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Biomedical subjects

P A Gentry

Publications and source records attributed to P A Gentry.

At least 55 records · Page 3Linked to original sources

Characterization of the normal bovine platelet aggregation response.

1. Bovine platelets are more sensitive to stimulation by platelet activating factor (PAF) than adenosine-di-phosphate (ADP) or thrombin. 2. While epinephrine, arachidonic acid and serotonin are ineffective by themselves as aggregatory stimulants of bovine platelets they enhance the aggregation response of other platelet agonists. 3. There is no correlation between thromboxane A2 production and release and the extent of platelet aggregation in bovine platelets. 4. The dependence of bovine platelet aggregation on a phospholipid pathway and calcium mobilization is indicated.

Adenosine Diphosphate↗

Failure of aspirin to impair bovine platelet function.

The effect of aspirin on bovine platelet function and thromboxane A2 (TXA2) production in stimulated platelets was evaluated. A single dose of aspirin (100 mg/kg of body weight) was administered orally to Holstein cows, and blood samples were obtained before and at regular intervals for 7 days after treatment. The production of TXA2 was assessed by measuring the stable metabolite thromboxane B2, using a specific radioimmunoassay. Within 4 hours of aspirin administration, the production of TXA2 was significantly (P less than 0.05) decreased, irrespective of whether collagen, adenosine diphosphate, or platelet activating factor was used to initiate platelet aggregation. Despite the inhibition of TXA2 release from the stimulated platelets, platelet function, assessed by initial rate of aggregate formation and extent of aggregation, was unaffected by aspirin administration. The extent of aggregate formation in response to collagen, adenosine diphosphate, or platelet activating factor was independent of the amount of TXA2 released from platelets before and after aspirin treatment. The results suggested that TXA2 formation is not the primary biochemical pathway involved in the aggregation of stimulated bovine platelets.

Animals↗

Comparative hemostatic protein alterations accompanying pregnancy and parturition.

Pregnancy and parturition represent adaptive, physiological stress situations that elicit both blood coagulation protein changes and endocrine alterations. This paper briefly reviews the interrelationships of these responses by comparing the available data in several mammalian species including man, dog, cow, and pig. Hemostasis is an enzymatically controlled cascade process involving platelets and specific coagulation proteins that results in the formation of insoluble strands of fibrin. Although qualitatively similar in most mammals, quantitative differences exist in the circulating levels of individual coagulation proteins which may contribute towards the different rates of clot formation. In the late gestation stage of human pregnancy, significant increases are observed in the circulating biological activities of the coagulation factors VII, VIII:C, IX, and X. In the dog, the activities of factors VII and IX reach peak values in midpregnancy, while in the cow little or no changes are observed except for factor VII values which show a significant increase only around the time of parturition. These coagulation changes appear to be associated with fluctuations in circulating hormone values, particularly plasma estrogen. In human pregnancy, the circulating levels of fibrinogen, the precursor of fibrin, increase during the gestation period reaching maximum values during and immediately following parturition. In the dog and the cow two distinct increases in fibrinogen values are observed, the first in the midgestation period and the second in the immediate postparturition period. In the pig, fibrinogen values also rise significantly at parturition. Oral contraceptive studies in the human female have indicated that changes in circulating activities of coagulation proteins are hormonally influenced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ovine platelet function and its inhibition by T-2 toxin.

Ovine platelets suspended in homologous plasma aggregated effectively in response to adenosine-diphosphate, acid-soluble collagen and aggregated moderately to serotonin and arachidonic acid. Ovine platelet aggregation, in response to each agent, was inhibited in a concentration dependent fashion by T-2 toxin. The platelet aggregates which formed in the presence of T-2 toxin appeared to be less stable than aggregates in comparable control platelet suspensions.

Adenosine Diphosphate↗

Inhibitory effect of trichothecene mycotoxins on bovine platelets stimulated by platelet activating factor.

Several species of fungi, which infect cereals and grains, can produce a class of compounds, known as trichothecene mycotoxins, which is characterized by a substituted epoxy-trichothecene ring structure. Cattle are susceptible to intoxication from feeds contaminated with T-2 toxin, one of the more potent trichothecene mycotoxins, while swine refuse to ingest feed contaminated with T-2 toxin. The bovine platelet has been used as a model cell system to evaluate the effects of T-2 toxin and its natural metabolites, HT-2 toxin and T-2 tetraol, on cell function in vitro. Due to the lipophilic nature of these mycotoxins, a biologically active phospholipid was used to stimulate the platelets in the presence and absence of the toxins. The mycotoxin T-2 toxin and its major metabolite HT-2 toxin inhibited platelet activating factor-stimulated bovine platelets, suspended in homologous plasma, in a concentration but not time dependent manner. Significant inhibition of platelet function (p less than 0.01) occurred with 135 ng T-2 toxin per 10(6) platelets and with 77 ng HT-2 toxin per 10(6) platelets. These mycotoxins exerted an additive inhibitory effect on the platelet aggregation response. In contrast, the minor metabolite T-2 tetraol had no inhibitory effect on platelet function and had no influence on the responses of T-2 toxin or HT-2 toxin when the mycotoxins were present together in the platelet suspensions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Failure of Routine Coagulation Screening Tests to Detect Heterozygous State of Bovine Factor XI Deficiency.

In a survey of coagulation, biochemical and hematological parameters in cattle homozygous (deficient), heterozygous (carrier) and non-affected (normal) for Factor XI deficiency, only the Activated Partial Thromboplastin Time (APTT) results correlated with plasma Factor XI activity levels. The APTT results and the thrombokinetics for the deficient animals were markedly different from the results of either the carrier or normal animals. However, the APTT assay was shown not to be sufficiently sensitive to differentiate between the normal and carrier state for the coagulation disorder. Not only was there no statistical difference between the mean APTT results for the normal and carrier animals, but the thrombokinetics for fibrin clot formation for the two groups were also similar.

Journal Article↗

T-2 toxin can cause vasoconstriction in an in vitro bovine ear perfusion system.

An in vitro bovine ear perfusion system was used to examine the effect of T-2 toxin on peripheral vasculature. T-2 toxin caused a dose-related increase in the perfusion pressure, with an apparent threshold concentration of 1 X 10(-5) M. The effect of the toxin was observed irrespective of the presence of either histamine or norepinephrine in the system. The presence of known histaminic or noradrenergic antagonists did not affect the response to the toxin. Once the vessel was exposed to T-2 toxin, the response to histamine or norepinephrine was decreased.

Animals↗

LD50 values and serum biochemical changes induced by T-2 toxin in rats and rabbits.

Experiments were conducted to study the acute and subacute effects of intramuscularly injected T-2 toxin in rats and rabbits. The LD50 values of T-2 toxin were 0.85 +/- 0.03 and 1.10 +/- 0.08 mg/kg body wt in rats and rabbits, respectively. The intoxication was characterized by a consistent decrease in serum alkaline phosphatase (ALP) activity following either a single injection of 0.5, 0.6, or 0.9 mg/kg T-2 toxin in rats or daily injections of 0.2 mg/kg T-2 toxin for 10 days in rats and rabbits. Significant increases in bromosulfalein (BSP) retention and ALP activity were also observed in rabbits 24 hr following a single injection of 0.6 mg/kg T-2 toxin. The results indicated that the hepatobiliary system is a major target organ for T-2 toxin. Alterations in the activity of lactate dehydrogenase (LDH) and creatine kinase (CK) and in the hematocrit values were also observed.

Animals↗

Inhibition of bovine platelet function by T-2 toxin, HT-2 toxin, diacetoxyscirpenol and deoxynivalenol.

The aggregation of bovine platelets suspended in homologous plasma is inhibited in the presence of T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) or deoxynivalenol (DON) when either collagen or ADP is used as the stimulatory agent for aggregation. For each of the mycotoxins the degree of inhibition is dependent on the amount of trichothecene present in the platelet suspension but is not dependent on the time of exposure of the platelets to the toxin. For both ADP- and collagen-stimulated platelets, the order of potency of inhibition is T-2 toxin greater than HT-2 toxin greater than DAS greater than DON. A significant (P less than 0.01) dose-dependent decrease was also observed in the amount of the thromboxane B2 released from collagen-stimulated platelets in the presence of each of the mycotoxins.

Adenosine Diphosphate↗

Effect of T-2 toxin on bovine hematological and serum enzyme parameters.

The single intravenous administration of T-2 toxin to calves (0.25 mg/kg body weight) caused a marked decrease in the total peripheral white cell count which correlated with a decline in the neutrophil count. The circulating lymphocyte and platelet counts were unaffected by the toxin. A decline of approximately 10% occurred in hematocrit following toxin administration. A small transient increase was observed in serum aspartate aminotransferase, and lactate dehydrogenase activity together with a transient increase in the BSP retention test. There was no consistent pattern in the alteration of serum alanine aminotransferase activity and serum alkaline phosphate activity was unaffected by the toxin. The results suggest that in cattle the liver may not be the primary target organ for the cytotoxin effects of T-2 toxin.

Alanine Transaminase↗

The relationship between factor XI coagulant and factor XI antigenic activity in cattle.

Factor XI protein, isolated from normal bovine plasma, was used to raise antiserum in rabbits. The antisera was partially purified and used in a neutralization-inhibition assay to investigate the relationship between factor XI coagulant activity and antigenic material in the plasma of normal cattle and cattle homozygous and heterozygous for factor XI deficiency. Factor XI antigen was reduced in both the homozygous and heterozygous animals to levels comparable to the factor XI coagulant activity. The reduction of immunologically cross-reactive material to normal factor XI suggests that the factor XI coagulation defect is associated with the absence of a normal protein.

Animals↗

Effect of intravenous administration of T-2 toxin on blood coagulation in calves.

The single IV administration of T-2 toxin to calves at a dosage of 0.25 mg/kg of body weight produced statistically significant decreases in plasma activity of factors VII, IX, X, and XI and in fibrinogen values (P less than 0.05). Similar changes in the coagulation factors were observed after the single IV administration of T-2 toxin to calves which were given vitamin K (25 mg daily) for 5 days before and after dosing with T-2 toxin. The procoagulant activity of factor VIII was unaffected by T-2 toxin administration to calves.

Animals↗

The effect of administration of a single dose of T-2 toxin on blood coagulation in the rabbit.

The single intravenous administration of T-2 toxin to rabbits at a dosage of 0.5 mg per kg body weight produced an alteration in several blood coagulation parameters. The activities of factors VII, VIII, IX, X and XI were decreased by approximately 40% six hours after T-2 toxin administration. Plasma fibrinogen concentration became elevated within 24 hours after T-2 toxin exposure. Circulating platelet numbers were unaffected by T-2 toxin administration. The similarity of coagulation parameter changes induced by T-2 toxin in animals receiving daily subcutaneous injections of vitamin K (0.5 mg per kg body weight) and those in nonvitamin K supplemented animals suggests that T-2 toxin does not function as a vitamin K antagonist.

Animals↗

Kinetic analysis of bovine factor VIII in the hemophilic dog.

Bovine factor VIII, which did not contain platelet aggregating factor activity, was infused into hemophilic dogs. Factor VIII procoagulant (VIII:C) levels in the dogs increased dramatically, then decreased in a biphasic manner. The half-life of the longest component was 3-7 hrs. The infusions were hemostatically effective and also caused a prolonged shortening of the activated partial thromboplastin time. These studies demonstrate that the platelet aggregating factor activity of bovine factor VIII is not essential for its maintenance in the circulation and that preparations lacking this activity may be clinically useful. When concentrates of partially purified factor VIII: C (essentially free of both platelet aggregating factor and factor VIII-related antigen) were infused, marked increases in VIII: C levels were also observed, but the half-life was significantly shorter (T1/2 of approximately 1 hr.).

Animals↗

Plasma clot-promoting effect of collagen in relation to collagen-platelet interaction.

The hemostatic function of several acid-soluble collagen preparations and a fibrillar-form collagen preparation have been compared. Pepsin-treated acid-soluble collagen isolated from burro and horse aortic tissue and acid-soluble collagen isolated from human umbilical cord readily promoted platelet aggregation, but failed to activate the coagulation mechanism even after prolonged incubation with plasma at 37 C. By contrast, fibrillar-form collagen isolated from burro aorta was both an efficient stimulant for the induction of platelet aggregation and a potent clot-promoting agent. Similar results were found for all the collagen preparations irrespective of whether the studies were conducted with sheep or with burro plasma. Heat denaturation studies showed that the hemostatic function of the fibrillar-form collagen was dependent on an intact triple-helical structure.

Animals↗

Effect of fusarium T-2 toxin on hematological and biochemical parameters in the rabbit.

The single intravenous administration of purified T-2 toxin to rabbits to 0.5 mg per kg body weight produced a decrease in hematocrit, while blood cell count, and serum alkaline phosphatase activity. The plasma clotting time, as measured by the activated partial thromboplastin time assay, was prolonged after intravenous T-2 toxin administration. In contrast, the administration of T-2 toxin to rabbits at 2.0 mg per kg body weight by gastric intubation produced oral lesions, diarrhea and anorexia in the animals but did not cause significant alteration in hematological and biochemical parameters. The results suggest that the rabbit may be a suitable model for further examination of the biochemical mechanisms involved in the cytotoxic action of T-2 toxin.

Administration, Oral↗