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Biomedical subjects

C Pieri

Publications and source records attributed to C Pieri.

At least 55 records · Page 3Linked to original sources
PubMed1992

A sodium channel opener inhibits stimulation of human peripheral blood mononuclear cells.

The role of membrane potential changes in T cell activation was studied on human peripheral blood lymphocytes stimulated with phytohemagglutinin. Addition of bretylium tosylate, a sodium channels opener, to PHA treated lymphocytes modified the membrane potential and consequently blocked cell activation in a dose-dependent fashion. BT was non-toxic even in long-term (72 hr) incubations. It was reversibly removable, and the removal restored the stimulatory effect of PHA. 3H-thymidine incorporation was blocked if BT was present during the first 20-24 hr of the mitogenic activation. The later BT was added after PHA, the less inhibition of proliferation was observed. BT hyperpolarized the lymphocytes also in the presence of PHA. BT hindered the depolarizing effect of high extracellular potassium concns. The sustained polarized state of the lymphocytes did not influence the intracellular calcium increase upon PHA treatment. IL-2 and transferrin receptor expression was not hindered by BT during PHA stimulation of lymphocytes. Addition of rIL-2 did not abolish the inhibitory effect of BT. According to cell-cycle analysis BT arrested the majority of the cells in G1 phase. It is suggested that cell activation demands the flexible maintenance of a relatively narrow membrane potential "window". Any sustained and significant hyper-, or depolarization, may dramatically decrease the effectivity of transmembrane signalling.

Bretylium Tosylate↗
PubMed1992

Dynamic physical interactions of plasma membrane molecules generate cell surface patterns and regulate cell activation processes.

Molecular interaction and transmembrane signal transducing events generate a very dynamic and ever changing "pattern" in the plasma membranes. Lymphocytes, the key functional elements of the immune system, are eminently suited to be the primary targets to investigate these proximity, mobility, or other physical-chemical changes in their plasma membranes. Recently, a number of experiments suggested that processed peptides from antigens can bind specific components of MHC molecules (Elliott et al., 1991). This is certainly a way to alter their structure. Cell surface patterns of topological nature, assembly and disassembly of oligomeric receptor structure like the IL-2 receptor have been investigated by sophisticated biophysical techniques. The dynamic changes in the two-dimensional cell surface pattern and intramolecular conformational changes within this "larger" macro-pattern may have a strong regulatory role in signal transducing and intercellular recognition processes. Recent data on these problems are presented together with brief and critical discussions.

Animals↗
PubMed1992

Lipid peroxidation causes an increase of lipid order and a decrease of 5'-nucleotidase activity in the liver plasma membrane.

The effect of peroxidation on 5'-nucleotidase activity as well as on membrane microviscosity has been investigated in liver plasma membranes from Wistar rats. The peroxidation was performed with 100 microM H2O2 and 200 microM FeSO4 and/or with 5 mM t-butylhydroperoxide. Treatment of the membranes with these oxidizing agents resulted in an elevation of the transition temperatures of the polarization of the lipid fluorescent probes 1,6 diphenyl-1,3,5 hexatriene (DPH), 3-p-(6-phenyl) 1,3,5 hexatriene phenylpropionic acid (PA-DPH) as well as of the fluorescent thiol reagent N-(1-pyrene) maleimide (1-PM). The peroxidation resulted in a decrease of the activity of 5'nucleotidase. Our data support that the increase of membrane microviscosity of the lipid domain regulates the activity of 5'-nucleotidase.

5'-Nucleotidase↗
PubMed1991

Electroimmunology: membrane potential, ion-channel activities, and stimulatory signal transduction in human T lymphocytes from young and elderly.

There are conflicting data on the functional role and direction of the changes in membrane potential and ion currents accompanying lymphocyte stimulation. Recently, we discovered that a known sodium channel opener, bretylium tosylate (BT), may influence the stimulatory processes of lymphocyte activation at more than one site. Parallel flow cytometric and electrophysiological measurements with patch clamp techniques showed that BT quickly repolarizes previously slightly depolarized human peripheral blood as well as splenic murine lymphocytes. The repolarization occurred through opening ligand- and voltage-gated, hitherto unknown sodium channels, and the sodium influx activated Na(+)-K(+)-dependent, electrogenic ATP-ase activity. A comparison of the flexible responsiveness of the membrane potential was carried out between lymphocytes from young and elderly using the above mechanism and a number of combinations of channel blockers and ionophores in order to obtain information on the alleged changes in immunological behavior. A significant difference has been found between lymphocytes from human young and elderly volunteers in the readiness to respond to channel-activating perturbations. An explanation is offered, based upon known physicochemical changes in the plasma membrane during aging.

Adult↗
PubMed1991

Food restriction slows down age-related changes in cell membrane parameters.

The effect of undernutrition on some plasma membrane parameters has been analyzed. Diet restriction was applied to female Wistar rats on every-other-day schedule (EOD), starting from the age of 3.5 months. Membrane microviscosity of splenic lymphocytes was lower in EOD rats than in the ad libitum (AL) fed ones even if one assumes a decrease of body temperature of 2 degrees C. The decrease of membrane microviscosity due to diet restriction ran parallel with the improvement of proliferative response of lymphocytes. The analysis of Arrhenius plots of 1,6-diphenyl-1,3,5-hexatriene as well as of 5'-nucleotidase activity showed a diet-dependent improvement of membrane properties also of liver plasma membranes. Diet restriction was able to partially recover the age-dependent decrease of beta-adrenoceptor density of cerebellar membranes. On the contrary, beta-adrenoceptor density of lymphocytes, which did not show any age-dependent alteration, was not influenced by diet restriction. Present results support that undernutrition exerted a protective effect on cell membranes of old animals and it was able to improve those alterations which are related to aging.

Aging↗
PubMed1991

Reversibility of age associated NK defect by endocrinological and/or nutritional intervention.

Several abnormalities arise at the level of NK cell function in both rodents and humans with increasing age. The age-related changes are not irreversible alterations since they can be reversed either by endocrinological or nutritional approaches, suggesting that age-related microenvironmental changes may play a relevant role in the age-related immune deterioration. Whether endocrine and nutritional factors have an additive effect or act through the same intracellular mechanisms remains to be established, though the first possibility seems more likely since the action of TSH and thyroid hormones is specifically directed towards lymphokine-boosted NK activity, while AL are able to prevent age-associated defect of basal NK cytotoxicity.

Aging↗
PubMed1991

Influence of membrane fluidity of 5'-nucleotidase activity in isolated hepatocyte plasma membrane.

The influence of membrane microviscosity on 5'-nucleotidase activity has been investigated on liver plasma membrane preparations from rats during aging and following diet restriction. In addition the microviscosity of membranes from old rats was changed in vitro by the Active Lipids. During aging the membrane microviscosity increased progressively and in parallel the activity of 5'-nucleotidase decreased. Diet restriction was able to slow down the modification of both parameters. The experiment performed with the Active Lipids further supports that membrane microviscosity modulated the enzyme activity.

5'-Nucleotidase↗
PubMed1990

Voltage gating of Ca2(+)-activated potassium channels in human lymphocytes.

The effect of membrane potential on Ca2+ activated K+ channels was studied on human peripheral lymphocytes. Membrane potential was monitored using bisoxonol and flow cytometry. 1 mM Ca2+ in the presence of 2 microM ionomycin depolarized the control cell population, while 100 microM Ca2+ caused hyperpolarization. However 1 mM Ca2+ had a hyperpolarizing effect on previously partially depolarized cells. Potassium channel blockers did not influence the depolarization, while they inhibited the hyperpolarization. Based on the experimental evidence a voltage gating of Ca2+ activated K+ channels is suggested.

Calcium↗
PubMed1990

Improvement of natural killer cell activity by in vitro active lipids (AL 721) administration in old mice.

Results of several experiments have given rise to the hypothesis that the decline of the immunocompetence with aging is at least in part related to alterations of the lipid membrane composition and, consequently, to a decrease in membrane fluidity. The age-dependent decline of mitogen responsiveness can, in fact, be reversed by a special lipid mixture designated as active lipids (AL 721), which acts by means of its fluidizing action on the plasma membrane. The purpose of this study was to examine the possibility of raising the low endogenous levels of Natural Killer (NK) activity by in vitro AL administration in old mice. When spleen cells from old mice were incubated in vitro with AL, a significant increase in cytotoxic activity was obtained over control cultures, without reaching, however, the levels observed in young mice. In spleen cells from young mice, the AL administration causes a slight augment of NK basal activity. These results suggest that cell membrane fluidity plays an important role in the efficiency of NK cells, giving support to the hypothesis that a rectification of rigidified cell membranes may represent a valuable approach to restore proper physiological functions in old age.

Aging↗
PubMed1990

Bretylium causes a K(+)-Na+ pump activation that is independent of Na+/H+ exchange in depolarized rat, mouse and human lymphocytes.

We have studied a bretylium tosylate induced increase of the membrane potentials of partially depolarized rat, mouse and human lymphocytes, using the potential sensitive dye, bis [1,3, dibutylbarbituric acid-(5) trimethine oxonol]. The extent of this repolarization is dose-dependent and decreased in magnitude as the temp was reduced from 37 degrees C to room temp. The repolarizing effect is inhibited by K(+)-Na(+)-pump blockers or lack of extracellular Na+. Sodium ion channel blockers are effective in abolishing repolarization only if applied prior to, or simultaneously with, bretylium. Activation of Na+/H+ exchange is not involved in the mechanism of the phenomenon as the latter is completely eliminated in the presence of 10 microM amiloride (concn of the diuretics having no measurable inhibition on the action of the exchanger). These data suggest that bretylium opens ligand- and voltage-gated Na+ channels, and repolarization occurs due to higher activity of the K(+)-Na(+)-pump stimulated by the enhanced intracellular Na+ accumulation.

Animals↗
PubMed1990

Antioxidant enzymes in erythrocytes from old and diet restricted old rats.

Diet restriction, prolonging the lifespan of rodents, represents an interesting model for gerontological studies. We analyzed the activity of antioxidant enzymes, Superoxide Dismutase, Catalase and Glutathione Peroxidase in erythrocytes from young, old and old food restricted Wistar rats. Diet restriction was applied feeding the animals on every-other-day schedule starting from the age of 3.5 months. The age-dependent decrease of Catalase and Glutathione Peroxidase activities was prevented by food restriction, whereas Superoxide Dismutase activity was not influenced either by aging and dietary intervention. Present results support the hypothesis that diet restriction increases the protection of cell structure against the peroxidative damage, preserving the activity of antioxidant enzymes.

Aging↗
PubMed1990

Diet restriction decreases the membrane microviscosity of cerebellar membranes of old female Wistar rats.

The microviscosity of cerebellar membranes from female Wistar rats during aging and subsequent to diet restriction has been investigated. Diet restriction was applied feeding the animals on every-other-day schedule starting from the age of 3.5 months. Undernutrition increased the lifespan of the animals and retarded the appearance of the age-dependent increase of microviscosity of cerebellar membranes.

Aging↗
PubMed1990

Improvement of decreased natural killer cell activity in cervical cancer patients by active lipids (AL 721).

In the present study we observed the absolute number of NK cells and the NK activity in 10 patients with cervical cancer. NK activity was determined before and after stimulation with Active Lipids. We reported a significant decrease of basal NK activity, but after AL stimulation NK activity was increased with statistical significance. Therefore our findings show that the reduction of NK activity in neoplastic patients is not an irreversible phenomenon since it can be restored by "in vitro" AL administration. This is important for the adoptive immunotherapy by which we could give LAK cells to the patients.

Drug Combinations↗
PubMed1989

Ligand and voltage gated sodium channels may regulate electrogenic pump activity in human, mouse and rat lymphocytes.

Bretylium tosylate - a sodium channel opener - resulted in an increase of membrane potential of depolarized human, rat and mouse T and B lymphocytes. Flow cytometric membrane potential measurements with bis-oxonol revealed that the above hyperpolarizing effect was amiloride, ouabain, tetrodotoxin, azide and temperature sensitive. The effect showed an absolute dependence on the extracellular sodium but it was insensitive to the extracellular Ca2+ level. The voltage gating of the effect can be eliminated by either an increase of the extracellular potassium concentration or low doses of veratrin. The existence of a voltage and ligand gated sodium channel is suggested in the plasma membrane of all kinds of lymphocytes. The hyperpolarization is explained by an increased activity of the electrogenic sodium-potassium ATP-ase. Induced opening of such sodium channels may regulate the electrogenic pump activity and indirectly cell activation.

Amiloride↗
PubMed1989

Chronic dietary choline influences the permeability of nerve cell membranes as revealed by in vivo Rb+ uptake and release.

The effect of chronic choline supplementation on the in vivo Rb+ uptake and release of rat brain cortical cells was investigated. Adult (11 months old) and old (22 months old) controls as well as old (22 months old) female rats treated with choline (approximately 100 mg/day in the drinking water) by the age of 11 months, were used. All the animals received a daily dose of 30 mg RbCl/100 g body weight for 14 days, given intraperitoneally, half in the morning, half in the evening. After discontinuation of the RbCl treatment, the animals were killed at intervals of 2, 4, 9 and 16 days, respectively. The intracellular Rb+ and K+ contents were analyzed by energy dispersive X-ray microanalysis, whereas concentrations of these two elements were determined by atomic absorption spectrophotometry in the cerebrospinal fluid. Old animals accumulate more Rb+ than the adult ones at any time taken into account. Choline treatment was able to reduce the amount of accumulated Rb+ in the old rats. Rb+-discrimination ratios calculated on the basis of Rb+ and K+ contents of both cortical cells and cerebrospinal fluid, is higher in old rats as compared to both adult and old choline treated rats. Present findings support that chronic choline treatment is effective improving the passive membrane permeability of nerve cells for Rb+ (and K+) in the old animals.

Animals↗
PubMed1989

Chronic choline treatment improves the "in vivo" membrane permeability of old hepatocytes to Rb+.

Adult and old controls as well as old female rats, treated with choline (100 mg/day in the drinking water) from adulthood, were daily injected intraperitoneally with 30 mg RbCl/100 g body with Rb+. After cessation of the RbCl treatment, the animals were killed at intervals of 2, 4, 9 and 16 days, respectively. The intracellular Rb+ and K+ contents were analyzed by energy dispersive X-ray microanalysis, whereas concentrations of these two ions were determined by atomic absorption spectrophotometry in the serum. Old animals accumulate more Rb+ than the adult ones at any given time. Choline treatment was able to reduce the amount of accumulated Rb+ in old rats. Rb(+)-discrimination ratio, calculated on the basis of Rb+ and K+ contents of both hepatocyte and serum, is higher in old rats as compared to both adult and old choline-treated rats. Present findings support that chronic choline treatment is effective in improving the passive membrane permeability of hepatocytes for Rb+ in the old animals.

Age Factors↗