DSpace Angular :: Browsing by Author "MEZZANO, D"

Browsing by Author "MEZZANO, D"

Now showing 1 - 12 of 12

ACCUMULATION OF 5-HYDROXYTRYPTAMINE BY AGING PLATELETS - STUDIES IN A MODEL OF SUPPRESSED THROMBOPOIESIS IN DOGS
(GEORG THIEME VERLAG KG, 1994) ARANDA, E; PIZARRO, M; PEREIRA, J; MEZZANO, D
Thrombocytopenia was induced in healthy, male mongrel dogs by intramuscular injection of a single dose of estradiol valerate (1 mg/kg). A steady, almost linear decay of the blood platelet count starting about day 6 post-estradiol and attaining a mean value of 14 x 10(3) platelets/mu l one week later was observed. Thrombocytopenia is explained mainly by suppression of thrombocytopoiesis, as established by two independent ways: 1. Megakaryocytes in the bone marrow were markedly reduced. 2. Kinetic studies with In-111 labeled autologous platelets revealed a nearly linear decay of the radioactivity and mean survival times within the expected range. The progressive reduction in the platelet count is associated with an increase in the mean age of the platelets still circulating. Following estradiol injection, platelet 5-hydroxytryptamine (5-HT) increased from a basal value of 130 +/- 30 ng/10(8) platelets (platelet count of 351 +/- 53 x 10(3) platelets/mu l) to 343 +/- 100 ng/10(8) platelets eleven days latter, when the platelet count dropped to 32 +/- 18 x 10(3) platelets/mu l. No significant changes in the number or affinity of the 5-HT uptake receptors could be demonstrated in platelets exposed in vitro and in vivo to estradiol. Our results indicate that aging platelets accumulate 5-HT, probably by a sustained exposure to the monoamine in plasma, confirming previous observations based on models in which thrombopenia was induced by immune and mechanical means.
BLEEDING-TIME IN PREECLAMPSIA
(MUNKSGAARD INT PUBL LTD, 1994) IVANKOVIC, M; PEREIRA, J; BIANCHI, M; GERMAIN, A; MEZZANO, D
The association of preeclampsia with thrombocytopenia and prolonged bleeding time is reported. The analysis of bleeding time (Simplate II) and the platelet count (Automatic Coulter Counter) in 41 patients with different grades of preeclampsia is presented. Our results suggest that the decrease in the bleeding time observed in moderate preeclampsia and the increase observed in severe preeclampsia are not mainly dependent on the platelet count.
COMPARATIVE-STUDY OF SIZE, TOTAL PROTEIN, FIBRINOGEN AND 5-HT CONTENT OF HUMAN AND CANINE PLATELET DENSITY SUBPOPULATIONS
(1986) MEZZANO, D; ARANDA, E; FORADORI, A
The size, total protein, fibrinogen and 5-HT content were evaluated in density subpopulations of human and canine platelets fractionated in linear arabinogalactan gradients. The methodology was assessed to ascertain that platelet separation was by density and to discard artifactual changes and platelet release during the procedure. EDTA or PGE1 increased the size of human PRP-platelets, but not of dog platelets. In humans, high density (HD) platelets were 1.26 times larger and contained 1.88 times more fibrinogen, 2.23 times more 5-HT and 1.37 times more protein than low density (LD) platelets; in dogs, these density cohorts did not differ in protein content, but LD platelets were 1.29 times larger and had 1.33 times more fibrinogen and 5-HT than HD platelets. These findings suggest that cell density is mostly dependent on the protein content per unit volume of platelets (and not on dense bodies). The differences in fibrinogen and 5-HT content between HD and LD cohorts in humans and dogs may be related to platelet age. The difference in volume between HD and LD platelets in dogs is of uncertain interpretation.
DECREASE IN MEAN PLATELET SURVIVAL-TIME IN ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS (APSGN)
(1990) MEZZANO, S; LOPEZ, MI; OLAVARRIA, F; ARDILES, L; MEZZANO, D
In an attempt to study further the possible participation of platelets in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), we studied the platelet survival time, as an index of platelet activation, in 22 patients with APSGN. Mean platelet survival time was computed from the disappearance of radioactivity from blood, sampled serially after injection of autologous 51Cr-labelled platelets. Clq solid phase ELISA and conglutinin (K) solid phase ELISA were used to measured the serum level of immune complexes. The platelet survival time in APSGN patients was 113 .+-. 10 h vs 197 .+-. 10 h in the control group (p < 0.001); 68% of the patients had a shortened platelet survival, lower than 95% confidence limit. There was a significant increase in the platelet survival in the six patients that were studied after recovery from acute nephritic syndrome. There was no significant association between the mean platelet time survival and CICs (circulating immune complexes). Similarly, no significant correlation was found between the mean platelet lifespan and the severity of the glomerular disease, as assessed by the serum creatinine level and the proteinuria. These results support evidence of platelet activation and consumption in APSGN and we suggest that this activation occurs in the glomeruli capillary wall, due to platelet-vascular wall interaction.
DECREASED PLATELET COUNTS AND DECREASED PLATELET SEROTONIN IN POSTSTREPTOCOCCAL NEPHRITIS
(KARGER, 1995) MEZZANO, S; KUNICK, M; OLAVARRIA, F; ARDILES, L; ARANDA, E; MEZZANO, D
Mean platelet survival time in patients with acute poststreptococcal glomerulo-nephritis (APSGN) is reduced to 50-60% of the control values, and glomerular deposits of platelet factor 4 are found in these patients. In order to investigate further systemic platelet changes of pathogenic, clinical or prognostic significance, we measured the platelet serotonin (5-HT) content and the blood platelet counts during the Ist week of the disease in 27 patients with APSGN. Platelet 5-HT was significantly reduced in patients with APSGN as compared with patients with impetigo without glomerular involvement (785+/-54 vs. 1,329+/-94 ng 5-HT/10(9) platelets; p<0.001). Similarly, the mean blood platelet count was reduced to 247+/-16x10(3) as compared with 303+/-14x10(3) in the controls (p<0.05). Thirteen (48%) of these patients had individual values of platelet 5-HT lower than the 95% confidence interval calculated in the control group. No significant correlation was observed between the concentration of 5-HT and either the severity of the disease judged by the amount of urinary protein excretion and the serum creatinine value or the presence of circulating immune complexes. Significant correction of the platelet 5-HT content (to 1,180+/-111 ng/10(9) platelets; p<0.01) and of the platelet counts (to 309+/-21x10(3); p<0.01) were observed in the longitudinal study at least 2 weeks later. Platelet activation, with secretion of granular content and increased consumption, may explain these findings. Additionally, the reduced mean age of the circulating platelets could contribute to their decreased 5-HT levels. The reduced platelet counts are not of clinical significance, but serial measurements of platelet 5-HT may be useful in predicting active glomerular inflammation.
EFFECTS OF DITERPENE FORSKOLIN ON THE RELEASE REACTION AND PROTEIN-PHOSPHORYLATION OF HUMAN-PLATELETS
(1983) GONZALEZ, A; ARANDA, E; MEZZANO, D; GARRIDO, J
GLOMERULAR LOCALIZATION OF PLATELET FACTOR-IV IN STREPTOCOCCAL NEPHRITIS
(1992) MEZZANO, S; BURGOS, ME; ARDILES, L; OLAVARRIA, F; CONCHA, M; CAORSI, I; ARANDA, E; MEZZANO, D
Since platelet factor 4 (PF4), a cationic (pI 7.6) platelet secretory protein, binds avidly to glomerular polyanions both in vitro and in vivo, and is implicated in neutrophil chemotaxis, we studied by indirect immunofluorescence microscopy the presence of PF4 deposits in glomeruli of patients with poststreptococcal nephritis (APSGN).
KINETICS OF PLATELET DENSITY SUBPOPULATIONS IN SPLENECTOMIZED MONGREL DOGS
(1984) MEZZANO, D; ARANDA, E; FORADORI, A; RODRIGUEZ, S; LIRA, P
Autologous 51Cr-platelet kinetic studies were performed in splenectomized mongrel dogs. Mean survival time of PRP[platelet-rich plasma]-platelets was 5.4 .+-. 1.5 (SD) days (n = 6). The curves, though slightly curvilinear, showed mostly a linear type of decay, denoting that platelet removal from the circulation is mainly determined by aging of the cells. High-density (HD) and low-density (LD) platelet cohorts were isolated in Stractan gradients from samples drawn daily after infusion of labeled platelets. Specific radioactivity in HD cohorts declined rapidly postinfusion (T1/2 [half-life] = 1.3 days), but specific radioactivity in LD platelets increased for 2 days and steadily declined for 4 days thereafter (n = 6). Labeled HD platelets, comprising 11.7% of the total population, lived significantly longer in circulation than LD platelets (19.1% of the total population) (n = 3). The patterns of decay of the radioactivity do not have all the characteristics of pure age-cohort survival curves; 3.7 days after the infusion of labeled HD platelets, the specific radioactivity in LD cohorts was 6 times higher than on day 1, but attained only 20% of the initial specific radioactivity in HD platelets. After the infusion of labeled LD platelets no radioactivity was recovered in circulating HD cohorts. Mongrel dog platelets apparently decrease in density with aging, but also platelet density heterogeneity is in part determined during the thrombopoietic process. These data are consistent with those of other authors in rabbits and rhesus monkeys, but contrast with the observations that platelets in humans, baboons and Macaca fasicularis monkeys increase in density with age, suggesting that the displacement of platelets toward compartments of either higher or lower density depends on the species under study.
PALMITOYL-COA AND THE ACYL-COA THIOESTER OF THE CARCINOGENIC PEROXISOME-PROLIFERATOR CIPROFIBRATE POTENTIATE DIACYLGLYCEROL-ACTIVATED PROTEIN KINASE-C BY DECREASING THE PHOSPHATIDYLSERINE REQUIREMENT OF THE ENZYME
(1990) ORELLANA, A; HIDALGO, PC; MORALES, MN; MEZZANO, D; BRONFMAN, M
To gain insight into the mechanism by which long-chain acyl-CoA thioesters potentiate diacylglycerol-activated protein kinase C, the cofactor dependence of this activating effect was studied with purified rat brain enzyme and histone H1 as substrate. Using two different assay systems, palmitoyl-CoA was found to decrease greatly the amount of phosphatidylserine required to activate the kinase. No relative changes were observed in the dependence of the enzyme for other cofactors (diacylglycerol, ATP, and Ca2+) in the presence of palmitoyl-CoA. The potentiating effect of palmitoyl-CoA and the decrease in phosphatidylserine requirement of the kinase was also demonstrated using the 47-kDa protein of human platelets as substrate and platelet protein kinase C as source of enzyme. The acyl-CoA thioester of the carcinogenic peroxisome-proliferator ciprofibrate was also found to decrease the phosphatidylserine requirement of protein kinase C. The data suggest that acyl-CoAs may play a role in the regulation of protein kinase C activity.
PLATELET 5-HYDROXYTRYPTAMINE INCREASES WITH PLATELET AGE IN DOGS
(GEORG THIEME VERLAG KG, 1991) MEZZANO, D; DELPINO, GE; MONTESINOS, M; GARCIA, ME; ARANDA, E; FORADORI, A
Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.
PLATELET AUTOANTIBODIES IN PATIENTS WITH CHRONIC LIVER-DISEASE
(1995) PEREIRA, J; ACCATINO, L; ALFARO, J; BRAHM, J; HIDALGO, P; MEZZANO, D
The thrombocytopenia in chronic liver disease (CLD) has been attributed mainly to hypersplenism, although other factors such as reduced mean life span with increased platelet turnover have also been demonstrated, Immunological abnormalities have been described in the pathogenesis and progression of CLD. In this sense, many studies have reported elevated levels of platelet associated IgG (PAIgG) in patients with CLD, and it has been suggested that PAIgG could represent true antiplatelet antibody. In this study we used a glycoprotein (GP)-specific immunoassay (MACE) to determine whether PAIgG or circulating antiplatelet antibodies, reacted against the GPIIb/IIIa or GPIb/IX complexes, in patients with CLD. Thirty-six patients with CLD of diverse etiology were studied (20 female, mean age 53 years, range 38-75 years). 23 out of 36 patients (64%) had anti-GP antibodies in MACE, Particularly, 12 had anti-GPIb, 4 anti-GPIIb/IIIa, and 7 had both types of autoantibodies, The existence of these anti-GP antibodies was not related with the blood platelet count or etiology of CLD,
TOTAL SIALIC-ACID IN HUMAN AND CANINE PLATELETS DOES NOT CHANGE WITH THE PLATELET AGE
(WILEY-LISS, 1992) MEZZANO, D; ARANDA, E; GARCIA, ME; PEREIRA, J; QUIROGA, T; PEREZ, M
Total platelet sialic acid (SA) was measured in three experimental conditions: (1) human and canine platelet density subpopulations obtained by centrifugation in arabinogalactan gradients, (2) circulating canine platelets during recovery from experimental immune and mechanical thrombocytopenias, and (3) platelets obtained from a patient with chronic immune thrombocytopenic purpura before and after splenectomy. The density of human and canine platelets is, in part, determined by their age. We found no significant differences in total SA between high-density (HD) and low-density (LD) platelets (9.32 +/- 2.0 vs. 9.55 +/- 1.3-mu-g/mg of platelet protein in dogs and 9.02 +/- 2.3 vs. 9.10 +/- 2.9 mu-g/mg in humans). In the human and canine thrombocytopenic models, the entrance of new platelets from the bone marrow is followed by their aging in the circulation. In these models, no significant changes in total SA content were detected in sequential measurements during the recovery of the thrombocytopenia. Accordingly, we conclude that total SA in human and canine platelets is unrelated to their age in circulation. These results do not support the notion that the loss of SA from membrane glycoproteins determines the recognition and removal of platelets from the circulation.

Browsing by Author "MEZZANO, D"

Results Per Page

Sort Options