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E Rosati

Publications and source records attributed to E Rosati.

At least 19 recordsLinked to original sources
PubMed2003

Minimal handling and bronchopulmonary dysplasia in extremely low-birth-weight infants.

UNLABELLED: Over the last 16 years a minitouch regime, i.e., nasal continuous positive airway pressure (n-CPAP) and/or nasal intermittent positive pressure ventilation (n-IPPV), together with a minimal intubation policy has been routinely used for the treatment of respiratory distress syndrome (RDS) in preterm infants. Only 1.39 (1 out of 72) of the extremely low-birth-weight babies admitted to our Neonatal Intensive Care Unit (NICU) and surviving for at least 36 weeks' postconceptional age developed bronchopulmonary dysplasia at 36 weeks (BPD 36-wk). The BPD-36 wk incidence observed in our population is significantly lower than expected (30%) from the literature (p=0.000002). CONCLUSION: Our experience supports the effectiveness of the minitouch regime as a way to ventilate premature babies, reducing BPD risk.

Birth Weight↗
PubMed2002

[Statine and endothelium dysfunction in diabetes].

Diabetes is associated with significant morbidity and mortality in the setting of acute coronary syndromes. Exists a progressive relationship between glucose levels and cardiovascular risk. Hyperglycemy in fact produces endothelial dysfunction recognised to be a key accessory to diabetic microangiopathy and macroangiopathy. Furthermore diabetics present high levels of cholesterol which elevate the risk of CHD. The statins, for their effects, may represent the fit therapy. The beneficial effects of statins may extend beyond improving the lipid profile. There are several proposed mechanisms for event reduction by lipid-lowering therapy, which include improved endothelium-dependent vasodilation, stabilization of atherosclerotic lesions, reduction in inflammatory stimuli, and prevention, slowed progression, or regression of atherosclerotic lesions (pleiotropic effects). Cellular experiments suggest that statins have an impact on endothelial function by preventing oxidized LDL-induced reduction of nitric oxide production and increased nitric oxide synthesis. Statins also impact chronic inflammation by reducing mitogen (PDGF) responsiveness, inhibiting smooth muscle cell proliferation, inhibiting monocyte chemotaxis and migration, and by reducing macrophage protease production. The absolute clinical benefit achieved may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events.

Diabetes Complications↗
PubMed2001

IL-7-enhanced T-cell response to myelin proteins in multiple sclerosis.

In this study, we investigated the in vitro proliferative response of peripheral blood T lymphocytes from MS patients and controls to MBP and MOG either in the absence or in the presence of the conditioning factor IL-7. In the absence of IL-7, T-cell reactivity to MOG and MBP was similar in MS patients and controls even if an increased MBP response was found in a subgroup of patients with active disease. In the presence of IL-7, increased T-cell reactivity to MBP was observed in MS patients suggesting that their MBP-specific T cells are in a different functional state.

Adult↗
PubMed2001

[Sweet syndrome in a female patient with intestinal multiple lipomas and diverticular disease of the colon].

Sweet's syndrome (SS), or acute febrile neutrophilic dermatosis, is a condition characterized by the sudden onset of fever, leukocytosis, and painful, erythematous, well-demarcated papules and plaques which show dense, neutrophilic infiltrates on histologic examination. Myalgias and arthralgias are common. Although it may occur in the absence of other known disease, SS is often associated with hematologic disease (including leukemia), and immunologic disease (rheumatoid arthritis, inflammatory bowel disease). A case of SS is reported. Furthermore the patient presented multiple intestinal lipomas and diverticular colon disease. The authors, on the ground of recent studies which correlate SS with several digestive system disorders, hypothesize an association between acute febrile neutrophilic dermatosis and patient's intestinal diseases. Treatment with systemic corticosteroids is usually successful.

Aged↗
PubMed2000

Group B Streptococcus induces apoptosis in macrophages.

Group B Streptococcus (GBS) is a pathogen that has developed some strategies to resist host immune defenses. Because phagocytic killing is an important pathogenetic mechanism for bacteria, we investigated whether GBS induces apoptosis in murine macrophages. GBS type III strain COH31 r/s (GBS-III) first causes a defect in cell membrane permeability, then at 24 h, apoptosis. Apoptosis was confirmed by several techniques based on morphological changes and DNA fragmentation. Cytochalasin D does not affect apoptosis, suggesting that GBS-III needs not be within the macrophage cytoplasm to promote apoptosis. Inhibition of host protein synthesis prevents apoptosis, whereas inhibition of caspase-1 or -3, does not. Therefore, GBS can trigger an apoptotic pathway independent of caspase-1 and -3, but dependent on protein synthesis. Inhibition of apoptosis by EGTA and PMA, and enhancement of apoptosis by calphostin C and GF109203X suggests that an increase in the cytosolic calcium level and protein kinase C activity status are important in GBS-induced apoptosis. Neither alteration of plasma membrane permeability nor apoptosis were induced by GBS grown in conditions impeding hemolysin expression or when we used dipalmitoylphosphatidylcholine, which inhibited GBS beta-hemolytic activity, suggesting that GBS beta-hemolysin could be involved in apoptosis. beta-Hemolysin, by causing membrane permeability defects, could allow calcium influx, which initiates macrophage apoptosis. GBS also induces apoptosis in human monocytes but not in tumor lines demonstrating the specificity of its activity. This study suggests that induction of macrophage apoptosis by GBS is a novel strategy to overcome host immune defenses.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

Group B streptococci persist inside macrophages.

Group B streptococci (GBS) are an important cause of neonatal sepsis, pneumonia and meningitis. In the early phase of infection, macrophages and polymorphonuclear cells (PMN) are the first immune cells that interact with GBS. In this in vitro study, to gain insight into GBS-macrophage interaction in the absence of type-specific antibodies, we examined the features of GBS survival in thioglycollate-elicited murine peritoneal macrophages and the effect of GBS on the protein kinase C (PKC)-dependent transduction pathway. Our results demonstrate that type Ia GBS, strain 090 (GBS-Ia) and type III GBS strain COH 31r/s (GBS-III), after in vitro phagocytosis survive and persist intracellularly in macrophages for up to 24 and 48 hr, respectively. However, macrophage activation by interferon-gamma (IFN-gamma) and lipopolysaccharide from Escherichia coli (LPS) caused a significant reduction in the time of intracellular persistence. Macrophage activation by IFN-gamma and LPS seems to be a multifactorial event involving multiple intracellular signal pathways also including PKC. Since PKC is one of the components in the signal network leading to macrophage activation and an important target for several intracellular micro-organisms, we wondered whether PKC could have a role in intracellular GBS survival. Both PKC depletion by treatment with phorbol 12-myristate 13-acetate (PMA) for 18 hr and PKC inhibition by Calphostin C rendered macrophages more permissive for the intracellular GBS survival. Furthermore, GBS-infected macrophages were unable to respond to PMA and LPS, activators of PKC, by inducing antimicrobial activity. The ability of GBS to impair PKC-dependent cell signalling was also demonstrated by the reduced c-fos gene expression in GBS-infected macrophages with respect to control macrophages, after LPS stimulation. In conclusion, our results indicate that GBS survive in macrophages and impairment of PKC signal transduction contributes to their intracellular survival.

Animals↗
PubMed1998

Cytokine response to group B streptococcus infection in mice.

This study was undertaken to better understand the complex relationship between specific and non-specific host defence mechanisms and group B streptococci (GBS). A comprehensive kinetics analysis of cytokine mRNA expression was performed, by Northern blot assay, in peritoneal exudate cells (PEC) and spleen cells (SC) recovered from CD-1 mice at various times during the course of an intraperitoneal infection with a lethal dose (5 x 10(3) microorganisms/mouse) of type Ia GBS, reference strain 090 (GBS-Ia). Analysis of cytokines involved in the development of a specific TH response shows that GBS-Ia in PEC induce only a weak increase of IL-2 mRNA expression and in SC a cytokine pattern characterized by IL-2, IFN-gamma and IL-12 in the absence of IL-4, IL-5 and IL-10. This selected cytokine pattern could provide appropriate conditions for the development of a TH1 response. Analysis of inflammatory cytokines, which are usually induced early during an in vivo infection, shows that there is a significant expression of mRNA specific for IL-1beta, TNFalpha and IL-6, both in PEC and SC only at 24 h which persists at a high level until 36 h. This delayed cytokine induction, accompanied by the contemporary activation of splenic phagocytic cells, occurs only when the number of GBS-Ia is extremely high. In fact, at 24 h GBS-Ia have heavily colonized all organs. In vitro infection of thioglycollate-elicited peritoneal macrophages confirms that the ability of GBS-Ia to induce a strong inflammatory cytokine response depends strictly on the number of infecting microorganisms. Indeed, macrophages respond to GBS-Ia with a very rapid induction of IL-1beta and TNFalpha mRNA when infected at a ratio of 1:10, but not at 100:1. Two major observations emerged from this study: (1) GBS-Ia, by inducing a cytokine pattern which seems to favour development of a TH1 response, could evade antibody production essential for resistance to GBS; and (2) inflammatory cytokine response is induced when a heavy microbial invasion of the host has already occurred. These novel features of GBS-Ia could contribute to the development and progression of lethal infection in mice.

Animals↗
PubMed1996

Activation of cytokine genes during primary and anamnestic immune response to inactivated c. albicans.

Recent evidence suggests that after repeated stimulations with inactivated C. albicans (CA) cells, CD2F1 mice respond with a cytokine pattern typical of T-helper 1 (ThI) subset development. The purpose of this study was to analyse the sequence of immunological events which, soon after priming mice with CA, lead to the development of primary and anamnestic response. A comprehensive kinetics analysis of cytokine mRNA expression was performed by Northern blot assay, in peritoneal exudate cells (PEC), at different phases of immune response to CA: after priming (one i.p. injection of 2 x 10(7) CA cells mouse), during development of the primary immune response (five progressive CA i.p. injections over a 2-week period) and in the anamnestic response (CA booster 30 days after the primary response). In vitro assays were performed 2 and 24 hr after every CA stimulation. The response to CA priming was characterized by an early and high expression of interleukin-2 (IL-2) and IL-1 beta mRNAs At 24hr. IL-2 mRNA was still at a high level, while IL-1 beta had greatly decreased. A weak expression of IL-10 was only induced at 2 hr. whereas IL-12 p40 subunit, interferon-7 (IFN-7) IL-4 and IL-5 mRNAs were undetectable. In this phase no in vitro proliferative response of PEC to CA was observed, whereas a significant natural killer (NK) activity was induced. From the second CA injection, the IFN-7 mRNA was already induced at 2 hr. Its expression level increased progressively with the number of CA injections persisting up to 24 hr after the fifth stimulation. A progressive increase of IL-2 mRNA expression was also induced whereas IL-1 beta and IL-10 mRNAs were always transiently expressed at 2 hr at levels similar to those observed after the priming. IL-12 p40 subunit. IL-4 and IL-5 mRNAs were never detectable. The expression of this selected cytokine pattern typical of Thl response was correlated with the development of CA-specific T lymphocytes as confirmed by the in vitro proliferative response of CA-5d-induced PEC to CA. NK activity also increased progressively with the number of CA injections and after the fifth stimulation lymphokine-activated killer (LAK) activity was also induced. The anamnestic response to CA was characterized by a very quick induction of high levels of IL-2, II N-gamma and IL-1 beta mRNAs. IL-2 and IFN-gamma mRNAs remained high up to 24 hr while IL-1 beta mRNA decreased strongly. A weak, transient expression of IL-10 mRNA was induced at 2 hr whereas the IL-12 p40 subunit, IL-4 and IL-5 mRNAs were not detectable. The presence of CA-specific memory lymphocytes was confirmed by the in vitro specific proliferative response of PEC to CA. CA booster caused also a very rapid and high level of NK/LAK activation. In conclusion, these results indicate that CA is able to progressively trigger differential on of the Th1 subset which develops in the absence of IL-12, and that Th memory cells retain the same selected Th1 cytokine profile developed in the primary immune response.

Animals↗
PubMed1996

Activity inhibition of cytolytic lymphocytes by omeprazole.

This study examined the in vitro effect of omeprazole (OM) on various types of murine cytocidal lymphocytes. The results show that OM caused a strong inhibition of basal natural killer (NK) activity in spleen cells (SC) from untreated CD2F1 mice; in peritoneal exudate cells and SC activated in vivo by injection of maleic anhydride divinyl ether 1,2-copolymer (MVE-2) or inactivated Candida albicans (CA); in lymphokine-activated killer (LAK) activity generated in vitro from splenocytes cultured with rhIL-2 and in allo-specific cytotoxic lymphocyte-mediated lysis generated in vitro. A significant inhibition of cytotoxic activity of all types of effector cells after 30 min incubation was already induced by OM at 1 x 10(-3) M concentration, after 1 h incubation at 5 x 10(-4) M and after 4 h incubation at 1 x 10(-4) M OM. Complete inhibition of lytic activity was obtained after 4 h incubation of effector cells with 1 x 10(-3) M OM. No inhibitory effect was observed at 5 x 10(-5) M OM concentration. Indomethacin did not abrogate the OM inhibitory effect on NK/LAK activity, suggesting that prostaglandins are not involved in the process leading to suppression of cytocidal activity. When effector cells were incubated with OM in presence of rhIL-2 (500 U/ml), the cytokine failed to antagonize the inhibitory effect of the drug. On the contrary, if OM pretreated cells were incubated with rhIL-2 for a further 18 h after drug removal, this cytokine was able to restore NK activity, but only when NK inhibition was incomplete. These results demonstrate for the first time that in vitro OM causes a rapid, strong effect on various types of cytotoxic lymphocytes ranging from cytotoxicity inhibition to irreversible cell damage.

Animals↗
PubMed1995

Neuronal ceroid-lipofuscinoses in Italy: an epidemiological study.

To establish the incidence of neuronal ceroid-lipofuscinoses (NCL) in Italy, we sent a questionnaire to all Neuropediatric and Child Neuropsychiatric Departments (answer rate 15/34 = 44%). Diagnoses were accepted only when based on firm clinical and/or electron microscopic criteria. We collected 58 cases born between 1966-1991 (2 infantile NCL, 37 late infantile NCL, and 19 juvenile NCL). The incidence was calculated only on patients born between 1974-1984. In this period, the incidence of overall NCL in the Italian population was calculated to be 0.56 per 100,000 live births (0.36 for late infantile NCL, and 0.20 for juvenile NCL). Our data show that infantile NCL is very rare in Italy, and that late infantile seems to be the most frequent form of NCL.

Adolescent↗
PubMed1995

Cytokine response to inactivated Candida albicans in mice.

Inactivated Candida albicans (CA) cells induce strong activation of natural cytotoxic effectors in mice. In the present study we examined the expression of cytokine genes involved in the immune response to CA. It has been reported that differential cytokine production by natural immune cells is important for regulating the development of specific TH response. Northern blot analysis was performed on peritoneal exudate cells (PEC) recovered from CD2F1 mice injected ip with five doses of CA (CA-5d, on Days -14, -10, -7, -3, 0 with respect to the in vitro assays at 2, 24, and 72 hr) or from mice injected ip with four doses of CA (CA-4d, on Days -14, -10, -7, -3 with respect to the in vitro assay on Day 0). On Day 0, before the fifth CA injection, PEC expressed a high level of IL-2 and a low level of IL-1 beta mRNAs while genes coding for IL-4, IL-5, IL-6, IL-10, IL-12, TNF alpha, and IFN gamma were not expressed and there was a high level of NK activity. Two hours after CA-5d a high level of IFN gamma and a low level of IL-10 mRNAs were already evident, while IL-2 and much more IL-1 beta had greatly increased. IL-6, TNF alpha, and IL-2R alpha chain mRNAs were also detectable, whereas IL-4, IL-5, and IL-12 were not expressed. IL-12 mRNA was also absent in earlier stages of the CA sensitization. Both cellularity and NK activity of peritoneal exudate had increased with respect to Day 0. At 24 hr whereas IL-2 mRNA remained high, both IL-1 beta and IFN gamma mRNAs expression had decreased. Expression of other cytokines was no longer detectable but NK activity remained high and a significant LAK activity was also induced. After 72 hr, while the IL-2 mRNA level and NK activity were still high the IL-1 beta mRNA expression had further decreased. These results indicate that CA induces a predominant production of IFN gamma and IL-2, cytokines involved in the development of TH1 response but it is unable to induce IL-12. This secondary pathway, without IL-12 involvement in the development of TH1 response, is probably the result of the ability of IL-2, IL-1 beta, and TNF alpha to synergize in inducing IFN gamma synthesis by NK cells.

Animals↗
PubMed1995

Local and systemic immune response to inactivated Candida albicans in mice.

To improve our understanding of the role natural-immunity cells play in regulating the immune response to Candida albicans (CA) we compared local versus systemic effects of intraperitoneal inoculations with inactivated CA cells in mice. Peritoneal exudate cells (PECs) and spleen cells (SCs) were recovered from CD2F1 mice after 5 intraperitoneal CA injections (2 x 10(7) cells/mouse on days -14, -10, -7, -3 and 0 (CA-5d) with respect to in vitro assays performed at 2 h, 24 h, 3 days and 5 days). Northern blot analysis revealed that 2 h after CA-5d, PECs expressed a high level of IL-2, IFN-gamma, IL-1 beta and a low level of IL-10 and TNF-alpha mRNAs, while IL-4 and IL-5 mRNAs were absent, suggesting the development of TH1 subset. At 24 h, while IL-2 mRNA remained high, IL-1 beta and IFN-gamma expression had decreased and IL-10 and TNF-alpha mRNAs were no longer detectable. Instead, in spleens of CA-treated mice, examined up to 5 days after CA-5d, only IL-2 and IL-1 beta mRNAs were detectable, but the expression level was similar to that of untreated control mice. CA-5d induced a high level of natural-killer (NK)/lymphokine-activated-killer (LAK) activity in the peritoneal cavity but did not affect spleen NK activity. After CA-5d, the proliferative response of PECs to mitogens and CA antigens was also different from that of SCs. Unfractionated PECs were unable to proliferate in response to concanavalin A (Con A), IL-2, CA cells and CA cell wall mannoprotein, but after removal of the nylon-wool-adherent fraction, the nonadherent peritoneal cells (Nad-PECs) showed a significant proliferative response to mitogens. After depletion of NK cells by anti-asialo-GM1 antibody plus complement, the proliferative response of Nad-PECs to Con A and CA increased further. Contrary to the PEC response, unfractionated SCs from the same animals responded very well to mitogens and CA antigens and the proliferative response was significantly higher compared to that of SC from control mice. In conclusion, these results cast some light on the mechanisms by which NK cells and macrophages regulated the development of the local specific response to CA: activated NK cells, by producing IFN-gamma, favor the development of TH1 subset, while suppressor macrophages keep proliferation of T lymphocytes under control because of the presence of highly activated NK cells.

Animals↗
PubMed1994

Induction and persistence in vivo of NK/LAK activity by a mannoprotein component of Candida albicans cell wall.

In a previous study we demonstrated that NK/LAK effectors are quickly induced in the peritoneal cavity of CD2F1 mice by a booster dose with inactivated Candida albicans (CA) cells or by the purified cell wall mannoprotein (MP), for a long time after CA sensitization. In this study we investigated the immunologic nature and kinetics of early events of the booster phenomenon. Intraperitoneal inoculation of CA in CD2F1 mice, 30 days after pretreatment with five doses of CA (2 x 10(7) cells/mouse) over a 2-week period (CA-5d treatment), elicited a very rapid recruitment of asialo GM1+ cells, L3T4+ cells, and Ly 2+ cells. Asialo GM1+ cells and Ly 2+ cells reached a maximum number 12 hr after the booster dose, while L3T4+ cells reached the maximum after 24 hr. The number of L3T4+ cells was about twofold greater than Ly 2+ cells at all times tested. A similar kinetic pattern was found after MP booster. In C57BL/6 mice we confirmed that CA and MP boosters induced LGL which express a NK antigen, detected by 3A4 mAb, and the activation marker CD25. The peak of non-MHC-restricted PEC cytotoxicity, which was reached 24 hr after MP or CA booster, did not correspond to the time (12 hr) for maximum number increase of asialo GM1+ cells and 3A4+ cells. Two hours after CA or MP booster in PEC there was a rapid and strong increase of IL-2 mRNA expression, which persisted at a high level 24 hr after booster. In CA-5d-pretreated mice, a persistent NK/LAK-like activity in the peritoneal cavity can be maintained by boosters with MP administered every 3 days. Such treatment, which we performed up to 15 days after CA sensitization, rendered the mice more responsive to further MP boosters. Effects of CA were not restricted to the peritoneal compartment because (a) there was a rebound of splenic NK activity about 10 days after CA-5d treatment by ip route and (b) CA given by iv route significantly increased splenic NK activity up to 15-20 days after CA-5d treatment. Recombinant human interleukin 2 (rhIL-2), given ip to mice (1000 U/mouse) in combination with CA during CA-5d treatment and with MP in the booster, strongly increased the level of peritoneal NK/LAK activity and PEC cellularity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Antibody-independent protection in mice against type Ia group B streptococcus lethal infection.

There is ample evidence that protection against group B streptococcal (GBS) disease, both in experimental animals and in humans, is related to the presence of specific antibodies and complement. However, until now the possibility of increasing resistance to GBS infection by potentiating natural cell-mediated immunity in the host, has not been explored. In this study we examine the effect of administering in vivo MVE-2 (a polymer fraction of 1,2-co-polymer of divinyl ether and maleic anhydride) and inactivated Candida albicans (CA) cells on mouse resistance to the reference strain type Ia 090 GBS (GBS-090) lethal infection. MVE-2 and CA, respectively a synthetic and a microbial biological response modifier (BRM), are strong inducers and activators of natural resistance effectors, such as natural killer (NK) cells, macrophages and polymorphonuclear cells (PMN). The results showed that MVE-2 protected 100% CD-1 mice from a systemic lethal challenge with GBS-090 (5 x 10(3) microorganisms/mouse) when administered 3 days before infection at dose of 50 mg kg-1. CA treatment, in five doses (CA-5d) over 14 days protected 100% mice when administered at 2 x 10(7) cells/mouse and when the last CA injection was given 1 day before the GBS-090 challenge. Instead, when the GBS-090 challenge was performed by intraperitoneal route, protection was obtained with CA-5d treatment but not with MVE-2. The possibility that MVE-2 or CA stimulated a rapid production of specific antibodies against GBS-090 infection was excluded by the ELISA assay. Evidence exists that NK cells do not play a primary role as effectors in the MVE-2 and CA conferred protection since the strong reduction in NK activity, due to in vivo administration of anti-asialo GM1 antibodies before GBS-090 infection, did not influence the BRM-induced protection. Besides, high NK activity levels, induced by in vivo rhIL-2 administration, did not protect the mice against GBS-090 infection. Both studies on in vivo clearance and in vitro microbicidal activity, showed that, after 1 h, immunopotentiated effectors were unable to kill GBS-090, but were highly effective against GBS type VI. These results seem to indicate that intracellular GBS-090 killing is a slow process requiring more than 1 h. This study demonstrates that it is possible to increase resistance to GBS-090 lethal infection by BRMs, by potentiating the antibody-independent microbicidal activity of the phagocytes.

Animals↗