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C Favalli

Publications and source records attributed to C Favalli.

At least 19 recordsLinked to original sources
PubMed1992

Glutathione inhibits replication and expression of viral proteins in cultured cells infected with Sendai virus.

Addition of reduced glutathione inhibited the production of Sendai virus in African green monkey kidney (AGMK) cells. This result could be accounted for by a direct action of GSH on viral replication. The inhibitory action was associated to an increase of the GSH intracellular level, while the host cell metabolism was unaffected. The antiviral effect was related to decrease and inactivation of the hemagglutinin-neuraminidase (HN) virus glycoprotein.

Animals↗
PubMed1992

Combination therapy with thymosin alpha 1 potentiates the anti-tumor activity of interleukin-2 with cyclophosphamide in the treatment of the Lewis lung carcinoma in mice.

In this study we have investigated the effects of thymosin alpha 1 (T alpha 1) and interleukin-2 (IL-2), singly or in combination with cyclophosphamide (CY), on tumor growth, survival and cytotoxicity in C57Bl/6NCrlBR mice with Lewis lung carcinoma (3LL). Combined administration of T alpha 1 plus IL-2, after CY treatment, was much more effective than use of each biological response modifier (BRM) alone, and induced complete tumor regression in all of the mice studied. Combination immunotherapy alone without CY only slightly reduced the rate of tumor growth, and these results are in accordance with previous studied which showed that the 3LL carcinoma is resistant to cytokines. Combined chemo-immunotherapy also increased the cytotoxicity of spleen cells and markedly enhanced long-term survival in all treated animals. Depletion of immune cells, using either total-body sub-lethal irradiation (400 rads) or antibodies directed against T-cell (anti-CD4 and CD8) or NK-cell (anti-asialo GM1) populations, abolished the positive response to combination therapy. Histological analysis of the tumors obtained from mice treated with combination chemo-immunotherapy revealed a high number of infiltrating lymphoid cells surrounding a well-circumscribed area of necrosis consisting solely of dead cells. Our studies show that T alpha 1 potentiates IL-2-induced cytotoxic activities in vitro as well in vivo, and that these compounds have a powerful anti-tumor action when associated with chemotherapy.

Animals↗
PubMed1992

Time-related interference of misoprostol with experimental gastric cancer formation induced by N-methyl-N'-nitro-N-nitrosoguanidine in the rat.

The purpose of this study was to investigate the effect of long-term misoprostol administration, at non-antisecretory doses, on N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-induced gastric carcinogenesis. The incidence of gastric carcinomas and precancerous lesions was evaluated in 50 male 250-g Sprague-Dawley rats after 52 weeks of continuous oral administration of MNNG (120 mg/l; n = 20), MNNG plus misoprostol (2 mg kg-1 day-1; n = 20) or tap water (n = 10) (experiment 1), and in 30 rats treated with MNNG for 30 weeks followed by tap water (n = 15) or by misoprostol (n = 15) for 22 weeks; a third group (n = 10) received tap water only for 52 weeks (experiment 2). After sacrifice, gastric mucosal lesions were macroscopically evaluated and their histology obtained. MNNG consumption was comparable in all groups (6.5 +/- 1.1 mg rat-1 day-1). Misoprostol consumption was 180 +/- 0.25 mg kg-1 day-1 rat-1. In experiment 1 the incidence of gastric carcinomas was 60% in the MNNG group and 25% in the group treated with MNNG plus misoprostol (P less than 0.05). Cytotoxic and hyperplastic gastric mucosal lesions were also significantly reduced by misoprostol. In experiment 2 the incidence of carcinomas was 31% and 38.6% respectively. Misoprostol significantly decreased the incidence of gastric cancer formation when given from the beginning of the experiment. By contrast, when administered after 30 weeks of MNNG treatment it did not interfere with experimental gastric cancer formation. Exogenous prostaglandins are able to prevent the early MNNG-induced gastric mucosal lesions, thus interfering with gastric carcinogenesis.

Adenocarcinoma↗
PubMed1992

In vivo cocaine administration influences lymphokine production and humoral immune response.

The effect of in vivo cocaine administration on in vitro mitogen-induced lymphokine production was examined. Splenocyte cultures from BALB/c mice treated with an acute (1 mg/kg) or daily cocaine administration (1 mg/kg/day for 7 consecutive days) were less responsive to induction of IFN-gamma, IL-2 and IL-4 production by mitogen stimuli. We also evaluated the humoral immune response to both a T-dependent (HEL) and a T-independent antigen (rHBcAg). It was found that cocaine inhibits T-dependent antibody production only. This inhibition was greatest when cocaine was given during immunization. The results suggest that T-cell-mediated responses may be more affected by cocaine use/abuse.

Animals↗
PubMed1992

Thymosin alpha one restores murine T-cell-mediated responses inhibited by in vivo cocaine administration.

The effects of different in vivo thymosin alpha one (T alpha 1) treatments on T-cell responses inhibited by cocaine abuse were studied. Administration during cocaine treatment promoted a faster recovery of normal natural killer (NK) cell activity after the suspension of abuse. Suspension of cocaine plus repeated T alpha 1 administrations strongly restored NK activity and, interestingly, spleen cells from mice treated with T alpha 1 during and after cocaine administration achieved a very rapid recovery and the greatest stimulation of natural cytotoxicity. This last treatment also restored the cocaine-inhibited specific T-cell response (i.e. allogeneic cytotoxic T-lymphocyte (CTL) generation) and abrogated the cocaine-induced suppression of interferon gamma (IFN-gamma), interleukin 2 (IL-2) and IL-4 production. Finally restoration and induction of thymic cellularity were significant when T alpha 1 was given during and after cocaine administration. The present investigation provides evidence for the first time that thymic hormones could be of potential value in controlling cocaine-induced impairment of T-cell-mediated immunity in the mouse.

Animals↗
PubMed1992

Induction of apoptosis in thymocytes by prostaglandin E2 in vivo.

In vivo administration in mice of a synthetic analog of prostaglandin E2 (PGE2) caused a selective and dramatic decrease of CD4+CD8+ double-positive, CD3/T-cell-receptor-alpha beta(lo) cells in the thymus. This loss was corticosteroid-independent and not affected by Cyclosporin A. The disappearance of CD4+CD8+ thymocytes was strictly correlated with the induction of apoptosis inside the thymus as shown by morphological studies and by the induction of intracellular transglutaminase expression. Considering that PGE2 has been found to be produced by different cell populations inside the thymus, these results indicate that PGE2 may act as endogenous signals for apoptosis during T-cell differentiation.

16,16-Dimethylprostaglandin E2↗
PubMed1991

Thymosin alpha 1 potentiates interleukin 2-induced cytotoxic activity in mice.

We have investigated the effects of interleukin 2 (IL-2) on cytotoxic activity of spleen lymphocytes, from normal and cyclophosphamide (200 mg/kg) or B-16 melanoma suppressed mice, after in vitro or in vivo pretreatment with thymosin alpha 1 (TA1). The results of this study indicate that pretreatment in vitro (100 ng/ml for 1 hr) or in vivo (200 micrograms/kg/day for 4 days) with thymosin alpha 1 (TA1), significantly increased the IL-2 (from 100 to 500 U/ml) in vitro induced cytotoxic activity of spleen lymphocytes, collected from both normal and cyclophosphamide and tumor-suppressed animals, against both YAC-1 (NK sensitive) and MBL-2 (NK resistant) cell lines. The potential use in combination of these two different biological response modifiers, useful in enhancing the immunological responses to IL-2 of lymphocytes, may provide a novel model of immunotherapeutic intervention in cancer.

Animals↗
PubMed1991

Susceptibility to influenza A virus infection in mice immunosuppressed with cyclophosphamide.

It is known that immunocompromised hosts show an enhanced susceptibility to microbial infections. Among these, viral infections represent a particular problem because of the lack of really efficient antiviral drugs. In the present report we have studied the effect of pharmacological immunosuppression with cyclophosphamide (CY) in virus infection in vivo, using Balb/c mice infected with influenza A virus (PR8). At the dose of 0.1 hemagglutinating units of viral inoculum, intranasal administration of PR8 virus caused the death of 50 to 60% of the animals within a period of 3-10 days. A single injection of CY (200 mg/kg) significantly increased mouse mortality to 90%, when PR8 virus challenge was performed 4 days after chemotherapy pretreatment. When the PR8 virus infection was performed at different times after CY-treatment, a similar appreciable effect was not observed. Severe alterations of some immunological parameters such as NK activity and analysis of lymphoid spleen cell subsets were related to the increased susceptibility to virus infection.

Animals↗
PubMed1991

Interaction between thymic hormones and other immunomodulatory agents.

We have investigated the effects of a combination in vivo treatment with thymosin alpha 1 (TA1) and murine alpha/beta interferon (IFN) on natural killer (NK) activity and on tumor growth in B-16 melanoma tumor-bearing mice. The results indicated that treatment with a single injection of IFN (3 x 10(4] 24 h before testing, enhanced NK activity in tumor-bearing mice if the test was performed 10 days after tumor inoculation, when the animals have normal NK responsiveness. On the other hand, the same treatment led to lower or no improvement of NK responses when the assay was performed 14 or 18 days after tumor inoculation, at a time when tumor growth caused NK-suppression. However, combination treatment with TA1 (200 micrograms/kg) for 4 days, followed by IFN was found to restore normal NK cell activity. On the other hand primary tumor growth was unaffected by combination therapy, while the same treatment with TA1 and IFN was able to significantly prolong survival time of B-16 tumor-bearing mice, when administered starting on day 6 after tumor inoculation. The last evidence, together with results on NK activity stimulation, indicates that combination therapy with TA1 and IFN could be an interesting approach to cancer immunotherapy.

Animals↗
PubMed1990

Combination treatment using thymosin alpha 1 and interferon after cyclophosphamide is able to cure Lewis lung carcinoma in mice.

A combination treatment with thymosin alpha 1 (200 micrograms/kg) for 4 days, followed by a single injection of murine interferon alpha/beta (3 x 10(4) international units/mouse). starting 2 days after cyclophosphamide treatment (200 mg/kg, single injection) demonstrated a dramatic and rapid disappearance of tumor burden in mice bearing Lewis lung carcinoma (3LL) tumor. The effectiveness of this new chemoimmunotherapy protocol was evident even on the long-term survival in a high percentage of animals, and was statistically significant when compared to treatment with the single agents in conjunction with chemotherapy or to chemotherapy itself. The same combination immunotherapy treatment strongly stimulated natural killer activity and cytotoxicity against autologus 3LL tumor cells in 3LL-tumor-bearing mice treated with cyclophosphamide, whereas treatments with each agent singly did not alter or only slightly modified the cytotoxic activity towards Yac-1 or 3LL target cells. Selective depletion with antibodies showed that killer cells stimulated by combination chemoimmunotherapy treatment bear phenotypic characteristics of asialo-GM1-positive cells. A histological study has shown a high number of infiltrating lymphoid cells in the tumors obtained from mice treated with combination chemoimmunotherapy.

Animals↗
PubMed1990

Sequential evaluation of gastric intraluminal prostaglandin E2 release, acid secretion and DNA-flow cytometry in N-methyl-N-nitro-N-nitrosoguanidine gastric carcinogenesis in the rat.

The study was initiated to evaluate the sequential changes of gastric intraluminal prostaglandin E2 (PGE2), gastric acid secretion and of the DNA-flowcytometric patterns during gastric carcinogenesis induced by 45-week N-methyl-N-nitro-N-nitrosoguanidine (NG) administration in the rat. Twenty male chronic gastric fistula Sprague-Dawley rats received NG solution (120 mg/l) for 45 weeks and 20 were used as controls. Samples of gastric juice (1 h) were obtained from all animals under basal conditions and every 5 weeks until the end of the experiment. Aliquots of gastric juice were titrated with 0.1 N NaOH. Other aliquots were extracted with ethylacetate and processed for specific PGE2 RIA. On the day following gastric juice collection a gastric lavage and gastric biopsies (n = 4) were obtained through the fistula and processed for flowcytometry. All surviving animals were killed after 45 weeks and histology was obtained. The incidence of cancer in NG treated chronic gastric fistula rats was 66%. Flowcytometry segregated at an early stage (30-35 weeks) those animals which were to develop gastric carcinoma from those which were not. Administration of NG decreased gastric secretion volume, acid and intraluminal PGE2 concentration both in animals developing and not developing cancer. During the last 10 weeks a sharp rise in gastric intraluminal PGE2 concentration was observed in tumor-bearing animals only probably due to production by tumor cells. Prostaglandin deficiency may contribute to the NG-induced mucosal damage and may be involved in gastric carcinogenesis.

Animals↗
PubMed1990

Inhibition of rat fibroblast cell proliferation at specific cell cycle stages by cocaine.

We have analyzed the role of cocaine in the control of the rat fibroblast (EL2) cell proliferation. Our data show a dose-related effect on the inhibition of DNA synthesis and cell growth when cocaine is added with serum or with a pure growth factor [Epidermal Growth Factor (EGF)]. Pretreatment by drug did not appreciably enhance the inhibition of S-phase entry above that obtained when cocaine and mitogen were added simultaneously. On the contrary, exposure of quiescent EL2 cells to cocaine has little or no effect on DNA synthesis, when drug is removed before the mitogenic stimulus. Moreover, even when cocaine is added after EGF, an exposure only within 1-8 hours is required in order to inhibit stimulation of DNA synthesis. Cocaine also suppressed the general increase in protein synthesis that occurs during the first hour after EGF addition. The combined data suggest that cocaine inhibits the traverse of mitogen-stimulated quiescent EL2 cells from Go to S phase by acting on processes that take place during the initial phase of the cell cycle.

Animals↗
PubMed1990

Effect of acute or daily cocaine administration on cellular immune response and virus infection in mice.

The effects of in vivo cocaine administrations on cellular cytotoxicity were studied. Cocaine induced a dose-related immunosuppression of natural killer cell activity, with maximal depression at 1-5 mg/kg. In addition, the degree of inhibition following a single intraperitoneal (i.p.) or intravenous cocaine dose (acute treatment, 1 mg/kg) was similar to that after repeated administration (subchronic treatment: 1 mg/kg/day i.p. for 7 consecutive days or subcutaneous administration by Alzet 2001 osmotic minipumps). T cells from cocaine-treated mice failed to generate cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures and acute or subchronic cocaine treatment also inhibited CTL generation in vivo. On the other hand, acute administration induced a very rapid (24-hour) inhibition of natural cytotoxicity, with a return to normal within 72 h after treatment. By contrast, repeated doses led to more protracted immunologic consequences and a delayed recovery (144 h). The effect of cocaine on susceptibility to influenza virus (PR8) infection was also investigated. Both acute and subchronic treatment significantly decreased resistance to PR8 infection. The results clearly indicate that cocaine has a potent suppressive effect on cellular immunity and that abuse can adversely affect the outcome of infectious diseases.

Animals↗
PubMed1989

Role of prostaglandins in the early phases of experimental gastric carcinogenesis in the rat.

The study was initiated to evaluate the effect of N-methyl-N-nitro-N-nitrosoguanidine (NG) on gastric intraluminal prostaglandin release during a 30-day treatment period and to investigate the effect of a stable prostaglandin E1 analogue (misoprostol) on NG-induced gastric mucosal damage during the same time period. Samples of gastric juice (1 h) were obtained from 40 male Sprague-Dawley rats with chronic gastric fistulas, in basal conditions and after 5, 15 and 30 days of continuous oral administration of NG (120 mg/l) or tap water. Aliquots of gastric juice were titrated with 0.1 M NaOH. Other aliquots were extracted with ethyl acetate and subjected to specific radioimmunoassay for prostaglandin E2. The severity of gastric mucosal lesions was evaluated in 60 rats after 5 days and 30 days of continuous oral administration of NG (120 mg/l) or NG plus misoprostol (200 micrograms/kg-1/day-1) or tap water, and a histological study was carried out. Administration of NG induced a significant decrease of gastric intraluminal prostaglandin E2 concentration at 15 and 30 days. Oral administration of misoprostol, at non-antisecretory doses, protected the rats against NG-induced gastric mucosal damage. Prostaglandins may be involved in the early phases of experimental gastric carcinogenesis.

Animals↗
PubMed1989

Synergistic effect of thymosin alpha 1 and alpha beta-interferon on NK activity in tumor-bearing mice.

We have investigated the possibility of thymosin alpha 1 (TH) cooperating with alpha beta-interferon (IFN) in boosting natural killer (NK) activity in tumor-bearing, immunosuppressed mice in vivo. Treatment with a single injection of 30,000 IU of IFN 24 h before testing enhanced NK activity in tumor-bearing mice if the IFN was administered 9 days after tumor inoculation, when the animals have normal NK responsiveness. On the other hand, the same treatment led to lower or no improvement of NK responses if the treatment was given 13 or 17 days after tumor inoculation, at a time when tumor growth causes immunosuppression. However, combination treatment with TH (200 micrograms/kg) for 4 days, followed by IFN was found to restore normal NK cell activity. Selective depletion of antigen-positive cells showed that killer cells stimulated by combination treatment with TH and IFN seem to bear phenotypic characteristics of NK cells. These studies provide the first documentation of a novel combination approach to reconstitution of immunosuppressed tumor-bearing mice using TH and IFN. We hypothesize that TH restores NK boosting activity by IFN by effecting the differentiation/induction of precursor populations of IFN-responsive cells.

Animals↗
PubMed1989

Enhanced immune response and antitumor immunity with combinations of biological response modifiers.

We have studied the effects of combination therapy with thymosin alpha 1 and IFN or IL-2 on natural killer cell activity in both normal and immunosuppressed animals after cyclophosphamide treatment and during B-16 melanoma and 3LL tumor growth. Our results suggest that while the combined treatment does not substantially modify the depressed natural killer cell response, thymosin alpha 1 pre-treatment significantly restores the boosting capacity of the two cytokines, IL-2 and IFN. Since thymosin alpha 1 proved capable of accelerating natural killer cell activity recovery in animals irradiated and reconstituted with symgenic marrow cells, we hypothesize that the synergistic effect between thymosin alpha 1 and IFN could result from the differentiation of natural killer cell lines by thymosin alpha 1 which can then become sensitive to IFN. Furthermore, we have demonstrated a good correlation between restoration of natural killer cell activity and regulation of tumor growth. Thus, these results may have important implications in tumor immunotherapy and patients with infectious diseases such as AIDS which is associated with low natural killer cell activity.

Animals↗
PubMed1988

Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus.

We have previously shown that prostaglandins of the A series potently inhibit virus replication in several virus-host systems in vitro. In the present report we have studied the effect of a long-acting synthetic analog of PGA, 16,16-dimethyl-PGA2(Di-M-PGA2), on virus infection in vivo, using as a model Balb/c mice infected with influenza A (PR8) virus. Depending upon the dose of viral inoculum, PR8 virus caused the death of 50 to 100% of the animals in a period of 8-20 days. Di-M-PGA2-treatment significantly increased mouse survival by an average of 40%, independently of the dose of inoculum and the age of the animals. The fact that Di-M-PGA2-treatment decreased virus titers in the lungs and did not alter the host immune response, suggested that PGA's therapeutic action was due to suppression of virus replication. Finally, two anti-inflammatory compounds, which inhibit prostaglandin synthesis, aspirin and indomethacin, were shown not to significantly alter mouse survival in this system.

Animals↗