GET WELL: an automated surveillance system for gaining new epidemiological knowledge

Background  

The assumption behind the presented work is that the information people search for on the internet reflects the disease status in society. By having access to this source of information, epidemiologists can get a valuable complement to the traditional surveillance and potentially get new and timely epidemiological insights. For this purpose, the Swedish Institute for Infectious Disease Control collaborates with a medical web site in Sweden.     

5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression.

The amygdala is a key structure in a limbic circuit involved in the rapid and unconscious processing of facial emotions. Increased amygdala reactivity has been discussed in the context of major depression. Recent studies reported that amygdala activity during conscious emotion processing is modulated by a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in healthy subjects. In the present study, amygdala reactivity to displays of emotional faces was measured by means of fMRI at 3T in 35 patients with major depression and 32 healthy controls. Conscious awareness of the emotional stimuli was prevented via backward-masking to investigate automatic emotion processing. All subjects were genotyped for the 5-HTTLPR polymorphism. Risk allele carriers (S or L(G)) demonstrated increased amygdala reactivity to masked emotional faces, which in turn was significantly correlated with life-time psychiatric hospitalization as an index of chronicity. This might indicate that genetic variations of the serotonin transporter could increase the risk for depression chronification via altering limbic neural activity on a preattentive level of emotion processing.     

Using biorelevant dissolution to obtain IVIVC of solid dosage forms containing a poorly-soluble model compound

The usefulness of selected biorelevant dissolution media (BDM) to predict in vivo drug absorption was studied. Dissolution profiles of solid formulations of a poorly soluble model compound were compared in BDM simulating fasted and two levels of fed state. A non-physiologically relevant medium containing the cationic surfactant, cetrimide, was also investigated. All the media studied were capable of differentiating between the formulations employed, with formulation A consistently ranking high and formulations C and D ranking low. An in vivo dog study was carried out and an attempt was made to obtain a level A correlation between the plasma absorption curves and in vitro dissolution curves, using non-linear regression software. The in vitro-in vivo correlation (IVIVC) models developed indicated that fed state media (BDM 3) containing high levels of both bile salts (BS) and lipolysis products (LP) were best able to predict in vivo pharmacokinetic parameters (Cmax and AUC) with prediction errors lower than 10%. Overall, design and use of appropriate media for in vitro dissolution is extremely important. This study demonstrates the potential of physiologically relevant media containing both BS and LP for use in formulation and early drug development.     

Intestinal lymphatic transport of halofantrine in rats assessed using a chylomicron flow blocking approach: The influence of polysorbate 60 and 80

The aim of the study was to examine the effects of polysorbate 60 and 80 on intestinal lymphatic transport of a poorly water-soluble compound, halofantrine, using a chylomicron flow blocking approach in rats. Male Sprague-Dawley rats were pretreated intraperitoneally with 3.0mg/kg cycloheximide or saline. One hour later, rats were dosed with 6.7mg/kg halofantrine in 0.4 or 1.0g/kg polysorbate 60 or 80, 0.33g/kg soybean oil or 0.33g/kg soybean oil+1.0g/kg polysorbate 80 by gavage, and plasma samples were collected. The fraction of halofantrine transported to the lymphatic system was determined as the difference between the bioavailability in saline-pretreated rats and cycloheximide-pretreated rats. No significant differences in halofantrine transport to the systemic blood and in the deduced lymphatic transport were observed between the two polysorbates, at the tested dosages. The lymphatic transport of halofantrine was the same whether dosing with polysorbate 60, polysorbate 80 or soybean oil; accordingly both surfactants can be used as lymphotropic carriers. Furthermore, there was a good correlation between the halofantrine transport to blood and lymphatics in the chylomicron flow blocking model and published results from the mesenteric lymph-cannulated model.     

Profiles and levels of fatty acid esters of okadaic acid group toxins and pectenotoxins during toxin depuration, Part I: Brown crab (Cancer pagurus)

In 2002, two outbreaks of diarrhetic shellfish poisoning (DSP) occurred in Norway, which was later confirmed to be caused by the consumption of brown crab (Cancer pagurus) contaminated predominantly by esters of okadaic acid (OA) after feeding on toxic blue mussels (Mytilus edulis). In addition to OA-group toxins, pectenotoxins (PTXs) are commonly detected in the toxin-producing algae (i.e. Dinophysis). In this paper, an experiment was set up to study the fatty acid ester profiles and depuration rates of OA-group toxins and PTXs from C. pagurus after feeding on M. edulis containing these toxin groups. OA, DTX1, DTX2 and PTX2 SA were all detected primarily in the form of fatty acid esters in the crab hepatopancreas (HP). Crabs preferentially assimilated toxins of the OA group after feeding on the mussels for 1 week. Detailed analysis of the fatty acid ester profile in crabs and mussels showed that the ester profiles in the crabs differed slightly from profiles of the fatty acid esters in M. edulis, but neither ester profile nor ester to free toxin ratio appeared to change in the crabs during the first 2 weeks of depuration. Calculations of depuration rates of the free forms of toxins resulted in similar reduction rates for OA and DTX2, whereas the depuration rate of DTX1, PTX2 and PTX2 SA was considerably faster. From the industrial perspective, the PTX-compounds are of minor importance compared to the OA group toxins in crabs, considering (1) the uncertainty regarding the oral toxicity of the PTXs, (2) the preferential ingestion of OA-group toxins compared to PTXs and (3) the faster depuration of PTXs.     

A cross-sectional study of personality traits in women previously treated or untreated for alcohol use disorders

Background  

A better understanding of the relationship between treatment-seeking for alcohol problems and personality traits could give useful insight in factors promoting or hindering treatment for alcohol use disorders (AUD). The aim of this study was to analyze the associations between treatment-seeking for AUD, personality traits, and psychiatric co-morbidity in women. The study was based on pooled cross-sectional data from three population based samples and one clinical sample (n = 1,339). Comparisons were made between treated and untreated women with AUD, and between those with resolved and unresolved AUD.     

Effects of an extract of oystercatcher (Haematopus ostralegus) eggs from the Zeehavenkanaal in The Netherlands, and of its major contaminant, hexachlorobenzene, on the chicken embryo

Oystercatchers (Haematopus ostralegus) foraging on the canal 'Zeehavenkanaal' in the Netherlands have been shown to accumulate appreciable amounts of contaminants, especially hexachlorobenzene. The present study was performed to assess the embryotoxic effects of the present contaminants. To this end, a two step approach was followed. In step one, the toxic effects of hexachlorobenzene were studied in the chicken embryo bioassay, using concentrations realistic for the field situation. In step two, yolks of oystercatcher eggs were extracted and the embryotoxic potency of this extract was studied in the same bioassay, using doses of 1, 10 and 100% of the contaminant load in one average egg. The extract contained hexachlorobenzene and PCBs. However, presence of other compounds could not be excluded, since these were not analysed. Hexachlorobenzene induced a nonsignificant decrease in lymphocyte density in the bursa of Fabricius. The egg extract caused a 3.5 fold induction of EROD activity at the highest dose applied, and decreased lymphocyte density in the bursa of Fabricius.