High-dose, short-term, anti-inflammatory treatment with dexamethasone reduces growth and augments the effects of 5-fluorouracil on dimethyl-alpha-benzanthracene-induced mammary tumors in rats.

OBJECTIVE: To evaluate the effects of dexamethasone (DXM) alone or in combination with 5-fluorouracil (5-FU) on dimethyl-alpha-benzanthracene (DMBA)-induced mammary tumors in rats. MATERIAL AND METHODS: Female Sprague-Dawley rats were divided into 4 groups receiving: 1) saline (controls), 2) DXM (3 mg/kg), 3) 5-FU (1.5 mg/kg) and 4) DXM and 5-FU combined. The drugs were given i.p. every day for 4 days. Interstitial fluid pressure (Pif) and tumor growth were determined in all tumors on days 1, 5 and 7 using the "wick-in-the needle" technique and by external size measurements, respectively. Vessel density and inflammatory cell infiltration of tumor tissue were analyzed by immunohistochemistry. RESULTS: DXM treatment significantly retarded tumor growth and reduced Pif. Treatment with a combination of DXM and 5-FU reduced tumor size significantly more than any of the agents alone (p<0.01-0.001). Enhanced uptake of 5-FU by DXM treatment was demonstrated by microdialysis. There were no differences in the density of CD31-positive vessels after DXM or 5-FU treatment, but inflammatory cell infiltration of tumor tissue was significantly reduced after DXM treatment. CONCLUSIONS: Our data suggest that DXM may be beneficial as an adjuvant to chemotherapy in the treatment of mammary cancer by increasing the uptake of 5-FU in the tumor.

No changes in lung function after a saturation dive to 2.5 MPa with intermittent reduction in Po2 during decompression.

Decompression stress and exposure to hyperoxia may cause a reduction in transfer factor of the lung for carbon monoxide and in maximal aerobic capacity after deep saturation dives. In this study lung function and exercise capacity were assessed before and after a helium-oxygen saturation dive to a pressure of 2.5 MPa where the decompression rate was reduced compared with previous deep dives, and the hyperoxic exposure was reduced by administering oxygen intermittently at pressures of 50 and 30 kPa during decompression. Eight experienced divers of median age 41 years (range 29-48) participated in the dive. The incidence of venous gas microemboli was low compared with previous deep dives. Except for one subject having treatment for decompression sickness, no changes in lung function or angiotensin converting enzyme, a marker of pulmonary endothelial cell damage, were demonstrated. The modified diving procedures with respect to decompression rate and hyperoxic exposure may have contributed to the lack of changes in lung function in this dive compared with previous deep saturation dives.

Increased oxygen before and during decompression reduces bubble formation in rats.

The aim of this study was to test the hypothesis that increased oxygen partial pressure shortly before and during decompression from hyperbaric pressures would decrease venous gas bubble formation. Bubbles were detected by an ultrasound Doppler technique in conscious, freely moving rats. All rats were exposed twice to 6 bar for 2 hours. In exposure A, the breathing gas mixture was 1 bar O2 and 5 bar N2. In exposure B, the breathing gas was changed to 2 bar O2 and 4 bar N2, 5 min prior to decompression. The decompression rate was 0.1 bar x s(-1) in both groups. Significantly fewer bubbles were detected after decompression in exposure B compared to A. The angiotensin converting enzyme (ACE) concentration in serum was measured as an indicator of possible damage to the pulmonary endothelium induced by bubbles. However, no correlation between ACE and bubble amount was found. In conclusion, this study in conscious rats indicates that safer decompression may be obtained by increasing the oxygen partial pressure before and during decompression.

Fluid pressure in human dermal fibroblast aggregates measured with micropipettes.

Previous studies indicated that connective tissue cells in dermis are involved in control of interstitial fluid pressure (Pif). We wanted to develop and characterize an in vitro model representative of loose connective tissue to study dynamic changes in fluid pressure (Pf) over a time course of a few minutes. Pf was measured with micropipettes in human dermal fibroblast cell aggregates of varying size (<100- and >100-microm diameter) and age (days 1-4) kept at different temperatures (approximately 15, 25, and 35 degrees C). Pressures were measured at different depths of micropipette penetration and after treatment with prostaglandin E1 isopropyl ester (PGE1), latanoprost (PGF2alpha), and ouabain. Pf was positive (more than +2 mmHg) during control conditions and increased with increasing aggregate size (day 2), age (day 4 vs. day 1), temperature, and depth of micropipette penetration. Pf decreased from 2.9 to 2.0 mmHg during the first 10 min after application of 10 microl of 1 mM PGE1 (P < 0.001). Pf increased from 3.0 to 4.8 mmHg (P < 0.01) after administration of 10 microl of 1.4 microM ouabain and from 3.1 to 4.4 mmHg after addition of 5 microl of 1.42 mM PGF2alpha (P > 0.05). In conclusion, we have developed and validated a new in vitro method for studying fluid pressure in loose connective tissue elements with the advantage of allowing reliable and rapid screening of substances that have a potential to modify Pf and studying in more detail specific cell types involved in control of Pf. This study also provides evidence that fibroblasts in the connective tissue can actively modulate Pf.

Effects of normobaric hyperoxia on water content in different organs in rats.

Pulmonary oxygen toxicity is a dose-dependent effect on alveolar epithelial and endothelial cells resulting in pulmonary oedema. Any concomitant effects on systemic capillary endothelium would be expected to result in capillary leakage and an increase in the tissues' water content. Total tissue water (TTW) in different organs was therefore studied in freely moving rats exposed to 100% O2 at normobaric pressure for 24 or 48 h, and compared to air-breathing control rats. The TTW for the following tissues was measured: Trachea, left bronchus, left lung, left and right ventricle, left kidney, skin (left paw-hindlimb), skin (back of the rat), left brain, left eye and thigh muscle left side. There was a significant increase in TTW of the lung accompanied by pleural effusion after 48 h of oxygen exposure as expected in all exposed animals. There was a small increase in TTW of the paw only, and a small decrease or no change in other tissues after 24 and 48 h of exposure. We conclude that there is no evidence of systemic capillary dysfunction as measured by tissue water content after exposure to hyperoxia in a dosage causing pulmonary oedema.