Insulin resistance in vascular endothelial cells promotes intestinal tumour formation.

The risk of several cancers, including colorectal cancer, is increased in patients with obesity and type 2 diabetes, conditions characterised by hyperinsulinaemia and insulin resistance. Because hyperinsulinaemia itself is an independent risk factor for cancer development, we examined tissue-specific insulin action in intestinal tumour formation. In vitro, insulin increased proliferation of intestinal tumour epithelial cells by almost two-fold in primary culture of tumour cells from ApcMin/+ mice. Surprisingly, targeted deletion of insulin receptors in intestinal epithelial cells in ApcMin/+ mice did not change intestinal tumour number or size distribution on either a low or high-fat diet. We therefore asked whether cells in the tumour stroma might explain the association between tumour formation and insulin resistance. To this end, we generated ApcMin/+ mice with loss of insulin receptors in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules and increased the frequency of neutrophils in tumours. We conclude that although insulin is mitogenic for intestinal tumour cells in vitro, impaired insulin action in the tumour microenvironment may be more important in conditions where hyperinsulinaemia is secondary to insulin resistance. Insulin resistance in tumour endothelial cells produces an activated, proinflammatory state that promotes tumorigenesis. Improvement of endothelial dysfunction may reduce colorectal cancer risk in patients with obesity and type 2 diabetes.

Dependence of tocopherol stability on different cooking procedures of food.

The influence of the kind of treatment during the preparation of hot meals (roasting, baking, stewing) on the stability of the tocopherols, which were added to the food through the margarines used, were examined in different food matrices. All preparation methods resulted in a loss of tocopherols. They could be divided into a group of only small loss of tocopherols (lower than 20%) and into a second group with nearly 70% loss of tocopherols (roasting of meat, steaming of peas). In the first group losses of tocopherols were directly associated with the fatty acid patterns of the used margarines, especially with the share of polyunsaturated fatty acids. On the other hand, during the roasting of meat nearly 70% of the tocopherols were destroyed by direct oxidation without a prohibitive effect on the lipid oxidation. The extreme high loss of tocopherols during the steaming of peas may be caused by the catalytic effect of the metal surface of the used pot. There were no losses of tocopherols observed when the experiments were repeated under identical conditions in an inert glass pot. Only tocopherol losses during baking may have a nutritional importance because of the great fat amount which are taken in with cookies.

[Modern anesthesiologic concepts supporting paranasal sinus surgery]. / Moderne Anästhesieverfahren in der endonasalen Nasennebenhöhlenchirurgie.

BACKGROUND: Optimal vision is essential for successful endonasal sinus surgery. Beside topical vasoconstriction general anaesthesia can contribute to reduce intraoperative bleeding. METHODS AND RESULTS: For many years deliberate hypotension was used to prevent intraoperative bleeding. The intentional reduction of systolic blood pressure to 50-60 mm Hg was achieved by the use of Sodium Nitroprusside alone or in combination with other vasoactive agents. However, intraoperative bleeding is not affected by this technique unless the systolic blood pressure falls below 60 mm Hg which can cause serious side effects for the patient. Recently, there is growing evidence that not only systolic blood pressure but also a low heart rate (< 60 beats per minute) can minimize surgical bleeding. With the introduction of total intravenous anaesthesia (TIVA) by the use of Propofol and Remifentanyl an anaesthetic technique has been established which fulfils the haemodynamic requirements in endonasal sinus surgery in many regards. The inhibiting effects on the cardiovascular system of these drugs alone can lead to a reduced bleeding. TIVA allows the reduction of the systolic blood pressure to 60 mm Hg as well as the heart rate below 60 beats per minute. If necessary it can be supported by vasoactive agents of which betablockers have a theoretical advantage. CONCLUSION: For general anaesthesia in endonasal sinus surgery Sodium Nitroprusside is no longer recommended. Instead a TIVA using Propofol and Remifentanil should be used.

Microbial spoilage and formation of biogenic amines in fresh and thawed modified atmosphere-packed salmon (Salmo salar) at 2 degrees C.

AIMS: To evaluate the microbial spoilage, formation of biogenic amines and shelf life of chilled fresh and frozen/thawed salmon packed in a modified atmosphere and stored at 2 degrees C. METHODS AND RESULTS: The dominating microflora, formation of biogenic amines and shelf life were studied in two series of storage trials with naturally contaminated fresh and thawed modified atmosphere-packed (MAP) salmon at 2 degrees C. Photobacterium phosphoreum dominated the spoilage microflora of fresh MAP salmon at more than 10(6) cfu g(-1) and the activity of this specific spoilage organism (SSO) limited the shelf life of the product to ca 14 and 21 d in the two experiments. Despite the high levels of P. phosphoreum, less than 20 mg kg(-1) histamine was observed in fresh MAP salmon prior to sensory spoilage. Freezing eliminated P. phosphoreum and extended the shelf life of MAP salmon at 2 degrees C by 1-2 weeks. Carnobacterium piscicola dominated the spoilage microflora of thawed MAP salmon and probably produced the ca 40 mg kg(-1) tyramine detected in this product at the end of its shelf life. CONCLUSIONS: Photobacterium phosphoreum dominated the spoilage microflora of fresh MAP salmon but produced only small amounts of biogenic amines in this product. The elimination of P. phosphoreum by freezing allowed this bacteria to be identified as the SSO in fresh MAP salmon. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of P. phosphoreum as the SSO in fresh MAP salmon facilitates the development of methods to determine and predict the shelf life of this product, as previously shown with fresh MAP cod.