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Aims: The main objectives of the present study was to establish an animal model of decompression sickness (DCS) after heliox saturation diving, and to use this model to evaluate possible morphological changes in the CNS induced by DCS using structural MRI., Methods: Two groups of rats were pressurized with heliox to 5 bar (pO2 = 50 kPa). The saturation time was three hours; decompression rate was 1 bar/10 seconds or 1 bar/20 seconds. A 7.0 Tesla small animal MRI scanner was used for detection of possible morphological changes in the brain and spinal cord, two hours and one week after the dive, compared to one week prior to the dive., Results: Neurological symptoms of DCS were observed in seven out of 10 animals. MRI of the brain and spinal cord did not reveal any morphological CNS injuries., Conclusion: This diving procedure was successful in causing DCS in a large proportion of the animals. However, despite massive neurological signs of DCS, no visible CNS injuries were observed in the MRI scans.

Stroma properties affect carcinoma physiology and direct malignant cell development. Here we present data showing that α(V)β(3) expressed by stromal cells is involved in the control of interstitial fluid pressure (IFP), extracellular volume (ECV) and collagen scaffold architecture in experimental murine carcinoma. IFP was elevated and ECV lowered in syngeneic CT26 colon and LM3 mammary carcinomas grown in integrin β(3)-deficient compared to wild-type BALB/c mice. Integrin β(3)-deficiency had no effect on carcinoma growth rate or on vascular morphology and function. Analyses by electron microscopy of carcinomas from integrin β(3)-deficient mice revealed a coarser and denser collagen network compared to carcinomas in wild-type littermates. Collagen fibers were built from heterogeneous and thicker collagen fibrils in carcinomas from integrin β(3)-deficient mice. The fibrotic extracellular matrix (ECM) did not correlate with increased macrophage infiltration in integrin β(3)-deficient mice bearing CT26 tumors, indicating that the fibrotic phenotype was not mediated by increased inflammation. In conclusion, we report that integrin β(3)-deficiency in tumor stroma led to an elevated IFP and lowered ECV that correlated with a more fibrotic ECM, underlining the role of the collagen network for carcinoma physiology.

Introduction: Dehydration may increase the risk for decompression sickness (DCS). Since DCS most probably is caused by endogenous gas phase formation, we hypothesized that decompression will induce more venous gas emboli (VGE) in dehydrated rats compared to controls., Methods: Two groups of rats were pressurized to 0.5 MPa (5 ATA) on heliox for 16 h, and thereafter decompressed to atmospheric pressure at a rate of 0.3 MPa x min(-1). The nine control rats had free access to water ad libitum whereas the eight dehydrated rats were water-deprived for 48 h before decompression. During and after decompression, VGE was measured in the vena cava for 60 min with the Doppler technique and graded into six bubble grade (BG) categories. Body mass (BM), and food and water intake were registered daily, and venous blood samples were taken before and after pressure exposure., Results: Serum osmolality and hematocrit increased significantly in dehydrated rats (306 +/- 5.2 to 315 +/- 7.3 mosmol x kg(-1) and 39.3 +/- 4.9 to 49.6 +/- 5.2%) but not in controls (300 +/- 8.9 to 303 +/- 6.7 mosmol x kg(-1) and 40.3 +/- 5.2 to 41.4 +/- 6.1%). Plasma volume decreased by 9.2% (P < 0.05) and 2.8% (n.s.) in dehydrated and control rats. VGE were detected in all control animals (average BG: 2.8 +/- 1.9), but only in four water-deprived rats (BG: 1.6 +/- 2.2). This difference was not significant., Conclusions: Our experiments do not support the idea that dehydration increases circulatory VGE.

The stroma of carcinomas shares several characteristics with inflamed tissues including a distorted vasculature, active angiogenesis and macrophage infiltration. In addition, the tumor interstitial fluid pressure (P(IF)) of the stroma is pathologically elevated. We show here that bevacizumab [rhuMab vascular endothelial growth factor (VEGF), Avastin], a monoclonal antibody to VEGF, at a dose of 5 mg/kg modulated inflammation in KAT-4 xenograft human anaplastic thyroid carcinoma tissue. At this dose, bevacizumab reduced the density of macrophages, MHC class II antigen expression by macrophages and IL-1beta mRNA expression. Furthermore, bevacizumab lowered tumor extracellular fluid volume, plasma protein leakage from tumor vessels, the number of CD31-positive structures and tumor P(IF). The tumor plasma volume and the number of alpha-smooth muscle actin-positive vessels, however, remained unchanged. Our data suggest that carcinoma cell-derived VEGF either directly or indirectly participates in maintaining an inflammatory microenvironment in experimental KAT-4 carcinoma. Furthermore, our data indicate that the reduction of inflammation resulting in reduced vascular permeability and decrease in the tumor extracellular fluid volume by bevacizumab contributes to reduced tumor P(IF)., (Copyright 2006 Wiley-Liss, Inc.)

Chemotherapy of solid tumors is presently largely ineffective at dosage levels that are compatible with survival of the patient. Here, it is argued that a condition of raised interstitial fluid pressure (IFP) that can be observed in many tumors is a major factor in preventing optimal access of systemically administered chemotherapeutic agents. Using prostaglandin E1-methyl ester (PGE1), which is known transiently to reduce IFP, it was shown that 5-fluorouracil (5-FU) caused significant growth inhibition on two experimental tumors in rats but only after administration of PGE1. Furthermore, timing experiments showed that only in the period in which IFP is reduced did 5-FU have an antitumor effect. These experiments uniquely demonstrate a clear and, according to the starting hypothesis, logical, synergistic effect of PGE1 and 5-FU that offers hope for better treatment of many tumors in which raised IFP is likely to be inhibiting optimal results with water-soluble cancer chemotherapeutic agents.