Shortening of bleeding time after intranasal administration of 1-deamino-8-D-arginine vasopressin to patients with chronic uremia

1-deamino-8-D-arginine vasopressin (DDAVP) was administered intranasally in a dose of 2 micrograms/kg BW to 17 uremic patients (16 maintained on chronic hemodialysis and 1 treated conservatively). The bleeding time was significantly shortened 120 minutes after DDAVP administration (from 18.1 +/- 7.5 minutes to 12.3 +/- 6.4 minutes p less than 0.001). Factor VIII related antigen (VIII: Ag) did not change. Factor VIII ristocetin cofactor activity (VIII: RCof) significantly increased (from 251.2 +/- 162.0 to 336.5 +/- 167.2 p less than 0.025). Platelet count decreased significantly after DDAVP (from 174.9 +/- 43.8 X 10(9)/l to 155.6 +/- 45.9 X 10(9)/l 30 minutes p less than 0.01 and 129.8 +/- 45.2 X 10(9)/l p less than 0.005 120 minutes after DDAVP). Antithrombin III concentration, and hematocrit did not change. Our data indicate that further clinical studies of intranasal DDAVP in uremic patients during episodes of bleeding are warranted.     

Vasopressin inhibits diuresis induced by water immersion in humans.

We tested the hypothesis that 1-desamino-8-D-arginine vasopressin (DDAVP), a V2-receptor agonist, could inhibit the diuresis induced by water immersion in humans. Water and electrolyte excretion, plasma atrial natriuretic factor concentration, and plasma aldosterone concentration were measured initially and after 3 h of water immersion in 13 healthy sodium-replete men given either placebo or 20 micrograms of intranasal DDAVP. Guanosine 3',5'-cyclic monophosphate and urea excretion and urine osmolality were also determined. DDAVP inhibited the diuresis induced by water immersion in men: 758 +/- 168 (SE) ml/3 h in the placebo group vs. 159 +/- 28 ml/3 h in the DDAVP group (P less than 0.05). After 3 h of water immersion, plasma atrial natriuretic factor concentrations were increased from 11 +/- 2 to 20 +/- 4 pg/ml in the placebo group and from 14 +/- 2 to 33 +/- 4 pg/ml in the DDAVP group (P less than 0.05). Plasma aldosterone concentrations were decreased from 98 +/- 18 to 45 +/- 6 pg/ml in the placebo group (P less than 0.05) and from 54 +/- 17 to 25 +/- 5 pg/ml in the DDAVP group (P less than 0.05). Despite these changes in aldosterone and atrial natriuretic factor concentrations, which should increase sodium excretion, DDAVP decreased the natriuresis induced by water immersion in humans: 56 +/- 8 meq Na+/3 h in the placebo group vs. 36 +/- 6 meq Na+/3 h in the DDAVP group (P less than 0.05). DDAVP may be used to prevent the diuresis associated with central redistribution of blood volumes that occur during water immersion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cryoprecipitate of intermediate purity produced in a closed thaw-siphon system from DDAVP stimulated blood donor plasma.

The effects of intravenous administration of DDAVP to blood donors and the use of DDAVP plasma for the production of cryoprecipitate in the closed thaw-siphon system were evaluated. DDAVP treatment produced on the average a 3.2-fold rise in plasma levels of factor VIII. Von Willebrand factor antigen increased to a lesser extent. Cryoprecipitate prepared from 220-280 ml aliquots of DDAVP stimulated donor plasma contained 472 +/- 210 units of factor VIII and 276 +/- 130 units of von Willebrand factor antigen. The average yield of factor VIII was 57% of that in the prefrozen plasma. The specific activity of factor VIII in cryoprecipitate was 0.77 +/- 0.44 U/mg protein, comparable to that for intermediate purity concentrates. Thus, by the use of DDAVP and the thaw-siphon technique it is possible to produce cryoprecipitate 4-7 times as potent as conventionally manufactured preparations.     

Effects of taprostene, a chemically stable prostacyclin analogue, in patients with ischaemic peripheral vascular disease: a placebo controlled double-blind trial

Thirty patients with ischaemic peripheral vascular disease and intermittent claudication were randomly allocated to receive either placebo or taprostene, a chemically stable prostacyclin analogue, intravenously at a rate of 25 ng/kg/min for 6 hours daily on 5 consecutive days. Taprostene produced a significant (p less than 0.05) increase in absolute walking time compared to placebo on one day after infusion and at 1, 4 and 8 weeks (14% vs 2.8%) later. Taprostene also produced a significant (p less than 0.05) increase in the pain-free walking time compared to placebo in the follow-up period (8 weeks after infusion: 23% vs 3.8%). During the infusion period systolic and diastolic blood pressure decreased (p less than 0.05) and heart rate was accelerated (p less than 0.05) in the taprostene treated group whereas no change was monitored in the placebo group. The ankle/brachial Doppler index was unaffected by taprostene. The platelet half-life was significantly (p less than 0.05) prolonged following taprostene-infusion (72.6 +/- 9.35 vs 77.9 +/- 7.44 hours). However, no change on platelet half-life was found in the placebo group (p less than 0.05). Various measures of platelet function parameters followed in vitro (ADP-induced aggregation, platelet sensitivity to PGI2, PGE1, PGD1 and taprostene, concentrations of platelet factor 4 and beta-thromboglobulin) showed no change with taprostene. Measures of circulating platelet aggregates and endothelial cells count showed no changes during the 2 months follow-up period too. It is assumed that taprostene may be of clinical benefit in patients with ischaemic peripheral vascular disease. However, future investigations have to be carried out to assess the optimal dose regime.     

Variability in response to cryoprecipitate treatment for hemostatic defects in uremia

Cryoprecipitate is frequently administered as treatment for hemostatic defects in patients with uremia. The only published data supporting this approach however, involves seven patients described by Janson and colleagues in whom bleeding times were shortened and bleeding complications reduced after cryoprecipitate infusion. We retrospectively reviewed our institution's experience with cryoprecipitate in this setting. Five patients had sufficiently complete data for evaluation of the efficacy of therapy with cryoprecipitate, including pretreatment bleeding time greater than 15 minutes, normal coagulation studies, and platelet count greater than 100,000/microliters. Two patients had normalization of their bleeding time and a favorable clinical outcome after cryoprecipitate infusion. Three patients failed to shorten their bleeding time after cryoprecipitate infusion or, in one case, multiple infusions. One of these latter patients had correction of his abnormal bleeding time after subsequent administration of deamino-8-D-arginine vasopressin (DDAVP). We conclude that the hemostatic response to cryoprecipitate therapy is variable, and that cryoprecipitate therapy does not achieve restoration of normal hemostasis in some patients with uremic bleeding.     

Chemically induced vasospasm: the effect of ischemia, vessel occlusion, and adrenergic blockade

Vasospasm in revascularized tissue can compromise tissue perfusion even though the microsurgical anastomoses remain patent. Circulating catecholamine stimulates peripheral vasoconstriction. Chemical vasospasm was induced by the intraarterial administration of norepinephrine to denervated rat hind limbs. Heel pad blood flow was assessed by laser-Doppler velocimetry. Mean blood flow was 463 +/- 106 in the denervated leg and 337 +/- 50 in the opposite (intact) leg (p less than 0.01). Flow in the denervated leg decreased 78 percent (463 +/- 106 to 100 +/- 23) within 5 minutes of norepinephrine administration and did not return to normal for 30 minutes. Norepinephrine administration in the presence of 1 and 3 hours of ischemia decreased flow at 5 minutes to 6.6 and 6.0 percent of normal, respectively (31 +/- 14, 28 +/- 14, control 100 +/- 23; p less than 0.001). Administration of intraarterial norepinephrine distal to a femoral artery occluded for 1 and 5 minutes reduced flow following clamp release to 11.2 and 7.1 percent of normal 5 minutes after clamp release (52 +/- 9, 33 +/- 7, control 100 +/- 23; p less than 0.001). Comparison of the 1-minute and 5-minute groups to each other showed a significant flow decrease in the 5-minute group (p less than 0.007). This indicates that the observed decrease in flow was related both to the presence of a vessel occlusion and to the length of the occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

The clinical significance of different routes of desmopressin (DDAVP) administration in various bleeding disorders

In our study, we wanted to evaluate the clinical effect of s.c. DDAVP on haemostasis in different kinds of bleeding disorders. A total of 109 patients was treated with DDAVP s.c. at a dose of 0.4 microgram/Kg body weight. An effect of DDAVP on F VIII modalities was found after s.c. injection in all patients, but in comparison to i.v. DDAVP, the effect seems to be somewhat less. From our data, the patients blood groups do not influence the amount of F VIII modalities. Furthermore, the s.c. injection of DDAVP was found to be effective in patients with disorders of primary haemostasis. A number of operations was performed under the use of s.c. DDAVP in 24 patients with different kinds of bleeding disorders, in none of them, bleeding complications occurred.     

Bleeding time in patients with hepatic cirrhosis.

OBJECTIVE--To determine the frequency of an abnormal bleeding time in patients with cirrhosis and to relate this to known factors that affect primary haemostasis and to the severity of liver disease. DESIGN--Prospective clinical and laboratory study in patients admitted for complications or investigations of liver disease. SETTING--Royal Free Hospital hepatobiliary and liver transplantation unit. SUBJECTS--100 Consecutive inpatients aged 17-74 with various forms of cirrhosis, including alcoholic, biliary, autoimmune, viral, and cryptogenic. At least 10 days had elapsed since any episodes of bleeding, resolution of sepsis, or alcohol intake. No patient was taking any drug known to affect primary haemostasis. MAIN OUTCOME MEASURES--Bleeding time as measured with the Simplate double blade template device. A bleeding time longer than 10 minutes was considered abnormal. Other measures were platelet count, prothrombin time, partial thromboplastin time, packed cell volume, and blood urea, serum bilirubin, and serum albumin concentrations, all measured on each subject at the same time by standard laboratory methods. RESULTS--A weak but significant correlation existed between the bleeding time and the platelet count (rs = 0.483; p less than 0.001). There were significantly lower platelet counts, longer prothrombin times, and higher blood urea and serum bilirubin concentrations in the 42 patients with bleeding times of 10 minutes or more compared with the 58 patients with bleeding times less than 10 minutes. Multiple linear regression analysis showed that the bilirubin concentration as well as the platelet count was independently correlated with the bleeding time. The combination of a platelet count greater than 80 x 10(9)/l and a prothrombin time less than 17 seconds (usually taken as safe limits for performing routine liver biopsy) did not predict a normal bleeding time. Ten of 39 patients fulfilling these criteria had a prolonged bleeding time. CONCLUSIONS--Prolonged bleeding time is common in patients with cirrhosis, even in those with prothrombin times and platelet counts within "safe limits" for invasive procedures. The severity of liver disease as assessed by the bilirubin concentration plays an important part in determining the bleeding time in cirrhosis. The bleeding time should be measured when assessing patients for invasive procedures who have a raised bilirubin concentration or poor hepatic function, even if the platelet count and prothrombin time are considered adequate.     

Nifedipine in hypertensive emergencies.

The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 +/- 22/126 +/- 14 mm Hg to 152 +/- 20/89 +/- 12 mm Hg after 30 minutes, p less than 0.001). Heart rate increased from 74 +/- 11 to 84 +/- 11 beats/minute (p less than 0.01); this effect was inversely related to age (r = -0.65, p less than 0.01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment ) r = 0.67, p less than 0.001 for systolic, and r = -0.58, p less than 0.01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%. Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.     

Effects of bopindolol on platelet function in hypertension at rest and during exercise

The effects of bopindolol, a new nonselective beta-blocking agent, on platelet function have been studied in 10 male hypertensive patients given the drug (1 mg/day) in turn for eight weeks. Bopindolol significantly (p less than 0.01) decreased the bicycle exercise- (1.5 W/kg body weight for 6 minutes) induced increase in platelet aggregation. During bopindolol-treatment both the slope and the height of the platelet aggregation response curve were moderately decreased at rest before exercise and significantly (p less than 0.05) decreased at rest after exercise. During exercise the slope amounted to 75.4 +/- 44 degrees before and to 70.8 +/- 5.3 degrees after therapy (p less than 0.01), the height to 64.0 +/- 11.9% before and to 58.1 +/- 14.7% (p less than 0.05) after therapy. Furthermore, bopindolol significantly increased the exercise-induced decrease in platelet sensitivity to PGI2 (p less than 0.05; IC-50-value: 2.10 +/- 0.47 vs 1.88 +/- 0.31 ng/ml) and PGD2 (p less than 0.05; IC-50-value: (19.88 +/- 2.10 vs 18.57 +/- 1.63 ng/ml). Bopindolol also significantly (p less than 0.05) decreased the exercise-induced elevation in serum-TXB2 (244.9 +/- 35.2 vs 237.3 +/- 27.2 ng/ml) and plasma-TXB2 (15.7 +/- 6.3 vs 13.1 +/- 3.7 pg/ml). The platelet count, the plasma levels of 6-oxo-PGF1 alpha, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were not affected by bopindolol. It is concluded that bopindolol favourably affects platelet function, in that it lowers exercise-induced platelet aggregation and TXB2-formation in therapeutical doses and increases platelet sensitivity to antiaggregatory prostaglandins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factor VIII complex in uraemia and effects of haemodialysis.

Levels of the factor VIII complex were found to be raised in patients with chronic renal failure and further raised by regular dialysis. Increased fibrinogen concentrations were also found. These results suggest the existence of a prothrombotic state in uraemia that is exacerbated by haemodialysis. Ristocetin-induced platelet agglutination, however, was depressed in uraemia and worsened by dialysis. This defect may be transferred to normal platelets from dialysed uraemic plasma, suggesting the existence of an inhibitor of the interaction between factor VIII and platelet glycoprotein. These results may help to explain the anomaly of a prolonged bleeding time together with accelerated atherogenesis that is found in patients with uraemia receiving dialysis.     

蝮蛇抗栓酶对冻伤家兔血凝系统某些指标的影响

本研究观察了家兔双后足重度冻伤后用蝮蛇抗栓酶（０．２５Ｕ／ｋｇ体重加入２０ｍｌ／ｋｇ体重生理盐水中,耳缘静脉点滴）进行治疗后其血凝系统某些指标的改变。结果表明,重度冻伤后家兔的出血时间及凝血时间明显缩短,血小板功能呈不同程度的改变,血浆纤维蛋白原含量增加,血液处于高凝状态;用蝮蛇抗栓酶治疗后,上述各项指标均有不同程度的改善,结果提示,蝮蛇抗栓酶可明显缓解冻伤所致的血凝增强的病变过程,这对重度冻伤的治疗将起到重要作用     

The role of Willebrand factor in platelet - blood vessel interaction, including a discussion of resistance to atherosclerosis in pigs with von Willebrand's disease

Von Willebrand pigs have all the manifestations of the severe human disease. The role of Willebrand antigen (VIII R:AG) and ristocetin cofactor (VIII: RWF) was assessed in these pigs by (1) transfusion and (2) "in vitro" bleeding time assay. The skin bleeding time became normal when the level of transfused Willebrand factor (VIII R:AG/RWF) was raised in the plasma above 30 U/dl. After single or repeated transfusions, skin capillary endothelium and platelets were still distinguished from normal by VIII R:AG deficiency. When incisions in excised porcine skin ("in vitro" bleeding time) were perfused with blood and plasma fractions, haemostasis occurred when plasmatic Willebrand factor exceeded 30 U/dl whether the skin or platelets came from normal or from von Willebrand pigs. The platelet plug occluding the skin incision contained VIII R:AG by immunofluorescence. Willebrand factor appears to coat surfaces and to serve as a platelet attachment protein. These bleeder pigs are resistant to atherosclerosis. If platelets are involved in early atherosclerotic lesions, the role of Willebrand factor in platelet - blood vessel interaction may be important.     

Inhibition of microsurgical thrombosis by the platelet glycoprotein IIb/IIIa antagonist SR121566A

Despite major improvements in tools and significant refinements of techniques, microsurgical anastomosis still carries a significant risk of failure due to microvascular thrombosis. The key to improving the success of microvascular surgery may lie in the pharmacologic control of thrombus formation. Central to pathologic arterial thrombosis are platelets. Glycoprotein IIb/IIIa is a highly abundant platelet surface receptor that plays a major role in platelet aggregation by binding platelets to each other through the coagulation factor fibrinogen. To explore the ability of antithrombotic agents to prevent microvascular thrombosis, a rabbit ear artery model was used in which a standardized arterial injury results in predictable thrombus formation. This model was used to examine whether SR121566A, a specific and potent glycoprotein IIb/IIIa inhibitor, can successfully prevent microsurgical thrombosis.Using a coded, double-blind experimental design, 20 rabbits (40 arteries) were assigned to four treatment groups: (1) saline injection (n = 10), (2) acetylsalicylic acid 10 mg/kg (n = 10), (3) heparin 0.5 mg/kg bolus with subsequent intermittent boluses of 0.25 mg/kg every 30 minutes (n = 10), and (4) SR121566A 2 mg/kg bolus (n = 10). After vessel damage and clamp release, arteries were assessed for patency at 5, 30, and 120 minutes by the Acland refill test. Coagulation assays, in vivo bleeding times, and ex vivo platelet aggregation studies were also conducted. Scanning electron microscopy was used to examine mural thrombus composition.A significant, fourfold increase in vessel patency following administration of SR121566A over saline control (80 percent versus 20 percent patency, respectively, at 35 minutes after reperfusion, p < 0.01) was noted. This was correlated with marked inhibition of ex vivo platelet aggregation. This antiplatelet treatment did not prolong coagulation assays (mean international normalized ratio: saline, 0.66 +/- 0.04; SR121566A, 0.64 +/- 0.03; mean thromboplastin time: saline, 19.63 +/- 0.67; SR121566A, 17.87 +/- 3.27) and bleeding times (mean bleeding time: saline, 42 +/- 4; SR121566A, 48 +/- 6). Scanning electron microscopy demonstrated extensive platelet and fibrin deposition in control vessel thrombi. In contrast, thrombi from SR121566A-treated vessels demonstrated predominance of fibrin with few platelets when examined under scanning electron microscopy.Administration of SR121566A was associated with a significant increase in vessel patency, without deleterious effects on coagulation assays or bleeding times. The increase in vessel patency was correlated with inhibition of platelet aggregation and decreased platelet deposition, as demonstrated by scanning electron microscopy. Glycoprotein IIb/IIIa antagonists represent a new class of anti-platelet agents that may be suited for inhibiting microsurgical thrombosis. This study supports further investigation into the use of these agents in microsurgery.     

Involvement of Na+/H+ exchanger in desmopressin-induced platelet procoagulant response

Desmopressin (DDAVP) action on platelets is associated with the development of procoagulant response but the underlying mechanism of this phenomenon is not known. We investigated whether this effect of DDAVP might be due to activation of plasma membrane Na+/H+ exchanger. The DDAVP-induced platelet procoagulant response, measured as phospholipid-dependent thrombin generation, was dose dependent and significantly weaker than that produced by collagen or monensin (mimics Na+/H+ antiport). Both the DDAVP- and collagen-produced procoagulant responses were less pronounced in the presence of EIPA, an Na+/H+ exchanger inhibitor. Flow cytometry studies revealed that in vitro treatment of platelets with DDAVP or collagen was associated with the appearance of both degranulated (and fragmented) and swollen cells. The DDAVP-evoked rise in size and granularity heterogeneity was similar to that produced by collagen or monensin and was not observed in the presence of EIPA. Using flow cytometry and annexin V-FITC as a probe for phosphatidylserine (PS) we demonstrated increased and uniform binding of this marker to all subsets of DDAVP-treated platelet population. The DDAVP-evoked PS expression was dose dependent, strongly reduced by EIPA and weaker than that caused by monensin or collagen. As judged by optical swelling assay, DDAVP in a dose dependent manner produced a rise in platelet volume. The swelling was inhibited by EIPA and its kinetics was similar to that observed in the presence of monensin. Electronic cell-sizing measurements showed an increase in mean platelet volume and a decrease in platelet count and platelet crit upon treatment with DDAVP. DDAVP elicited a slow (much slower than collagen) alkalinization of platelet cytosol. Altogether the data indicate an involvement of Na+/H+ exchanger in the generation of procoagulant activity in DDAVP-treated platelets.     

Gliclazide mainly affects insulin secretion in second phase of type 2 diabetes mellitus.

We studied the effect of the acute administration of gliclazide at 160 mg on insulin release during hyperglycaemic clamps in 12 type 2 diabetes patients, age 50 +/- 9.0 years, diabetes duration 5.5 +/- 4.8 years, fasting blood glucose 9.6 +/- 2.1 mmol/L (means +/- SD). After a 210 min of hyperinsulinaemic euglycaemic clamp (blood glucose 4.6 +/- 0.14mmol/L), gliclazide or placebo (randomised, double-blind, cross-over) was administered; 60 minutes later, a hyperglycaemic clamp (4hr) at 8mmol/L was started. Plasma C-peptide levels increased significantly after the administration of gliclazide (increment 0.17 +/- 0.15 vs. 0.04 +/- 0.07 nmol/L, p = 0.024) before the clamp. After the start of the hyperglycaemic clamp, the areas under the curve (AUC) for insulin and C-peptide did not differ from 0-10 min (first phase) with gliclazide. However, second-phase insulin release (30-240 min) was markedly enhanced by gliclazide. AUC plasma insulin (30 to 240 min) was statistically significantly higher after gliclazide (12.3 +/- 13.9 vs. -0.56 +/- 9.4 nmol/L x 210 min, p = 0.022); similarly, AUC plasma C-peptide (30 to 240 min) was also higher: 128 +/- 62 vs. 63 +/- 50 nmol/L x 210 min, p = 0.002). In conclusion, in long-standing type 2 diabetes the acute administration of gliclazide significantly enhances second phase insulin release at a moderately elevated blood glucose level. In contrast to previous findings in mildly diabetic subjects, these 12 type 2 diabetes patients who had an inconsiderable first phase insulin release on the placebo day, only showed an insignificant increase in first phase with gliclazide.     

Prediction of haemorrhagic diathesis in thrombocytopenia by mean platelet volume.

The Coulter counter, model S Plus, Provides a platelet count and a mean platelet volume in all routine specimens of blood for cell count. The value of mean platelet volume in the prediction of the haemostatic potential of thrombocytopenic patients was investigated in 175 patients with haematological disorders who underwent 1473 blood counts over five months. Eighty-four haemorrhagic episodes were detected, most in thrombocytopenic patients. The mean platelet volume of patients with haemorrhagic tendency was significantly lower (5.52 +/- SD 0.7 fl) than that of patients without these tendencies (7.87 +/- SD 1.75 fl) (p less than 0.001). In cases of severe thrombocytopenia (less than 20 x 10(9)/1 platelets) haemorrhagic episodes were frequent; however, the frequency of bleeding was considerably lower in cases in which the mean platelet volume was higher than a suggested cut-off point of 6.4 fl. Discriminant analysis selected mean platelet volume as more important than platelet count for prediction of haemorrhagic state in severe thrombocytopenia. In view of the useful discrimination that mean platelet volume provides between thrombocytopenic patients who bleed and those who do not bleed, it may serve as a guide to predict the danger of haemorrhage and the need for prophylactic platelet transfusion.     

A simple and reliable method for monitoring platelet serotonin levels in rats

A simple and reliable method for individual monitoring of platelet serotonin in rats is developed. Platelet-rich plasma is prepared under standardized conditions from 1 mL of venous blood and the platelets are quantitatively separated by a highly reproducible procedure. Platelet serotonin content is determined spectrophotofluorometrically and the results are comparatively expressed per standardized platelet rich plasma sample (1.01 +/- 0.18 microgram), per mg of platelet protein (1.57 +/- 0.15 microgram) and per 10(9) platelets (2.16 +/- 0.38 micrograms). Normal distribution of platelet serotonin levels in a sample of 338 animals is shown. By use of the described method, the intraindividual stability of platelet serotonin concentration in rats is demonstrated for the first time.     

Effect of intravenous administration of cimetidine on renal excretion of calcium, phosphates, magnesium and adenosine cyclic monophosphate

An effect of cimetidine on parathyroid glands functioning in healthy subjects was evaluated. Serum calcium, phosphate, and magnesium concentrations together with renal excretion++ of these ions in healthy subjects as well as cAMP excretion++ in selected individuals were determined before and following intravenous administration of cimetidine (Altratmet Lek Ljublijana) in total dose of 500 mg (50 mg injected rapidly as a bolus following with 450 mg in an intravenous infusion during 60 minutes). No significant changes in serum calcium, phosphates, and magnesium concentrations were noted. Renal clearance of calcium and magnesium remained unchanged whereas renal phosphate excretion++ increased from 10.69 +/- 4.9 mL/min to 15.1 +/- 5.41 mL/min (p less than 0.02). Excretion++ of 3.5 cAMP increased from 2.65 +/- 2.19 nM/min to 5.16 +/- 2.0 nM/min (p less than 05). The obtained results do not exclude stimulating effect of intravenous cimetidine on parathyroid glands. Cimetidine given intravenously in the bleeding gastric or duodenal ulcers in the course of the primary hyperparathyroidism+ may decrease serum phosphate levels due to increased exretion of this ion with the urine.