scholarly journals Parenteral Plant Sterols Accumulate in the Liver Reflecting Their Increased Serum Levels and Portal Inflammation in Children With Intestinal Failure

2016 ◽  
Vol 41 (6) ◽  
pp. 1014-1022 ◽  
Author(s):  
Maria Hukkinen ◽  
Annika Mutanen ◽  
Markku Nissinen ◽  
Laura Merras-Salmio ◽  
Helena Gylling ◽  
...  
2009 ◽  
Vol 296 (3) ◽  
pp. G643-G650 ◽  
Author(s):  
Aaron P. Garrison ◽  
Christopher M. Dekaney ◽  
Douglas C. von Allmen ◽  
P. Kay Lund ◽  
Susan J. Henning ◽  
...  

Expansion of intestinal progenitors and putative stem cells (pISC) occurs early and transiently following ileo-cecal resection (ICR). The mechanism controlling this process is not defined. We hypothesized that glucagon-like peptide-2 (GLP-2) would augment jejunal pISC expansion only when administered to mice immediately after ICR. Since recent reports demonstrated increases in intestinal insulin-like growth factor (IGF)-I following GLP-2 administration, we further hypothesized that increased intestinal IGF-I expression would correlate with pISC expansion following ICR. To assess this, GLP-2 or vehicle was administered to mice either immediately after resection (early) or before tissue harvest 6 wk following ICR (late). Histological analysis quantified proliferation and intestinal morphometrics. Serum levels of GLP-2 were measured by ELISA and jejunal IGF-I mRNA by qRT-PCR. Expansion of jejunal pISC was assessed by fluorescent-activated cell sorting of side population cells, immunohistochemistry for phosphorylated β-catenin at serine 552 (a pISC marker), percent of crypt fission, and total numbers of crypts per jejunal circumference. We found that early but not late GLP-2 treatment after ICR significantly augmented pISC expansion. Increases in jejunal IGF-I mRNA correlated temporally with early pISC expansion and effects of GLP-2. Early GLP-2 increased crypt fission and accelerated adaptive increases in crypt number and intestinal caliber. GLP-2 increased proliferation and intestinal morphometrics in all groups. This study shows that, in mice, GLP-2 promotes jejunal pISC expansion only in the period immediately following ICR. This is associated with increased IGF-I and accelerated adaptive increases in mucosal mass. These data provide clinical rationale relevant to the optimal timing of GLP-2 in patients with intestinal failure.


2014 ◽  
Vol 100 (4) ◽  
pp. 1085-1094 ◽  
Author(s):  
Annika Mutanen ◽  
Markku J Nissinen ◽  
Jouko Lohi ◽  
Päivi Heikkilä ◽  
Helena Gylling ◽  
...  

2013 ◽  
Vol 111 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Jogchum Plat ◽  
Elke Theuwissen ◽  
Constanze Husche ◽  
Dieter Lütjohann ◽  
Marion J. J. Gijbels ◽  
...  

Oxysterols (oxidised cholesterol) may play a role in the pathogenesis of CVD. Similar to cholesterol, plant sterols are susceptible to oxidation. However, less is known about the potential atherogenicity of oxidised plant sterols (oxyphytosterols). In the present study, the atherogenicity of a mixture of oxyphytosterols was examined by feeding female LDL receptor-deficient (LDLR+/ −) mice for 35 weeks a control diet (atherogenic high-fat diet; n 9), an oxysterol diet (control diet+0·025 % (w/w) oxysterols; n 12) or an oxyphytosterol diet (control diet+0·025 % (w/w) oxyphytosterols; n 12). In the LDLR+/ − mice, serum levels of cholesterol, lipoprotein profiles, cholesterol exposure and inflammatory markers at the end of the experiment were comparable between the three diet groups. Nevertheless, the proportion of severe atherosclerotic lesions was significantly higher after oxysterol (41 %; P= 0·004) and oxyphytosterol (34 %; P= 0·011) diet consumption than after control diet consumption (26 %). Oxyphytosterol levels in the lesions were the highest in the oxyphytosterol group. Here, we show that not only dietary oxysterols but also dietary oxyphytosterols increase the proportion of severe atherosclerotic lesions. This suggests that plant sterols when oxidised may increase atherosclerotic lesion severity instead of lowering the size and severity of lesions when fed in their non-oxidised form. Therefore, this finding might give an indication as to where to find the answer in the current hot debate about the potential atherogenicity of plant sterols. However, to what extent these results can be extrapolated to the human situation warrants further investigation.


2012 ◽  
Vol 54 (6) ◽  
pp. 803-811 ◽  
Author(s):  
Annika Kurvinen ◽  
Markku J. Nissinen ◽  
Sture Andersson ◽  
Päivi Korhonen ◽  
Tarja Ruuska ◽  
...  

Author(s):  
Julio H. Garcia ◽  
Janice P. Van Zandt

Repeated administration of methyl alcohol to Rhesus monkeys (Maccaca mulata) by intragastric tube resulted in ultrastructural abnormalities of hepatocytes, which persisted in one animal twelve weeks after discontinuation of the methyl alcohol regime. With dosages ranging between 3.0 to 6.0 gms. of methanol per kg. of body weight, the serum levels attained within a few hours averaged approximately 475 mg. per cent.


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