| 1. |
- Ekelund, Mikael, et al.
(författare)
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Total Parenteral Nutrition Causes Circumferential Intestinal Atrophy, Remodeling of the Intestinal Wall, and Redistribution of Eosinophils in the Rat Gastrointestinal Tract.
- 2007
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 52:8, s. 1833-1839
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Tidskriftsartikel (refereegranskat)abstract
- Total parenteral nutrition (TPN) is held to cause intestinal atrophy and weaken mechanical and immunological barriers. To monitor the degree of atrophy caused by TPN, female Sprague-Dawley rats were, for 8 days, maintained on TPN (n = 6) and compared to identically housed controls given food and water ad libitum (n = 6). Specimens from jejunum, ileum, and colon were taken for histology and morphometric analysis. Topographic distribution and presence of eosinophils, by eosinophil peroxidase (EPO) staining, were examined in the gastric fundus, jejunum, ileum, and colon. Atrophy in terms of a markedly reduced circumference was noted throughout the intestinal tract in all rats subjected to TPN. The width of jejunal and ileal villi was narrowed and the length of jejunal villi was decreased. Furthermore, submucosal thickness in the jejunum and ileum increased. The height of ileal enterocytes remained unaltered. The number of goblet cells decreased in jejunal but not in ileal villi. The Paneth cells, suggested to play important roles in innate defense, increased in size. In the gastric fundus a marked increase in eosinophils was revealed predominantly in the mucosa and submucosa. The number and distribution of jejunal and ileal eosinophils were identical to those of controls. In colon from TPN rats, a redistribution of eosinophils was noted, causing a "band-like" accumulation of eosinophils in the basal portion of the mucosa. In conclusion, TPN causes gut atrophy and an increase in Paneth cell size. Eosinophils increase in number in the gastric fundus and a topographic redistribution occurs in the colon.
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| 2. |
- Berggren, Sofia, et al.
(författare)
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Gene and protein expression of P-glycoprotein, MRP1, MRP2 and CYP3A4 in the small and large human intestine
- 2007
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 4:2, s. 252-257
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Tidskriftsartikel (refereegranskat)abstract
- The cytochrome P450 3A4 enzyme and the ABC-transporters may affect the first-pass extraction and bioavailability of drugs and metabolites. Conflicting reports can be found in the literature on the expression levels of efflux transporters in human intestine and how they vary along the intestine. The relative levels of mRNA and protein of CYP3A4 and the ABC tranporters Pgp (ABCB1), MRP1 (ABCC1), and MRP2 (ABCC2) were determined using RT-PCR and Western blot for human intestinal tissues (n = 14) from jejunum, ileum and colon. The expression of mRNA for CYP3A4, Pgp, and MRP2 was highest in jejunum and decreased toward more distal regions, whereas MRP1 was equally distributed in all intestinal regions. For CYP3A4, a more significant correlation could be established between mRNA and protein expression than for the ABC transporters. The samples showed considerable interindividual variability, especially at the protein level. The apically located Pgp and MRP2 showed a similar expression pattern along the human intestine as for CYP3A4. The gene expression of MRP1 exhibited a more uniform distribution.
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| 3. |
- Mamboya, Florence Alex, 1971-
(författare)
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Heavy metal contamination and toxicity : Studies of Macroalgae from the Tanzanian Coast
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Concentrations of various metals are elevated above background levels in several intertidal areas along the Tanzanian coasts. However, there is little available information concerning the toxicity of these metals and how the uptake of these metals by bioindicators are influenced by external factors, such as heavy rains and increased coastal eutrophication, which tend to fluctuate.The present study focused on the uptake and toxicity of Cu and Zn in two common macroalgal species, Padina gymnospora (Phaeophyta) and Ulva reticulata (Chlorophyta). Laboratory studies were performed where metal content, growth (DGR), maximal quantum yields (Fv/Fm) and protein expression patterns (in Ulva) were measured as a response to exposure to Cu and Zn. The levels of metals accumulated in algal tissues correlated well to exposure concentrations and the longer the exposure time, the greater the uptake. However, an increased nutrient load (tested on Padina) or dilution of the seawater (tested on Ulva) affected both uptake of metals and their toxic effects. Here, DGR was more affected than Fv/Fm, suggesting DGR to be the more sensitive indicator of Cu and Zn toxicity. As shown by 2-D gel electrophoresis, more than ten proteins were up-regulated in U. reticulata after being exposed to Cu (1μg/L), while at higher concentrations (10 and 100 μg/L) of Cu numerous proteins were down-regulated.P. gymnospora was also used as a bioindicator to monitor long-term (1994–2005) and seasonal in-year variations in heavy metal concentrations in the Zanzibar Channel. No clear overall trends were revealed, but analysis of the combined dataset clearly pinpointed the most contaminated sites. It was concluded that seasonal and long-term variations, as well as environmental conditions need to be taken into consideration when using macroalgae as bioindicators.
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| 4. |
- Qader, Saleem, et al.
(författare)
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Expression of islet iNOS and inhibition of glucose stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27.
- 2007
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Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 292:5, s. 1447-1455
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Tidskriftsartikel (refereegranskat)abstract
- Chronic exposure of pancreatic islets to elevated plasma lipids ( lipotoxicity) can lead to beta-cell dysfunction, with overtime becoming irreversible. We examined, by confocal microscopy and biochemistry, whether the expression of islet inducible nitric oxide synthase ( iNOS) and the concomitant inhibition of glucose-stimulated insulin release seen after lipid infusion in rats was modulated by the islet neuropeptide pituitary adenylate cyclase-activating polypeptide ( PACAP) 27. Lipid infusion for 8 days induced a strong expression of islet iNOS, which was mainly confined to beta-cells and was still evident after incubating islets at 8.3 mmol/l glucose. This was accompanied by a high iNOS-derived NO generation, a decreased insulin release, and increased cyclic GMP accumulation. No iNOS expression was found in control islets. Addition of PACAP27 to incubated islets from lipid-infused rats resulted in loss of iNOS protein expression, increased cyclic AMP, decreased cyclic GMP, and suppression of the activities of neuronal constitutive ( nc) NOS and iNOS and increased glucose-stimulated insulin response. These effects were reversed by the PKA inhibitor H-89. The suppression of islet iNOS expression induced by PACAP27 was not affected by the proteasome inhibitor MG-132, which by itself induced the loss of iNOS protein, making a direct proteasomal involvement less likely. Our results suggest that PACAP27 through its cyclic AMP- and PKA-stimulating capacity strongly suppresses not only ncNOS but, importantly, also the lipid-induced stimulation of iNOS expression, possibly by a nonproteasomal mechanism. Thus PACAP27 restores the impairment of glucose-stimulated insulin release and additionally might induce cytoprotection against deleterious actions of iNOS-derived NO in beta-cells.
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