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Biomedical subjects

M Marczak

Publications and source records attributed to M Marczak.

40 records · Page 3Linked to original sources

Ascorbic acid enhances hypoxic ventilatory reactivity in elderly subjects.

The reducing properties of ascorbic acid in the carotid body make it a likely modifier of hypoxia-sensing mechanisms. This open-label study aimed to determine the effect of ascorbic acid on the hypoxic ventilatory response (HVR) in a population of elderly women, in whom both hypoxic reactivity and ascorbic acid levels may be deficient. We examined the HVR to progressive eucapnic hypoxia in 18 healthy females aged 60-80 years, before and after 10 days' ascorbic acid supplementation, given as a sustained release preparation of 1 g twice daily. Respiratory variables were recorded breath by breath, and hypoxic sensitivity was assessed from the linear slopes of minute ventilation and mouth occlusion pressure plotted against oxygen saturation. We found that ascorbic acid increased the HVR by a mean of 44%, this effect being driven by a higher occlusion pressure. We conclude that augmentation of hypoxic reactivity by ascorbic acid may have therapeutic potential in pathologies associated with hypoxia, which frequently develop in old age.

Aged↗

Potentiated antitumor effects of interleukin 12 and matrix metalloproteinase inhibitor batimastat against B16F10 melanoma in mice.

The application of antiangiogenic agents in cancer therapy has been studied extensively. Combination of agents with antiangiogenic properties could possibly enhance antitumor effects. Interleukin 12 is a cytokine with potent antitumor activity mediated also via antiangiogenic mechanisms. These effects are attributed to IFN-gamma production stimulated by IL-12. Since IFN-gamma has been reported to augment antitumor effects when combined with one of the metalloproteinase inhibitors--batimastat (BB-94), we have examined a combined treatment with IL-12 and BB-94 in a murine melanoma model. The administration of both agents showed potentiated antitumor activity. Furthermore, we have shown in a tumor-induced angiogenesis model that the combined application of IL-12 and batimastat inhibits the formation of new blood vessels to a greater extent than either agent alone. Our observations show that antiangiogenic effects are at least partly responsible for the enhanced antitumor effects of the combined treatment with IL-12 and BB-94.

Adjuvants, Immunologic↗

Synergistic antitumor effects of a selective proteasome inhibitor and TNF in mice.

The ubiquitin-proteasome pathway is becoming an attractive target in cancer therapy. The inhibitors of proteasomes have recently been shown to induce apoptosis of tumor cells in vitro and to exert significant antitumor effects in murine tumor models in vivo. Proteasome inhibitors, also prevent NF-kappa B activation. Since this transcription factor is responsible for counteracting apoptosis induced by numerous agents, and proteasome inhibitors have already proved efficacious in increasing the proapoptotic activity of TNF in vitro, we decided to evaluate the antitumor effects of the combined PSI and TNF treatment against a murine C-26 carcinoma. Both agents separately exerted moderate antitumor efficacy. However, their combination proved to exert dramatic antitumor activity with retardation of tumor growth and prolongation of mice survival time. Moreover, 50% of the mice were completely cured by this drug combination. Unexpectedly, there was no potentiation of the cytostatic/cytotoxic effects of these drugs in in vitro assays which argues against the direct influence on C-26 cells. Similarly, the influence of these drugs on tumor induced angiogenesis does not seem to explain the observed antitumor effects. Further studies are necessary to explain the striking antitumor effects of the PSI and TNF combination.

Acetylcysteine↗

[Studies of the role of cellular immunity and angiogenetic changes in the pathogenesis of circumscribed scleroderma].

The studies were performed in 48 patients with morphea and included evaluation of 1) antinuclear antibodies 2) lymphocyte induced angiogenesis 3) natural killer (NK) cell activity and 4) T cell subpopulations in peripheral blood. The presence of antinuclear antibodies was found in 44.4% (8/18) patients with scleroderma linearis and in 21% (4/19) patients with morphea disseminata. Lymphocyte induced angiogenesis was increased in 41.5% (17/41) morphea patients, mainly in cases with pronounced vascular changes. The E rosette forming test showed a decreased percentage of active rosette forming cells (ARFC) and total rosette forming cells (TRFC) in peripheral blood and the NK cell activity was lowered in patients with morphea. These results obtained in patients with morphea show some similarities and differences in comparison to cellular immunity disturbances in patients with systemic scleroderma.

Angiogenesis Inducing Agents↗