Intracerebroventricular injection of oxidant and antioxidant molecules affects long-term potentiation in urethane anaesthetized rats.

Production of superoxide anions in the incubation medium of hippocampal slices can induce long-term potentiation (LTP). Other reactive oxygen species (ROS) such as hydrogen peroxide are able to modulate LTP and are likely to be involved in aging mechanisms. The present study explored whether intracerebro-ventricular (ICV) injection of oxidant or antioxidant molecules could affect LTP in vivo. With this aim in mind, field excitatory post-synaptic potentials (fEPSPs) elicited by stimulation of the perforant pathway were recorded in the dentate gyrus of the hippocampal formation in urethane-anesthetized rats. N-acetyl-L-cysteine, hydrogen peroxide (H2O2) or hypoxanthine/xanthine-oxidase solution (a superoxide producing system) were administrated by ICV injection. The control was represented by a group injected with saline ICV. Ten minutes after the injection, LTP was induced in the granule cells of the dentate gyrus by high frequency stimulation of the perforant pathway. Neither the H(2)O(2) injection or the N-acetyl-L-cysteine injection caused any variation in the fEPSP at the 10-min post-injection time point, whereas the superoxide generating system caused a significant increase in the fEPSP. Moreover, at 60 min after tetanic stimulation, all treatments attenuated LTP compared with the control group. These results show that ICV administration of oxidant or antioxidant molecules can modulate LTP in vivo in the dentate gyrus. Particularly, a superoxide producing system can induce potentiation of the synaptic response. Interestingly, ICV injection of oxidants or antioxidants prevented a full expression of LTP compared to the saline injection.

Long-term clinical experience with weekly interferon beta-1a in relapsing multiple sclerosis.

Post-marketing surveillance studies are needed to assess the long-term safety, compliance and clinical efficacy of interferon beta-1a (IFNbeta-1a) therapy in multiple sclerosis (MS) patients. The goals of this study were to (i) assess the safety, compliance and clinical efficacy of long-term intramuscular (i.m.) IFNbeta-1a therapy in a large cohort of patients, and (ii) suggest possible predictors of therapeutic response. A total of 255 patients were included in the study. Mean time on therapy was 31.7 +/- 19.3 months. Within 3 years, 31% of patients discontinued treatment, mainly for disease activity. No significant sustained blood analysis alteration was observed over time, apart from a decrease of cholesterol levels. After 3 years of treatment, mean Expanded Disability Status Scale (EDSS) scores increased by 0.4 points compared with baseline. The mean annual relapse rate was reduced compared with baseline. Patients with < or = 2 relapses in the previous 2 years and with baseline EDSS scores of < or = 2 had a longer estimated time to first relapse and to progression and first relapse, respectively. These results confirm the safety and suggest a sustained effectiveness of i.m. IFNbeta-1a, extending the reported follow-up period to 6.3 years, and hypothesize the presence of possible predictors of clinical outcome.

Post-exercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation: a study in multiple sclerosis.

OBJECTIVE: To evaluate motor cortex excitability changes by transcranial magnetic stimulation (TMS) following repetitive muscle contractions in patients with multiple sclerosis (MS); to state whether a typical pattern of post-exercise motor evoked potentials (MEPs) is related to clinical fatigue in MS. METHODS: In 41 patients with definite MS (32 with fatigue and 9 without fatigue according to Fatigue Severity Scale) and 13 controls, MEPs were recorded at rest: at baseline condition, following repetitive contractions until fatigue, and after fatigue, to evaluate post-exercise MEP facilitation (PEF) and depression (PED). RESULTS: After exercise, MEP amplitude significantly increased both in patients and controls (PEF). When fatigue set in, MEP amplitude was significantly reduced in normal subjects (PED), but not in patients. Post-exercise MEP findings were similar both in patients with and without fatigue. CONCLUSIONS: Our findings suggest an intracortical motor dysfunction following a voluntary contraction in MS patients, possibly due to failure of depression of facilitatory cortical circuits, or alternatively of inhibitory mechanisms.

Carotid atherosclerosis and ischemic stroke in young patients.

BACKGROUND: Epidemiological studies indicate a high prevalence of carotid atherosclerosis in elderly patients with ischemic stroke. The aim of this study was to investigate the presence of early carotid atherosclerotic lesions in young subjects with ischemic stroke, in the absence of the common atherosclerotic risk factors. METHODS: We studied 98 young patients with first ischemic stroke (54 males and 44 females; mean age 41.2 years; range 32-50) and 96 healthy controls. All subjects underwent ultrasonographic scanning of the carotid arteries according to a standardized protocol. RESULTS: The carotid intima-media thickness was significantly increased in the patient group (p<0.001) compared with controls. In addition, the prevalence of carotid atherosclerotic plaques was greater in the patients than in the controls (p<0.001). In particular, we detected 18 non-occlusive carotid plaques and 16 thrombotic occlusions. In 8 patients, the lesions were bilateral. The echographic pattern of the plaques was hard in 8 cases, soft in 5 cases, and mixed in the remaining 5 cases. CONCLUSIONS: We detected an increased wall thickness of the carotid arteries and an increased prevalence of carotid atherosclerotic lesions and carotid thrombotic occlusions in young patients with ischemic stroke, with a relative low incidence of cardiovascular risk factors. This finding suggests that arterial intima-media thickness per se is an important determinant of vascular disease in young patients. The data also provide indirect support for the potential role of genetic factors in the genesis of atherosclerosis in young patients.

[Diagnosis and treatment of heart failure in primary health care. Low correlation between Pro-ANF and heart failure]. / Diagnostik och behandling av hjärtsvikt i primärvården. Låg korrelation mellan Pro-ANF och hjärtsvikt.

Three eastern Swedish primary care clinics serving a predominantly rural clientele monitored for 13 months all patients under 80 years of age with a diagnosis based on clinical signs alone of heart failure (n = 56) or suspected incipient heart failure (n = 62). Echocardiography was performed on all patients. For 64% of the former group, the putative diagnosis matched echocardiography findings. Results showed a purely diastolic disorder in one-fifth of all 118 patients, and a hemodynamically significant, hitherto unknown heart defect in about as many. Pro-ANF assays correlated poorly with manifest heart failure. Pharmacological treatments were registered, and at 6-month follow-up, 82% of patients with systolic failure were receiving ACE-inhibition.