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Biomedical subjects

A Gaiti

Publications and source records attributed to A Gaiti.

At least 19 recordsLinked to original sources

Physical exercise, oxidative stress and muscle damage in racehorses.

Since it has been suggested that lipid peroxidation following free radical overproduction may be one of the causes of physical exercise-induced myopathies and hemolysis in horses, we looked for the possible relationships between these phenomena and muscle fiber damage. We use a homogeneous group of Maremmana stallions which, after a 3-month training period, underwent a series of physical exercises of increasing intensity. We determined the contents of malondialdehyde (MDA), one of the main lipid peroxidation end-products, and glutathione the substrate of one of the most important free radical scavenger enzymes. We also measured creatine phosphokinase and serum lactate dehydrogenase isoenzyme activities whose modification may be indicative of muscle fiber damage. The results obtained indicated that the physical exercise we adopted was able to modify both MDA and glutathione contents in blood. However, its effect on some LDH isoenzyme activities suggested possible damage to tissues other than muscle.

Animals

Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease.

Impaired energy metabolism is an early, predominant feature in Alzheimer's disease. In order to find out simple, reliable 'in vivo' markers for the clinical-biological typization of the disorder, we measured cerebrospinal fluid (CSF) glucose, lactate and pyruvate levels in patients suffering from dementia of Alzheimer type (DAT) and in healthy elderly controls. DAT group showed remarkably higher levels of pyruvate (P = 0.01), with no overlap with the values obtained in controls. CSF pyruvate levels were also significantly associated with the severity of dementia. Therefore, CSF pyruvate levels neatly separate DAT patients from controls, having also pathogenetic value.

Aged

Possible involvement of L-glycero-phosphoryl-ethanolamine in the phospholipid methylation pathway.

It is usually accepted that GPEtn is only an intermediate in glycerophospholipid degradation. However, some years ago J. P. Infante published a review-hypothesis concerning the possible involvement of GPEtn and GPCho in the biosynthesis of acyl-specific glycerophospholipids in mammalian tissues. This paper reports the results obtained by incubating brain cortex slices in the presence of labeled GPEtn. GPEtn enters the cells and the radioactivity of the precursor is found in both PE and PC. When these results were compared with those obtained by incubating brain slices in the presence of 3H-Etn, a significantly higher amount of radioactivity was found in PC, mainly after short incubations in the presence of low concentrations of the precursors. The slopes of the methylated forms of PE further underline the above differences found by comparing the results obtained with the two precursors. The results presented in this paper suggest a possible role of GPEtn in phospholipid biosynthesis and methylation pathway of PE.

Analysis of Variance

Training-induced modifications in some biochemical defences against free radicals in equine erythrocytes.

Oxidative stress develops when the generation of free radicals exceeds the antioxidant capacity of cells or extracellular fluids. It can also occur as a result of physical exercise, and the pathogenesis of exercise-induced myopathies and haemolysis in horses may be related to changes in lipid peroxidation caused by free radicals. Cells have developed biochemical protection against oxidative stress and, as tissues seem to increase their antioxidant defences under chronic activation, training may be one of the ways of increasing antioxidant defences. Accordingly, we tested some enzymatic antioxidant activities as well as nonenzymatic antioxidants in horses undergoing special training. The results indicated a decrease in both chemical and biochemical defences against free radicals during training. It was deduced that the horses' diet may have been unable to provide the increased need for antioxidant defences resulting from training.

Analysis of Variance

Acute phase reactant alpha 1-antichymotrypsin is increased in cerebrospinal fluid and serum of patients with probable Alzheimer disease.

Levels of alpha 1-antichymotrypsin (alpha 1-ACT) in cerebrospinal fluid (CSF) and serum from patients with probable Alzheimer disease (AD) of both early (e-AD) and late (l-AD) onset assessed by a competitive enzyme-linked immunosorbent assay were higher than those found in controls or in patients with vascular dementia (VD). A negative correlation between CSF levels of alpha 1-ACT and the stage of the disease was present in patients with both e-AD and l-AD. No difference in alpha 2-macroglobulin levels in CSF and serum from patients with e-AD, l-AD, VD, and nondemented controls was found. Serum concentrations of alpha 1-antitrypsin from l-AD subjects were within the normal range. Thus, increased levels of alpha 1-ACT in CSF and serum were specifically associated with AD, and the detection of this serpin in CSF may be useful in monitoring the progression of the disease.

Aged

Linoleic acid passage through the blood-brain barrier and a possible effect of age.

It has already been established that the blood-brain barrier is readily crossed by unsaturated fatty acids, while saturated fatty acid transport appears to be protein mediated. When the passage of the fatty acids is tested in vivo by using perfusion buffers containing both linoleate and palmitate in different concentrations, linoleate is able to decrease the palmitate passage, while palmitate increases the linoleate passage. These results could be related to the effect of two fatty acids on the ratio between the fatty acids bound to the serum albumin and the free fatty acid pool, which is only available for transport through membranes. However, on the basis of some results obtained with aged rats, the possibility that a relationship may exist between palmitate and linoleate during their passage through the BBB is discussed. Moreover, it seems likely that in aged rats a moderate modification for fatty acids takes place in the BBB.

Aging

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

Defence mechanisms against free radical-induced damage in sheep, cattle and dog erythrocytes.

1. Erythrocytes from sheep were to be found the least resistant to peroxidative stress induced in vitro as compared to those from cattle and dogs. 2. The differences found among species in alpha-tocopherol content and glutathione peroxidase activity were probably insufficient to explain the lowest resistance. 3. One of the main reasons of the lowest resistance may be found in the membrane composition and characteristics (membrane fluidity).

Animals

Arachidonic and palmitic acid utilization in aged rat brain areas.

We have previously demonstrated that the arachidonic acid (20:4) incorporation into brain lipids differs according to the age of the animals used and the experimental conditions adopted. These differences led to a further investigation of arachidonic acid uptake in both aged and adult rat brains, its transformation into CoA derivatives, its incorporation into diacyl-glycerols and polar lipids, and finally its oxidation to CO2. These metabolic parameters were then compared with those obtained after using the saturated fatty acid palmitate (16:0). In both cases slices or mitochondria from different brain areas of 24-month-old and 4-month-old rats were examined. The results obtained indicate that the uptake of the fatty acids into cells is not modified by age. However, the successive metabolic transformations of the acids are altered to a considerable extent. In particular, in 24-month-old animals (compared with 4-month-old rats) there is a significant decrease of 20:4 in its incorporation into lipids as well as its oxidation to CO2, while arachidonoyl-CoA content increases by about 50%. This increased amount of CoA derivative, which has a potent detergent effect, may interfere with membrane structure and affect membrane physiological functions. Furthermore, because the free arachidonate pool is maintained in a dynamic equilibrium with its esterified forms, the final result may be a perturbation of this equilibrium.

Aging

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

Erythrocyte membrane composition in pregnancy-induced hypertension: evidence for an altered lipid profile.

OBJECTIVE: To investigate whether the increased membrane fluidity postulated as a possible contributing factor to the hypertensive states of pregnancy is related to the lipid composition of the erythrocyte membrane. DESIGN: An observational case control study. SUBJECTS: 30 women with pregnancy induced hypertension, 26 normotensive pregnant women matched for gestational age, and 10 normotensive non pregnant nulliparous women. INTERVENTIONS: Erythrocyte membranes were prepared from venous blood samples obtained from all the women. MAIN OUTCOMES MEASURES: Lipid analysis, including cholesterol to phospholipids ratio, distribution of phospholipid classes and fatty acid composition of total phospholipids in erythrocyte ghosts. RESULTS: The cholesterol/phospholipid ratio was significantly higher in the women with pregnancy induced hypertension compared with the normotensive pregnant women (mean 1.24, SD 0.31, 95% CI 1.12 to 1.35 vs mean 0.90, SD 0.09, 95% CI 0.86 to 0.94; P less than 0.01). Normotensive non-pregnant erythrocyte membrane cholesterol/phospholipid ratio was 0.88 (SD 0.11, 95% CI 0.79 to 0.96). The percentage distribution of different phospholipid classes and fatty acid composition was similar in all the four groups. CONCLUSIONS: The increased cholesterol/phospholipid ratio of the erythrocyte membrane found in pregnancy-induced hypertension represents one factor involved in the pathophysiology of this condition and a possible biochemical marker of the disease.

Adult

Evidence for an altered dopamine beta-hydroxylase activity in migraine and tension-type headache.

Sympathetic dysfunction is often present in migraine. It has been suggested that serum dopamine-beta-hydroxylase (D beta H) can be taken as an index of peripheral sympathetic activity. We studied the serum D beta H activity in migraine with and without aura and in tension-type headache patients compared with healthy control subjects. The serum D beta H activity was significantly lower in migraine and tension-type headache patients than in the control group. No significant difference was observed among the three groups of patients studied. These findings suggest that patients with migraine and tension-type headache have a sympathetic hypofunction that may play an important role in the pathogenesis.

Adult

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

Choline incorporation into phospholipids in brain areas from spontaneously hypertensive rats: effect of oxiracetam treatment.

It has been demonstrated that spontaneously hypertensive rats (SHR) develop severe hypertension and cerebrovascular lesions on drinking 1% NaCl from weaning. These animals present a learning and memory impairment as well as impairment of both energy metabolism and membrane phospholipid turnover. We tested both choline uptake into the cells and incorporation into choline phosphoglyceride (CPG) by incubating slices from hippocampus and cortex. After 5 min of incubation, a noticeable decrease in free labelled choline content inside the cells as well as its incorporation into phospho-choline (PC) and CPG were found in the brain of SHR, as compared to Wistar-Kyoto (WK) rats. This may indicate that in the SHRs with cerebrovascular lesions there is a reduction in choline uptake which in turn causes a decline in CPG biosynthesis through de novo pathway. Oxiracetam treatment is able to restore the labeled choline content in the cells from SH rats, as well as the incorporation of choline into its derivatives PC and CPG, to the levels found in the WK or more. Tests performed in the presence of such a high affinity choline uptake as hemicholinium (HC) confirmed the capacity of oxiracetam to stimulate choline uptake into the cells even if the results obtained up to now are not sufficient to hypothesize a direct effect of oxiracetam on acetylcholine metabolism. In conclusion, from the results obtained it would seem reasonable to hypothesize that the effects of the drug above mentioned on the cholinergic system may be secondary to its effect on choline phosphoglycerides biosynthesis.

Animals

Synaptic vesicle-bound phospholipase(s) acting on phosphatidylinositol exhibit(s) high susceptibility to brain ischemia.

The activity of phospholipase C acting against [3H]-inositol-phosphatidylinositol (PI) and the activity of arachidonic acid (AA) release from [1-14C]arachidonoyl-phosphatidylinositol by enzyme(s) located in synaptic vesicles (SV) isolated from normoxic and ischemic brains was investigated. Brain ischemia significantly activated phospholipase C (PhLC) by about 90% and AA release by about 50%. PhLC and AA release in SV isolated from brain submitted to ischemia were not further activated by 2 mM CaCl2 contrary to the enzymes from normoxic brain. The activation of PhLC and PhLA2 may produce conformational changes and rearrangement of the SV membranes leading to vesicle-membrane fusion and subsequently to massive neurotransmitter release known to occur during ischemia.

Animals

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