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Biomedical subjects

C Galli

Publications and source records attributed to C Galli.

At least 109 records · Page 6Linked to original sources
PubMed1999

Modulation of the atrioventricular node conduction to achieve rate control in patients with atrial fibrillation: long-term results.

Modulation of the AV node reduces the ventricular rate during AF, without affecting AV conduction during sinus rhythm. Acute and long-term results of AV node modulation in 75 patients with AF and severe related symptoms of heart failure are presented in this study. The procedure involved, in all cases, the selective ablation of the posterior inputs to the AV node; in a subgroup of 15 patients with poor modification of AV conduction properties, a sequential approach involving subsequent anterior input ablation was performed. The procedure caused acutely a prolongation of the Wenckebach cycle length (38 patients in sinus rhythm) from 334 +/- 88 to 470 +/- 80 ms (P < 0.01), and a reduction of the average ventricular rate (37 patients in AF) from 154 +/- 31 to 88 +/- 40 beats/min (P < 0.01); permanent complete AV block was induced in 9 of 75 patients (12%). Considering the "sequential" approach, an increase of the Wenckebach cycle length from 362 +/- 50 to 530 +/- 45 ms (P < 0.01) and a reduction of the average heart rate in patients with AF from 158 +/- 16 to 81 +/- 20 beats/min (P < 0.01) was obtained in this subgroup of patients, in whom the AH interval prolonged from 93 +/- 12 to 175 +/- 27 ms, and no complete AV block was observed. At a mean follow-up of 23 +/- 9 months (range 2-48), the mean number of hospital admissions per patient per year decreased from 4.2 to 0.2. Five of 49 patients with paroxysmal AF and 3 of 26 patients with chronic AF had high rate recurrences (1 > 120 beats/min) that caused severe palpitations; these patients were considered as late clinical failures (8/75; 11%). All patients reported a substantial subjective improvement and an increased exercise tolerance, as documented by a semiquantitative questionnaire. There were no episodes of late AV block or sudden cardiac deaths. In conclusion, modulation of the AV node--either by slow pathway ablation, or by a "sequential" posterior and anterior approach in refractory patients--allows a long-term control of the ventricular rate and prevents the recurrence of severe clinical symptoms in more than 75% of patients with drug refractory AF.

Adult↗
PubMed1999

Long-chain polyunsaturated fatty acids in human milk.

Arachidonic acid and docosahexaenoic acid are the most representative long-chain polyunsaturated fatty acids (LCPUFA) since they may affect infants' growth and development. LCPUFA are present in the milk of all lactating women throughout lactation. The mothers' dietary habits may affect the levels of these fatty acids in maternal blood lipids and then in milk. LCPUFA show marked differences in levels as wt%, particularly from colostrum to mature human milk, but only mild differences in absolute content. Both the major presence of LCPUFA in human milk phospholipids and some regulatory mechanisms in the mammary gland cells could contribute to the LCPUFA levels in milk beyond those in maternal plasma.

Arachidonic Acid↗
PubMed1999

Taylor's cortical dysplasia: a confocal and ultrastructural immunohistochemical study.

In the present report we describe the neuropathological characteristics of tissue surgically resected from three patients affected by intractable epilepsy secondary to cortical dysplasia. Common features, suggestive of a focal cortical dysplasia of Taylor, were observed in all specimens. Immunocytochemical procedures were performed using neuronal and glial markers and the sections were observed at light traditional and confocal microscopes. This part of the investigation pointed out: 1. cortical laminar disruption; 2. very large neurons displaying a pyramidal or round shape; 3. ballooned cells; 4. decrease of calcium binding proteins immunoreactivity; 5. abnormal nets of parvalbumin- and glutamic acid decarboxylase-positive puncta around giant neurons but not around ballooned cells. Ultrastructural investigation on the same material provided evidence of a high concentration of neurofilaments in giant neurons and of glial intermediate filaments in ballooned cells. In addition, immunolabeled GABAergic terminals clustered around giant neurons were not found to establish synapses on their cell bodies. The present data, derived from a limited sample of patients but showing very consistent features, suggest that in Taylor's type of cortical dysplasia a disturbance of migratory events could be paralleled by a disruption of cell differentiation and maturation and by an impairment of synaptogenesis. This latter mechanism seemed to affect especially the inhibitory elements, and could account for the hyperexcitability of this tissue and thus for the high epileptogenicity of Taylor's dysplasia.

Adult↗
PubMed1999

Fish intake, independent of apo(a) size, accounts for lower plasma lipoprotein(a) levels in Bantu fishermen of Tanzania: The Lugalawa Study.

Plasma lipoprotein(a) [Lp(a)] levels are largely genetically determined by sequences linked to the gene encoding apolipoprotein(a) [apo(a)], the distinct protein component of Lp(a). Apo(a) is highly polymorphic in length due to variation in the numbers of a sequence encoding the apo(a) kringle 4 domain, and plasma levels of Lp(a) are inversely correlated with apo(a) size. In 2 racially homogeneous Bantu populations from Tanzania differing in their dietary habits, we found that median plasma levels of Lp(a) were 48% lower in those living on a fish diet than in those living on a vegetarian diet. Considering the relationship between apo(a) size and Lp(a) plasma concentration, we have extensively evaluated apo(a) isoform distribution in the 2 populations to determine the impact of apo(a) size in the determination of Lp(a) values. The majority of individuals (82% of the fishermen and 80% of the vegetarians) had 2 expressed apo(a) alleles. Additionally, the fishermen had a high frequency of large apo(a) isoforms, whereas a higher frequency of small isoforms was found in the vegetarians. When subjects from the 2 groups were matched for apo(a) phenotype, the median Lp(a) value was 40% lower in Bantus on the fish diet than in those on the vegetarian diet. A significant inverse relationship was also found between plasma n-3 polyunsaturated fatty acids and Lp(a) levels (r=-0.24, P=0.01). The results of this study are consistent with the concept that a diet rich in n-3 polyunsaturated fatty acids, and not genetic differences, is responsible for the lower plasma levels of Lp(a) in the fish-eating Bantus and strongly suggest that a sustained fish-based diet is able to lower plasma levels of Lp(a).

Adult↗
PubMed1999

Increased thrombogenic potential of human monocyte-derived macrophages spontaneously transformed into foam cells.

This study investigated whether spontaneous lipid enrichment of human macrophages affects their thrombogenic potential as measured by increased production of tissue factor (TF) and plasminogen activation inhibitor types 1 and 2 (PAI-1 and PAI-2). Macrophages were obtained following a 7-day culture period of monocytes, isolated from the same donor, in autologous serum (HS) or in fetal bovine serum (FBS). Those cultured in HS underwent marked lipid accumulation relative to those cultured in FBS that was accompanied by increased production of TF and PAI-1, but not of PAI-2, and decreased production of interleukin-1beta. They also contained more arachidonic and linoleic acid and lower amounts of n-3 polyunsaturated fatty acids, particularly docosahexaenoic acid (22: 6). These data indicate that the transformation of macrophages into foam cells results in an increase in their thrombogenic and antifibrinolytic potential and provide a possible explanation of the thrombotic sequelae frequently consequent on plaque fissuring and disruption.

Arteriosclerosis↗
PubMed1999

Persistent impairment of platelet aggregation following cessation of a short-course dietary supplementation of moderate amounts of N-3 fatty acid ethyl esters.

The duration of the effect of a short-course (1-mo twice-daily) supplementation of moderate amounts (2.28 g) of n-3 fatty acid ethyl esters (FA) on platelet lipid composition and aggregation was compared with that of olive oil (3 g/d) supplementation in 14 healthy volunteers. The FA preparation employed contained eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) in a ratio of 1:1.4. A marked rise (p <0.05) in the plasma and platelet content of EPA and DHA, and minimal changes in the content of arachidonic acid (AA) were documented at withdrawal of the n-3 FA supplementation. EPA/AA and DHA/AA ratios in platelet phospholipids showed that the FA accumulation persisted 8-12 wks after stopping the supplementation (p <0.05). The aggregation of platelets in response to collagen or ADP, and thromboxane B2 (TXB2) formation were impaired at withdrawal. The impaired aggregation lasted 8-12 weeks (p always <0.05), whereas TXB2 formation returned to basal values 4 weeks after stopping the n-3 supplementation. No correlation was found between impaired aggregation and TXB2 formation. In contrast, the impaired sensitivity to ADP (p = 0.036) and, to a lesser extent, to collagen (p = 0.068) were related to changes in the intracellular pH (pHi) of the Na+/H+ reverse transport. No changes in platelet composition or function were observed either during or following olive oil supplementation. These results document a long-lasting impairment of platelet sensitivity to ADP and collagen; changes in the pHi values of the Na+/H+ reverse transport, and a simultaneous persistent accumulation of EPA and DHA in platelet phospholipids, after stopping a short-course dietary supplementation of moderate amounts of n-3 fatty acid ethyl esters.

Adult↗
PubMed1998

Adenosine and ADP prevent apoptosis in cultured rat cerebellar granule cells.

Cerebellar granule cells (CGCs) explanted in vitro undergo death via apoptosis when the concentration of potassium is shifted from 25 mM to 5 mM. We report that adenosine and ADP, which act as neurotransmitters and neuromodulators in the brain, exert in cultured cerebellar granule cells a specific and marked antiapoptotic action with half-maximal effect in the 10-100 microM range. The action of adenosine is partly inhibited by the A1AR antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and is mimicked by the A1AR agonist 2-chloro-N6-cyclopentyladenosine (CCPA), while ADP effect, that is completely blocked by the P2x, P2y receptors noncompetitive antagonist suramine, is restored in the presence of the selective P2x purinoceptors agonist beta, gamma-methylene-L-ATP. These findings demonstrate that adenosine and ADP markedly inhibit the program of cell death in cerebellar granule cells and suggest that such an action is mediated via interaction with, respectively, A1 and P2x receptors.

Adenosine↗
PubMed1998

The acid activation of Helicobacter pylori toxin VacA: structural and membrane binding studies.

The cell vacuolating activity of the protein toxin VacA, released by Helicobacter pylori, is strongly increased in vitro by exposure to acidic pH followed by neutralization. This short acid exposure does not increase significantly the binding of VacA to cell or to lipid membranes. However, membrane photolabeling with photoactivatable radioactive phospholipids and ANS binding studies show that VacA transiently exposed to pH equal or lower than 5 changes conformation and exposes on its surface hydrophobic segments. Both the 32 and the 58 kDa subunits of the toxin insert in the lipid bilayer and interact with the fatty acid chains of phospholipids. Membrane binding and penetration are enhanced by incubating target cells or liposomes with the toxin at mild acidic pH values, similar to those present around H. pylori on the stomach mucosa. These findings are discussed with respect to the critical step in cell intoxication consisting in the translocation of the active toxin domain into the cell cytosol. We suggest that membrane translocation takes place at the plasma membrane level.

Affinity Labels↗
PubMed1998

The beta-oxidation of arachidonic acid and the synthesis of docosahexaenoic acid are selectively and consistently altered in skin fibroblasts from three Zellweger patients versus X-adrenoleukodystrophy, Alzheimer and control subjects.

The beta-oxidation of [3H] arachidonic acid (AA; 20:4 n-6) and the conversion of [1-14C]eicosapentaenoic acid (EPA, 20:5 n-3) to docosahexaenoic acid (DHA, 22:6 n-3) have been studied in skin fibroblasts from patients with inherited peroxisomal diseases, such as Zellweger (ZW) and X-linked adrenoleukodystrophy (X-ALD), from patients with Alzheimer's disease (AD), a non-inherited neuropathology, and from controls. EPA is not converted to DHA, while there is enhanced formation of the intermediate product 22:5 n-3 in ZW, when compared to X-ALD, AD and controls. We also confirmed that AA is not beta-oxidized to 4,7,10-hexadecatrienoic acid (16:3), a metabolite produced by peroxisomes, while being more effectively converted to the elongation product 22:4, in ZW, in comparison to X-ALD, AD and controls. The data demonstrate a defect in DHA synthesis and in AA beta-oxidation, and the occurrence of associated adaptative modifications in the metabolism of these long chain PUFA, in three Italian ZW patients.

Adrenoleukodystrophy↗
PubMed1998

Free radical-scavenging properties of olive oil polyphenols.

Plants in the Mediterranean basin, such as vine and olive trees, have developed an array of antioxidant defences to protect themselves from environmental stress. Accordingly, the incidence of coronary heart disease and certain cancers is lower in the Mediterranean area, where olive oil is the dietary fat of choice. As opposed to other vegetable oils, extra virgin olive oil, which is obtained by physical pressure from a whole fruit, is rich in phenolic components that are responsible for the particular stability of the oil. We have investigated the scavenging actions of some olive oil phenolics, namely hydroxytyrosol and oleuropein, with respect to superoxide anion generation, neutrophils respiratory burst, and hypochlorous acid. The low EC50S indicate that both compounds are potent scavengers of superoxide radicals and inhibitors of neutrophils respiratory burst: whenever demonstrated in vivo, these properties may partially explain the observed lower incidence of CHD and cancer associated with the Mediterranean diet.

Antioxidants↗
PubMed1998

Oxidation of individual fatty acids yields different profiles of oxidation markers.

Free radicals attack lipid molecules and initiate a chain of reactions that may trigger several diseases such as atherosclerosis and cancer. Several markers of oxidative stress have been proposed, including measurements of lipid peroxides and short-chain aldehydes levels and evaluation of conjugated diene formation. Although it is generally assumed that fatty acid oxidizability is directly proportional to their degree of unsaturation, little is known about the contribution of individual fatty acids to each of these markers. We investigated such contributions in a model of AAPH-mediated peroxidation of individual fatty acid micelles by assessing several indices of oxidative stress. The results suggest that the generation of oxidation products by individual fatty acids is not directly related to their degree of unsaturation and indicate that the differential contribution of individual fatty acids should be taken into account and more than one marker of lipid peroxidation should be included in in vivo studies of oxidative stress.

Amidines↗
PubMed1998

Increased amyloidogenic secretion in cerebellar granule cells undergoing apoptosis.

Some clues suggest that neuronal damage induces a secondary change of amyloid beta protein (Abeta) metabolism. We investigated this possibility by analyzing the secretion of Abeta and processing of its precursor protein (amyloid precursor protein, APP) in an in vitro model of neuronal apoptosis. Primary cultures of rat cerebellar granule neurons were metabolically labeled with [35S]methionine. Apoptosis was induced by shifting extracellular KCl concentration from 25 mM to 5 mM for 6 h. Control and apoptotic neurons were then subjected to depolarization-stimulated secretion. Constitutive and stimulated secretion media and cell lysates were immunoprecipitated with antibodies recognizing regions of Abeta, full-length APP, alpha- and beta-APP secreted forms. Immunoprecipitated proteins were separated by SDS/PAGE and quantitated with a PhosphorImager densitometer. Although intracellular full-length APP was not significantly changed after apoptosis, the monomeric and oligomeric forms of 4-kDa Abeta were 3-fold higher in depolarization-stimulated secretion compared with control neurons. Such increments were paralleled by a corresponding increase of the beta-APPs/alpha-APPs ratio in apoptotic secretion. Immunofluorescence studies performed with an antibody recognizing an epitope located in the Abeta sequence showed that the Abeta signal observed in the cytoplasm and in the Golgi apparatus of control neurons is uniformly redistributed in the condensed cytoplasm of apoptotic cells. These studies indicate that neuronal apoptosis is associated with a significant increase of metabolic products derived from beta-secretase cleavage and suggest that an overproduction of Abeta may be the consequence of neuronal damage from various causes.

Amyloid beta-Peptides↗
PubMed1998

Selective inhibition of Ii-dependent antigen presentation by Helicobacter pylori toxin VacA.

A major virulence factor in the stomach chronic infection by Helicobacter pylori is a protein toxin (VacA), which alters cell membrane trafficking of late endosomal/prelysosomal compartments. Its role in the chronic infection established by H. pylori is unknown. To test the possibility that VacA alters antigen processing taking place in prelysosomal compartments, we have used the well-established model of antigen processing and presentation consisting of tetanus toxoid-specific human (CD4(+)) T cells stimulated by autologous antigen-pulsed Epstein-Barr virus-transformed B cells. We found that VacA interferes with proteolytic processing of tetanus toxin and toxoid and specifically inhibits the Ii-dependent pathway of antigen presentation mediated by newly synthesized major histocompatibility complex (MHC) class II, while leaving unaffected the presentation pathway dependent on recycling MHC class II. The results presented here suggest that VacA may contribute to the persistence of H. pylori by interfering with protective immunity and that this toxin is a new useful tool in the study of the different pathways of antigen presentation.

Antigen Presentation↗
PubMed1998

S-adenosyl-L-methionine: role in phosphatidylcholine synthesis and in vitro effects on the ethanol-induced alterations of lipid metabolism.

Hepatic lipid metabolism is extremely modified by excessive ethanol consumption, but the cellular mechanisms of such alterations are still largely unexplored. S-Adenosyl-L-methionine (SAMe) is known as an important methylating agent and as a precursor of glutathione and it has been shown to prevent some of the toxic effects of ethanol in the liver. We therefore studied the effects of ethanol on cholesterol synthesis in a human hepatomal cell line (HepG2), the kinetics of SAMe, and its putative protective effects on the alterations of lipid metabolism induced by toxic concentrations of alcohol. Incubation of HepG2 cells with [3H]SAMe resulted in a progressive increase in the labelling of phosphatidylcholine and of its two intermediates during synthesis starting from phosphatidylethanolamine. This process is enzymatic, since it does not take place in heat-inactivated cells. Also, ethanol induced an increase in cholesterol and triglycerides syntheses and a decrease in phospholipid labelling. These alterations were not prevented by SAMe 10(-4) M, indicating that the protective effects of the drug are related to other mechanisms of action such as reduced formation of collagen, restoration of glutathione levels, and normalization of membrane functions.

Acetates↗
PubMed1998

Action site and cellular effects of cytotoxin VacA produced by Helicobacter pylori.

Cells treated with the VacA toxin from Helicobacter pylori develop large membrane-bound vacuoles that originate from the late endocytotic pathway. Using different experimental approaches, we showed that VacA can induce vacuoles by acting within the cell cytosol. Moreover, separation of VacA-induced vacuoles at an early stage of formation, using a novel isopycnic density ultracentrifugation method, allowed us to show that they resemble a hybrid compartment, containing elements of both late endosomes and lysosomes. Functional defects of the endocytotic pathway were also studied before any macroscopic vacuolation is evident. VacA-intoxicated cells degrade extracellular ligands with reduced efficiency and, at the same time, they secrete acidic hydrolases into the extracellular medium, normally sorted to lysosomes. All these findings indicate that VacA translocates into the cell cytosol where it causes a lesion of the late endosomal/lysosomal compartments, such that protein trafficking across this crucial cross-point is altered with consequences that may be relevant to the pathogenesis of gastroduodenal ulcers.

Bacterial Proteins↗
PubMed1998

Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages.

The Mediterranean diet, rich in fresh fruits and vegetables, has been associated with a lower incidence of cardiovascular disease and cancer, partly because of its high proportion of bioactive compounds such as vitamins, flavonoids and polyphenols. The major lipid component of such diet is the drupe-derived olive oil, that can be distinguished from other seed oils for the peculiar composition of its non-triglyceride fraction. In fact, several minor components, including polyphenols, grant the oil its particular taste and aroma. Oleuropein, the most abundant among these components, has been shown to be a potent antioxidant endowed with antiinflammatory properties. We investigated the effects of oleuropein on NO release in cell culture and its activity toward nitric oxide synthase (iNOS) expression. The results show that oleuropein dose-dependently enhance nitrite production in LPS-challenged mouse macrophages. This effect was blocked by the iNOS inhibitor L-NAME, indicating increased iNOS activity. Also, Western blot analysis of cell homogenates show that oleuropein increases iNOS expression in such cells. Taken together, our data suggest that, during endotoxin challenge, oleuropein potentiates the macrophage-mediated response, resulting in higher NO production, currently believed to be beneficial for cellular and organismal protection.

Animals↗