Gert Laekeman

Nutmeg oil: identification and quantitation of its most active constituents as inhibitors of platelet aggregation.

Three distilled or commercially available nutmeg oils were analysed and their chemical composition compared with their capacity to inhibit platelet aggregation in vitro. It could be clearly shown that eugenol and isoeugenol play the major role in the detected activity of nutmeg. Medicinally, it appears that nutmeg oil and nutmeg powder can be replaced by eugenol and/or isoeugenol.

Inhibition of rabbit platelet activation by lipoxygenase products of arachidonic and linoleic acid

The hydroperoxy fatty acids, 15-hydroperoxyeicosatetraenoic acid (15-HPETE), 13-hydroperoxy and 9-hydroperoxyoctadecadienoic acid (13- and 9-HPODE) and the corresponding hydroxy compounds (15-HETE and 13-HODE) were synthesized and purified. Washed rabbit platelets were incubated with these fatty acid derivatives before aggregation was induced. Arachidonic acid-induced aggregation, as well as the secretion of ATP and the formation of thromboxane B2 (TXB2) were dose-dependently inhibited by these compounds. Low thrombin-, collagen- and ADP-induced aggregations were also suppressed by 15-HPETE. Platelet activation induced by the calcium ionophore A23187 and by high thrombin concentrations were not affected by 15-HPETE. In addition, doses of 15-HPETE which were inactive by themselves, potentiated the anti-aggregating activity of prostacyclin (PGI2). It is suggested that the hydroperoxy and hydroxy compounds suppress platelet activation by interference with the rise in cytoplasmic calcium in addition to the inhibition of cyclo-oxygenase.

Formation of prostanoids during intravascular complement activation in the rabbit

1 Plasma concentrations of 6‐oxo‐prostaglandin F1α (6‐oxo‐PGF1α) and thromboxane B2 (TXB2) were measured by radioimmunoassay in arterial blood before and after injections of the complement activator, cobra venom factor (CVF). 2 During the control period, the concentration of 6‐oxo‐PGF1α, which gives the sum of prostacyclin plus 6‐oxo‐PGF1α, and TXB2 were, respectively, less than 20 pg ml−1 and 70 ± 15 pg ml−1. 3 Intravenous injections of CVF induced dose‐dependent, reversible elevations in the plasma levels of both prostanoids. 4 The time courses for the increases of 6‐oxo‐PGF1α and TXB2 paralleled the arterial hypotension and thrombocytopenia, suggesting the existence of a causal relationship between these parameters. 5 The results further support our hypothesis that complement‐dependent formation of arachidonic acid metabolites contributes to some of the haemodynamic and haematological changes occurring during endotoxin shock.

Isolation and identification of two isomeric trihydroxy octadecenoic acids with prostaglandin E-like activity from onion bulbs (Allium cepa).

Two fractions with prostaglandin E-like activity were isolated from onion (Allium cepa) by using XAD-2 adsorption, silicic acid column chromatography and thin layer chromatography. The fractions were analyzed by gas chromatography/mass spectrometry and were characterized as isomeric mixtures of 9,10,13-trihydroxy-11-octadecenoic and 9,12,13-trihydroxy-10-octadecenoic acid, which are lipoxygenase metabolites of linoleic acid. Bio-assay, for which cascade superfusion was used and the rabbit coeliac and mesenteric arteries and the rat fundus strip were employed as assay organs, was utilized to monitor the bio-active profile throughout the isolation procedures. The activity of 1 microgram of the pharmacologically active fractions T1 and T2 was found to be equivalent to that of respectively 1.33 and 0.63 ng of prostaglandin E2.

Endotoxic shock in the piglet: beneficial effects of prostaglandin synthesis inhibition

In anesthetized piglets the intravenous injection of a lethal dose of endotoxin, 0.5 mg/kg, resulted in a progressively evolving deterioration of the cardiovascular system (hypotension, decrease in cardiac output), in an increase in pulmonary vascular resistance and in the death of all animals within 210 min following endotoxin administration. Endotoxin induced a significant increase in immunoreactive (i) i-6-oxo-PGF1 alpha, i-TXB2, and i-15-oxo-13,14-dihydro-PGF2 alpha levels in peripheral plasma. Pretreatment with the PG-synthesis inhibitor, flurbiprofen, abolished the profound rise in PG-levels, whereas cardiovascular performance was more sustained. The results suggest the involvement of several prostanoids during the evolution of endotoxic shock in the piglet.

Divergent Intentions to Use Antibiotic Guidelines A Theory of Planned Behavior Survey

Background. To improve physicians’ antimicrobial practice, it is important to identify barriers to and facilitators of guideline adherence and assess their relative importance. The theory of planned behavior permits such assessment and has been previously used for evaluating antibiotic use. According to this theory, guideline use is fueled by 3 factors: attitude, subjective norm (perceived social pressure regarding guidelines), and perceived behavioral control (PBC; perceived ability to follow the guideline). The authors aim to explore factors affecting guideline use in their hospital. Methods. Starting from their earlier observations, the authors constructed a questionnaire based on the theory of planned behavior, with an additional measure of habit strength. After pilot testing, the survey was distributed among physicians in a major teaching hospital. Results. Of 393 contacted physicians, 195 completed questionnaires were received (50.5% corrected response rate). Using multivariate analysis, the overall intention toward using antibiotic guidelines was not very predictable (model R2 = .134). Habit strength (relative weight = .391) and PBC (relative weight = .354) were the principal significant predictors. A moderator effect of respondents’ position (staff member v. resident) was found, with staff members’ intention being significantly influenced only by habit strength and residents’ intention by PBC. Regarding previously identified barriers, education on antibiotics and guidelines was rated unsatisfactory. Conclusions. These divergent origins of influence on guideline adherence point to different approaches for improvement. As habits strongly influence staff members, methods that focus on changing habits (e.g., automated decision support systems) are possible interventions. As residents’ intention seems to be guided mainly by external influences and experienced control, this may make feedback, convenient guideline formats, and guideline familiarization more suitable.

Drug information in psychiatric hospitals in Flanders: a study of patient-oriented leaflets.

Objective: This study reviews written information sources that inform patients about their drugs used in psychiatric institutions in Flanders.Methods: Pharmacists working in psychiatry were asked to participate. Seven leaflets were collected and evaluated using the Flesh readability formula and twelve hospital pharmacists scored ten propositions on a Likert scale. Questionnaires were mailed to the participants.Results: There was wide variation within the three readability parameters: reading ease varied from easy to difficult, personal interest from tedious/scientific to very interesting/illustrated magazines and the quick reading test varied from formal to very popular. Two brochures were tedious and formal. As to the content, only three were significantly considered ‘very interesting for patients’ (P < 0.05). Most were found to be clear and not too long. Concrete information about administration, dosage and duration of therapy appeared to be absent from several leaflets. Adverse effects and possible complications were thought to be well rendered in most screened sources. According to the respondents, the role of the pharmacist was not sufficiently mentioned.Conclusion: Only three leaflets appeared to be suitable as a patient-oriented information tool. Pharmacists in psychiatric institutions can contribute to patient counselling by providing high-quality leaflets.

Prostaglandins restore the hyoscine-induced inhibition of the guinea-pig ileum

Prostaglandins E1, E2 and F2alpha as well as arachidonic acid partially increase the hyoscine inhibited twitch and tetanic responses of the guinea-pig ileum to electrical stimulation. They also produce a shift to the left of the dose-effect curve for acetylcholine and histamine previously displaced to the right by the administration of hyoscine or mepyramine. These results indicate a postsynaptic sensitization effect of the prostaglandins rather than a presynaptic facilitatory activity.

Activation of rabbit blood platelets by endotoxin: Significance of thromboxane biosynthesis and release reaction

Patients and methods Nine patients with liver cirrhosis (8 men, 1 woman, aged 34 to 66 years) were studied. The liver cirrhosis was due to alcohol in seven patients. Plasma TXB2 levels were measured by radio-immunoassay on one or more occasions, and blood was taken simultaneously for liver function tests, creatinine, platelet count, Normotest | fibrinogen, antithrombin III, and antiplasmin levels. Normal values for the TXB2 determination were obtained from 33 healthy individuals who had not taken non-steroidal anti-inflammatory drugs during a three month period.

The Use of a Virtual Learning Environment During the Internship of Final Year Pharmacy Students

An assessment was designed using Questionmark Perception, one of the programmes embedded in the TOLEDO-platform, to evaluate students’ progress in knowledge on 12 classes of OTC-medication. We investigated the use of the programme after one trimester of internship in pharmacy. Students do not use the programme intensively to monitor their progress, probably because of inadequate but requisite skill attainment prior to course enrolment. If we want to use the TOLEDO platform as a tool in guided self-study, we have to realise that demand for computer literacy, along with the need to identify computer skills of students prior to starting the course, would have to increase.