Pituitary adenylyl cyclase activating peptide (PACAP) is expressed in central, sensory, autonomic, and enteric neurons. Although it classically acts as a neurotransmitter/neuromodulator, recent studies indicate that PACAP can also regulate immune function. To this effect, PACAP has been shown to reduce clinical symptoms and inflammation in mouse models of human immunebased diseases such as rheumatoid arthritis, Crohn's Disease, septic shock and multiple sclerosis. Despite these findings, the role of the endogenous peptide in regulating immune function is unknown. To determine if endogenous PACAP plays a protective role in inflammatory bowel disease (IBD) and IBD-associated colorectal cancer in mice, PACAP-deficient (KO) mice were subjected to 3 cycles of dextran sulfate sodium (DSS) in drinking water over 2 months, an established mouse model for colitis. Compared to wild type (WT) controls, PACAP KO mice exhibited more severe clinical symptoms of colitis and had significantly higher colonic inflammation on pathological examination. Moreover, 60% of the PACAP KO mice developed colorectal tumors with an aggressive-appearing pathology. Consistent with published data, DSS-treated WT mice did not develop such tumors. The results demonstrate a new mouse model which rapidly develops inflammation-associated colorectal cancer in the absence of a carcinogen. ' 2007 Wiley-Liss, Inc.Key words: pituitary adenylyl cyclase activating peptide (PACAP); inflammation; colorectal cancer; colitis; cancer Chronic inflammatory diseases are known to be linked to the development of cancer.1 In one of the more prominent examples, colorectal cancer (CRC) occurs at a significantly higher rate in patients with inflammatory bowel disease (IBD) compared to the normal population. The increased incidence of CRC in IBD patients appears to be most pronounced in individuals with extensive and long-term ulcerative colitis.2 The rate of CRC begins to increase significantly after 10 years of colitis, with a cumulative probability of 18% after 30-year duration. Like its more common counterpart, sporadic CRC, the prognosis for IBD-associated CRC is poor: the 5-year survival rate is about 50%. Preventative treatment includes colectomy and the use of drugs. Retrospective studies suggest that chronic treatment with 5-aminosalicylic acid or related drugs can reduce the incidence of CRC in patients with IBD, although the studies are not conclusive, and the mechanism of drug action is uncertain. COX-2 inhibitors may also provide protection and appear to have less potential to aggravate IBD than other nonsteroidal antiinflammatory drugs. Despite potential preventative measures in these patients, the incidence of CRC remains high, and new therapeutic modalities must be explored. Moreover, improved animal models are needed to better understand the disease, to test new treatments, and to understand the mechanisms of action of various treatments. In this regard, several rodent models have been developed to study the pathogenesis of chronic ulcerative colitis and...
A non‐refined, organic pumpkin seed oil (PSO) was chosen for the isolation and structure verification of the rare vitamin E compound γ‐tocomonoenol (γ‐T1). Initial measurements indicated the presence of ~0.4 mg γ‐T1 per 100 g PSO. Saponification of ~2 L of PSO, followed by repeated countercurrent chromatography (CCC) with the solvent system n‐hexane/benzotrifluoride/acetonitrile (v/v/v) and silica gel column chromatography enabled the isolation of 6.8 mg γ‐T1 with a purity of 96.0% according to gas chromatography with mass spectrometry (GC/MS) analysis. Structural analysis by 1H nuclear magnetic resonance (NMR) spectroscopy and GC/MS of the γ‐T1 isolate confirmed the presence of a double bond in C‐11′‐position (11′‐γ‐tocomonoenol). In addition, CCC fractionation enabled the detection of 18 different tocochromanols, many of which were reported for the first time in PSO. This unmatched variety included among others α‐/γ‐tocopherol, α‐/γ‐tocomonoenol, two α‐ and two γ‐tocodienol isomers, α‐/γ‐tocotrienol as well as the rare 11′‐β‐tocomonoenol (β‐T1) and δ‐T1. Three uncommon tocochromanols were also detected whose origins and structure remained unclear.
Berry pomace, rich in polyphenols, especially anthocyanins, accumulates during the production of red juices. Pomace from chokeberry (Aronia melanocarpa Michx.), bilberry (Vaccinium myrtillus L.), and elderberry (Sambucus nigra L.) represent good sources of coloring foodstuffs. Pomace powders (PP) were prepared by milling the seedless fractions of the three dried berry pomaces (50 °C, 8 h). Techno-functional properties of the powders such as particle size distribution, bulk density, sedimentation velocity, and swelling capacity were determined to evaluate the powders for possible food applications. Total anthocyanin content was quantified by UHPLC-DAD before and during a storage experiment to monitor the degradation of anthocyanins in the PP and in a yogurt model application. The high content of phenolic compounds and the still intact cell structure ensured high stability of anthocyanins over 28 days of storage. In the model application, color saturation was stable over the whole storage time of 14 days. Regarding the techno-functional properties, only a few differences between the three PP were observed. The particle size of elderberry PP was larger, resulting in lowest bulk density (0.45 g/mL), high cold-water solubility (16.42%), and a swelling capacity of 10.16 mL/g dw. Sedimentation velocity of the three PP was fast (0.02 mL/min) due to cluster formation of the particles caused by electrostatic and hydrophobic properties. Compared to other high-intensity coloring foodstuffs, the use of PP, showing acceptable color stability with potential health-promoting effects, represents a wide applicability in different food applications and especially in products with a longer shelf-life.
Bei Vitamin E handelt es sich um den Überbegriff für eine Klasse natürlich vorkommender, fettlöslicher Antioxidationsmittel [1]. Ihr Grundgerüst besteht aus einem 6-Chromanolring, an welchem sich u.a. eine isoprenoide Seitenkette befindet. Diese ist bei den Tocopherolen vollständig gesättigt, die Tocotrienole enthalten hingegen drei Doppelbindungen in der Seitenkette [2]. Die jeweils vier klassischen α-, β-, -und δ-Homologe der Tocopherole und Tocotrienole unterscheiden sich durch unterschiedliche Substitution des 6-Chromanolsrings mit Methylgruppen [1]. In jüngerer Vergangenheit wurden außerdem Tocomonoenole und Tocodienole (eine bzw. zwei Doppelbindungen in der Seitenkette) entdeckt [2]. Diese neuen Vertreter kommen in pflanzlichen Ölen viel seltener und meist in geringeren Mengen vor als die klassischen Vitamin-E-Verbindungen, weshalb es bisher nur gelingen konnte, α-Tocomonoenol als Reinsubstanz zu gewinnen [3]. Für eine exakte Quantifizierung und physiologische Studien sind Standardsubstanzen jedoch notwendig [3].
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