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Prostaglandin (PG) E2 (PGE2) plays a predominant role in promoting colorectal carcinogenesis. The biosynthesis of PGE2 is accomplished by conversion of the cyclooxygenase (COX) product PGH2 by several terminal prostaglandin E synthases (PGES). Among the known PGES isoforms, microsomal PGES type 1 (mPGES-1) and type 2 (mPGES-2) were found to be overexpressed in colorectal cancer (CRC); however, the role and regulation of these enzymes in this malignancy are not yet fully understood. Here, we report that the cyclopentenone prostaglandins (CyPGs) 15-deoxy-Δ12,14-PGJ2 and PGA2 downregulate mPGES-2 expression in the colorectal carcinoma cell lines Caco-2 and HCT 116 without affecting the expression of any other PGES or COX. Inhibition of mPGES-2 was subsequently followed by decreased microsomal PGES activity. These effects were mediated via modulation of the cellular thiol-disulfide redox status but did not involve activation of the peroxisome proliferator-activated receptor γ or PGD2 receptors. CyPGs had antiproliferative properties in vitro; however, this biological activity could not be directly attributed to decreased PGES activity because it could not be reversed by adding PGE2. Our data suggest that there is a feedback mechanism between PGE2 and CyPGs that implicates mPGES-2 as a new potential target for pharmacological intervention in CRC.
Ferric carboxymaltose (FCM) has been shown to achieve rapid replenishment of iron stores and correction of anaemia in various populations with iron deficiency. A decrease in serum phosphate (PO43−) levels, which in most cases is asymptomatic, has been reported with IV iron preparations. Hypophosphataemia (HP) is a known adverse drug reaction with FCM. This post hoc pooled analysis investigates the frequency, duration, risk factors, and clinical signs of HP as reported in interventional clinical trials with FCM. Pooled data from subjects enrolled across 45 clinical trials in different therapy areas were included. A three-step adjudication process was utilised to identify adverse events of HP. Stratified analyses by therapy group and stepwise logistic regression analysis were used to identify predictors of HP. This pooled analysis confirms that FCM is associated with increased rates of serum PO43− lowering, but mean serum PO43− values were seen to recover at Week 4 and further recover at Week 8. Among all subjects receiving FCM therapy (n = 6879), 41.4% (n = 2847) reached a PO43− nadir value <2.5 mg/dL at any point on study and 0.7% (n = 49) reached a nadir <1 mg/dL. Although gastroenterology and women’s health subjects were identified to be at higher risk, occurrence of severe HP (<1 mg/dL [0.3 mmol/L]) following FCM administration was not observed to be common among subjects in these studies. Furthermore, there was no correlation between laboratory serum PO43− values and the occurrence of reported adverse events related to low PO43− levels.
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).
Background: Anemia is a common condition in the elderly and a significant risk factor for increased morbidity and mortality, reducing not only functional capacity and mobility but also quality of life. Currently, few data are available regarding anemia in hospitalized geriatric patients. Our retrospective study investigated epidemiology and causes of anemia in 405 hospitalized geriatric patients.
Methods: Data analysis was performed using laboratory parameters determined during routine hospital admission procedures (hemoglobin, ferritin, transferrin saturation, C-reactive protein, vitamin B12, folic acid, and creatinine) in addition to medical history and demographics.
Results: Anemia affected approximately two-thirds of subjects. Of 386 patients with recorded hemoglobin values, 66.3% were anemic according to WHO criteria, mostly (85.1%) in a mild form. Anemia was primarily due to iron deficiency (65%), frequently due to underlying chronic infection (62.1%), or of mixed etiology involving a combination of chronic disease and iron deficiency, with absolute iron deficiency playing a comparatively minor role.
Conclusion: Greater awareness of anemia in the elderly is warranted due to its high prevalence and negative effect on outcomes, hospitalization duration, and mortality. Geriatric patients should be routinely screened for anemia and etiological causes of anemia individually assessed to allow timely initiation of appropriate therapy.
Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.
Chronic intestinal failure (CIF) is a rare but feared complication of Crohn’s disease. Depending on the remaining length of the small intestine, the affected intestinal segment, and the residual bowel function, CIF can result in a wide spectrum of symptoms, from single micronutrient malabsorption to complete intestinal failure. Management of CIF has improved significantly in recent years. Advances in home-based parenteral nutrition, in particular, have translated into increased survival and improved quality of life. Nevertheless, 60% of patients are permanently reliant on parenteral nutrition. Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy. The outcomes of patients with CIF could be greatly improved by more effective prevention, understanding, and treatment. In complex cases, the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation, nutritional support, and an improved quality of life. Here, we summarize current literature on CIF and short bowel syndrome, encompassing epidemiology, pathophysiology, and advances in surgical and medical management, and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.
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. ...
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. ...