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Biomedical subjects

M Salvetti

Publications and source records attributed to M Salvetti.

At least 19 recordsLinked to original sources
PubMed2006

Multiple sclerosis: pharmacogenomics and personalised drug treatment.

Multiple sclerosis (MS) is a disorder of the central nervous system with an inflammatory and a neurodegenerative component. We do not yet have a definitive therapy for MS. Attempts to develop new treatments are long and costly and should be paralleled by studies aimed at increasing the therapeutic index of the existing treatments, interferon beta and glatiramer acetate. Pharmacogenetics and pharmacogenomics may be of use in this respect though their application may not be straightforward, particularly in MS.

Humans↗
PubMed2005

Sex hormones modulate brain damage in multiple sclerosis: MRI evidence.

BACKGROUND: Sex related differences in the course and severity of multiple sclerosis (MS) could be mediated by the sex hormones. OBJECTIVE: To investigate the relation between serum sex hormone concentrations and characteristics of tissue damage on conventional magnetic resonance imaging (MRI) in men and women suffering from relapsing-remitting MS. RESULTS: Serum testosterone was significantly lower in women with MS than in controls. The lowest levels were found in women with a greater number of gadolinium enhancing lesions. A positive correlation was observed between testosterone concentrations and both tissue damage on MRI and clinical disability. In men, there was a positive correlation between oestradiol concentrations and brain damage. CONCLUSIONS: The hormone related modulation of pathological changes supports the hypothesis that sex hormones play a role in the inflammation, damage, and repair mechanisms typical of MS.

Adult↗
PubMed2003

Physiopathology of multiple sclerosis.

Pleiotropy and redundancy are distinctive elements of the immune response. Recent research into the inflammatory component of multiple sclerosis (MS) indicates that, as expected, pleiotropy and redundancy characterize various physiopathological mechanisms of the disease. A certain degree of redundancy is becoming apparent also as far as the degenerative component is concerned. Cumulatively, these data suggest that treatments that target single pathogenetic pathways are unlikely to provide a definitive solution. Combination therapies may offer, in principle, some advantage, although there is a need for more information on the aetiology of the disease.

Animals↗
PubMed2003

Circulating adhesion molecules and carotid artery structural changes in patients with noninsulin-dependent diabetes mellitus.

Hypertension and non insulin-dependent diabetes mellitus (NIDDM) are well-known risk factors for atherosclerotic disease. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may exert a relevant role in the pathogenesis of atherosclerosis; their prognostic relevance has been recently demonstrated. The aim of the study was to investigate possible inter-relation between circulating adhesion molecule levels, carotid artery structure and endothelial function in 15 patients with NIDDM, as well as in 15 patients with both NIDDM and essential hypertension (NIDDM+EH) compared with 15 normal subjects (NS) and 15 euglycaemic patients with EH, matched for age, sex and body weight. All subjects were submitted to a biopsy of the gluteal subcutaneous fat. Small arteries were dissected and mounted on a micromyograph, and the media-to-lumen (M/L) ratio was then calculated. Carotid artery structure was investigated by Doppler ultrasound. Endothelial function was evaluated by investigation of the flow-mediated dilatation (FMD) of the brachial artery. ICAM-1 and VCAM-1 plasma levels were measured by ELISA. ICAM-1 and VCAM-1 plasma levels were significantly greater and FMD smaller in EH, NIDDM and NIDDM+EH than in NS, but no difference was observed among the three pathological groups. Carotid artery structural changes were more pronounced in NIDDM+EH. No significant difference was observed among NIDDM, EH and NS. The M/L ratio of subcutaneous small resistance arteries was significantly greater in NIDDM+EH than in NIDDM or EH. NS had a smaller M/L ratio than the other groups. Significant correlations were observed between ICAM-1 plasma levels and indices of carotid artery structure in diabetic patients. However, the relations were close only in NIDDM+EH. In conclusion, our data suggest that NIDDM+EH may present more pronounced vascular structural alterations than NIDDM, and that adhesion molecules plasma levels are closely inter-related with carotid artery structural alterations, at least in NIDDM+EH, but not with M/L ratio of small resistance arteries.

Carotid Arteries↗
PubMed2001

Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the Limone sul Garda study.

BACKGROUND: Carriers of the apolipoprotein A-I(Milano) (apoA-I(M)) mutant present with very low plasma HDL cholesterol and moderate hypertriglyceridemia, apparently not leading to premature coronary heart disease. The objective of this study was to establish whether this high-risk lipid/lipoprotein profile is associated with structural changes in the carotid arteries and heart, indicative of preclinical atherosclerosis. METHODS AND RESULTS: Twenty-one A-I(M) carriers were compared with age- and sex-matched control subjects from the same kindred and with 2 series of matched subjects with primary hypoalphalipoproteinemia (HA). Structural changes in the carotid arteries were defined as the intima-media thickness (IMT) measured by B-mode ultrasound. HA subjects, both recruited among patients attending our Lipid Clinic and blood donors, showed significant thickening of the carotids (average IMT, 0.86+/-0.25 and 0.88+/-0.29 mm, respectively) compared with control subjects (average IMT, 0.64+/-0.12 mm); the apoA-I(M) carriers instead showed normal arterial thickness (average IMT, 0.63+/-0.10 mm). Moreover, a significantly higher prevalence of atherosclerotic plaques was found in patients and blood donors with HA (both 57%) compared with apoA-I(M) carriers (33%) and control subjects (21%). Echocardiographic findings and maximal treadmill ECG did not differ significantly between apoA-I(M) carriers and control subjects, apart from a slight increase in left ventricular end-diastolic dimension in the carriers. CONCLUSIONS: Despite severe HA, carriers of the apoA-I(M) mutant do not show structural changes in the arteries and heart, in contrast to HA subjects, who are characterized by a marked increase in carotid IMT and increased prevalence of atherosclerotic plaques.

Adult↗
PubMed2001

T cell response to N-formylated peptides in humans.

We present the first evidence of a T lymphocyte response to N-formylated peptides in humans. N-formylated peptide sequences from self (mitochondrial) and foreign (microbial) antigens were used to isolate antigen-specific T cell clones from healthy individuals, including a set of monozygotic twins. The observed response differed from that previously described in mouse (CD4(+) phenotype and MHC class II restriction in humans vs. CD8(+) phenotype and class I restriction in mice). These lymphocytes produce substantial amounts of IFN-gamma. They were isolated in only one of the monozygotic twins, which suggests that their expansion in the healthy immune repertoire is independent of the genetic background. Our result will help in assessing the relevance of N-formylated peptide-specific T cells in protection against infections within the human immune system.

Adult↗
PubMed2001

Night time blood pressure and cardiovascular structure in a middle-aged general population in northern Italy: the Vobarno Study.

The aim was to determine, in a cross-sectional study, the relation between structural alterations in the heart and carotid arteries, and blood pressure (BP) changes from day to night time, measured by ambulatory BP (ABP). In 225 untreated subjects (107 F, 118 M, age range 48-64 years) and 59 treated subjects (24 M, 35 F, age range 50-64), living in a small town of northern Italy (Vobarno, Brescia) carotid intima media thickness as well as the occurrence of plaque, were evaluated by ultrasound. Echocardiographic left ventricular (LV) mass was measured according to the Penn Convention. BP was determined by clinic measurement and by 24-h non-invasive ABP monitoring. Subjects were divided in two groups, according to the decrease of night time systolic BP (SBP) "dippers" (SBP decreased by at least 10% during night time) and "non-dippers" (decrease of night time SBP <10%). The intima-media thickness in the common carotid, in the carotid bifurcation, in the internal carotid artery and average intima-media thickness were significantly greater in untreated non-dippers as compared with dipper subjects (ANOVA P < 0.05). A significantly higher prevalence of plaque was observed in untreated non-dippers as compared with dippers (P = 0.002). After adjusting for age, sex, 24-h SBP, and smoking, IMT in the carotid bifurcation and average intima-media thickness remained significantly greater in non-dipper subjects (P < 0.05 for all comparisons). No significant differences in LV mass were observed between dippers and non-dipper subjects. In conclusion, in a general population of unselected middle-aged subjects, night time BP values, among other risk factors, seem to represent an important determinant of carotid wall structure.

Age Distribution↗
PubMed2001

Flow-mediated dilatation of the brachial artery and left ventricular geometry in hypertensive patients.

OBJECTIVES: In arterial hypertension, the spectrum of geometric patterns in the left ventricle may parallel the structural alterations detected in the carotid arteries and in subcutaneous small arteries. It has been also reported that hypertensive left ventricular hypertrophy (LVH) may be associated with endothelial dysfunction, as evaluated by the response of coronary or forearm vasculature to acetylcholine infusion. The aim of this study was to evaluate the flow-mediated vasodilatation (FMD) of the brachial artery, non-invasive estimate of endothelium-dependent vasodilatation according to left ventricular geometric adaptations in hypertensive patients. METHODS AND RESULTS: In 16 normotensive (nine males, seven females, aged 40-68 years) and in 78 hypertensive subjects (50 males, 28 females, aged 42-67 years), we performed an echocardiographic study for the measurement of left ventricular mass index (LVMI) and relative wall thickness (RWT); we measured to a high resolution the brachial artery diameter at rest, during reactive hyperaemia (5 min of brachial artery occlusion) and after sublingual glyceril trinitrate (GTN); brachial artery flow velocity was measured by pulsed Doppler. Twenty-six hypertensive patients had a normal LVMI (LVMI < 51 g/ m2.7) and geometry (RWT < 0.44), five had concentric remodelling (RWT > or = 0.44), and concentric and eccentric LVH were observed in 19 and 28 patients, respectively. FMD was reduced in hypertensive patients as compared with normotensive subjects (P< 0.01). No correlation was found between FMD and LVMI (r= -0.078) or RWT (r = 0.049); in addition, no difference in FMD was found among the left ventricular geometric patterns in hypertensive patients. CONCLUSIONS: In hypertensives, the presence of endothelial dysfunction is not associated with the LVH or with different left ventricular geometric patterns, suggesting that different and independent mechanisms may be responsible for the presence of LVH and of endothelial dysfunction.

Adult↗
PubMed2001

The smoothness index, but not the trough-to-peak ratio predicts changes in carotid artery wall thickness during antihypertensive treatment.

BACKGROUND: It has recently been demonstrated that the smoothness index (SI) (the ratio between the average of the blood pressure changes computed for each hour of the recording and its standard deviation), a new and reproducible measure of the homogeneity of blood pressure reduction by antihypertensive treatment, has evident advantages over trough-to-peak ratio (T/P) in the prediction of the regression of left ventricular hypertrophy. Therefore we considered it to be worthwhile to compare the ability of SI and T/P to predict changes of the carotid artery intima-media thickness (IMT) during pharmacological treatment in patients with essential hypertension. METHODS: In 100 patients with essential hypertension, 24 h ambulatory blood pressure and carotid artery IMT were measured after 3 weeks of therapeutic wash-out and after 12 months of antihypertensive treatment (calcium antagonists, diuretics, angiotensin converting enzyme (ACE) inhibitors or beta-blockers). The homogeneity of the effect of treatment over blood pressure was evaluated by computing T/P and SI. RESULTS: Twenty-four hour blood pressure was significantly reduced by therapy, while, on average, a small but significant increase in indices of carotid artery wall thickness was observed. However, IMT was clearly reduced in patients with high SI. Statistically significant correlations were observed between changes in indices of carotid artery IMT during therapy and SI. No significant correlation was observed between indices of carotid artery morphology and T/P, basal 24 h blood pressure or changes in blood pressure during therapy. CONCLUSIONS: SI, but not T/P is the predictor of changes in carotid artery wall thickness. The information provided by SI is independent from basal blood pressure values. For carotid artery morphology, the smoothness of blood pressure reduction is even more important than its absolute change.

Adult↗
PubMed2001

Endothelial dysfunction in small resistance arteries of patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: Arterial hypertension is frequently associated with the presence of endothelial dysfunction in human subcutaneous small resistance arteries, as evaluated by responses to acetylcholine or bradykinin; however it is not known whether patients with diabetes mellitus show similar alterations. Therefore, we have investigated endothelial function in subcutaneous arteries of normotensive subjects (NT), of patients with essential hypertension (EH), of patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as of patients with both essential hypertension and non-insulin-dependent diabetes mellitus (NIDDM+EH). PATIENTS AND METHODS: All subjects were submitted to a biopsy of the subcutaneous fat Small arteries were dissected and mounted on a micromyograph. The media to lumen ratio (M/L) was calculated. A concentration-response curve to acetylcholine, to bradykinin as well as to the endothelium-independent vasodilator sodium nitroprusside were performed. We also evaluated the contractile response to endothelin-1. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) plasma levels were also measured. RESULTS: The vasodilatation to acetylcholine and bradykinin (but not to sodium nitroprusside) was significantly and similarly reduced in EH, in NIDDM, and in NIDDM+EH compared with NT. The contractile response to endothelin-1 was similarly reduced in EH, in NIDDM and in NIDDM+EH. Plasma ICAM-1 and VCAM-1 concentrations were higher in EH, NIDDM and NIDDM+EH than in NT. CONCLUSIONS: An evident endothelial dysfunction was detected in patients with NIDDM, and the simultaneous presence of EH did not seem to exert an additive effect. The contractile responses to endothelin-1 were reduced possibly as a consequence of ET(A) receptor down-regulation.

Arteries↗
PubMed2000

Myelin basic protein intramolecular spreading without disease progression in a patient with multiple sclerosis.

A case with stable multiple sclerosis (MS) and T cell responses which initially focused on peptide 16-38 of myelin basic protein (MBP) allowed us to investigate the dynamics of the MBP-specific T cell repertoire and its relationship with disease progression. Epitope mapping experiments and T cell receptor usage of MBP-reactive T cell lines (obtained at four distinct time points over a 7-year period) showed a spreading of the response. Transient expansions and persistence of T cells recognizing different MBP epitopes were also detected. The patient's expanded disability status scale and magnetic resonance imaging lesion load remained stable. Our case shows both persistent self-recognitions and determinant spreading in stable MS. This finding suggests that the relationship between dynamics of self-recognition and disease progression is highly complex.

Adult↗
PubMed2000

Global immune disregulation in multiple sclerosis: from the adaptive response to the innate immunity.

Increasing evidences show a global immune disregulation in multiple sclerosis (MS). The possible involvement of myelin and non-myelin (auto-)antigens in the autoaggressive process as well as the disregulation of both adaptive and innate immunity challenge the concept of specific immunotherapy. T cells at the boundary between innate and adaptive immunity, whose immunoregulatory role is becoming increasingly clear, have recently been shown to bear relevance for MS pathogenesis. Global immune interventions (and type I interferons may be considered as such) aimed at interfering with both innate and acquired immune responses seem to be a most promising therapeutic option in MS.

Humans↗
PubMed2000

Evidence for a role of gammadelta T cells in demyelinating diseases as determined by activation states and responses to lipid antigens.

In this report we review current information on the phenotypic and functional properties of gammadelta T cells in demyelinating disorders. The results support the conclusion that although gammadelta T cells show evidence of activation in patients with either multiple sclerosis (MS) or Guillain Barrè syndrome (GBS), differences exist in the phenotypic and functional properties of these cells between the two diseases. In particular, our data indicate that in patients with MS the Vdelta2 subset is activated and that these cells can be induced to secrete high levels of proinflammatory cytokines. In contrast, in patients with GBS, the Vdelta1 subset is expanded and can be induced to secrete cytokines more associated with a humoral response.

Guillain-Barre Syndrome↗
PubMed2000

Diagnostic and interventional radiology in the post-operative period and follow-up of patients after rectal resection with coloanal anastomosis.

Surgical treatment of carcinoma of the distal third of the rectum with anal sphincter preservation is increasingly used in accredited cancer centers. This study aimed to evaluate the diagnostic usefulness of radiological investigations in the management of patients who had undergone resection with coloanal anastomosis for carcinoma of the rectum, in the immediate post-operative period, during closure of the protective colostomy and in the follow-up of symptomatic recanalized patients. A total of 175 patients who had undergone total rectal resection with end-to-side anastomosis for carcinoma of the distal third of the rectal ampulla, most of whom had received postoperative radiotherapy, were evaluated radiologically. In the postoperative period radiological investigation was ordered only for symptomatic patients to detect pathology of the anastomosis and the pouch sutures and was used direct film abdominal radiography and contrast-enhanced radiography of the rectal stump with a water-soluble radio-opaque agent. Before closure of the colostomy, 2 months after rectal excision or approximately 4 months after if postoperative radiotherapy was given, the anastomosis and pouch of all patients, even asymptomatic ones, were studied with water-soluble contrast enema to check for normal canalization. In the follow-up after recanalization radiological examinations were done to complete the study of the large intestine if the endoscopist was not able to examine it up to the cecum. Of the 175 patients examined radiologically during the postoperative period and/or subsequent follow-up, 95 showed no pathological findings. Seventy-nine patients had fistulas of the coloanal anastomosis or the pouch, 23 of which supplied a presacral collection. In the absence of severe sepsis, the only therapeutic measures were systemic antibiotics and washing of the surgical catheters to maintain efficient operation. In 2 patients in whom transanal drainage was performed radiologically the fistula was cured in 1 week. In 36 cases of cicatricial stenosis, 17 at the coloanal anastomosis and 19 at the pouch, radiological examination always detected the lesion, correctly defining its anatomical characterisitics, nature and extension. Of the 19 cases of stenosis treated radiologically, 15 recovered an adequate intestinal calibre for tients operated on, 21 cases of reccurrence were detected. Radiological examination was requested as the first investigation in only one of these cases, for a patient with subocclusion. Radiological investigations in patients who have undergone colonanal anastomosis are of read diagnostic value in the immediate post-operative period, during closure of the protective colostomy and in the follow-up of symptomatic recanalized patients.

Anal Canal↗
PubMed2000

Twins: mirrors of the immune system.

Twin studies are a powerful tool to assess genetic and nongenetic factors in multifactorial, immune-mediated diseases. Here, Marco Salvetti and colleagues review important results from such studies and highlight their potential value. Future developments that should help to realize the potential of twin studies are discussed.

Humans↗