Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents.

Artemisia afra (Jacq. Ex. Willd), "African Wormwood" is widely used traditionally in South Africa with no literature evidence substantiating its safety. The aim of this study was to investigate the safety of the aqueous extract of Artemisia afra by determining its pharmaco-toxicological effects after acute and chronic administration in mice and rats, respectively. The aqueous extract mimicked the traditional decoction dosage form of Artemisia afra. In mice, single intraperitoneal injections of Artemisia afra-extract (1.5-5.5g/kg) induced a regular dose-dependent increase in the death rate and incidence of general behaviour adverse effects, while with single oral doses (2-24g/kg) the increases in incidence of general behaviour adverse effects and mortality rate were dose-independent. The LD(50s) after acute intraperitoneal and oral doses were 2.45 and 8.96g/kg, respectively. Rats given oral doses of Artemisia afra-extract (0.1 or 1g/kg/day) survived the 3 months of dosing (i.e. LD(50) much higher than 1g/kg), experienced no significant changes in general behaviour and haematological and biochemical parameters, except for transient decrease in AST activity. No significant changes were observed in organ weights, and histopathological results showed normal profile suggesting no morphological alterations. Collectively, the results indicate that Artemisia afra-extract is non-toxic when given acutely, has low chronic toxicity potential and, in high doses, may have a hepatoprotective effect.

The design and evaluation of placebo material for crude herbals: Artemisia afra herb as a model.

Herbal materials are known to present significant challenges with regard to designing credible placebos. This study intended to demonstrate the possibility of designing placebo material for crude herbals and used Artemisia afra, a popular traditional herbal medicine in South Africa, as a model. To produce the placebo, step-wise solvent extractions were conducted on the plant leaves and the process was monitored spectrophotometrically and using high performance liquid chromatography (HPLC) with diode array detection. The odour and taste between the placebo and A. afra was matched by inclusion of linalool and sodium saccharin, respectively. The muscle relaxant activity of the placebo was evaluated using an isolated guinea-pig tracheal muscle preparation. The UV absorbance of the extracts and the HPLC chromatograms, showed that most of the phytochemical constituents had been removed and the placebo closely resembled the A. afra leaves. The EC(50) of the placebo and the leaves were 4846.00 and 68.49 mg/mL, respectively, which showed that not only did the A. afra leaves possess muscle relaxant activity, but that the placebo did not possess any significant activity compared with the A. afra leaves (p value 0.0001). These results demonstrated that it is possible to design credible, pharmacologically inert placebo material for crude herbals.

Peak expiratory flow rate and symptom self-monitoring of asthma initiated from community pharmacies.

OBJECTIVE: To compare the use of patient-performed peak expiratory flow (PEFR) and symptom monitoring as asthma self-management tools initiated from community pharmacies. DESIGN AND SETTING: 110 patients over 6 years of age were recruited from five private-sector community pharmacies. Patients were identified from pharmacist recall as having 'asthma'. Information on the frequency of their asthma symptoms, medication use, level of physical activity, school or work attendance and lung function was obtained using a questionnaire to classify patients as either mild, moderate or severe. Each patient was alternately assigned to either the symptom or PEFR monitoring procedure in the order they were recruited. Patients performing symptom monitoring used a visual analogue scale to assess symptoms, whereas those in the PEFR monitoring group assessed symptoms and used a pocket-size peak flow meter to measure lung function. Both self-monitoring groups were required to adhere to an individualized management plan based on guideline recommendations and to record their monitored data in a diary card for 2 months. Data from the diary cards were reviewed, collated, transcribed and analysed using the Student t and Mann-Whitney tests. OUTCOME MEASURES: The average monthly frequency of appropriate patient responses determined from their adherence to the self-management plan was used to compare the usefulness of symptom and PEFR self-monitoring. In particular, appropriate use of medication and need for medical consultation was compared. RESULTS: 21 symptom and 40 PEFR-assigned patients completed 2 months' monitoring. The average monthly frequency of appropriate responses in patients using PEFR (0.76) was significantly higher than that of patients using symptom monitoring (0.53, P < 0.006). Patients applying symptom monitoring had a higher monthly frequency (0.39) of inappropriate medication use compared to the PEFR group (0.14). Furthermore, the patients' mean daily symptom scores (2.85) were significantly lower than that estimated by the researcher (4.12, P < 0.03). For all three asthma severity groups a higher monthly average of appropriate responses was observed in patients using PEFR monitoring compared to those who used symptom monitoring. CONCLUSION: PEFR self-monitoring proved to be a more useful asthma tool than symptom self-monitoring. Patients applying symptom monitoring tend to underestimate the severity of their condition and use medication inappropriately. Active involvement of community pharmacists in facilitating and reinforcing out-patient self-monitoring would help to optimize asthma management.

The effect of fenfluramine on the pulmonary disposition of 5-hydroxytryptamine in the isolated perfused rat lung: a comparison with chlorphentermine.

A possible mechanism for fenfluramine-induced pulmonary hypertension has been investigated. Fenfluramine, like chlorphentermine, may inhibit the pulmonary uptake and/or metabolism of 5-hydroxytryptamine (5-HT). This allows more 5-HT to remain in the pulmonary circulation, where it may exert a greater vasoconstrictor action resulting in pulmonary hypertension. Chlorphentermine has been shown to inhibit the uptake and metabolism of 5-HT. The effect of fenfluramine on the pulmonary disposition of [14C]5-HT has been investigated, in comparison with chlorphentermine, using a recirculating isolated perfused rat lung system. The pulmonary disposition of [14C]5-HT was assessed by measuring the change in [14C]5-HT concentration in the perfusion medium during the experiment and at the end, and the concentration in the lung at the end of the experiment. The concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-HT, was measured in perfusate and lung samples. Mean pulmonary clearance of 5-HT for the control lung and lungs challenged with either fenfluramine (2.5 microM) or chlorphentermine (25 microM) was 4.514, 1.316 and 1.007 mL min(-1), respectively (n = 5). The concentration of 5-HT found in the lungs at the end of the experiment for the control and the lungs preloaded with fenfluramine or chlorphentermine was 695.05+/-9.69, 638.65+/-10.27 and 617.3+/-14.38 ng g(-1), respectively. Fenfluramine, like chlorphentermine, inhibited the pulmonary disposition of 5-HT resulting in an elevated perfusate level of 5-HT. This is a possible contributing mechanism for fenfluramine-induced pulmonary hypertension. The effect of fenfluramine was less pronounced than chlorphentermine.

Antimicrobial and anticonvulsant activities of Viscum capense.

Dichloromethane, methanol and water extracts of Viscum sapense L.f., of the Loranthaceae family, were tested for antimicrobial activities against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Methanol extract was also tested for activity against seizures in albino mice induced by pentylenetetrazole (PTZ), bicuculline and N-methyl-DL-aspartic acid (NMDLA). Methanol extract of V. capense inhibited the growth of S. aureus. Methanol extract also protected the mice against PTZ- and bicuculline-induced tonic seizures but did not significantly alter NMDLA-induced tonic seizures. The data indicate that the extract of V. capense has antibacterial activity against S. aureus and also anticonvulsant activity.

An assessment of asthmatic patients at four Western Cape community pharmacies.

OBJECTIVES: To identify the profile of asthmatic patients visiting community pharmacies and to assess the appropriateness of their current asthma therapy. DESIGN: Patients were identified as either chronic, newly diagnosed or undiagnosed. Asthma status was assessed from their current symptom and medication profiles and from performance in an airways responsiveness test. Reversibility of > 15% was suggestive of probable airflow obstruction and such patients were referred to a medical practitioner. SETTING: Four community pharmacies located in different socio-economic areas, viz. Khayelitsha, Wynberg, Mitchell's Plain and Vrijzee, were selected. SUBJECTS: Participants over the age of 6 years, who suffered from recurrent cough, wheeze, chest tightness and/or breathlessness and used over-the-counter (OTC) and/or asthma medications, completed a questionnaire and participated in the airways responsiveness test. OUTCOME MEASURES: Effective control of asthma based on minimal symptoms, appropriate use of bronchodilator and anti-inflammatory therapies and absence of airflow obstruction. RESULTS: Of the 220 participants, 120 were identified as chronic, 7 as newly diagnosed and 93 as undiagnosed. Chronic asthmatics suffered daily symptoms and used inadequate prophylactic anti-inflammatory therapy. Many undiagnosed asthmatics were unaware of their symptoms and took OTC medication indiscriminately. Based on peak expiratory flow rate measurements, > 50% of the screened patients displayed a reversibility of > 15%. CONCLUSIONS: Chronic and many undiagnosed asthmatic patients frequent community pharmacies for their medication. Such patients suffer recurrent asthma symptoms and use medication inappropriately, which results in suboptimal lung function. Pharmacists should play a more participatory role in the detection and management of asthma in the community.

Propranolol-induced seizures in mice: the role of noradrenaline.

The effects of some noradrenergic agents, phenobarbitone, diazepam and phenytoin on seizures produced by propranolol were investigated in mice. Isoprenaline and DL-threo-3,4-dihydroxyphenylserine (DOPS) effectively antagonized the seizures elicited by propranolol. Pargyline and imipramine significantly attenuated propranolol-induced seizures and also significantly potentiated the protecting effect of DOPS against the seizures. alpha-Methyl-p-tyrosine, disulfiram and reserpine significantly potentiated propranolol-elicited seizures. However, DOPS significantly antagonized the seizure-potentiating effects of alpha-methyl-p-tyrosine, disulfiram and reserpine. Phenylephrine, clonidine, prazosin, idazoxan, phenobarbitone, diazepam and phenytoin did not significantly alter propranolol-induced seizures. These results suggest that propranolol-induced seizures in mice may involve a noradrenergic mechanism mediated via central beta-adrenoceptors.

Characterization of pulmonary alveolar esterases of the primate Cercopithecus pygerythrus.

PURPOSE: To evaluate and classify the hydrolases of the primate lung. METHODS: Homologous series of aromatic, aliphatic, and choline ester substrates were assayed with the pH-stat method to obtain the Michaelis-Menten kinetic constants, Vmax and K(m), for the enzymes in pulmonary alveolar tissue with esterase activity. Polyacrylamide gel electrophoresis was employed to determine the number of such hydrolytic enzymes. Inhibition studies with selective esterase inhibitors were carried out to classify enzymes as either arylesterases, carboxylesterases, or cholinesterases. RESULTS: Aromatic, aliphatic, and choline ester drugs were hydrolyzed by alveolar tissue of the primate lung. The catalytic enzymes were more specific for aromatic esters since these were metabolized at faster rates than the other substrates. Aromatic ester hydrolysis was also inhibited by triorthocresylphosphate (TOCP), a potent inhibitor of carboxylesterases. Inhibitors of arylesterases and cholinesterases had minimal effect on the enzymic hydrolysis of all substrates. Polyacrylamide gel electrophoresis demonstrated three enzymes to have esterolytic activity, two (MWs 269 and 281 kDa) of which were sensitive to TOCP and are therefore carboxylesterases. The third enzyme (MW 34 kDa), was unaffected by esterase inhibitors and, thus, cannot be classified as an esterase. CONCLUSIONS: Primate pulmonary alveolar tissue contains two isozymes of carboxylesterases.

The effect of ketanserin on serotonin-induced vascular responses in the isolated perfused rat lung.

Based on a vasoconstrictor role for serotonin (5-HT) in various types of cardiopulmonary conditions the effect of the 5-HT2 receptor antagonist, ketanserin, on 5-HT-induced responses in the intact, isolated rat lung was investigated. 5-HT produced biphasic responses consisting of weak vasodilator and predominant, dose-dependent constrictor components. Ketanserin showed no direct vasodilator effects but could completely antagonise the 5-HT-induced vasoconstrictor responses, suggesting that this response was 5-HT2 receptor-mediated.