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1.
J Oncol Pharm Pract ; : 10781552211042271, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605320

RESUMO

INTRODUCTION: Osimertinib is a tyrosine kinase inhibitor that targets the epidermal growth factor receptor. Elevated serum creatine kinase level is an uncommon adverse event associated with osimertinib treatment for lung cancer. CASE REPORT: We report a previously healthy 56-year-old woman who developed elevated serum creatine kinase levels during osimertinib monotherapy for epidermal growth factor receptor mutation-positive lung adenocarcinoma. MANAGEMENT & OUTCOME: During treatment, she experienced leg cramps and her serum creatine kinase levels increased, peaking at 989 U/l. Further investigation revealed no evidence of cardiotoxicity or myositis; thus, osimertinib-induced myopathy was assumed to be the cause of her elevated serum creatine kinase levels. We successfully managed both lung cancer and osimertinib-induced myopathy using 1-week pauses of osimertinib therapy without dose reduction. DISCUSSION: Short-term suspension of osimertinib without dose reduction may be a reasonable option for osimertinib-induced myopathy.

2.
BMC Microbiol ; 21(1): 275, 2021 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627158

RESUMO

BACKGROUND: Fecal microbiota transplantation (FMT) in patients with ulcerative colitis has shown variable efficacy depending on the protocol used. A previous randomized controlled trial reported that anaerobic preparation of donor stool contributes to improved efficacy. Despite the suggestion that viable obligate anaerobes would be decreased through aerobic handling, there have been only a limited number of reports on how these aerobic or anaerobic procedures affect the composition of viable microbiota in the fecal slurries used for FMT. METHODS: We adopted 16S and 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction to quantify viable bacteria in fecal slurries. This study utilized specific primers designed to detect obligate anaerobes (including Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, Atopobium cluster, and Prevotella) and facultative anaerobes (including total lactobacilli, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus). We then calculated the ratio change (RC) between before and after mixing, and compared the resulting values between anaerobic-prep and aerobic-prep in samples fixed immediately after blending (RCAn0 vs. RCAe0) and in samples maintained (under anaerobic or aerobic conditions) for 1 h after blending (RCAn1 vs. RCAe1). RESULTS: For most obligate anaerobes, the median RC tended to be less than 1, indicating that the number of obligate anaerobes was decreased by the blending procedure. However, in samples maintained for 1 h after blending, anaerobic-prep counteracted the decrease otherwise seen for the C. coccoides group and B. fragilis groups (P < 0.01 for both). The C. leptum subgroup also tended to show higher RC by anaerobic-prep than by aerobic-prep, although this effect was not statistically significant. Among facultative anaerobes, Enterobacteriaceae, Enterococcus, and Staphylococcus showed median RC values of more than 1, indicating that these organisms survived and even grew after mixing. Moreover, oxygen exposure had no significant influence on the survival of the facultative anaerobes. CONCLUSIONS: The conditions under which the blending procedure was performed affected the proportion of live anaerobes in fecal slurries. The obligate anaerobes tended to be decreased by blending processes, but anaerobic-prep significantly mitigated this effect. Anaerobic-prep may improve the efficacy of FMT by permitting the efficient transfer of obligate anaerobes to patients with ulcerative colitis.

3.
Macromol Rapid Commun ; 42(19): e2100374, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34347338

RESUMO

A newly designed radical polymer with a polynorbornene backbone and unsaturated derivative of tetramethylpyrrolidine 1-oxyl (PROXYL) as pendant groups displays reversible redox at 3.75 V (vs Li/Li+ ). The robust polymer design enables the high voltage while maintaining a promising cyclability (over 1000 cycles). The polymer is also beneficial as an additive to the regular lithium iron phosphate electrodes, where the quickly responding organic material facilitates the charging reactions catalytically.


Assuntos
Lítio , Polímeros , Fontes de Energia Elétrica , Eletrodos , Norbornanos
4.
NPJ Microgravity ; 7(1): 10, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750800

RESUMO

The Faraday forcing method in levitated liquid droplets has recently been introduced as a method for measuring surface tension using resonance. By subjecting an electrostatically levitated liquid metal droplet to a continuous, oscillatory, electric field, at a frequency nearing that of the droplet's first principal mode of oscillation (known as mode 2), the method was previously shown to determine surface tension of materials that would be particularly difficult to process by other means, e.g., liquid metals and alloys. It also offers distinct advantages in future work involving high viscosity samples because of the continuous forcing approach. This work presents (1) a benchmarking experimental method to measure surface tension by excitation of the second principal mode of oscillation (known as mode 3) in a levitated liquid droplet and (2) a more rigorous quantification of droplet excitation using a projection method. Surface tension measurements compare favorably to literature values for Zirconium, Inconel 625, and Rhodium, using both modes 2 and 3. Thus, this new method serves as a credible, self-consistent benchmarking technique for the measurement of surface tension.

5.
ISME J ; 15(9): 2574-2590, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33723382

RESUMO

Infant gut microbiota development affects the host physiology throughout life, and short-chain fatty acids (SCFAs) are promising key metabolites mediating microbiota-host relationships. Here, we investigated dense longitudinally collected faecal samples from 12 subjects during the first 2 years (n = 1048) to identify early life gut SCFA patterns and their relationships with the microbiota. Our results revealed three distinct phases of progression in the SCFA profiles: early phase characterised by low acetate and high succinate, middle-phase characterised by high lactate and formate and late-phase characterised by high propionate and butyrate. Assessment of the SCFA-microbiota relationships revealed that faecal butyrate is associated with increased Clostridiales and breastfeeding cessation, and that diverse and personalised assemblage of Clostridiales species possessing the acetyl-CoA pathway play major roles in gut butyrate production. We also found an association between gut formate and some infant-type bifidobacterial species, and that human milk oligosaccharides (HMO)-derived fucose is the substrate for formate production during breastfeeding. We identified genes upregulated in fucose and fucosylated HMO utilisation in infant-type bifidobacteria. Notably, bifidobacteria showed interspecific and intraspecific variation in the gene repertoires, and cross-feeding of fucose contributed to gut formate production. This study provides an insight into early life SCFA-microbiota relationships, which is an important step for developing strategies for modulating lifelong health.


Assuntos
Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Clostridiales , Feminino , Humanos , Lactente , Redes e Vias Metabólicas , Leite Humano
6.
J Anus Rectum Colon ; 5(1): 1-10, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33537495

RESUMO

Approximately 10% of patients with colorectal cancer (CRC) develop malignant large bowel obstruction (MLBO) at diagnosis. Furthermore, for 35% of patients with MLBO, curative primary tumor resection is unfeasible because of locally advanced disease and comorbidities. The practice of placing a self-expandable metallic stent (SEMS) has dramatically increased as an effective palliative treatment. Recent advances in systemic chemotherapy for metastatic CRC have significantly contributed to prolonging patients' prognosis and expanding the indications. However, the safety and efficacy of systemic chemotherapy in patients with SEMS have not been established. This review outlines the current status of this relatively new therapeutic strategy and future perspectives. Some reports on this topic have demonstrated that 1) systemic chemotherapy and the addition of molecular targeted agents contribute to prolonged survival in patients with SEMS; 2) delayed SEMS-related complications are a major concern, and this requires strict patient monitoring; however, primary tumor control by chemotherapy might result in decreased complications, especially regarding re-obstruction; and 3) using bevacizumab could be a risk factor for SEMS-related perforation, which may be lethal. Although this relatively new approach for unresectable stage IV obstructive CRC requires a well-planned clinical trial, this therapy could be promising for patients who are unideal candidates for emergency surgery and require immediate systemic chemotherapy.

7.
Macromol Rapid Commun ; 42(4): e2000607, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33458885

RESUMO

A poly(ethylene sulfide) backbone is introduced as the main chain of a radical polymer. Anionic ring-opening polymerization of an episulfide monomer substituted with 2,2,6,6tetramethylpiperidin1oxyl (TEMPO), a robust nitroxide radical, yields the corresponding polythioether. Compared to the traditional poly(ethylene oxide) backbone, the new polymer shows a lower glass transition temperature (-10 °C), and about threefold higher solid-state ionic conductivity. The polythioether is also shown to improve the charge/discharge properties of a cathode in solid-state lithium-ion batteries.


Assuntos
Fontes de Energia Elétrica , Lítio , Óxidos N-Cíclicos , Polietilenoglicóis , Sulfetos
8.
Asian J Endosc Surg ; 14(2): 232-240, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32911571

RESUMO

INTRODUCTION: Laparoscopic surgery is a minimally invasive surgery; however, obstacles to its functional optimization remain. Surgical ports can accommodate only one instrument at a time so complex exchange manipulations are necessary during surgery which increases operation times and patient risk. We developed a new laparoscopic instrument that functions as both forceps and a suction tube, which renders intraoperative tool exchange unnecessary. This pilot study was undertaken to evaluate the safety and efficacy of this novel dual-function device in laparoscopic surgery for gastric cancer. METHODS: This single-center pilot study assessed patient safety during and after laparoscopic distal gastrectomy for gastric cancer with the suction-forceps using intraoperative video and clinical follow-up, respectively. To evaluate instrument efficacy, we measured the time interval between the start of any bleeding and the start of aspiration ("suction access time") and compared this time with that of a conventional surgical setup. RESULTS: In total 15 patients participated, with all procedures being successful. No excess tissue damage occurred during surgery. Suction access time was significantly shorter in cases of bleeding when the suction-tip forceps were used for aspiration (2.01 seconds) compared to an ordinary suction tube (12.5 seconds; P < .01). CONCLUSION: These findings suggest that our new suction-tip forceps are a useful, safe, and efficacious operative tool. This surgical innovation may considerably simplify gastric laparoscopic surgery. This pilot study was registered with Japan Clinical Trial Registration on 22 June 2017 (registration number: UMIN000027879).


Assuntos
Laparoscopia , Neoplasias Gástricas , Gastrectomia , Humanos , Japão , Projetos Piloto , Neoplasias Gástricas/cirurgia , Sucção , Instrumentos Cirúrgicos
9.
Curr Mol Pharmacol ; 14(2): 220-233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32048982

RESUMO

BACKGROUND: The enhancement of learning and memory through food-derived ingredients is of great interest to healthy individuals as well as those with diseases. Ergothioneine (ERGO) is a hydrophilic antioxidant highly contained in edible golden oyster mushrooms (Pleurotus cornucopiae var. citrinopileatus), and systemically absorbed by its specific transporter, carnitine/organic cation transporter OCTN1/SLC22A4. OBJECTIVE: This study aims to examine the possible enhancement of object recognition memory by oral administration of ERGO in normal mice. METHODS: Novel object recognition test, spatial recognition test, LC-MS/MS, Golgi staining, neuronal culture, western blotting, immunocytochemistry, and quantitative RT-PCR were utilized. RESULT: After oral administration of ERGO (at a dose of 1-50 mg/kg) three times per week for two weeks in ICR mice, the novel object recognition test revealed a longer exploration time for the novel object than for the familiar object. After oral administration of ERGO, the spatial recognition test also revealed a longer exploration time for the spatially moved object than the unmoved one in mice fed ERGO-free diet. The discrimination index was significantly higher in the ERGO-treated group than the control in both behavioral tests. ERGO administration led to an increase in its concentration in the plasma and hippocampus. The systemic concentration reached was relevant to those found in humans after oral ERGO administration. Golgi staining revealed that ERGO administration increased the number of matured spines in the hippocampus. Exposure of cultured hippocampal neurons to ERGO elevated the expression of the synapse formation marker, synapsin I. This elevation of synapsin I was inhibited by the tropomyosin receptor kinase inhibitor, K252a. Treatment with ERGO also increased the expression of neurotrophin-3 and -5, and phosphorylated mammalian target of rapamycin in hippocampal neurons. CONCLUSION: Oral intake of ERGO may enhance object recognition memory at its plasma concentration achievable in humans, and this enhancement effect could occur, at least in part, through the promotion of neuronal maturation in the hippocampus.

10.
Surg Today ; 51(6): 986-993, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33247782

RESUMO

PURPOSE: This study investigated the short- and long-term outcomes of 18- and 22-mm-diameter self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) in patients with malignant large bowel obstruction (MLBO). METHODS: Sixty-nine pathological stage II and III colorectal cancer patients who underwent BTS were included in this multi-institutional retrospective study. Patients were divided into two groups regarding the diameter of SEMS: an 18-mm group (n = 30) and a 22-mm group (n = 39). RESULTS: There was no significant difference in the clinical success rate, but both of the two re-obstructions observed occurred in the 18-mm group. The 18-mm group showed a trend toward a higher incidence of overall postoperative complications (Clavien-Dindo grading ≥ II) than the 22-mm group (33.3% vs. 10.3%, P = 0.061). The 3-year disease-free and overall survival showed no significant differences between the 18- and 22-mm groups (78.2% vs. 68.8%, P = 0.753 and 92.8% vs. 82.1%, P = 0.471, respectively). CONCLUSION: SEMS of 18 and 22 mm diameter confer statistically equivalent short- and long-term outcomes as a BTS.

11.
Gan To Kagaku Ryoho ; 47(9): 1383-1385, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-33130706

RESUMO

A 70-year-old male with defecation difficulties was referred to our hospital. A colonoscopy and computed tomography revealed multiple advanced rectal cancers in the rectosigmoid and lower rectum with swollen lymph nodes. After 6 courses of neoadjuvant capecitabine and oxaliplatin and bevacizumab without radiotherapy(CapeOX plus BV therapy), a colonoscopy revealed that the tumors had significantly reduced. A low anterior laparoscopic resection with diverting ileostomy was performed. Histopathological examination showed no residual tumor cells or lymph node metastasis. A final diagnosis of pathological complete response was made. The patient has currently survived 1-year disease-free. Neoadjuvant CapeOX plus BV therapy can be a promising therapeutic option for locally advanced rectal cancer.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Humanos , Masculino , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Reto
12.
J Clin Med ; 9(11)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187280

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the global coronavirus disease 2019 (COVID-19) outbreak. Along with the respiratory tract, the gastrointestinal (GI) tract is one of the main extra-pulmonary targets of SARS-CoV-2 with respect to symptom occurrence and is a potential route for virus transmission, most likely due to the presence of angiotensin-converting enzyme 2. Therefore, understanding the mechanisms of GI injury is crucial for a harmonized therapeutic strategy against COVID-19. This review summarizes the current evidence for the clinical features of and possible pathogenic mechanisms leading to GI injury in COVID-19.

13.
Phys Rev E ; 102(3-1): 033109, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33075995

RESUMO

Recent experimental results indicate that mixing is enhanced by a reciprocal flow induced inside a levitated droplet with an oscillatory deformation [T. Watanabe et al., Sci. Rep. 8, 10221 (2018)2045-232210.1038/s41598-018-28451-5]. Generally, reciprocal flow cannot convect the solutes in time average, and agitation cannot take place. In the present paper, we focus on the diffusion process coupled with the reciprocal flow. We theoretically derive that the diffusion process can be enhanced by the reciprocal flow, and the results are confirmed via numerical calculation of the over-damped Langevin equation with a reciprocal flow.

14.
Appl Environ Microbiol ; 86(24)2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33036985

RESUMO

Arabinoxylan hydrolysates (AXH) are the hydrolyzed products of the major components of the dietary fiber arabinoxylan. AXH include diverse oligosaccharides varying in xylose polymerization and side residue modifications with arabinose at the O-2 and/or O-3 position of the xylose unit. Previous studies have reported that AXH exhibit prebiotic properties on gut bifidobacteria; moreover, several adult-associated bifidobacterial species (e.g., Bifidobacterium adolescentis and Bifidobacterium longum subsp. longum) are known to utilize AXH. In this study, we tried to elucidate the molecular mechanisms of AXH utilization by Bifidobacterium pseudocatenulatum, which is a common bifidobacterial species found in adult feces. We performed transcriptomic analysis of B. pseudocatenulatum YIT 4072T, which identified three upregulated gene clusters during AXH utilization. The gene clusters encoded three sets of ATP-binding cassette (ABC) transporters and five enzymes belonging to glycoside hydrolase family 43 (GH43). By characterizing the recombinant proteins, we found that three solute-binding proteins of ABC transporters showed either broad or narrow specificity, two arabinofuranosidases hydrolyzed either single- or double-decorated arabinoxylooligosaccharides, and three xylosidases exhibited functionally identical activity. These data collectively suggest that the transporters and glycoside hydrolases, encoded in the three gene clusters, work together to utilize AXH of different sizes and with different side residue modifications. Thus, our study sheds light on the overall picture of how these proteins collaborate for the utilization of AXH in B. pseudocatenulatum and may explain the predominance of this symbiont species in the adult human gut.IMPORTANCE Bifidobacteria commonly reside in the human intestine and possess abundant genes involved in carbohydrate utilization. Arabinoxylan hydrolysates (AXH) are hydrolyzed products of arabinoxylan, one of the most abundant dietary fibers, and they include xylooligosaccharides and those decorated with arabinofuranosyl residues. The molecular mechanism by which B. pseudocatenulatum, a common bifidobacterial species found in adult feces, utilizes structurally and compositionally variable AXH has yet to be extensively investigated. In this study, we identified three gene clusters (encoding five GH43 enzymes and three solute-binding proteins of ABC transporters) that were upregulated in B. pseudocatenulatum YIT 4072T during AXH utilization. By investigating their substrate specificities, we revealed how these proteins are involved in the uptake and degradation of AXH. These molecular insights may provide a better understanding of how resident bifidobacteria colonize the colon.


Assuntos
Proteínas de Bactérias/metabolismo , Bifidobacterium pseudocatenulatum/metabolismo , Proteínas de Transporte/metabolismo , Glicosídeo Hidrolases/metabolismo , Oligossacarídeos/metabolismo , Xilanos/metabolismo
15.
In Vivo ; 34(5): 2667-2673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871798

RESUMO

BACKGROUND/AIM: The efficacy of aflibercept plus 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) therapy has been demonstrated in patients with metastatic colorectal cancer (mCRC) in global and Japanese clinical trials. However, a practical biomarker to predict its efficacy is lacking. PATIENTS AND METHODS: This was a single-institution retrospective study of 21 patients with mCRC consecutively treated with aflibercept plus FOLFIRI from March 2018 to July 2019. We investigated the association and predictive value of pretreatment blood inflammation and immune-based scores, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio, using their median values as cut-offs, in regard to disease control (DC), progression-free (PFS), and overall (OS) survival. RESULTS: The number of patients in each treatment line of aflibercept was as follows: Second, 14 (66.7%); third, four (19.0%); fourth, two (9.5%); eighth, one (4.8%). The median number of aflibercept treatment courses was seven (range=2-17). The median follow-up time was 391 days. In univariate analysis, patients with DC had a significantly lower PLR than those without DC. Only the PLR was significantly negatively associated with PFS, but not with OS. Multivariate analysis showed a significantly poor prognostic impact of a high PLR on PFS (hazard ratio=10.28; p=0.003). CONCLUSION: A low pretreatment PLR might be a predictor of aflibercept efficacy in patients with mCRC and may be clinically useful for selecting patient responders.


Assuntos
Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila , Humanos , Linfócitos , Prognóstico , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Estudos Retrospectivos
16.
J Oleo Sci ; 69(9): 1087-1093, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32788522

RESUMO

Previously, we reported that the polar lipid fraction from the golden oyster mushroom, Pleurotus citrinopileatus, suppresses colon injuries which result from apoptosis induced by inflammatory stresses in vivo and in vitro (Yamashita et al., J. Oleo Sci., 69, 751-757 (2020)). Here, we investigated the use of lipid classes in mushroom polar lipid fraction in alleviating colon injury using differentiated Caco-2 cells as an intestinal tract model. The mushroom polar lipid fraction was separated into four fractions using silica thin layer chromatography. Each mushroom polar lipid fraction suppressed lipopolysaccharide (LPS)-induced decreases in the viability of intestinal cells, and the effects of sphingolipid fractions were significantly stronger than those of fraction that did not contain sphingolipids. Addition of sphingolipid fractions suppressed the expression of apoptosis-related proteins (e.g., death receptors and caspases) in the LPS-treated cells. Mushroom polar lipids, especially sphingolipids suppress intestinal apoptosis induced by inflammatory stress, and highly polar sphingolipids may exert stronger suppressive effects.


Assuntos
Apoptose/efeitos dos fármacos , Doenças do Colo/tratamento farmacológico , Doenças do Colo/patologia , Fitoterapia , Pleurotus/química , Esfingolipídeos/isolamento & purificação , Esfingolipídeos/farmacologia , Apoptose/genética , Células CACO-2 , Caspases/genética , Caspases/metabolismo , Fracionamento Químico , Doenças do Colo/induzido quimicamente , Expressão Gênica , Humanos , Técnicas In Vitro , Inflamação , Lipopolissacarídeos , Esfingolipídeos/uso terapêutico
17.
Nutrients ; 12(8)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806561

RESUMO

Although diet is an important factor influencing gut microbiota, there are very few studies regarding that relationship in Japanese people. Here, we analyzed the relationship between habitual dietary intake surveyed by food frequency questionnaire and the quantitative features of gut bacteria by quantitative PCR and next generation sequencer in 354 healthy Japanese adults. The α-diversity of gut microbiota was positively correlated with the intake of mushrooms and beans and negatively correlated with the intake of grains. The ß-diversity was significantly associated with the intake of fruits, mushrooms, seaweeds, seafoods, and alcoholic beverages. Multiple linear regression analysis of the relationship between food groups associated with the diversity of gut microbiota and the number of gut bacteria at the genus level found 24 significant associations, including a positive association between alcoholic beverages and the number of Fusobacterium. These results support that habitual dietary intake influenced the diversity of gut microbiota and was strongly associated with the number of specific gut bacteria. These results will help us to understand the complex relationship between habitual diet and gut microbiota of the Japanese.


Assuntos
Contagem de Colônia Microbiana/estatística & dados numéricos , Dieta/estatística & dados numéricos , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/fisiologia , Adulto , Agaricales , Dieta/métodos , Inquéritos sobre Dietas , Grão Comestível , Fabaceae , Feminino , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Japão , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
18.
J Oleo Sci ; 69(7): 751-757, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612025

RESUMO

The rising incidence of inflammatory bowel disease (IBD) in East Asian countries has necessitated the implementation of preventive methods in the form of dietary supplementation and changes in dietary habits. We have previously reported that dietary golden oyster mushroom (Pleurotus citrinopileatus) ethanol extract (GOMEE) suppresses intestinal inflammation in mouse models of IBD induced by dextran sulfate sodium salt (DSS). Here, we investigated the components of GOMEE that exert suppressive effects on colon inflammation in vivo and in vitro. The total lipid fraction was extracted from GOMEE, and the polar and neutral lipid fractions were subsequently separated via solvent fractionation. Mice were assigned to dietary groups-control, 1% total lipid, 1% polar lipid, or 1% neutral lipid diet-and fed the respective diets for one week; mice were administered 1.5% DSS in drinking water ad libitum for 20 days. Dietary supplementation with the total or polar lipid fraction alleviated DSS-induced chorionic crypt injury as determined by morphological observation, while dietary supplementation with the neutral lipid fraction did not produce such effects. In the in vitro study, using differentiated Caco-2 cells as the colon model, treatment with the total or polar lipid fraction suppressed cell decrease by lipopolysaccharide (LPS)-induced apoptosis whereas treatment with the neutral lipid fraction did not. Moreover, accumulation of glucosylceramide (GlcCer), a fungal sphingolipid, was observed in the intestinal cells after treatment with polar lipid fraction. These results suggest that the active components of GOMEE that suppress colon inflammation are polar lipids, especially GlcCer. The structure of mushroom GlcCer differs from that of the plant counterpart and is therefore expected to exert different food functions.


Assuntos
Apoptose/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fitoterapia , Pleurotus/química , Esfingolipídeos/farmacologia , Esfingolipídeos/uso terapêutico , Animais , Células CACO-2 , Fracionamento Químico , Suplementos Nutricionais , Modelos Animais de Doenças , Glucosilceramidas , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Esfingolipídeos/isolamento & purificação
19.
Ann Gastroenterol Surg ; 4(1): 64-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32021960

RESUMO

Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control postoperative pain; however, their postoperative use has been associated with anastomotic leakage after gastrointestinal surgery. This systematic review and meta-analysis aimed to determine the correlation between the use of NSAIDs and anastomotic leakage. Methods: We conducted a comprehensive electronic literature search up to August 2018 to identify studies comparing anastomotic leakage in patients with and without postoperative NSAID use following gastrointestinal surgery. We then carried out a meta-analysis using random-effects models to calculate odds ratios (OR) with 95% confidence intervals (CI). Results: Twenty-four studies were included in this meta-analysis, including a total of 31 877 patients. Meta-analysis showed a significant association between NSAID use and anastomotic leakage (OR 1.73; 95% CI = 1.31-2.29, P < .0001). Subgroup analyses showed that non-selective NSAIDs, but not selective cyclooxygenase-2 inhibitors, were significantly associated with anastomotic leakage. However there was no significant subgroup difference between selective and non-selective NSAIDs. Conclusion: Results of this meta-analysis indicate that postoperative NSAID use is associated with anastomotic leakage following gastrointestinal surgeries. Caution is warranted when using NSAIDs for postoperative analgesic control in patients with gastrointestinal anastomoses.

20.
J Cereb Blood Flow Metab ; 40(12): 2505-2520, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31910709

RESUMO

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria and a potent inflammatory stimulus for the innate immune response via toll-like receptor (TLR) 4 activation. Type 2 diabetes is associated with changes in gut microbiota and impaired intestinal barrier functions, leading to translocation of microbiota-derived LPS into the circulatory system, a condition referred to as metabolic endotoxemia. We investigated the effects of metabolic endotoxemia after experimental stroke with transient middle cerebral artery occlusion (MCAO) in a murine model of type 2 diabetes (db/db) and phenotypically normal littermates (db/+). Compared to db/+ mice, db/db mice exhibited an altered gut microbial composition, increased intestinal permeability, and higher plasma LPS levels. In addition, db/db mice presented increased infarct volumes and higher expression levels of LPS, TLR4, and inflammatory cytokines in the ischemic brain, as well as more severe neurological impairments and reduced survival rates after MCAO. Oral administration of a non-absorbable antibiotic modulated the gut microbiota and improved metabolic endotoxemia and stroke outcomes in db/db mice; these effects were associated with reduction of LPS levels and neuroinflammation in the ischemic brain. These data suggest that targeting metabolic endotoxemia may be a novel potential therapeutic strategy to improve stroke outcomes.


Assuntos
Isquemia Encefálica/metabolismo , Endotoxemia/metabolismo , Lipopolissacarídeos/metabolismo , Inflamação Neurogênica/metabolismo , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Isquemia Encefálica/patologia , Estudos de Casos e Controles , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/complicações , Endotoxemia/tratamento farmacológico , Endotoxemia/fisiopatologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Bactérias Gram-Negativas/metabolismo , Imunidade Inata/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/veterinária , Lipopolissacarídeos/sangue , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Modelos Animais , Inflamação Neurogênica/tratamento farmacológico , Inflamação Neurogênica/fisiopatologia , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Acidente Vascular Cerebral/metabolismo , Taxa de Sobrevida , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
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