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Biomedical subjects

R Castillo

Publications and source records attributed to R Castillo.

At least 127 records · Page 7Linked to original sources
PubMed1988

Asialo von Willebrand factor enhances platelet adhesion to vessel subendothelium.

Native von Willebrand factor (N-vWF) binds to platelets activated by thrombin, ADP or ristocetin. Asialo vWF (As-vWF) induces platelet aggregation in absence of platelet activators. N-vWF mediates platelet adhesion to vessel subendothelium at high shear rates. We have investigated the role of As-vWF in supporting platelet deposition to rabbit vessel subendothelium at a shear rate of 2,000 sec-1, using the Baumgartner perfusion system. We have studied the effects of the addition of As-vWF (from 2 to 12 micrograms/ml) to perfusates consisting of washed red blood cells, 4% human albumin and washed platelets. Our results show a significant increase in platelet deposition on subendothelium (p less than 0.01) in perfusions to which As-vWF had been added. Blockage of the platelet glycoproteins Ib and IIb/IIIa (GPIb and GPIIb/IIIa) by specific monoclonal antibodies (LJIb1 and LJCP8, respectively) resulted in a decrease of platelet deposition in both types of perfusates prepared with N-vWF and As-vWF. Our results indicate that As-vWF enhances platelet deposition to vessel subendothelium under flow conditions. Furthermore, they suggest that this effect is mediated by the binding of As-vWF to platelet membrane receptors, which in turn, promote platelet spreading and adhesion to the subendothelium.

Antibodies, Monoclonal↗
PubMed1988

Ristocetin induces platelet aggregation: a morphological demonstration.

Changes in the morphology of human platelets induced by ristocetin in platelet-rich plasma (PRP) have been analysed at the ultrastructural level by means of a tannic acid procedure. Studies were also undertaken to measure the release of serotonin. Modifications of the aggregation tests induced by apyrase, a monoclonal antibody (Mab) to GPIIb/IIIa and by EDTA were also investigated. Transmission electron microscopy revealed that ristocetin precipitated adhesive proteins on the platelet membrane. An electron-dense deposit was seen within 20 s after ristocetin was added. When experiments were carried out in the aggregometer cuvette during stirring, groups of platelets became activated, changed their shape, and finally aggregated releasing part of their contents. The morphology of aggregates did not differ from those formed in the presence of ADP. Aggregation studies demonstrated that a Mab to GPIIb/IIIa modified the extent and the rate of the aggregation curve when RIPA was performed in citrated platelet-rich plasma (c-PRP), while apyrase modifies the extent, but not the slope, of the curve. Neither the antibody nor apyrase modified RIPA when it was performed in PRP obtained in the presence of EDTA. All this evidence suggests that RIPA in c-PRP, besides reflecting the interaction of GPIb with vWF, may also test other mechanisms of the platelet function including: assembly of GPIIb/IIIa complex, interaction of fibrinogen with this glycoprotein complex, and possibly the release reaction.

Antibodies, Monoclonal↗
PubMed1987

Ticlopidine inhibits platelet thrombus formation studied in a flowing system.

We have studied the effect of ticlopidine on platelet function. This effect was assessed by aggregation studies and by the Baumgartner perfusion system as an ex vivo approach to study modifications in the interaction of platelets with vascular subendothelium. Platelets from volunteers, that were given 250 mg of ticlopidine twice a day showed a significantly decreased aggregation of platelets induced by several agonists. In the perfusion studies a marked reduction in the parameters that measure platelet interaction with subendothelium was also observed. The decrease in thrombus formation, and the diminished size of platelet aggregates, clearly indicated that ticlopidine impaired platelet-platelet interaction in this experimental flowing system. Our results suggest that ticlopidine is a potent inhibitor of platelet function and that its antiplatelet activity might be related to the mechanisms that regulate the interaction between platelets at the membrane level.

Administration, Oral↗
PubMed1987

Correction of the bleeding time in treated patients with severe von Willebrand disease is not solely dependent on the normal multimeric structure of plasma von Willebrand factor.

Even though it is generally held that cryoprecipitate and fraction I-O correct the prolonged bleeding time (BT) in patients with von Willebrand disease (VWD), perusal of reported data indicates that the correction is usually short-lasting and often partial. We decided to do a controlled study of the relationship between the multimeric structure of von Willebrand factor (VWF) and the BT in five patients with severe (type III) VWD after infusion of three plasma concentrates ("wet" cryoprecipitate, lyophilized cryoprecipitate, and fraction I-O) given in random order. The dosage of concentrates was tailored from in vitro measurements to achieve post-infusion levels of ristocetin cofactor above the lower normal limit (50 U/dL) for at least 3 hours. The postinfusion BT became transiently normal in only two of five patients treated with wet cryoprecipitate, whereas it remained prolonged in all five patients treated with lyophilized cryoprecipitate or fraction I-O. For all the concentrates, the proportion of large VWF multimers calculated by scanning the electrophoretic gels were the same as those for normal standard plasmas. An intact multimeric structure was recovered in postinfusion plasmas of patients treated with wet cryoprecipitate, whereas there was a postinfusion loss of large multimers after lyophilized cryoprecipitate and fraction I-O. These findings indicate that the attainment of a normal BT is the exception rather than the rule after the infusion of three plasma fractions used in the treatment of severe VWD, and that an intact multimeric structure in concentrates and postinfusion plasmas is necessary but not sufficient to sustain a normal BT.

Bleeding Time↗
PubMed1986

Sex-related differences in the effects of aspirin on the interaction of platelets with subendothelium.

Using the Baumgartner perfusion technique, marked sex-related differences in the extent of platelet-subendothelium interaction and in the effect of aspirin (ASA) have been observed. The administration of ASA (150 mg daily for 15 days) to two groups of healthy volunteers, one composed of males and the other of females, proved to block the generation of TXB2 in both cases. The basic pattern of platelet subendothelium interaction, however, was found to be markedly different in both groups studied. In men, aspirin treatment induced a significant reduction in the percentage of platelet thrombi, whereas in women, post ASA values remained at the same level as in control experiments. These results show that in the Baumgartner perfusion system women display a less thrombogenic tendency than men and that 150 mg of ASA administered daily are effective in reducing the extent of platelet-subendothelium interaction in the male group but not in the female group. These findings could explain the absence of benefit observed for women in clinical trials with aspirin.

Administration, Oral↗