Intracellular oxidative activity and respiratory burst of leukocytes isolated from multiple sclerosis patients.

Oxidative damage induced by free radicals and reactive oxygen species (ROS) have been suggested to play an important role in the development of autoimmune diseases such as multiple sclerosis (MS) disease and it has been hypothesised that oxidative injury could mediate demyelination and axonal injury in MS subjects. In our study, we compared intracellular oxidative activity and the respiratory burst activity in MS patients (n=20) and healthy controls (n=15) using leukocytes as cellular model. At this purpose, intracellular ROS levels were evaluated by fluorometric assay using the 2'-7'-dichlorodihydrofluorescin diacetate probe (H(2)DCFDA) in untreated or in leukocytes stimulated with phorbol-12-myristate-13-acetate (PMA). Our results demonstrate that the intracellular spontaneous ROS production in leukocytes from MS patients was higher with respect to cells from control subjects (p<0.001). PMA addition induced a higher formation of ROS both in leukocytes from MS patients and controls (p<0.001). The PMA-induced production of ROS was significantly higher in leukocytes from MS with respect to controls (p<0.001). Significant positive correlations were established between intracellular spontaneous or PMA-induced production of ROS in leukocytes isolated from MS patients and the clinical parameters used to evaluate disease disability such as expanded disability status scale (EDSS), brain lesions evaluated by MRI and visual evoked potential (VEP) (p<0.001). In conclusion, our results demonstrate higher levels of intracellular ROS in untreated or in PMA-treated leukocytes isolated from MS patients with respect to healthy subjects confirming the role of oxidative stress in multiple sclerosis.

Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity.

Paraoxonase, an enzyme associated with high density lipoproteins (HDL), plays an important role in the anti-oxidant and anti-inflammatory properties exerted by HDL. Increasing evidence supports a role of free radicals and oxidative stress in the inflammatory processes and in the pathogenesis of multiple sclerosis (MS). The aim of this study was to further investigate the relationship between oxidative damage and MS; therefore we compared the paraoxonase activity and levels of cholesteryl ester hydroperoxides (CE-OOH), as marker of lipid peroxidation, in plasma isolated from healthy subjects (n = 89) and from MS patients (n = 24) in the early stage disability (EDSS<3.5). Our results demonstrated for the first time that the activity of paraoxonase in the plasma of MS subjects was significantly lower with respect to controls (P <0.001). Moreover, our results showed a significant increase in the levels of CE-OOH in plasma from MS subjects (P<0.001). CE-OOH are biologically active substances derived from the oxidation of cholesteryl ester localized in the hydrophobic core of plasma lipoproteins (HDL, LDL). Therefore, our study demonstrates alterations of lipoprotein peroxidation in MS and provides further evidence that oxidative stress and impairment of the anti-oxidant system may play a role in MS.

Depression after stroke: an investigation through catamnesis.

BACKGROUND: In the early stage of stroke, depression appears to be linked to certain brain areas. The study evaluated the importance of the side of the lesion in depressed patients 3 years after their first stroke. METHOD: Patients who had suffered a stroke and been discharged after rehabilitation were identified by hospital records. We interviewed 180 patients at home. Demographic as well as socioeconomic data were collected. The North-western University Disability Scale, the Beck Depression Inventory (BDI), the Relatives' Stress Scale, and the Social Dysfunction Rating Scale were applied. The diagnosis was confirmed for each patient by a clinical assessment according to the ICD-10 criteria. Patients with previous psychiatric treatment, comprehension problems, or severe hemi-inattention were excluded. RESULTS: By using a score of 14 on the BDI as a cutoff, 62 patients (34%) proved to be affected by depressive disorders. Clinical records showed that the location of the lesion was in the right hemisphere for 37 patients and in the left hemisphere for 25 patients. Statistical analysis of the mean scores obtained in this subgroup of depressed patients showed (1) no significant relation between depression and the hemispheric location of the lesion or between depression and level of education; (2) relation between BDI score and social activities; and (3) stress on the relatives that was mainly dependent on both the disability of the patients and their loss of social activities, whereas depression played a minor role. CONCLUSION: A high percentage of patients have depressive disorders 3 years or more after the stroke, independent of the side. Such mood disorders worsen the relationship between the disabled patients and their relatives and worsen leisure independent of the affected hemisphere.

Pergolide compared with bromocriptine in Parkinson's disease: a multicenter, crossover, controlled study.

We compared the efficacy and safety of pergolide and bromocriptine in 57 patients with Parkinson's disease (PD) with a declining response to levodopa therapy in a single-blind, crossover study. Patients were placed randomly on the sequence bromocriptine-pergolide (12 + 12 weeks) or vice versa. Regular evaluations using the New York University Parkinson's Disease Scale were performed by a clinician blinded to treatment assignment. Patients' and clinicians' impressions also were recorded. The average daily dose of pergolide was 2.3 +/0- 0.8 mg, and that of bromocriptine was 24.2 +/- 8.4 mg. Significantly greater efficacy was demonstrated by both drugs as adjunctive therapy to levodopa compared with previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005; Wilcoxon t test). Pergolide was more effective than bromocriptine in daily living scores (p = 0.020) and motor scores (p = 0.038). No difference in dyskinesias, dystonias, and psychosis was observed. Adverse events were more frequent in bromocriptine-treated patients. Most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.

The influence of depression, social activity, and family stress on functional outcome after stroke.

BACKGROUND AND PURPOSE: This study was designed to assess the quality of life after an active poststroke period of rehabilitation and to investigate the possibility of a return to a working environment for those still of working age. METHODS: The study was conducted on 180 consecutive patients affected by stroke who were hospitalized for the first time and discharged at least 1 year before the study. The group consisted of 65% men and 35% women with a mean age 65.29 years (SD, 11.22). The period between the stroke and the interview ranged from 12 to 196 months, with a mean of 37.5 months. The average Rankin score on discharge from the rehabilitation center was 2.718 (moderate handicap). The interview took place at home after consent obtained by telephone. The questionnaire included general and personal information regarding the individuals, their socioeconomic position, and scales for daily activity, depression, social activity, and stress produced in the family. The control group consisted of 167 age-matched subjects. RESULTS: A close correlation was observed in all patients between depression, social activity, and stress caused to relatives. The scores on the individual scales were clearly worse than those for control subjects. The patients received approximately 5 months of rehabilitation after the stroke. Differences emerged between men and women for depression and social activities, with the women scoring worse. In reference to daily life, 70% of prestroke ability was required on average after rehabilitation. The daily activity score at the time of the interview was also strongly influenced by the discharge score. The majority of patients were retired. Of the total, 20.64% returned to work, but not always to the same job and often after readapting to new conditions. Of this population, only 31.5% were women. With regard to the population aged younger than 65 years, 21.42% returned to work. Lesions in the dominant hemisphere do not necessarily seem to rule out return to work, even if associated with aphasia. The main discriminating element was the ability to understand language. The patients were often criticized by their cohabitants; the criticisms most often raised concerned apathy, irritability, and self-centeredness. Sexual activity was depressed in almost all cases. CONCLUSIONS: Despite the progress made in studying cerebral vasculopathies, patients in the aftermath of a stroke still seem to live unsatisfactorily, as they did many years ago. Useful measures include valid treatment against spasticity, psychological assistance, and greater social support.

Sympathetic skin response in chronic renal failure and correlation with sensorimotor neuropathy.

Twenty subjects suffering from chronic renal failure and undergoing continual treatment by haemodialysis were examined, and the following values assessed: maximum conduction velocity of the sensory and motor fibres of the common peroneal nerve, the relative electromyographic parameters, and the sympathetic skin response at the level of the foot. The results obtained have shown that autonomic neuropathy involving the sympathetic sudomotor is less frequent than sensorimotor neuropathy. The autonomic failures are scanty in the mild forms of sensorimotor neuropathy, with minor latency in the onset of uremia.