The pharmacokinetics of recombinant human erythropoietin (RhEPO) were investigated after subcutaneous (s.c.) injection in the thigh and in the abdominal wall. Eleven healthy subjects, age 24.4 years (median), were studied. Each subject received two s.c. injections of 100 U.kg-1 RhEPO dissolved in 1 ml water: one injection in the thigh and another in the abdomen. Serum erythropoietin was measured regularly by radioimmunoassay until 144 h after each injection. The mean residence time was significantly longer after injection in the thigh than in the abdomen (32.7 vs 26.2 h). The estimated half-life of absorption was significantly longer after injection in the thigh than after abdominal application (14.9 vs 12.3 h). The estimated half-life of elimination was not significantly different (4.4 vs 4.8 h). The relative difference in the area under the curve between injection in the abdomen and the thigh in the same subject ranged from -36% to +68% but there was no significant difference in bioavailability. The peak concentration was not significantly different and appeared at around 10 h (Cmax thigh, 175 U.l-1 vs Cmax abdomen, 216 U.l-1). A twin-peak configuration of the concentration vs time curve with a significant second peak at 24 h was found after injection in the thigh but not after abdominal injection. In conclusion, the mean residence time was longer after administration in the thigh, probably due to delayed absorption, but bioavailability was not significantly different. Following injection in the thigh the concentration curve had two peaks. The differences may be due to regional variations in lymph flow and to physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The effect of a diet rich in monounsaturated fatty acids (MUFA) on blood pressure, glycemic control, lipids and insulin sensitivity was evaluated in women with gestational diabetes mellitus. Design and methods: A randomized, unpaired diet intervention was performed in 27 women with gestational diabetes mellitus in an outpatient clinic. After randomization the women received either a high-carbohydrate diet (H-CHO) or a high-MUFA diet (H-MUFA) from the 33rd gestational week of pregnancy. Outcome measures were 24 h ambulatory blood pressure, blood lipids, glycemic control and insulin sensitivity estimated by an intravenous glucose tolerance test. Results: The 24 h diastolic blood pressure increased more in the H-CHO group than in the H-MUFA group (P`0.04). Conclusions: After 5 weeks of treatment with a MUFA-enriched diet, no increase in 24 h diastolic blood pressure and no adverse effects on blood lipids were seen. The favorable effect on the blood pressure by the MUFA diet is a possible non-medication treatment. The H-MUFA diet had no advantage to the H-CHO diet in ameliorating the decline of insulin sensitivity in third term of pregnancy in GDM.

Abstract-Experimental studies have demonstrated that intravenous magnesium (Mg) can protect the ischemic myocardium and has an antithrombotic effect. In patients with myocardial infarction, the reperfusion injury is complicated by the presence of a thrombogenic area in the affected coronary artery that may cause repetitive thrombus formation and embolization. We investigated the effect of Mg on infarct size in a randomized study in pigs. Myocardial infarction was induced by a 50-minute mechanical occlusion of the left anterior descending artery combined with an arterial injury, which stimulated a dynamic thrombus formation with emboli shedding on reperfusion. Magnesium sulfate (6 mmol/20 min plus 3 mmol/h) or saline was started at 30 minutes after coronary occlusion. Real-time ventricular pressure-volume loops were generated from the left ventricle by using a microtip pressure manometer and a conductance catheter. Platelet accumulation in the myocardium was evaluated by using 111 In-labeled platelets. After 4 hours of reperfusion, the infarct size/area at risk ratio in the placebo group was 46Ϯ0.06% (nϭ8) compared with 22Ϯ0.07% (nϭ6) in the Mg-treated animals (Pϭ0.03). Ejection fraction decreased significantly in the control group but not in the Mg-treated animals (Pϭ0.03). Platelet accumulation in the myocardium did not change significantly between the Mg-and placebo-treated animals (placebo group, 191Ϯ19%; Mg group, 177Ϯ29%; NS). The present study demonstrates that intravenous Mg infusion is able to reduce infarct size by Ͼ50% and preserve the ejection fraction in this model where ischemia/reperfusion injury was evaluated in the presence of a thrombogenic area in the nutrient artery. Key Words: magnesium Ⅲ animals Ⅲ reperfusion injury Ⅲ thrombosis Ⅲ platelets E xperimental data indicate that intravenous magnesium (Mg) may be a promising agent in the treatment of acute infarction not only during reperfusion of the ischemic myocardium, 1,2 but also as an antithrombotic drug. 3,4 Acute myocardial infarction (MI) is caused, in most cases, by the formation of an occlusive thrombus in the coronary artery. 5 The therapeutic aim in MI patients is to obtain recanalization of the artery, to salvage the ischemic myocardium. However, after thrombolysis or angioplasty, intermittent occlusion of the artery often occurs because of recurrent thrombus formation at the thrombogenic plaque. Thrombus formation and embolization is likely to occur repetitively, until the disrupted plaque is sealed off as part of a healing process. This may lead to recurrent episodes of ischemia/ reperfusion as well as accumulation of microaggregates from the thrombus in the myocardium downstream to the lesion.In animal models of reperfusion injury, a mechanical and standardized occlusion of the nutrient artery has generally been used. However, the clinical setting differs with respect to the experimental setup, because reestablishment of coronary blood flow is not always well defined in patients. In the present model, reperfusion injury was combine...

The purpose of this study was to assess the blood pressure profile and to measure vasoactive hormones in patients with essential hypertension (n=61), secondary hypertension (n=32) and chronic renal failure (n=32) matched with healthy control subjects (n=35), and to study the relationship between circadian changes in blood pressure and baseline levels of vasoactive hormones and renal function. Non-invasive, automatic blood pressure measurement was performed for 24 or 48 h. Venous plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide and endothelin were measured. The mean 24-h blood pressure was higher in all groups of hypertensive patients than in control subjects. The nocturnal blood pressure fall was preserved in essential hypertension, in contrast to secondary hypertension in which it was attenuated. In the patients with chronic renal failure the 24-h mean blood pressure was the same as in the controls. Night-time blood pressure was higher among the chronic renal failure patients than in the control group, and the nightly blood pressure fall in both diastolic and systolic blood pressure was reduced. Plasma concentrations of renin activity, arginine vasopressin, atrial natriuretic peptide, aldosterone and endothelin were significantly increased in secondary hypertension and chronic renal failure, compared to essential hypertension and control subjects. Plasma angiotensin II was increased in chronic renal failure compared to essential hypertension and controls. Estimated creatinine clearance and nightly blood pressure dips were inversely correlated in essential and secondary hypertension, i.e. with a decreasing renal function both systolic and diastolic nightly blood pressure dips were gradually attenuated. In the whole group of patients the nightly systolic and diastolic blood pressure dips were negatively correlated to basal plasma renin activity, plasma aldosterone and atrial natriuretic peptide levels, i.e. the higher the basal plasma hormone level the lower the blood pressure dip. In conclusion, patients with essential hypertension have elevated but normally configured 24-h blood pressure profiles, and patients with different kinds of secondary hypertension have elevated 24-h blood pressure profiles and attenuated nightly systolic and diastolic blood pressure falls. The more the renal function is reduced and the more the plasma levels of renin and aldosterone are increased, the more the nocturnal fall in blood pressure is reduced. It is suggested that the attenuated or absent decrease in nocturnal blood pressure in secondary renal hypertension is caused by an abnormally increased secretion of vasoactive hormones and/or by so far unknown factors released from the diseased kidney.