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Biomedical subjects

N Fabris

Publications and source records attributed to N Fabris.

At least 55 records · Page 3Linked to original sources
PubMed1994

Plasma zinc level and thymic hormone activity in young cancer patients.

It has been reported that in many neoplastic diseases, including leukemia, alterations in plasma zinc levels may frequently occur, although the causes for such alterations have yet to be clearly defined. Since zinc is required to induce biological activity to thymulin (Zn-FTS), a biochemical defined thymic hormone, and marginal zinc deficiencies may prevent its peripheral biological activation, we investigated the plasma level of zinc and of both active thymulin (Zn-FTS) and total zinc saturable thymulin (Zn-FTS + FTS) in 91 young patients affected by acute lymphoblastic leukemia (ALL) at various stages of the disease. It was discovered that the plasma zinc level was reduced at the onset and relapse, whereas in complete remission and in off-therapy it was in the normal range. Total zinc-saturable thymulin concentration did not change during the disease, whereas the active fraction was reduced at the onset and in relapse when compared with values observed in the other stages of the disease or in healthy controls. These data suggest that zinc plasma deficiency is present in ALL patients at the onset and during relapse, and that such a deficiency causes a decrease in the activity of thymulin despite a nearly normal production by the thymus. An impairment of peripheral immune efficiency in ALL patients is commonly found. The existence of positive correlations between zinc or active thymulin and peripheral immunological parameters (phytohemagglutinin [PHA] and concanavalin A [ConA]) at various stages of the disease suggests a link between derangement of peripheral immune function, thymic hormone activity, and zinc failure. These findings, considered together, suggest the possibility of a carefully controlled clinic trial with zinc in ALL patients at the onset and in relapse even in the light of in vitro ineffectiveness of physiological zinc or thymulin concentrations on the duplicative index of human lymphoblastoid cells.

Adolescent↗
PubMed1994

Influence of neoadjuvant polychemotherapy on natural killer cell activity in patients with locally advanced cervical squamous carcinoma.

Peripheral blood natural killer (NK) cell activity against K562 tumor line was monitored in 16 patients with locally advanced squamous cervical carcinoma (II and III FIGO stages) during neoadjuvant polychemotherapy (cisplatin at 80 mg/m2 and bleomycin at 30 mg/m2). There was a significant progressive decrease in NK activity during the three cycles of antiblastic treatment (P = 0.008) without significant depletion of NK cell (CD56 and CD16 monoclonal antibody positive cell percentage and absolute number). A significant relationship was shown between basal NK activity levels and response to polychemotherapy; in fact, nonresponder patients had a significantly lower mean value of NK activity before polychemotherapy than responders (P = 0.044). In conclusion, NK activity declines as a result of antiblastic therapy; although polychemotherapy reduces tumor spread, its antineoplastic action may be affected by this decreased immune reactivity.

Adult↗
PubMed1994

Natural killer cell activity in stage I endometrial carcinoma: correlation with nuclear grading, myometrial invasion, and immunoreactivity of proliferating cell nuclear antigen.

The purpose of this study was to examine the relationship between natural killer cell activity and biological behavior of tumor, expressed by architectural (FIGO) and nuclear grading, depth of myometrial invasion, and proliferating cell nuclear antigen (PCNA) index in patients with endometrial carcinoma. Forty patients with FIGO stage I endometrial carcinoma, treated with radical surgery, were included in this retrospective study. At the time of diagnosis, natural killer cell activity of peripheral blood was evaluated against K562 target tumor cells and correlated with architectural and nuclear grading, depth of myometrial invasion, and PCNA index of the tumor. Natural killer activity diminished with increasing nuclear grade of the tumor (P = 0.004); similarly, natural cytotoxicity decreased with myometrial invasion: for stages IC and IB endometrial carcinoma, the mean values of natural cytotoxicity were significantly lower than stage IA disease (P = 0.0001). Natural killer activity was significantly correlated with PCNA immunostaining of the tumor (r = -0.8). It is concluded that the natural immune reactivity seems to be related to the pathologic features of early stage endometrial carcinoma, showing a significant reduction in presence of nuclear pleomorphism and/or myometrial invasion, and also an inverse relationship with PCNA index.

Adult↗
PubMed1994

The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice.

It has been demonstrated that melatonin, the main neuro-hormone of the pineal gland, affects thymic functions and the regulation of the immune system. In addition, experimental evidences indicate that melatonin can modulate zinc turnover. The knowledge that with advancing age both melatonin and zinc plasma levels decline, and that zinc supplementation in old mice is able to restore the reduced immunological functions, has prompted investigations on the effect of chronic melatonin treatment or pineal graft in old mice on the age-related decline of thymic endocrine activity, peripheral immune functions and zinc turnover. Both melatonin treatment in old mice and pineal graft into the thymus of old mice correct the reduced thymic endocrine activity and increase the weight of the thymus and its cellularity. A restoration of cortical thymic volume, as detected by the percentage of tissue in active proliferation, is also observed in old mice after both treatments. Thymocyte CD phenotype expression is also restored to young values. At peripheral level, recovery of peripheral blood lymphocyte number and of spleen cell subsets, with increased mitogen responsiveness also occurs. Melatonin treatment or pineal graft induce also a restoration of the altered zinc turnover in aged mice with an increment of the crude zinc balance from negative (-1.6 microgram/day/mouse) to positive value (+1.2 microgram/day/mouse), similar to that one of young mice (+1.4 microgram/day/mouse). The reduced zinc plasma level is restored to normal values. These findings support the idea that the effect of melatonin on thymic endocrine activity and peripheral immune functions may be mediated by the zinc pool.

Aging↗
PubMed1994

Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters.

The effect of 4 months of oral zinc supplementation on immune functions in non-institutionalized young female and male Down's syndrome (DS) subjects was studied. Along with plasma levels of zinc, the immune parameters, measured before and after zinc treatment, were plasma levels of thymulin, the percentage and the absolute number of circulating white blood cells, total lymphocytes, lymphocyte subpopulations, the mitogen-induced lymphocyte proliferation, the production of interleukin-2, and the activity of stimulated granulocytes. Some immune parameters were significantly influenced by zinc treatment. In particular, a normalization of thymulin and zinc plasma levels were found in these subjects after zinc supplementation. At the end of the clinical trial, in vitro lymphocyte proliferation and polymorphonuclear activity also increased and reached normal values. Zinc administration exerted a positive clinical effect in these children, since a reduced incidence of infections was found.

Administration, Oral↗
PubMed1994

Interferon alpha 2b treatment of cervical intraepithelial neoplasia grade 2: modulation of natural killer cell.

The objective was to evaluate natural cytotoxicity of peripheral blood during interferon treatment in cervical intraepithelial neoplasia grade 2 (CIN2), as index of interferon activity. Twenty-one patients with CIN2, histologically proven, were treated with interferon alpha 2b (Intron A, Sheering-Plough Corp.), in a dose of 3,000,000 units three times per week for 8 weeks self-administered by intramuscular injection. The rate of remission to the interferon treatment was 38.1%. Eight healthy patients had a significant increase in natural killer activity during and after the treatment (p < 0.001), whereas the 13 nonresponder patients remained with low values of natural killer activity. By analyzing the basal natural killer activity before the treatment, the patients with clinicopathologic remission had a significantly higher mean value than nonresponder patients (p = 0.007). Notwithstanding the specimen exiguity, the individual basal natural killer activity seems to be a predictive parameter of interferon treatment response in patients with CIN2.

Adult↗
PubMed1994

The relationship of clinical-pathologic status and adjuvant treatment with natural killer cell activity in stage I and II endometrial carcinoma.

OBJECTIVE: The aim of our study was to evaluate the basal immune reactivity in patients with locally advanced endometrial carcinoma, and the immune modulating effect of adjuvant treatment in cancer population randomized to endocrine or radiation therapy. MATERIAL AND METHODS: Forty-three patients with FIGO stage I and II endometrial carcinoma, treated with primary radical surgery, were randomly selected to receive endocrine (medroxy-progesterone acetate 30 mg weekly and Tamoxifen 300 mg weekly, given consecutively) or radiation adjuvant treatment (external beam photon treatment of the whole pelvis, with an average total dose of 3680 cGy rad). The immune assay included the evaluation of natural killer cell activity by target cell retention of the fluorescent dye carboxyfluoresceyn diacetate, using sensitive cell line K 562. The immunological monitoring was performed before surgery, and then before, during, and after adjuvant treatment. Nine patients, who refused any adjuvant treatment, were recruited as controls. RESULTS: Patients, matched for age and demographic characteristics, with locally advanced endometrial carcinoma had significantly lower mean values of natural killer activity than in healthy controls; the decrease of natural cytotoxicity was significantly related to the depth of myometrial invasion. The adjuvant treatment was associated with a significant immune modulation: patients in endocrine therapeutic regimen showed an increase of natural killer activity, while patients in radiation therapy had a reduction; in the control group there was no significant modification of natural cytotoxicity during negative follow up. CONCLUSIONS: Natural killer cell activity of peripheral blood is significantly reduced in local advanced endometrial carcinoma patients. The natural cytotoxicity evaluation, as a function of therapeutic modality, may be useful in establishing a relationship between adjuvant treatment and immune status in endometrial carcinoma.

Adenocarcinoma↗
PubMed1993

Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease.

The aim of this work was to evaluate whether oral supplementation with zinc sulphate (ZnSO4) could restore thymic endocrine function in patients with Crohn's disease who showed decreased plasma concentrations of zinc and active thymulin, a zinc-dependent thymic hormone. Twenty-seven patients in clinical remission were randomly assigned to receive, for 3 months, one of the following treatments: 60 mg/day ZnSO4; 200 mg/day ZnSO4 or placebo. Plasma thymulin activity and zinc concentrations significantly increased only in patients treated with 200 mg/day ZnSO4. Lymphocyte subpopulations, within the range of normality before zinc supplementation, were unaffected by any of the administered treatments. In conclusion, low plasma concentrations of zinc and thymulin in Crohn's disease patients were restored by the administration of high doses of zinc.

Adult↗
PubMed1993

Natural killer cell activity and progression-free survival in ovarian cancer.

A longitudinal evaluation of the natural killer (NK) cell activity of peripheral blood lymphocytes was performed in 17 patients with advanced ovarian cancer (treated surgically and with subsequent multiagent chemotherapy) for a median follow-up period of 32 months. At the time of primary treatment, the mean value of NK cell activity was significantly lower in patients who then had disease progression (p < 0.05) than in patients with progression-free survival. During the follow-up period, no significant modifications of the NK cell activity were observed; only at the time of clinical disease progression did the NK cell activity show a significant reduction. We conclude that the NK cell activity is a potentially important prognostic factor.

Adenocarcinoma↗
PubMed1993

Modulation of the neuroendocrine system and immune functions by zinc supplementation in children with Down's syndrome.

Plasma levels of TSH, T4, T3, and reversal T3 (rT3) were measured in 51 children with trisomy of the chromosome 21 and in 15 controls. Levels of TSH were higher in children with DS than in controls and rT3 levels were decreased. However, T3 and T4 levels were in the normal range. Plasmic zinc and thymulin, a zinc-dependent thymic hormone, were also decreased. After dietary supplementation with ZnSO4, levels of plasmic zinc, thymulin, TSH and rT3 were restored. A follow up of DS children one year after the cessation of zinc therapy showed that plasma levels of zinc decreased and TSH lightly increased. Zinc deficiency may play a crucial role in the pathogenesis of thyroid gland disfunction which leads to the autoimmune hypothyroidism often observed in this syndrome.

Down Syndrome↗
PubMed1993

Natural killer cell activity in endometriosis: correlation between serum estradiol levels and cytotoxicity.

OBJECTIVE: To evaluate the correlation between natural killer cell activity and serum estradiol (E2) levels in patients with different stages of endometriosis. METHODS: Natural killer cell activity of peripheral blood lymphocytes and serum E2 levels were evaluated in 73 women who underwent laparoscopy for pelvic pain, infertility, and benign adnexal masses. RESULTS: The 33 patients (45%) with endometriosis showed a significant decrease in natural killer cell activity in relationship to an increase in disease stage (correlation coefficient r = -0.83, P < .001). A significant inverse relationship was observed between cytotoxicity and serum E2 levels (correlation coefficient r = -0.89, P < .001). CONCLUSION: The relationship between natural killer cell activity and serum E2 levels suggests that an immunoendocrine interaction plays an important role in the progression of endometriosis.

Adult↗
PubMed1992

Biomarkers of aging in the neuroendocrine-immune domain. Time for a new theory of aging?

A common and generally accepted assumption is that with advancing age, the thymus undergoes progressive and irreversible involution. This is considered the main cause for the age-related deterioration of various immune functions and, ultimately, for the increased incidence of infectious, neoplastic, and automimmune diseases in old age. This assumption is no longer tenable because of several clear-cut demonstrations that age-related thymic involution is not an intrinsic and irreversible phenomenon. Various neuroendocrine or nutritional manipulations can to induce a regrowth of the thymus, even when applied in old age. This thymic reconstitution is followed by a consistent recovery of peripheral immune functions. These data strongly support the idea that thymic involution is a phenomenon secondary to age-related alterations in neuroendocrine-thymus interactions and that it is the disruption of such interactions in old age that is responsible for most of the age-associated dysfunctions. On the basis of this experimental and clinical evidence and as an alternative to purely immune or neuroendocrine theories of aging, a neuroendocrine-immune hypothesis is proposed. Further work is required to determine if the age-related disruption of neuroendocrine-immune interactions occurs because of progressive accumulation of stressor-dependent consequences at the level of one or the other system or if it may depend on a single common cause.

Aging↗
PubMed1992

Optimization of cytotoxic assay by target cell retention of the fluorescent dye carboxyfluorescein diacetate (CFDA) and comparison with conventional 51CR release assay.

This paper describes the comparison between a fluorimetric NK assay based on the target cell retention of fluorescent dye carboxyfluorescein diacetate (cFDA) and standard 51Cr release assay. The results provide several suggestions to improve the cytotoxic assay based on the use of the fluorogenic substrate showing that the measurements of cFDA retained by target cells represent a method of evaluating cytotoxicity completely comparable to the 51Cr release assay.

Chromium Radioisotopes↗