Biomedical subjects
Publications and source records attributed to F Savoldi.
A numerical method is applied to calculate an optimal distribution of currents in air which generate the magnetic field gradients required to spatially encode the radiofrequency signal in a NMR tomographic experiment. We compare the performances of the gradient circuits for the whole body air-core electromagnet described by Bangert and Mansfield (J. Phys. E 15; 1982) with the results of our optimization.
Endogenous opioids have been shown to produce beneficial effects in experimental stroke. To evaluate both neurophysiological and biochemical parameters, we induced massive cerebral ischemia in 11 rabbits according to the method standardized in our laboratory, using microspheres injected through the internal carotid artery. Binding studies were performed in the 11 embolized, in nine control, and in five sham-operated rabbits using the appropriate concentration of [3H]dynorphin A (1-8). Neurophysiological parameters were evaluated under baseline conditions and 1 hour after embolization, surgical preparation, or sham operation in 17 rabbits. Comparison of visual readings of the electroencephalograms and analyses of the quantified electroencephalograms under baseline conditions and after embolization indicated a marked and statistically significant (p less than 0.01) increase in bilateral delta activity; histologic examination confirmed bilateral brain edema. Binding studies on kappa-opioid receptors indicate that 1 hour after embolization there were significantly more (28%) kappa-opioid receptors (Bmax) in six embolized rabbits than in five sham-operated animals. No significant changes were observed in the affinity parameters, particularly in the dissociation constant (Kd). Our results indicate a role for endogenous dynorphin peptides in the pathogenesis of stroke.
Thirty out-patients suffering from panic disorders associated with agoraphobia were enrolled in a double-blind, controlled trial to compare the effectiveness and tolerability of etizolam and placebo. After a 1-week washout period on placebo, patients were allocated at random to receive twice daily doses of either 0.5 mg etizolam or placebo over a period of 4 weeks. Assessments, made at baseline and after 2 and 4 weeks of treatment, used the Hamilton Rating Scales for Anxiety and for Depression, the Covi Anxiety Scale, and determination of the weekly panic crises frequency. The results showed that etizolam produced significant improvements in chronic anxiety, phobic ideas, associated depressive symptoms and episodic anxiety, and was significantly more effective than placebo. Etizolam treatment was generally well tolerated and was not significantly different from placebo in this respect.
Herpes simplex virus type 1 (HSV-1) IgG and IgM ELISA titers were serially determined in serum and cerebrospinal fluid (CSF) samples from 4 patients with HSV-1 encephalitis during a follow-up period of 1-26 months. In 3 out of 4 patients HSV-1 IgM titers raised in CSF during the acute phase of disease, thus allowing differentiation between primary and reactivated forms of HSV-1 encephalitis. HSV-1 IgG titers showed a sharp elevation earlier in serum than in CSF. Specific IgG index documented a large intrathecal production of HSV-1 IgG and their persistence 2 years following clinical onset. The initial trend of serum and CSF specific IgG titer represents a reliable tool for a retrospective diagnosis of HSV-1 encephalitis.
Total and virus-specific immunoglobulin (Ig) G oligoclonal bands were studied in paired serum and cerebrospinal fluid (CSF) of four patients with herpes simplex virus type 1 (HSV-1) encephalitis. We used the isoelectric focusing in agarose gel, a sensitive technique for protein separation, followed by passive transfer of proteins on nitrocellulose paper and specific immunostaining. Oligoclonal bands were observed in serum and CSF of all patients. HSV-1-specific oligoclonal IgG bands were present in the CSF only during a limited period of the disease, having their counterpart in serum during the remaining periods. Our findings contribute to tackle the issue of B-cell activation within central nervous system and peripheral blood compartments in course of HSV-1 encephalitis.
Memory performance, central monoaminergic function and sympathetic nerve activity were studied in patients with dementia of the Alzheimer type (DAT) or with multi-infarct dementia before and after 4 weeks with single or combined drug therapy (choline-piracetam). Analysis of the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxy-4-hydroxyphenylacetic acid (HVA) and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) and also in urine (plus 3-methoxy-4-hydroxy mandelic acid) showed that the basal values of HVA in the CSF and urine were lower in the more severely demented compared with the mildly demented subjects in both groups. The combined drug treatment resulted in a statistically significant increase in the MHPG level in the CSF of mildly demented subjects of the DAT group, while it seemed not to influence the other monoamine metabolites. The sympathetic nerve activity was similar in both patient groups and was unchanged after therapy. These findings suggest a dopaminergic deficit in advanced stages of the disease and a possible enhancement of the central noradrenergic output with therapy. No effects of therapy on memory performance or correlations between monoamine levels and memory test scores were noted.
The measurement of the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) in 59 unipolar depressed women before and during administration of 100 mg amitriptyline (AMT) i.m. daily for four weeks showed that the patients could be divided into high or low MHPG excretors. An analysis of the excretion course of MHPG and 3-methoxy-4-hydroxy mandelic acid during therapy showed, in most patients, a lower urinary excretion of both these noradrenaline (NA) metabolites in comparison with basal values. Therapy also decreased plasma noradrenaline concentrations and blood pressure values both at rest and on orthostatic challenge. Available evidence seems to suggest that AMT administration caused a lower overall noradrenergic output that might be partially responsible for a diminished sympathetic nervous activity. The authors were unable to confirm that the baseline MHPG level can predict the clinical response to antidepressant treatment and they found no significant correlations between changes in bio-chemical or physiological variables and drug plasma concentrations or clinical response. The possibility that depressed patients might be grouped according to their different NA metabolism needs to be validated in a larger patient sample.
Alterations in cerebrospinal fluid in 2 cases of viral myelopathy associated with herpes zoster infection are reported. Viral myelopathy is a rare complication of herpes zoster. Quantitatively there was a slight increase in IgG production and oligoclonal IgG bands were detected by isoelectric focusing. These parameters returned to normal after 1 year suggesting a transient involvement of the central nervous system.
Within the framework of an investigation at present under way at the Neurological Clinic of Pavia on experimental focal ischaemia, the peculiarities of platelet aggregation observed, have led to a more accurate assessment of both the phenomenon itself and the validity of the method used. In a group of 30 rabbits (17 of them submitted to embolization by means of microspheres introduced into the carotid and 13 used as controls), biohumoral electrical and histological parameters were examined. The spontaneous platelet aggregation test proved significantly related to the extent of changes taking place, as measured by PDS levels and QEEG "delta" activity (respectively, P less than 0.005 and P less than 0.05). Platelet aggregation, in relation to the occurrence or absence of focal ischaemia, revealed a "sensitivity" of 80% and a "specificity" of 92.3%. When not only the onset of but also the increase in aggregation is taken into account, the "sensitivity" figure appears to go up to 93.3%. Endothelial damage and "cascade" platelet aggregation appeared to be a prerequisite for the occurrence of the changes found. In these changes, the pathogenetic role of the regional vasospasm as opposed to mere mechanical obstruction seems to be confirmed. On the basis of these findings, it is concluded that the identification of spontaneous platelet aggregation using K. Breddin's method and its quantification based on Born's turbidimetric principle, may be usefully employed to assess the risk factor constituted by an abnormal tendency to platelet hyperaggregation.
Blockade of dopamine (DA) receptors by neuroleptics tends to produce sedation, as shown by increased sleeping time, reduction of the arousal response to sensory stimuli and slowing of the electrical (EEG) activity of the brain. The EEG and behavioural effects of the selective compounds, SCH 23390 and raclopride, which block either D1 or D2 receptor subtypes, respectively were evaluated. Groups of rabbits were prepared for the measurement of EEG activity (neocortex and hippocampus). The EEG was analyzed visually and by spectral power analysis. Gross behaviour was also observed. The D1 antagonist, SCH 23390, by itself (0.03-0.3 mg/kg i.v.) produced small changes in the EEG and no evidence of sedation. Periods of slow waves occurred sporadically. Computerized EEG analysis showed moderate increases of total power density. The D2 receptor blocker, raclopride, alone (1-3 mg/kg i.v.) produced changes of the activity of the EEG, mostly, short periods of slow waves and slight increases of total power. No sedation was noted. Although both selective antagonists were studied at larger doses than those minimally effective, they produced slight EEG and behavioural changes which were not comparable with the marked actions produced by classical neuroleptics, such as haloperidol. However, when raclopride (1 mg/kg) was given after treatment with SCH 23390 (0.03 mg/kg) there was a marked synchronized activity in the EEG, associated with a state of sedation and diminished responsiveness to sensory stimuli. The data indicate that EEG synchronization and sedation, classically associated with treatment with neuroleptics, do not depend upon the selective blockade of either D1 or D2 receptors but, instead, require concurrent blockade of both subtypes of receptor.
This report describes the effects of a fungal polysaccharide mixture on the Experimental Allergic Encephalitis (EAE) in guinea pigs. The clinical, histopathological and IgG intrathecal synthesis related studies in the EAE sensitized group was compared with that observed in EAE sensitized groups treated with fungal polysaccharides. The results indicate that the fungal polysaccharide mixture is capable of inducing a more localized and milder inflammatory reaction in the guinea pig with EAE. We hypothesize that the fungal polysaccharides can activate complement by the alternative pathway, subtracting it to the specific immune response to EAE.
The central effects of carboxyethyl-gamma-aminobutyric acid (CEGABA) have been studied both in rabbits and in the guinea pig myoclonus model. This drug caused EEG synchronization and behavioural sedation both after intravenous (i.v.) and intracerebroventricular (i.c.v.) administration in a dose-dependent manner, in rabbits. CEGABA showed a protective action against myoclonus induced by means of L-5-HTP in young guinea pigs. These data substantiate the hypothesis that CEGABA is a drug active on the central nervous system and probably exerts its action by strengthening cortical inhibition and/or directly acting on lower brainstem.
The di-carboxylated derivative of spermidine, N-carboxyethyl gamma-aminobutyric acid (CEGABA) has been identified in bovine brain and human cerebrospinal fluid by HPLC. This discovery strongly suggests the existence of a metabolic pathway connecting polyamines and GABA via putreanine and CEGABA through progressive oxidative deamination of the amino terminal groups in spermidine.
Cerebral ischemic lesions were induced in rabbits through internal carotid artery embolization by means of microspheres. Different models of stroke ranging from single focal cortical lesion to massive bilateral brain edema were reproduced and monitored up to the 24th hour by electroencephalogram (EEG and QEEG), somatosensory evoked potentials (SEPs), cerebral blood flow (CBF), platelet aggregation. The site and extent of the lesions were verified by histological examinations. Results obtained and physiopathological implications are discussed.
Median survival times 1 month after intraperitoneal inoculation of Streptococcus pneumoniae Felton UC 41 show that the difference between hemisplenectomized and control rats is not at all significant (chi 2 = 0.04). On the other hand, comparing splenectomized rats with hemisplenectomized and control rats taken together, there is a significant difference: 10% level (chi 2 = 2.84; 1 degree of freedom; p less than 0.10). The blood concentrations of pneumococci at different time intervals after inoculation do not differ between control and hemisplenectomized rats (F = 0.02; 1 and 135 degrees of freedom), but they differ very significantly when the splenectomized rats are compared with the hemisplenectomized rats and controls taken together (F = 10.00; 1 and 135 degrees of freedom; p less than 0.01).
The effect of the 1-24, 1-17, 1-13, 4-11, 1-4 ACTH fragments on cortical and hippocampal electrical activity, behavior, heart rate and rectal temperature of non-anesthetized rabbits was studied. All the fragments proved to be active in modifying cerebral electrical activity of both structures, although no common point of attack based on our data could be hypothesized. Animal behavior was not significantly modified. On the contrary, changes in rectal temperature were observed in all the animals treated. The hypothermal effect seemed to be related to the 11-13 aminoacid sequence.
In a previous study we noted that some drugs, which exert their action by inhibiting serotonin (5-HT) reuptake, caused different EEGraphic, behavioural and autonomic patterns. These drugs (Alaproclate, Citalopram, Fluoxetine, Fluvoxamine, Indalpine, Zimelidine) have now been studied in two groups of animals pretreated with L-5-hydroxytryptophan (L-5-HTP), the 5-HT precursor, and with DL-p-chlorophenylalanine (PCPA), a 5-HT depletor. The administration of 5-HT reuptake inhibitors, after pretreatment with L-5-HTP, caused homogeneous changes, i.e. EEG cortical desynchronization and behavioural serotonergic syndrome. No significant modifications of the parameters examined were observed in the animals of the second group (pretreated with PCPA). The possible mechanisms of action of these drugs and some aspects of the role of serotonin in the central nervous system are discussed.
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