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Biomedical subjects

A Nicoletti

Publications and source records attributed to A Nicoletti.

At least 37 records · Page 2Linked to original sources
PubMed2001

Chlamydia pneumoniae infection does not induce or modify atherosclerosis in mice.

BACKGROUND: Seroepidemiological studies have linked Chlamydia pneumoniae (CP) to coronary heart disease, and recent experimental studies suggest that it may accelerate or even induce atherosclerosis. We therefore evaluated the effect of CP infection on atherosclerosis in atherosclerosis-prone apolipoprotein E-knockout (apoE-KO) and wild-type C57BL/6J mice. METHODS AND RESULTS: Six- to 8-week-old female mice were infected intranasally with live CP and then fed a standard chow diet for 22 weeks. A subgroup of mice was reinfected 18 weeks after primary infection. Polymerase chain reaction analysis of lung tissue confirmed successful infection with CP, and ELISA assays demonstrated development of a humoral immune response. Despite this, no statistically significant differences in aortic atherosclerotic lesions were found between CP-infected and control apoE-KO mice. Furthermore, CP infection did not induce atherosclerosis in C57BL/6J mice. CONCLUSIONS: CP does not induce atherosclerosis in wild-type mice and does not accelerate atherosclerosis in chow-fed apoE-KO mice. Further studies will be necessary to clarify the explanation for the seroepidemiological association between CP and coronary heart disease in humans.

Animals↗
PubMed2001

Prevalence and incidence of multiple sclerosis in Catania, Sicily.

OBJECTIVE: An epidemiologic survey was conducted to determine the prevalence and incidence of MS in the city of Catania, Sicily, Italy. Prevalence rate was calculated as point prevalence at January 1,1995, and incidence during 1974 to 1995. METHODS: The authors studied the frequency of MS in the community of Catania in a population of 333,075 inhabitants according to the 1991 census. The primary sources for the case ascertainment were the neurologic and motor rehabilitation departments, the MS Center, the Italian MS Association, private neurologists, and family doctors. All patients who satisfied the Poser criteria for clinically definite MS, laboratory-supported definite MS, clinically probable MS, and laboratory-supported probable MS were considered prevalent and incident cases. RESULTS: One hundred ninety-five patients with MS who had had the onset of disease on prevalence day in a population of 333,075 inhabitants were detected. The prevalence rate was 58.5 per 100,000 (95% CI 50.7 to 67.5). Prevalence was higher in women (62.0/100,000) than in men (54.8/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 (145.1/100,000). From 1975 to 1994, 170 subjects with MS had the clinical onset of the disease. The mean annual incidence was 2.3 per 100,000 (95% CI 2.0 to 2.6). Age-specific incidence showed a peak in the group aged 25 to 34 (6.32/100,000). Incidence for 5-year intervals increased from 1.3 during 1975 to 1979 to 3.9 during 1990 to 1994. CONCLUSIONS: These prevalence and incidence rates are close to those reported in other similar surveys carried out in Italy and southern Europe.

Adult↗
PubMed2001

Combination of cyclophosphamide and interferon-beta halts progression in patients with rapidly transitional multiple sclerosis.

The effects of combined treatment with cyclophosphamide (CTX) and interferon-beta (IFN-beta) are described in selected patients with "rapidly transitional" multiple sclerosis. This form of multiple sclerosis is extremely active with very frequent and severe attacks which produce a dramatic increase on the expanded disability status scale (EDSS). Ten patients with rapidly transitional multiple sclerosis were previously treated with interferon-beta, but none benefited by this treatment. Monthly treatment with intravenous CTX, from 500 mg/m(2) to 1500 mg/m(2) to obtain a chronic lymphocytopenia (600/mm(3) to 900/mm(3)) produced a marked and significant reduction in the number of relapses (p<0.0001), disability previously accumulated (p<0.0001), and a reduction of T2 MRI burden of lesion. This particular group of patients benefited by combining cyclophosphamide and IFN-beta. The possibility is considered of carrying out further studies to test the efficacy of the association between the two drugs for patients who are not responsive to IFN-beta or other active disease modifying therapies.

Adjuvants, Immunologic↗
PubMed2001

Sodium fusidate (fusidin) ameliorates the course of monophasic experimental allergic encephalomyelitis in the Lewis rat.

We have evaluated the effect of the immunosuppressant sodium fusidate (fusidin) on the course of acute monophasic experimental encephalomyelitis (EAE) in male Lewis rats. Prophylactic treatment with fusidin, 80 or 120 mg/kg bd wt., markedly ameliorated the course of the disease in rats immunized with myelin basic proteins in complete Freund's adjuvant, entailing delayed onset of symptoms, lower clinical scores and more rapid recovery than PBS-treated control rats. The fusidin-treated, immunized rats exhibited milder mononuclear cell infiltration of brains and spinal cords than control animals. These data provide further evidence for the anti-inflammatory effect of fusidin and suggest that this drug may be valuable for the treatment of human multiple sclerosis.

Animals↗
PubMed2000

Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice.

BACKGROUND: Atherosclerosis is associated with immune responses to oxidized lipoproteins and certain microorganisms, but the role of specific immunity has remained unclear. METHODS AND RESULTS: To study the role of immunity in atherosclerosis, we crossed atherosclerosis-prone apoE(-/-) mice with immunodeficient scid/scid mice. The offspring showed a 73% reduction in aortic fatty streak lesions when compared with immunocompetent apoE(-/-) mice. Transfer of CD4(+) T cells from apoE(-/-) to immunodeficient apoE(-/-)/scid/scid mice increased lesions by 164%. This was associated with the infiltration of transferred T cells into lesions, increased circulating interferon-gamma levels, and increased I-A expression in lesions. CONCLUSIONS: CD4(+) T cells carry disease-promoting immunity in atherosclerosis.

Animals↗
PubMed2000

Evidence for antigen-driven T-cell response in unstable angina.

BACKGROUND: Activation of T cells and macrophages has been associated with unstable angina (UA), but whether this reflects specific immune responses remains unclear. METHODS AND RESULTS: We analyzed the repertoire and the length of complementarity-determining region 3 of the T-cell receptor (TCR) beta-chain variable (BV) gene segments of activated lymphocytes in 23 patients with UA, 13 patients with chronic stable angina (CSA), and 6 normal control subjects. We also tested the proliferation of systemic T cells in response to autologous coronary plaque proteins, oxidized LDL, and Chlamydia pneumoniae as candidate antigens, in vitro. The activated T cell-TCRBV repertoire was perturbed in 13 (57%) of 23 UA patients versus 3 (23%) of 13 CSA patients (P=0.016) and was restricted to 6 (28%) of 21 expanded TCRBV families; all were significantly higher in UA than in CSA patients. At least one monotypic or oligotypic activated TCRBV population was found in 15 (65%) of 23 UA patients and in 3 (23%) of 13 CSA patients (P<0.001). Finally, T cells from UA patients, but not from CSA patients or normal control subjects, proliferated in response to autologous proteins from coronary culprit lesions and/or to oxidized LDL. CONCLUSIONS: Our findings suggest that the T-cell response observed in UA patients is antigen-driven and directed to antigens contained in the culprit coronary atherosclerotic plaques.

Angina, Unstable↗
PubMed2000

Short-term treatment of relapsing remitting multiple sclerosis patients with interferon (IFN)-beta1B transiently increases the blood levels of interleukin (IL)-6, IL-10 and IFN-gamma without significantly modifying those of IL-1beta, IL-2, IL-4 and tumour necrosis factor-alpha.

We have studied the impact of short-term treatment with interferon (IFN)-beta1b of relapsing remitting (RR) multiple sclerosis (MS) patients' blood levels of type 1 and type 2 cytokines such as IFN-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10 and tumour necrosis factor (TNF)-alpha. These cytokines were measured by solid-phase ELISA. Serum samples were obtained prior to, and 2 and 12 hours after beginning of the treatment and 48 h after the last of 5 s.c. injections with 8 million IU IFN-beta1b given on alternate days for 10 days. The treatment was found to increase the circulating levels of IL-2, IL-6, IL-10 and IFN-gamma at some of the time points considered, with the effect acquiring statistical significance for IL-6, IL-10 and IFN-gamma. The blood levels of IL-1beta, IL-4 and TNF-alpha remained below the limit of sensitivity of the assays at any of the time points considered. If this in vivo study mirrors the impact of IFN-beta1b on MS patients' immune cells, these data demonstrate an activation of the immune system upon early treatment with the drug that does not lead to either type 1 or type 2 cytokine prevalence.

Adjuvants, Immunologic↗
PubMed2000

Is season of birth associated with multiple sclerosis?

OBJECTIVE: To compare the monthly distribution of multiple sclerosis (MS) patients' births with that of the Sicilian population. BACKGROUND: Studies on the association between season of birth and risk of MS are scanty and controversial. DESIGN AND METHODS: Archives of the Institute of Neuropsychiatry of the Universities of Palermo and Catania were searched up to 1995 for definite MS patients (McDonald & Halliday criteria). The monthly distribution of MS patients' births (N= 965) was compared with that of the Sicilian population (N= 5,608,307). RESULTS: The distribution of births among MS patients compared with the general population was not different when tested by the chi2 statistic (P> 0.25). The Hewitt's non-parametric test for seasonality showed an excess of births between June and November among MS patients (P=0.004). CONCLUSION: A different pattern of MS patients' births is observed in Sicily and in Northern countries.

Age Factors↗
PubMed2000

Immunomodulation of atherosclerosis: myth and reality.

Atherosclerosis is an inflammatory disease which displays features of immune activation both locally and systemically. In the present review, we discuss the evidence for immune activation in human disease and experimental models, and survey candidate antigens associated with atherosclerosis. Studies of atherosclerosis in genetic models of immunodeficiency are analysed, as well as immunomodulating therapies and immunization protocols. Based on recent research, it is concluded that immunomodulation represents an interesting approach to the development of new prevention and treatment methods for atherosclerosis.

Animals↗
PubMed2000

Isolated, unilateral, reversible palsy of the hypoglossal nerve.

We report three patients with isolated unilateral hypoglossal nerve palsy who experienced an excellent outcome. In two patients no cause was found. Our study seems to confirm that the occurrence of benign and idiopathic isolated unilateral palsy of the hypoglossal nerve is more frequent than previously reported. We would like to stress that neuroimaging studies remain mandatory in order to exclude other common causes, such as tumour and spontaneous or traumatic vascular lesions, in which a specific treatment is necessary.

Adolescent↗
PubMed2000

Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress.

The recruitment of monocytes via the endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) is a key step in the formation of the initial lesion in atherosclerosis. Because angiotensin (Ang) II may be involved in this process, we investigated its role on the signaling cascade leading to VCAM-1 expression in endothelial cells. Ang II stimulates mRNA and protein expression of VCAM-1 in these cells via the AT(1) receptor. This effect was enhanced by N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, and blocked by pyrrolidinedithiocarbamate, an antioxidant molecule. Ang II activated the redox-sensitive transcription factor nuclear factor-kappaB and stimulated the degradation of both inhibitor of kappaB (IkappaB)alpha and IkappaBbeta with different kinetics. The degradation of IkappaBs induced by Ang II was not modified by incubation with exogenous superoxide dismutase and catalase, suggesting that this effect was not mediated by the extracellular production of O(2)(-). In contrast, rotenone and antimycin, 2 inhibitors of the mitochondrial respiratory chain, inhibited the Ang II-induced IkappaB degradation, showing that generation of reactive oxygen species in the mitochondria is involved on Ang II action. BXT-51702, a glutathione peroxidase mimic, inhibited the effect of Ang II, and aminotriazole, an inhibitor of catalase, enhanced it, suggesting a role for H(2)O(2) in IkappaB degradation. This is confirmed by experiments showing that Ang II stimulates the intracellular production of H(2)O(2) in endothelial cells. These results demonstrate that Ang II induced an intracellular oxidative stress in endothelial cells, which stimulates IkappaB degradation and nuclear factor-kappaB activation. This activation enhances the expression of VCAM-1 and probably other genes involved in the early stages of atherosclerosis.

Angiotensin II↗
PubMed2000

Prevalence of stroke : a door-to-door survey in rural Bolivia.

BACKGROUND AND PURPOSE: We carried out a door-to-door survey in rural areas of the Cordillera Province, Santa Cruz Department, Bolivia. A cluster sample of 10 124 inhabitants was selected, and 9955 subjects were screened. The aim was to determine the prevalence of the most common neurological diseases (epilepsy, stroke, parkinsonism, and peripheral neuropathy) in this population. METHODS: We used a modified version of the World Health Organization screening instrument. On screening we found that 1130 subjects tested positive, and 1027 underwent a complete neurological examination. According to the World Health Organization guidelines, we defined stroke as "rapidly developing clinical signs of focal (or global) disturbance of cerebral functions, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin." We considered only first stroke and excluded a possible stroke. RESULTS: We found 16 subjects (cases) who had experienced 1 complete stroke on prevalent day (November 1, 1994). The crude prevalence of stroke was 174/100 000 (322/100 000 age-adjusted to the world standard population) and 663/100 000 in subjects aged >/=35 years. Prevalence was >2-fold higher in men than in women (247/100 000 and 99/100 000, respectively) and increased rapidly with age. Seven cases were hospitalized and received specific treatment. CONCLUSIONS: Our crude prevalence is lower compared with rates from developed countries, probably because of a high case fatality rate. Our findings are comparable with those reported from other surveys carried out in rural developing countries.

Adolescent↗