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Biomedical subjects

S Sotgiu

Publications and source records attributed to S Sotgiu.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

Multiple sclerosis-associated retrovirus and optic neuritis.

One prognostic factor for early multiple sclerosis (MS) patients to develop a definite MS may be the presence of the MS-associated retrovirus (MSRV) in the cerebrospinal fluid (CSF). We designed a specific study on a cohort of optic neuritis (ON) patients to evaluate the MSRV-dependent conversion to MS relative to the prediction conferred by magnetic resonance imaging (MRI) and CSF abnormalities. At follow-up, 33.3% MSRV+ and 0% MSRV- ON patients developed MS (P = 0.03). The prediction value is lower than that given by CSF and MRI abnormalities (42.3%). This intriguing finding is discussed in the light of the abundant discrepancies observed in the MSRV literature. Multiple Sclerosis 2006; 12: 357-359. www.multiplesclerosisjournal.com

Adolescent↗

Chronic subdural collection after endoscopic third ventriculostomy.

Endoscopic third ventriculostomy (ETV) is considered a safe technique for the treatment of obstructive hydrocephalus. We describe a case of chronic subdural haematoma (CSDH) after ETV, revealed by MRI four weeks after the procedure, and requiring surgical evacuation, in a 69 y.o. asymptomatic male patient. In our opinion, overdrainage may evolve also in endoscopic treatment of obstructive hydrocephalus. This complication could be the starting point of the subdural collection. We review the literature and discuss the causes that may lead to CSDH after ETV procedure.

Aged↗

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↗

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↗

Neuroendoscopy: one year of experience--personal results, observations and limits.

After reading reports of successful neuroendoscopic treatment of hydrocephalus, colloid cysts and arachnoid cysts as well as tumor biopsy, we started using endoscopic procedures in our Department, one year ago. One surgeon (E.S.) skilled in the Decq Endoscope, performed a series of sixteen procedures, from January 2001 to March 2002 (in patients aged 28 to 69 years). The most common pathology was obstructive hydrocephalus (14 cases), one was colloid cyst, and the last case was tumor biopsy. The surgical treatment consisted of third ventriculostomy, cyst opening and shrinking and tumor biopsy. In fourteen patients treated for hydrocephalus with third ventriculostomy (ETV), one required a definitive shunt. Complication occurred in one case with chronic subdural collection. We further report one case of aqueductal restoration after third ventriculostomy. Our results, with no neurological deficits or deaths, confirmed our opinion that neuroendoscopy is a safe surgical technique in well-selected patients and we believe it is the ideal treatment in obstructive hydrocephalus.

Aged↗

Overdrainage after endoscopic third ventriculostomy: an unusual case of chronic subdural hematoma--case report and review of the literature.

Endoscopic third ventriculostomy is considered a safe technique for the treatment of obstructive hydrocephalus. However, the literature contains several reports of complications related to this procedure. We describe a case of chronic subdural hematoma (CSDH) after ETV, which required surgical evacuation, in a 69-year-old male patient completely asymptomatic up to the control MRI four weeks after the operation. We believe this unusual complication could result from the ICP changes caused by ETV. In our opinion, successful ETV gives a boost to CSF absorption, and overdrainage may evolve also in endoscopic treatment of obstructive hydrocephalus. This situation could be the starting point of the subdural collection. We review the literature and discuss the causes that may lead to CSDH after ETV procedure.

Aged↗

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↗

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↗

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↗

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↗

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↗

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↗