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Biomedical subjects

C Franceschi

Publications and source records attributed to C Franceschi.

At least 235 records · Page 13Linked to original sources
PubMed1993

Corticotropin-releasing hormone modulates cytokines release in cultured human peripheral blood mononuclear cells.

Immune and neuroendocrine systems interact at various levels. In particular, either cytokines activate the hypothalamus-pituitary-adrenal axis (HPA) or corticotropin-releasing hormone (CRH) induces the release of beta-endorphin from peripheral human mononuclear cells. The aim of the present study was to investigate whether CRH may affect cytokine production and activity in human peripheral blood mononuclear cells (PBMC). Primary cultures of human PBMC and monocytes were used. They were incubated in presence of different doses of synthetic human CRH. Media were collected and interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels were measured by ELISA, while interferon-gamma (IFN-gamma) levels were measured by bioassay. In addition, phytohemoagglutinin-induced lymphocyte proliferation was evaluated by testing [3H]thymidine incorporation in the presence of various doses of CRH. CRH significantly increased IL-6 release from PBMC (p < 0.01). The addition of CRH to PBMC significantly decreased IFN-gamma levels, in a dose dependent manner (p < 0.01). No significant effect of CRH was observed on lymphocyte proliferation or IL-1 beta production. The present results suggest a role for CRH as a paracrine mediator for human immune cells, increasing the evidence of a clear correlation between immune and neuroendocrine system.

Adult↗
PubMed1993

Enhanced DNA repair in lymphocytes of Down syndrome patients: the influence of zinc nutritional supplementation.

Oral zinc supplementation is able to correct zinc deficiency and some immune defects present in Down's syndrome (DS), while other beneficial effects can be predicted because of the broad spectrum of biochemical pathways and the great variety of enzymes which depend on zinc bio-availability. To test if the maintenance of DNA integrity is also affected by zinc supplementation, DNA damage and repair after gamma-radiation was studied by alkaline elution assay in phytohemagglutinin-stimulated lymphocytes from Down's syndrome children before and after an oral zinc supplementation given for 4 months to correct their immune defects. In comparison with lymphocytes from normal children the DNA damage induction after ionizing radiation in DS lymphocytes both before and after zinc supplementation was normal. On the other hand, the rate of DNA repair in DS was highly and significantly accelerated before zinc treatment. After supplementation with zinc sulfate, the DNA repair rate was consistently slowed down becoming similar to that of control subjects. This is the first demonstration that a nutritional intervention in humans is apparently able to modify the biochemical steps which control the rate of DNA repair.

Administration, Oral↗
PubMed1993

The effect of L-carnitine and acetyl-L-carnitine on the disappearance of DNA single-strand breaks in human peripheral blood lymphocytes.

DNA single-strand breaks (SSBs) and their disappearance during repair incubation were determined by alkaline filter elution in freshly isolated human peripheral blood lymphocytes (PBLs) after in vitro treatment with either the oxygen radical-generating system of xanthine oxidase (XOD) plus hypoxanthine (HYP) or the alkylating agent N-ethyl-N'-nitrosourea (ENU). The elution curves obtained with DNA from PBLs treated with XOD/HYP were markedly nonlinear, possibly as a result of a nonrandom induction of SSBs along the DNA strands. The disappearance of XOD/HYP-induced SSBs during the initial repair period was quite slow; only 20 +/- 7% (n = 6) of the induced SSBs had disappeared after a 2 1/2 h repair incubation. However, by 24 h the elution curves obtained with DNA from treated PBLs were indistinguishable from those obtained with DNA from nontreated control cells, indicating complete repair. Treatment of PBLs with ENU resulted in linear elution curves. Approximately 50% of the total amount of ENU-induced SSBs had disappeared within 1 h in PBLs from most donors; the additional SSBs were found to be persistent (Beorrigter, M.E.T.I., Mullaart, E., Berends, F., and Vijg, J. (1991) Induction and disappearance of DNA strand breaks and/or alkali-labile sites in human lymphocytes exposed to N-ethyl-N'-nitrosoureas. Carcinogenesis, 12, 77-82). Preincubation of PBLs with 5 mM L-carnitine, a trans-mitochondrial carrier of acetyl and long-chain acyl groups, or 5 mM acetyl-L-Carnitine, resulted in a more rapid disappearance of XOD/HYP-induced SSBs (48 +/- 23% and 48 +/- 30% respectively). Preincubation of PBLs with different doses of L-carnitine, before exposure to 0.5 mM ENU, increased SSB disappearance dependent on the dose and donor PBLs. In conclusion, these studies suggest that treatment with L-carnitine accelerates the disappearance of SSBs induced by oxygen radicals and alkylating agents.

Acetylcarnitine↗
PubMed1993

Complex alteration of thyroid function in healthy centenarians.

Several changes in thyroid function have been described in the elderly and largely attributed to concomitant nonthyroidal illness. The extent to which aging per se contributes to these changes remains to be elucidated, and scanty data are available in extremely old subjects. The present study was designed to focus on thyroid function during physiological aging, taking advantage of two groups of selected aged individuals: group A of healthy centenarians (n = 41; age range, 100-110 yr) and group B including healthy elderly subjects selected by the criteria of the EURAGE SENIEUR protocol (n = 33; age range, 65-80 yr). Control groups included 98 healthy normal adult subjects (group C; age range, 20-64 yr) and 52 patients with miscellaneous nonthyroidal illness (group D; age range, 28-82 yr). Our previous report of a low prevalence of thyroid autoantibodies in centenarians was confirmed and extended by the finding of a similar low autoantibody prevalence in the highly selected healthy elderly population of group B. Subclinical primary hypothyroidism was found in 3 (7.3%) centenarians, and their data were excluded from further statistical evaluation. No significant difference was found in the median serum free T4 levels of groups A-C. Median (and range) serum free T3 (FT3) was lower in centenarians [3.67 pmol/L (2.3-5.5)] than in group B [5.22 pmol/L (3.4-6.1)] and group C [5.38 pmol/L (2.9-8.4); P < 0.0001 vs. both groups]. Similarly, the median serum TSH level of centenarians [0.97 mU/L (< 0.09 to 2.28)] was lower than those in groups B [1.17 mU/L (0.53-2.74)] and C [1.7 mU/L (0.4-4.8); P < 0.0001 vs. both groups]; moreover, serum TSH was also significantly (P < 0.01) lower in group B than in group C. Both serum FT3 and TSH concentrations showed a significant inverse correlation (r = -0.634; P < 0.0001 and r = -0.377; P < 0.0001, respectively) with age. Median serum FT3 in centenarians was lower than that in group D patients [4.61 pmol/L (2.15-6.6); P < 0.0001]. In contrast, median serum rT3 in centenarians [0.40 nmol/L (0.20-0.77)], although higher than those in groups B [0.24 nmol/L (0.15-0.37); P < 0.0001] and C [0.22 nmol/L (0.05-0.46); P < 0.0001], was significantly lower than that in group D [0.60 nmol/L (0.13-2.08); P < 0.0001]. In conclusion, thyroid function appears to be well preserved until the eighth decade of life if healthy subjects are studied, whereas a reduction of serum FT3 is observed in extreme aging.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

50 Hz AC sinusoidal electric fields do not exert genotoxic effects (micronucleus formation) in human lymphocytes.

Electromagnetic fields produce a variety of effects in several biological systems, including human peripheral blood lymphocytes. A great concern exists regarding possible carcinogenic effects in subjects exposed environmentally to such fields in the vicinity of power lines and electric domestic appliances. Using human lymphocytes from 33 healthy donors and a sensitive cytogenetic method, the cytokinesis-block micronucleus assay, we have demonstrated that the exposure to 50-Hz AC sinusoidal electric fields over a wide range of intensities (0.5-10 kV/m in air) does not increase the spontaneous frequency of micronuclei. Moreover, these fields did not affect the mitomycin-C-induced micronucleus formation, suggesting that they did not exert any synergistic or antagonistic effect.

Adult↗
PubMed1992

Studies of the relationship between cell proliferation and cell death. II. Early gene expression during concanavalin A-induced proliferation or dexamethasone-induced apoptosis of rat thymocytes.

Several data in the literature suggest that an intriguing relationship exists between cell proliferation and cell death. Accordingly, we studied the early expression of different genes in the same cells, i.e. rat thymocytes, undergoing cell proliferation upon stimulation with Concanavalin A or cell death following dexamethasone treatment. We showed that an early accumulation of c-fos, c-jun and c-myc mRNA occurred in both phenomena but with different kinetics. It can be speculated that the early induction of nuclear oncogenes is necessary to allow the later induction of other genes probably regulated at the transcriptional level by the AP-1 complex and/or by Myc protein. The accumulation of the transcript for another gene, i.e. poly(ADP-ribose)polymerase, an enzyme responsible for posttranslational modifications of several nuclear proteins, could instead be related to chromatin modifications occurring in both processes.

Animals↗
PubMed1992

Inhibition of apoptosis by zinc: a reappraisal.

Apoptosis--or programmed cell death--is an active type of cell death, occurring in several pathophysiological conditions. One of the most important characteristics of apoptosis is that cell death is preceded by DNA fragmentation, consequent to the activation of nuclear calcium- and magnesium-dependent endonuclease(s). DNA fragmentation can be inhibited by zinc ions. By using several techniques, such as DNA agarose gel electrophoresis, cytofluorimetric analysis of DNA content and of cell cycle, 3H-thymidine incorporation and trypan blue dye exclusion test, we show that zinc, despite completely inhibiting DNA fragmentation and the consequent loss of nuclear DNA content, does not protect rat thymocytes from spontaneous or dexamethasone-induced death. Our data also suggest that DNA fragmentation, although characteristic, is not a critical event for thymocyte death of apoptotic type.

Animals↗
PubMed1992

Stress response in the freshwater snail Planorbarius corneus (L.) (Gastropoda, Pulmonata): interaction between CRF, ACTH, and biogenic amines.

Previous studies reported that ACTH molecules influence chemotactic and phagocytic activities of hemocytes in the freshwater snail, Planorbarius corneus. The present study reveals that ACTH and CRF affect the release of biogenic amines. Hemocytes from P. corneus hemolymph incubated in vitro with ACTH for 15, 30, and 45 min released epinephrine, norepinephrine, and dopamine. The greatest release occurred after 15 min, while after 45 min the values were similar to those of the controls. Similar incubations with CRF also provoked a release of biogenic amines, this being mainly mediated by the release of endogenous ACTH. These data suggest that (i) ACTH and CRF provoke the release of biogenic amines; (ii) there is a direct relationship between CRF, ACTH, and biogenic amines, with the hemocytes as the target; (iii) exogenous ACTH can mimic an ancestral type of stress response; (iv) the major pathway of the stress response in P. corneus is mediated by a CRF-ACTH-biogenic amine axis. These data should help to unravel part of the complex molecular signaling mechanisms involved in the physiological/endocrinological reaction of invertebrate organisms to stress, and suggest that a stress response unexpectedly similar to that present in mammalian cells is detectable in invertebrates.

Adrenocorticotropic Hormone↗
PubMed1992

Apoptosis--programmed cell death: a role in the aging process?

Cells continuously exposed to genotoxic agents, such as oxygen free radicals (OFRs), deeply involved in the aging process use a variety of cellular defense mechanisms. These defense mechanisms include DNA repair enzymes, antioxidants, poly(ADP-ribosyl)polymerase (pADPRP), and stress proteins and they constitute an integrated network. An age-related failure of the efficiency of this network can affect cell proliferation and cell death, two phenomena tightly linked and regulated. Recent data from our laboratory on the role of DNA damage and pADPRP activation and on the type of cell death induced by OFRs in human lymphocytes are reviewed. In vitro and in vivo data on possible strategies to reduce oxidative stress in lymphocytes from normal and Down syndrome subjects, by using natural compounds and trace elements, are presented. They indicate that nicotinamide and L-carnitine protect human cells from OFR-induced damage and suggest that they are possible candidates as antiaging substances.

Aging↗