Training of overseas qualified doctors in Britain. Training programmes in countries overseas should be supported.
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Biomedical subjects
Publications and source records attributed to A Marston.
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LC-UV-mass spectrometry and bioassay co-directed fractionation of an aqueous acetone extract of the roots of Gentiana macrophylla gave three new chromene derivatives and two novel and six known secoiridoids, along with kurarinone, kushenol I, beta-sitosterol, stigmasterol, daucosterol, beta-sitosterol-3-O-gentiobioside, alpha-amyrin, oleanolic acid, isovitexin, gentiobiose and methyl 2-hydroxy-3-(1-beta-D-glucopyranosyl)oxybenzoate. The structures of the new products were established from spectral and chemical evidence as 2-methoxyanofinic acid and macrophyllosides A-D. The six known secoiridoids were gentiopicroside, sweroside, 6'-O-beta-D-glucosylgentiopicroside, 6'-O-beta-D-glucosylsweroside, trifloroside and rindoside. The new acid (2-methoxyanofinic acid), its methyl ester, kurarinone and kushenol I were shown to be active against the plant pathogenic fungus Cladosporium cucumerinum. The methyl ester and kurarinone inhibited also the growth of the human pathogenic yeast Candida albicans. Structure-activity relationships were studied. Thus, addition of a methoxyl group to the benzene nucleus of anofinic acid (2,2-dimethyl-2H-1-benzopyran-6-carboxylic acid) increased the antifungal activity remarkably whereas glycosylation at the carboxylic moiety was found to remove the activity. Esterification of the new acid induced its activity against C. albicans, but decreased its growth inhibition properties against C. cucumerinum. Hydroxylation of kurarinone at the 3 beta-position removed its activity against C. albicans and decreased the inhibition of C. cucumerinum. In addition, the chemotaxonomic significance of the identified constituents is discussed.
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Three known phloroglucinols (japonicine A, uliginosin A and isouliginosin B) and a new phloroglucinol (hyperbrasiol A) have been isolated from a petrol extract of the leaves and flowers of Hypericum brasiliense. Their structures were established by spectroscopic methods (UV, DCI-MS, 1H and 13CNMR, including SINEPT, HMBC, HSQC, DQFCOSY experiments). The substitution pattern of hyperbrasilol A was confirmed by X-ray crystallography. All four phloroglucinols were antibacterial against Bacillus subtilis in a TLC bioautographic assay. The flavonoids, kaempferol, luteolin, quercetin, quercitrin, isoquercitrin, hyperoside and guaijaverin, were isolated from a methanol extract of the same organs.
Three phenylpropanoids, myristicin [1], elemicin [2], and trans-isoelemicin [3], together with two furanocoumarins, oxypeucedanin [4] and oxypeucedanin hydrate [5], have been isolated from the leaves of Diplolophium buchanani by a separation strategy involving the almost exclusive use of centrifugal partition chromatography. All five compounds were antifungal in a tlc bioautography test using Cladosporium cucumerinum. Compounds 1-4 exhibited larvicidal activity against Aedes aegypti.
Bioactivity-guided fractionation has led to the isolation of two larvicidal diterpenes, active against the yellow fever-transmitting mosquito Aedes aegypti, from a dichloromethane root extract of Melantheria albinervia (Asteraceae), a plant from Zimbabwe. These diterpenes were identified as ent-kaur-16-en-19-oic acid and 9(11),16-kauradien-19-oic acid. The diterpenes were also weakly active against Bacillus subtilis.
Plants from Africa and Mauritius with a history of use in traditional medicine have been investigated for their antiviral activities. Extracts were tested against poliovirus, herpes simplex virus and rhinovirus in plaque reduction assays. Their general toxicity and effects on interferon production were also studied.
A new gamma-pyrone (hyperbrasilone), three known xanthones (1,5-dihydroxyxanthone, 5-hydroxy-1-methoxyxanthone and 6-deoxyjacareubin) and betulinic acid have been isolated from a dichloromethane extract of stems and roots of Hypericum brasiliense. Their structures were established by spectroscopic methods (UV, EI-MS, 1H and 13C NMR) and that of the gamma-pyrone was confirmed by X-ray crystallography. Hyperbrasilone and the xanthones were all antifungal against Cladosporium cucumerinum, while the three xanthones showed differing degrees of inhibition of monoamine oxidase A and B.
A major constraint in vascular surgery is the failure of the currently available prosthetic grafts to match the patency of autogenous vein below the inguinal ligament. Endothelial seeding aims to produce an endothelial lining which is otherwise absent from prosthetics. This could improve patency by preventing thrombosis and the release of mitogens by activated platelets implicated in the development of neointimal hyperplasia. Experimental evidence supports the potential of the technique but clinical trials have been less conclusive. A number of problems need to be solved if this application of cell biology is to become a part of vascular surgical practice.
Bilateral superficial femoral artery replacement using knitted Dacron was performed in 38 dogs. One side was seeded with omental mesothelium and the other acted as an unseeded control. 111In-labelled platelet accumulation on grafts was measured at 5 days and 2 months and the thrombogenicity index of seeded and unseeded grafts calculated. Patency was monitored for 2 months, at which time grafts were removed and luminal thrombus, ultrastructural cell cover and prostacyclin release were measured. Cell seeding did not influence the mean(s.e.m.) thrombogenicity index of 0.95(0.25) and 0.88(0.24) at 5 days in control and seeded grafts respectively; nor was there any difference between the groups at 2 months. Occlusion occurred in six control and four seeded grafts. Seeding did not significantly improve the percentage thrombus-free area or luminal cell cover. Neither did it enhance mean(s.e.m.) luminal 6-keto-prostaglandin F1 alpha release of 2.58(0.80) pg cm-2 in controls and 2.63(0.78) pg cm-2 in seeded grafts. Further studies demonstrated that only a mean(s.e.m.) of 4.4(1.9) per cent of the seeded inoculum was present on grafts 48 h after implantation, providing too few cells to achieve confluent cover. Mesothelial cell seeding might be useful in promoting a healed graft surface but critical levels of seeding density must be achieved before the technique can be properly evaluated.
African medicinal plants provide a rich source of biologically-active natural products. By the use of simple bioassays in conjunction with an approach involving bioactivity guided fractionation, it is possible to isolate novel compounds with interesting properties. Several hundred plant extracts have been submitted to different screens, including bioautography on TLC plates with the fungi Cladosporium cucumerinum and Candida albicans. Among the other test systems are a bioassay for molluscicidal activity with the schistosomiasis-transmitting snail Biomphalaria glabrata and a benchtop assay for larvicidal activity with larvae of the mosquito Aedes aegypti, the vector of yellow fever. Using a variety of modern separation techniques, a number of compounds with activity in these bioassays have been isolated. These include prenylated xanthones, tetracyclic phenols and saponins. The role of saponins and saponin-containing plants in the control of schistosomiasis is outlined.
Greyhounds (n = 38) were randomized to aspirin and dipyridamole (ASA + DPM), the thromboxane synthetase inhibitor (TSI) CGS12970 (CIBA-GEIGY) or placebo twice daily for 48 hours prior to bilateral implantation of femoral artery Dacron grafts. In-vivo 111In-platelet deposition on grafts was measured at 5 days and 2 months. Grafts were removed at 2 months when ex-vivo graft and arterial release of 6-ketoprostaglandin F1a (6-keto PGF1a) was measured by radioimmunoassay. Graft 6-keto-PGF1a was significantly increased by CGS12970 but ASA + DPM had no significant effect. ASA + DPM significantly reduced arterial 6-keto-PGF1a although this was marginally increased by CGS12970. Neither active treatment reduced in-vivo 111In-platelet deposition. Preservation of vascular or graft prostacyclin by thromboxane synthetase inhibitors may represent an alternative strategy in preventing prosthetic graft thrombosis.
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Thirty-eight dogs were randomized to the thromboxane synthetase inhibitor CGS12790 (3 mg/kg), aspirin 150 mg and dipyridamole 50 mg (ASA + DPM) or placebo (PLA), all twice daily. Two days later, animals underwent bilateral superficial femoral artery replacement with knitted Dacron. Grafts were removed at two months and subjected to macroscopic and histological examination. Thirty dogs survived to two months. Percentage thrombus free area (TFA) was increased from 15.1 +/- 2.2 with PLA to 46.6 +/- 5.2 with CGS12970 (P < 0.001) and to 32.9 +/- 5.0 with ASA + DPM (P < 0.01). At the anastomoses, only CGS12970 significantly reduced neointimal thickness, promoted pannus ingrowth and improved endothelialization. Percentage luminal occlusion at the midgraft was reduced from 48.2 +/- 5.9 with PLA to 33.9 +/- 2.7 with CGS12970 (P < 0.05). These results provide further evidence that platelet inhibitory therapy reduces thrombosis but also that the platelet is involved in anastomotic maturation. Therapy directed against thromboxane synthesis has potential that may be useful in clinical practice.
Six greyhounds underwent bilateral femoral artery replacement with knitted Dacron, one side seeded with omental digest at graft preclotting, the other acting as an unseeded control. Grafts were removed at 24 hours and two months. Tissue was examined using a monoclonal antibody (MNF116) directed against a broad range of human cytokeratins to differentiate mesothelial cells (MC) from microvascular endothelial cells (MEC), which stained only with a polyclonal antibody directed against von Willebrand Factor (anti-vWF). Cells released from omentum by collagenase stained with MNF116 and reacted poorly with anti-vWF. Identical cells were observed to be within the interstices of seeded but not control knitted Dacron. Few remained in seeded grafts (n = 2) removed at 24 hours and none at two months (n = 4).