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Biomedical subjects

G Escolar

Publications and source records attributed to G Escolar.

At least 163 records · Page 9Linked to original sources
PubMed1989

Effects of zinc acexamate on blood flow and prostanoid levels in the gastric mucosa of the rat.

The effects of the new antiulcer compound zinc acexamate on blood flow and prostanoid levels in the gastric mucosa have been studied. Zinc acexamate (30 and 300 mg/kg) dose-dependently prevents the reduction induced by the perfusion of noradrenaline (3.5 micrograms/kg.min, 30 min) in gastric mucosal blood flow, as measured by 3H-aniline clearance. Zinc acexamate pretreatment also increases the levels of prostaglandin E2 in the gastric mucosa of the rat, both under control conditions and after infusion with noradrenaline. The levels of thromboxane A2 and prostacyclin were not modified by zinc acexamate. These results confirm the importance of microcirculation in pathogenesis and the idea that the antiulcer activity of zinc acexamate is due in part to its action in increasing the mechanism which defend the gastric mucosa against aggression.

Aminocaproates↗
PubMed1989

Zinc acexamate reduces gastric damage induced by platelet-activating factor.

We have tested the ability of zinc acexamate (ZAC) to prevent platelet-activating-factor (Paf) induced gastric damage in rats. Lesions were characterized by a vascular congestion affecting the entire mucosa, oedema, haemorrhage and frequent necrosis of the more superficial areas. The gastric damage appearing after Paf was accompanied by degranulation of gastric mast cells. Leukocytes were often seen at the submucosal level. Oral pretreatment with ZAC reduced in a dose-dependent manner both gastric damage and mast cell degranulation observed after Paf. ZAC administered orally at a dose of 100 mg kg-1 statistically inhibited (p less than 0.01) gastric damage and mast cell degranulation. ZAC did not affect the hypotension induced by Paf confirming that gastric damage and hypotension appearing in rats after Paf administration are two independent phenomena. The present findings indicate that the inhibitory effect of ZAC upon gastric lesions induced by Paf may be related to the different protective actions exhibited by this zinc compound in a wide variety of experimental models of gastric ulcer.

Aminocaproates↗
PubMed1989

Zinc compounds, a new treatment in peptic ulcer.

Effects of zinc in gastric ulcer have been reviewed through investigations carried out on zinc acexamate (ZAC). ZAC is an organic compound that has been shown to possess an experimental antiulcer effect and a wide therapeutic index, making it a useful drug in the treatment of peptic ulcer disease. ZAC protects from ulceration in several experimental models such as pylorus occlusion, reserpine-induced ulcer, necrotizing agents, PAF-induced ulcer and cold-restraint stress. ZAC first reduces the gastric acid output by inhibiting the mast cell degranulation, an action likely to be mediated through a membrane stabilizing action. Secondly, it enhances the mucosal protection factors by increasing mucus secretion, inhibiting the H+ retrodiffusion and improving microcirculation. ZAC is also effective in acetic acid-induced chronic ulcer, restoring the continuity of the damaged mucosa. Several clinical trials have shown the usefulness of ZAC in acute and maintenance treatment of both gastric and duodenal ulcers. Endoscopic studies showed that ZAC reduced the inflammatory processes (gastritis and duodenitis) associated with ulcer healing. This reduction was statistically significant and not observed with other comparative treatments (H2-antagonists). The observed side-effects were minimal and affected less than 2% of treated patients. The pharmacological profile, clinical effectiveness and good tolerance of ZAC suggest this compound as an interesting option in the treatment of peptic disease.

Aminocaproates↗
PubMed1989

Uremic plasma after infusion of desmopressin (DDAVP) improves the interaction of normal platelets with vessel subendothelium.

Effects of 1-deamino-8-D-arginine vasopressin (DDAVP; 0.4 microgram/kg iv) were studied in 11 patients with uremia. Bleeding time, platelet retention on glass beads, factor VIII activities, plasma catecholamine levels, and studies on platelet interaction with the subendothelium were performed before, 1 hour after, and 6 hours after DDAVP infusion. Perfusates consisting of normal washed platelets, uremic platelet-poor plasma (u-PPP) and washed red blood cells were perfused through the Baumgartner perfusion system at a shear rate of 800 sec-1. One hour after DDAVP infusion, a shortening in the bleeding time and an increase in platelet retention on glass beads were noticed in these patients (p less than 0.01). Simultaneously, plasma levels of noradrenaline, factor VIII coagulant (FVIII:C), and von Willebrand factor (vWF) activities were statistically increased. Platelet deposition and platelet aggregate formation on subendothelium were consistently increased (p less than 0.05) in perfusions carried out with blood reconstituted with u-PPP obtained 1 hour after DDAVP. The "in vitro" addition of 1 U/ml vWF or 1 U/ml vWF plus 1 U/ml factor VIII to the pretreatment u-PPP had no significant influence on the parameters that quantify platelet-subendothelium interaction. However, after the addition of 10 ng/ml noradrenaline to a similar system containing basal u-PPP, a clear improvement (p less than 0.05) in platelet deposition was noticed. Our results confirm the hemostatic effectiveness of DDAVP in patients with uremia and reveal an increased platelet interaction with subendothelium mediated by a factor present in uremic plasma after DDAVP administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effects of zinc acexamate on gastric mucosal production of prostaglandin E2 in normal and stressed rats.

Changes in PGE2 levels induced by zinc acexamate (ZAC) at gastricmucosal level were assessed in a rat model. Experiments were performed in normal rats and rats subjected to cold-restraint stress and in experimental conditions in which prostaglandins (PGs) synthesis was inhibited by prior administration of indomethacin. Gastric injuries after different treatments were quantified macro and microscopically. Total amount of PGE2 and mucus material recovered from gastric mucosa were increased after ZAC treatment. Indomethacin aggravated gastric damage secondary to stress and inhibited PGE2 and mucus increase appearing after ZAC treatment. These data confirm the relation between PGE2, mucus production and gastric protection. ZAC 200 mg/kg was able to reduce the gastric damage induced by stress. This decrease was also evident in the group receiving indomethacin before ZAC administration. These experiments indicate that ZAC exhibits its antiulcer action by increasing prostaglandins but other mechanisms independent of PGs synthesis are also involved.

Aminocaproates↗
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↗
PubMed1988

Development of a simple embedding procedure allowing immunocytochemical localization at the ultrastructural level.

Immunobed solution A is a water-soluble acrylic compound recently developed for immunocytochemical localization at the light microscopic level. In this study, we combined it with methyl methacrylate (MMA) to achieve sufficient hardness to obtain ultra-thin sections. Samples of platelets were dehydrated and embedded in the water-soluble acrylic mixture (WSAM). The embedding process was carried out at 4 degrees C and final polymerization was induced with either chemical (benzoyl peroxide) or physical (UV light) catalysts. Tubulin was localized at the ultrastructural level in sections embedded according to these two methods. Results were compared with those obtained in platelets processed in Lowicryl. Dehydration and embedding with the WSAM yielded a preservation of antigenicity similar to that obtained in Lowicryl. The new procedure benefits from the low temperature achieved during polymerization, providing good ultrastructural morphology and immunolocalization of protein antigens with the simplicity of a routine embedding procedure for light microscopy.

Acrylates↗
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

Immunogold staining of microtubules in resting and activated platelets.

A circumferential microtubule is known to support the discoid form of resting platelets, but its fate following exposure of the cells to aggregating agents is uncertain. The present study has employed an immunocytochemical approach to follow the fate of the circumferential microtubule in activated platelets. Monoclonal antibodies to tubulin and to vinculin and a polyclonal antibody to actin were incubated with isolated microtubule coils and stained with staphylococcal protein A coupled to immunogold in order to test their specificity. Thin sections of glycolmethacrylate embedded platelets before and after exposure to thrombin for 15, 30 and 60 s were stained with antibodies to tubulin and actin. Immunogold particles showed a high specificity for isolated MT coils stained for tubulin, modest intensity for actin, and none for vinculin. Gold particles were randomly distributed in thin sections of resting and activated platelets stained for actin. Immunogold was limited to the circumferential microtubule in resting platelets and constricted coils in thrombin-activated cells. The number of gold particles in areas of cytoplasm away from microtubules in platelets stained with antitubulin antibody increased slightly following thrombin activation, but the change was not significant. Results support the concept that microtubule coils supporting the discoid form of resting platelets do not dissolve following exposure of the cells to potent agonists.

Actins↗
PubMed1987

Effect of cold-restraint stress and zinc acexamate on gastric mucus production in intact glands.

Gastric mucus content was morphometrically evaluated in gastric glands of normal and cold-restraint stressed rats. Variations induced by treatment with zinc acexamate (200 mg/kg p.o.) were also investigated. Stress decreased the glycoprotein content in glands located in areas of injury. However, in intact glands from the same animals, the glycoprotein content was increased and the proportion of sulphated macromolecules greatly augmented. Zinc acexamate reduced the severity of damage in stressed rats. Although it augmented mucus content it prevented the modification in sulphated macromolecules in these rats. These findings are discussed in relation to the role of gastric mucus in preventing gastric damage.

Aminocaproates↗
PubMed1987

Anti-ulcer and membrane stabilizing actions of zinc acexamate.

The effects of zinc acexamate on stress and reserpine ulcers as well as on gastric mast cells degranulation and membrane stability were evaluated in the rat. Zinc acexamate (100 mg/kg) has demonstrated an inhibitory effect on cold-restraint stress and reserpine-induced ulcer in a dose-dependent manner. Pretreatment of rats, prior to cold restraint stress, reduced gastric mast cell degranulation. Zinc acexamate (10(-4) M) inhibits Triton X-100 release of beta-glucuronidase in isolated hepatic lysosomes. These observations suggest that ulcer protective actions of zinc acexamate may be exerted in part through enhancing gastric mucosal resistance by stabilizing biological membrane integrity.

Aminocaproates↗
PubMed1987

Fibronectin is required for platelet adhesion and for thrombus formation on subendothelium and collagen surfaces.

Fibronectin (FN) plays a role in several adhesion mediated functions including the interaction of platelets with subendothelium. We investigated the role of plasma FN in platelet adhesion and platelet thrombus formation under flow conditions. We used two different perfusion models: the annular chamber with alpha-chymotrypsin-treated rabbit vessel segments, and the flat chamber with coverslips coated with fibrillar purified human collagen type III. Perfusates consisted of washed platelets and washed RBCs, suspended in normal or FN-depleted plasma. Perfusions were carried out for ten minutes at shear rates of 300 or 1,300 s-1. Platelet deposition and thrombus dimensions were evaluated morphometrically by a computerized system. We found that depletion of plasma fibronectin significantly reduced the percentage of total coverage surface and percentage of platelet thrombus, at both shear rates studied, and in both perfusion systems (P less than .01) (P less than .01). The dimensions of the platelet thrombi formed in perfusions at high shear rate were also significantly reduced in perfusions carried out with FN depleted plasma (P less than .01). Addition of purified FN to FN-depleted perfusates restored all values to those measured in the control perfusions. These results indicate that plasma FN is required for platelet aggregate and thrombus formation following adhesion under flow conditions.

Aorta, Abdominal↗
PubMed1987

Antiulcerogenic activity of zinc acexamate in different experimental models.

The antiulcerogenic activity of zinc acexamate (ZAC; Laboratorios Viñas, S.A.) has been tested in several models of gastric injury induced by acid hypersecretion, prostaglandin blockade and disruption of the gastric barrier. Lowest doses which have demonstrated to significantly prevent gastric damage ranged from 10 to 100 mg/kg depending on the experimental model used. The benefit obtained with this compound was always dose-dependent. These findings would support the hypothesis that ZAC acts by a complex inhibition of several of the mechanisms involved in the development of peptic diseases.

Aminocaproates↗
PubMed1987

Interaction of long-term stored platelets with vascular subendothelium.

Platelets stored as platelet-rich plasma under mildly alkaline conditions in vitro maintain morphologic integrity and functional capability for 2 to 3 weeks. We used the Baumgartner method to assess the ability of long-term stored platelets to interact with exposed vascular subendothelium. After 3 days in storage the size and number of thrombi on damaged surfaces decreased. However, the percentage of vascular surface covered was not reduced significantly until the cells had been stored for 14 days. Treatment of vascular segments with chymotrypsin to increase thrombogenicity caused platelets stored for 14 days to adhere and form aggregates on denuded surfaces in a manner similar to that of fresh platelets, but the ability to develop thrombi remained depressed. Thus long-term storage that maintains physical and functional integrity also preserves a reasonable capacity of platelets to interact with damaged blood vessels.

Adult↗
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↗