Human biomonitoring pilot study DEMOCOPHES in Germany: Contribution to a harmonized European approach

Human biomonitoring (HBM) is an effective tool to assess human exposure to environmental pollutants, but comparable HBM data in Europe are lacking. In order to expedite harmonization of HBM studies on a European scale, the twin projects COPHES (Consortium to Perform Human Biomonitoring on a European Scale) and DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) were formed, comprising 35 partners from 27 European countries.In COPHES a research scheme and guidelines were developed to exemplarily measure in a pilot study mercury in hair, cadmium, cotinine and several phthalate metabolites in urine of 6–11 year old children and their mothers in an urban and a rural region. Seventeen European countries simultaneously conducted this cross-sectional DEMOCOPHES feasibility study.The German study population was taken in the city of Bochum and in the Higher Sauerland District, comprising 120 mother-child pairs. In the present paper features of the study implementation are presented. German exposure concentrations of the pollutants are reported and compared with European average concentrations from DEMOCOPHES and with those measured in the representative German Environmental Survey (GerES IV).German DEMOCOPHES concentrations for mercury and cotinine were lower than the European average. However, 47% of the children were still exposed to environmental tobacco smoke (ETS) outside their home, which gives further potential for enhancing protection of children from ETS.Compared with samples from the other European countries German participating children had lower concentrations of the phthalate metabolites MEP and of the sum of 3 DEHP-metabolites (MEHP, 5OH-MEHP and 5oxo-MEHP), about the same concentrations of the phthalate metabolites MBzP and MiBP and higher concentrations of the phthalate metabolite MnBP. 2.5% of the German children had concentrations of the sum of 4 DEHP-metabolites and 4.2% had concentrations of MnBP that exceeded health based guidance values, indicating reasons for concern.Continuous HBM is necessary to track changes of pollutant exposure over time. Therefore Germany will continue to cooperate on the harmonisation of European human biomonitoring to support the chemicals regulation with the best possible exposure data to protect Europe’s people against environmental health risks.     

A simple method for preparation of pure 68Ga‐acetate precursor for formulation of radiopharmaceuticals: Physicochemical characteristics of the 68Ga eluate of the SnO2 based‐68Ge/68Ga column generator

Gallium‐68 radioisotope is an excellent source in clinical positron emission tomography application due to its ease of availability from germanium‐68 (⁶⁸Ge)/gallium‐68 (⁶⁸Ga) generator having a shelf life of 1 year. In this paper, a modified method for purification of the primary eluate of ⁶⁸Ge‐⁶⁸Ga generator by using a small cation exchange resin (Dowex‐50) column has been described. The breakthrough of ⁶⁸Ge before and after purification of ⁶⁸Ga eluate was 0.014% and 0.00027%, respectively. The average recovery yield of ⁶⁸Ga after purification was 84% ± 8.6% (SD, n  = 335). The results of the physiochemical studies confirmed that the ⁶⁸Ga‐acetate obtained is suitable for labeling of radiopharmaceuticals.     

Retrospective study on the reliability of an “approximate LD50” determined with a small number of animals

Based on 364 LD₅₀ determinations in mice and rats after intravenous and oral administration of drugs, the reliability of an approximate LD₅₀ was retrospectively tested.The difference between approximate LD₅₀ and LD₅₀ is — independent of species and route of administration — not greater than ± 20% of the LD₅₀ in 90% of the cases.Four to five doses — uniformly distributed over the dose-mortality range can suffice in reliably determining the approximate LD₅₀.The probability is 10% that an approximate LD₅₀ and LD₅₀ are significantly different from each other.152 parallel studies on male and female animals show that the LD₅₀ or approximate LD₅₀ must not be determined for both sexes. It is sufficient to test a dose near the LD₅₀ in the opposite sex. A 50–75% reduction of expenditure in animal material is possible in most of LD₅₀ determinations.     

工频磁场刺激小鼠MSCs体外增殖与分化的初步研究

通过实验初步研究了工频磁场对小鼠骨髓间充质干细胞体外增殖与分化的影响。实验结果显示工频电磁场对骨髓间充质干细胞的增殖与分化有明显的诱导效应,且具有一定的重复性,同时,磁效应不是一种线性关系,存在着窗口效应。文末讨论了磁刺激治疗骨折不愈合研究的国内外现状,并提出了我们的研究构想。     

Local modulation of adrenal catecholamines release by beta-2 adrenoceptors in the anaesthetized dog

Summary The release of adrenal catecholamines into the adrenal vein elicited by splanchnic nerve stimulation, was evaluated in the presence of a -adrenoceptor agonist and both -1 and -2 adrenoceptor antagonists in anaesthetized and vagotomized dogs. Stimulations (0.5 V pulses of 2 ms duration for 3 min at 1 Hz) were applied before and after the i.v. infusion of the -adrenoceptor agonist, isoproterenol (0.1 /kg/min). While maintaining the infusion of isoproterenol, either ICI 118551 (0.3 mg/kg), a selective -2 adrenoceptor antagonist, or 204-155 (0.2 mg/kg), a selective -1 adrenoceptor antagonist (Sandoz Co., Dorval, PQ, Canada), were injected intravenously and the stimulation was repeated. The results show that isoproterenol increased significantly both pre-stimulation basal levels and the stimulated release of catecholamines. These potentiated responses were significantly reversed by ICI 118551, but not by 204155. These results suggest that the release of adrenal catecholamines is locally modulated by a positive feedback mechanism through activation of -2 adrenoceptors. Send offprint requests to S. Foucart     

Skin conductance reaction (SCR)-habituation test, a tool to detect anxiolytic activity. Its justification by the correlation between SCR-habituation test activities and specific binding potencies in benzodiazepines

Correlation between specific binding potencies "in vitro" of several benzodiazepines and activities in SCR-habituation test is very satisfactory. As the SCR-habituation test might be considered as an elementary model of anxiety state, the test is suggested to be used as an intermediate psychopharmacological tool before clinical study. SCR-magnitude test exhibits no correlation of this kind proving that sedative activity is of a different mechanism.     

A kinetic study of the release of noradrenaline by electrical stimulation: influence of presynaptic α-adrenoceptors

Summary Dog saphenous vein strips were incubated with 1.4 mol/l ³H-(-)-noradrenaline for 60 min, after inhibition of the noradrenaline-metabolizing enzymes and of extraneuronal uptake. At the end of the incubation period the strips were perifused for 150 min; cocaine (10 mol/l) was added to the perifusion fluid from t=75 min onwards. In some experiments either phentolamine (10 mol/l) or clonidine (0.1 mol/l) was also added at this time. Some strips were subjected to electrical stimulation from t=100 to 150 min of perifusion (t=0 being the start of perifusion), with frequencies ranging from 0.5 to 13.5 Hz. A compartmental analysis of spontaneous or electrically-induced efflux of ³H-noradrenaline was made. The spontaneous efflux had a long half time (t/2=124 min) and most of the ³H-noradrenaline which had accumulated in the strips did not participate in the efflux (bound fraction, representing 90% of tissue activity at t=100 min of perifusion). Neither phentolamine nor clonidine modified the half time or the bound fraction observed for spontaneous efflux. Electrical stimulation (>0.5 Hz) mobilized only one compartment of noradrenaline, which represented about 50% of the noradrenaline accumulated in the strips. The half time of ³H-efflux induced by electrical stimulation decreased when the frequency increased from 0.5 Hz up to 13.5 Hz. Phentolamine increased the rate of efflux for all frequencies of stimulation and decreased the half time of efflux. However, the releasable pool of noradrenaline was only increased by phentolamine at 0.5 Hz, but not at higher frequencies. Clonidine was used only at two frequencies of stimulation, 1.5 and 4.5 Hz. For the low frequency clonidine decreased the releasable pool, but no change was observed at 4.5 Hz.The results support the view that there is a norarenaline pool which is resistant to electrical stimulation and that its magnitude is not dependent on the activity of presynaptic -adrenoceptors.Results presented in part to the 13th Annual Meeting of the Portuguese Pharmacological Society (Porto, December 1982) and to the 5th Meeting on Adrenergic Mechanisms (Porto, October 1983)Work supported by a grant from Instituto Nacional de Investigação Científica (FmPl)     

Atrial septal defect in patients over the age of 50

Clinical, haemodynamic and follow-up data are presented for a group of 49 patients with atrial septal defect who first presented between the ages of 50 and 79. The incidence of supraventricular arrhythmias, pulmonary vascular disease and "heart failure" all increased with increasing age. Those who had the defect closed tended to be the more symptomatic and surgery resulted in symptomatic improvement in almost all. The combined early and late surgical mortality was 6.6%. Surgery appears to be of benefit in symptomatic patients below the age of 70. Above this age our small experience would suggest caution in recommending closure of the defect.     

Antihypertensive and neuroprotective activities of rhynchophylline: The role of rhynchophylline in neurotransmission and ion channel activity

Ethnopharmacological relevance

Uncaria species (Gouteng in Chinese) have been used as ethnopharmacological medicines to treat ailments of the cardiovascular and central nervous systems. As the main alkaloid constituent of Uncaria species, rhynchophylline has drawn extensive attention in recent years for its antihypertensive and neuroprotective activities, and its pharmacological effects are related to ethnopharmacological medicine properties of Uncaria species.

Aim of the review

This review examined the pharmacological studies and mechanisms of rhynchophylline, with an emphasis on cardiovascular and central nervous system diseases linked to the ethnopharmacological uses of Uncaria species.

Methods

We conducted both an electronic search and a library search of in vivo and in vitro studies. The terms and keywords for the search included rhynchophylline, Uncaria species, Gouteng, pharmacological effects, and mechanism. We focused on the papers, including ours, with studies on all related pharmacological effects and mechanisms of rhynchophylline.

Results

Rhynchophylline was the main constituent of several components identified from Uncaria species. Rhynchophylline mainly acts on cardiovascular and central nervous system diseases, including hypertension, bradycardia, arrhythmia, sedation, vascular dementia, epileptic seizures, drug addiction, and cerebral ischemia. Rhynchophylline also has effects on anticoagulation, inhibits vascular smooth muscle cell proliferation, and has been shown to be anti-endotoxemic. The active mechanisms are related to modulation of calcium and potassium ion channels, protection of neural and neuroglial cells, and regulation of central neurotransmitter transport and metabolism. More studies are necessary to verify the pharmacological activities and determine the exact mechanisms of rhynchophylline activity.

Conclusions

Rhynchophylline treatment of cardiovascular and central nervous system diseases has a strong linkage with traditional concepts and uses of Uncaria species in ethnopharmacological medicine, such as treatment for lightheadedness, convulsions, numbness, and hypertension. As a candidate drug for several cardiovascular and central nervous system diseases, rhynchophylline will attract scientists to pursue the potential pharmacological effects and mechanisms with new technologies. Relatively few clinically relevant studies of rhynchophylline have been conducted. Thus, more in vivo validations and investigations of antihypertensive and neuroprotective mechanisms of rhynchophylline are necessary.