiquitously expressed by bacteria. Several studies have shown that inflammation-related biological activities were synergistically induced by interactions between LPS and MDP. MDP synergistically enhances production of proinflammatory cytokines that are induced by LPS exposure. Injection of MDP induces lethal shock in mice challenged with LPS. LPS also induces osteoclast formation and pathological bone resorption; MDP enhances LPS induction of both processes. Furthermore, MDP enhances the LPS-induced receptor activator of NF-κB ligand (RANKL) expression and toll-like receptor 4 (TLR4) expression both in vivo and in vitro. Additionally, MDP enhances LPS-induced mitogen-activated protein kinase (MAPK) signaling in stromal cells. Taken together, these findings suggest that MDP plays an important role in LPS-induced biological activities. This review discusses the role of MDP in LPS-mediated biological activities, primarily in relation to osteoclastogenesis.


Assuntos
Acetilmuramil-Alanil-Isoglutamina/farmacologia , Lipopolissacarídeos/farmacologia , Osteoclastos/metabolismo , Acetilmuramil-Alanil-Isoglutamina/química , Animais , Remodelação Óssea/efeitos dos fármacos , Humanos , Lipopolissacarídeos/química , Modelos Biológicos , Osteoclastos/efeitos dos fármacos
17.
Oncotarget ; 9(23): 16477-16488, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29662660

RESUMO

We clarified the clinical prevalence of ovarian metastases from colorectal cancers (CRCs) in 296 female patients with CRC and evaluated clinical outcomes with relation to their mutational profiles, such as BRAF/KRAS mutation and microsatellite instability (MSI) status. The female CRCs were categorised into three subsets: CRCs with ovarian metastases [6.4% (n = 19), 5-year overall survival (OS) = 24.7%], CRCs with extra-ovarian metastases only [32.4% (n = 96), 5-year OS = 34.5%] and CRCs without any recurrence or metastasis [61.2% (n = 181), 5-year OS = 91.3%]. All patients with ovarian metastases underwent oophorectomy; of these, 9 who received preoperative chemotherapy had measurable metastases to extra-ovarian sites and the ovaries. Although 5 of 9 (56%) achieved partial response or complete response at extra-ovarian sites, no patient archived objective response at ovarian sites. Regarding the mutation profiles, in CRCs with extra-ovarian metastases only, the median survival time (MST) after initial treatments to progression to stage IV or recurrence was 13 [95% confidence interval (CI): 7-16 months] in BRAF-mutant and 34 months (95% CI: 22-58 months) in BRAF wild-type (P = 0.0033). Although ovarian metastases demonstrated poor response to systemic chemotherapy in CRCs with ovarian metastases, the MST after initial treatments to progression to stage IV or recurrence was 22 (95% CI: 21-25 months) in BRAF-mutant and 38 months (95% CI: 24-42 months) in BRAF wild-type (P = 0.0398). The outcomes of patients with ovarian metastases could be improved by oophorectomy regardless of their mutation profiles.

18.
Dent Mater J ; 37(2): 286-292, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29109336

RESUMO

Titanium nitride (TiN) coating by ion plating has properties such as high hardness, wear resistance, corrosion resistance, and surface lubricity, therefore TiN coating is often used in various dental appliances and materials. In this study, we evaluated the corrosion behaviors and mechanical properties of TiN coated stainless steel (SS) and nickel titanium (Ni-Ti) orthodontic wires prepared by ion plating. TiN coating by ion plating improves the corrosion resistance of orthodontic wires. The corrosion pitting of the TiN coated wire surface become small. The tensile strength and stiffness of SS wire were increased after TiN coating. In contrast, its elastic force, which is a property for Ni-Ti wire, was decreased. In addition, TiN coating provided small friction forces. The low level of friction may increase tooth movement efficiently. Therefore, TiN coated SS wire could be useful for orthodontics treatment.


Assuntos
Materiais Revestidos Biocompatíveis/química , Ligas Dentárias/química , Fios Ortodônticos , Titânio/química , Corrosão , Galvanoplastia , Dureza , Teste de Materiais , Níquel/química , Aço Inoxidável/química , Propriedades de Superfície , Resistência à Tração
19.
Mol Clin Oncol ; 6(6): 833-838, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28588773

RESUMO

The aim of the present study was to determine the optimal dose and optimal target volume for marginal zone lymphoma of the ocular adnexa. Between January, 2008 and December, 2013, 40 patients with histologically proven primary marginal zone lymphoma of the ocular adnexa who underwent radiotherapy at the Tokyo Medical University were evaluated. The prescribed dose was 30 Gy in 15 fractions to the iso-center. Doses to the gross tumor volume (GTV), conjunctiva, bulbus oculi, retina and retrobulbar space were investigated, and the association between dose-volume factors and clinical outcome was analyzed. The overall and local progression-free survival rates at 3 and 5 years were 100% during a median observation period of 32 months. Two patients relapsed in the contralateral ocular adnexa. The progression-free survival rates at 3 and 5 years were 100 and 93.3%, respectively. The mean dose was 2.0 and 1.9 Gy for targets receiving 95% of the GTV dose (D95). The minimum dose was 0.9-2.0 Gy (median, 1.8 Gy). Thus, primary marginal zone lymphoma of the ocular adnexa favorably responded to lower doses of radiation, compared with prescribed doses to the iso-center. A radiation dose of 27 Gy in 15 fractions at D95 of GTV appeared to be optimal.

20.
J Biosci Bioeng ; 124(3): 296-301, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28527827

RESUMO

Chitin is the second most abundant organic compound on the planet and thus has been regarded as an alternative resource to petroleum feedstocks. One of the key challenges in the biological conversion of biomass-derived polysaccharides, such as cellulose and chitin, is to close the gap between optimum temperatures for enzymatic saccharification and microbial fermentation and to implement them in a single bioreactor. To address this issue, in the present study, we aimed to perform an in vitro, one-pot bioconversion of chitin to pyruvate, which is a precursor of a wide range of useful metabolites. Twelve thermophilic enzymes, including that for NAD+ regeneration, were heterologously produced in Escherichia coli and semi-purified by heat treatment of the crude extract of recombinant cells. When the experimentally decided concentrations of enzymes were incubated with 0.5 mg mL-1 colloidal chitin (equivalent to 2.5 mM N-acetylglucosamine unit) and an adequate set of cofactors at 70°C, 0.62 mM pyruvate was produced in 5 h. Despite the use of a cofactor-balanced pathway, determination of the pool sizes of cofactors showed a rapid decrease in ATP concentration, most probably due to the thermally stable ATP-degrading enzyme(s) derived from the host cell. Integration of an additional enzyme set of thermophilic adenylate kinase and polyphosphate kinase led to the deceleration of ATP degradation, and the final product titer was improved to 2.1 mM.


Assuntos
Reatores Biológicos , Quitina/metabolismo , Enzimas/metabolismo , Ácido Pirúvico/metabolismo , Acetilglucosamina/metabolismo , Trifosfato de Adenosina/metabolismo , Adenilato Quinase/metabolismo , Coenzimas/metabolismo , Estabilidade Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Fermentação , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo
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