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INTRODUCTION: The significant maternal and neonatal outcomes of gestational diabetes mellitus (GDM) make it a major public health concern. Mothers with GDM are at greater risk of pregnancy complications and their offspring are at higher risk of diabetes and obesity. Currently, GDM is diagnosed with glucose load methods which are time-consuming and inconvenient to administer more than once during pregnancy; for this reason, there is a recognised need for a more accurate and simpler test for GDM. Previous studies indicate that plasma-glycated CD59 (pGCD59) is a novel biomarker for GDM. We present here the protocol of a prospective cohort study designed to (1) determine the accuracy of pGCD59 as an early, first trimester predictor of GDM and gestational impaired glucose tolerance and (2) assess the associations between pGCD59 levels and adverse maternal and neonatal outcomes. METHODS AND ANALYSIS: We will obtain discarded plasma samples from pregnant women at two time points: first prenatal visit (usually <14 weeks gestation) and gestational weeks 24-28. A study-specific medical record abstraction tool will be used to obtain relevant maternal and neonatal clinical data from the EPIC clinical database. The prevalence of GDM will be determined using standard of care glucose load test results. We will determine the sensitivity and specificity of pGCD59 to predict the diagnosis of GDM and gestational impaired glucose tolerance, as well as the associations between levels of pGCD59 and the prevalence of maternal and neonatal outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Mass General Brigham Institutional Review Board (protocol 2011P002254). The results of this study will be presented at international meetings and disseminated in peer-reviewed journals.
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Diabetes Gestacional , Intolerancia a la Glucosa , Biomarcadores , Glucemia , Antígenos CD59 , Diabetes Gestacional/epidemiología , Femenino , Glucosa , Humanos , Recién Nacido , Embarazo , Estudios ProspectivosRESUMEN
Blocking tumor vascularization has not yet come to fruition to the extent it was hoped for, as angiogenesis inhibitors have shown only partial success in the clinic. We hypothesized that under-appreciated vascular wall-resident stem and progenitor cells (VW-SPCs) might be involved in tumor vascularization and influence effectiveness of anti-angiogenic therapy. Indeed, in patient samples, we observed that vascular adventitia-resident CD34+ VW-SPCs are recruited to tumors in situ from co-opted vessels. To elucidate this in detail, we established an ex vivo model using concomitant embedding of multi-cellular tumor spheroids (MCTS) and mouse aortic rings (ARs) into collagen gels, similar to the so-called aortic ring assay (ARA). Moreover, ARA was modified by removing the ARs' adventitia that harbors VW-SPCs. Thus, this model enabled distinguishing the contribution of VW-SPCs from that of mature endothelial cells (ECs) to new vessel formation. Our results show that the formation of capillary-like sprouts is considerably delayed, and their number and network formation were significantly reduced by removing the adventitia. Substituting iPSC-derived neural spheroids for MCTS resulted in distinct sprouting patterns that were also strongly influenced by the presence or absence of VW-SPCs, also underlying the involvement of these cells in non-pathological vascularization. Our data suggest that more comprehensive approaches are needed in order to block all of the mechanisms contributing to tumor vascularization.
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Adventicia/patología , Neoplasias/irrigación sanguínea , Neoplasias/patología , Células Madre/patología , Animales , Antígenos CD34/metabolismo , Aorta/patología , Capilares/patología , Humanos , Ratones , Modelos Biológicos , Neovascularización Patológica , Neovascularización Fisiológica , Ratas , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The recent main focus of the researches on Attention-deficit Hyperactivity Disorder is on identifying behavioral phenotypes. For this purpose, neuroanatomical factors have recently become a focus. This study aimed to investigate whether the individuals diagnosed with Attention-deficit Hyperactivity Disorder differ from healthy individuals in terms of facial anthropometric measurements. Forty children, diagnosed with Attention-deficit Hyperactivity Disorder, were included in the study as the case group, and forty healthy children were included in the study as the control group. Two photographs were taken from the facial region, and anthropometric measurements were performed using the computer program "Image J" in the computer environment. It was found that a strong relationship between Attention-deficit Hyperactivity Disorder and nasal width, ear length and upper face debt length. The results obtained from the research support the knowledge that there is a close relationship between the forebrain development process and the facial development process during the embryonic development process.
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The aim of this study was to investigate serum levels of cortisol and adrenocorticotropic hormone in adolescents with first-episode early onset schizophrenia. A total of 23 adolescent patients, who did not receive prior therapy and who were diagnosed with psychosis according to DSM-IV, were included. Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, Positive and Negative Symptom Scale, and Clinical Global Impression Scale were conducted with the participants. No significant differences were found between the patients and the control subjects in serum cortisol and adrenocorticotropic hormone levels (P > .05). Our study's findings do not support the hypothesis of increased hypothalamic-pituitary-adrenal axis activity in first-episode early onset schizophrenia.
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Hormona Adrenocorticotrópica/sangre , Hidrocortisona/sangre , Esquizofrenia/sangre , Adolescente , Niño , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/fisiopatología , Masculino , Sistema Hipófiso-Suprarrenal/fisiopatología , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologíaRESUMEN
OBJECTIVE: The aim of this study was to investigate whether cortisol and oxidative stress levels and DNA damage differ between individuals who developed PTSD or not following a sexual trauma. METHODS: The study included 61 children aged between 5 and 17 years who sustained sexual abuse (M/F: 18/43). The patients were divided into two groups: patients with PTSD and patients without PTSD based, based on the results of a structured psychiatric interview (K-SADS-PL and CAPS-CA). Cortisol, glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q, 8-Hydroxy-2-Deoxyguanosine (8-OHdG) were all evaluated by the ELISA method. RESULTS: Our evaluation revealed a diagnosis of PTSD in 51% (n=31) of victims. There was no significant difference between the groups with or without PTSD in terms of cortisol, GPx, SOD, coenzyme Q, and 8-OHdG levels. There was no correlation between CAPS scores and GPx, SOD, coenzyme Q, and 8-OHdG levels between patients with or without PTSD. In patients with PTSD, both cortisol and 8-OHdG levels decreased with increasing time after trauma, and there was no significant correlation with cortisol and 8-OHdG levels in patients without PTSD. CONCLUSION: Although the present study did not find any difference between the groups in terms of 8-OHdG concentrations, the decreases in both cortisol and 8-OHdG levels with increasing time after trauma is considered to indicate a relationship between cortisol and DNA damage.
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OBJECTIVE: Oxidative stress has been reported to play a role in the psychopathology of schizophrenia, though only a few studies have investigated the relationship between early-onset schizophrenia and oxidative stress. The aim of the present study is to evaluate the level of oxidative stress and the presence of DNA damage in first-episode psychosis (FEP) in adolescents. METHODS: This study was conducted in the Department of Child Psychiatry of the Dicle University Hospital. It included 20 adolescent patients (age 11-17 years) with psychosis (acute psychosis, schizophreniform disorder, or schizophrenia) according to DSM-IV criteria who had received no previous psychiatric therapy (patient group) and 20 age/gender-matched healthy adolescents (control group). Structured psychiatric interviews [Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL) and Positive and Negative Symptom Scale (PANSS)] were conducted on the patients, and the Clinical Global Impressions (CGI) scale was used to evaluate the severity of disease. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were determined using the ELISA method and commercial ELISA kits. RESULTS: The mean age was 14.5 ± 1.6 years in the FEP group (male-to-female ratio: 8/12) and 14.4 ± 1.5 years in the control group (male-to-female ratio: 8/12). There were no differences between the patient and control groups in terms of SOD, GPx, or 8-OHdG values (p > 0.05). CONCLUSIONS: This study on DNA damage and oxidative stress in FEP in adolescents had a small sample size, and our data suggest that oxidative stress is associated with a chronic disease course rather than being an early sign of early-onset schizophrenia.
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Daño del ADN/fisiología , Estrés Oxidativo/fisiología , Trastornos Psicóticos/metabolismo , Esquizofrenia/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Adolescente , Niño , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Ensayo de Inmunoadsorción Enzimática , Femenino , Glutatión Peroxidasa/metabolismo , Humanos , Entrevista Psicológica , Masculino , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/genética , Esquizofrenia/genética , Índice de Severidad de la Enfermedad , Superóxido Dismutasa/metabolismo , Ubiquinona/metabolismoRESUMEN
INTRODUCTION: Brain-derived neurotropic factor (BDNF) has been suggested to play a role in the pathogenesis of attention-deficit hyperactivity disorder (ADHD). In addition, impairment in executive functions has been reported in children with ADHD. This study investigated the presence of a relationship between Stroop test scores and BDNF levels in children with ADHD. METHODS: The study was conducted in the Department of Child Psychiatry at Dicle University. The study included 49 children between 6 and 15 years of age (M/F: 42/7), who were diagnosed with ADHD according to DSM-IV, and who did not receive previous therapy. Similar in terms of age and gender to the ADHD group, 40 children were selected in the control group. The Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version was administered to all participants. Parents and teachers were administered Turgay DSM-IV-based Child and Adolescent Behavior Disorders Screening and Rating Scale to measure symptom severity in children with ADHD. Children with ADHD underwent the Stroop test. BDNF levels were evaluated in serum by ELISA. RESULTS: The ADHD and control groups did not differ in terms of BDNF levels. BDNF levels did not differ between ADHD subtypes. There was also no relationship between the Stroop test interference scores and BDNF levels. CONCLUSION: The findings of the present study are in line with those in studies that demonstrated no significant role of BDNF in the pathogenesis of ADHD.
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OBJECTIVE: Brain-derived neurotropic factor (BDNF) is known to play a role in the pathogenesis of schizophrenia. However, the relationship between early onset schizophrenia and BDNF has not been extensively studied. The aim of the study was to compare the levels of BDNF between adolescent patients with first-episode psychosis (FEP) and the healthy control subjects. METHOD: The study was conducted in the Department of Child Psychiatry at Dicle University. A total of 26 adolescent patients aged between 11 and 17 years who had not received previous therapy and whose conditions were diagnosed with psychosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and 26 age- and sex-matched healthy adolescent control subjects were included. Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and the Positive and Negative Symptom Scale were conducted with all participants. The clinical global impression was used to evaluate disease severity. The BDNF levels were measured in the serum by enzyme-linked immunosorbent assay method. RESULTS: The mean (SD) age was 14.6 (1.6) years in both FEP group (male/female, 11/15) and the control group (P > 0.05). The FEP group had significantly lower serum BDNF levels (2.0 ± 1.9 ng/mL) compared with the control group (3.4 ± 3.0 ng/mL, P = 0.03). There was no significant relationship between BDNF concentration and the Positive and Negative Symptom Scale (positive and negative scores) scores (r = -0.14, P = 0.74 and r = 0.49, P = 0.22, respectively). There was no significant relationship between the duration of untreated psychosis and serum BDNF levels (r = -0.22, P = 0.32). CONCLUSIONS: High incidence of schizophrenia in patients with FEP suggests a relationship between BDNF levels and the pathogenesis of schizophrenia. We suggest that BDNF may be a useful neurobiological marker of early onset schizophrenia.
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Factor Neurotrófico Derivado del Encéfalo/sangre , Trastornos Psicóticos/sangre , Esquizofrenia/sangre , Adolescente , Estudios de Casos y Controles , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/fisiopatología , Esquizofrenia/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: There are studies reporting that cortisol and brain-derived neurotropic factor (BDNF) play a role in the pathophysiology of post-traumatic stress disorder (PTSD). However, up-to-date no study evaluated the relationship between PTSD and the levels of cortisol and BDNF in children and adolescents who have sustained trauma. The aim of this study was to investigate whether BDNF, cortisol and adrenocorticotropine (ACTH) levels differ between individuals who developed PTSD or not following a sexual trauma. METHOD: The study included 55 children aged between 6 and 17 years who sustained sexual assault (M/F: 13/42). The patients were divided into two groups, with or without PTSD based on the results of a structured psychiatric interview (K-SADS-PL and CAPS-CA). Of the participants, 49% (n=27) were diagnosed with PTSD. Cortisol, ACTH, and BDNF levels were evaluated using the ELISA method. RESULTS: There were no significant differences between patients with or without PTSD in terms of cortisol, ACTH, BDNF levels. There were no correlations between CAPS-CA scores and cortisol, ACTH, and BDNF levels in patients with or without PTSD. In patients with PTSD, decreased cortisol levels were found with increasing time after trauma, and no significant correlation was found with the cortisol levels in patients without PTSD. CONCLUSION: Although no significant association was found between biochemical parameters and the presence or severity of PTSD; decreasing cortisol levels with increasing time after trauma in patients with PTSD suggest that cortisol might have played a role in the pathophysiology of this disorder.
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Factor Neurotrófico Derivado del Encéfalo/sangre , Abuso Sexual Infantil/psicología , Hidrocortisona/sangre , Trastornos por Estrés Postraumático/sangre , Trastornos por Estrés Postraumático/psicología , Adolescente , Hormona Adrenocorticotrópica/sangre , Niño , Depresión/psicología , Femenino , Humanos , Entrevista Psicológica , Masculino , Trastornos del Humor/epidemiología , Trastornos del Humor/psicología , Esquizofrenia/epidemiología , Psicología del Esquizofrénico , Factores Socioeconómicos , Trastornos por Estrés Postraumático/etiologíaRESUMEN
BACKGROUND: Acute pancreatitis is a significant potential complication with double-balloon enteroscopy. Hyperamylasemia is frequently observed after both double-balloon enteroscopy and single-balloon enteroscopy but often without associated pancreatitis. Whether the same phenomenon occurs with spiral enteroscopy is currently unknown. AIMS: To determine the incidence of pancreatitis and hyperamylasemia following spiral enteroscopy. METHODS: A prospective cohort study of consecutive patients undergoing proximal spiral enteroscopy was conducted. Serum amylase levels were measured immediately before and following the procedure, combined with observation for clinical signs of pancreatitis. RESULTS: A total of 32 patients underwent proximal spiral enteroscopy, with a mean total procedure time of 51 min (range 30 min to 100 min) and mean depth of insertion of 240 cm (range 50 cm to 350 cm). The diagnostic yield was 50%, with 31% of all procedures being therapeutic. While no patients exhibited signs that raised suspicion of pancreatitis, hyperamylasemia was common (20%). Hyperamylasemia was not significantly associated with procedure duration or depth of insertion but was linked to patients with Peutz-Jeghers syndrome and with the use of propofol sedation, suggesting that it may be more common in difficult cases. CONCLUSIONS: Postprocedural hyperamylasemia occurred frequently with proximal spiral enteroscopy, while no associated pancreatitis was observed. This finding suggests that hyperamylasemia may not necessarily reflect pancreatic injury nor portend a risk for pancreatitis.
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Anemia/terapia , Enteroscopía de Doble Balón/efectos adversos , Hiperamilasemia/epidemiología , Pancreatitis/epidemiología , Síndrome de Peutz-Jeghers/terapia , Adulto , Anciano , Anciano de 80 o más Años , Amilasas/sangre , Anemia/enzimología , Anemia/patología , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Femenino , Humanos , Hiperamilasemia/diagnóstico , Incidencia , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico , Síndrome de Peutz-Jeghers/enzimología , Síndrome de Peutz-Jeghers/patologíaRESUMEN
The small intestine has been difficult to examine by traditional endoscopic and radiologic techniques. Until the end of the last century, the small bowel follow through was the primary diagnostic tool for suspected small bowel disease. In recent years capsule endoscopy, deep enteroscopy using balloon-assisted or spiral techniques, computerized tomography and magnetic resonance enteroclysis or enterography have facilitated the diagnosis, monitoring, and management of patients with small bowel diseases. These technologies are complementary, each with its advantages and limitations. In the present article, we will discuss the different options and indications for modern diagnostic methods for visualization of the small bowel. We also try to provide a clinical rationale for the use of these different diagnostic options in less established, newly emerging, indications for small bowel evaluation.
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Endoscopía Gastrointestinal/métodos , Enfermedades Intestinales/diagnóstico , Intestino Delgado , Endoscopía Capsular/métodos , Enfermedad de Crohn/diagnóstico , Endoscopía Gastrointestinal/instrumentación , Hemorragia Gastrointestinal/diagnóstico , Humanos , Enfermedades Intestinales/diagnóstico por imagen , Enfermedades Intestinales/patología , Pólipos Intestinales/diagnóstico , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/patología , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: The usefulness of single-balloon enteroscopy (SBE) has not been evaluated in children with known or suspected Crohn's disease (CD). OBJECTIVE: The objectives of this study are to evaluate the diagnostic yield of SBE for pediatric CD by comparing it with US and magnetic resonance enterography (MRE). DESIGN: Single-center prospective study. SETTING: Tertiary-care referral hospital. PATIENTS: Between February 2009 and April 2010, 20 pediatric patients (ages 8-18 years) with suspected inflammatory bowel disease (IBD) or with a previous diagnosis of CD with suspected persistent small-bowel disease were enrolled. INTERVENTIONS: All patients underwent proximal and distal SBE, 17 patients also underwent US combined with Doppler flow measurements, and 18 underwent MRE. MAIN OUTCOME MEASUREMENTS: The findings of US with Doppler flow measurements and MRE were compared with those with SBE. RESULTS: The mean patient age was 15.0 years (range 11.3-18 years, 70% male). Of 14 patients with suspected IBD, 8 had a diagnosis of CD made after SBE. Activity in the small bowel was found in 14 patients (70%) with both suspected and previously diagnosed CD. Twelve patients (60%) had small-bowel disease that was out of reach of conventional endoscopy. Three patients (15%) had small-bowel activity solely in the jejunum, which was not detected by either MRE or US. LIMITATIONS: Single-center study with small sample size. CONCLUSIONS: SBE can be used in children to accurately assess small-bowel disease and CD. Small-bowel activity may be identified by SBE in some patients in whom it may not be apparent despite use of conventional upper endoscopy, ileocolonoscopy, US with Doppler flow measurements, or MRE.
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Enfermedad de Crohn/diagnóstico , Endoscopía Gastrointestinal , Imagen por Resonancia Magnética , Ultrasonografía Doppler , Adolescente , Niño , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Endoscopios Gastrointestinales , Femenino , Humanos , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/patología , Enfermedades del Yeyuno/diagnóstico , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: Retrograde double balloon enteroscopy (DBE) is important for evaluating the distal small bowel, but it is more challenging compared to the oral route. Optimizing small bowel insertion may enhance the diagnostic utility of the examination. We sought to determine if insertion depths achieved with retrograde DBE when performed as an isolated procedure differed significantly from when performed immediately following anterograde DBE. MATERIAL AND METHODS: A retrospective analysis was conducted of all retrograde DBE procedures performed at our center with comparisons made between "distal-only" DBE without preceding anterograde DBE and "combined" DBE after a prior same-day anterograde DBE. RESULTS: Two hundred ninety retrograde DBE procedures were performed in 264 patients over 5 years. Success of terminal ileal intubation exceeded 95%. The mean insertion depth into the distal small bowel differed significantly with 112 cm (95% CI 95-129) in the "distal-only" group and 92 cm (95% CI 85-98) in the "combined" group (p = 0.01), with a trend toward a corresponding increased diagnostic yield of 48% versus 37%, respectively (p = 0.15). Multivariate regression analysis identified both insertion route strategy (distal-only > combined; p = 0.01) and type of DBE endoscope (diagnostic > therapeutic; p = 0.02) as significant predictors of retrograde insertion depth. CONCLUSIONS: The insertion depth of retrograde DBE is significantly greater when carried out as a separate distal procedure and not in combination with a preceding anterograde DBE, and when performed using a diagnostic as opposed to the therapeutic DBE endoscope. This increased retrograde depth of insertion may be associated with an increased diagnostic yield.
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Enteroscopía de Doble Balón/métodos , Enfermedades Gastrointestinales/diagnóstico , Intestino Delgado/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Enteroscopía de Doble Balón/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis de Regresión , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Despite advances in training and equipment, complete colonoscopy fails, even in experienced hands, in up to 10% of cases. Double-balloon endoscopy (DBE) has been successfully used to complete colonoscopy in these patients. Single-balloon endoscopy (SBE) has become established for small-bowel enteroscopy. However, it has yet to be studied for use in colonoscopy. OBJECTIVE: To assess the efficacy, performance, and safety of single-balloon colonoscopy. DESIGN: Prospective cohort study. SETTING: Academic tertiary referral center. PATIENTS: Patients with previously failed conventional colonoscopy. RESULTS: 23 single-balloon colonoscopy procedures were performed in 22 patients: median age 53 (range 19-75) years; 14 females, 8 males. SBE colonoscopy succeeded in cecal intubation in 22 (96%) procedures, with a median total procedure time of 30 (range 20-60) minutes. SBE colonoscopy was normal in 9 cases but resulted in a positive diagnosis in 13 (57%) procedures, including polyps (n = 6), active Crohn's disease (n = 4), Crohn's-related stricture (n = 1), and diverticulosis (n = 2). Seven (30%) procedures were therapeutic including 1 case with balloon dilation and 6 cases with polypectomy. No complications were encountered. LIMITATIONS: Limited sample size, no direct comparison with double-balloon endoscopy. CONCLUSIONS: Single-balloon-assisted colonoscopy seems a safe and effective method for completing colonoscopy in patients with previously failed or difficult colonoscopy. The outcomes are similar compared with previous studies with DBE colonoscopy in this patient group.
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Cateterismo/instrumentación , Enfermedades del Colon/diagnóstico , Colonoscopios , Colonoscopía/métodos , Adulto , Anciano , Diagnóstico Diferencial , Diseño de Equipo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Complement system, an innate immunity, has been well documented to play a critical role in many inflammatory diseases. However, the role of complement in the pathogenesis of abdominal aortic aneurysm, which is considered an immune and inflammatory disease, remains obscure. METHODS AND RESULTS: Here, we evaluated the pathogenic roles of complement membrane attack complex and CD59, a key regulator that inhibits the membrane attack complex, in the development of abdominal aortic aneurysm. We demonstrated that in the angiotensin II-induced abdominal aortic aneurysm model, deficiency of the membrane attack complex regulator CD59 in ApoE-null mice (mCd59ab(-/-)/ApoE(-/-)) accelerated the disease development, whereas transgenic overexpression of human CD59 (hCD59(ICAM-2+/-)/ApoE(-/-)) in this model attenuated the progression of abdominal aortic aneurysm. The severity of aneurysm among these 3 groups positively correlates with C9 deposition, and/or the activities of MMP2 and MMP9, and/or the levels of phosphorylated c-Jun, c-Fos, IKK-alpha/beta, and p65. Furthermore, we demonstrated that the membrane attack complex directly induced gene expression of matrix metalloproteinase-2 and -9 in vitro, which required activation of the activator protein-1 and nuclear factor-kappaB signaling pathways. CONCLUSIONS: Together, these results defined the protective role of CD59 and shed light on the important pathogenic role of the membrane attack complex in abdominal aortic aneurysm.
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Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/prevención & control , Antígenos CD59/metabolismo , Proteínas del Sistema Complemento/metabolismo , Angiotensina II/efectos adversos , Animales , Aneurisma de la Aorta Abdominal/inducido químicamente , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Antígenos CD59/genética , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Femenino , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Modelos Animales , FN-kappa B/metabolismo , Transducción de Señal , Factor de Transcripción AP-1/metabolismoRESUMEN
OBJECTIVE: It is estimated that 10%-30% of Crohn's disease (CD) patients have small-bowel lesions, but the exact frequency and clinical relevance of these findings are unknown. Double-balloon enteroscopy (DBE) enables endoscopic visualization of the small bowel. The aim of this study was to evaluate the use of DBE for detecting small-bowel lesions in CD patients suspected of having small-bowel involvement. Furthermore, the clinical impact of adjusting treatment in these patients was assessed. MATERIAL AND METHODS: A prospective study was performed in a tertiary referral center. CD patients suspected of small-bowel involvement and in whom distal activity had previously been excluded were included. All patients underwent DBE, followed by step-up therapy in patients with small-bowel lesions. The presence of small-bowel lesions during DBE was noted and clinical outcome was assessed after adjusting therapy. RESULTS: Thirty-five patients (70%) showed small-bowel lesions; these lesions could not be assessed by conventional endoscopy in 23 (46%). At 1-year follow-up, step-up therapy in 26 patients (74%) led to clinical remission in 23 (88%). This was confirmed by a significant decrease in Crohn's disease activity index and mucosal repair on second DBE. CONCLUSIONS: DBE showed a high frequency of small-bowel lesions in known CD patients with clinically suspected small-bowel activity. Most of these lesions were not accessible for conventional endoscopy. Adjusting treatment in patients with small-bowel CD involvement led to clinical remission and mucosal repair in the majority of cases.
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Cateterismo , Enfermedad de Crohn/patología , Endoscopía Gastrointestinal , Intestino Delgado/patología , Adulto , Anciano , Distribución de Chi-Cuadrado , Enfermedad de Crohn/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Obesity is a complex, multifactorial chronic disease frequently associated with cardiovascular risks, hypertriglyceridemia, low high-density lipoprotein-cholesterol, high blood pressure, and the insulin resistance that appears to be central to the pathogenesis of Type II diabetes. Plasminogen activator inhibitor-1 expression induced in differentiating adipose tissue, but its role in adipogenesis and obesity is poorly understood. Circulating plasminogen activator inhibitor-1 levels are elevated at an early stage of impaired glucose tolerance, resulting in diabetes and metabolic syndrome. Plasminogen activator inhibitor-1 levels are also significantly elevated in the plasma of obese individuals and in adipose tissues of obese mice and humans. Some investigators proposed that the -675 4G/5G polymorphism in plasminogen activator inhibitor-1 promoter caused overexpression of this gene and predisposed carriers to obesity. In this study, we investigated the role of -675 4G/5G polymorphism in plasminogen activator inhibitor-1 promoter in the expression of this gene and the contribution of plasminogen activator inhibitor-1 to adipogenesis. Using a dual-luciferase promoter assay, we determined that the -675 4G/5G polymorphism contributes significantly to overexpression of plasminogen activator inhibitor-1 in the course of adipogenesis. The antidiabetic agents troglitazone and ciglitazone inhibited reporter gene expression driven by wild-type and -675 4G/5G mutant promoter, as well as the expression of endogenous plasminogen activator inhibitor-1, indicating that suppression of plasminogen activator inhibitor-1 expression may contribute to antidiabetic effects of these agents. The results indicate that absence of plasminogen activator inhibitor-1 in adipocytes may protect the cells against insulin resistance by promoting glucose uptake and adipocyte differentiation via a decrease in the peroxisome proliferator activated receptor-gamma expression that modulates the adipocyte differentiation.
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Adipocitos/citología , Diferenciación Celular , Inhibidor 1 de Activador Plasminogénico/genética , Células 3T3-L1 , Animales , Células Cultivadas , Cromanos/farmacología , Humanos , Resistencia a la Insulina , Ratones , PPAR gamma/fisiología , Inhibidor 1 de Activador Plasminogénico/fisiología , Polimorfismo Genético , Regiones Promotoras Genéticas , Tiazolidinedionas/farmacología , TroglitazonaRESUMEN
The objective of this study was to determine the distribution frequency of the fungi associated with wheat (Triticum aestivum) crowns and roots in cereal producing areas of Turkey through a targeted survey of 518 commercial fields over a 2-year period. More than 26% of the fields had one or more of the fungal species commonly reported as part of the dryland root rot complex, Fusarium culmorum (14%) > Bipolaris sorokiniana (10%) > F. pseudograminearum (2%). The fungi considered to be part of the high rainfall root rot complex were found at very low frequencies: 2% for Gaeumannomyces graminis and 3% for Pythium spp. Species of Rhizoctonia were found in 22% of the fields. Several Fusarium species considered to be less or nonpathogenic to cereals were also found in high frequencies at 11% (F. oxysporum, F. chlamydosporum), 10% (F. sporotrichioides), and 8% (F. avenaceum and F. solani). The mostly random distribution of cereal root-rotting species across the survey area suggests the fungi are not distributed in any distinct agroecological relationship. As a result, the relative economic importance of a given species on wheat will be determined by a number of factors, such as their fungal pathogenicity, host susceptibility/tolerance, and the seasonal conditions. Results from this study suggest that there are a wide range of fungal species associated with root and crown tissues of wheat.
RESUMEN
Since the introduction of the first balloon-based enteroscopic technique in 2001, therapeutic balloon-assisted enteroscopy (BAE) using either the single or double balloon enteroscopy technique (respectively SBE and DBE) has evolved rapidly. Argon plasma coagulation (APC), polypectomy, dilation therapy of strictures, and therapy of the pancreatico-biliary system in patients with surgical altered proximal intestinal anatomy: all have been successfully introduced to treat pathological findings in all segments of the small bowel. The clinical impact of treatment of vascular malformations, strictures caused by chronic inflammation (especially Crohn's disease) and polypectomy therapy (especially in the Peutz-Jeghers syndrome) seems evident. The decrease of, often repeated, surgical therapy after successful therapeutic BAE in the latter 2 patient groups appears to be a big step forward in treatment. The development of newer enteroscopes, specialized equipment and improved sedation of patients adds positively to the clinical management of undergoing therapeutic BAE. The overall complication rate of therapeutic BAE seems acceptable, but is higher compared to therapeutic colonoscopy which needs further attention in future.