Biomedical subjects

A T Palamara

Publications and source records attributed to A T Palamara.

31 records · Page 2Linked to original sources

PubMed1996

Efficacy of combination therapy with amantadine, thymosin alpha 1 and alpha/beta interferon in mice infected with influenza A virus.

The aim of this study was to examine the effects of the antiviral drug amantadine (AMN) administered in combination with thymosin alpha 1 (T alpha 1) and murine alpha/beta interferon (IFN) on mice infected with influenza A PR8 virus. Combined treatment with AMN and T alpha 1, for 4 days, followed by a single injection of IFN, was initiated 1 h after intranasal viral inoculation. The effectiveness of this new chemoimmunotherapy protocol was seen in the long-term survival of a high percentage of animals and was statistically significant when compared to treatment with single agents in conjunction with chemotherapy or to chemotherapy alone. In addition, chemoimmunotherapy treatment reduces the viral titre in the lungs as well as restoring the immunological parameters tested (natural killer cell activity; cytotoxic T-lymphocyte responses; CD4+/CD8+ lymphocyte subsets) with respect to all other groups. These results suggest the potential use of these immunomodulating agents in combination with an antiviral drug in controlling PR8 influenza virus infection.

Amantadine↗

PubMed1995

Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication.

The role of glutathione (GSH) in the in vitro infection and replication of human herpes simplex virus type 1 (HSV-1) was investigated. Intracellular endogenous GSH levels dramatically decreased in the first 24 h after virus adsorption, starting immediately after virus challenge. The addition of exogenous GSH was not only able to restore its intracellular levels almost up to those found in uninfected cells, but also to inhibit > 99% the replication of HSV-1. This inhibition was concentration-dependent, not related to toxic effects on host cells and also maintained if the exogenous GSH was added as late as 24 h after virus challenge, i.e. when virus infection was fully established. Electron microscopic examination of HSV-1-infected cells showed that GSH dramatically reduced the number of extracellular and intracytoplasmic virus particles, whereas some complete nucleocapsids were still detected within the nuclei of GSH-treated cells. Consistent with this observation, immunoblot analysis showed that the expression of HSV-1-glycoprotein B, crucial for the release and the infectivity of virus particles, was significantly decreased. Data suggest that exogenous GSH inhibits the replication of HSV-1 by interfering with very late stages of the virus life cycle, without affecting cellular metabolism.

Animals↗

PubMed1994

Combined effect of fluconazole and thymosin alpha 1 on systemic candidiasis in mice immunosuppressed by morphine treatments.

Treatment of systemic infection with Candida albicans with a combination of an antifungal agent (i.e. fluconazole) and a thymus-derived immunostimulant (i.e. thymosin alpha 1 (T alpha 1)) in mice immunosuppressed by morphine treatments was investigated. In normal mice, fluconazole given after infection with 10(6) C. albicans cells was more effective than in mice treated with morphine. Combination treatment with fluconazole and T alpha 1 prolonged survival and reduced the fungal burden in the kidneys of immunosuppressed mice. We also investigated the influence of this combined treatment on killing properties of polymorphonuclear leucocytes (PMN) and natural killer (NK) cell activity, inhibited by morphine administrations. Treatment with T alpha 1 or fluconazole as single agents promoted a recovery of normal NK cell activity and intracellular killing of C. albicans by PMN, while the combination significantly increased both of these responses, probably through the modulation of lymphokine production. Our data suggest that the additive effect of T alpha 1 and fluconazole is due to a direct antifungal action and activation of the immunocompetence.

Animals↗

PubMed1994

Inhibitory effect of morphine on the control of rat fibroblast cell proliferation.

The G0/G1 to S-phase transition in quiescent EL2 rat fibroblast cells stimulated by mitogen (such as the epidermal growth factor) can be blocked by the addition of morphine to the system. The drug must be actively present when quiescent EL2 cells are induced to enter the proliferative state. Even when morphine is added after mitogenic stimulus, an exposure only within 6 hours is required to inhibit DNA synthesis. These results suggest that morphine can directly influence the proliferation of the nonlymphoid cell system, particularly during the establishment of a competence state (i.e. G0/S phase transition).

Animals↗

PubMed1993

Induction of thermotolerance by prostaglandin A in human cells.

Cyclopentenone prostaglandins (PGs) induce the synthesis of heat shock proteins (HSPs) in mammalian cells. Since arachidonic acid metabolites are implicated in the control of fever, we investigated the effect of PG treatment on thermal injury in human K562 erythro-leukemia cells. Prostaglandin A1 (PGA1) was found to protect cells after severe heat shock and to induce a thermotolerant state, which persisted for 24-48 h. Prostaglandins of the B, E, and F type were not effective. Kinetics of thermotolerance induction was comparable to heat-induced heat resistance. Establishment of a thermotolerant state was not a direct effect of PGA1, since it was dependent on de novo protein synthesis and was associated with HSP70 induction. This activity of PGA1 could be part of a protective control mechanism during fever.

Body Temperature Regulation↗

PubMed1993

Antitumor effect of thymosin alpha 1/interleukin-2 or thymosin alpha 1/interferon alpha,beta following cyclophosphamide in mice injected with highly metastatic Friend erythroleukemia cells.

We investigated the effects of the systemic administration of thymosin alpha 1 plus relatively low doses of human recombinant interleukin-2 or very low doses of interferon alpha,beta in untreated and cyclophosphamide (CY)-treated DBA/2 mice challenged either subcutaneously or intravenously (i.v.) with Friend erythroleukemia cells (FLC). Both treatments resulted in the complete regression of subcutaneous tumor and cured a significative percentage of mice. They also increased the survival time of mice i.v. injected with large numbers of FLC. Neither immunotherapy alone nor CY, alone or in combination with single cytokines, produced similar effects. The antitumor action of these combined chemoimmunotherapy protocols seems to involve activation of the immune response since (a) a synergistic increase of the cytotoxicity of spleen cells was demonstrated in treated mice; (b) selective in vivo depletion of asialo-GM1, CD4, or CD8-positive cells abrogated this antitumor activity; and (c) a high lymphoid cell infiltration was found at the tumor site and in the livers of treated mice.

Animals↗

PubMed1993

In vitro phencyclidine-induced inhibition of lymphocyte proliferation: prevention by cell activation.

The proliferative response of phytohemagglutinin (PHA)- and interleukin 2 (IL-2)-activated murine splenocytes was studied in the presence of phencyclidine (PCP), a potent psychotomimetic drug of abuse. PCP inhibited [3H]-thymidine incorporation in lymphocytes treated with PHA or IL-2. This inhibitory action was dependent upon the drug doses and the time of incubation with the cultures. There was no significant inhibitory activity of PCP when it was added 24 hrs or 48 hrs after mitogenic stimuli. Parallel, a lower inhibitory effect was observed when IL-2 or PHA were simultaneously present in the incubation medium. Moreover, the pretreatment for 18 hrs with IL-2 completely counteracted PCP-induced depression of PHA-stimulated lymphocytes. We suggest that PCP affects some pathway that regulates the activation of resting T cells rather than affecting already cycling cells.

Animals↗

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

Inhibition of Sendai virus replication by delta 12-prostaglandin J2: induction of heat shock protein synthesis and alteration of protein glycosylation.

delta 12-Prostaglandin J2 (delta 12-PGJ2), a natural dehydration product of prostaglandin D2 present in human body fluids, was shown to suppress Sendai virus replication in monkey kidney cells, at doses non-toxic to uninfected cells. Dramatic inhibition of virus production could be obtained at doses of delta 12-PGJ2 which did not inhibit cellular or viral protein synthesis, suggesting an effect on virus assembly and/or maturation. At the active concentration, delta 12-PGJ2 caused a decrease in glucosamine incorporation into the virus glycoproteins HN and F, and in at least one host cell polypeptide, while it did not affect most cellular glycoproteins and it induced the glycosylation of a 47-kDa cellular polypeptide. These effects were accompanied by the induction of heat shock protein synthesis, which was found to differ in its specificity and kinetics from induction by prostaglandin A1.

Animals↗

PubMed1990

Growth inhibition of Friend erythroleukaemia cell tumours in vivo by a synthetic analogue of prostaglandin A: an action independent of natural killer-activity.

Prostaglandins of the A series (PGAs) have been previously shown to inhibit the growth and to stimulate the differentiation of Friend erythroleukaemic cells (FLC) in vitro. In the present report we analysed the effect of PGA treatment in vitro on FLC tumorigenicity, and in vivo on FLC proliferation and on natural killer (NK) activity. PGA1 pretreatment of FLC in vitro for 5 days before inoculation into syngeneic mice slightly delayed tumour appearance, but did not significantly alter the pattern of tumour growth or mice survival, indicating that PGA1, at least in the conditions studied, did not affect FLC tumorigenicity. Daily treatment of mice with a long-acting synthetic analogue of PGA2 (16, 16 dimethyl-PGA2-methyl ester, di-M-PGA2) delayed tumour appearance, inhibited tumour growth, as measured by tumour weight and diameter, and increased the median mice survival time by 15-35%, depending on the schedule of treatment. Daily treatment with di-M-PGA2 strongly suppressed NK activity in normal mice but had no significant effect in tumour-bearing immunodepressed mice. PGA treatment of effector or target cells in vitro, or PGA added during the NK assay, had no effect on NK activity. We suggest that the chemotherapeutic effect of PGA is due to a direct action on tumour cell replication rather than to a stimulation of the host NK activity.

Animals↗

PubMed1985

[Effect of thymosin alpha 1 on prostaglandin release by murine lymphocytes].

The effects on PGE2 release by lymphocytes obtained from adult thymectomized mice and from normal mice, after incubation with Thymosin alpha 1, were studied. Splenocytes from Tx mice release PGE2 at short time of incubation (15') using 4 micrograms/ml of Thymosin alpha 1 and at longer time of incubation (60'-180' using 4-8 micrograms/ml of Thymosin alpha 1. On the other hand thymocytes release the highest amounts of PGE2 after longer time of incubation (60'-180'). However lymphocytes obtained from normal mice do not release PGE2 amounts comparable with that released by the control samples. This effect shows an interesting interaction between thymic hormones and PGs.

Animals↗

PubMedDate not supplied

Synthesis, cytotoxic effect and antiviral activity of 1-(beta-D-arabinofuranosyl)-5-bromo-N4-substituted cytosine and 1-(beta-D-arabinofuranosyl)-5-bromo-4-methoxypyrimidin-2(1H)-one derivatives.

A convenient and mild synthesis of 5-bromo-N4-substituted-1-(beta-D-arabinofuranosyl)cytosine and 5-bromo-O4-methyl-1-(beta-D-arabinofuranosyl)pyrimidin-2(1H)-one derivatives by selective oxyfunctionalization of the corresponding 4-thionucleosides with 3,3-dimethyldioxirane is reported. The cytotoxicity and the antiviral activity against parainfluenza 1 (Sendai virus) of all new synthesized products are also reported.

3T3 Cells↗

PubMedDate not supplied

Antifungal and immunoadjuvant properties of fluconazole in mice immunosuppressed with morphine.

We investigated the efficacy of fluconazole on experimental disseminated candidiasis in mice immunocompromised by chronic morphine treatment. CD1 mice were severely immunosuppressed by repeated morphine administrations, i.e., subcutaneous (s.c.) injections of 75 mg/kg/day, 3 days before and 5 days after a systemic Candida albicans infection induced by intravenous administration of 1 x 10(6) fungal cells/mouse. Fluconazole (2.5 mg/kg, s.c., at 6, 24 and 48 h postinfection) was very effective in prolonging survival time of morphine-treated mice. Fluconazole treatment also promotes a recovery of killing activity of polymorphonuclear leukocyte cells suppressed by morphine administrations.

Animals↗