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Biomedical subjects

N Fabris

Publications and source records attributed to N Fabris.

At least 37 records · Page 2Linked to original sources
PubMed1995

Thyroid and thymic endocrine function and survival in severely traumatized patients with or without head injury.

OBJECTIVE: Functional links among the brain, endocrine and immune system have been described previously. An impairment of both immunological defence mechanisms and thyroid hormone turnover was present in trauma conditions. An investigation on the relevance of thymulin and thyroid hormones in multiple trauma patients with or without head injury has been performed. The role of these hormones as predictive factors for patients outcome was also evaluated. DESIGN: Plasma thymulin levels and plasma thyroid hormone concentrations were tested in multiple trauma patients 24 h after admission to the Intensive Care Unit (ICU) and again after 5 and 10 days. SETTING: Department of Immunology Ctr. INRCA, IInd ICU, S. Matteo Hospital Pavia and ICU "Umberto I" Hospital, Ancona. PATIENTS: 45 patients were evaluated including 14 multiple trauma patients without head injury and 31 multiple trauma patients with head injury at various level of coma, graded according to the Glascow Coma Score (GCS). INTERVENTIONS: Routine protocol interventions were performed in all head injured patients. MEASUREMENTS AND RESULTS: Thymulin and triiodothyronine (T3) levels were reduced, and reverse triiodothyronine (rT3) increased in all traumatized patients, but multiple trauma patients with head injury and GCS < or = 5 had the lowest levels of thymulin and T3 and the highest levels of rT3. No difference in plasma thyroxine (T4) and thyrotropin (TSH) levels was observed among injured patients. The analysis of predictive factors for the outcome has assigned to thymulin the highest score (29.6%) compared with the score for T3 (19.3%) and rT3 (26.3%). The total relative risk (delta %) calculated on the basis of T3 or rT3 rises significantly when thymulin relative risk is added. CONCLUSIONS: Thymulin is markedly reduced in multiple trauma patients with head injury and it represents a predictive factor for the outcome better than the one deriving from the single measurements restricted to thyroid hormones.

Accidental Falls↗
PubMed1995

Zinc, human diseases and aging.

Zinc is one of the most important trace elements in the body for many biological functions; it is required as a catalytic component for more than 200 enzymes, and as a structural constituent of many proteins, hormones, neuropeptides, hormone receptors, and probably polynucleotides. Due to its role in cell division and differentiation, programmed cell death, gene transcription, biomembrane functioning and obviously many enzymatic activities, zinc is considered a major element in assuring the correct functioning of an organism, from the very first embryonic stages to the last periods of life. This biological role together with the many factors that modulate zinc turnover explains on one hand, the variety of clinical and laboratory signs resulting from its reduced bioavailability, and on the other, the high number of human pathologies characterized by alterations in the zinc pool. As zinc supplementation is efficacious in most of these conditions, it is regarded more as an oriented therapeutical support, than a simple dietary integrator. Furthermore, the relevance of zinc status to many age-associated diseases and, according to experimental studies, the aging itself of the major homeostatic mechanisms of the body, i.e., the nervous, neuroendocrine and immune systems, places zinc in a pivotal position in the economy of the aging organism.

Aging↗
PubMed1995

Relationship between 17-beta-estradiol and prolactin in the regulation of natural killer cell activity during progression of endometriosis.

Endometriosis is an estrogen-dependent disease affecting women during their reproductive years. An abnormal immune function and, in particular, a decreased natural killer (NK) cell activity have been found in endometriosis, suggesting a role of the immune system in the pathophysiology of the disease. We have recently evidenced a significant inverse relationship between 17-beta-estradiol plasma levels and NK cytotoxicity in endometriosis patients. In this study we have investigated the combined role of 17-beta-estradiol (E2) and prolactin (PRL) in the regulation of NK cell activity during the progression of endometriosis, by evaluating the correlation among E2, PRL, and other immunomodulating neurohormones on both the cytotoxic activity and the number of NK cells in women at different stages of endometriosis. The early stages (I/II) of endometriosis are characterized by increased plasma levels of either E2 or PRL without significant alterations of NK cell activity in comparison with healthy subjects. The progression to advanced stages (III/IV) of the disease is associated with a further increase of E2 levels, a decrease of PRL plasma concentrations (with an increase of E2/PRL ratio), and an impairment of NK cytotoxicity. The plasma levels of both E2 and PRL and the E2/PRL ratio are significantly correlated with the values of NK cytotoxicity in advanced stages of endometriosis. Either the absolute number or the relative percentage of CD16+ or CD56+ peripheral lymphocytes are not significantly different between patients at either stages I/II or III/IV and healthy controls. Plasma levels of progesterone (P) and luteinizing hormone (LH), are not significantly changed in different stages of endometriosis with respect to healthy controls. The significant decrease of follicle-stimulating hormone (FSH) plasma levels found in either stages I/II or III/IV endometriosis patients is not correlated with the NK cell activity. In conclusion, at advanced stages of endometriosis the impairment of NK cell activity occurs with increased E2, and decreased PRL plasma levels. Additional studies are required to determine whether the E2/PRL ratio represents a possible biochemical marker of endometriosis.

Adult↗
PubMed1995

Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old mice.

With advanced ageing the zinc pool undergoes progressive reduction as shown by the low zinc plasma levels and the negative crude zinc balance, both in humans and in rodents. It has been suggested that such zinc deficiency might be involved in many age-related immunological dysfunctions, including thymic failure. The relevance of zinc for good functioning of the entire immune system is, at present, well documented. In particular, zinc is required to confer biological activity to one of the best-known thymic peptides, thymulin, which is responsible for cell-mediated immunity. In deep zinc deficiencies, in humans and other animals, the low thymulin levels are due not to a primary failure of the thymus, but to a reduced peripheral saturation of thymic hormones by zinc ions. In aged mice both a reduced peripheral saturation of the hormone and a decreased production by the thymus were present. Oral zinc supplementation in old mice (22 months old) for 1 month induced a complete recovery of crude zinc balance from negative (-1.82) to positive values (+1.47), similar to those of young animals (+1.67). A full recovery of thymic functions with a regrowth of the organ and a partial restoration of the peripheral immune efficiency, as measured by mitogen responsiveness (PHA and ConA) and natural killer cell (NK) activity, were observed after zinc supplementation. These findings clearly pin-point for relevance of zinc for immune efficiency and suggest that the age-related thymic involution and peripheral immunological dysfunctions are not intrinsic and irreversible events but are largely dependent on the altered zinc pool.

Administration, Oral↗
PubMed1995

Benefit of oral zinc supplementation as an adjunct to zidovudine (AZT) therapy against opportunistic infections in AIDS.

Zinc is perhaps the most important trace element for immune function. Congenital or acquired zinc deficiencies are associated with immune abnormalities and increased susceptibility to infectious diseases. AIDS subjects suffer from reduced zinc bioavailability, more severe in stage IV than in stage III. Such zinc deficiency causes, among other effects, a profound reduction in the biological activity of one of the thymic hormones, thymulin (zinc-facteur-timique-serique, ZnFTS). With these premises, zinc sulphate was administered orally at a daily dose of 200 mg for 30 days to AZT-treated stage III subjects with generalized lymphadenopathy (17 subjects) and stage IV subgroup C1 (12 subjects) AIDS patients. 18 stage III subjects with generalized lymphoadenopathy and 10 stage IV subgroup C1 subjects treated only with AZT served as controls. Zinc sulphate supplementation of stage III and in stage IV C1 patients was followed by an increase or a stabilization in the body weight and an increase of the number of CD4+ cells and the plasma level of active zinc-bound thymulin. The frequency of opportunistic infectious episodes in the 24 months following entry into the study was reduced after zinc supplementation in stage IV C1 subjects (11 infections vs 25 in controls) and delayed in stage III zinc-treated subjects (1 infection/24 months vs 13 infections/24 months in controls). The effect of zinc on opportunistic infections is restricted to infections due to Pneumocystis carinii and Candida, whereas no variations have been observed in the frequencies of cytomegalovirus and toxoplasma infections. These data may support the benefit of zinc as an adjunct to AZT therapy in AIDS pathology.

AIDS-Related Opportunistic Infections↗
PubMed1995

Dose-dependent opposite effect of zinc on apoptosis in mouse thymocytes.

Zinc is a crucial nutritional component required for the normal development and maintenance of immune functions. It has been reported that zinc is a potent inhibitor of DNA fragmentation, the specific marker of apoptosis. The effect of zinc on apoptotic cell death has been previously studied in a narrow range of high zinc concentrations, and the role of physiological zinc doses has not yet been elucidated. In this paper we evaluate the effect of in vitro Zn2+ administration at concentrations higher than, corresponding to, and lower than the physiological concentration, in thymocytes from young mice. We demonstrate that Zn2+ has an opposite effect on apoptosis, inhibiting or increasing it depending on the Zn2+ concentration used. High Zn2+ concentrations (from 600 to 75 microM) inhibit both serum-free medium and DEX-induced thymocyte apoptosis. Low Zn2+ concentrations (from 15 to 7.5 microM) induce apoptosis or increase serum-free medium-induced apoptosis. The effect of low Zn2+ concentrations on DEX-induced apoptosis is dependent on the length of incubation, since Zn2+ has an additive effect with DEX in inducing DNA fragmentation at 8 h of culture, whereas it blocks DEX-induced apoptosis after 20 h incubation. Both DEX and 15 microM Zn(2+)-induced DNA fragmentation require protein synthesis, being blocked through cycloheximide. The inhibiting and inducing effects of Zn2+ on apoptosis are exerted on G0/G1 phase thymocytes. The inhibiting effect of Zn2+ on apoptosis is related to an increase in the number of CD4+CD8+ thymocytes. Concentrations of Zn2+ inducing apoptosis sometimes cause a decrease of CD4+CD8+ cells with a corresponding increase of CD4+CD8-thymocytes. These data show that in vitro Zn2+ has a dose-dependent opposite effect on apoptosis, suggesting that Zn2+ not only acts as an inhibitor but also plays a more complex role in physiological intrathymic cell selection.

Analysis of Variance↗
PubMed1995

Age-related thymus involution: zinc reverses in vitro the thymulin secretion defect.

The inevitability of thymic involution in aging has been opened to question by two recent findings. First, it has been demonstrated that the synthesis and/or secretion of one thymic factor, zinc-thymulin (Zn-FTS), is still present, although reduced, in humans over 90 yr of age and in mice over 24 months of age. The major defect resides in the zinc saturation of thymulin, rather than in the synthesis and secretion rate of the polypeptide by the thymus. Zinc pool is in fact reduced in old age. Thymic explants from old mice in vitro for a short period (6 h) produce nearly the same amount of thymulin as young thymuses, but the zinc-bound form is nearly absent. Zinc addition to the cultures fully recovers the defect. These findings clearly suggest that thymic involution is not an intrinsic and irreversible phenomenon, but is largely due to microenvironmental factors, among which zinc is crucial.

Aging↗
PubMed1995

Pituitary-thyroid axis and immune system: a reciprocal neuroendocrine-immune interaction.

A good body of experimental and clinical results has supported the existence of numerous reciprocal interactions among the nervous, endocrine and immune systems. Increasing evidence has been accumulated in the last years on the interaction between pituitary-thyroid hormones and the immune system on the basis of either the existence of receptors for thyreotropic and thyroid hormones on lymphocytes or the frequent immune alteration in physiological and pathological fluctuations of thyroid hormones. The data were obtained either in animals with experimentally induced hyper- or hypothyroidism or in humans with various hyperthyroid or hypothyroid situations. Conversely, immune-derived products such as lymphokines and monokines have been shown able to influence the pituitary-thyroid axis modulating either the thyroid hormone levels or the hormone/cytokine production by thyrocytes. The present paper aims at summarizing the data available on the existence of thyroid-immune interactions, and at analyzing the possible integration between pituitary-thyroid hormones and immune factors in favoring the development and maintenance of both thymic and peripheral immune efficiency. The relevance of pituitary-thyroid-immune interactions is discussed for its implication in the ageing process.

Aging↗
PubMed1995

Natural killer cell activity in patients with invasive cervical carcinoma: importance of a longitudinal evaluation in follow-up.

OBJECTIVE: To analyze longitudinally the basal natural killer cell activity in patients with invasive cervical carcinoma, the natural cytotoxicity was related to the most important known prognostic factors, and evaluated with respect to the clinical outcome of cervical disease. MATERIALS AND METHODS: Forty-six patients with histologically proven invasive cervical carcinoma treated and followed at the Institute of Gynecology and Obstetrics, Ancona University, Salesi Hospital, were consecutively recruited from 1989 to 1992 and included into the study. For immunologic investigation, natural killer cell activity and peripheral blood T-lymphocyte subsets were tested before primary treatment and during the follow-up period, every 6 months. Natural killer activity was determined by target cell retention of the fluorescent dye carboxyfluorescein diacetate; the K 562 cell line was used as target cells. RESULTS: A significant inverse relationship was observed between natural killer activity and disease stage (p = 0.001); patients with stage IV disease had the lowest level of natural cytotoxicity. The reduction of natural cytotoxicity was not accompanied by any alteration of lymphocyte distribution. The longitudinal analysis showed an increase of natural killer activity after surgical removal of the tumor, persisting during the follow-up, but all the 9 patients who recurred showed, at the time of disease recurrence, a significant decrease of their natural cytotoxic potential. CONCLUSION: Natural killer cell activity seems to be a functional index of immune status, significantly related to the stage and the clinical outcome of disease.

Adenocarcinoma↗
PubMed1995

HPV DNA positivity and natural killer cell activity in the clinical outcome of mild cervical dysplasia: integration between virus and immune system.

The objective was to examine the prevalence of human papillomavirus (HPV) DNA infection in mild cervical dysplasia and to evaluate longitudinally the persistence of HPV DNA positivity in an observational study, aiming at identifying the role of peripheral blood lymphocyte natural killer activity in the natural history of dysplastic disease. Twenty-three patients with histologically proven mild cervical dysplasia were selected. The HPV DNA positivity, determined by polymerase chain reaction, and cervical dysplasia were monitored cytologically and colposcopically at the 3rd (time 1), 6th (time 2) and 12th months (time 3), and defined by biopsies for routine histology taken at times 2 and 3. For each patient included in the study, the immune reactivity was evaluated at the time of diagnosis and afterwards, longitudinally during the follow-up. The immune status analysis included T lymphocyte subsets (CD3, CD4, CD8, CD56, CD16 monoclonal antibodies by Beckton Dickinson, Mountain View, Calif., USA) and determinations of natural killer cell activity (against the sensitive cell line K 562). Eighteen out of the 23 women with mild cervical dysplasia (78.3%) were found positive for HPV DNA, with a significantly high representation of HPV DNA type 16 (55.6% of cases). At the end of the study, 12 out of 18 HPV-DNA-positive women became negative (defined by two or more negative tests) for the original HPV DNA type, with 66.7% of spontaneous HPV DNA negativization rate (p = 0.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Natural killer activity in stage III and IV endometriosis: impaired cytotoxicity and retained lymphokine responsiveness of natural killer cells.

Our objective was to investigate the role of estrogens in the development and progression of endometriosis, and evaluate the in vitro boosting effect of lymphokines on the activity of natural killer cells from endometriosis patients, with respect to the estradiol concentrations. Natural killer activity of peripheral blood was evaluated in 42 endometriosis patients who underwent laparoscopy for pelvic pain, infertility and benign adnexal masses, and it was correlated with serum estradiol levels. Twenty-five women with moderate and severe disease were re-evaluated for immune and endocrine parameters 4-8 weeks after surgery, before any specific adjuvant medical treatment, and analyzed for in vitro responsiveness of cytotoxic cells to interferon (IFN) alpha 2 beta and interleukin-2 (IL-2) incubation. Patients with moderate and severe endometriosis showed a significant decrease of natural cytotoxicity when compared with patients with mild and minimal disease (p = 0.01). The decrease of immune reactivity was independent of a reduced representation of natural killer cells, and persisted after surgical removal of all macroscopic endometriosis foci. A significant inverse relationship was observed between natural killer activity and serum estradiol levels, which resulted in moderate and severe disease (r = -0.4, p = 0.009) but not in stages I and II. The in vitro responsiveness of cytotoxic cells to lymphokine incubation was preserved; both IFN alpha 2 beta and IL-2 were able to increase the cytotoxicity of natural killer cells significantly from advanced-stage patients (p = 0.014 and p = 0.006 for IFN alpha 2 beta and IL-2 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Evaluation of lymphokine-activated killer cell development in young and old healthy humans.

The kinetics of the development of lymphokine-activated killer (LAK) cell activity, the surface phenotype, and the expression of p55 and p75 interleukin 2 receptors (IL-2R) on IL-2-activated peripheral lymphocytes have been investigated in young and old healthy humans selected according to the Senieur Protocol criteria. No difference is present between young and old healthy subjects in terms of LAK cell activity development. The proliferative capacity of lymphocytes incubated with IL-2 shows similar kinetics in young and old subjects. The mean percentages of CD56+ and CDl6+ cells reach higher levels in old than in young donors. The proportion of CD56+/CD25+ cells in culture is significantly higher in old than in young individuals. A progressive decrease of CD4+ population occurs during LAK cell development, both in young and old subjects. The proportion of CD4+ T cells in culture is lower in old than in young individuals. No age-related difference is present in the mean percentage of cells positive for p55 or p75 IL-2R at any culture time. Thus, our findings show similar kinetics of development of LAK cell activity in young and old subjects, indicating that aging per se does not represent an exclusion criterion of cancer patients from clinical trials of adoptive immunotherapy. A higher proportion of CD56+ and CDl6+ cells seems to be required in old subjects to obtain the same levels of LAK cell activity present in young age.

Adult↗
PubMed1994

Adjuvant effect of low-dose interleukin-2 on antibody response to influenza virus vaccination in healthy elderly subjects.

It is well known that immune efficiency is frequently deteriorated in elderly people. The age-diminished antibody response to T-cell dependent antigens, such as influenza virus antigens, may explain the low protection offered by influenza vaccination in the elderly population. To investigate the possibility of increasing the antibody response to influenza virus vaccinations, we have conducted a nursing home-based study on the efficacy of IL-2. Seventy-five institutionalized elderly subjects (82 +/- 8 years) were enrolled in the study in the course of winter season 1991-1992. Thirty-nine subjects were treated with three subcutaneous daily injections of interleukin-2 (IL-2, 1 x 10(6) I.U./day) before vaccination and their antibody response was compared to that of 36 aged people receiving the vaccine only. An increased antibody response against influenza virus was present in vaccine plus IL-2 treated subjects (P < 0.001) but not in subjects treated with vaccine only. The number of protected subjects 45 days after vaccination was increased only in the IL-2-treated group (P = 0.045). The low-dose of IL-2 administered and the short-term treatment allowed a good tolerance to the IL-2 injection. In conclusion, the low-dose IL-2 treatment represents an effective means of inducing antibody response to influenza virus antigens in elderly subjects without appreciable toxicity.

Adjuvants, Immunologic↗
PubMed1994

Immune enhancement by conditioning of senescent mice. Comparison of old and young mice in learning ability and in ability to increase natural killer cell activity and other host defense reactions in response to a conditioned stimulus.

It has been clearly demonstrated that immune responses may be conditioned in a manner similar to that of the classical Pavlovian experiments. Evidence of impaired immune function in aging has raised the question of whether psychological conditioning of an immune response can also be effective in old age. The knowledge that aged mice have decreased spleen cell natural killer (NK) activity and that NK cytotoxicity, at least in young mice, can be psychologically conditioned led us to explore in old mice the possibility of conditioning the response of NK cell activity using the odor of camphor as the conditioned stimulus (CS) and the injection of Poly I:C as the unconditioned stimulus (US). Young and old male mice were divided into five and six groups, respectively. They received the CS and/or the US in association (conditioning) trials (sessions 1-9). Mice were exposed to the camphor odor alone at 72 hours after the final association trial to observe the conditioning phenomenon (session 10). The group conditioned with Poly I:C and camphor and receiving the CS at session 10 showed statistically significant increases in spleen cell NK activity over those of the control groups that did not receive the CS treatment at session 10 (2.6- and 4.0-fold increase in young and old, respectively). Treatment with camphor odor alone had no effect on boosting NK cell activity. These findings demonstrate the possibility of conditioning immune responses in old age, offering a valuable tool for attenuating age-related immune deterioration in various species, including the human. In addition, these results again confirm highly significant immune enhancement by classical conditioning and extend previous findings from female mice to males as well.

Aging↗