1,722,817 research outputs found
Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets
In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor beta1 (TGF-beta1) and interleukin-8 (IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limb ischemia treated with O3 autohaemoteraphy (O3-AHT)
Free Radicals and Antioxidants: How to Reestablish Redox Homeostasis in Chronic Diseases?
This review examines the biological role of oxidants and antioxidants continuously produced by all living cells. Physiologically in human beings, who have inherited good genes, used to eat moderately a healthy diet and practising exercise every day, both systems are equally important and essential to maintain a normal long life. However the aging process slowly leads to a disequilibrium that becomes accentuated in pathologies such as diabetes, cardiovascular, degenerative, pulmonary, infective diseases and cancer. All of these diseases shorten the life span in about 80% of individuals and represent a huge social-economic problem for health authorities. Several factors as excessive feeding, smoking, alcoholism and a poor life-style conjure up to their realization. Their progress, initially promoted by some pathogens and a wrong life-style, is deeply accentuated by an excessive and deranged production of deadly oxidants no longer tamed by an inhibited control of the antioxidant defences. Effective orthodox drugs are able to slow down these ailments but they impoverish the quality of life because they cannot reactivate the innate ability to restore the complexity of the antioxidant system. Several potential approaches to renew this system have been discussed and their possible role to reactivate a valid protection in at least some of the outlined pathologies. It is hoped to pursue the evaluation of this integrated medical approach because it represents a sheet anchor for many patients
Studies on the biological effects of ozone 1. Inductionof interferon gamma on human leucocytes
In this study we have investigated the effects of ozone on human blood, as well as on resuspended buffy coats and Ficoll-purified mononuclear cells. Samples were exposed at different ozone concentrations (from 2.2 micrograms to 108 micrograms/ml) for 30 sec and then incubated for different times at 37 degrees C in a 95% air-5% CO2 humidified atmosphere. Supernatants were collected and frozen at-20 degrees C until tested for interferon (IFN) activity. We have determined that the ozone concentration is critical for lymphokine induction. In fact, while low concentrations (2.2 micrograms/ml) are effective in lymphocytes, they do not induce IFN in either whole or diluted (1:1) human blood, or resuspended buffy coats. In such cases levels as high as 42 micrograms/ml are required. On the other hand, a very high ozone concentration (108 micrograms/ml) is not effective and probably toxic. Maximal IFN production occurs 72-96 h after ozone exposure, and the kinetics of IFN release is similar to that after Staphylococcal Enterotoxin B addition. Because ozonization of blood is a medical procedure followed in several countries for treatment of viral diseases, this study can open a new field of investigation that may yield useful results both in biological and practical terms
Studies on the biological effects of ozone: 11. Release of factors from human endothelial cells
BACKGROUND: Empirical observations have shown that ozonated autohemotherapy markedly improves the symptoms of chronic limb ischemia (muscular pain at rest, intermittent claudication, etc) in atherosclerotic patients, but mechanisms of action remain unclear.
AIMS: Human endothelial cells (HUVECs) are known to release nitrogen monoxide (NO) and we investigated the biological effects of human ozonated serum on HUVECs in culture.
METHODS: We assessed the relevance of peroxidation, the release of NO as nitrite and of three classical cytokines.
RESULTS: The treatment of HUVECs with ozonated serum yields a dose dependent increase of thiobarbituric acid reactive substances (TBARS) and of hydrogen peroxide (H2O2) and a decrease of protein thiol groups (PTG). Concomitantly, in comparison to either the control or the oxygenated sample, there is a significant and steady increase of nitric oxide (NO) production; this is markedly enhanced by the addition of L-arginine (20 microM) and inhibited in the presence of the NO inhibitor, L-NAME (20 mM). The main mediator of ozone action is H2O2 as it has been shown either after its direct measurement or by the addition of 20, 40 and 100 microM. Moreover, during 24 hours incubation we have investigated the production of endothelin 1 (ET-1), E-selectin and Interleukin 8 (IL-8) and it appears that ozonation enhances IL-8, inhibits E-selectin and hardly modifies ET-1 production.
CONCLUSIONS: It appears that reinfusion of ozonated blood, by enhancing release of NO, may induce vasodilation in ischemic areas and reduce hypoxia
The lymphatic route- III. Pharmacokinetics of human natural interferon-beta injected with albumin as a retarder in rabbits
1. The aim of the present investigation was to define whether multisite, subcutaneous (s.c.) administration in unanesthetized, unrestrained rabbits of human natural interferon-β (nat. IFN-β) either in saline, or in a human albumin (ALB) solution (10 and 13% final concentrations) modified the pharmacokinetic parameters calculated from the IFN plasma levels. 2. 2. Plasma disappearance rates of nat. INF-β were measured in two rabbits after intravenous (i.v.) administration and the kinetic was adequately represented by a bi-exponential curve. 3. 3. The highest ALB concentration (13%) caused a significant reduction of the plasma IFN Cmax, a longer half-life, a three-fold increase of the area under curve (AUC value) and a marked decrease of the plasma clearance. Interestingly, the bio-availability of IFN was increased almost four-fold. 4. 4. The data suggest that, when nat. IFN-β is injected subcutaneously, the presence of a high concentration of ALB may prevent its inactivation and may favour its absorption via lymphatics rather than blood capillaries. 5. 5. It is remarkable that by using this approach, low but constant IFN levels are maintained for as long as two days, a fact that may well increase the therapeutic index of IFN in patients. © 1986
The lymphatic route. IV.Pharmacokinetics of human recombinant interferon alpha2 and natural interferon beta administered intradermally in rabbits
We have evaluated the feasibility of administering human recombinant interferon α2 and human natural interferon β via the intradermal route with an air-pressure injector in the rabbit model. This is the first report showing pharmacokinetic parameters after intradermal administration of interferon. The prolonged permanence of circulating interferon α2 and its excellent bioavailability make this route an attractive one to be tested in patients because it may increase the therapeutic index of IFN. On the other hand. this route seems less practical for IFN β for reasons probably connected with inactivation and/or scarce absorption of this drug from the skin
Hypoxia modifies the antiproliferative activity of interferon on a human melanoma cell line
The physiological interferon response: IV. Production of interferon by the perfused human placenta at term
Human placentas at term, free of bacterial and viral diseases, have been perfused and maintained sterile for up to 13 hr. Several parameters indicate that the organs remained viable and released interferon into the perfusate in a progressive fashion. The amount of interferon was small and the individual variations indicate that there are "poor" and "good" placenta producers. Both interferons -alpha and -beta were produced with a prevalence of the latter type. The partial acid lability and the type heterogeneity suggest that under physiological conditions the placentas produce unusual interferons, the function of which remains speculative
Studies on the biological effects of ozone: 2. Induction of tumor necrosis factor (TNF-alpha) on human leucocytes
The effect of ozone as a probable inducer of tumor necrosis factor (TNF-alpha) has been investigated on human blood and on Ficoll-purified blood mononuclear cells (PBMC). Samples were exposed at different ozone concentrations ranging from 2.2 to 108 micrograms/ml and incubated at 37 degrees C in an 95% air-5% CO2 atmosphere. At predetermined times, all cell supernatants were tested for TNF activity and some PBMC cultures were examined for DNA synthesis. We have shown that ozone concentration is critical in terms of TNF production and of cell mitogenesis and that, owing to the presence of erythrocytes, higher ozone concentrations are required to be effective in blood than in PBMC. Because ozonization of blood is a procedure followed in several European countries for the treatment of viral diseases and tumors, the release of factors with antiviral and immunomodulatory activities by leukocytes may explain the mechanism of action of ozone and of autohemotherapy
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