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Biomedical subjects

D Monti

Publications and source records attributed to D Monti.

At least 91 records · Page 5Linked to original sources
PubMed1996

Successful immunosenescence and the remodelling of immune responses with ageing.

In recent decades, major theoretical and technological advances have been achieved in the field of immunology. These have allowed the scientific community to analyse the immune system in a much more sophisticated manner than was possible even 20 years ago. Moreover, great theoretical changes have also occurred in gerontology-in particular, the hypothesis has been put forward that ageing and diseases are two different phenomena, and that successful ageing, i.e. ageing in good psychophysical conditions, is really possible for most humans and animals. Immunosenescence was then carefully investigated, either in selected healthy people of advanced age or in the oldest old people, such as healthy centenarians. The main results showed that most immune parameters are indeed well preserved even at this far advanced age. This paper deals with some of the most important theoretical problems of immunosenescence. An immunological tenet was that the most important phenomenon of immunosenescence is the involution of the thymus. In most textbooks and papers it is taken for granted that the thymus starts its involution immediately after puberty. When people aged 60-65 were considered old, it was not difficult to think that they could live for the rest of their life with a fully involuted thymus. The findings on centenarians challenge this tenet, as they have only a small reduction of T lymphocytes, and a relatively normal number of virgin and memory T cells, together with a functional T cell repertoire. Other observations reported here on centenarians, concerning the activity of B lymphocytes and the cytokine network, as well as those on the well-preserved innate immunity and the cells' capability of undergoing proliferation after appropriate stimuli, suggest that complex immune changes occur with age, but also indicate that we have to modify our attitude, to grasp the new scenario which is emerging. Immunosenescence can no longer be considered as a unidirectional deterioration, and this complex phenomenon is much better described by terms such as 'remodelling', 'reshaping' or 'retuning'.

Aging↗
PubMed1996

Sleep in patients with chronic primary insomnia during long-term zolpidem administration and after its withdrawal.

A double-blind trial was carried out to determine the effect of zolpidem or a placebo on sleep in two groups of insomniac patients with a diagnosis of moderate chronic primary insomnia. Zolpidem was given at a daily dose of 10 mg for 27 nights and was preceded (two nights) and followed (three nights) by a placebo. Zolpidem induced a significant increase of total sleep time, while total wake time and wake time after sleep onset were reduced. Values corresponding to stage 2 sleep were augmented, while stage 3 sleep and REM sleep showed no significant changes. Tolerance did not develop during the zolpidem administration period, and rebound insomnia did not show following abrupt interruption of drug administration. In addition, patients on zolpidem had a more peaceful sleep with no decrement of levels of alertness.

Adult↗
PubMed1996

Effects of inspired gas on sleep-related apnea in the rat.

Central apneas have been reported to occur in the rat during all stages of sleep. Two types of apnea have been described: spontaneous and postsigh, which are immediately preceded by an augmented breath. We studied the effect of inspired gas on the number and type of apneas in nine adult male Sprague-Dawley rats that were surgically prepared with cortical electroencephalogram and nuchal electromyogram electrodes. In addition to the electroencephalogram and electromyogram, we recorded respiration by the barometric method by using a single-chamber plethysmograph. Each rat was recorded from 1000 until 1600 on 4 separate days by using different inspired gases: room air, 100% O2, 15% O2, and 5% CO2. We found that the sleep-related apnea index was significantly higher during 100% O2 compared with room air (P < 0.05) and was significantly lower during 15% O2 and 5% CO2 compared with room air (P < 0.05). Postsigh apneas occurred more frequently than did spontaneous apneas (P < 0.0001). The coupling between sighs and apneas was strengthened by hyperoxia and weakened by hypoxia and hypercapnia (P < 0.05 for each). We conclude that stimulation of chemoreceptors acts to oppose apnea in the rat.

Animals↗
PubMed1995

Apoptosis, DNA damage and ubiquitin expression in normal and mdx muscle fibers after exercise.

The current view indicates that after eccentric exercise myofibers are mechanically damaged and therefore an inflammatory and necrotic process occurs. In the present paper we examine the possibility that apoptosis plays a role in normal and dystrophin-deficient muscles after running. We analysed for apoptosis normal and dystrophin-deficient mouse muscles after a night of spontaneous wheel-running followed by two days of rest. Terminal deoxynucleotidyl transferase-mediated end-labeling of DNA in nuclei in tissue sections and gel electrophoresis of extracted DNA showed the presence of fragmented DNA. Furthermore, ubiquitin, a protein whose appearance is related to apoptosis, increased in muscles of both dystrophic and normal runner mice. The present findings which confirm that DNA damage is absent in muscles of sedentary mice but present in muscles of runner mice offer a new hypothesis on early events of muscle damage.

Animals↗
PubMed1995

Involvement of CD45 in dexamethasone- and heat shock-induced apoptosis of rat thymocytes.

CD45 is a transmembrane tyrosine-specific phosphatase which participates in lymphoid cell signal transduction during T cell activation, as well as in intrathymic negative and positive selection. In mammals, this molecule exhibits a variety of isoforms of different molecular weight, whose roles have still to be fully elucidated. We report here that apoptosis of rat thymocytes after in vitro dexamethasone and heat shock treatment was accompanied by an early significative increase of cells expressing CD45RC, the high molecular weight isoform of CD45 molecule. The same phenomenon was observed in thymocytes derived from in vivo dexamethasone-treated rats. However, the increase of CD45RC+ cells was not apparently characteristic of cells undergoing apoptosis, as the same phenomenon was also observed in rat thymocytes induced to proliferate by Concanavalin A. On the whole, these results suggest that CD45 modulation can be added to the list of early molecular events, such as the increased expression of genes (ornithine decarboxylase), proto-oncogenes (c-fos, c-jun, c-myc) and activation of transcription factors (AP-1, NFkB), we previously demonstrated in the same experimental model to occur and to be shared by these two apparently opposite biological processes, i.e., cell proliferation and apoptosis, both likely depending on a complex balance of protein phosphorylation and dephosphorylation.

Animals↗
PubMed1995

Increased waking after intra-accumbens injection of m-chlorophenylbiguanide: prevention with serotonin or dopamine receptor antagonists.

Bilateral injection of the selective 5-HT3 receptor agonist m-chlorophenylbiguanide (5.0-40.0 micrograms) into the nucleus accumbens of the rat significantly increased waking and decreased slow wave sleep. Rapid eye movement (REM) sleep remained unchanged. Pretreatment with the 5-HT3 receptor antagonist MDL 72222 (1aH,3a,5a, H-tropan-3-yl-3,5-dichloro-benzoate) (0.5 mg/kg s.c.) reversed the effects of m-chlorophenylbiguanide (10.0-20.0 micrograms) on sleep and waking. Blockade of the dopamine D1 or D2 receptor with (+)-SCH 23390 (0.25 mg/kg s.c.) or YM-09151-2 (cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide) (0.5 mg/kg s.c.), respectively antagonized the increase of waking and reduction of slow wave sleep induced by m-chloro-phenylbiguanide (10.0 micrograms). Our results tend to indicate that the increase of wakefulness after injection of the selective 5-HT3 receptor agonist m-chlorophenylbiguanide into the nucleus accumbens is partly related to the release of endogenous dopamine. In addition, they suggest that concomitant stimulation of both accumbens dopamine D1 and D2 receptor-related mechanisms is a necessary prerequisite to increase wakefulness.

Animals↗
PubMed1995

3-Aminobenzamide protects cells from UV-B-induced apoptosis by acting on cytoskeleton and substrate adhesion.

3-aminobenzamide (3-ABA) is an inhibitor of poly-(ADP-ribose)-polymerase, an enzyme involved in numerous subcellular processes, including cell death. Recently, a target effect of the drug on some cytoskeletal elements has also been described (Malorni et al., Biochem. Biophys. Res. Commun. 202: 915-922, 1994). In this study we evaluated the ability of 3-ABA to interfere with UV-B ray-induced apoptosis in cells selected for their cytoskeletal features and their different capability to adhere to the substrate. Human melanoma (M14) and epithelial (A431) cell lines and murine primary fibroblastic cultures (MFC) were studied. Our results indicate that cytoskeleton is indeed an important cellular target of 3-ABA, which can prevent apoptotic cell death by UV-B through a specific effect on the adhesion properties of the cells. Indeed, an inverse correlation was observed between sensitivity to UV-B-induced apoptosis (M14 > A431 > MFC) and substrate adhesion (MFC > A431 > M14). The potential relevance of these observations to understand the possible relationships among apoptosis, cytoskeletal functions and substrate adhesion is discussed.

Animals↗
PubMed1995

Sendai virus and herpes virus type 1 induce apoptosis in human peripheral blood mononuclear cells.

Recent reports suggest that several viruses, besides human immunodeficiency virus, induce apoptosis in infected cells. We report here that Sendai virus or Herpes simplex virus type 1 (HSV-1), two potent inducers of interferon-alpha, caused cell death in a consistent number of human peripheral blood mononuclear cells. A careful analysis of infected cells by different techniques, such as optical and electron microscopy, DNA agarose gel electrophoresis, and cytofluorimetric analysis of DNA content, showed that cell death was of apoptotic type. Sendai virus was more apoptogenic than HSV-1, and it was further studied to understand the mechanism(s) by which it induced apoptosis. Physical (uv and heat) and chemical (beta-propiolactone) inactivation reduced or abolished the apoptogenic power of Sendai virus. The use of a novel technique, which allows the study of mitochondrial membrane potential (MMP) in intact cells by flow cytometry, showed that a decrease of MMP is concomitant with the appearance of the hypodiploid peak. These results suggest that Sendai virus and HSV-1 can be added to the list of viruses causing apoptosis, which appears to be a general mechanism occurring during viral infection.

Apoptosis↗
PubMed1995

Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitochondria.

The existence of two different pathways for cell death has been postulated. In addition to the passive and traumatic process leading to necrosis, an active program characterized by organelle integrity and called apoptosis has been described. A positive correlation between the apoptotic cell death process and oxidative imbalance has been demonstrated. In fact, the antioxidant N-acetylcysteine (NAC) seems to be capable of impairing the apoptotic program, replenishing intracellular reduced glutathione content in cells exposed to tumor necrosis factor-alpha (TNF) as apoptotic inducer. Moreover, protein synthesis inhibitors such as cycloheximide (CHX) can facilitate apoptotic triggering by TNF, and mitochondrial function was suggested to be essential in the TNF-mediated apoptotic process. With this in mind, a specific analysis using the JC-1 probe, a fluorescent dye which is capable of indicating mitochondrial membrane potential (delta psi m) changes, was carried out. Our results show that TNF exposure is capable of altering the mitochondria and that NAC protection from CHX + TNF-induced apoptosis could be due to a direct effect of the drug on mitochondrial integrity and function.

Acetylcysteine↗
PubMed1995

The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages.

To investigate the effect of the heme moiety of malaria pigment, hemozoin, on phagocyte functions, mouse macrophages were fed with insoluble beta-hematin, the synthetic heme-polymer chemically identical to the native pigment, or the soluble monomer, hematin. Production of inflammatory cytokines, interleukin 1 (IL1), tumor necrosis factor alpha (TNF alpha), and nitric oxide (NO) was assayed in the supernatants after stimulation with lipopolysaccharide. The results indicate that both beta-hematin and hematin induce a dose-dependent inhibition of macrophage production of TNF alpha and NO, but not of IL1. One-hour pretreatment with soluble hematin inhibited production of cytotoxic mediators by more than 50% compared to controls, while 6-hr exposure was necessary for insoluble beta-hematin to induce the same level of inhibition. However, the same treatment did not modify the production of TNF alpha and NO by mouse microglia cell lines. The inhibition was partially counterbalanced by adding sulphydryl group donors such as 2-mercaptoethanol, glutathione, or N-acetyl-cysteine during the preincubation time. The results of the present study confirm the inhibitory role of malaria pigment and show that such effect is due to the heme moiety and may be selective for the production of cytotoxic mediators by specific phagocytes. The implications of these findings in the control of malaria infection and disease and in the pathogenesis of severe malaria are discussed.

Animals↗
PubMed1995

Effects of selective activation of the 5-HT1B receptor with CP-94,253 on sleep and wakefulness in the rat.

The effects of the 5-HT1B receptor agonist CP-94,253 were compared with those of the mixed beta-adrenoceptor and 5-HT1A/B receptor antagonist (+/-)pindolol in rats implanted for chronic sleep recordings. CP-94,253 (5.0-10.0 mg/kg) significantly increased waking and reduced slow wave sleep (SWS) and REM sleep (REMS). At 2.0-4.0 mg/kg (+/-)pindolol reduced REMS. Pretreatment with (+/-)pindolol (2.0-4.0 mg/kg) reversed the effect of CP-94,253 on waking and SWS, while REMS remained suppressed. It is suggested that the 5-HT1B receptor together with other 5-HT receptor subtypes may have a direct regulatory action on sleep and waking in the rat.

Animals↗
PubMed1995

Adenosine analogues modulate the incidence of sleep apneas in rats.

The effects of adenosine A1 and A2 agonists on spontaneous central sleep apneas in rats have been examined by simultaneously monitoring sleep and respiration in freely moving unanesthetized animals. Intraperitoneal administration of 1.0 mg/kg of the A1 receptor agonist R(-)N6-L-(2-phenyl-isopropyl)adenosine (L-PIA) and 150 and 300 micrograms/kg of 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido-adenosine hydrochloride (CGS 21680), a selective A2 agonist, decreased the apnea index (AI) during sleep. Within a sleep period, AI increased over time in both control and drug-treated animals. For both agonists, doses effective in reducing AI also significantly reduced sleep efficiency.

Adenosine↗
PubMed1995

The immunology of exceptional individuals: the lesson of centenarians.

Centenarians are the best example of successful ageing, since they have escaped the major age-associated diseases, and most are in good mental and physical condition. Here, Claudio Franceschi and colleagues discuss how the study of their immune systems reveals that several immune parameters are well conserved, suggesting that a complex remodelling of most immune parameters occurs with age, rather than a unidirectional deterioration.

Aged↗
PubMed1994

3-Aminobenzamide induces cytoskeleton rearrangement in M14 melanoma cells.

3-aminobenzamide (3-ABA) is an inhibitor of poly-ADP-ribose-polymerase, an enzyme involved in numerous subcellular processes including cell death. With the aim of contributing to clarify the mode of action of the drug, which is still poorly understood, its effects on cultured melanoma cells M14 have been assessed. In particular, an impairment of cell growth accompanied by the formation of long and numerous dendritic-like protrusions has been detected. This finding appears to be due to a specific effect of the drug on some cytoskeletal elements and could be associated with its differentiating capability. This finding, together with previous data from our group--Biochem. Biophys. Res. Commun., (1994) 199, 525-530 and 1250-1255--suggests that cytoskeleton is an important target of 3-ABA.

Benzamides↗
PubMed1994

D-ribose and deoxy-D-ribose induce apoptosis in human quiescent peripheral blood mononuclear cells.

In previous papers we reported that D(-)-ribose and 2-deoxy-D-ribose, which rank at the top among reducing sugars, kill a variety of human and animal cells and cell lines. Here we demonstrate that these two sugars induce apoptosis in human quiescent peripheral blood mononuclear cells which are relatively insensitive to apoptosis. Apoptosis was assessed by morphological changes, DNA fragmentation by agarose gel electrophoresis and the appearance of an hypodiploid peak by flow cytometry. 2-deoxy-D-ribose was more potent than D(-)-ribose and apoptosis was evident from 48 hours of culture onwards. 2-deoxy-D-ribose-induced apoptosis was inhibited by N-acetyl-L-cysteine, suggesting that glutathione metabolism and/or oxidative stress are involved in this type of apoptosis. Thus, D(-)-ribose and 2-deoxy-D-ribose can be useful tools to study the cellular and molecular events of apoptosis in human quiescent lymphocytes.

Acetylcysteine↗