The effect of radioprotective agents on erythropoiesis In irradiated mice

1969 ◽  
Vol 47 (1) ◽  
pp. 65-71
Author(s):  
P. V. Vittorio ◽  
E. A. Watkins ◽  
S. Dziubalo-Blehm

The radioiron test (i.e. 59Fe uptake by blood, spleen, and liver) was used to evaluate the degree of protection (1 day after irradiation) and effect on recovery (7 days after irradiation) of the erythropoietic system when radioprotective agents were administered. In blood, spleen, and liver, AET administered prior to irradiation caused a decreased radiation effect on 59Fe uptake 1 day after irradiation, and a subsequent parallel return with the irradiated nonprotected group to the control value. This indicated that the early recovery by the protected group was probably due to less initial damage. The amount of protection afforded the erythropoietic system by sulfhydryl agents was in good agreement with irradiation survival studies and indicated that a good sulfhydryl radioprotective agent provided good protection, and a poor sulfhydryl radioprotective agent provided poor protection to the erythropoietic system. Thus the radioiron test is a good method to evaluate sulfhydryl compounds as radioprotective agents. Endotoxin demonstrated poor correlation between the early (1 day) erythropoietic effect and survival in irradiated mice, but recovery studies (7 days) showed much better agreement. The biological amine serotonin produced poorer initial protection to the erythropoietic system and slower recovery than AET even though the dose reduction factor of each was comparable. Serotonin must, therefore, protect other systems which then contribute to the eventual recovery of the erythropoietic system, and survival.

1987 ◽  
Author(s):  
E M Essien ◽  
A L Inyang

Reduced circulating platelet count sometimes to thrombocytopenic levels in man and normally severe thrombocytopenia in animals are well known features of acute Plasmodium falciparum or experimental P. bergei infections in these respective organisms. Suggested mechanism(s), disseminated intravascular coagulation or immune mediated mechanism, thought to be involved in these observations are disputed. Shortened platelet survival has been reported in man.We now present data on platelet survival and total platelet sialic acid concentration in P. bergei-infected Wistar rats. A total of 52 rats were used. For the platelet survival studies each of the 8 suckling test animals was infected by intraperi-toneal route with mouse-passaged P. bergei 4-5 days before inaction of Cr-labelled homologous rat platelets (50 μCi Na51 CrC4/rat) the platelets being obtained from adult Wistarrats. Blood samples were then collected 2 hr after the injection (zero hr sample) and subsequently at 17.0, 42.5 and 66 hr s.Platelet recovery and survival curves were determined on these samples. It was found dat fewer platelets (as % recovery) were obtained from each infected rat sample compared with control, the difference was significant in the 42.5 and 66 hr samples: 7.9 ± 8.1 (test) vs 41.4 ± 15.2% (C) for 42.5 hr and 2.8 ±4.1 (t) vs 26.8 ± 6.2% (C) for the 66 hr samples (p < 0.005 for each). For sialic acid determinations, 40 suckling Wistar rats (30 test, 10 control) were treated as for survival studies.At identical periods, blood was collected, washed platelets obtained, lysed and protein and total sialic acid determined by Lowry (1951) and Aminoff (1961) methods respectively. Total sialic acid of 7.02 ± 4.21 nM/mg protein at 42.5 hrs and 4.8 ± 2.14 at 66 hrs were significantly less than control value of 11.43 nm/mg protein and also showed a negative correlation (r = -0.95) with % parasitaemia.It is concluded that P. bergei infection causes a reduction in total platelet sialic acid with resultant significant shortening of the platelet life span.


2003 ◽  
Vol 40 (6) ◽  
pp. 618-623 ◽  
Author(s):  
Telma Vidotto de Sousa ◽  
Ilza Lazarini Marques ◽  
Araken Fernando Carneiro ◽  
Heloisa Bettiol ◽  
JoséAlberto de Souza Freitas

Objective To correlate nasopharyngoscopic findings with clinical manifestations during the first month of life and study the course of respiratory obstruction during the first year in infants with Robin sequence (RS). Design A longitudinal prospective study of children with RS. Setting Hospital de Reabilitação de Anomalias Craniofaciais, University of São Paulo, Bauru-SP, Brazil, 1998 to 2000. Patients Fifty-six children were studied from the age of 1 month to 12 months. Interventions The type of respiratory obstruction was defined by nasopharyngoscopy. Patients for whom glossoptosis was the only mechanism of respiratory obstruction were classified as having mild, moderate, or severe glossoptosis by nasopharyngoscopy and as mild, moderate, or severe cases with respect to the clinical manifestations. Results Forty-two (75%) patients showed respiratory obstruction caused by glossoptosis; seven (43.7%) of these infants with mild clinical manifestations showed moderate glossoptosis during the first month of life and five (31.3%) presented severe glossoptosis; 10 (45.5%) of the infants with severe clinical manifestations showed moderate and 11 (50.0%) severe glossoptosis. At 12 months of age, glossoptosis was mild or absent in 83.3% of the patients, moderate in 14.3% and severe in 2.4%. Conclusions A poor correlation between the severity of glossoptosis and the severity of clinical manifestations was observed for patients with respiratory obstruction caused by glossoptosis during the first month of life, but the correlation between glossoptosis and respiratory distress according to age was statistically significant. Nasopharyngoscopy is not a good method for predicting the severity of the clinical course of respiratory obstruction caused by glossoptosis.


1993 ◽  
Vol 75 (6) ◽  
pp. 2580-2585 ◽  
Author(s):  
G. Manier ◽  
J. Moinard ◽  
H. Stoicheff

To determine the effect of maximal exercise on alveolocapillary membrane diffusing capacity (Dm), 12 professional handball players aged 23.4 +/- 3.3 (SD) yr were studied before and during early recovery from a progressive maximal exercise [immediately (t0), 15 min, and 30 min (t30) after exercise]. Lung capillary blood volume and Dm were determined in a one-step maneuver by simultaneous measurement of CO and NO lung transfer (DLCO and DLNO, respectively) with use of the single-breath breath-hold method. At t0, DLCO was elevated (13.1 +/- 12.0%; P < 0.01) but both DLNO and Dm for CO remained unchanged. Between t0 and t30, both DLCO and DLNO decreased significantly. At t30, DLCO was not different from the control resting value. DLNO (and consequently Dm for CO) was significantly lower than the control value at t30 (-8.9 +/- 8.1%; P < 0.01). Lung capillary blood volume was elevated at t0 (18.0 +/- 19.0%; P < 0.01) but progressively decreased to near control resting values at t30. Differences in the postexercise kinetics of both DLCO and DLNO point to a role of the transient increase in pulmonary vascular recruitment during the recovery period. We concluded that Dm was somewhat decreased in the 30 min after maximal exercise of short duration, but the exact pulmonary mechanisms involved remain to be elucidated.


1987 ◽  
Vol 253 (2) ◽  
pp. C205-C209 ◽  
Author(s):  
P. R. Morrison ◽  
G. W. Muller ◽  
F. W. Booth

The purpose of this study was to correlate actin synthesis rate and alpha-actin mRNA level in the gastrocnemius-plantaris muscles of limbs during their recovery from 7 days of immobilization in 200- to 280-g female rats. The fractional synthesis rate of actin in control muscle was 1%/day. Actin synthesis rate was 33% of control level at the 7th day of hindlimb immobilization, returned to control value at the 2nd recovery day, and was three times higher than control on the 4th day of recovery. The alpha-actin mRNA was 53% of control at the 7th day of immobilization, and its increase during the 1st 2 recovery days paralleled the increase in actin synthesis rate; this suggests that pretranslational mechanisms caused the initial increase in actin synthesis. Further increases in actin synthesis from the 2nd to the 4th day appear to be under translational control, since actin synthesis was 300% of control on the 4th recovery day and alpha-actin mRNA was only 128% of control.


2018 ◽  
Vol 63 (4) ◽  
pp. 588-594
Author(s):  
Daniel W. Klyce ◽  
Kristin M. Graham ◽  
Russell W. Lacey ◽  
William E. Carter

1990 ◽  
Vol 64 (03) ◽  
pp. 402-406 ◽  
Author(s):  
M D Oethinger ◽  
E Seifried

SummaryThe present in vitro study investigated dose-, time- and temperature-dependent effects of two-chain urokinase plasminogen activato(u-PA, urokinase) on normal citrated plasma. When 10 μg/ml u-PA wereadded to pooled normal plasma and incubated for 30 min at an ambient temperature (25° C), α2-antiplas-min decreased to 8% of the control value. Incubation on ice yielded a decrease to 45% of control,whereas α2-antiplasmin was fully consumed at 37° C. Fibrinogen and plasminogen fell to 46% and 39%, respectively, after a 30 min incubation at 25° C. Thrombin time prolonged to 190% of control.Various inhibitors were studied with respect to their suitability and efficacy to prevent these in vitro effects. Aprotinin exhibited a good protective effect on fibrinogen at concentrations exceeding 500 KlU/ml plasma. Its use, however, was limited due to interferences with some haemostatic assays. We could demonstrate that L-Glutamyl-L-Glycyl-L-Arginyl chloromethyl ketone (GGACK) and a specific polyclonal anti-u-PA-antibody (anti-u-PA-IgG) effectively inhibited urokinase-induced plasmin generation without interfering with haemostatic assays. The anti-u-PA-antibody afforded full protection ofα2-antiplasmin at therapeutic levels of u-PA.It is concluded that u-PA in plasma samples from patients during thrombolytic therapy may induce in vitro effects which should be prevented by the use of a suitable inhibitor such as GGACK or specific anti-u-PA-antibody.


1987 ◽  
Vol 58 (03) ◽  
pp. 921-926 ◽  
Author(s):  
E Seifried ◽  
P Tanswell

SummaryIn vitro, concentration-dependent effects of rt-PA on a range of coagulation and fibrinolytic assays in thawed plasma samples were investigated. In absence of a fibrinolytic inhibitor, 2 μg rt-PA/ml blood (3.4 μg/ml plasma) caused prolongation of clotting time assays and decreases of plasminogen (to 44% of the control value), fibrinogen (to 27%), α2-antiplasmin (to 5%), FV (to 67%), FVIII (to 41%) and FXIII (to 16%).Of three inhibitors tested, a specific polyclonal anti-rt-PA antibody prevented interferences in all fibrinolytic and most clotting assays. D-Phe-Pro-Arg-CH2Cl (PPACK) enabled correct assays of fibrinogen and fibrinolytic parameters but interfered with coagulometric assays dependent on endogenous thrombin generation. Aprotinin was suitable only for a restricted range of both assay types.Most in vitro effects were observed only with rt-PA plasma concentrations in excess of therapeutic values. Nevertheless it is concluded that for clinical application, collection of blood samples on either specific antibody or PPACK is essential for a correct assessment of in vivo effects of rt-PA on the haemostatic system in patients undergoing fibrinolytic therapy.


1975 ◽  
Vol 34 (01) ◽  
pp. 050-062
Author(s):  
Dale H Cowan ◽  
Richard C Graham ◽  
Patricia Shook ◽  
Ronda Griffin

SummaryTo determine the effect on platelet behavior of transient exposure of platelets to ascorbic acid, studies of platelet function and ultrastructure were done before exposure to ascorbic acid at pH 6.5, during exposure to pH 6.5, and after restoration of pH to pre-acidifìcation levels. The effect of ascorbic acid (A. A.) was compared to that of HCl and citric acid (C. A.). ADP- and collagen-induced aggregation of normal platelets were significantly impaired by both A. A. and C. A. but were less affected by HCl. The release of 14C-serotonin was significantly reduced by each agent. The ultra-structure of normal platelets brought to pH 6.5 by A.A. was normal. After neutralization, there was marked dilatation of the open channel system and loss of the disc shape. When platelets were brought to pH 6.5 by A. A., then neutralized, the aggregates which formed after stimulation by ADP or collagen were smaller than normal, the platelets were less closely approximated, and degranulation was less complete. The data show that exposure of platelets to ascorbic acid for short intervals impairs their function when measured after restoration of pH to levels compatible with maximal responses. Platelet survival studies using autologous platelets labelled with 51Cr in the presence or absence of ascorbic acid showed that the recovery of normal platelets was unaffected by ascorbic acid, whereas recovery of platelets from patients with idiopathic thrombocytopenic purpura, idiopathic thrombocythemia, and alcohol-related thrombocytopenia was markedly reduced. The injury resulting from the use of ascorbic acid in preparing platelets for studies of platelet survival in patients with disorders affecting platelets may impair the recovery of the cells, resulting in artifactual changes in the survival studies.


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