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Biomedical subjects

U Senin

Publications and source records attributed to U Senin.

At least 73 records · Page 4Linked to original sources
PubMed1995

Glycosaminoglycan polysulfate in primary degenerative dementia. Pilot study of biologic and clinical effects.

To test the hypothesis that the therapeutic effects of glycosaminoglycan polysulfate (GAP) in primary degenerative dementia of the Alzheimer type (PDD) is associated with a reversal of biochemical changes seen in PDD, a two-phase, clinical-biochemical study was conducted. In the first phase of this study a number of biochemical parameters were compared in 12 patients with PDD and their sex- and age-matched controls, and it was found that platelet monamine oxidase B activity was significantly higher and cerebrospinal fluid (CSF) homovanillic acid levels significantly lower in the PDD than in the normal control group. In the second phase of this study the same 12 PDD patients were treated with GAP at a daily dosage of 250 lipasemic-releasing units for a period of 1 month and it was found that all four biochemical parameters shifted towards normal values during therapy with the changes in CSF 5-hydroxy-indole acetic acid levels attaining statistical significance. Although clinical changes were minimal, in light of prior clinical findings in studies conducted with GAP in similar populations, the possibility was entertained that clinical improvement with GAP in PDD patients is preceded by biochemical changes.

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PubMed1994

Pathogenetic mechanisms in vascular dementia.

Vascular dementia accounts for approximately 20% of all cases of dementia and for about 50% in subjects over 80 years. Thromboembolism with multiple cerebral infarcts was considered to be almost the only pathogenetic pathway of vascular dementia, with multi-infarct dementia as its clinical manifestation. However, there is a great heterogeneity of vascular dementia syndromes and pathological subtypes, as documented by the number of pathogenetic mechanisms now known to underlie the clinical picture. They include thromboembolism and extracerebral and cerebral factors. Among the extracerebral factors are ischemic hypoxic dementia (i.e., dementia due to hypoperfusion), vasculitis, hyperviscosity and abnormalities of hemostasis. Among the cerebral factors are lipohyalinosis, cerebral amyloid angiopathy, disruption of the blood-brain barrier and altered regulation of cerebral blood flow. Therefore, the approach to vascular dementia should take the heterogeneity into account. In this context, the importance of non-infarct type should be considered; subcortical white matter disorder seems to be a noteworthy common pathway of vascular dementia produced by various vascular mechanisms. Finally, the heterogeneity of the vascular mechanisms involved in vascular dementia--namely hypoperfusion--might be a factor that can be positively influenced by targeted therapeutic intervention.

Arteriosclerosis↗
PubMed1994

Platelet MAO-B activity as a marker of behavioural characteristics in dementia disorders.

Both low and high platelet MAO-B (pMAO-B) activity is considered an indicator of increased vulnerability in psychopathology. How the activity of this peripheral enzyme can be linked with the sophisticated functions of the central nervous system (CNS) is not clear; in man, evidence exists that the genetic mechanisms determining the size or capacity of the central serotonin system are common to platelet and brain MAO. In the present study pMAO-B activity was evaluated in demented patients suffering from early-onset Alzheimer's disease (AD), late-onset Alzheimer's disease (SDAT), vascular dementia (VD), and controls. In these dementia categories, the relationship between pMAO-B activity and clinical features, and between pMAO-B activity and cerebrospinal fluid (CSF) monoamine metabolites (3-methoxy-4-hydroxyphenyl-glycol, MHPG; 5-hydroxy-indoleacetic acid, 5-HIAA; homovanillic acid, HVA) was also investigated. pMAO-B activity was significantly higher in SDAT patients, compared to controls and AD. Age, as covariate, failed to show any significant effect, and no association was found between pMAO-B activity and CSF monoamine metabolites. The correlation analysis between pMAO-B and neuropsychological scores showed a highly significant positive relationship with GBS-emotional impairment (N = 40, r = 0.72, p < 0.01) in the SDAT group. This result suggests the importance of platelet MAO-B activity as biological marker also in old-age dementias, namely senile dementia of Alzheimer type, where the increased activity of this enzyme might constitute a marker for vulnerability toward behavioural disturbance, i.e., emotional deterioration.

Affective Symptoms↗
PubMed1993

Antihistone and anti-dsDNA autoantibodies in Alzheimer's disease and vascular dementia.

In order to evaluate their prevalence in senile dementias, serum titer of antibodies against histones and double stranded deoxyribonucleic acid (dsDNA) were measured by means of the ELISA test in patients suffering from vascular dementia (VD), presenile Alzheimer's disease (AD), and senile dementia of the Alzheimer's type (SDAT). Only three subjects out of 87 had dsDNA autoantibodies. On the contrary, VD and SDAT showed high titers of antibodies against histones when compared to healthy controls. A significant relationship was also found between antihistone serum titer and degree of dementia in AD. Results were not influenced by gender, age, or duration of illness. Presence of antihistone antibodies in dementias might reflect an alteration of membrane fluidity and integrity with leakage of nuclear immunogens or disturbances of immune functions, as frequently observed in dementia disorders.

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PubMed1993

Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study.

5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5'-MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12-23 at the Mini Mental State Examination (MMSE) and > or = 18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5'-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey's Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23 +/- 5 to 20 +/- 6 in the 5'-MTHF (p < 0.05 vs baseline), and from 23 +/- 3 to 21 +/- 4 in the TRZ group (p < 0.05 vs baseline). A further significant decrease to 18 +/- 6 and 19 +/- 5 respectively was obtained at the end of the treatment period (p < 0.05 vs week 4) with 5'-MTHF and TRZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Carotid atherosclerotic disease: role of hypertension and other risk factors.

1224 out-patients who consecutively underwent a Biosound examination of carotid arteries were retrospectively analyzed in order to estimate prevalence of carotid lesions and the role played by age, sex and major vascular risk factors with respect to carotid atherosclerosis. They were subdivided in asymptomatic and symptomatic subjects, making a distinction in both subgroups between patients with (RF+) or without (RF-) major vascular risk factors. Carotid lesions were present in 41% of asymptomatic RF- subjects; in 53% of asymptomatic RF+ subjects; in 53% of symptomatic RF- subjects and in 75% of symptomatic RF+ subjects. Carotid disease increases along with age, being more frequent in men than in women. The logistic regression model has then shown that increasing age, male gender, cigarette smoking and hyperlipidaemia are predictors of carotid atherosclerosis, while hypertension has been proved to play significant role only in the age class 61-69 yr.

Adult↗
PubMed1992

Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type.

Acetyl-L-carnitine (ALC), a physiological component of the L-carnitine family, has been proposed for treating Alzheimer's disease in pharmacological doses. As this condition requires prolonged therapy, its kinetics has been examined after a multiple dose regimen, involving different routes of administration, in 11 patients suffering from Senile Dementia of Alzheimer Type. The study design comprised a 3-day basal observation period, sham treatment with repeated blood sampling; treatment with 30 mg.kg-1 i.v. [corrected] for 10 days (plasma kinetics was studied on the 7th day), and 50 days of 1.5 g/day [corrected] p.o. given in three daily doses. Total acid soluble L-carnitine, L-carnitine and acetyl-L-carnitine in plasma and CSF were evaluated using an enantioselective radioenzyme assay. Short chain L-carnitine esters were calculated as the difference between total and free-L-carnitine. The plasma concentrations of individual components of the L-carnitine family did not change during the three days of the basal period, nor were they affected during the sham therapy period. Following the i.v. bolus injections, the plasma concentrations showed a biphasic curve, with average t1/2 of 0.073 h and 1.73 h, respectively. At the end of oral treatment, plasma acetyl-L-carnitine and L-carnitine short chain esters were significantly higher than during the run-in phase. The CSF concentrations paralleled those in plasma, suggesting that ALC easily crosses the blood-brain barrier. It is concluded that i.v. and oral administration of multiple doses of ALC can increase its plasma and CSF concentration in patients suffering from Alzheimer's disease.

Acetylcarnitine↗
PubMed1992

Serum autoantibodies against glial fibrillary acidic protein in brain aging and senile dementias.

Autoantibodies against glial fibrillary acidic protein (GFAP) were investigated by ELISA test in sera of patients suffering from senile dementias and in healthy aging people. One hundred eight subjects divided into control, vascular dementia (VD), presenile Alzheimer's disease (AD), and senile Alzheimer's disease (SDAT) groups were included in the study. VD patients showed the highest antibody titers when compared to controls, whereas AD had the lowest titers when compared to the other groups. These results do not support the utility of anti-GFAP antibodies as useful markers of Alzheimer's disease, suggesting that their presence is a secondary phenomenon to blood-brain barrier disruption.

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PubMed1991

Prognostic value of the dense middle cerebral artery sign in patients with acute ischemic stroke.

The presence of a dense appearance of the horizontal part of the middle cerebral artery (the "dense middle cerebral artery sign") was looked for on CT scans taken on admission in 90 consecutive patients with ischemic stroke in the carotid artery distribution. The outcome of the 14 patients with the sign was poorer than that of 76 patients without the sign (Odds ratio 4.3). We suggest that this sign could be a useful prognostic variable in the acute phase of an ischemic stroke.

Brain Ischemia↗
PubMed1991

Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.

One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

Aged↗
PubMed1991

Blood-brain-barrier in a geriatric population: barrier function in degenerative and vascular dementias.

Albumin and IgG were determined in serum and cerebrospinal fluid (CSF) of patients with early-onset Alzheimer's disease (AD, n. 13), senile dementia of Alzheimer type (SDAT, n. 33), vascular dementia divided into multi-infarct (MID, n. 9) and probable vascular (PVD, n. 11) dementia. Albumin and IgG ratio and IgG index were calculated. CSF albumin and albumin ratio were significantly higher in MID patients indicating an increased BBB permeability. IgG ratio and IgG index did not show any significant difference among groups. These results do not provide evidence for BBB damage in AD/SDAT, while in MID the increase of CSF albumin and albumin ratio is suggestive of BBB dysfunction.

Aged↗
PubMed1990

Double-blind multicenter trial on a new medium molecular weight glycosaminoglycan. Current therapeutic effects and perspectives for clinical use.

The ability of glycosaminoglycans to bind to a wide number of biologically active macromolecules has already been investigated. Recent clinical trials on the possible therapeutic benefits of glycosaminoglycans must be placed in perspective, even if they appear to be particularly encouraging, especially as regards the glycosaminoglycan effects on certain coagulation factors. A multicenter, medium-term, double-blind, crossover trial was performed by several Italian Lipid Clinics to determine whether administration of a medium molecular weight glycosaminoglycan (Sulodexide) has a significant clinical effect. Patients affected by peripheral vascular disease and/or hyperlipidemia (type IIa, IIb and IV) were submitted to a 4-week wash-out period, followed by parenteral Sulodexide (S) or placebo (P) administration for 2 weeks, another 2 week wash-out period, parenteral crossover drug or P administration for 2 weeks and, finally, oral S administration for 6 months. Sulodexide lowered plasma viscosity and plasma fibrinogen in all patients. There was also a drop in triglycerides together with a rise in apo A-I and HDL-C in type IV hyperlipoproteinemics, whereas there was no significant effect on total or LDL-plasma cholesterol in type IIa and IIb patients. Moreover, there was a percent increase in peak flow and rest flow in the lower limbs of peripheral vascular disease patients. No side effects or intolerance phenomena were detected. The results indicate that Sulodexide administration may be useful in long-term treatment of patients with peripheral vascular disease and a concomitant increase in plasma triglycerides and/or fibrinogen and/or viscosity.

Adult↗
PubMed1990

Is multi-infarct dementia representative of vascular dementias? A retrospective study.

Multi-infarct dementia (MID) indicates a dementia disorder primarily caused by multiple cerebral infarcts. Since other pathogenetic mechanisms cause vascular dementia we evaluated clinical, CT scan and CSF neurochemical parameters of 134 MID and 67 PVD (probable vascular dementia) patients. We found no differences with regard to the presence of major risk factors. Only TIA/stroke episodes and focal neurological signs were significantly more frequent in MID than in PVD cases, an anticipable result on the basis of MID definition. CT scan findings showed a prevalence of subcortical with respect to cortical lesions in both groups, with a higher frequency in MID patients. Subjects with deep infarcts more frequently showed TIA/stroke episodes and diabetes mellitus. No differences were detectable in CSF monoamine metabolite levels. We conclude that in the majority of vascular dementias subcortical damage seems to have a major pathogenetic role.

Aged↗
PubMed1990

Effects of ticlopidine on the neurologic outcome and the hemorheologic pattern in the postacute phase of ischemic stroke: a pilot study.

This double-blind pilot study observed the effects of a twenty-one day oral ticlopidine treatment (250 mg/twice daily) on the neurologic outcome and the hemorheologic pattern of 15 patients and 15 placebo-treated controls. Patients and controls (age range sixty-six to eighty-six years) were included in the study within twelve hours of the onset of ischemic stroke, confirmed clinically and by computerized tomography. Scores on Hachinski's Scale and the following hemorheologic parameters were monitored weekly for twenty-one days: fibrinogen levels, the whole blood, unfractionated white and red blood cell filterability rates (through 5-micron-pore-diameter filters using a constant-flow positive-pressure system), and the leukocyte count and activation (by microscopic observation). The results showed treatment with ticlopidine improved the neurologic outcome (Hachinski's Score +36%, p less than 0.03) slightly but significantly (p less than 0.001) increased the average values of the whole blood (+19%) and red cell (+17%) filterability rates and decreased fibrinogen levels (-17%).

Aged↗
PubMed1990

Acetyl-L-carnitine in the treatment of mildly demented elderly patients.

It has been hypothesized that acetyl-L-carnitine has a cholinomimetic action. It is for this reason that it has been used in the therapy of Alzheimer's type senile dementia impairment. In the present controlled double-blind study the authors followed two randomized homogeneous groups of both sexes of 30 patients each, aged over 65 years and suffering from mild mental impairment. One group of patients underwent therapy with acetyl-L-carnitine, 2 g/day for three months, while the other group was treated with a placebo. The statistical evaluation of the results was carried-out using non-parametric methods (Friedman-Nemenyi two-way ANOVA). It was possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural scales, in the memory tests, in the attention barrage test and in the Verbal Fluency test. These satisfactory results confirm the therapeutic importance of acetyl-L-carnitine in the treatment of elderly patients with mental impairment, which could be related principally to acetylcholine defects.

Acetylcarnitine↗
PubMed1989

Leucocyte rheology in the early stages of ischaemic stroke.

Within 5 hours of the onset of ischaemic stroke the filterability patterns and the counts of the granulocyte, monocyte and lymphocyte subfractions were monitored. The results were compared to those of a healthy matched control group and to those of a matched group with cardiovascular risk factors. The granulocyte filterability rate was significantly impaired in the group at risk and even more so in the stroke group suggesting alterations in it may be a sign of latent ischaemia.

Aged↗
PubMed1989

Neuropsychological results of long-term therapy with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia in comparison with a control group.

The cognitive and behavioral effects of oxiracetam therapy during long-term treatment in patients with dementia of Alzheimer type (DAT) and multi-infarct dementia (MID) were studied in comparison with a historical control group. Twenty DAT/MID outpatients, aged 54-86 years, received oxiracetam (800 mg twice a day) for a period of 6 months. Another 20 DAT/MID outpatients, aged 67-85 years, were selected from our clinical records in order to obtain a control group of patients matched for age, sex, diagnosis, baseline Mini Mental State Examination (MMSE) score and follow-up duration. All the patients were diagnosed as having mild to moderate degrees of dementia as defined by a baseline MMSE score between 14 and 24. The patients of both groups underwent, both at baseline and after 6 months, the following neuropsychological tests: MMSE, Idiopathic Cerebral Dysfunction Scale, Babcock Test, Gibson Spiral, Toulouse-Pieron Test. Statistical analysis of experimental data demonstrated that at baseline the two groups were comparable. At the end of the study period the oxiracetam group scored significantly better on the majority of the tests evaluating memory, attention, orientation, concentration and psychomotricity than the control group, in which a worsening trend was seen on the whole. No side effects were seen during oxiracetam treatment. The present study, showing positive clinical findings after long-term oxiracetam therapy in controlled conditions, confirms that this drug can be a useful pharmacological treatment for mild to moderate degrees of dementia.

Aged↗