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In order to define the pharmacodynamic profile of salmon calcitonin (sCT) in humans, several markers of the biological activity of the drug have been studied, namely cAMP, adenosine and pO in venous blood, and the cytosolic free calcium level in circulating cells. Different dosages and routes of administration (1.5 IU. kg and 0.75 IU kg IM, and 1.5 IU. kg via nasal spray) were compared. sCT caused an increase in cAMP, adenosine and pO, and a decrease in cytosolic free calcium in neutrophils, lymphocytes and platelets. The peak times of all these parameters ranged between 109 and 182 min, and 101 and 168 min after IM and nasal spray administration respectively. There was greater variability in the values after IM than nasal spray of administration of sCT. It is concluded that adenosine and p02 in venous blood, and cytosolic free calcium in circulating cells are valuable markers of the activity of sCT and that sCT decreases the cytosolic free calcium level in neutrophils, lymphocytes and platelets. Pharmacodynamic analysis of the biological effects of the drug is highly reliable and valuable in predicting its pharmacological profile. sCT administration via a nasal spray is able to produce significant biological effects, although they are less marked than after IM dosing. [ABSTRACT FROM AUTHOR]

Acquired hemophilia is a rare coagulopathy in adults, associated with bleeding complications. Although the etiology of this disorder remains obscure, an autoimmune mechanism produces the development of autoantibodies against factor VIII. About half of cases are associated with other conditions, mainly post-partum, underlying cancer, autoimmune disease. An 81-year-old male was admitted to the hospital with extensive hematomas (neck, chest, arms and lower limbs). There was no family or personal history of congenital bleeding diathesis. He had chronic bronchitis and cerebrovascular disease; no drugs had been used during the month prior to noted symptoms. Laboratory parameters revealed: hemoglobin 10.9 g%, normal platelet count and white blood cells, prolonged activated partial thromboplastin time (98 s), with normal prothrombin time and fibrinogen concentration. An activated partial thromboplastin time mixing study did not show any correction, suggesting a coagulation inhibitor. Lupus anticoagulant and anticardiolipin antibodies were negative. Biochemical, immunological tests and tumor markers were normal. Thoracic and abdominal computed tomographic scan did not reveal pathological images or hematomas. Analysis of clotting factors revealed decreased factor VIII (< 2%) and elevated factor VIII inhibitor (55 Bethesda units). Idiopathic acquired hemophilia diagnosis was made. Red blood cell transfusion and human factor VIII (2000 U/day for 7 days) infusion were initiated, intravenously with methylprednisolone. A progressive improvement in clinical conditions and laboratory parameters was observed. After 18 days the patient was discharged and treated with prednisone. At follow-up control the clinical conditions and laboratory parameters were normal.

The transcutaneous pO2 (tcpO2) changes induced by the increase of temperature to 45 degrees C after electrode stabilization at 37 degrees C were continuously recorded. The mathematical analysis of the curve led us to identify three different parameters: the half-slope "b" time, the angular "mT" coefficient and the angular "mb" parameter, which are not simply the expression of the maximum vasodilation capacity but mainly of the dynamic response of the microcirculatory system to skin heating. These parameters derived from the computerized mathematical analysis of the curve can be also obtained by a graphical approach with a very good approximation. The angular "mb" coefficient was shown to possess the highest statistical power in discriminating the POAD patients from normal controls. The clinical relevance and the possible pathophysiological meaning of these preliminary observations have to be confirmed.

In the first part of the study 5 control subjects were submitted to iv infusion of 0.2 mM/kg of calcium gluconate in 20 min. Total calcium (atomic absorbtion method), ionized calcium (ion-selective electrode method) and adenosine (HPLC technique) were measured at the following times: 0 (baseline), 5, 10, 15, 20 (end of infusion), 25, 30, 35, and 50 min. The increase of total and ionized calcium serum levels was associated with a significant increase of adenosine plasma levels (from 207 +/- 41 to 362 +/- 63 nM, p < 0.001). Since the increase of adenosine plasma levels, obtained either with adenosine or dipyridamole (an adenosine reuptake inhibitor), has been used to test the coronary reserve in patients with coronary artery disease (CAD), in the second part of the study we compared the effects of calcium infusion with dipyridamole in 15 CAD subjects. Pharmacological stress tests were evaluated by monitoring two-dimensional echocardiography, ECG, heart rate, blood pressure and rate-pressure product. Ten patients were positive both to dipyridamole stress test and to calcium infusion, ad demonstrated by the onset of new areas of transient asynergy in the same myocardial regions. Dipyridamole infusion determined a significant increase in heart rate and rate pressure-product in all patients (both in positive and in negative), whereas calcium induced a slight, not significant decrease of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)