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Biomedical subjects

M Del Rio

Publications and source records attributed to M Del Rio.

46 records · Page 3Linked to original sources

Age-related changes in specificity of human natural autoantibodies to thyroglobulin.

We have analysed the epitopic and idiotypic specificity of thyroglobulin antibodies in infants, young adults, aged subjects and pregnant women in order to evaluate the changes that occur in the autoantibody repertoire with age in physiological situations. No increase in IgG anti-Tg autoreactivity in whole serum and purified IgG from serum was observed with aging. However, IgG from elderly individuals exhibited increased reactivity, as compared to other groups of donors, against particular epitopes commonly recognized by both natural and disease-associated Tg-autoantibodies. The acquisition of a distinct epitopic reactivity in aged individuals suggests that qualitative rather than quantitative criteria could characterize alteration in regulation of the autoreactive B-cell repertoire that occurs with aging. No correlation was observed between the age of the donors and expression of a thyroid disease-associated idiotype (T44 Id) by hTg-autoantibodies. The expression of T44 Id on IgG obtained from serum of a small number of pregnant women may be an effect of the modifications of immune system function in pregnancy, which could lead to increased incidence of autoimmunity during pregnancy or in the post-partum period.

Adult↗

Effects of indapamide on vascular reactivity in hypercholesterolemic rabbits.

We tested the effects of indapamide (IND), an antihypertensive drug, on the contractile responsiveness of femoral and mesenteric arteries isolated from rabbits fed with a 1% cholesterol diet for 16 weeks. IND (0.1, 0.3, 1 mg/kg/day) was given to the experimental groups of rabbits, whereas control groups received either a standard or a cholesterol-enriched diet. Contractions caused by submaximal doses of norepinephrine (NE) or high-K were significantly decreased in the femoral artery of untreated hypercholesterolemic rabbits. The responses to NE(10(-6) M) or to KCI (80 mM) expressed as a percentage of the control group (standard diet) contractions were 77.0 +/- 3.3% and 55.0 +/- 4.2%, respectively. Vascular reactivity was preserved in the rabbits fed the atherogenic diet supplemented with IND in a concentration-dependent manner. In addition, in the experimental groups dose-response curves to NE (10(-8) to 10(-4) M) and to KCI (20-120 mM) were shifted upward and to the left with respect to the control hypercholesterolemic group. In the mesenteric artery (fifth branch) NE- and K-induced contractions were not significantly altered by hypercholesterolemia. We conclude that IND treatment may prevent femoral arteries from a loss of reactivity probably by reducing the severity of atherosclerosis.

Animals↗

Stimulation of murine peritoneal macrophage functions by neuropeptide Y and peptide YY. Involvement of protein kinase C.

The peptides neuropeptide Y (NPY) and peptide YY (PYY) at concentrations from 10(-12) M to 10(-8) M have been shown in this study to stimulate significantly, in vitro, several functions of resting peritoneal macrophages from BALB/c mice: adherence to substrate, chemotaxis, ingestion of inert particles (latex beads) and foreign cells (Candida albicans), and production of superoxide anion measured by nitroblue tetrazolium reduction. A dose-response relationship was observed, with a maximal stimulation of the macrophage functions studied at 10(-10) M. These effects seem to be produced by specific receptors for the neuropeptides studied in peritoneal macrophages. Whereas the two peptides induced no change of intracellular cyclic AMP, they caused a significant stimulation of protein kinase C (PKC) in murine macrophages. These results suggest that NPY and PYY produce their effects on macrophage function through PKC activation.

Animals↗

Modulation of phagocytic function in murine peritoneal macrophages by bombesin, gastrin-releasing peptide and neuromedin C.

Bombesin, as well as the two mammalian bombesin-like peptides gastrin-releasing peptide and neuromedin C, have been shown in this study to stimulate in vitro all steps of the phagocytic process in murine peritoneal macrophages: adherence to substrate, chemotaxis, ingestion of cells (Candida albicans) and inert particles (latex beads), and production of superoxide anion as measured by nitroblue tetrazolium reduction. A dose-response relationship was observed, with maximal stimulation of phagocytic process between 10(-12)M and 10(-9)M. Gastrin-releasing peptide (GRP) and neuromedin C caused a higher activation of adherence, chemotaxis and ingestion of C. albicans than bombesin. The three neuropeptides induced in murine macrophages a significant, but transient, increase of inositol 1,4,5-trisphosphate (IP3) levels at 60 seconds. On the contrary, these neuropeptides produced a rapid, transient and significant decrease of cAMP at 30 seconds. These results suggest that there are close relations between IP3 and cAMP messenger systems and the phagocytic process in murine peritoneal macrophages when these cells are incubated in the presence of bombesin, GRP or neuromedin C.

Animals↗

The effects of cyclophosphamide on the toxicity and immunogenicity of ricin A chain immunotoxin in rats.

We conducted a study to determine if treatment with cyclophosphamide (CY) could suppress the formation of anti-murine and anti-ricin A chain antibodies in rats treated with a murine monoclonal antibody-ricin A chain immunotoxin (IT). Female Sprague-Dawley rats received intravenous doses of IT at a dose of 5 mg/kg body weight alone or in combination with CY at a dose level of either 10 or 20 mg/kg body weight. The IT was given as one or two courses consisting of five consecutive daily intravenous injections (days 0 to 4, or days 0 to 4 and days 21 to 25 of the study). Cyclophosphamide was given on days 2, 4, 6, 13, and 17 of the study to the group receiving a single course of IT; additional doses of CY were administered on days 23, 25, and 27 to the group receiving two courses of IT. On days 4, 14, 21, 28, and 35, animals from each group were evaluated for antibodies to murine IgG and ricin A chain, and for clinical laboratory parameters and histopathology. Animals receiving IT alone developed significant titers of both anti-murine and anti-ricin A chain antibodies. Compared with the response in the animals receiving single-course IT, the response to both of the components of the IT was significantly increased on days 28 and 35 in the animals receiving a second course of IT. The groups receiving a combination of either one or two courses of CY and IT demonstrated a significantly decreased antibody response to both the murine IgG and the ricin A chain compared with the group receiving IT alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunohistochemical demonstration of a mRNA-transport protein in rat liver putative preneoplastic foci.

A 65K protein, known for promoting nucleocytoplasmic mRNA transport in a cell-free system, was previously found in fetal and tumor cells of the rat. The primary objective of this study was to show specificity of immunohistochemical staining for the 65K protein in the livers of rats subjected to a hepatocarcinogenesis protocol. Altered hepatic foci were induced by feeding male weanling Sprague-Dawley rats 2-acetylaminofluorene (AAF) followed by a phenobarbital (PB) diet. It was shown, using polyclonal antibodies produced in rabbits, that the 65K protein was present in the cells of rat liver putative preneoplastic foci, with little or none being detected in the surrounding cells.

Animals↗

Pharmacokinetics and cerebrospinal fluid bactericidal activity of ceftriaxone in the treatment of pediatric patients with bacterial meningitis.

Single-dose pharmacokinetics of ceftriaxone were determined in 19 patients with proven bacterial meningitis. The dosage was 50 mg of ceftriaxone per kg. The plasma concentration time curve declined in a biexponential manner. The mean peak plasma concentration was 207 micrograms/ml, and the elimination half-life was 4 h. In 12 patients, multiple-dose pharmacokinetics were determined after a loading dose of 75 mg of ceftriaxone per kg, followed by 50-mg/kg doses every 8 h in 5 patients or every 12 h in 7 patients. The mean peak plasma concentration was 230 micrograms/ml after the first dose and 263 micrograms/ml after the last dose. Of 12 patients, 5 had trough values that were larger after multiple doses than after a single dose. Mean penetration of ceftriaxone into cerebrospinal fluid was 3.1%. The median cerebrospinal fluid bactericidal titer against the patients pathogens was greater than 1:1,024 and less than 1:2,048. The drug was well tolerated without adverse effects.

Bacteria↗

Stimulation of natural killer and antibody-dependent cellular cytotoxicity activities in mouse leukocytes by bombesin, gastrin-releasing peptide and neuromedin C: involvement of cyclic AMP, inositol 1,4,5-trisphosphate and protein kinase C.

Bombesin and the two mammalian bombesin-related peptides, gastrin-releasing peptide (GRP) and neuromedin C, at physiological concentrations ranging from 10(-11) M to 10(-9) M have been shown in this study to significantly stimulate in vitro the antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activities in BALB/c mouse leukocytes from axillary nodes, spleen and thymus. The three neuropeptides studied induced no change in interleukin-2 production. In addition, these neuropeptides induced in leukocytes from axillary nodes a rapid, transient and significant decrease of intracellular cyclic AMP at 30 s, but a significant transient increase of inositol 1,4,5-trisphosphate levels at 30 and 60 s and a stimulation of protein kinase C activity in membrane fractions after 5 min incubation. These results suggest that inositol phospholipid signalling and cAMP messenger systems are involved in the increase of NK and ADCC activities when leukocytes are incubated in the presence of bombesin, GRP or neuromedin C.

Animals↗