Availability and choice of antimalarials at medicine outlets in Ghana: the question of access to effective medicines for malaria control.

Although national and international efforts to combat malaria have intensified over the years, problems with availability, distribution, and choice of antimalarials at medicine outlets in Africa continue to exist. This article presents the results of an indicator-based assessment of availability and choice of antimalarials at 130 licensed medicine outlets in Ghana. We also discuss how the choice of an antimalarial to dispense conforms to recommendations of the national policy for malaria therapy. Data were obtained through face-to-face interviews, by reviewing facility records, and by observing the practices of dispensing staff in the medicine outlets. Antimalarials recommended in the policy were not readily available in the most accessible medicine outlets. Few outlets adhered to the policy when choosing antimalarials. Interventions targeting medicine outlets should be initiated to improve availability and access to effective medicines in order to support the national program for malaria control.

Pseudo-akuammigine, an alkaloid from Picralima nitida seeds, has anti-inflammatory and analgesic actions in rats.

Pseudo-akuammigine, an alkaloid from Picralima nitida seed extract was investigated for anti-inflammatory and analgesic actions using the carrageenan-induced rat paw oedema and the rat tail flick. The alkaloid, at 1.0, 5.0 and 50 mgkg(-1)(,) dose-dependently inhibited the mean maximal paw swelling attained during 6 h to 78.2+/-2.1, 74.7+/-4.3 and 59.5+/-2.3% of the mean control value respectively when administered p.o. 1 h before induction of oedema. At the same dose levels, the total paw swelling over the 6-h period was also significantly (P<0.05) reduced to 83.2+/-9.7, 73.0+/-5.0 and 55.8+/-8.3% of the mean control response respectively. When administered after induction of oedema, psi-akuammigine (5.0 mgkg(-1)) significantly (P<0.05) reduced established rat paw swelling to 82.8+/-4.6% of the control response after 5 h. As an analgesic, psi-akuammigine was 3.5 and 1.6 times less potent than morphine and indomethacin respectively. The ED(50) values were Morphine (2.9 microM), psi-akuammigine (10 microM) and indomethacin (6.3 microM). Naloxone (1.0 mgkg(-1)) significantly (P<0.05) antagonised the analgesic action of the alkaloid by 35.8+/-6.8%. Pseudo-akuammigine therefore exhibits anti-inflammatory and analgesic actions. The analgesic actions are mediated via interaction with opioid receptors.

The anti-inflammatory compounds of Polygonum bistorta: isolation and characterisation.

A bioassay-guided technique has been used to isolate anti-inflammatory compounds from the dried rhizomes of Polygonum bistorta, for structural identification. Anti-inflammatory activity was detected using the carrageenan-induced rat paw oedema. Two compounds were isolated which significantly suppressed the inflammatory response. Spectral data from EIMS and NMR together with some physical characteristics revealed the identities of the two active compounds as 5-glutinen-3-one and friedelanol. The results indicate that these two compounds largely account for the anti-inflammatory actions of the rhizomes of P. bistorta.

Opioid activity of alkaloids extracted from Picralima nitida (fam. Apocynaceae).

Extracts of the seeds of Picralima nitida (fam. Apocynaceae) have been reported to have opioid analgesic activity. In this investigation, isolated tissue bioassays and radioligand binding assays have been used to determine the opioid activity of five alkaloids--akuammidine, akuammine, akuammicine, akuammigine and pseudoakuammigine--extracted from the seeds of P. nitida. Akuammidine showed a preference for mu-opioid binding sites with Ki values of 0.6, 2.4 and 8.6 microM at mu-, delta- and kappa-opioid binding sites, respectively. The agonist actions of akuammidine in the mouse-isolated vas deferens were antagonised by naloxone and the mu-opioid receptor selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) confirming an action at mu-opioid receptors. In contrast, akuammine also showed highest affinity for mu-opioid binding sites (Ki 0.5 microM) but was an antagonist at mu-opioid receptors with a pK(B) of 5.7 against the selective mu-opioid receptor agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO). Akuammicine has the highest affinity for kappa-opioid binding sites (Ki 0.2 microM) and was a full agonist at kappa-opioid receptors in the guinea pig ileum preparation but a partial kappa-opioid receptor agonist in the vasa deferentia of the mouse and the rabbit. Akuammigine and pseudoakuammigine showed little or no efficacy in the opioid bioassays. None of the alkaloids had significant activity for opioid receptor-like binding sites (ORL1-binding sites) with Ki values >> 10 microM. These data show that some alkaloids extracted from the medicinal plant P. nitida possess varying degrees of agonist and antagonist activity at opioid receptors but possess neither high affinity nor selectivity for mu-, delta- or kappa-opioid receptors or the ORL1-receptor.

Anti-inflammatory activity of Polygonum bistorta, Guaiacum officinale and Hamamelis virginiana in rats.

The aqueous ethanolic extracts of Polygonum bistorta L. Polygonaceae, Guaiacum officinale L. Zygophyllaceae and Hamamelis virginiana L. Hamamelidaceae were screened for anti-inflammatory activity. Administered (100 and 200 mg kg-1, p.o.) before the induction of carrageenan rat paw oedema, extracts of P. bistorta significantly suppressed both the maximal oedema response and the total oedema response (monitored as area under the time course curve). H. virginiana was inactive and G. officinale was only active at 200 mg kg-1. At 200 mg kg-1 administered before the induction of adjuvant arthritis, P. bistorta significantly inhibited both the acute and chronic phases of the adjuvant-induced rat paw swelling, while G. officinale and H. virginiana were only active against the chronic phase. Further studies on P. bistorta (100-800 mg kg-1) revealed a dose-dependent inhibition of the carrageenan-induced rat paw oedema over the dose range 100-400 mg kg-1, the E50 value being approximately 158.5 mg kg-1. The extract (200 mg kg-1), administered after the onset of the inflammatory responses reversed the course of both the carrageenan- and adjuvant-induced rat paw swelling. The results confirm that the extracts of P. bistorta, G. officinale and H. virginiana contain anti-inflammatory substances.

Anti-inflammatory activity of resins from some species of the plant family Burseraceae.

The anti-inflammatory activities of extracts from the resins of four species of the plant family Burseraceae, Boswellia dalzielli, Boswellia carteri (gum olibanum), Commiphora mukul, and Commiphora incisa, were studied. The aqueous extracts of the resins of B. dalzielli, C. incisa, and C. mukul significantly inhibited both the maximal edema response and the total edema response during 6 h of carrageenan-induced rat paw edema. The octanordammarane triterpenes, mansumbinone and mansumbinoic acid, isolated from the resin of C. incisa, were separated and tested. Administered prophylactically, mansumbinone proved to be more than 20 times less potent than indomethacin and prednisolone in inhibiting carrageenan-induced rat paw edema. However, the molar potency of mansumbinoic acid was within one order of magnitude of those of indomethacin and prednisolone. The anti-inflammatory action of the acid on the carrageenan-induced edema was dose-related between 1.3 x 10(-5) and 2.5 x 10(-4) mol kg-1 when given before the inflammatory stimulus. The acid was able to reverse an established carrageenan-induced inflammatory response when administered 2 h after induction. Daily administration of mansumbinoic acid at a single dose level (1.5 x 10(-4) mol kg-1) significantly reduced joint swelling in adjuvant arthritis in rats. The results indicated that this compound is worthy of further investigation as an anti-inflammatory drug.