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Biomedical subjects

G Rosati

Publications and source records attributed to G Rosati.

At least 19 recordsLinked to original sources
PubMed2006

Glatiramer acetate reduces lymphocyte proliferation and enhances IL-5 and IL-13 production through modulation of monocyte-derived dendritic cells in multiple sclerosis.

Dendritic cells (DC), as the most effective antigen presenting cells, are protagonists of the complex immune network involved in multiple sclerosis (MS) lesion formation. Glatiramer acetate (GA), a synthetic random copolymer, is thought to exert its therapeutical effect in MS by favouring both Th2 cell development and IL-10 production from peripheral lymphocytes as well as by systemically affecting the antigen presenting cells. In the present study we further analysed the mechanisms of action of GA by using an autologous DC-lymphocytes (Ly) coculture system from 11 MS patients and 12 matched healthy controls (HC). We found that, in MS patients, pretreatment with GA significantly decreases the in vitro proliferative effect of DC on lymphocytes as compared to HC and to unpulsed or myelin basic protein (MBP)-pulsed DC from MS patients (P < 0.05). In addition, GA-treated DC from both MS patients and HC significantly increase the lymphocyte production of IL-5 and IL-13 as compared to MBP-treated DC (P < 0.05). In conclusion our in vitro study may provide new therapeutical mechanisms of GA on lymphocytes, antiproliferative and Th2-favouring effects, which are mediated by monocyte-derived DC.

Adult↗
PubMed2006

Inflammatory biomarkers in blood of patients with acute brain ischemia.

Although many failed surrogate markers are provided in the literature, inflammation may contribute to the outcome of ischemic stroke. In 50 consecutive patients with acute ischemic stroke, in the absence of symptoms and signs of concomitant infection, we evaluated a panel of biomarkers reported to be variably associated with brain ischemia, and correlate their serum level with the brain lesion volume and clinical outcome. Infarct size was calculated on computed tomography (CT) scans by means of the Cavalieri's method. Neurological impairment was scored by using the Glasgow Coma Scale, Glasgow Outcome Scale and National Institutes of Health (NIH) scales at stroke onset and 3-month follow-up. Some markers showed a direct significant correlation with both initial and final NIH scale and with infarct size, particularly tumor necrosis factor alpha (TNF-alpha) (P=0.002), intercellular adhesion molecule-1 (P<0.01) and matrix metalloproteinase-2/9 (P=0.001). In contrast to previous reports, interleukin-6 (IL-6) serum level showed a significant inverse correlation with both final neurological impairment and infarct size (P<0.001). This novel finding allows us suggesting that IL-6, in the context of a complex pro-inflammatory network occurring during stroke, is associated with neuroprotection rather than neurotoxicity in patients with ischemic brain injury.

Acute Disease↗
PubMed2006

The epidemiology of multiple sclerosis in Europe.

Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of non-traumatic disability in young adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100,000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35-64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100,000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost-of-illness studies.

Disability Evaluation↗
PubMed2006

Intrathecal chitotriosidase and the outcome of multiple sclerosis.

Activated macrophages are major effectors at all stages of lesion formation in multiple sclerosis (MS) brain. Here, we report that the macrophage enzyme chitotriosidase (Chit) is significantly elevated both in plasma and cerebrospinal fluid (CSF) of patients with MS as compared to healthy controls and other neurological patients (P<0.001). Furthermore, the Chit activity in blood significantly associates with the MS clinical course (higher in secondary progressive relative to relapsing-remitting, P=0.01) and the clinical severity as measured by Kurtkze's Expanded Disability Status Scale (P<0.001). Also, we found that Chit activity is compartmentalized in the central nervous system of early MS patients and that its CSF/plasma quotient, in the presence of a preserved albumin quotient, correlates with the extent of future clinical deterioration (r=0.91; P<0.001). These findings confirm that innate immunity, here represented by Chit, is clinically relevant in MS and allows, if confirmed, reconsidering novel MS therapeutic strategies specifically aimed at this branch of the immune response.

Adult↗
PubMed2005

A bacterium belonging to the Rickettsiaceae family inhabits the cytoplasm of the marine ciliate Diophrys appendiculata (Ciliophora, Hypotrichia).

Bacteria of the family Rickettsiaceae (order Rickettsiales, alpha-Proteobacteria) are mainly known to be endosymbionts of arthropods with the capability to infect also vertebrate cells. Recently, they have also been found as leech endocytobionts. In the present paper, we report the first finding of a bacterium belonging to the family Rickettsiaceae in a natural population of a marine ciliate protozoan, namely Diophrys appendiculata, collected in the Baltic Sea. Bacteria were unambiguously identified through morphological characterization and the "full-cycle rRNA approach" (i.e., 16S rRNA gene characterization and use of specifically designed oligonucleotide probes for in situ detection). Symbionts are rod-shaped bacteria that grow freely in the cytoplasm of the host cell. They present two different morphotypes, similar in size, but different in cytoplasmic density. These are typical morphological features of members of the family Rickettsiaceae. 16S rRNA gene sequence showed that Diophrys symbionts share a high similarity value (>92%) with bacteria belonging to the genus Rickettsia. Phylogenetic analysis revealed that these new endosymbionts are clearly included in the clade of the family Rickettsiaceae, but they occupy an independent phylogenetic position with respect to members of the genus Rickettsia. This is the first report of a member of this family from a host protozoan and from a marine habitat. This result shows that this bacterial group is more diversified and widespread than supposed so far, and that its ecological relevance could until now have been underestimated. In light of these considerations, the two 16S rRNA oligonucleotide probes here presented, specific for members of the Rickettsiaceae, can represent useful tools for further researches on the presence and the spread of these microorganisms in the natural environment.

Animals↗
PubMed2005

Randomised, open-label, phase II trial of paclitaxel, gemcitabine and cisplatin versus gemcitabine and cisplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium.

The purpose of the study was to evaluate the antitumor activity and the safety of paclitaxel combined with gemcitabine and cisplatin in patients affected by advanced transitional cell carcinoma of the urothelium (TCC). Eighty-five patients affected by advanced TCC and measurable disease were randomized to receive either paclitaxel at dosage of 70 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks (GCP) or gemcitabine 1000 mg/m2 on days 1, 8, 15 and cisplatin 70 mg/m2 on day 2 every 4 weeks (GC). All enrolled patients were considered evaluable for response and toxicity (intention to treat). The observed response rate was 43% for GCP and 44% for GC combination, respectively. Median time to treatment failure was 32 weeks for GCP and 26 weeks for GC and overall survival 61 vs 49 weeks, respectively (p-value not significant). Grade 3-4 neutropenia was observed in 49% of patients treated with GCP vs 35% of those treated with GC (P=0.05) and grade 3-4 thrombocytopenia was observed in 36% of GCP treated patients as compared to 21% of those treated with GC (P=0.01). Seven patients over 70 years old or with poor PS were removed from the study: 6 patients from GCP group (2 toxic deaths, 2 grade 4 myelotoxicity and 2 grade 3 asthenia) and 1 from GC group was lost to follow-up after the first cycle. The combination of paclitaxel, gemcitabine and cisplatin is effective in the treatment of TCC. However, the addition of paclitaxel to the combination of gemcitabine plus cisplatin seems to increase toxicity, therefore it seems not suitable for poor PS patients and those over 70 years old. Larger and more powered studies are needed to exactly define the role of paclitaxel in this combination.

Aged↗
PubMed2004

Gemcitabine versus FLEC regimen given intra-arterially to patients with unresectable pancreatic cancer: a prospective, randomized phase III trial of the Italian Society for Integrated Locoregional Therapy in Oncology.

Gemcitabine is considered the gold standard treatment for unresectable pancreatic adenocarcinoma. Intra-arterial drug administration had shown some interesting results in small phase II studies. In this study, patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or FLEC: 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles. The primary endpoint was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=0.036). Survival at 1 year increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=0.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both groups (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2003

Neurological disorders associated with Mycoplasma pneumoniae infection.

Neurological syndromes caused by Mycoplasma pneumoniae (MP) infection are occasionally reported in adults, usually in the post-infectious period, and three computed tomography documented cases have recently appeared in this journal. Here we present the cases of three young women with recent respiratory tract infection caused by MP some weeks prior to neurological complication documented by magnetic resonance imaging. Two cases suffered from demyelinating disorders of the central nervous system (CNS). The other case had a middle cerebral artery thrombosis, a rare complication of MP infection. Another potential risk factor for stroke in the latter case was the use of oral contraceptives. Recent infection with MP is discussed as a risk factor for cerebrovascular disorders and CNS demyelinating diseases.

Adolescent↗
PubMed2003

Alpha B-crystallin is not a dominant peripheral T-cell autoantigen in multiple sclerosis amongst Sardinians.

The heat shock protein alpha B-crystallin appears to be the dominantly recognized autoantigen in the early demyelinative process of multiple sclerosis (MS) in brain of patients. In Sardinia, MS is linked to human leucocyte antigen (HLA)-DR alleles that might influence the production of cytokines from peripheral lymphocytes. We tested the nature of peripheral anti-alpha B-crystallin-specific T-cell response in the context of predisposing HLA haplotypes both in MS patients and healthy controls. The alpha B-crystallin specific T-cell lines were generated by using the 'split-well' technique. The results indicate that the presence of short-term T-cell lines towards alpha B-crystallin is numerically comparable between the two groups and not restricted to MS-predisposing HLA-DR alleles. As for the T-cell characterization, CD4+ anti-alpha B-crystallin T cells secreting high levels of interferon-gamma are similarly identified in MS and healthy donors. In conclusion, the peripheral response towards the myelin antigen alpha B-crystallin is neither quantitatively nor qualitatively peculiar to MS, in contrast to the theoretical paradigm suggesting peripheral activation of myelin-reactive T cells to be the prerequisite for MS induction.

Alleles↗
PubMed2003

Randomised trial of gemcitabine versus flec regimen given intra-arterially for patients with unresectable pancreatic cancer.

Gemcitabine is considered the golden standard treatment for unresectable pancreatic adenocarcinoma. Intra-arte-rial drug administration had shown a deep rationale with some interesting results. In a multicenter phase III trial, we compared gemcitabine given weekly with a combination of 5-fluoruracil, leucovorin, epirubicin, carboplatin (FLEC) administered intra-arteriously as first-line therapy in unresectable pancreatic adenocarcinoma. Patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arteriously at three-weekly interval for 3 times. The primary end point was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=.036). Survival at 1 year was increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both group (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, FLEC regimen given intra-arteriously, improved survival in patient with unresectable pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2002

In situ identification by fluorescently labeled oligonucleotide probes of morphologically similar, closely related ciliate species.

Ciliate protozoa are important members of microbial communities in which they play specific ecological roles. The determination of single species distribution is fundamental for food web analysis, but species recognition, which is mainly based on morphological characters, is often difficult between closely related species. The use of species-specific, purposely designed, fluorescently labeled probes for in situ hybridization is here presented as an easy and fast identification method for three closely related species belonging to the widespread genus Euplotes, namely E. crassus, E. vannus, and E. minuta, that in spite of their remarkable morphological similarity have significant metabolic and ecological differences. These three species can be detected simultaneously, provided the probes employed are bound to different fluorescent dyes: in this way their relative abundance and their population dynamics in the natural environment can be evaluated. As more ciliate sequences become available in databases, species-specific probes can be designed for other ciliates, thus rendering the application of the method of more general importance. The probes used in this study may also provide a tool to prevent erroneous species identification in future studies.

Animals↗
PubMed2002

Multiple sclerosis-associated retrovirus and MS prognosis: an observational study.

MS-associated retrovirus (MSRV) in the CSF may have gliotoxic properties and could be associated with a more disabling MS. The authors tested this hypothesis in 15 untreated patients with MS: 6 MSRV- and 9 MSRV+ at the time of CSF withdrawal. After a 3-year mean follow-up, MSRV- patients showed a stable MS course, whereas MSRV+ patients had a progressive course (p = 0.01).

Adolescent↗
PubMed2002

Multiple sclerosis-associated retrovirus (MSRV) in Sardinian MS patients.

Blood and CSF of Sardinian patients with MS and neurologic control subjects were tested for MS-associated retrovirus (MSRV). CSF detection in MS was 50% at clinical onset, increasing with temporal disease progression, and 40% in control subjects. In blood, MSRV was detected in all MS patients, in most patients with inflammatory neurologic diseases, and rarely in healthy blood donors. MSRV may represent a marker of neurologic diseases of inflammatory origin.

Adult↗
PubMed2002

Multiple sclerosis distribution in northern Sardinia: spatial cluster analysis of prevalence.

BACKGROUND: A heterogeneous geographic distribution of MS has been reported among different ethnic groups, and also within small communities. Epidemiologic studies conducted over the past two decades using repeated assessments clearly show that Sardinia is at high risk for MS, with a prevalence of 150 per 100,000 in 1997. OBJECTIVE: To present spatial analysis of the disease prevalence to disclose possible "hot" or "cold" spots of disease, further allowing correlations with risk factors. METHODS: A spatial analysis of the whole province of Sassari, in northern Sardinia, at a microgeographic level (i.e., in the 89 administrative communes and 6 linguistic areas) was conducted. Because of the small number of cases per commune and to overcome random variability, a hierarchical Bayesian approach was adopted. The distribution of prevalent cases by commune of residence on December 31, 1997 and from age 5 to 15 years was analyzed. RESULTS: A clustering pattern was found in the southwestern communes of the province based on geographic distribution by both prevalence and residence at age 5 to 15 years. A west-to-east gradient also was observed. CONCLUSIONS: This study highlights a hot spot of MS in the southwestern part of Sassari province, bordering with the commune of Macomer, where MS was once hypothesized as having occurred as an epidemic. Interestingly, these areas of MS clustering comprise the Common Logudorese linguistic domain. The Catalan area, linguistically and genetically distant from the remaining Sardinian domains, does not show such high estimates. Because MS is not a single-source infectious disease, this study may help test the hypothesis that a widely and evenly spread environmental (infectious?) agent may produce disease in subgroups of genetically more susceptible individuals in areas at higher inbreeding rates, wherein a disease mode of inheritance could be better investigated.

Adolescent↗
PubMed2002

P300 and executive function alterations: possible links in a case of Morgagni-Stewart-Morel syndrome.

To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.

Cognition Disorders↗
PubMed2002

Serum uric acid and multiple sclerosis.

Several studies indicate that patients with multiple sclerosis (MS) have low serum levels of the endogenous antioxidant uric acid (UA), although it has not been established whether UA is primarily deficient or secondarily reduced due to its peroxynitrite scavenging activity. We measured serum urate levels in 124 MS patients and 124 age- and sex-matched controls with other neurological diseases. In addition, we compared UA levels when MS patients were stratified according to disease activity (by means of clinical examination and MRI), duration, disability and course. MS patients had significantly lower serum urate levels than controls (p= 0.001). However, UA levels did not significantly correlate with disease activity, duration, disability or course. Our study favors the view that reduced UA in MS is a primary, constitutive loss of protection against oxidative agents, which deserves further pathogenetic elucidation aimed at future therapeutic strategies.

Adolescent↗
PubMed2002

Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy.

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high- and low-risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world-wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population.

Humans↗