Properties and function of the calcium-dependent incorporation of choline, ethanolamine and serine into the phospholipids of isolated rat brain microsomes.
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Biomedical subjects
Publications and source records attributed to M Brunetti.
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Platelet MAO-B activity, serum vitamin B12 levels, and plasma folate were measured in patients suffering from presenile (AD) and senile (SDAT) dementia of Alzheimer-type, and vascular dementia (VD). MAO-B was higher in the SDAT group than in AD and controls. An inverse relationship between MAO-B activity and vit. B12 levels was documented in the whole group and in each category studied; furthermore, MAO-B was positively related to age. All the patients were then divided into two groups, according to vit. B12 levels (Group I: less than 200 pg/mL; Group II: greater than or equal to 200 pg/mL); Group I showed a significantly higher MAO-B activity with respect to Group II. The results indicate the existence of a negative association between platelet MAO-B activity and serum levels of vitamin B12 and confirm the existence of biological differences between presenile and senile dementia of Alzheimer type.
Cerebrospinal Fluid (CSF) levels of the main metabolites of monoamines (MHPG, 5-HIAA, and HVA) were measured in patients with early onset (AD) and late-onset (SDAT) Alzheimer's disease, vascular dementia (VD), and elderly controls. Psychobehavioral assessment was carried out by means of MMSE and GBS. Mean MHPG levels did not differ from controls; 5-HIAA was lower in VD when compared to both controls and SDAT. HVA was decreased in AD, SDAT, and VD with respect to controls. Significant correlations between HVA and psycho-behavioral parameters were observed in SDAT and VD groups, whereas no relationship was documented in AD. The SDAT group was divided in SDAT-A (age at onset: greater than 65 less than or equal to 80 yr) and SDAT-B (age at onset: greater than 80 yr). SDAT-A had significantly lower CSF HVA values than SDAT-B (165 +/- 64 vs 235.7 +/- 85). SDAT-B HVA levels were similar to those observed in controls. Correlation analysis between HVA and neuropsychological variables was significant in SDAT-A, but not in SDAT-B. These results might support the evidence of SDAT heterogeneity.
Serine phosphoglycerides (SPG) in the nervous tissue are synthesized by base-exchange reaction. SPG may be decarboxylated and converted into ethanolamine phosphoglycerides (EPG). This latter reaction may be followed in turn by several enzymatic reactions leading to choline phosphoglycerides (CPG) via three successive methylations. These metabolic pathways are important for several reasons and their contribution to membrane phospholipid renewal has been clearly demonstrated. Base-exchange is the only metabolic route to synthesize SPG; it was therefore possible to test this pathway in vivo by injecting labeled serine. Serine incorporation into phosphoglycerides was reduced in cortex and hippocampus from aged rat brain as compared to adult, while no change in the SPG successive metabolic transformation was found. Based on both the results presented herein and previous ones obtained in vitro the authors suggest that the reduced serine incorporation may be due to reduced uptake into cells from aged animals. This finding leads to the conclusion that the above mechanisms for partial renewal of the phospholipid molecule may play an important role in the brain structure of aged animals.
It has been previously demonstrated that spontaneously hypertensive adult rats (SHR) develop severe hypertension and cerebrovascular lesions on drinking 1% NaCl from weaning and that the phospholipid metabolism in the whole brain is actively altered in these lesioned animals (SHR-NaCl) as compared to SHRs which drink only water and show only sporadic cerebrovascular lesions. We have now assayed the incorporation of labelled choline, ethanolamine, glycerol and arachidonic acid into the phospholipids from the cortex and hippocampus of SHR-water and SHR-NaCl at different time intervals from injection into the lateral ventricle of the brain. A noticeable decrease of both choline and arachidonate specific activity (SA) in the phospholipids was found in the cortex and hippocampus (where the effect is most evident) from SHR-NaCl. Based on the literature and the data obtained, we suggest that in SHR-NaCl brain areas a release of choline and fatty acid also occurs from choline glycerophospholipids as a consequence of the cerebrovascular lesions caused by NaCl treatment. Even if a relatively minor loss of the amount of the lipids studied is evident from our results as compared to their entire pool, this change may be quite important if it causes a modification of the lipidic bilayer in excitable membranes. In a parallel group of SHR-NaCl animals, treated with the nootropic drug oxiracetam, we observed that the metabolic utilization of the precursors was completely restored. These experimental data favour the hypothesis that oxiracetam is effective in stimulating the phospholipid metabolism rate at levels even higher than those of the SHR-water animals.
BACKGROUND: Severe hyperhomocysteinemia is common in hemodialysis patients, who also present a dramatic increase in plasma concentrations of sulfate, one of the main products of methionine and cysteine catabolism. The aim of this study was to verify the relationship between high plasma sulfate levels and cysteine or homocysteine concentrations in hemodialysis patients. METHODS: Plasma sulfate, cysteine and homocysteine concentrations and some renal efficiency parameters were determined in 18 patients with end-stage renal failure, all undergoing 4h hemodialysis three times a week. The pattern of post-dialysis rises on plasma concentrations of sulfate, cysteine and homocysteine was established. RESULTS: Plasma sulfate, cysteine and homocysteine levels were significantly higher in patients than in normal controls. Plasma sulfate concentrations positively correlated with cysteinemia (p = 0.031; r = 0.482) which, in turn correlated with homocysteinemia (p = 0.042; r = 0.460). Sulfate levels also correlated with blood creatinine (p = 0.004; r = 0.630), nitrogen (p = 0.000; r = 0.899), protein (p = 0.014; r = 0.555), and albumin (p = 0.003; r = 0.642). Post-dialysis rises in sulfate and cysteine were detected some hours before homocysteine. CONCLUSION: The results suggest that high sulfate levels, due mainly to impaired renal function, are involved in the altered metabolism of homocysteine in hemodialysis patients.
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The linoleic acid metabolism was examined in the brain cortex of 4 month-old and 24 month-old rats. After the injection of [1-14C]-linoleate into the lateral ventricle of the brain the animals were sacrificed at 1,3 and 6 hours from the injection. The linoleate (18:2) incorporation into lipids, the presence of fatty acid peroxidation products, as well as the 18:2 transformation into elongated and desaturated derivatives were determined. Both an age-related reduction in linoleate incorporation rate into glycerophospholipids and a decrease in fatty acid turnover were found. Furthermore, in glycerophospholipids from 24 month-old rat brain cortex a higher level of hydroperoxide derivative of linoleate was found as compared to 4 month-old animals, and this damaged fatty acid is eliminated more slowly in aged rats than in adults. Finally, unlike 4 month-old animals, a stimulation of the transformation rate of linoleate into desaturation (6,9,12-C18:3) and elongation (8,11,14,C20:3) products was found in 24 month-old rat brain cortex. On the contrary, as far as arachidonic acid (one of the most important end products of the mechanism of linoleate modification) is concerned, the differences between aged and control animals were small, making it quite difficult to attribute a physiological meaning to this phenomenon.
The effect of the base-exchange reaction upon the production of cyclic-AMP at the level of rat brain synaptic membranes has been examined. The exchange with ethanolamine produces a significant decrease of the NaF-stimulated production of the cyclic nucleotide, whereas it increases the noradrenaline-induced production. With some exceptions, the exchange with L-serine produces opposite effects.
Domestic and wild animals have been always considered very important as reservoir of agents of human infections. Particularly birds, because of their great mobility from a continent to another or within the limits of the same ecosystem may transfer pathogenic micro-organisms. The present survey was undertaken in order to evaluate the presence of Campylobacter, Yersinia and Salmonella in migratory and permanent birds. During the period October 1986 to March 1988 intestinal loops were collected from a total of 217 birds representing 17 different species shot, during hunting seasons, in the inland of Versilia in the district of Lucca. Each sample was divided into three parts and examined for the presence of Campylobacter, Yersinia and Salmonella. Campylobacter was isolated from 74 of the 217 birds examined (34.10%). Yersinia was recovered from 26 birds (11.98%), while only 8 birds (3.68%) harboured Salmonella. Most of the samples carried only one of the three bacterial genera investigated while 9 harboured at the same time Yersinia and Campylobacter, 1 Salmonella and Campylobacter, and 1 Salmonella, Yersinia and Campylobacter. Campylobacter spp.: On the ground of Lior's biotyping scheme, the 74 strains, isolated from 16 of the 17 species of birds examined, have assigned to three biochemically different species. C. coli was the most commonly isolated followed by C. jejuni and C. laridis. Of the 54 isolates of C. coli 30 belonged to biotype I and 24 to biotype II. 19 C. jejuni organisms were differentiated into 5 belonging to biotype I and 14 to biotype II. The only C. laridis isolated belonged to biotype I. Yersinia spp.: 37 strains belonging to the genus Yersinia were isolated from 26 birds. In 10 samples different types of Yersinia were identified. Most of the strains could be ascribed to Yersinia enterocolitica (28 strains), 3 to Yersinia frederiksenii, 3 to Yersinia intermedia and 1 to Yersinia pseudotuberculosis. 2 strains were identified as atypical Yersinia. Salmonella spp.: 8 strains belonging to the genus Salmonella were isolated from 3 different species of birds. The isolates were identified as Salmonella typhi-murium (7 strains) and Salmonella blockley (1 strain). Salmonella has been isolated from 8 birds, six of which were pheasants shot during the same day in the same area and probably coming from the same breeding. In fact, in Tuscany, pheasants are bred and then set free in many hunting areas.(ABSTRACT TRUNCATED AT 400 WORDS)
The synthesis of choline phosphoglycerides and ethanolamine phosphoglycerides has been examined in brain cortex microsomes and neuronal populations of rats during various times of aging as compared to 2 months-old animals. A noticeable decrease of synthesis of both lipid classes takes place in these conditions in vitro. The concentration of the endogenous diacylglycerol is not changed during aging neither in microsomes nor in neurons. The molar distribution of fatty acids in brain microsomal diacylglycerols of aging rats is noticeably different from that of adult animals. The content of monoenoic and dienoic species is increased, whereas that of the tetraenoic species is decreased. The addition of soybean diacylglycerol to microsomes or neuronal preparations from aged rat brain restores practically the decreased synthesizing activity of CPG and partially that of EPG. It is proposed that adding diacylglycerols to aged membranes affects the properties of the membranes and probably enzyme-lipid interactions.
A spontaneous mammary adenocarcinoma of BALB/c mice was transduced with the murine interleukin (IL)-2, IL-4, and interferon (IFN)-gamma genes. The ability of clones releasing IL-2, IL-4 or IFN-gamma to form tumors after s.c. challenge was compared to the TS/A parental cells (TS/A-pc) and to cells transduced with the neomycin resistance gene alone. Cytokine-gene-transduced clones activated a strong inflammatory reaction. The elicited by IL-2 and IL-4-gene-transduced cells efficiently led to tumor rejection. This reaction depended on the activation of several cell mechanisms, those classed as nonspecific being predominant. The repertoire of reactive leukocytes recruited in the reaction varies as a function of the secreted cytokine. The growth of a secondary contralateral TS/A-pc challenge after clone rejection was significantly impaired.