Search PubMed⌕ Search

Biomedical subjects

C Tortorella

Publications and source records attributed to C Tortorella.

At least 73 records · Page 4Linked to original sources

Investigations on the acute effects of neuropeptides on the pituitary-adrenocortical function in normal and cold-stressed rats. II. Neurotensin and neuromedin N.

The effects of a subcutaneous bolus injection of 2 micrograms neurotensin (NT) or neuromedin N (NMN) on the function of the hypothalamo-pituitary-adrenocortical axis were investigated in both normal and cold-stressed rats. The blood concentrations of ACTH, corticosterone (B) and aldosterone (ALDO) were measured by specific radioimmunoassays 1, 2 or 4 h after the neuropeptide administration. Cold stress enhanced plasma levels of ACTH, B and ALDO, and these rises lasted unchanged until 4 h. NT did not affect either basal or stress-stimulated plasma levels of ACTH and B, while it lowered the plasma ALDO concentration at 4 h in normal rats and increased it at 1 h in stressed animals. NMN did not change the basal plasma level of ACTH, but it did markedly raise blood levels of both B and ALDO; on the other hand, in cold-stressed rats NMN strongly depressed ACTH response and decreased B plasma concentration at 2 h, without evoking apparent changes in ALDO response. In light of these findings the following conclusions and hypotheses can be drawn and suggested: (i) NT and NMN, when administered at a relatively high dose, do not affect ACTH release in rats under basal conditions; (ii) NMN, but not NT, is able to prevent cold stress-induced stimulation of ACTH secretion, probably by inhibiting hypothalamic thermoregulatory centers; and (iii) NT and NMN exert direct adrenocortical antisecretagogue and secretagogue effects, respectively, which could explain the evident lack of correlation between the levels of circulating ACTH and the plasma concentrations of the main adrenal steroid hormones in both normal and stressed rats after neuropeptide administration.

Adrenocorticotropic Hormone↗

Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact: a possible role for membrane-associated interleukin-6 and interleukin-8.

Polymorphs (PMN) and monocytes/macrophages (Mo) play a very important role in the host defence since they participate to inflammatory processes, tissue repairing and antitumor activity. Previous studies showed that lipopolysaccharide (LPS)-activated Mo are able to upregulate PMN phagocytic ability via cell-to-cell contact mechanisms mediated by bound to Mo membrane (m) cytokines (CKs), such as Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-1 alpha and IL-1 beta. Based on these grounds, the role of Mo m-associated IL-6 and IL-8 on the modulation of PMN activity has been evaluated. In the first step, PMN incubated with lipid A (LA)-activated Mo showed an increased phagocytosis dependent on cell-to-cell contact only. In the second step, LA-activated Mo were pretreated with antirecombinant human (Rhu) IL-6 and IL-8 monoclonal antibodies (MoAbs), respectively and, in such a way, the enhanced phagocytic activity of PMN was abrogated. In the third step, PMN incubated with LA-activated supernatants (AS) from PBMC cultures exhibited an enhanced phagocytic activity, that was abrogated when LA-AS were pretreated with anti-Rhu IL-6 and anti-Rhu IL-8 MoAbs, respectively. These data suggest that IL-6 and IL-8 associated to Mo membrane may modulate PMN activation through a cell-to-cell contact dependent pathway.

Adult↗

Effects of in vitro nutrient supplementation on polymorphonuclear cell respiratory burst in primary IgA nephropathy.

Since recent findings have pointed out a key role for reactive oxygen species in kidney diseases, we investigated superoxide anion (O2-) and hydrogen peroxide (H2O2) generation by peripheral blood polymorphonuclear cells (PMN) in 20 patients with primary IgA nephropathy (IgAN). Results provided evidence for a significant enhancement of O2- and H2O2 production in IgAN subjects in comparison to patients affected by hypertensive renal injury and healthy donors. Among the IgAN group, the highest oxidative metabolism was observed in patients with severe histologic lesions. On the other hand, in vitro vitamin and/or trace element supplementation to PMN suspensions led to a down modulation of their oxidative responsiveness. These data were further supported by the assessment of O2- release on a kinetic basis. Nutrient pretreatment was in fact able to antagonize either the IgAN-related shortening of the lag period or the increase of maximum O2- production rate following agonist stimulation. Taken together, these findings indicate that an exaggerated PMN oxidative metabolism occurs in IgAN and suggest a potential role for micronutrients in the modulation of PMN metabolic pathway.

Adolescent↗

Alteration of mitochondrial bioenergetics due to intravenous injection of a perfluorocarbon emulsion.

Wistar albino rats were intravenously injected with 1 ml of an oxyphoretic emulsion of perfluorobutyl-furane and killed 3, 7 or 30 days later. Mitochondria isolated from the liver and kidneys of treated rats showed a small decrease in the transmembrane electrical potential and a substantial depression of the rates of both ATP synthesis and ADP-stimulated respiration. These alterations in mitochondrial oxidative phosphorylation appear to be induced by perfluorocarbon and/or tensioactive molecules interacting with hydrophobic cell structures.

Adenosine Triphosphate↗

Proton magnetic resonance spectroscopy in patients with ischemic stroke.

Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive technique which has proved to be useful for monitoring various brain metabolites (N-acetyl-aspartate, choline, creatine-phosphocreatine, lactate). A total of 18 patients underwent a combined magnetic resonance imaging (MRI)/1H-MRS protocol in order to evaluate the distribution of the metabolites in the various stages of cerebral ischemia. Our results show a marked decrease of N-acetyl-aspartate and a large content of Lactate during the early phases, and a decrease in N-acetyl-aspartate, choline and creatine-phosphocreatine (Cr-PCr) during the chronic phase.

Adult↗

Effects of neuromedin U (NMU)-8 on the rat hypothalamo-pituitary-adrenal axis. Evidence of a direct effect of NMU-8 on the adrenal gland.

A 6-day subcutaneous (s.c.) treatment of adult rats with NMU-8 (1.5 or 6 micrograms/100 g/day) increased the average volume of zona fasciculata cells and decreased the number of zona reticularis cells in the adrenal cortex. The lower dose of NMU-8 did not change blood ACTH concentration and adrenal weight, but it notably enhanced serum corticosterone level and basal corticosterone output by adrenal slices. ACTH blood level increased after ether stress in both control and NMU-8-treated rats, but stress-evoked rise in serum corticosterone was observed only in control rats. The higher dose of NMU-8 increased the level of circulating ACTH; however, it decreased adrenal weight and had no effect on serum corticosterone concentration and basal corticosterone output by adrenal slices. NMU-8 (10(-10)/10(-6) M) did not affect basal and ACTH-stimulated corticosterone yield by isolated adrenocortical cells, nor did it change their cytosolic Ca2+ concentration. NMU-8 (10(-8) M) markedly raised basal corticosterone secretion by adrenal slices (including cortex and medulla); higher concentrations of NMU-8 (10(-7)/10(-6) M) were ineffective on basal corticosterone secretion, but strongly inhibited the response to ACTH stimulation. On the ground of these findings it seems reasonable to suggest that NMU-8 exerts a biphasic effect on the function of the peripheral branch of the hypothalamo-pituitary-adrenal axis in rats: NMU-8 at low doses directly stimulates the function and growth of the adrenal cortex, while at high doses exerts a direct inhibitory action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Evidence that endogenous vasoactive intestinal peptide (VIP) is involved in the regulation of rat pituitary-adrenocortical function: in vivo studies with a VIP antagonist.

The effect of a subcutaneous bolus injection of 2 micrograms magnitude of Ac,Tyr1,D-Phe2-GRF(1-29) amide, a specific VIP antagonist (VIP-A), on the hypothalamo-pituitary-adrenocortical (HPA) axis were investigated in both normal and ether- or cold-stressed rats. Blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA 1, 2 or 4 h after VIP-A injection. VIP-A administration to normal rats strikingly lowered the plasma concentration of ALDO, without significantly affecting those of ACTH and B. Ether and cold stresses notably raised the blood levels of ACTH, ALDO and B, and these rises lasted unchanged until 4 h. VIP-A did not affect the response of HPA axis to ether stress, but provoked a marked depression of that to cold stress. In light of these findings the following conclusions can be drawn: (i) endogenous VIP does not regulate HPA-axis function under basal conditions, but it plays a pivotal role in the mechanisms involved in the activation of HPA axis induced by cold exposure; and (ii) endogenous VIP exerts a tonic stimulatory action on ALDO secretion, probably by acting directly on the adrenal zona glomerulosa.

Adrenal Cortex↗

Evidence that endogenous vasoactive intestinal peptide (VIP) plays a role in the maintenance of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

The effects of a 7-day intraperitoneal infusion with VIP (0.03 nmol.kg-1.min-1) and its antagonist [4-Cl-D-Phe6,Leu17]-VIP (VIP-A; 3 nmol.kg-1.min-1) were studied in sham and bilaterally adrenalectomized rats bearing ACTH and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. VIP significantly increased plasma aldosterone (ALDO) concentration (PAC) and lowered plasma renin activity (PRA) in both groups of animals, without affecting plasma levels of ACTH and corticosterone. This treatment caused a marked hypertrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells (without inducing any significant change in the zona-fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant quarters obtained from VIP-infused rats evidenced a notable increase in both their basal and maximally ACTH- or ANG-II-stimulated ALDO secretion. The simultaneous infusion of rats with VIP-A completely reversed all these effects of VIP. The infusion with VIP-A alone caused, in sham-operated rats, a net decrease in PAC, coupled with a rise in PRA, and a marked atrophy of ZG and ZG cells; basal and maximally stimulated ALDO secretion of dispersed ZG cells was also significantly lowered. Conversely, VIP-A did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous VIP is specifically involved in the maintenance of the growth and secretory capacity of rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to VIP but not to VIP-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal medulla may be the source of endogenous VIP regulating ZG function.

Adrenocorticotropic Hormone↗

Effects of cyclosporine-A on steroid secretion of dispersed rat adrenocortical cells.

The acute effect of cyclosporine-A (CSA), a potent immunosuppressive agent, on the secretory activity of dispersed rat adrenocortical cells was investigated. The production of the following steroid hormones was assayed by high performance liquid chromatography: pregnenolone (PREG), progesterone (PROG), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO); B and ALDO outputs were also measured by radioimmunoassay. Low concentrations of CSA (0.1-0.2 mg/ml) enhanced basal, but not ACTH- or angiotensin-II (ANG-II) 10(-8) M-stimulated, secretions of PREG, non-18-hydroxylated steroids (PROG, DOC and B) and 18-hydroxylated steroids (18OH-DOC, 18OH-B and ALDO) of both zona glomerulosa (ZG) and zonae fasciculata and reticularis (ZF/ZR) cells. Middle concentrations of CSA (from 0.3 to 0.5 mg/ml) did not affect PREG yield, nor did they alter basal and ACTH-stimulated post-PREG output of both ZG and ZF/ZR cells; however, they elicited a marked decrease in ANG-II-enhanced production of 18-hydroxylated steroid by AG cells. Concentrations of CSA higher than 0.5 mg/ml strikingly reduced either basal and agonist-stimulated over-all steroidogenesis of both ZG and ZF/ZR cells. These findings suggest that CSA at low concentrations strongly stimulates the conversion of cholesterol to PREG (i.e. the rate-limiting step of steroidogenesis), while at middle concentrations it did not affect this early step, but specifically interferes with the intracellular events which transduce the stimulatory signal of ANG-II on the late steps of mineralocorticoid production (i.e. the conversion of B to ALDO). At higher concentrations, CSA probably exerts a cytotoxic effect.

Adrenal Cortex↗

Age-associated changes of neutrophil responsiveness in a human healthy elderly population.

Conflicting results have been reported on polymorphonuclear (PMN) cell responsiveness during senescence. Consequently, neutrophil absolute numbers and PMN-mediated chemotaxis, phagocytosis, killing and superoxide anion (O2-) generation in healthy aged volunteers divided into different groups according to increasing age criteria, were investigated and evaluated. Data provide evidence that absolute amounts of PMN cells declined in a significant manner in donors over 85 years old only when compared with young subjects. On the contrary, regardless of age, the aged individuals exhibited a significant impairment of PMN chemotactic, phagocytic and killing functional capacities. Finally, formyl-methionyl-leucyl-phenylanaline (FMLP)-triggered O2- release was reduced in all elderly groups, while depression of O2- production was seen in subjects between the age of 86 and 104 years using phorbol 12-myristate 13-acetate (PMA) as agonist. These findings indicate that an imbalance in the PMN cell immune reactivity occurs throughout the senescence process.

Adult↗

Modulation of pokeweed mitogen-induced B cell differentiation by polymorphonuclear cells: effects of bacterial lipopolysaccharides.

The capacity of polymorphonuclear (PMN) cells to release several cytokines stresses the potential immunomodulatory role of these cells. The effects mediated by purified PMN cell suspensions on pokeweed mitogen (PWM)-driven B cell differentiation was investigated. Results showed that the addition of increasing concentrations of resting PMN cells to peripheral blood mononuclear cell (PBMC) cultures gave rise to inhibition of immunoglobulin (Ig) production. At the same time, similar results were obtained using lipopolysaccharide (LPS)-pretreated PMN cells. In contrast, when LPS, at different concentrations, and PMN cells were both added to PBMC cultures an enhancement of IgG or IgM release in comparison with cultures treated with PMN cells only occurred at low PMN cell/PBMC ratios (1:20 and 1:10), which was maximal in the presence of 10 or 100 ng/ml LPS. This effect was probably mediated by LPS-induced monocyte stimulation, since the supplementation of LPS-activated monocyte supernatants to PMN cell/PBMC cocultures led to an Ig synthesis which mimicked that seen in similarly-treated PBMC cultures. These data suggest the occurrence of various in vitro modulatory effects in the interactions between PMN, LPS and lymphocytes in a PWM-induced B cell polyclonal responsiveness system.

B-Lymphocytes↗

In vitro vitamin E and selenium supplementation improves neutrophil-mediated functions and monocyte chemoattractant protein-1 production in the elderly.

The in vitro effects of vitamin E and selenium on either polymorphonuclear cell (PMN)-mediated chemotaxis and phagocytosis or monocyte chemoattractant protein-1 (MCP-1) production in 21 well-nourished elderly donors were evaluated. Results show that, before treatment, old subjects were characterized by a decrease of both PMN functions and cytokine (CK) release. By contrast, in vitro vitamin E and selenium supplementation was able to enhance significantly the depressed PMN activities and MCP-1 synthesis. These findings suggest a role for both nutrients in the modulation of impaired phagocyte responsiveness during senescence.

Aged↗

Pancreatic polypeptide stimulates corticosterone secretion by isolated rat adrenocortical cells.

Pancreatic polypeptide (PP) dose-dependently enhanced both basal and submaximally ACTH-stimulated corticosterone production by dispersed zona fasciculata/reticularis cells of the rat adrenal gland. Conversely PP did not affect either basal or ACTH- and angiotensin-II-stimulated aldosterone and corticosterone secretion of zona glomerulosa cells. These findings could throw light on the physiological significance of the marked increase in the pancreatic release of PP during stresses.

Adrenocorticotropic Hormone↗

Relationship between respiratory burst and adhesiveness capacity in elderly polymorphonuclear cells.

Polymorphonuclear cell (PMN) activation was assessed in 30 aged donors, in terms of either adherence to different substrates or superoxide anion (O2-) generation by adhering and suspended cells in response to several agonists. Results showed that PMN in suspension from elderly individuals displayed a phorbol 12-myristate 13-acetate (PMA)-triggered O2- responsiveness which overlapped that seen in the younger counterpart, while a significant decrease of respiratory burst was observed in the presence of formyl-methionyl-leucine-phenylalanine (FMLP). Moreover, in spite of a normal nylon fiber adhesiveness, aged individuals exhibited a reduced PMN adherence to foetal calf serum (FCS)-coated plastic surfaces by using either PMA or FMLP as stimulant. However, elderly adhering cells produced higher amounts of O2- than homologous neutrophils in suspension. Cell pretreatment with anti-CD11b, anti-CD11c and anti-CD18 antibodies led to a further inhibition of PMN adhesion to FCS-coated plates. By contrast, under the same experimental conditions, O2- generation from adhering cells was reduced by using anti-CD18 antibody only. Altogether, these findings provide additional evidence for an imbalance of PMN-mediated functions in the elderly.

Adult↗

Polymorphonuclear cell-mediated phagocytosis and superoxide anion release in insulin-dependent diabetes mellitus.

It is well known that patients with insulin-dependent (or type I) diabetes mellitus are at high risk for bacterial infections. Since conflicting results have been reported on non-specific immune responses in type I diabetes, polymorphonuclear cell (PMN)-mediated phagocytosis and superoxide anion (O2-) generation in a group of individuals with well-controlled type I diabetes mellitus were assessed. Results showed that diabetic subjects were characterized by a significant impairment of phagocytic capacity when compared with healthy donors, while O2- release mimicked that seen in controls. Cell pretreatment with beta-hydroxybutyric acid (beta-HB) gave rise to a significant reduction in either phagocytosis or O2- production by PMN from type I diabetic individuals. Finally, beta-HB and glucose mixture supplementation to PMN suspensions did not induce any modification of their functional activities in comparison with those exerted by cells treated with beta-HB only. A disease-related or beta-HB-mediated PMN dysfunction in insulin-dependent diabetes mellitus is indicated.

3-Hydroxybutyric Acid↗

Biochemical and morphological observations on rat liver and kidneys six months after intravenous injection of a perfluorocompound emulsion.

The histological appearance of liver and kidneys and the energy metabolism of isolated liver and kidney mitochondria were evaluated in rats 6 months after intravenous administration of 1 ml of a perfluorocompound emulsion. Both liver and kidney specimens showed neither significant histological alteration nor the presence of intracytoplasmic perfluorocompound particles. A substantial depression of the rate of ATP synthesis was observed both in liver and kidney isolated mitochondria (with respect to control mitochondria) although the magnitude of the transmembrane electrical potential was unaltered. The depression of ATP synthesis in mitochondria isolated from perfluorocompound-treated rats appeared then unrelated to the presence of perfluorocompound micelles within the cells, and might result from the interaction of either the perfluorocompound or the emulsifying agent with the mitochondrial ATP synthetase.

Adenosine Triphosphate↗

Thymostimulin administration modulates polymorph metabolic pathway in patients with chronic obstructive pulmonary disease.

Several studies outline the imbalance of phagocyte functions in chronic obstructive pulmonary disease (COPD). In this regard, here, we have assessed either monocyte- and polymorphonuclear cell (PMN)-mediated chemotactic, phagocytic and killing capacities or PMN-triggered metabolic pathway in a group of COPD patients before and at different times after thymostimulin administration. Before therapy, an increase of O2-generation and a decrease of myeloperoxidase release were found in these individuals when compared to controls. Moreover, a reduction of either PMN-mediated chemotaxis and killing or monocyte chemotactic capacities was observed. By contrast, no differences were seen in terms of beta-glucuronidase release, monocyte-mediated killing and PMN or monocyte phagocytic function. During a one-year monitoring following immunotherapy, O2- production and myeloperoxidase activity fell within normal values, while phagocyte functional capacities were unaffected by such a treatment. Furthermore, COPD subjects exhibited a significant improvement of their clinical status as assessed during a one-year followup. All together, these findings suggest a potential role for thymostimulin in the treatment of COPD patients.

Adjuvants, Immunologic↗