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Biomedical subjects

D E Sharp

Publications and source records attributed to D E Sharp.

29 records · Page 2Linked to original sources
PubMed1978

Quantification of the morphological reaction of platelets to aggregating agents and of its reversal by aggregation inhibitors.

1. In rabbit citrated platelet-rich plasma, the changes in shape of the platelets produced by adenosine diphosphate (ADP) or 5-hydroxytryptamine (5-HT) were observed by photometric and volumetric techniques and by measurements of platelet images on electron micrographs either directly or with an image analysing computer. This permitted the indirect manifestations of the shape changes to be correlated with the morphological features responsible for them, i.e. transformation of disks to more spherical forms and extrusion of blebs and spikes. 2. Following the addition of ADP, an initial brief peak in the light scattering records was associated with marked but transient irregularities in the surface of the platelets. These effects were absent when the other shape changes were produced by 5-HT. 3. When the optical manifestations of the shape changes induced by ADP were reversed by the addition of antagonists adenosine triphosphate, 2-chloroadenosine or prostaglandin E1, the morphological changes were reversed by a diminution in the number of spikes and the conversion of spherical platelet bodies to a more discoid form. 4. The volume of extracellular plasma trapped between platelets sedimented by centrifugation was proportional to the number of spikes which they extruded. Under all conditions, the volume of the platelets themselves remained remarkably constant at approximately 5 X 10(-9) microliter./platelet. 5. Addition of a calcium chelating agent alone produced a rapid persistent alteration in the optical properties of platelet-rich plasma. The magnitude of this alteration was proportional to chelator concentration but greater in some plasmas than in others. Similar optical effects were produced when the calcium concentration of platelet-rich plasma was increased by adding calcium. The optical effects produced by calcium or its chelators were unusual in that the changes in transmitted and horizontally scattered light were in opposite directions (transmitted light decreased, scattered light increased) whereas, in all other circumstances so far examined, these changes were in the same direction. The chelators caused the formation of spikes on the platelets without appreciably altering their disk shape, which may explain the unusual nature of the optical effects.

Adenosine↗
PubMed1976

Blood components deposited on used and reused dialysis membranes.

Hemodialysis cartridges used once and reused once or twice were examined by scanning and transmission electron microscopy. Blood deposits consisting of leukocytes, platelets, and amorphous material covered 15 to 25% of the dialysis membrane surface of cartridges used once. This deposit increased somewhat with cartridge reuse but did not appear to impair the dialysis efficiency of membranes significantly. Leukocytes formed a major part of the blood deposit and spreading of these cells upon dialysis membranes was marked. Single and aggregated platelets were adherent to the dialysis membranes, to leukocytes, and to amorphous debris. Few erythrocytes were present, and fibrin was not identified. There was little evidence for build up or layering of the blood deposit with cartridge reuse. The procedures for dialysis cartridge rinsing used in these studies appear to be highly efficient in removal of adherent blood components.

Blood↗
PubMed1972

The initiation of platelet thrombi in normal venules and its acceleration by histamine.

1. In cheek pouch preparations of anaesthetized hamsters, platelet thrombi or ;white bodies' were produced in venules by the micro-ionto-phoretic application of adenosine diphosphate (ADP). Currents of 10-400nA were passed through micropipettes containing 10 mM-ADP, the tips of which were less than 5 mu from the outer wall of the venule. The effect was quantitated by determining the time between starting the currents and the first appearance of platelets adhering inside the venule opposite the tip of the micropipette.2. Repeated applications of ADP to the same site on a venule caused the appearance of white bodies after intervals which were almost constant for up to 3 hr.3. The time to first appearance of a white body was inversely related to the iontophoretic current between about 10 and 200 nA. Currents smaller than 10 nA had no effect on the platelets. With currents of 200 nA or more the time remained at a minimum of less than 20 sec.4. With currents of about 300 nA the minimum time increased little as the pipette tip was withdrawn up to 20 mu from the venule; with greater distances the time increased progressively.5. Histamine caused gaps to appear between endothelial cells in cheek pouch venules. Histamine at a concentration of 10 mM in micropipettes was applied iontophoretically by currents of 300 nA to venules at the same sites as ADP. Histamine alone had no effect on circulating platelets. When applied before and together with ADP, histamine decreased the time to first appearance of white bodies by up to 40% below that determined with ADP alone. Iontophoretically applied histamine did not alter the mean blood flow velocity in the venules.6. After stopping the application of histamine, the time to first appearance of white bodies produced by ADP increased again in about 5 min to the control values.7. Bradykinin, which does not cause endothelial gaps in cheek pouch venules, did not accelerate the induction of white bodies like histamine.8. There were no microscopic abnormalities in venules in which white bodies had formed. Venules exposed to histamine accumulated circulating carbon particles in discrete wall areas.9. It is concluded that adhering white bodies can be induced repeatedly in normal venules by direct action of externally applied ADP on circulating platelets and that the accelerating effect of histamine on white body formation is due to the separation of endothelial cells which accelerates the inward diffusion of ADP.

Adenine Nucleotides↗
PubMedDate not supplied

Metabolism and distribution of [2,3-14C]acrolein in Sprague-Dawley rats.

The metabolism and disposition of [2,3-14C]acrolein was studied in Sprague-Dawley rats after oral or intravenous dosing. Four groups of ten rats (five male and five female) were dosed with radiolabeled acrolein intravenously at 2.5 mg kg-1 (Group 2), orally by gavage at 2.5 mg kg-1, either as a single dose (Group 3) or after 14 daily doses of unlabeled acrolein (Group 4), or orally by gavage at 15 mg kg-1 (Group 5). Urine, feces, expired air and organic volatiles were collected for 7 days, after which the animals were sacrificed and tissues collected. All samples were analyzed for total radioactivity. After 7 days, the excretory patterns of male and female rats were almost identical. Urinary excretion was highest in the intravenously dosed animals (66-69%) and lowest in the Group 5 animals (36-40%), whereas the reverse was true for feces (< 2% for i.v. Group 2 animals and 28-30% for the Group 5 animals). Carbon dioxide expiration was comparable (26-31%) across all groups. Tissue concentrations of radioactivity were minimal in all groups (< 1.2%), but concentrations of radioactivity were highest in the intravenous Group 2 animals. The time course of excretion for all groups was similar with the exception of the high-dose animal group, which showed a pronounced delay in excretion during the first 12 h.

Acrolein↗
PubMedDate not supplied

Prevention of transfusion-associated cytomegalovirus infection in very low-birthweight infants using frozen blood and donors seronegative for cytomegalovirus.

During a 15-month period, 34 low birthweight infants (less than 1300 g) lacking maternal antibody to cytomegalovirus (CMV) received transfusions from an average of 10 donors per infant. Blood products consisted of predominantly washed deglycerolized frozen red cells from donors lacking antibody to CMV (an average of nine seronegative donors per infant). None of these infants acquired CMV infection while hospitalized. The absence of acquired CMV infections in these infants was in marked contrast (p less than 0.001) to the incidence of CMV infections in seronegative low-birthweight infants during the previous 21-month period when 28 percent acquired CMV (7 of 25 infants). The infants in this previous group received transfusions from an average of 11 donors per infant with an average of four seropositive donors per infant. These results confirm that hospital-acquired CMV infections can be prevented for very low-birthweight infants by donor selection and/or blood processing.

Antibodies, Viral↗
PubMedDate not supplied

Disposition of 8-methoxypsoralen in the rat. Induction of metabolism in vivo and in vitro and identification of urinary metabolites by thermospray mass spectrometry.

The pharmacokinetics and metabolism of 8-methoxypsoralen (8-MOP) were measured in the catheterized rat after pretreatment for 3 days with phenobarbital (PB), beta-naphthoflavone (BNF), 8-MOP, or vehicle. After an iv injection of 10 mg/kg of [14C]8-MOP, timed blood samples were collected and analyzed using a sensitive and specific assay for [14C]8-MOP. Total body clearance of 8-MOP increased from 0.55 +/- 0.06 liter/kg/hr in control rats to 5.6 +/- 0.4, 2.7 +/- 0.4, and 1.2 +/- 0.0 liters/kg/hr in rats pretreated with BNF, PB, and 8-MOP, respectively, indicating that all three compounds are inducers of 8-MOP metabolism. The pattern of urinary metabolites was altered by the enzyme inducers. The urinary excretion of the sulfate conjugate of 5-hydroxy-8-methoxypsoralen was increased from 10 to 40% of the dose after pretreatment with PB. This intact conjugate was identified using thermospray and fast atom bombardment mass spectrometry. Pretreatment with 8-MOP and BNF increased 2- and 3-fold, respectively, the urinary excretion of a labile sulfate conjugate of 5,8-dihydroxypsoralen. Metabolism of 8-MOP was demonstrated in the 9000 g supernatant and microsomes of rat liver and shown to be inducible by pretreatment of rats with BNF, PB, and 8-MOP. 8-MOP was metabolized in incubations with liver microsomes at rates of 0.22 +/- 0.06, 0.38 +/- 0.06, 0.78 +/- 0.07, and 0.91 +/- 0.03 nmol/min/mg of protein for vehicle, 8-MOP-, PB-, and BNF-pretreated rats, respectively. Results of our investigation indicate that the success of therapy with 8-MOP may be influenced by pharmacokinetic interactions with other drugs.

Animals↗
PubMedDate not supplied

Salicylate removal during plasma exchange in normal volunteers.

The removal of salicylate by plasma exchange in normal subjects was studied. Six healthy men volunteers were given aspirin 975 mg every six hours for five days before undergoing plasma exchange. Blood samples for determination of serum salicylate concentrations were obtained from each subject before the 0730 aspirin dose on study days 3-6 and at hourly intervals for several hours before and after plasma exchange, which was performed at approximately 1500 on study day 5. Blood cell counts, serum albumin concentrations, and other blood chemistry values were also evaluated. Salicylate concentrations in serum and in plasma removed by exchange were determined spectrophotometrically. In each subject, serum salicylate concentrations before and after plasma exchange were compared, as were total area under the serum concentration-time curve and salicylate clearance on and off plasma exchange. The mean trough salicylate concentration at 1930 after plasma exchange on day 5 was significantly lower than the mean trough concentration at 1330 before plasma exchange on the same day. The mean AUC during the six-hour period in which plasma exchange occurred was significantly smaller than the AUC in the six-hour period before plasma exchange. Serum albumin concentrations decreased by a mean of 1.7 g/dl as a result of plasma exchange; however, the mean +/- S.D. amount of salicylate removed was only 191.0 +/- 52.4 mg. The amount of salicylate removed by plasma exchange in this study does not appear to be clinically important.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗