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Biomedical subjects

C Mauri

Publications and source records attributed to C Mauri.

At least 19 recordsLinked to original sources
PubMed2006

Haematological parameters in elite rugby players during a competitive season.

We assessed haematological parameters and possible modifications in elite rugby players throughout a competitive season for increasing the knowledge of physiological characteristics of these sportsmen. Blood samples were collected from the members of the Italian National rugby team at four consecutive training camps during a whole competitive season. Forty-four athletes were recruited for the first camp, 36 for the second, 30 for the third and 32 for the fourth. Due to turnover of the subjects during the season only 13 athletes could be examined at all four camps, and another six in the first three camps. Therefore, we selected the data of these 19 athletes. Iron and transferrin saturation were stable, whilst ferritin increased at the end of the season. The modifications of the soluble transferrin receptor (sTFR) were linked to those of haematocrit: sTFR increased after training and during the competition period when haemoglobin and haematocrit decreased, and decreased at the end of the season. Haemoglobin and haematocrit showed slightly higher levels during the first part of the season and decreased in the second half, when physical demand was high, as demonstrated by biochemical additional tests. Leucocytes and platelets were stable throughout the season. Haematological and iron metabolism parameters in the elite rugby players examined during a whole season fall within physiological range of values. The variability of the parameters during the season is related to training and competition workload. Reticulocytes and sTFR are the most sensitive parameters for studying the iron metabolism of the athletes.

Analysis of Variance↗
PubMed2000

A comparative study into the mechanisms of action of anti-tumor necrosis factor alpha, anti-CD4, and combined anti-tumor necrosis factor alpha/anti-CD4 treatment in early collagen-induced arthritis.

OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNFalpha) therapy is very effective in rheumatoid arthritis (RA), whereas depleting anti-CD4 therapy is relatively ineffective. To explain the differences in efficacy between these 2 therapies, we used an animal model of RA to compare their effects on different aspects of the disease process. METHODS: Mice with collagen-induced arthritis were treated with depleting anti-CD4 monoclonal antibodies (mAb), anti-TNFalpha mAb, or phosphate buffered saline. Another group was given a combination of anti-TNFalpha plus anti-CD4. The treatments were compared for their ability to down-regulate the expression of proinflammatory cytokines and adhesion molecules, reduce the cellularity of the joint, and inhibit Th1 activity. RESULTS: Anti-TNFalpha significantly reduced the numbers of cells expressing TNFalpha, interleukin-1beta (IL-1beta), very late activation antigen 4 (VLA-4), vascular cell adhesion molecule 1 (VCAM-1), and numbers of CD4+ T cells and macrophages in the joint. Anti-CD4 treatment led to a small reduction in the expression of TNFalpha, IL-1beta, VLA-4, and VCAM-1, but this did not reach statistical significance. Depleting anti-CD4 was also surprisingly ineffective in eliminating CD4+ T cells from the joint. Anti-TNFalpha therapy was also more effective than anti-CD4 in reducing Thl activity, as assessed by the production of interferon-gamma in lymph node cell cultures. There was a synergistic relationship between anti-TNFalpha and anti-CD4 in the reduction of histologic score and inhibition of TNFalpha/IL-1beta expression in the joints. CONCLUSION: The efficacy of the 3 treatments correlated with their ability to modulate the expression of inflammatory cytokines and adhesion molecules in the joint, reduce the cellularity of the joint, and inhibit Th1 activity. This kind of analysis may prove useful in the testing of novel therapies for RA.

Animals↗
PubMed2000

Therapeutic activity of agonistic monoclonal antibodies against CD40 in a chronic autoimmune inflammatory process.

The use of agonistic monoclonal antibody against CD40 has emerged as one the most effective ways to boost immune responses against infectious agents or to fight cancer. Here, we report that the same monoclonal antibodies against CD40 (FGK45 and 3/23) previously used to elicit protective immune responses treated the autoimmune inflammatory process of chronic collagen-induced arthritis in DBA/1-TCR-beta transgenic mice, as well as collagen-induced arthritis in DBA/1 mice, both animal models of rheumatoid arthritis. This study indicates that agonistic monoclonal antibody against CD40 can potentially be used to treat chronic autoimmune inflammatory processes.

Animals↗
PubMed1998

Importance of cyclophosphamide-induced bystander effect on T cells for a successful tumor eradication in response to adoptive immunotherapy in mice.

Cyclophosphamide (CTX) increases the antitumor effectiveness of adoptive immunotherapy in mice, and combined immunotherapy regimens are now used in some clinical trials. However, the mechanisms underlying the synergistic antitumor responses are still unclear. The purpose of this study was (a) to evaluate the antitumor response to CTX and adoptive immunotherapy in mice bearing four different syngeneic tumors (two responsive in vivo to CTX and two resistant); and (b) to define the mechanism(s) of the CTX-immunotherapy synergism. Tumor-bearing DBA/2 mice were treated with a single injection of CTX followed by an intravenous infusion of tumor-immune spleen cells. In all the four tumor models, a single CTX injection resulted in an impressive antitumor response to the subsequent injection of spleen cells from mice immunized with homologous tumor cells independently of the in vivo response to CTX alone. Detailed analysis of the antitumor mechanisms in mice transplanted with metastatic Friend leukemia cells revealed that (a) the effectiveness of this combined therapy was dependent neither on the CTX-induced reduction of tumor burden nor on CTX-induced inhibition of some putative tumor-induced suppressor cells; (b) the CTX/immune cells' regimen strongly protected the mice from subsequent injection of FLC, provided the animals were also preinoculated with inactivated homologous tumor together with the immune spleen cells; (c) CD4(+) T immune lymphocytes were the major cell type responsible for the antitumor activity; (d) the combined therapy was ineffective in mice treated with antiasialo-GM1 or anti-IFN-alpha/beta antibodies; (e) spleen and/ or bone marrow cells from CTX-treated mice produced soluble factors that assisted in proliferation of the spleen cells. Altogether, these results indicate that CTX acts via bystander effects, possibly through production of T cell growth factors occurring during the rebound events after drug administration, which may sustain the proliferation, survival, and activity of the transferred immune T lymphocytes. Thus, our findings indicate the need for reappraisal of the mechanisms underlying the synergistic effects of CTX and adoptive immunotherapy, and may provide new insights into the definition of new and more effective strategies with chemotherapy and adoptive immunotherapy for cancer patients.

Animals↗
PubMed1998

Therapeutic actions of cyclosporine and anti-tumor necrosis factor alpha in collagen-induced arthritis and the effect of combination therapy.

OBJECTIVE: To define the mechanisms of action of 2 novel drugs, cyclosporine and anti-tumor necrosis factor alpha (TNFalpha), in collagen-induced arthritis and to determine the effect of combination therapy. METHODS: Type II collagen-immunized DBA/1 mice with established arthritis were treated with cyclosporine alone, anti-TNFalpha alone, cyclosporine plus anti-TNFalpha, or saline. RESULTS: Cyclosporine was found to ameliorate arthritis, suppress interferon-gamma (IFNgamma) production by CD4+ T cells, and reduce TNFalpha expression in arthritic joints. However, cyclosporine did not directly inhibit TNFalpha production by macrophages, indicating that the decrease in TNFalpha expression observed in vivo was probably an indirect consequence of the reduction in type 1 T helper cell activity. Anti-TNFalpha also reduced IFNgamma production by T cells, indicating that TNFalpha is involved in the cellular immune response to collagen. Combined treatment with cyclosporine plus anti-TNFalpha had an additive therapeutic effect. CONCLUSION: Although cyclosporine and anti-TNFalpha target different points in the inflammatory pathway, there is an overlap in the consequences of their actions in vivo.

Animals↗
PubMed1997

Suppression of TNF-alpha expression, inhibition of Th1 activity, and amelioration of collagen-induced arthritis by rolipram.

Rolipram is a type IV phosphodiesterase inhibitor that suppresses inflammation and TNF-alpha production. As anti-TNF-alpha therapy is effective in rheumatoid arthritis, we investigated the effect of rolipram on collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis. Rolipram was administered after the onset of clinical arthritis at doses of 0.5, 3, 5, or 10 mg/kg twice daily, with a dose-dependent therapeutic effect on clinical severity and joint erosion. Immunohistochemical analysis of joints of rolipram-treated mice revealed 67% reduction in TNF-alpha-expressing cells compared with control arthritic mice. In vitro studies using bone marrow-derived macrophages confirmed that rolipram directly suppressed TNF-alpha and IL-12 production following stimulation with IFN-gamma and LPS. The effect of rolipram on T cell activity was studied by measuring Th1/Th2 cytokine production by collagen-stimulated draining lymph node cells from arthritic mice treated in vivo with rolipram. Rolipram reduced IFN-gamma production and increased IL-10, indicating that rolipram down-regulated the ongoing Th1 response to type II collagen. Finally, the effect on CIA of combination therapy was studied using rolipram plus either anti-TNF-alpha or anti-CD4 mAbs. Rolipram plus anti-TNF-alpha was not therapeutically additive, whereas rolipram plus anti-CD4 mAb was clearly additive. This result indicates that the therapeutic effects of rolipram overlap with TNF-alpha blockade, but are complementary to anti-CD4 treatment. It is therefore proposed that a major mechanism of action of rolipram in CIA is suppression of TNF-alpha activity. These findings suggest that type IV phosphodiesterase inhibitors may be effective in pathologic conditions, such as RA, with overexpression of TNF-alpha.

Animals↗
PubMed1997

Treatment of a newly established transgenic model of chronic arthritis with nondepleting anti-CD4 monoclonal antibody.

We established a novel animal model for rheumatoid arthritis (RA) by following backcrossing to DBA/1 of (SWR/J x DBA/1)F1 TCR-beta Tg mice, previously reported to be highly susceptible to collagen-induced arthritis. These mice evolved, upon collagen type II immunization, into a chronic arthritis that histopathologically resembles RA. The availability of such a model prompted us to study the role of CD4+ T cells throughout the evolution of disease. Here, we show that administration of nondepleting anti-CD4 not only prevented the evolution of disease but also treated established arthritis. Moreover, functional analyses of T cells isolated from anti-CD4-treated mice demonstrated that the mechanism of protection is not achieved by suppression of the Th1 population but is mediated by induction of collagen type II-specific T cell anergy. Our study suggests that: 1) CD4+ T cells have a fundamental role both in the induction and in the perpetuation of disease; 2) targeting T cells may be an appropriate therapeutic option; and 3) a suitable and well-balanced anti-CD4 treatment may be a valid approach to the control of RA.

Animals↗
PubMed1997

Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA).

This report contains a description of the cellular localization and kinetics of proinflammatory cytokine expression in murine CIA, a model for rheumatoid arthritis. Tissue cryostat sections of undecalcified paws from type II collagen-immunized DBA/1 mice, taken 1-10 days after the onset of clinical arthritis, were examined for the presence of tumour necrosis factor-alpha (TNF-alpha), IL-1beta and IL-6 using an indirect immunoperoxidase technique. In parallel, interferon-gamma (IFN-gamma) production by lymph node cells, stimulated in vitro with type II collagen, was assessed as a marker of T cell activity. The main areas of TNF-alpha, IL-1beta and IL-6 expression were in the synovial lining layer and in tissue contiguous with cartilage and bone (the marginal zone), in particular at sites of pannus formation and joint erosion. There was a progressive increase in the number of TNF-alpha-, IL-1beta- and IL-6-positive cells from day 1 to day 10 of arthritis, during which time IFN-gamma production by CD4+ T cells from draining lymph nodes declined sharply. A further finding of potential significance was that TNF-alpha was consistently detected at day 1 of arthritis, whereas IL- 1beta-positive cells were not found until day 3, suggesting that the expression of TNF-alpha precedes that of IL-1beta.

Animals↗
PubMed1997

Suckling CD1 mice as an animal model for studies of Legionella pneumophila virulence.

On the assumption that specific host defences are lower in newborn and infant animals, the susceptibility of CD1 suckling mice to Legionella pneumophila was studied with the hypothesis that this model could detect consistent differences in virulence among Legionella isolates from various clinical and environmental sources. Mice 3-14 days old were indeed markedly susceptible to intraperitoneal challenge with fresh clinical isolates, but not to serially subcultured or type collection strains of L. pneumophila. For example, intraperitoneal inoculation of 10(7) cells of a fresh clinical isolate of L. pneumophila (strain Monza 3) caused 60% mortality of suckling mice in 1 day whereas the same number of cells of a culture-attenuated derivative (strain Monza 3p50) caused <10% mortality in >15 days. Lethal infection by the 'virulent' Monza 3 strain was strictly dependent on mouse age (no death was observed in mice >26 days old), required the inoculation of viable cells and was not related to endotoxin production. The 'virulent' L. pneumophila strain was cleared from mouse lungs less rapidly, while adhering to, and being internalised into the peritoneal exudate cells (PEC) of suckling mice to a greater extent, than the avirulent derivative, as shown by immunofluorescence and confocal microscopy. The Monza 3 strain also induced the production by PEC in vivo of 5-to-10 times more tumour necrosis factor-alpha (TNF-alpha) mRNA than the Monza 3p50 strain. Overall, suckling CD1 mice appear to provide a promising, easily handled, highly reproducible and relatively inexpensive animal model for studies of the virulence of L. pneumophila, and possibly, of the role of pro-inflammatory cytokine production in this phenomenon.

Animals↗
PubMed1996

Relationship between Th1/Th2 cytokine patterns and the arthritogenic response in collagen-induced arthritis.

It is hypothesized that the balance of cytokines produced by Th1/Th2 subsets of T helper cells plays an important role in the development of autoimmune diseases. Murine collagen-induced arthritis (CIA) is an example of an autoimmune disease in which immunization with cartilage-derived type II collagen induces, firstly, a T cell response to type II collagen and, secondly, the manifestation of a destructive inflammatory response in affected joints. We have investigated the role of Th1/Th2 responses in the development of CIA by monitoring levels of interferon (IFN)-gamma (a Th1 cytokine) and interleukin (IL)-4 and IL-10 (Th2 cytokines), and IL-1 beta and tumor necrosis factor (TNF) (pro-inflammatory cytokines) produced by cultured draining lymph node cells (LNC) from collagen-immunized DBA/1 mice during the induction phase of arthritis and throughout the time of clinical manifestation and subsequent remission of the disease. Although a transient increase in IL-10 was detected 3 days after immunization, Th2 cytokine production was found to be almost completely suppressed 6 days after immunization. In contrast, IFN-gamma was detected in LNC cultures as early as 6 days after immunization and the addition of type II collagen to the culture medium resulted in an approximately 10-fold increase in IFN-gamma production, indicating that a predominantly Th1 response had become established by this time. IFN-gamma production by LNC was found to be further increased at the time of clinical manifestation of arthritis and could be up-regulated by co-culture with type II collagen. IL-10 was not detected in LNC cultures at the onset of arthritis and IL-4, although present, was found to be markedly suppressed in LNC cultures containing type II collagen. These findings indicate that Th1 responses are predominant at the time of onset of arthritis and that the activation of collagen-specific Th1 cells may result in suppression of Th2 activity. IFN-gamma production declined progressively during the progression and subsequent remission of arthritis whereas levels of IL-10 increased and low, though persistent, levels of IL-4 were detected throughout this period. High levels of IL-1 beta and TNF-alpha production were detected at the onset of the disease. The role of Th1 responses in the development of CIA was further emphasized by the observation that immunization of mice with type II collagen in incomplete Freund's adjuvant, which normally fails to induce arthritis, resulted in a predominantly Th2 cytokine profile.

Animals↗
PubMed1989

Free-from-failure survival in Hodgkin's disease. Long-term analysis of 148 cases treated with a MOPP-modified protocol.

The incidence of relapses and second malignant neoplasms was investigated in a group of 148 patients with bad-risk stage II, or stage III and IV Hodgkin's disease treated with a MOPP-modified protocol between 1973 and 1979. Sixty-eight patients received chemotherapy alone, 80 a combined modality treatment including radiotherapy. One hundred and twelve patients achieved complete remission with induction therapy. Thirty-six patients relapsed 3-120 months (median 27 months) after the induction program with a 10-year cumulative risk of relapse of 33.6%. Seven out of 112 complete responders developed a second malignancy 65-145 months from the start of therapy; one more neoplasm has been recorded in a patient with active Hodgkin's disease. Survival after diagnosis of second malignant neoplasm did not exceed 12 months. The cumulative risk of developing a second malignancy was 6.2% at 10 years. The free-from-failure survival was 49.2% at 10 years, being 64.7% for patients achieving complete remission and 92.4% for long-term complete responders. Although an increased number of second malignant neoplasms may occur in patients treated for Hodgkin's disease, the high risk of early relapse, together with the limited effectiveness of salvage therapy, suggests that intensive induction programs should be carried out in patients with advanced or poor-prognosis Hodgkin's disease in order to achieve long-lasting complete remission.

Adolescent↗
PubMed1989

Increasing interdependency of prognosis- and therapy-related factors in Hodgkin's disease.

Two subsequent series of patients with Hodgkin's disease (HD) treated according to different therapeutic plans were compared: the study made it possible to analyze the role played by therapy in influencing the individual importance of a group of well-known prognostic factors. Study 1 concerned 667 patients treated in the period 1971-1979 without special measures for mediastinal bulky disease and with four-drug chemotherapy regimens (MOPP, COPP, ABVD) for stage B or IV. Study 2 included 220 patients treated between 1980 and 1984 with combined sandwich chemoradiotherapy when mediastinal bulk was present, and with eight-drug alternating chemotherapy regimens for stages B or IV (MOPP/ABVD, CcVPP/ABVD). Distribution of epidemiologic and clinical characteristics as well as staging accuracy were comparable in the two series. Only sex, serum albumin at onset and success or failure in achieving complete remission showed the same ability to discriminate survival in both studies. Age, stage and histology retained a reduced role in Study 2, where it was found they could be handled as binary variables, i.e. more or less than 50 years of age, stage IV or other stages, lymphocyte depletion histotype or other types. The influence of B symptoms on survival was sharply decreased in patients treated with alternating chemotherapy regimens, whereas combined sandwich therapy showed a truly leveling effect on the role of mediastinal bulk, which has to be considered a very unfavorable factor with other treatments. In HD the evaluation of clinical findings with respect to their impact on prognosis is crucial for validating and graduating the staging process, and for matching the intensity of the therapy to the needs of the patient. The ongoing evolution in the roles of single prognostic factors due to therapy needs periodic reevaluation for proper adjustments of therapeutic strategies.

Adolescent↗
PubMed1988

Hodgkin's disease prognosis: a directly predictive equation.

586 patients with Hodgkin's disease diagnosed between 1970 and 1979 were staged and treated in the same way. Multivariate analysis was used to delineate the prognostic roles of several clinical features at diagnosis. A multiple regression analysis was applied to an exponential model for survival-time distribution, which proved to fit the data accurately. Several clinical characteristics were studied and those that could singly discriminate survival significantly were chosen as predictive variables for the multiple regression. These were: sex, age, stage, histological subtype, presence of constitutional symptoms, mediastinal mass, and erythrocyte sedimentation rate (ESR), and haemoglobin and serum albumin concentrations. ESR, stage, histological subtype, and age proved to be the best prognostic factors, while sex and albumin had minor value. The presence of symptoms, mediastinal bulk, and haemoglobin were not so important. A linear equation for the six variables was derived to calculate the estimated median survival time for any given patient. This equation was validated on an external group of 179 similar patients.

Actuarial Analysis↗
PubMed1987

Severe platelet dysfunction in a patient with autoantibodies against membrane glycoproteins IIb-IIIa.

A young women affected by Hodgkin's disease developed chronic autoimmune thrombocytopenic purpura. Splenectomy induced normalization of her platelet count, but hemorrhagic symptoms did not disappear. The patient's platelets did not aggregate in response to collagen and ADP and the IgG fraction of the patient's plasma induced the same defect in normal platelets. The women's IgG recognized glycoproteins IIb and IIIa of normal platelet membranes. Prednisone therapy induced the disappearance of bleeding symptoms and the normalization of platelet aggregation.

Adult↗
PubMed1986

[Perinatal cerebral ischemic injury. Neuropathologic bases and correlations with computerized tomography].

The term "hypoxic-ischemic encephalopathy" covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarct necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis.

Brain Ischemia↗