Distribution of enteric glia and GDNF during gut inflammation

<p>Abstract</p> <p>Background</p> <p>The enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD). Enteric glia cells (EGCs) are the major source of glial-derived neurotrophic factor (GDNF), which regulates apoptosis of enterocytes. The aim of the study was to determine the distribution of EGCs and GDNF during gut inflammation and to elucidate a possible diminished enteric glia network in IBD.</p> <p>Methods</p> <p>The expression of glial fibrillary acidic protein (GFAP) in colonic biopsies of patients with IBD, controls and patients with infectious colitis was detected by immunohistochemistry and Western blot. Tissue GDNF levels were measured by ELISA.</p> <p>Results</p> <p>The expression of GFAP and GDNF in the mucosal plexus is highly increased in the inflamed colon of patients with ulcerative colitis (UC) and infectious colitis. Although the GDNF and GFAP content are increased in Crohn's disease (CD), it is significantly less. Additionally the non-inflamed colon of CD patients showed a reduced GFAP and no GDNF expression compared to controls and the non-inflamed colon of UC patients.</p> <p>Conclusions</p> <p>GFAP and GDNF as signs of activated EGCs are increased in the inflamed mucosa of patients with UC and infectious colitis, which underline an unspecific role of EGC in the regulation of intestinal inflammation. The reduced GFAP and GDNF content in the colon of CD patients suggest a diminished EGC network in this disease. This might be a part of the pathophysiological puzzle of CD.</p

Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's Disease

<p>Abstract</p> <p>Background</p> <p>Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures or motility disturbances. Hence, patients with Crohn's Disease (CD) are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence and abdominal pain, mimicking acute flare in these patients.</p> <p>Methods</p> <p>One-hundred-fifty patients with CD reporting increased stool frequency, meteorism and/or abdominal pain were prospectively evaluated for SIBO with the Hydrogen Glucose Breath Test (HGBT).</p> <p>Results</p> <p>Thirty-eight patients (25.3%) were diagnosed with SIBO based on positive findings at HGBT. SIBO patients reported a higher rate of abdominal complaints and exhibited increased stool frequency (5.9 vs. 3.7 bowel movements/day, p = 0.003) and lower body weight (63.6 vs 70.4 kg, p = 0.014). There was no correlation with the Crohn's Disease Activity Index. SIBO was significantly more frequent in patients with partial resection of the colon or multiple intestinal surgeries; there was also a clear trend in patients with ileocecal resection that did not reach statistical significance. SIBO rate was also higher in patients with affection of both the colon and small bowel, while inflammation of the (neo)terminal ileum again showed only tendential association with the development of SIBO.</p> <p>Conclusion</p> <p>SIBO represents a frequently ignored yet clinically relevant complication in CD, often mimicking acute flare. Because symptoms of SIBO are often difficult to differentiate from those caused by the underlying disease, targeted work-up is recommended in patients with corresponding clinical signs and predisposing factors.</p

Auswirkungen des Ernährungszustandes auf die Verträglichkeit einer Chemotherapie bei Patientinnen mit gynäkologischen Malignomen

In der klinischen Diagnostik gewinnt die Untersuchung des Ernährungszustandes zunehmend an Bedeutung. Denn die Güte des Ernährungszustandes hat einen Einfluss auf die Mortalität und Morbidität der Patienten. Zur groben Evaluierung des Ernährungszustandes dient der Body Mass Index (BMI). Eine differenzierte Beurteilung des Ernährungszustandes wird durch die Analyse der Körperzusammensetzung erreicht. Die phasensensitive bioelektrische Impedanzanalyse (BIA) ist eine schnelle, preisgünstige und nicht-invasive Methode zur Messung der Körperzusammensetzung. Insbesondere der Phasenwinkel, der ein direkter Messparameter der BIA ist, gibt einen schnellen Überblick über den Ernährungszustand der Patienten. Er spiegelt das Verhältnis von Extrazellulärmasse zu Körperzellmasse wieder, welches in vielen Studien als Indikator zur frühzeitigen Erfassung einer beginnenden Mangelernährung validiert wurde. Bei der Applikation einer Chemotherapie ist es von großer Bedeutung, dass die vorgesehene Dosis und Dosisintensität der Therapie eingehalten wird. Insbesondere unerwünschte Nebenwirkungen sind häufig für Dosisreduktionen und Verschiebungen der Chemotherapie verantwortlich. In einer prospektiven Studie wurde bei 40 Frauen, die sich aufgrund eines gynäkologischen Malignoms einer Chemotherapie unterzogen haben, die Körperzusammensetzung mit der BIA vor jedem Chemotherapiezyklus gemessen. Diese Studie zeigt, dass durch die Messung der Körperzusammensetzung ein Risikokollektiv, welches für Nebenwirkungen der Therapie anfällig ist, ermittelt werden kann. Der Body Mass Index (BMI) erwies sich als unzureichender Parameter zur Beschreibung des Ernährungszustandes der Patientinnen. Insbesondere muss mit einer erhöhten Rate von Nebenwirkungen der Chemotherapie bei einem verminderten Phasenwinkel, welcher einen reduzierten Ernährungszustand widerspiegelt, gerechnet werden.In clinical diagnostics the nutritional status is becoming more and more of interest. The nutritional status is closely connected with morbidity and mortality. It is usually evaluated by the body mass index (BMI). An exact estimation of nutritional status can be given by the measurement of body composition. The bioelectrical impedance analysis (BIA) allows a quick and non-invasive measurement of the body composition for each patient. A main point of interest is the phase angle, which is measured directly. It gives a prompt view on the nutritional status. There is a relation between the phase angle and the ECM/BCM-Ratio, a sensitive marker for early signs of malnutrition which was validated in many studies. For patients receiving chemotherapy (CT) it is especially important that the application of the therapy is administered in the right dose and dose intensity. Adverse events often lead to a dose reduction or delay of CT administration. In a prospective clinical study we measured consecutively 40 women receiving chemotherapy for a gynaecological malignancy. BIA was performed before each course of CT. The study demonstrates that an evaluation of the nutritional status can be used to predict the risk for adverse events in patients under chemotherapy. The BMI showed not to be a reliable parameter to estimate the nutritional status. A decreased phase angle which is a parameter for a reduced nutritional status showes that a higher rate of side effects in chemotherapy can be expected

GDNF protects enteric glia from apoptosis: evidence for an autocrine loop

Abstract Background Enteric glia cells (EGC) play an important role in the maintenance of intestinal mucosa integrity. During the course of acute Crohn's disease (CD), mucosal EGC progressively undergo apoptosis, though the mechanisms are largely unknown. We investigated the role of Glial-derived neurotrophic factor (GDNF) in the regulation of EGC apoptosis. Methods GDNF expression and EGC apoptosis were determined by immunofluorescence using specimen from CD patients. In primary rat EGC cultures, GDNF receptors were assessed by western blot and indirect immunofluorescence microscopy. Apoptosis in cultured EGC was induced by TNF-α and IFN-γ, and the influence of GDNF on apoptosis was measured upon addition of GDNF or neutralizing anti-GDNF antibody. Results Increased GDNF expression and Caspase 3/7 activities were detected in in specimen of CD patients but not in healthy controls. Moreover, inactivation of GDNF sensitized in EGC cell to IFN-γ/TNF-α induced apoptosis. Conclusions This study proposes the existence of an autocrine anti-apoptotic loop in EGC cells which is operative in Crohn's disease and dependent of GDNF. Alterations in this novel EGC self-protecting mechanism could lead to a higher susceptibility towards apoptosis and thus contribute to disruption of the mucosal integrity and severity of inflammation in CD.</p