Reduced blood flow and oxygenation in SA-1 tumours after electrochemotherapy with cisplatin.

Electrochemotherapy is an antitumour treatment that utilises locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. Besides increased drug delivery, application of electric pulses affects tumour blood flow. The aim of this study was to determine tumour blood flow modifying effects of electrochemotherapy with cisplatin, its effects on tumour oxygenation and to determine their relation to antitumour effectiveness. Electrochemotherapy of SA-1 subcutaneous tumours was performed by application of electric pulses to the tumours, following administration of cisplatin. Tumour blood flow modifying effects of electrochemotherapy were determined by measurement of tumour perfusion using the Patent blue staining technique, determination of tumour blood volume, and microvascular permeability using contrast enhanced magnetic resonance imaging, and tumour oxygenation using electron paramagnetic resonance oximetry. Antitumour effectiveness was determined by tumour growth delay and the extent of tumour necrosis and apoptosis. Tumour treatment by electrochemotherapy induced 9.4 days tumour growth delay. Tumour blood flow was reduced instantaneously and persisted for several days. This reduction in tumour blood flow was reflected in reduced tumour oxygenation. The maximal reduction in partial oxygen pressure (pO2) levels was observed at 2 h after the treatment, with steady recovery to the pretreatment level within 48 h. The reduced tumour blood flow and oxygenation correlated well with the extent of tumour necrosis and tumour cells apoptosis induced by electrochemotherapy with cisplatin. Therefore, the data indicate that antitumour effectiveness of electrochemotherapy is not only due to increased cytotoxicity of cisplatin due to electroporation of tumour cells, but also due to anti-vascular effect of electrochemotherapy, which resulted in reduced tumour blood flow and oxygenation.

Reduced tumor oxygenation by treatment with vinblastine.

Vinblastine (VLB) previously has been shown to perturb tumor blood flow, but the effect of these perturbations on tissue oxygenation is not known. The recent development of electron paramagnetic resonance (EPR) oximetry now has made it feasible to measure the effects of changes of perfusion on the pO(2) in tumors and normal tissues as a function of time and dose. We measured changes in tumor perfusion by Patent blue staining, tumor blood volume and microvascular permeability by contrast-enhanced magnetic resonance imaging, and tumor oxygenation by EPR in s.c. SA-1 murine tumors. We found that treatment with VLB induced dose-dependent reduction in tumor perfusion. One hour after i.p. treatment of mice with 2.5 mg/kg VLB, tumor perfusion was reduced to 20% of the pretreatment value and returned to close to original values within 48 h. A transient tumor blood flow-modifying effect of VLB was demonstrated also by contrast-enhanced magnetic resonance imaging; reduction of tumor blood volume and microvascular permeability was found. Reduced tumor oxygenation was found as measured by EPR oximetry, with the same time course of changes in tumor blood flow. Tumor oxygenation was reduced to 50% of pretreatment value 1 h after the treatment with 2.5 mg/kg VLB and returned to pretreatment levels within 24 h after the treatment. Although the directions of the changes in perfusion and oxygenation were similar, they were quantitatively different. Reduction in oxygenation of normal tissues, muscle, and subcutis also occurred but was smaller and returned to pretreatment values more quickly compared to the changes induced in the tumors. In conclusion, the present study demonstrates that VLB causes a profound reduction in tumor blood flow and oxygenation, which may have implications in controlling side effects of therapy and the planning of combined treatment with VLB, either with other chemotherapeutic drugs or with radiotherapy.

Local delivery of liposome-encapsulated superoxide dismutase and catalase suppress periodontal inflammation in beagles.

BACKGROUND, AIMS: The purpose of this study was to evaluate the influence of oxygen free radical scavengers on periodontal inflammation and healing process. METHOD: Experimental periodontitis was induced by elastic ligatures around premolars (P2, P3, P4) and 1st molars (M1) in the upper and lower jaws of 15 beagle dogs. 9 months after the beginning of the experiment, the ligatures were removed. After 3 weeks of stabilization period, all teeth were supragingivally scaled. The animals were divided into 3 groups of 5 dogs. The 1st group received a liposome-encapsulated superoxide dismutase (SOD), the 2nd group a liposome-encapsulated catalase (CAT) and the 3rd group received both enzymes encapsulated in liposomes. 4 treatment modalities were tested in each group; i.e., supragingival scaling only (1), supragingival scaling and enzymes (2), supra- and sub-gingival scaling and root planing (3) and supra- and sub-gingival scaling and root planing with subgingival application of enzymes (4). Enzymes were delivered subgingivally on a daily basis for a period of 6 weeks. Gingival index (GI), probing depth (PD), clinical attachment level (CAL), radiographic analysis and the histological evaluation were performed. RESULTS: Around the teeth with scaling and root planing followed by the application of SOD, the greatest suppression of gingival inflammation (GI = 1.8 +/- 0.1 before versus GI = 1.2 +/- 0.2 after treatment) (p<0.003), the smallest size of connective tissue infiltrate (5.5 +/- 4.3%) (p<0.01), the greatest reduction of PD (PD= 3.2 +/- 1.0 mm before versus 2.00.7 mm after treatment) (p<0.001), and gain of CAL (CAL=3.0 +/- 1.7 mm before versus CAL=2.4 +/- 1.1 mm after treatment) (p<0.001) were observed. In addition, radiographic analysis showed the greatest alveolar bone apposition in the group of teeth treated with scaling and root planing followed by subgingival application of SOD or both enzymes (p<0.001). CONCLUSION: In conclusion, we demonstrated that scaling and root planing with subgingival application of liposome-encapsulated SOD suppress peridontal inflammation on experimentally induced periodontitis in beagle dogs.

Diagnostic systems for assessing alveolar bone loss.

Radiological diagnostics serves as a basic monitoring technique for alveolar bone loss which is a severe consequence of periodontal disease. To evaluate efficacy of Conventional Visual Radiography (CVR), and to assess a complete clinical status, we had used two more diagnostic systems. These are Digital Subtraction Radiography (DSR) and Probing Pocket Depth (PPD). Experimental Periodontitis was studied in 20 beagle dogs based on the measurements taken in the beginning (baseline), and before (11th month) and after the medical treatment (12th month). Data analyses pointed out the same clinical trend, i.e. a significant bone loss prior to medical treatment and its recovery to the initial state. Differences in metrics and measurement errors could be identified as causes for discrepancies between the systems, but a relationship between the CVR and PPD is worth of further research, as these systems do not appear to be entirely compatible, but rather complementary to each other.