Hyperbaric oxygen treatment did not significantly affect radiation injury in the mandibular area of rats.

OBJECTIVE: Hyperbaric oxygen therapy (HBOT) has been used to enhance microcirculation and thereby oxygen tension in tissues. The present study aimed to investigate the effect of HBOT on radiation injury in the mandibular area of rats. STUDY DESIGN: The left mandibles of rats were irradiated by external radiotherapy (15 Gy every other week for a total of 75 Gy). Four HBOT strategies were used: 2 prophylactic groups receiving HBOT either between each radiation treatment or immediately following terminated radiation treatment, and 2 therapeutic groups receiving HBOT after the latent period of 6 weeks after irradiation either every day (standard HBOT protocol) or 3 days a week for 6 weeks. Tissue samples of the irradiated area were taken from skin, the salivary gland, and the mandible. All tissues were stained with hematoxylin and eosin for morphologic examination. Furthermore, skin samples were stained with CD31 for blood vessel analysis. RESULTS: There was no change in blood vessel density or morphology between controls and HBOT tissues after radiation. The dentin of 2 of the 5 rats that received HBOT either normalized or was not affected by irradiation. CONCLUSIONS: HBOT did not affect radiation injury of the mandibular area in rats within 12 weeks after irradiation.

Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma.

BACKGROUND: Hypoxia is associated with increased resistance to chemo- and radiation-therapy. Hyperoxic treatment (hyperbaric oxygen) has previously been shown to potentiate the effect of some forms of chemotherapy, and this has been ascribed to enhanced cytotoxicity or neovascularisation. The aim of this study was to elucidate whether hyperoxia also enhances any actual uptake of 5FU (5-fluorouracil) into the tumor tissue and if this can be explained by changes in the interstitium and extracellular matrix. METHODS: One group of tumor bearing rats was exposed to repeated hyperbaric oxygen (HBO) treatment (2 bar, pO(2)= 2 bar, 4 exposures à 90 min), whereas one group was exposed to one single identical HBO treatment. Animals housed under normal atmosphere (1 bar, pO(2) = 0.2 bar) served as controls. Three doses of 5FU were tested for dose response. Uptake of [3H]-5FU in the tumor was assessed, with special reference to factors that might have contributed, such as interstitial fluid pressure (Pif), collagen content, oxygen stress (measured as malondialdehyd levels), lymphatics and transcapillary transport in the tumors. RESULTS: The uptake of the cytostatic agent increases immediately after a single HBO treatment (more than 50%), but not 24 hours after the last repeated HBO treatment. Thus, the uptake is most likely related to the transient increase in oxygenation in the tumor tissue. Factors like tumor Pif and collagen content, which decreased significantly in the tumor interstitium after repeated HBO treatment, was without effect on the drug uptake. CONCLUSION: We showed that hyperoxia increases the uptake of [3H]-5FU in DMBA-induced mammary tumors per se, independently of changes in Pif, oxygen stress, collagen fibril density, or transendothelial transport alone. The mechanism by which such an uptake occur is still not elucidated, but it is clearly stimulated by elevated pO(2).

A novel function of insulin in rat dermis.

In this study we present a novel function of insulin in rat dermis. We investigated local effects of insulin on interstitial fluid pressure (Pif), and capillary albumin leakage and pro-inflammatory cytokine production in skin and serum after intravenous lipopolysaccharide (LPS), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) challenge treated with a glucose-insulin-potassium regimen (GIK). The main objective for this study was to investigate anti-inflammatory effects of insulin. Work by others shows that insulin stimulates cell adhesion, and that this effect is dependent upon phosphatidylinositol 3-kinase (PI3K) activity. Cytokines like platelet-derived growth factor BB (PDGF-BB) attenuate lowering of Pif, possibly via PI3K. LPS and pro-inflammatory cytokines contribute to oedema development during acute inflammation by lowering the Pif. Intravenous injection of LPS, TNF-alpha or IL-1beta to Wistar Møller rats caused a lowering of Pif, but after local injection of insulin in the paw, Pif increased back to control values. IL-1beta caused a lowering in control from -0.5 +/- 0.2 mmHg to -3.0 +/- 0.2 mmHg after 20 min (mean +/- S.E.M.) (P < 0.05). Within 50 min after insulin injection the pressure was increased to -0.6 +/- 0.2 mmHg (P > 0.05 compared with control). Insulin was given together with a PI3K inhibitor (wortmannin) locally in the skin, almost abolishing the effect of insulin on Pif. A GIK regimen was given as a continuous intravenous infusion, significantly attenuating the oedema formation after LPS or TNF-alpha/IL-1beta challenge. The same GIK regimen caused a significant reduction in pro-inflammatory cytokines in serum and in interstitial fluid in skin of endotoxaemic rats. These experiments show a possible role for insulin in the interstitium during inflammation induced by LPS and TNF-alpha/IL-1beta. Insulin can attenuate a lowering of Pif possibly via PI3K, and it has an anti-inflammatory effect by inhibiting production of pro-inflammatory cytokines.