| 1. |
- Iresjö, Britt-Marie, 1963, et al.
(författare)
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Initiation factors for translation of proteins in the rectus abdominis muscle from patients on overnight standard parenteral nutrition before surgery.
- 2008
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Ingår i: Clinical science (London, England : 1979). - 1470-8736. ; 114:9, s. 603-10
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have provided conflicting conclusions concerning the efficacy of improving protein balance in patients by standard intravenous nutrition [TPN (total parenteral nutrition)], which is either explained by suboptimal nutritional regimens or insensitive clinical methods. The aim of the present study was therefore to evaluate the effects on the initiation of translation of skeletal muscle proteins by standard overnight TPN. A total of 12 patients who underwent standard surgery were included. TPN was provided as an all-in-one treatment by constant infusion [0.16 gN.kg(-1) of body weight.day(-1) (30 kcal.kg(-1) of body weight.day(-1))]. Saline-infused patients served as controls. Rectus abdominis muscle biopsies were taken at the time of the operation. The phosphorylation state of the proteins for initiation of translation was quantified. Plasma glucose, and serum insulin, glycerol, triacylglycerols (triglycerides) and NEFAs (non-esterified fatty acids; 'free fatty acids') were not significantly altered during TPN infusion, whereas total plasma amino acids increased, as shown by increases in methionine, phenylalanine, threonine, alanine, arginine, aspartic acid, glycine and histidine (P<0.05). Overnight TPN increased the formation of active eIF4G-eIF4E (where eIF is eukaryotic-initiation factor) complexes (P<0.05), whereas the inhibitory complex 4E-BP1 (eIF4E-binding protein)-eIF4E was moderately decreased (P<0.06). TPN increased the amount of the most phosphorylated form of 4E-BP1 (P<0.05), and increased the amount (P<0.04) and phosphorylation (P<0.01) of p70(S6K) (70 kDa ribosomal protein S6 kinase). In conclusion, an overnight pre-operative constant infusion of standard TPN altered initiation factor complexes, indicating activation of the initiation of protein translation in rectus abdominis muscle in the presence of increased plasma amino acid levels, but without a concomitant increase in energy substrates and insulin. In contrast with our results from previous studies, the methodology used in the present study appears to be more sensitive in reflecting directional changes in human muscle protein synthesis compared with traditional methods, particularly based on measurements of amino acid flux.
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| 2. |
- Lönnroth, Christina, 1946, et al.
(författare)
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Survival and erythropoietin receptor protein in tumours from patients randomly treated with rhEPO for palliative care.
- 2008
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Ingår i: Medical oncology (Northwood, London, England). - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 25:1, s. 22-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recombinant erythropoietin (rhEPOalpha) corrects anaemia, improves physical functioning and quality of life in cancer patients. However, published reports have suggested risks for tumour stimulation by provision EPO to patients with remaining tumour cells perhaps related to the presence of EPO receptor protein in tumour tissue. Therefore, the aim of the present study was to exclude a possibility that cancer patients who respond favourably to EPO treatment have mainly tumours with low EPO receptor protein expression. METHODS: Tumour tissue was evaluated in 87 patients out of 108 randomly allocated for treatment with rhEPOalpha (n = 50) versus controls (n = 58). Tumour cell proliferation (Ki-67 index) and EPO receptor protein expression were evaluated by immunohistochemistry. RESULTS: EPO treatment varied between 2 and 35 months, in doses between 10,000 and 40,000 Units/week. Ki-67 index did not differ between study and control patients before EPO treatment. Tumour tissue erythropoietin receptor protein was also similar between treated and untreated patients. Around 40% of tumour cells contained EPO receptors. Survival did not differ among EPO treated and control patients analysed as intention to treat, while survival was significantly improved in EPO treated patients per protocol treatment (P < 0.05). Ki-67 index and tumour tissue erythropoietin receptor protein did not predict survival, which systemic inflammation (ESR) did (P < 0.02). CONCLUSIONS: Our results support that reported risk to accelerate disease progression by EPO treatment in palliative care is not justified in patients with solid, gastrointestinal cancer despite tumour presence of EPO receptor protein.
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