Atmospheric deposition of lead in Norway: spatial and temporal variation in isotopic composition.

Moss samples collected from 22 sites all over Norway at five different times during 1977-2000 were analysed for stable lead isotope ratios. These data together with total lead concentrations and relevant literature lead isotope data from UK, western/central Europe and eastern Europe/Russia were used to elucidate major source regions for lead deposited in different parts of the country at different times. The southernmost part of the country was most affected from western/central Europe around 1975, but the deposition declined rapidly and UK became a more significant source region in the 1980s. Recently, the influence is mostly from Eastern Europe. In the west, UK was the dominant source region during the whole period. In the middle and northern regions, the deposition was low but also decreasing regularly, and the main source region was probably the North Atlantic. In the far north-east, influence from Russia and eastern Europe was dominant during the whole period.

Inhibitors of angiotensin converting enzyme decrease early atherosclerosis in hyperlipidemic hamsters. Fosinopril reduces plasma cholesterol and captopril inhibits macrophage-foam cell accumulation independently of blood pressure and plasma lipids.

The effect of two angiotensin converting enzyme (ACE) inhibitors on the development of atherosclerosis was determined in hyperlipidemic hamsters. Preliminary studies indicated that only fosinopril (50 mg/kg) temporarily decreased mean arterial pressure, while after chronic dosing fosinopril and captopril (50 mg/kg) were ineffective. The same dose of fosinopril and captopril inhibited the angiotensin I pressor response, indicating these agents suppressed ACE activity in vivo. In the 3 week atherosclerosis experiment, all hamsters were fed chow supplemented with 0.05% cholesterol and 10% coconut oil. Control hamsters were compared with those receiving either 50 mg/kg per day of fosinopril or 50 mg/kg per day of captopril. After 3 weeks, fosinopril reduced plasma total cholesterol, low density lipoprotein (LDL) plus very low density lipoprotein cholesterol and total triglycerides by 17%, 27% and 45%, respectively. Captopril only reduced high density lipoprotein cholesterol by 20%. Neither fosinopril or captopril altered blood pressure at 3 weeks. Atherosclerosis was quantified from en face preparations of the lesion-prone aortic arch that were stained with oil red O (for cholesteryl ester and triglycerides). In control hamsters, oil red O labeled numerous subendothelial macrophage-foam cells located along the inner curvature of the aortic arch. Compared with controls, fosinopril reduced the number of intimal macrophage-foam cells/mm2, foam cell size and the fatty streak area by 85%, 38% and 90%, respectively. Captopril decreased these parameters by 44%, 16% and 53%. Thus captopril decreased early atherosclerosis without affecting plasma LDL cholesterol or blood pressure, which suggested that inhibiting ACE (or kininase II) directly impeded the accumulation and formation of macrophage-foam cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Substituted 1,2,3,4-tetrahydroaminonaphthols: antihypertensive agents, calcium channel blockers, and adrenergic receptor blockers with catecholamine-depleting effects.

Substituted 1,2,3,4-tetrahydroaminonaphthols were found to be calcium channel blockers with antihypertensive properties. These compounds also possessed adrenergic beta-receptor blocking activity. From the structure-activity studies, no clear correlation emerged between the in vitro calcium channel blocking activity and the acute anti-hypertensive activity in cannulated spontaneously hypertensive rats. Extensive pharmacological testing of selected compounds indicated that aminonaphthols are antihypertensive agents with many pharmacological properties. The relative contribution of various pharmacological actions toward the observed antihypertensive activity is unclear. Since the clinically useful calcium channel blocker verapamil is structurally related to these compounds, one of the aminonaphthols, trans-3-[(3,3-diphenylpropyl)amino]-1,2,3,4-tetrahydro-6,7 -dimethoxy-2-naphthalenol (12), was compared with verapamil for calcium channel blocking activity, adrenergic blocking activity, and catecholamine-depleting activity. Both compounds were found to be equipotent in these test systems.

The effect of age on -adrenoceptor activity in tracheal smooth muscle.

There was an age-related reduction of the sensitivity of rat and guinea-pig isolated tracheal smooth muscles to stimulation of beta-adrenoceptors, but the ability of tracheal smooth muscle to relax to isoprenaline was not completely lost.

Man, nutrition and mobility: a comparison of teeth and bone from the Medieval era and the present from Pb and Sr isotopes.

Naturally occurring isotopic systems, such as strontium (Sr) and lead (Pb), are very useful for characterizing different sources and to produce background information. Norwegian teeth from the Medieval era have 206Pb/204Pb ratios between 18.8 and 18.2, in comparison with present day ratios of between 18.0 and 17.6 showing the impact of Pb from modern industrialization and from traffic. Sr analyses of Medieval teeth show that an individual living in a coastal town on the west coast of Norway can easily be distinguished from one in a rural area at that time. The Sr signature shows that Medieval people lived on local products while present people to a greater degree live on imported or domestic industrially processed food. Medieval and modern teeth from one site give similar Pb signatures and concentrations indicating no increase in pollution over time. However, the impact of industrial pollution can be seen from Pb analyses on contemporary teeth, so that the method can be used to monitor emission of heavy metals from local industry. Whilst the Pb and Sr natural isotopic systems individually provide valuable information, a combination of the two techniques is a very powerful tool in environmental and archaeological research.

Studies on the duration of local anesthesia: a possible mechanism for the prolonging effect of "vasoconstrictors" on the duration of infiltration anesthesia.

Attempts have been made to correlate the duration of the local anesthetic effect with the amount of the local anesthetic compound remaining at the injection site at different times after an injection. In addition to delaying the absorption of the local anesthetic, adrenaline but not a vasopressin-derivate decreased the minimal anesthetic concentration of the local anesthetic agent. It is assumed that the pH value of the tissues at the injection site was kept down through the metabolic effects of adrenaline, thereby transforming the local anesthetic agent into cations, which is the form in which the amide-type of local anesthetics mainly exerts their nerve blocking activity.

Studies on the duration of local anesthesia. Effects of volume and concentration of a local anesthetic solution on the duration of dental infiltration anesthesia.

In animals and humans the rate of resorption and the duration of the anesthesia have been investigated, using mepivacaine in different concentrations and volumes without addition of a vasoconstrictor. A linear relationship between duration of anesthesia and the logarithm to the concentration of mepivacaine was found.

Haemodynamic effects of the quaternary ammonium compound QX 572 in anaesthetized cats. III. Interactions with adrenergic beta-adrenoceptor blockade.

The positive cardiac chronotropic effects of the antiarrhythmic compound, QX 572, in anaesthetized cats has been shown mainly to be due to a release of catecholamines from sympathetic nerve-endings. Furthermore, these undesired effects of QX 572 on heart rate were decreased by adrenergic beta blockade in the animals. In the present study it was found that an adrenergic beta-blockade did not reveal any cardiodepressive effects of QX 572, that in the normal animals might have been masked by the effects of the drug-induced catecholamine-release.

Effects of captopril on atherosclerosis in cynomolgus monkeys.

A study was performed to investigate if oral dosing of captopril could influence the development of atherosclerosis in cholesterol-fed cynomolgus monkeys. Twenty-four monkeys were divided into four groups: (a) a control group given a normal monkey diet and placebo medication; (b) a high cholesterol group given a high cholesterol diet and placebo medication; (c) a low-dose captopril group given the cholesterol diet and 25 mg/kg of captopril twice daily; and (d) a high-dose captopril group given the cholesterol diet and 50 mg/kg of captopril twice daily. The doses of captopril used in this study did not change the levels of total serum cholesterol, high-density lipoprotein (HDL), or triglycerides. The total cholesterol/HDL ratio was also unaffected by captopril. The animals were killed after 6 months of treatment. The progression of atherosclerosis was assessed by gross pathology, histopathology, and biochemical methods. The results showed a significantly reduced progression of arterial lesions in monkeys given captopril; the effects of captopril were most evident in the coronary arteries, which were practically free from atherosclerosis in captopril-treated animals.