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Background: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure.
Methods: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated.
Discussion: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment.
Trial registration: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).
Die Bewertung des Kastenwesens bei Mahatma Gandhi als Element des nationalen Unabhängigkeitskampfes
(1998)
Da die Kasten die gesellschaftliche Realität Indiens in vielen Bereichen noch immer bestimmen und sie aufgrund der Demokratisierung Indiens nach der Unabhängigkeit als einheitliche Wählergruppe auch verstärkt politischen Einfluß ausüben, hält die Diskussion über dieses gesellschaftliche Phänomen unvermin-dert an. Die dabei zu Tage tretenden Kontroversen betreffen nicht nur die wis-senschaftliche Theoriebildung bezüglich der Entstehung, Entwicklung und Funktionsweise des Kastenwesens, sondern prägen auch die Diskussion über zukunftsorientierte Gesellschaftsentwürfe. Solche Entwürfe haben entweder die völlige Zerschlagung aller Kastenstrukturen zum Ziel oder fordern zumindest deren umfassende Reform. So macht vor allem die Dalit-Bewegung das Kas-tenwesen für die eigene Unterdrückung und Diskriminierung in der Gesellschaft verantwortlich und zielt auf die Herauslösung der Dalits aus der bestehenden Gesellschaft ab, ohne jedoch explizit einen alternativen Gesellschaftsentwurf zu entwickeln.[1] Die Hindutva-Bewegung dagegen hat den Blick auf einen mo-dernen (Hindu-) Nationalstaat gerichtet, in dem ein die Gesellschaft zergliedern-des Kastenwesen ebenfalls keinen Platz hat, auch wenn dieser Bewegung von ihren Gegnern regelmäßig das Gegenteil unterstellt wird.[2] Swami Vivekanan-da sah den Weg zu einer Überwindung des Kastenwesens in der Brahmanisie-rung der gesamten Gesellschaft, die er religiös begründete, indem er das Ende des Kali-Yuga verkündete.[3] Die Hare-Krishna-Bewegung fordert eine Abwen-dung von einem erblich determinierten Kastenwesen hin zu einem System, in dem die Einordnung gemäß den Fähigkeiten und Leistungen des Individuums erfolgt. Ein solches System soll sich an vedischen Traditionen orientieren und an das viergliedrige Ständewesens des im Rigveda beschriebenen ‘Varnashrama’ angelehnt sein.[4] Der Gesellschaftsentwurf Mahatma Gandhis und vor allem die darin vertretene Sichtweise des Kastenwesens werden in der gegenwärtigen Diskussion ebenfalls immer wieder aufgegriffen, wobei je nach eigener ideologischer Ausrichtung sehr unterschiedliche Interpretationen gegeben werden. So wird Gandhi gelegentlich unterstellt, das Kastenwesen bedingungslos verteidigt zu haben, wäh-rend er anderen als scharfer Kritiker des Systems gilt. Dieses breite Spektrum an Einschätzungen erstaunt jedoch keineswegs, da Gandhis Aussagen zum Kas-tenwesen von großer Zurückhaltung geprägt sind und damit nur durch die ver-gleichende Analyse verschiedener Aussagen verständlich werden. Diese Analyse soll hier geleistet werden, wobei auch der historische Kontext miteinbezogen werden muß, durch den Gandhis Gedankengang erst seine Plausibilität gewinnt. ...
Wirkungen von Heilpflanzen, Gewürzen, Tees und Lebensmitteln werden in der Naturheilkunde seit der Antike genutzt. Pharmakologisch wirksam sind in der Regel nur die sekundären Pflanzeninhaltsstoffe. Diese in den oft aus vielen Bestandteilen zusammengesetzten Naturstoffen aufzuspüren und ihren molekularbiologischen Wirkungsmechanismus im Körper aufzuklären, ist das Ziel eines Forschungsnetzwerks am Frankfurter ZAFES (Zentrum für Arzneimittelforschung, -Entwicklung und -Sicherheit). So konnten Pharmazeuten und Kliniker gemeinsam herausfinden, wie ein Bestandteil des Rotweins, das Resveratrol, vor Darmkrebs schützt. Die Inhaltsstoffe von Salbei und Rosmarin bieten vielversprechende Ausgangspunkte für neue Medikamente gegen Altersdiabetes. Weihrauch, Myrte und Johanniskraut enthalten Wirkstoffe, die Schlüsselenzyme für Entzündungsreaktionen – etwa bei rheumatischen Beschwerden – hemmen.
Castes still determine the social reality of India in many fields and affect politics more and more by functioning as vote banks which are decisive in elections. Thus it is small wonder that there is an ongoing discussion about this social phe-nomenon. The controversies in the course of this discussion not only relate to academic theories concerning the origin, the evolution and the mode of opera-tion of the caste system but also determine the discussion about reform models for the Indian society. Such models either strive for the complete abolition of the caste system or at least call for a comprehensive reform of it. Especially the Dalit movement blames the caste system for the oppression and discrimination of the Dalits in society and tries to withdraw them from this system.[1] Yet the Dalit movement does not develop any alternative social draft. The Hindutva movement makes a strong effort to establish a modern (Hindu) nation which is only possible by overcoming the caste system that totally divides the society. Thus Hindutva is against the caste system though the antagonists of this move-ment usually maintain the contrary.[2] Swami Vivekananda holds that the only way to overcome the caste system is the Brahmanization of the whole society. For this he gives a religious explanation as he announces the end of the Kali-Yuga.[3] The Hare Krishna movement wants to turn away from a hereditary caste system towards a system where every individual is classified according to his skills and performance. Such a system should be based on Vedic traditions and especially on the fourfold varna system which is described in the ancient Rigveda.[4] Gandhi’s social draft and above all its attitude towards the caste system are often part of the current discussion but the interpretations differ according to the inter-preter’s ideological direction. Thus some charge Gandhi with having defended the caste system unconditionally, while others consider him a sharp critic of the system. This large spectrum is hardly surprising, since Gandhi’s comments are very reserved and can only become understandable by a comparative analysis of different statements on the caste system made by him during his political career. This article intends to provide such an analysis without neglecting the historical context which is vital to make Gandhi’s ideas clear. ...
Das Christentum in Kerala
(2000)
Nach der letzten indischen Volkszählung aus dem Jahre 1991 bekannten sich in Indien knapp 20 Mio. Menschen zum christlichen Glauben, was einem Bevölkerungsanteil von 2,34% entsprach. [1] Unter der Annahme, dass sich der Anteil der Christen an der Gesamtbevölkerung nicht signifikant verändert hat, liegt unter Berücksichtigung des allgemeinen Bevölkerungswachstums die Zahl der indischen Christen gegenwärtig bei etwa 23 Mio. Hinsichtlich der Verteilung der Christen gibt es erhebliche regionale Unterschiede. Über die Hälfte leben in den vier südlichen Unionsstaaten Kerala, Tamil Nadu, Karnataka und Andhra Pradesh, eine weitere Konzentration liegt im Nordosten Indiens (Assam, Nagaland, Meghalaya, Mizoram und Manipur) vor, wo noch einmal gut 20% der Christen leben. In den anderen Landesteilen sind sie dagegen sehr viel weniger zahlreich vertreten. ...
Observation of enhanced subthreshold K+ production in central collisions between heavy nuclei
(1994)
In the very heavy collision system 197Au+197Au the K+ production process was studied as a function of impact parameter at 1 GeV/nucleon, a beam energy well below the free N-N threshold. The K+ multiplicity increases more than linearly with the number of participant nucleons and the K+/ pi + ratio rises significantly when going from peripheral to central collisions. The measured K+ double differential cross section is enhanced by a factor of 6 compared to microscopic transport calculations if secondary processes (Delta N-->K Lambda N and Delta Delta -->K Lambda N) are ignored.
Protein catabolism should be reduced and protein synthesis promoted with parenteral nutrion (PN). Amino acid (AA) solutions should always be infused with PN. Standard AA solutions are generally used, whereas specially adapted AA solutions may be required in certain conditions such as severe disorders of AA utilisation or in inborn errors of AA metabolism. An AA intake of 0.8 g/kg/day is generally recommended for adult patients with a normal metabolism, which may be increased to 1.2–1.5 g/kg/day, or to 2.0 or 2.5 g/kg/day in exceptional cases. Sufficient non-nitrogen energy sources should be added in order to assure adequate utilisation of AA. A nitrogen calorie ratio of 1:130 to 1:170 (g N/kcal) or 1:21 to 1:27 (g AA/kcal) is recommended under normal metabolic conditions. In critically ill patients glutamine should be administered parenterally if indicated in the form of peptides, for example 0.3–0.4 g glutamine dipeptide/kg body weight/day (=0.2–0.26 g glutamine/kg body weight/day). No recommendation can be made for glutamine supplementation in PN for patients with acute pancreatitis or after bone marrow transplantation (BMT), and in newborns. The application of arginine is currently not warranted as a supplement in PN in adults. N-acetyl AA are only of limited use as alternative AA sources. There is currently no indication for use of AA solutions with an increased content of glycine, branched-chain AAs (BCAA) and ornithine-α-ketoglutarate (OKG) in all patients receiving PN. AA solutions with an increased proportion of BCAA are recommended in the treatment of hepatic encephalopathy (III–IV).
Introduction: Despite the excellent anti-inflammatory and immunosuppressive action of glucocorticoids (GCs), their use for the treatment of inflammatory bowel disease (IBD) still carries significant risks in terms of frequently occurring severe side effects, such as the impairment of intestinal tissue repair. The recently-introduced selective glucocorticoid receptor (GR) agonists (SEGRAs) offer anti-inflammatory action comparable to that of common GCs, but with a reduced side effect profile.
Methods: The in vitro effects of the non-steroidal SEGRAs Compound A (CpdA) and ZK216348, were investigated in intestinal epithelial cells and compared to those of Dexamethasone (Dex). GR translocation was shown by immunfluorescence and Western blot analysis. Trans-repressive effects were studied by means of NF-κB/p65 activity and IL-8 levels, trans-activation potency by reporter gene assay. Flow cytometry was used to assess apoptosis of cells exposed to SEGRAs. The effects on IEC-6 and HaCaT cell restitution were determined using an in vitro wound healing model, cell proliferation by BrdU assay. In addition, influences on the TGF-β- or EGF/ERK1/2/MAPK-pathway were evaluated by reporter gene assay, Western blot and qPCR analysis.
Results: Dex, CpdA and ZK216348 were found to be functional GR agonists. In terms of trans-repression, CpdA and ZK216348 effectively inhibited NF-κB activity and IL-8 secretion, but showed less trans-activation potency. Furthermore, unlike SEGRAs, Dex caused a dose-dependent inhibition of cell restitution with no effect on cell proliferation. These differences in epithelial restitution were TGF-β-independent but Dex inhibited the EGF/ERK1/2/MAPK-pathway important for intestinal epithelial wound healing by induction of MKP-1 and Annexin-1 which was not affected by CpdA or ZK216348.
Conclusion: Collectively, our results indicate that, while their anti-inflammatory activity is comparable to Dex, SEGRAs show fewer side effects with respect to wound healing. The fact that SEGRAs did not have a similar effect on cell restitution might be due to a different modulation of EGF/ERK1/2 MAPK signalling.
Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.
The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise questions regarding the unclarified heterogeneity of pathological mechanisms promoting disease progression. While biomarkers for the differentiation of Crohn’s disease (CD) versus ulcerative colitis (UC) have been suggested, specific markers for a CD subclassification in ileal CD versus colonic CD are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterize potential biomarkers by focusing on the downstream enzymes and metabolites of kynurenine metabolism. Using immunohistochemical stainings, we analyzed and compared the mucosal tryptophan immune metabolism in bioptic samples from patients with active inflammation due to UC or CD versus healthy controls. Localization-specific quantification of immune cell infiltration, tryptophan-metabolizing enzyme expression and mucosal tryptophan downstream metabolite levels was performed. We found generally increased immune cell infiltrates in the tissue of all patients with IBD. However, in patients with CD, significant differences were found between regulatory T cell and neutrophil granulocyte infiltration in the ileum compared with the colon. Furthermore, we observed decreased kynurenine levels as well as strong kynureninase (KYNU) expression specifically in patients with ileal CD. Correspondingly, significantly elevated levels of the kynurenine metabolite 3-hydroxyanthranilic acid were detected in the ileal CD samples. Highlighting the heterogeneity of the different phenotypes of CD, we identified KYNU as a potential mucosal biomarker allowing the localization-specific differentiation of ileal CD versus colonic CD.
