French summaries of product characteristics: content in relation to therapeutic monitoring of psychotropic drugs.

The prescription information (summary of product characteristics, SPC) is compiled by the pharmaceutical industry as required by the national regulatory authorities. They vary in their content about the properties of drugs and about the usefulness of therapeutic drug monitoring (TDM) in the blood of patients. Based on a previous study carried out in Germany, the degree of agreement of French SPC for 59 psychotropic drugs with the existing medico-scientific evidence in the area of TDM was examined using a recently developed instrument. A summary score of SPC content (SPCC) related to TDM (SPCC(TDM)) has been calculated and compared with the level of recommendation of TDM of the AGNP-TDM expert group consensus guidelines for TDM in psychiatry [AGNP: Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (Association for neuropsychopharmacology and pharmacopsychiatry)]. Among the antidepressants, antipsychotics, tranquillizers/hypnotic agents and mood stabilizers, the highest SPCC(TDM) scores in the French SPC were reached for imipramine (16), haloperidol (6), clonazepam (8) and lithium (23), respectively. Results were similar to those obtained from the analysis of German SPC, and considerable disagreement was found between the information on TDM in SPC and existing medico-scientific evidence, albeit less in the case of mood stabilizers. Taking into account the recommendations of the AGNP-TDM expert group guidelines, there is a deficit in the French SPC concerning TDM-relevant information. An amelioration of this situation could help to improve the clinical practice of TDM of psychotropic drugs, as the SPC is a widely used tool.

Flight energetics in relation to sexual differences in the mating behaviour of a mayfly, Siphlonurus aestivalis

Mayflies (Ephemeroptera) are known to have short adult life-spans. Adults are unable to feed, and they utilize reserves stored during their aquatic larval stage. Energy reserves (fat, glycogen, and free sugars) of mature larvae, subimagoes and imagoes of both sexes of Siphlonurus aestivalis Eaton were compared. All the stages of both sexes had low glycogen and free sugar contents, and the only significant change occurred during the transformation of the mature larva to subimago when almost all the reserves of free sugars were used up. Glycogen and free sugars may serve as energy sources permitting individuals to swim and fly out of the water during emergence. Fat made up most of the energy reserves of mature larvae and was the main source of energy used during the final development of both sexes. Young adult males had high fat reserves which they used as a source of energy for their swarming flights. In contrast, females did not seem to use a significant amount of fat for flight. This difference is probably related to the different mating strategies of the sexes in this species. Males perform long flights waiting for females, whereas females perform only brief flights to mate and reproduce.

Summer ozone cycles in the Lisbon metropolitan area and its relation to some meteorological variables

The aim of this work is to study the tropospheric ozone concentrations and daily peak cycles in the Lisbon MetropolitanArea (LMA) during the summer season (June, July and August, JJA) covering the 4-yr study period 2002-2005. Theresults show that all the stations have the same pattern: a minimum in the early morning followed by an increase at 1000UTC reaching to a peak at 1300-1400 UTC, dropped again to minimum values 1800 UTC but with different concentrationsdue to regional and local wind circulations and complex dynamic interactions. We identified in Lisbon city the ozone “weekendeffect”. Finally, we studied an episode of very high levels of tropospheric ozone and related daily ozone concentrationswith some meteorological variables.

The role of cisplatin and NAMI-A plasma-protein interactions in relation to combination therapy

The aim of the study is to evaluate the differences of protein binding of NAMI-A, a new ruthenium drug endowed with selective antimetastatic properties, and of cisplatin and to ascertain the possibility to use two drugs based on heavy metals in combination to treat solid tumour metastases. For this purpose, we have developed a technique that allows the proteins, to which metal drugs bind, to be identified from real protein mixtures. Following incubation with the drugs, the bands containing platinum and/or ruthenium are separated by native PAGE, SDS-PAGE and 2D gel electrophoresis, and identified using laser ablation inductively coupled plasma mass spectrometry. Both drugs interact with essentially the same proteins which, characterised by proteomics, are human serum albumin precursor, macroglobulin alpha 2 and human serotransferrin precursor. The interactions of NAMI-A are largely reversible whereas cisplatin forms stronger interactions that are less reversible. These data correlate well with the MCa mammary carcinoma model on which full doses of NAMI-A combined with cisplatin show additive effects as compared to each treatment taken alone, independently of whether NAMI-A precedes or follows cisplatin. Furthermore, the implication from this study is that the significantly lower toxicity of NAMI-A, compared to cisplatin, could be a consequence of differences in the mode of binding to plasma proteins, involving weaker interactions compared to cisplatin.

Sedimentation of macroscopic rigid knots and its relation to gel electrophoretic mobility of DNA knots.

We address the general question of the extent to which the hydrodynamic behaviour of microscopic freely fluctuating objects can be reproduced by macrosopic rigid objects. In particular, we compare the sedimentation speeds of knotted DNA molecules undergoing gel electrophoresis to the sedimentation speeds of rigid stereolithographic models of ideal knots in both water and silicon oil. We find that the sedimentation speeds grow roughly linearly with the average crossing number of the ideal knot configurations, and that the correlation is stronger within classes of knots. This is consistent with previous observations with DNA knots in gel electrophoresis.

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male SpragueDawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokineticpharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

Intra-specific variation in cell wall constituents of needle age classes of Pinus sylvestris in relation to soil fertility status in Southwest England

Abstract

Adaptability and stability of white oat cultivars in relation to chemical composition of the caryopsis

The objective of this work was to characterize the chemical properties of white oat (Avena sativa) caryopsis and to determine the adaptability and stability of cultivars recommended for cultivation in the state of Rio Grande do Sul, Brazil. The trials were carried out in the 2007, 2008 and 2009 crop seasons, in three municipalities: Augusto Pestana, Capão do Leão, and Passo Fundo. Fifteen cultivars were evaluated in a randomized block design, with four replicates. The contents of protein, lipid, and nitrogen-free extract were evaluated in the caryopsis. Cultivar performances for the measured characters varied according to location and year of cultivation. The cultivar URS Guapa showed high content of nitrogen-free extract and low contents of protein and lipid in the caryopsis. 'FAPA Louise' showed high content of lipid, whereas 'Albasul', 'UPF 15', and 'UPF 18' showed high content of protein and low content of nitrogen-free extract. There is no evidence of an ideal biotype for the evaluated characters, which could simultaneously show high average performance, adaptability to favorable and unfavorable environments, and stability.

Size and fat content of gynes in relation to the mode of colony founding in ants (Hymenoptera; Formicidae)

In ants, there are two main processes of colony founding, the independent and the dependent modes. In the first case young queens start colony founding without the help of workers, whereas in the second case they are accompanied by workers. To determine the relation between the mode of colony founding and the physiology of queens, we collected mature gynes of 24 ant species. Mature gynes of species utilizing independent colony founding had a far higher relative fat content than gynes of species employing dependent colony founding. These fat reserves are stored during the period of maturation, i.e. between the time of emergence and mating, and serve as fuel during the time of colony founding to nurture the queen and the brood. Gynes of species founding independently but non claustrally were found to have a relative fat content intermediate between the values found for gynes founding independently and those founding dependently. This suggests that such gynes rely partially on their fat reserves and partially on the energy provided by prey they collect to nurture themselves and the first brood during the time of colony founding. Study of the fat content of mature gynes of all species has shown that it gives a good indication of the mode of colony founding.

Analysis of vineyard differential management zones and relation to vine development, grape maturity and quality

The objective of research was to analyse the potential of Normalized Difference Vegetation Index (NDVI) maps from satellite images, yield maps and grapevine fertility and load variables to delineate zones with different wine grape properties for selective harvesting. Two vineyard blocks located in NE Spain (Cabernet Sauvignon and Syrah) were analysed. The NDVI was computed from a Quickbird-2 multi-spectral image at veraison (July 2005). Yield data was acquired by means of a yield monitor during September 2005. Other variables, such as the number of buds, number of shoots, number of wine grape clusters and weight of 100 berries were sampled in a 10 rows × 5 vines pattern and used as input variables, in combination with the NDVI, to define the clusters as alternative to yield maps. Two days prior to the harvesting, grape samples were taken. The analysed variables were probable alcoholic degree, pH of the juice, total acidity, total phenolics, colour, anthocyanins and tannins. The input variables, alone or in combination, were clustered (2 and 3 Clusters) by using the ISODATA algorithm, and an analysis of variance and a multiple rang test were performed. The results show that the zones derived from the NDVI maps are more effective to differentiate grape maturity and quality variables than the zones derived from the yield maps. The inclusion of other grapevine fertility and load variables did not improve the results.

Simultaneous use of alcohol, tobacco and cannabis in relation to severity of substance dependence: a study among young Swiss men

Objective: This study investigated patterns of the simultaneous use of alcohol, tobacco and cannabis among young polydrug users, and whether use of one substance might be a cue for use of another and associations with the severity of substance dependence. Methods: The study focused on 3 subsamples from the ongoing Swiss Cohort Study on Substance Use Risk Factors (C-SURF, N=5,990). It used 12 months of data on alcohol/tobacco co-users, alcohol/cannabis co-users and tobacco/cannabis co-users (N=2,660, 1,755 and 1,460 respectively. Simultaneous use, numbers of symptoms of substance dependence, and hazardous use of alcohol, tobacco and cannabis were assessed. The effect of simultaneous polydrug use (SPU) on the numbers of symptoms of substance dependence was tested using analysis of variance. Results: Polydrug use was most common as SPU, and less common as non/occasional SPU. Moreover, when participants started to use one substance while using another, the severity of substance dependence was more strongly associated with the triggered substance than with cue. Conclusions: This study highlights the necessity to take SPU into account. First, SPU rather than separate drug use was the most common pattern for polydrug users. Second, frequent SPU was associated with increased numbers of symptoms of substance dependence compared to non/occasional SPU. Furthermore, SPU may reveal the severity of substance use dependence, when substance use is triggered by a cue substance. For these reasons, SPU should be a serious cause for concern for prevention and intervention purposes.

Prevalence of iodine inadequacy in Switzerland assessed by the estimated average requirement cut-point method in relation to the impact of iodized salt.

OBJECTIVE: To assess the iodine status of Swiss population groups and to evaluate the influence of iodized salt as a vector for iodine fortification. DESIGN: The relationship between 24 h urinary iodine and Na excretions was assessed in the general population after correcting for confounders. Single-day intakes were estimated assuming that 92 % of dietary iodine was excreted in 24 h urine. Usual intake distributions were derived for male and female population groups after adjustment for within-subject variability. The estimated average requirement (EAR) cut-point method was applied as guidance to assess the inadequacy of the iodine supply. SETTING: Public health strategies to reduce the dietary salt intake in the general population may affect its iodine supply. SUBJECTS: The study population (1481 volunteers, aged ≥15 years) was randomly selected from three different linguistic regions of Switzerland. RESULTS: The 24 h urine samples from 1420 participants were determined to be properly collected. Mean iodine intakes obtained for men (n 705) and women (n 715) were 179 (sd 68.1) µg/d and 138 (sd 57.8) µg/d, respectively. Urinary Na and Ca, and BMI were significantly and positively associated with higher iodine intake, as were men and non-smokers. Fifty-four per cent of the total iodine intake originated from iodized salt. The prevalence of inadequate iodine intake as estimated by the EAR cut-point method was 2 % for men and 14 % for women. CONCLUSIONS: The estimated prevalence of inadequate iodine intake was within the optimal target range of 2-3 % for men, but not for women.

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.