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Biomedical subjects

V Bocci

Publications and source records attributed to V Bocci.

At least 37 records · Page 2Linked to original sources
PubMed1999

Biological and clinical effects of ozone. Has ozone therapy a future in medicine?

Although ozone therapy has been used as an alternative medical approach for four decades, it has encountered scepticism, if not outright objection, by orthodox medicine. This prejudice is not unjustified because ozone therapy often has been used without rational basis or appropriate controls. With the advent of precise medical ozone generators, it is now possible to evaluate some mechanisms of action and possible toxicity. In contrast with the respiratory tract, human blood exposed to appropriate ozone concentrations is able to tame its strong oxidant properties and neither acute nor chronic side effects have ensued in millions of patients treated with ozonated autohaemotherapy. This paper summarises studies aimed at clarifying biological effects, defining any possible damage, the therapeutic window, and suitable doses able to express therapeutic activity. Although an unfashionable and unpopular approach, it is hoped that orthodox medicine will help to critically assess the validity of ozone therapy.

Humans↗
PubMed1998

Thrombin receptor expression and responsiveness of human monocytic cells to thrombin is linked to interferon-induced cellular differentiation.

Human thrombin has been shown to stimulate monocyte chemotaxis, phagocytosis, and interleukin (IL8) production, but the mechanisms responsible for stimulation are not well defined. In some cells, thrombin stimulation of proliferation appears to require both cleavage of the proteolytically activated receptor for thrombin (PAR1) and activation of a nonproteolytically activated thrombin receptor (N-PAR), while in others activation of either receptor alone may be sufficient for stimulation. We, therefore, have initiated studies to address thrombin receptor expression and cell responsiveness to thrombin in interferon gamma (IFNgamma)-differentiated and nondifferentiated U937 monocytic cells. Northern blot analysis shows that PAR1 expression is upregulated upon differentiation. Experiments with biotinylated and 125I-thrombin show that specific thrombin binding is dramatically increased by differentiation although it is not clear if this binding is to PAR1 or to a separate binding component such as N-PAR which is present on fibroblasts and other cells. Addition of thrombin at concentrations of 1-10 microg/ml (30-300 nM, concentrations where specific thrombin binding is observed) stimulates proliferation of IFNgamma-differentiated U937 cells but not of undifferentiated U937 cells. Thrombin also stimulates interleukin-6 (IL6) production in IFNgamma-differentiated U937 cells. Moreover, thrombin induces high levels of IL6, interleukin-1beta (IL1beta), and tumor necrosis factor-alpha (TNF alpha) production by peripheral blood mononuclear cells (PBMC) and monocytes. These results show that differentiated U937 cells and mature PBMC are responsive to thrombin whereas nondifferentiated U937 are not. Further, this responsiveness appears to correlate with expression of PAR1 and to a dramatic increase in specific thrombin binding. That thrombin stimulates cytokine production and proliferation in populations of differentiated monocytes suggests that thrombin may be an important regulator of inflammation and wound healing.

Cell Differentiation↗
PubMed1998

Studies on the biological effects of ozone: 8. Effects on the total antioxidant status and on interleukin-8 production.

Ozone (O3) is a controversial gas because, owing to its potent oxidant properties, it exerts damaging effects on the respiratory tract and yet it has been used for four decades as a therapy. While the disinfectant activity of O3 is understandable, it is less clear how other biological effects can be elicited in human blood with practically no toxicity. On the other hand plasma and cells are endowed with a powerful antioxidant system so that a fairly wide range of O3 concentrations between 40 and 80 microg/ml per gram of blood (approximately 0.83-1.66 mM) are effective but not deleterious. After blood ozonation total antioxidant status (TAS) and plasma protein thiol groups (PTG) decrease by 20% and 25%, respectively, while thiobarbituric acid reactive substances (TBARS) increases up to five-fold. The increase of haemolysis is negligible suggesting that the erythrocyte membrane is spared at the expense of other sacrificial substrates. While there is a clear relationship between the ozone dose and IL-8 levels, we have noticed that high TAS and PTG values inhibit the cytokine production. This is in line with the current idea that hydrogen peroxide, as a byproduct of O3 decomposition, acts as a messenger for the cytokine induction.

Adult↗
PubMed1998

Ozone oxidative preconditioning: a protection against cellular damage by free radicals.

There is some anecdotal evidence that oxygen-ozone therapy may be beneficial in some human diseases. However so far only a few biochemical and pharmacodynamic mechanisms have been elucidated. On the basis of preliminary data we postulated that controlled ozone administration would promote an oxidative preconditioning preventing the hepatocellular damage mediated by free radicals. Six groups of rats were classified as follows: (1) negative control, using intraperitoneal sunflower oil; (2) positive control using carbon tetrachloride (CCl4) as an oxidative challenge; (3) oxygen-ozone, pretreatment via rectal insufflation (15 sessions) and after it, CCl4; (4) oxygen, as group 3 but using oxygen only; (5) control oxygen-ozone, as group 3, but without CCl4; group (6) control oxygen, as group 5, but using oxygen only. We have evaluated critical biochemical parameters such as levels of transaminase, cholinesterase, superoxide dismutase, catalase, phospholipase A, calcium dependent ATPase, reduced glutathione, glucose 6 phosphate dehydrogenase and lipid peroxidation. Interestingly, in spite of CCl4 administration, group 3 did not differ from group 1, while groups 2 and 4 showed significant differences from groups 1 and 3 and displayed hepatic damage. To our knowledge these are the first experimental results showing that repeated administration of ozone in atoxic doses is able to induce an adaptation to oxidative stress thus enabling the animals to maintain hepatocellular integrity after CCl4 poisoning.

Animals↗
PubMed1997

Hypoxia affects cytokine production and proliferative responses by human peripheral mononuclear cells.

We have shown that hypoxia (2% O2 approximately pO2 14 mmHg) as opposed to O2 atmospheric pressure (20.9% O2 approximately pO2 140 mmHg) can deeply affect the production of cytokines in human peripheral mononuclear cells (PBMC) in the presence or absence of a specific T-cell activator such as phytohemagglutinin (PHA). In hypoxia, interleukin (IL)-2, IL-4, and interferon (IFN)-gamma production increased by 110, 70, and 50% over that of controls, respectively, in PHA-stimulated PBMC (P < 0.05). Moreover, in hypoxia, IL-6 production was significantly enhanced in both resting and PHA-stimulated PBMC by 36 and 37%, respectively (P < 0.05). However, in hypoxia, IL-10 production decreased in both resting and stimulated PBMC, being 80 and 67% of controls, respectively (P < 0.05). PBMC proliferation was not significantly affected by hypoxia, although PBMC susceptibility to PHA was about 80% of that of the control (P < 0.05) after 40 hr of treatment, whereas the cycle progression of hypoxic PBMC was delayed. From an evaluation of these results, hypoxia apparently modifies the production of cytokines by PBMC. These results have both theoretical and practical interest because local hypoxia is very common in several conditions, such as inflammation and local ischemia, and is a host-nonspecific defense against infection. Furthermore, these results suggest a differential pattern of cytokine production in vivo in hypoxic tissues.

Apoptosis↗
PubMed1996

Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases.

The role of ozone on earth is controversial, as in the stratosphere it is protective against excessive ultra violet irradiation, and in the troposphere it is toxic for animals and plants. The effectiveness of ozone against pathogens is well recognized and ozone appears to be the best agent for sterilization of water. In spite of this, the use of ozone in medicine has been overlooked or despised, mostly because it has been either misused or used without appropriate controls. Studies carried out in our laboratory have revealed that ozone can display relevant biological effects and that, having defined its therapeutic index, can become an important and reliable drug for the treatment of several diseases. An exciting new aspect is that ozone, being a strong oxidizer, can stimulate the increase of cellular anti-oxidant enzymes, eventually inhibiting the oxidative stress.

Blood Transfusion, Autologous↗
PubMed1996

Pulmonary catabolism of interleukin 6 evaluated by lung perfusion of normal and smoker rats.

Cytokines such as interleukin 6 are involved in the pulmonary inflammation arising as a result of smoking. By use of isolated and perfused lung preparations we have evaluated the role of the lungs in the catabolism of human recombinant interleukin 6 both in normal rats and in rats subjected to an acute cigarette smoking episode. When interleukin 6 was incorporated into the lung perfusion medium, neither control nor smoke-exposed rat lungs cleared the cytokine and only 0.1 +/- 0.2% of the total dose was recovered in the bronchoalveolar lavage fluid. When, on the other hand, the same amount of interleukin 6 was instilled into the bronchoalveolar tree, concentrations of the cytokine in the perfusate increased progressively so that after 3 h up to 70.1 +/- 9.8% and 40.9 +/- 22.5% of the administered dose, as measured by immunoenzymatic test, had been transferred from the bronchial lumen to the perfusion medium of either control or smoker rat lungs, respectively, indicating significantly (P < or = 0.05) different behaviour of the cytokine in the two experimental groups. Total recoveries of the administered interleukin 6 evaluated in smoke-exposed rat lungs were 55.3 +/- 23.2%, significantly lower than those for control rat lungs (83.9 +/- 11%). Determination of biological activity gave values always lower than those measured by immunoenzymatic test, indicating loss of biological activity during the transalveolar transit. It appears that the transfer of interleukin 6, especially in smokers, is almost exclusively unidirectional, from the alveolar space to the plasmatic pool with degradation during the transalveolar passage.

Animals↗
PubMed1995

Pharmacokinetics and catabolism of tumor necrosis factor-alpha in rat lungs.

The role of the lungs in the catabolism of tumor necrosis factor alpha (TNF-alpha) either in normal rats, or in rats subjected to an acute cigarette smoking episode has been evaluated by using isolated and perfused lung preparations. After administration of TNF-alpha into the lung perfusion medium, there was no clearance of the cytokine in both control and smoker rat lungs and only 0.2 +/- 0.1% of the administered dose was recovered in the bronchoalveolar lavage fluid. When TNF-alpha was instilled into the bronchoalveolar tree, concentrations of the cytokine in the perfusate increased progressively so that after 3 h up to 68.8 +/- 8% and 52.7 +/- 11.4% of the administered dose had been transferred from the bronchial lumen to the perfusion medium of either control or smoker rat lungs, respectively, the latter values being significantly lower (p < or = 0.05) than those obtained in control lungs. Moreover, total recoveries of TNF-alpha evaluated in smoker rat lungs (65.5 +/- 10.2%) were also significantly lower than those observed in control rat lungs (82.8 +/- 7.1%). In conclusion, it appears that transfer of TNF-alpha is almost exclusively unidirectional, from the alveolar space to the plasma pool with partial degradation during the transalveolar passage. These results may be useful when attempting to deliver TNF-alpha by aerosol.

Animals↗
PubMed1995

Effects of hypoxia on the antiproliferative activity of human interferons.

We studied the effects of pharmacologically attainable concentrations of interferon-alpha (IFN-alpha) and gamma (IFN-gamma) on the growth of cells incubated under hypoxic conditions (2% O2; approximately 14 mm Hg partial pressure) or exposed to oxygen at atmospheric pressure (21% O2; approximately 147 mm Hg). The cells were from four IFN-sensitive lines: A-549 lung carcinoma and G-361 human melanoma cells grow better under hypoxic conditions, but the growth of Hep-2 laryngeal carcinoma and WISH amnion cells is not affected by the environmental oxygen tension. The antiproliferative effects of the IFN were assessed in terms of cell cloning efficiency and also from the number of cells, relative to controls, measured 1, 2, and 3 days after seeding. Under hypoxic conditions, the cloning efficiency of A-549 and G-361 cells was increased, and they became significantly less responsive to the antiproliferative effect of IFN, and especially of IFN-gamma. No such effects were seen with WISH or Hep-2 cells. Hypoxic conditions are found in the necrotic areas present in most solid tumors, and our results suggest that these may decrease the antiproliferative effects of IFN. They may in part explain why IFNs have so little antitumor activity in such tumors, and they also suggest methods that may increase this activity.

Antineoplastic Agents↗
PubMed1995

Pulmonary catabolism of interferon-gamma evaluated by lung perfusion of both normal and smoke-exposed rats.

The role of the lungs in the catabolism of rat recombinant interferon-gamma, either in normal rats or in rats subjected to an acute cigarette smoking episode, was evaluated using an isolated and perfused lung preparation. After administration of interferon-gamma into the lung perfusion medium, there was no clearance of the cytokine in either control or smoke-exposed rat lungs, and only 0.1 +/- 0.2% of the total dose was recovered in the bronchoalveolar lavage fluid. When the same amount of interferon-gamma was instilled into the bronchial alveolar tree, concentrations of the cytokine in the perfusate increased progressively so that after 3 h up to 71.2 +/- 4.3 and 62 +/- 5.7% of the administered dose, as measured by ELISA test, had been transferred from the bronchial lumen to the perfusion medium of either control or smoke-exposed rat lungs, respectively, the latter values being significantly lower (p < or = 0.05) than those obtained in control lungs. Moreover, total recoveries of interferon-gamma evaluated in smoke-exposed rat lungs (78.4 +/- 8.6%) were also significantly lower than those observed in control rat lungs (91.4 +/- 11.8%). Biologic activity evaluations on the same samples gave values significantly lower than those obtained using ELISA, indicating a partial loss of biologic activity during transalveolar transit. In conclusion, it appears that the transfer of interferon-gamma is almost exclusively unidirectional from the alveolar space to the plasmatic pool, with partial degradation during transalveolar passage.

Animals↗
PubMed1995

Maternal and neonatal plasma cytokine levels in relation to mode of delivery.

After birth, host defences must be recruited to manage the transition from an almost sterile to a normal environment. The present study was undertaken to evaluate the relationship between cytokine plasma levels and phagocyte burst in mothers and neonates during the peripartal period. Plasma levels of interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and whole blood superoxide anion (.O2-) generation were evaluated in 27 healthy mothers, 16 undergoing vaginal delivery (VD) and 11 elective caesarean section (ECS) and in their babies. Blood specimens were taken from the mothers at the beginning of labour, during labour, immediately after delivery and 4 days later in the VD group, and before anaesthesia, immediately after delivery and 4 days later in the ECS group; neonatal samples were taken at birth (cord blood) and 4 days later. After delivery by VD, these mothers had higher plasma levels of IL-1 beta, IL-6, IFN-gamma and higher .O2- generation than those delivered by ECS. IL-6 plasma levels and .O2- generation were higher in babies born by VD than in those born by ECS. A statistically significant correlation between IL-6 plasma levels and .O2- release was observed in cord blood of babies born by VD (r = 0.69; p < 0.006). The study demonstrates that labour plays an important role in modulating host defences in the newborn.

Adult↗
PubMed1994

Pharmacology and side-effects of interferons.

The distribution, catabolic sites and turnover of interferons are reviewed in order firstly to improve their utilization, secondly to reduce toxicity and thirdly to evaluate alternative routes of administration. In fact catabolic pathways are now seen as a salutary system capable in most cases to reduce toxicity to an acceptable level.

Animals↗
PubMed1994

Effects of hypoxia on the cytotoxicity mediated by tumor necrosis factor-alpha.

We investigated whether hypoxia (2% O2, approximately 14 mm Hg partial pressure) in comparison to O2 atmospheric pressure (20.9% O2, approximately 140 mm Hg) can affect the cytotoxic effects of tumor necrosis factor-alpha (TNF) on the murine cell line L929. Under hypoxic conditions, L929 cells were significantly less inhibited by TNF treatment, even in the presence of actinomycin D. Moreover, under hypoxic conditions, TNF cytotoxicity was significantly inhibited by glutathione, which has been shown to protect cells against oxidative damage induced by various agents. On the other hand, under aerobic conditions treatment with other antioxidant agents and active species oxygen scavengers, as superoxide dismutase and catalase, did not markedly affect the cytotoxicity of TNF. Since hypoxia occurs normally in most solid tumors, these results are interesting because they suggest a disadvantageous inhibition of the cytotoxic effects of TNF in vivo in hypoxic tissues and confirm that oxygen-dependent metabolic processes or free radicals are required to exert TNF-induced cytotoxicity.

Aerobiosis↗
PubMed1993

Thrombin enhances T cell proliferative responses and cytokine production.

Human alpha-thrombin, in addition to its procoagulant activity, is a mitogen for fibroblasts and endothelial cells and a chemotactic agent for monocytes. To further understand the complex physiological functions of thrombin, we investigated whether thrombin has any immunoregulatory function with regard to T cell activation. Using highly purified human alpha-thrombin and peripheral blood mononuclear cells (PBMC), we investigated whether thrombin has any effect on cytokine production and/or proliferation induced by different T cell stimuli. At physiological concentrations (1-10 micrograms/ml, 30-300 nM), thrombin significantly enhances T cell proliferation in response to mitogens, superantigens, alloantigens, and anti-CD3 stimulation. Enhanced proliferation was associated with increased IL2 and IL6 production and with an increase in the number of IL2r+ (CD25)-bearing T cells. Thrombin alone was not mitogenic nor did it induce IL2 production or increase the number of IL2r+ T cells. However, PBMC exposed to thrombin alone produced high levels of IL6. Thrombin also enhanced IL2-induced proliferation of murine and human IL2-dependent cell lines. These results suggest that thrombin may play an important role in regulating cell-mediated immunity.

Cytokines↗
PubMed1993

The lymphatic route. VIII. Distribution and plasma clearance of recombinant human interleukin-2 after SC administration with albumin in patients.

It has been postulated that favouring the absorption of interleukin-2 via lymphatics rather than venous capillaries after subcutaneous administration may improve its therapeutic index. We have now evaluated in 12 cancer patients the plasma pharmacokinetic of interleukin-2 either dissolved in water or in 20% albumin solution with an internal cross-over after at least three days. Our data show that when albumin is present, the plasma concentrations of interleukin-2 versus time is increased and swelling at the injection sites is reduced. It remains to be seen whether efficacy improves during a prolonged treatment.

Adult↗
PubMed1993

Hypoxia enhances the antiviral activity of interferons.

WISH and Hep-2 cells were incubated in an environment with atmospheric oxygen (20% O2, approximately 140 mmHg partial pressure), and under hypoxic conditions (2% O2, approximately 14 mmHg). The oxygen tension greatly affected the metabolism of the cells and their response to interferon-alpha (IFN-alpha) and IFN-gamma. Under hypoxic conditions, the cytopathogenicity of vesicular stomatitis virus (VSV) was reduced by about 50%, and the antiviral effects of the interferons (IFNs) were increased, both in terms of VSV-induced cytopathic effect (CPE), and yields of infectious virus. Local hypoxia is a nonspecific host defense against virus infection. The present results suggest that one of the mechanisms is by potentiation of the effects of the IFN produced at the sites of virus replication.

Cell Hypoxia↗