Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Curr Pharm Teach Learn ; 12(2): 119-126, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32147152

RESUMO

INTRODUCTION: Sleep deprivation is associated with poor academic performance, although the impact on pharmacy students has been minimally reported. This study examined sleep quality in pharmacy students in the first (P1), second (P2), and third (P3) professional years during perceived low and high stress periods in a course. Individual sleep and environmental factors were also explored. METHODS: This prospective cohort study used an 18-item survey adapted from the Pittsburgh Sleep Quality Index (PSQI) that included demographics, individual sleep components, and factors affecting sleep. Surveys were administered at the beginning of the quarter (low stress) and the week before final exams (high stress). Chi-square tests compared categorical variables; ANOVA/ANCOVA tests compared continuous variables. RESULTS: During high stress, PSQI scores worsened among all classes and was significant for the P3s. Average sleep duration was 6.64 (SD 1.18) and 6.8 (SD 1.18) hours per night for P1s and P3s, respectively, at the beginning of the quarter; both groups had significant reduction in sleep duration at the end of the quarter. There were no significant correlations between PSQI and exam scores. Factors impacting sleep such as exercise, use of technology at bedtime, and work hours outside of school decreased during high times of stress, for P1s, P2s, and P3, respectively. CONCLUSIONS: Students demonstrated worsening sleep quality during high stress periods and less sleep than recommended. Academic performance was not adversely affected. Future research should use sleep logs and other performance measures to determine the impact of sleep quality on academic success and wellbeing.

2.
Nature ; 575(7783): 505-511, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31723265

RESUMO

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1-3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.


Assuntos
Bacteriófagos/fisiologia , Enterococcus faecalis/patogenicidade , Enterococcus faecalis/virologia , Microbioma Gastrointestinal , Hepatite Alcoólica/microbiologia , Hepatite Alcoólica/terapia , Terapia por Fagos , Alcoolismo/complicações , Alcoolismo/microbiologia , Animais , Enterococcus faecalis/isolamento & purificação , Etanol/efeitos adversos , Fígado Gorduroso/complicações , Fígado Gorduroso/microbiologia , Fezes/microbiologia , Feminino , Vida Livre de Germes , Hepatite Alcoólica/complicações , Hepatite Alcoólica/mortalidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Perforina/metabolismo
3.
Am J Pharm Educ ; 83(7): 6971, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31619818

RESUMO

Objective. To describe the revision of a pharmacology course series taught over three quarters within a Doctor of Pharmacy (PharmD) curriculum and assess changes in students' attitudes toward and performance after the revision. Methods. Based in part on students' dissatisfaction regarding a pharmacology course series, a course director was hired and tasked with teaching a major portion of the course content, rewriting course examinations, and facilitating active learning in the course series. Course evaluations and examination scores of students who completed the course series after the implementation of the redesigned curriculum (classes of 2015 and 2016) were assessed and compared with those of students who completed the course before the revisions were made (classes of 2013 and 2014). Results. Qualitative analysis of second-year pharmacy student evaluations identified a lack of integration and coordination within the pharmacology course sequence. Poor examination quality and the absence of active teaching methods were other frequently described shortcomings of the pharmacology curriculum. Course evaluations dramatically improved after shortcomings were addressed and students' performance in the subsequent therapeutics course also increased significantly. Conclusion. Adding additional structure to and oversight for a pharmacology course series by adding a course director improved student satisfaction with the course and improved performance in the subsequent therapeutics course. This study highlights the importance of a well-designed pharmacology curriculum for continued success in core courses in the PharmD curriculum.

4.
Proc Natl Acad Sci U S A ; 116(30): 15184-15193, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31289229

RESUMO

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates glucose, lipid, and energy homeostasis. While gene expression of FGF21 is regulated by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha in the fasted state, little is known about the regulation of trafficking and secretion of FGF21. We show that mice with a mutation in the Yip1 domain family, member 6 gene (Klein-Zschocher [KLZ]; Yipf6 KLZ/Y ) on a high-fat diet (HFD) have higher plasma levels of FGF21 than mice that do not carry this mutation (controls) and hepatocytes from Yipf6 KLZ/Y mice secrete more FGF21 than hepatocytes from wild-type mice. Consequently, Yipf6 KLZ/Y mice are resistant to HFD-induced features of the metabolic syndrome and have increased lipolysis, energy expenditure, and thermogenesis, with an increase in core body temperature. Yipf6 KLZ/Y mice with hepatocyte-specific deletion of FGF21 were no longer protected from diet-induced obesity. We show that YIPF6 binds FGF21 in the endoplasmic reticulum to limit its secretion and specifies packaging of FGF21 into coat protein complex II (COPII) vesicles during development of obesity in mice. Levels of YIPF6 protein in human liver correlate with hepatic steatosis and correlate inversely with levels of FGF21 in serum from patients with nonalcoholic fatty liver disease (NAFLD). YIPF6 is therefore a newly identified regulator of FGF21 secretion during development of obesity and could be a target for treatment of obesity and NAFLD.


Assuntos
Fatores de Crescimento de Fibroblastos/genética , Fígado/metabolismo , Proteínas de Membrana/genética , Síndrome Metabólica/genética , Hepatopatia Gordurosa não Alcoólica/genética , Obesidade/genética , Animais , Temperatura Corporal , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/genética , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo , Dieta Hiperlipídica/efeitos adversos , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Metabolismo Energético/genética , Fatores de Crescimento de Fibroblastos/sangue , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Lipólise/genética , Fígado/patologia , Proteínas de Membrana/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Ligação Proteica , Transdução de Sinais , Termogênese/genética , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
5.
J Med Educ Curric Dev ; 6: 2382120519848048, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31206030

RESUMO

Introduction and background: In 2010, the UC San Diego School of Medicine launched a new curriculum, the integrated scientific curriculum. As part of this curricular redesign, the school instituted academic communities. This perspective article outlines our experience with the first 8 years of these academic communities. Single-institution experience: We initiated academic communities with the hope that this structure would cultivate enhanced student-student and student-faculty engagement, improve faculty-student mentoring, and create additional service-learning and student leadership opportunities. The communities would also provide an environment for small group learning throughout the 4-year curriculum. After 8 years of experience, a comparison of student survey data pre- and post establishment of academic communities demonstrated enhanced connectedness between students and faculty and higher scores for faculty mentoring and for career planning. Our own lived experience with the communities revealed several unanticipated outcomes. The community directors became a source of support and advice for one another. Some faculty and administrators whose previous roles were affected by start of the academic communities needed to adjust expectations. Conclusions: The establishment of academic communities was associated with improvement in student-faculty engagement, student assessment of faculty mentoring, and career planning.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30321914

RESUMO

In addition to online questionnaires, many medical schools use supplemental evaluation tools such as focus groups to evaluate their courses. Although some benefits of using focus groups in program evaluation have been described, it is unknown whether these in-person data collection methods provide sufficient additional information beyond online evaluations to justify them. In this study we analyze recommendations gathered from student evaluation team (SET) focus group meetings and analyzed whether these items were captured in open-ended comments within the online evaluations. Our results indicate that online evaluations captured only 49% of the recommendations identified via SETs. Surveys to course directors identified that 74% of the recommendations exclusively identified via the SETs were implemented within their courses. Our results indicate that SET meetings can provide information not easily captured in online evaluations and that these recommendations result in actual course changes.


Assuntos
Grupos Focais , Internet , Avaliação de Programas e Projetos de Saúde , Estudantes de Medicina , Inquéritos e Questionários , Currículo , Educação de Graduação em Medicina , Humanos , Pesquisa Qualitativa , Estados Unidos
8.
J Hepatol ; 69(2): 396-405, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29654817

RESUMO

BACKGROUND & AIMS: The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis. METHODS: Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis. RESULTS: We found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis. CONCLUSION: Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans. LAY SUMMARY: Understanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis.


Assuntos
Ácidos e Sais Biliares , Colestase , Fatores de Crescimento de Fibroblastos/sangue , Hepatite Alcoólica , Neutrófilos/patologia , Ácidos e Sais Biliares/biossíntese , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo , Biomarcadores/sangue , Colestase/etiologia , Colestase/metabolismo , Correlação de Dados , Feminino , Hepatite Alcoólica/sangue , Hepatite Alcoólica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos , Índice de Gravidade de Doença , Transdução de Sinais/fisiologia
10.
Adv Health Sci Educ Theory Pract ; 23(3): 499-511, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29340892

RESUMO

Medical schools with a diverse student body face the challenge of ensuring that all students succeed academically. Many medical schools have implemented prematriculation programs to prepare students from diverse backgrounds; however, evidence on their impact is largely lacking. In this study, we analyzed participants' demographics as well as the impact of the prematriculation program on Year 1 performance. Predictive validity of the program was assessed and compared to other traditional predictors, including grade point average (GPA) and Medical College Admission Test (MCAT) scores and subscores. Linear mixed effect models determined the impact of the prematriculation program, and linear regression analysis assessed the predictive value of the overall score in the prematriculation program and other traditional predictors. Demographics of students participating in the prematriculation program from 2013 to 2015 (n = 75) revealed a significantly higher prevalence of academically disadvantaged students including older students, students with lower GPA and MCAT scores and students of racial and ethnic populations that are underrepresented in medicine, compared to non-participants (n = 293). Participants performed significantly better in Year 1 courses that were covered in the prematriculation program compared to courses that were not covered. The overall performance in the prematriculation program correlated significantly with Year 1 performance and was found to be a strong predictor for Year 1 performance. This study suggests that a prematriculation program can help students to succeed in the first year of medical school. The results have implications for medical schools seeking to implement or evaluate the effectiveness of their prematriculation program.


Assuntos
Sucesso Acadêmico , Diversidade Cultural , Faculdades de Medicina/organização & administração , Adulto , Feminino , Humanos , Modelos Lineares , Masculino , Avaliação de Programas e Projetos de Saúde , Fatores Socioeconômicos , Adulto Jovem
11.
12.
Am J Pharm Educ ; 81(3): 48, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28496268

RESUMO

Objectives. This study investigated the impact of an optional 12-week summer research program on the publication outcomes and satisfaction with the required research projects of doctor of pharmacy (PharmD) students at the Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) at the University of California San Diego. Methods. PubMed and Google searches provided student publications, and satisfaction surveys submitted by students provided their perceptions of the research project value. Results. Of the studied cohort, the 130 students who fulfilled the requirement through the optional summer research program provided 61 full-text manuscripts and 113 abstracts. The 305 students who chose the standard pathway provided 35 full-text manuscripts and 34 abstracts. Students in both pathways agreed or strongly agreed that the research project was a valuable experience. Conclusions. The 12-week intensive summer research program improved the publication rate of pharmacy students and provided a high overall satisfaction with this independent learning experience.


Assuntos
Educação de Pós-Graduação em Farmácia/estatística & dados numéricos , Editoração/estatística & dados numéricos , Projetos de Pesquisa , Relatório de Pesquisa , Estudantes de Farmácia/estatística & dados numéricos , California , Humanos , Faculdades de Farmácia , Estudantes de Farmácia/psicologia
13.
Med Teach ; 39(8): 813-819, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28440094

RESUMO

BACKGROUND: The University of California, San Diego, School of Medicine implemented a curriculum change that included reduction of lectures, incorporation of problem-based learning and other small group activities. Six academic communities were introduced for teaching longitudinal curricular content and organizing extracurricular activities. METHODS: Surveys were collected from 904 first- and second-year medical students over 6 years. Student satisfaction data with their sense of connectedness and community support were collected before and after the implementation of the new curriculum. In a follow-up survey, medical students rated factors that contributed to their sense of connectedness with faculty and students (n = 134). RESULTS: Students' perception of connectedness to faculty significantly increased following implementation of a curriculum change that included academic communities. Students ranked small group clinical skills activities within academic communities significantly higher than other activities concerning their sense of connectedness with faculty. Students' perception of connectedness among each other was high at baseline and did not significantly change. Small group activities scored higher than extracurricular activities regarding students' connectedness among themselves. CONCLUSIONS: The implementation of a new curriculum with more small group educational activities including academic communities enhanced connectedness between students and faculty and resulted in an increased sense of community.


Assuntos
Currículo , Docentes de Medicina , Estudantes de Medicina , Educação de Graduação em Medicina , Humanos , Aprendizagem Baseada em Problemas
14.
Curr Opin Gastroenterol ; 33(3): 128-133, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28257306

RESUMO

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is a liver disease with high prevalence in western countries. Progression from NAFLD to nonalcoholic steatohepatitis (NASH) occurs in 10-20%. NASH pathogenesis is multifactorial including genetic and environmental factors. The gut microbiota is involved in disease progression and its role is complex. RECENT FINDINGS: NASH is associated with changes in the intestinal microbiota, although findings in recent studies are inconsistent. Dysbiosis can trigger intestinal inflammation and impair the gut barrier. Microbial products can now reach the liver, induce hepatic inflammation and contribute to NAFLD and NASH progression. As the gut microbiota is also involved in the regulation of metabolic pathways, metabolomic approaches identified unique metabolomic profiles in patients with NASH. Altered metabolite patterns can serve as biomarkers, whereas specific metabolites (such as ethanol) have been linked with disease progression. Modifying metabolic profiles might serve as new therapeutic microbiome-based approaches. SUMMARY: In this review, we will highlight findings from the recent literature important to the gut-liver axis. We will predominantly focus on human studies with NASH.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica/microbiologia , Translocação Bacteriana , Progressão da Doença , Disbiose/complicações , Disbiose/metabolismo , Humanos , Metabolômica , Hepatopatia Gordurosa não Alcoólica/metabolismo
15.
Am J Physiol Gastrointest Liver Physiol ; 312(5): G413-G419, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28232456

RESUMO

Liver and intestine are tightly linked through the venous system of the portal circulation. Consequently, the liver is the primary recipient of gut-derived products, most prominently dietary nutrients and microbial components. It functions as a secondary "firewall" and protects the body from intestinal pathogens and other microbial products that have crossed the primary barrier of the intestinal tract. Disruption of the intestinal barrier enhances microbial exposure of the liver, which can have detrimental or beneficial effects in the organ depending on the specific circumstances. Conversely, the liver also exerts influence over intestinal microbial communities via secretion of bile acids and IgA antibodies. This mini-review highlights key findings and concepts in the area of host-microbial interactions as pertinent to the bilateral communication between liver and gut and highlights the concept of the gut-liver axis.


Assuntos
Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiologia , Fígado/microbiologia , Fígado/fisiologia , Animais , Humanos
16.
Med Educ ; 51(2): 215-227, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27917517

RESUMO

CONTEXT: Most medical schools use online systems to gather student feedback on the quality of their educational programmes and services. Online data may be limiting, however, as the course directors cannot question the students about written comments, nor can students engage in mutual problem-solving dialogue with course directors. We describe the implementation of a student evaluation team (SET) process to permit course directors and students to gather shortly after courses end to engage in feedback and problem solving regarding the course and course elements. METHODS: Approximately 16 students were randomly selected to participate in each SET meeting, along with the course director, academic deans and other faculty members involved in the design and delivery of the course. An objective expert facilitates the SET meetings. SETs are scheduled for each of the core courses and threads that occur within the first 2 years of medical school, resulting in approximately 29 SETs annually. SET-specific satisfaction surveys submitted by students (n = 76) and course directors (n = 16) in 2015 were used to evaluate the SET process itself. Survey data were collected from 885 students (2010-2015), which measured student satisfaction with the overall evaluation process before and after the implementation of SETs. RESULTS: Students and course directors valued the SET process itself as a positive experience. Students felt that SETs allowed their voices to be heard, and that the SET increased the probability of suggested changes being implemented. Students' satisfaction with the overall evaluation process significantly improved after implementation of the SET process. CONCLUSIONS: Our data suggest that the SET process is a valuable way to supplement online evaluation systems and to increase students' and faculty members' satisfaction with the evaluation process.


Assuntos
Currículo/normas , Educação de Graduação em Medicina/normas , Satisfação Pessoal , Estudantes de Medicina/psicologia , California , Humanos , Percepção , Avaliação de Programas e Projetos de Saúde
17.
Adv Physiol Educ ; 40(2): 229-33, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27105742

RESUMO

The introduction of PowerPoint presentation software has generated a paradigm shift in the delivery of lectures. PowerPoint has now almost entirely replaced chalkboard or whiteboard teaching at the undergraduate and graduate levels. This study investigated whether undergraduate biology students preferred to have lectures delivered by PowerPoint or written on the board as well as the reasons behind their preference. Two upper-division physiology courses were surveyed over a period of 7 yr. A total of 1,905 students (86.7%) indicated they preferred lectures delivered by "writing on the board" compared to 291 students (13.3%) who preferred PowerPoint. Common themes drawn from explanations reported by students in favor of writing on the board included: 1) more appropriate pace, 2) facilitation of note taking, and 3) greater alertness and attention. Common themes in favor of PowerPoint included 1) increased convenience, 2) focus on listening, and 3) more accurate and readable notes. Based on the students' very strong preference for writing on the board and the themes supporting that preference, we recommend that instructors incorporate elements of the writing on the board delivery style into whatever teaching modality is used. If instructors plan to use PowerPoint, the presentation should be paced, constructed, and delivered to provide the benefits of lectures written on the board. The advantages of writing on the board can be also incorporated into instruction intended to occur outside the classroom, such as animated narrated videos as part of the flipped classroom approach.


Assuntos
Fisiologia/educação , Estudantes de Ciências da Saúde , Ensino , Redação , Humanos
18.
Am J Physiol Gastrointest Liver Physiol ; 310(5): G310-22, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26702135

RESUMO

Nonalcoholic fatty liver disease (NAFLD) and obesity are characterized by altered gut microbiota, inflammation, and gut barrier dysfunction. Here, we investigated the role of mucin-2 (Muc2) as the major component of the intestinal mucus layer in the development of fatty liver disease and obesity. We studied experimental fatty liver disease and obesity induced by feeding wild-type and Muc2-knockout mice a high-fat diet (HFD) for 16 wk. Muc2 deficiency protected mice from HFD-induced fatty liver disease and obesity. Compared with wild-type mice, after a 16-wk HFD, Muc2-knockout mice exhibited better glucose homeostasis, reduced inflammation, and upregulated expression of genes involved in lipolysis and fatty acid ß-oxidation in white adipose tissue. Compared with wild-type mice that were fed the HFD as well, Muc2-knockout mice also displayed higher intestinal and plasma levels of IL-22 and higher intestinal levels of the IL-22 target genes Reg3b and Reg3g. Our findings indicate that absence of the intestinal mucus layer activates the mucosal immune system. Higher IL-22 levels protect mice from diet-induced features of the metabolic syndrome.


Assuntos
Endotoxinas/imunologia , Microbioma Gastrointestinal , Inflamação , Interleucinas/metabolismo , Mucosa Intestinal , Mucina-2 , Hepatopatia Gordurosa não Alcoólica , Obesidade , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Knockout , Mucina-2/deficiência , Mucina-2/metabolismo , Mucina-2/farmacologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/metabolismo , Obesidade/patologia , Obesidade/prevenção & controle , Proteínas Associadas a Pancreatite , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Proteínas/metabolismo , Regeneração/imunologia
19.
Expert Rev Gastroenterol Hepatol ; 9(8): 1069-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26088524

RESUMO

Changes in the intestinal microbiota composition contribute to the pathogenesis of many disorders including gastrointestinal and liver diseases. Recent studies have broadened our understanding of the "gut-liver" axis. Dietary changes, other environmental and genetic factors can lead to alterations in the microbiota. Dysbiosis can further disrupt the integrity of the intestinal barrier leading to pathological bacterial translocation and the initiation of an inflammatory response in the liver. In this article, the authors dissect the different steps involved in disease pathogenesis to further refine approaches for the medical management of liver diseases. The authors will specifically discuss the role of dysbiosis in inducing intestinal inflammation and increasing intestinal permeability.


Assuntos
Disbiose/fisiopatologia , Enterite/fisiopatologia , Microbioma Gastrointestinal , Mucosa Intestinal/metabolismo , Hepatopatias/fisiopatologia , Animais , Enterite/microbiologia , Humanos , Hepatopatias/microbiologia , Permeabilidade
20.
Crit Care Med ; 42(1): e32-41, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24145837

RESUMO

OBJECTIVES: Annexin A5 is a 35-kDa protein with high affinity binding to negatively charged phospholipids. However, its effects on sepsis are not known. Our aim was to study the effects of annexin A5 on myocardial tumor necrosis factor-α expression, cardiac function, and animal survival in endotoxemia. DESIGN: Prospective experimental study. SETTING: University laboratory. SUBJECTS: Adult male C57BL/6 mice. INTERVENTIONS: Mice were challenged with lipopolysaccharide (4 or 20 mg/kg, i.p.) to induce endotoxemia with and without recombinant human annexin A5 treatment (5 or 10 µg/kg, i.v.). Cytokine expression and cardiac function were assessed, and animal survival was monitored. MEASUREMENTS AND MAIN RESULTS: Treatment with annexin A5 inhibited myocardial mitogen-activated protein kinase, and nuclear factor-κB activation in mice with endotoxemia. Furthermore, annexin A5-treated animals showed significant reductions in myocardial and plasma levels of tumor necrosis factor-α and interleukin-1ß while cardiac function was significantly improved during endotoxemia. Additionally, 5-day animal survival was significantly improved by either an immediate or a 4-hour delayed annexin A5 treatment after lipopolysaccharide challenge. Importantly, annexin A5 dose-dependently inhibited lipopolysaccharide binding to a toll-like receptor-4/myeloid differentiation factor 2 fusion protein. CONCLUSIONS: Annexin A5 treatment decreases cytokine expression and improves cardiac function and survival during endotoxemia. These effects of annexin A5 are mediated by its ability to inhibit lipopolysaccharide binding to toll-like receptor-4, leading to reductions in mitogen-activated protein kinase and Akt signaling. Our study suggests that annexin A5 may have therapeutic potential in the treatment of sepsis.


Assuntos
Anexina A5/farmacologia , Endotoxemia/tratamento farmacológico , Coração/efeitos dos fármacos , Inflamação/prevenção & controle , Animais , Relação Dose-Resposta a Droga , Endotoxemia/mortalidade , Endotoxemia/fisiopatologia , Coração/fisiopatologia , Humanos , Inflamação/fisiopatologia , Interleucina-1beta/sangue , Interleucina-1beta/fisiologia , Lipopolissacarídeos/farmacologia , Antígeno 96 de Linfócito/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/fisiologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/fisiologia , Proteínas Recombinantes/farmacologia , Receptor 4 Toll-Like/fisiologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA