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Biomedical subjects

D Mezzano

Publications and source records attributed to D Mezzano.

At least 55 records · Page 3Linked to original sources
PubMed1990

Decrease in mean platelet survival time in acute poststreptococcal glomerulonephritis (APSGN).

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. C1q solid phase ELISA and conglutinin (K) solid phase ELISA were used to measure the serum levels of immune complexes. The platelet survival time in APSGN patients was 113 +/- 10 h vs 197 +/- 10 h in the control group (p less than 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 times 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.

Acute Disease↗
PubMed1986

Comparative study of size, total protein, fibrinogen and 5-HT content of human and canine platelet density subpopulations.

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.

Aging↗
PubMed1986

Changes in platelet beta-thromboglobulin, fibrinogen, albumin, 5-hydroxytryptamine, ATP, and ADP during and after surgery with extracorporeal circulation in man.

Surgery with extracorporeal circulation (ECC) is associated with transient alterations of platelet function whose pathogenic mechanisms are not completely understood. To define further the platelet abnormalities, we determined the changes in platelet content of several granule-associated substances during and after ECC in patients subjected to aortocoronary bypass surgery. Platelet beta-thromboglobulin (beta-TG) decreased to 79.8% of the preoperative level at the end of ECC (p less than 0.01) and, as expected, did not recover 1 hr after the end of surgery. Platelet fibrinogen and albumin decreased to 67.9% (p less than 0.01) and to 29.8% (p less than 0.01) of baseline, respectively. However, 1 hr after surgery, platelet fibrinogen rose to 92% and albumin to 55.5% of baseline, denoting that during the recovery from ECC, platelets incorporate some plasma proteins. During ECC, platelet 5-hydroxytryptamine (5-HT) and total ATP and ADP decreased to 50.8% (p less than 0.01), 63.2% (p less than 0.01), and 69.9% (p less than 0.01) of their respective preoperative values, indicating dense body release. One hour after surgery, ATP recovered to 83.8%, suggesting that previous depletion compromised also the metabolic pool of adenine nucleotides. In summary, Our results confirm and extend previous observations demonstrating alpha-granule release during ECC. Platelets undergoing ECC can incorporate plasma proteins as evidenced by the rapid increase of platelet fibrinogen and albumin after bypass. Although the mechanisms of this increase and site of storage of the exogenous substances are unknown, this observation justifies further studies to determine if internalization of plasma proteins, especially fibrinogen, may take place in physiological conditions. Dense body depletion with transient storage pool deficiency appears to be a component of the reduced platelet function during ECC. Consumption of metabolic ATP with alteration of platelet energy metabolism may further impair platelet function, contributing to the bleeding episodes observed during surgery with ECC.

Adenosine Diphosphate↗
PubMed1984

Increase in density and accumulation of serotonin by human aging platelets.

51Cr-labeled autologous platelets were infused into splenectomized subjects and the specific radioactivities of high-density (HD) and low-density (LD) platelet subpopulations were determined sequentially in postinfusion samples. A rapid decrease in the specific radioactivity of LD cohorts (T1/2 = 2.5 days) was observed, but the specific radioactivity of HD platelets remained constant or increased slightly during the first 4 days and then gradually declined for the next 5 days. No experimental artifacts during the platelet-labeling steps that could account for these results were demonstrated. These findings confirm previous observations in eusplenic individuals and support the hypothesis that human LD platelets are, on the average, younger than HD platelets. LD platelets contain 33.8 +/- 13.5 ng serotonin (5HT)/10(8) platelets and HD platelets 76.8 +/- 9.5 ng 5HT/10(8) platelets (P less than 0.001). Sequential measurements of 5HT in PRP platelets were performed during the recovery phase of thrombocytopenia following splenectomy in patients with idiopathic thrombocytopenic purpura (ITP), a condition associated with aging of platelets in circulation. Presplenectomy platelet 5HT was 17.7 ng/10(8) platelets and on days 1, 6, and 12 after surgery it increased to 18.1, 37.8, and 61.0 ng/10(8) platelets (n = 7). When three healthy volunteers were given aspirin (500 mg/day) for up to 15 days, no significant change in the 5HT content of circulating platelets was observed. If aspirin blocks, at least partially, the secretory process in vivo without interfering the 5HT uptake by the platelets, this finding stands against the possibility that a net depletion of 5HT occurs during the life-span of normal human platelets. The observation that human HD platelets, enriched with older cells, contain more 5HT than LD platelets taken together with the parallel increase in platelet 5HT and age during the recovery from thrombocytopenia in ITP patients and the lack of effect of aspirin on platelet 5HT content, provides initial evidence that human platelets accumulate 5HT during their life-span in circulation.

Adolescent↗
PubMed1984

Kinetics of platelet density subpopulations in splenectomized mongrel dogs.

Autologous 51Cr-platelet kinetic studies were performed in splenectomized mongrel dogs. Mean survival time of PRP-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 = 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, however, 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 six 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. These findings indicate that mongrel dog platelets decrease in density with aging, but also that 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 fascicularis 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.

Animals↗
PubMed1983

Effects of diterpene forskolin on the release reaction and protein phosphorylation of human platelets.

The effects of diterpene forskolin on the human platelet release reaction and on platelet protein phosphorylation were studied. This drug is shown to have the same effects as other agents which increase cAMP levels, namely, it inhibits the secretory response to diverse agonists and causes changes in the phosphorylation of several specific proteins. An increase of the 32P content is seen in the MW 47 000, 24 000 and 21 000 polypeptides while a decrease is observed in the MW 41 000 and 27 000 and 20 000 species. Forskolin also inhibits the changes in protein phosphorylation pattern induced by the powerful platelet secretagogue, thrombin. Our results relate the effects of antagonists of platelet secretion such as prostaglandins more closely to changes in cAMP levels and in protein phosphorylation than to other possible effects of the receptor-ligand interaction, which is by-passed by the use of forskolin. Our results also provide additional evidence involving these changes in the mechanisms which regulate the secretory process in platelets.

Blood Platelets↗
PubMed1981

Evidence that platelet buoyant density, but not size, correlates with platelet age in man.

Following infusion of 51Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radio-activity of LD platelets declined rapidly post-infusion (T1/2 = 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3--4-day period and gradually declined for 6--7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P less than 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33) days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P less than 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets = 7.57 mu3, LD platelets = 6.87 mu3, 0.05 less than P less than 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.

Adult↗