[Effects of beta-glycerophosphate on junctions between reticuloepithelial cells and thymocytes in mice].
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Biomedical subjects
Publications and source records attributed to C Favalli.
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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.
OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) are important regulators of cancer invasion and metastasis. Their associations to high-risk (HR) human papillomavirus (HPV) in cervical intra-epithelial neoplasia (CIN) and cervical cancer (CC) are unexplored and their prognostic significance in CC remains controversial. MATERIALS AND METHODS: As part of our HPV-PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using immunohistochemical (IHC) staining for MMP-2 and TIMP-2 and tested for HPV using PCR with 3 primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available from all squamous cell carcinoma patients and 67 CIN lesions had been monitored with serial PCR for HPV after cone treatment. RESULTS: MMP-2 increased with the grade of CIN, with major up-regulation upon transition to invasive cancer (OR 20.78) (95%CI 7.16-60.23) (p=0.0001). TIMP-2 retained its normal expression until CIN3, with dramatic down-regulation in invasive disease (p=0.0001 for trend). Thus, the MMP2:TIMP-2 ratio increased with progressive CIN, exceeding the value 1.0 only in invasive disease. Both MMP-2 and TIMP-2 are highly specific (TIMP-2; 100%) discriminators of CIN with 100% positive predictive value (TIMP-2), but suffer from low sensitivity and negative predictive value. Neither MMP-2 nor TIMP-2 showed any significant association with HR HPV or virus persistence/clearance. TIMP-2 (but not MMP-2) was a significant predictor of survival in univariate (Kaplan-Meier) analysis (p=0.007), but lost its significance in multivariate (Cox) analysis. CONCLUSION: The activities of MMP-2 and TIMP-2 in cervical carcinogenesis seem to be unrelated to HR-HPV The inverse MMP-2:TIMP-2 ratio is a sign of poor prognosis. A combination of a TIMP-2 assay with another test showing high SE and high NPV (e.g., HCII for HPV) should provide a potential screening tool capable of accurate detection of CIN.
The effects of arachidonic acid metabolites on mitogen-induced interferon (IFN)-gamma production by human peripheral blood mononuclear cells (PBMC) were examined. Both prostaglandins E2 (PGE2) and leukotrienes B4 (LTB4) were produced after macrophage activation stimulated by galactose oxidase (GO) and Staphylococcal enterotoxin B (SEB), two well known inducers of IFN-gamma. To test the involvement of PGE2 and LTB4 in IFN-gamma production, GO- and SEB-activated PBMC were treated with two inhibitors of cyclooxygenase (aspirin and indomethacin) and with an inhibitor of lipoxygenase [nordihydroguaiaretic acid (NDGA)]. The results of these experiments showed that aspirin and indomethacin cause a marked increase of IFN-gamma production by GO- and SEB-activated PBMC. On the contrary, NDGA treatment reduced IFN-gamma production induced by the same agents. Moreover, whereas the addition of exogenous PGE2 reduces IFN gamma production, the addition of exogenous LTB4 does not affect IFN-gamma production. Taken together these findings indicate that arachidonic acid metabolites, produced during mitogenic activation, are involved in the regulation of IFN-gamma production and suggest that, in our system, LTB4 exerts a positive modulating signal while PGE2 represents a negative signal.
Infection by hepatitis B (HBV) and/or delta virus (HDV), is the most frequent acquired pathology in patients affected by end-stage hepatic disease, candidates for liver transplant. To reduce the risk of virus reactivation after surgery, we used alpha Interferon (IFN) therapy in patients who were HBV-DNA and/or HDV-RNA positives before transplant. Our protocol included alpha IFN at low dosage associated to a thymic hormone that seems to have a synergistic activity with IFN. We have evaluated in four patients, affected by post hepatitic end-stage liver disease, the outcome of HBV and HDV markers in relation to immunological response during treatment. Our interest has been focused on monocyte and natural killer cytotoxic activity. The data show that all patients, before starting therapy, had evidence of active phase viral replication. They also displayed low values of the immunological parameters tested. The study of viral markers showed decrease of HBV and HDV in all patients. The relation between viral markers and natural killer and monocyte cytotoxicity was very interesting; during the treatment we observed a marked increase of both activities. At the same time no relevant modifications in the other immunological parameters tested were found.