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Recent developments confirm predictions by the IEEE that Massive Open Online Courses (MOOCs) will have extensive impact on the future landscape of higher education. New degree structures are being introduced and awarding of verified MOOC credentials is becoming more widespread, as is recognition of MOOC credits by universities and employers. The question is whether this disruptive influence is being sufficiently used as an incentive for re-evaluation of standard practices and for driving strategic change in higher education.

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The lichen compound usnic acid is used for its antimicrobial activities in cosmetic products and is also a component of slimming agents. Its effect against cancer cells was first noted over 30 years ago. In this study possible mechanisms of this effect were investigated using two human cell lines, the breast cancer cell line T-47D and the pancreatic cancer cell line Capan-2. Pure (+)-usnic acid from CLADONIA ARBUSCULA and (-)-usnic acid from ALECTORIA OCHROLEUCA were shown to be equally effective inhibitors of DNA synthesis, with IC (50) 4.2 microg/mL and 4.0 microg/mL for (+) and (-)-usnic acid against T-47D, and 5.3 microg/mL and 5.0 microg/mL against Capan-2, respectively. Flow cytometric analysis confirmed the inhibited entry into the S-phase and showed reduction in cell size. Classical apoptosis, as assessed by TUNEL staining, was not observed. Necrosis, measured by LDH release, was seen only in Capan-2 after exposure for 48 hours. Staining with the mitochondrial dye JC-1 demonstrated dose-dependent loss of mitochondrial membrane potential following treatment with usnic acid in both cell lines. In conclusion, usnic acid had a marked inhibitory effect on growth and proliferation of two different human cancer cell lines and led to loss of mitochondrial membrane potential. Cell survival was little affected; late necrosis was seen in one of the cell lines. No difference was noted between the two enantiomers.

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The depside atranorin and depsidone fumarprotocetraric acid, isolated from the lichens Stereocaulon alpinum and Cetraria islandica, respectively, were chosen as prototypes for poorly soluble natural compounds in an effort to facilitate testing in pharmacological models. Solubilizing agents previously identified as being non-toxic towards a malignant leukemic (K-562) cell line and suitable for testing of anti-proliferative activity of the dibenzofuran lichen metabolite (+)-usnic acid were used in solubilization studies of the depside and depsidone. Cyclodextrin derivatives were found to be most suitable for solubilizing the lichen compounds, the greatest rise in solubility being witnessed for fumarprotocetraric acid, increasing almost 300-fold from 0.03 mg/ml in water to 8.98 mg/ml in 10% 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). Subsequently, the lichen compounds, including (+)-usnic acid, were solubilized in 10% HPbetaCD and tested for effects on three malignant human cell lines; T-47D (breast), Panc-1 (pancreas) and PC-3 (prostate) in a standard proliferation assay. Atranorin and fumarprotocetraric acid did not exhibit anti-proliferative effects but usnic acid was active against all test cell lines with EC50 values of 4.3-8.2 microg/ml. The non-toxic solubilizing agents used in this study could prove useful for pharmacological testing of other poorly soluble natural products.

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Lipoxygenases (LOXs) have been implicated in carcinogenesis in various cancer types. In the current study, three structurally different lichen metabolites, protolichesterinic acid (1), lobaric acid (2) and baeomycesic acid (3) were tested for anti-proliferative effects against 12 different human cancer cell lines. All compounds have known in vitro 5-LOX inhibitory activity, and 1 and 2 also inhibit 12-LOX. The activity of the lichen metabolites was compared to that of a specific 5-LOX inhibitor, zileuton (4). The following cancer cell lines were tested: Capan-1, Capan-2 and PANC-1 (all from pancreas), T47-D (breast), PC-3 (prostate), NCI-H1417 (small cell lung), NIH:OVCAR-3 (ovary), AGS (stomach), WiDr (colorectal), HL-60, K-562 and JURKAT (acute promyelocytic, erythro- and T-cell leukemia, respectively). Compound 1 showed the greatest inhibitory effect against all cell lines, with EC50 ranging from 2.4-18.1 microg mL(-1) (7.4-55.8 microM), followed by 2, with EC50 of 15.2 - 65.5 microg mL(-1) (33.2-143.6 microM). The effects of 3 and 4 were of similar orders of magnitude, with EC50 of 28.7 - >80 microg mL(-1) (76.8 - > 213.9 microM) and 12.9 - > 80 microg mL(-1) (50.4 - > 313.7 microM). The dual 5- and 12-LOX inhibitors 1 and to some extent 2 thus exert significant anti-proliferative effects against a variety of human cancer cell lines, while the selective 5-LOX inhibitors 3 and 4 are considerably less active.

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The pharmacological testing of natural products can often be hampered by the poor solubility of such compounds in non-toxic solvents. There is thus a need for a suitable agent for solubilization of natural substances to allow testing on a variety of cell lines in-vitro. Such an agent should ideally have no direct effects on any of the commonly used cell lines from a variety of tissues and mammalian species to allow proper comparison. In this study, the lichen metabolite (+)-usnic acid, a dibenzofuran derivative, was used as a prototype for an insoluble natural product with the aim of finding a solvent that was both capable of solubilizing usnic acid and was free of direct activity against a test cell line. Solubilization was measured at different pH values in various concentrations of co-solvents (glycofurol 75, propylene glycol, polyethylene glycol 400), surfactants (polysorbate 20 and Cremophor RH40), and the complexing agent 2-hydroxypropyl-beta-cyclodextrin. The solubility achieved in a 20% aqueous solution was 0.11 mg mL(-1) for propylene glycol, 0.19 for PEG 400, 0.27 for glycofurol 75, 0.57 for Cremophor RH40, 0.68 for 2-hydroxypropyl-beta-cyclodextrin and 0.84 for polysorbate 20. The direct effects of the various solvent systems were tested on the human leukaemia cell line K-562 in a standard proliferation assay. Most of the solvents proved toxic with the exception of propylene glycol, PEG 400 and 2-hydroxypropyl-beta-cyclodextrin. Anti-proliferative activity of usnic acid could be demonstrated with an ED50 (amount of substance required to reduce thymidine uptake to 50% of uptake by untreated control culture) of 4.7 microg mL(-1) using PEG 400 and 2-hydroxypropyl-beta-cyclodextrin but only the latter gave satisfactory solubility. 2-Hydroxypropyl-beta-cyclodextrin was thus identified as a solubilizing agent that fulfilled both set criteria of solubility and lack of toxicity against the test cells.

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OBJECTIVE: The aim of the study was to estimate the frequency of adverse effects and drug-interactions attributable to the use of herbal medicine and dietary supplements in Iceland. A further objective was to assess the perception and attitudes of Icelandic physicians towards these products. MATERIAL AND METHODS: A questionnaire was sent to all physicians registered in Iceland, a total of 1083. Physicians were questioned as to whether they had become aware of adverse effects or drug interactions that could be related to the use of herbal medicines or dietary supplements. Several questions concerned education and attitudes towards these products. A search was made using the computer system of the University Hospital in order to find cases of hospitalization resulting from consumption of herbal medicine. Details on admissions to the Emergency Department of the hospital were studied daily for one month. Enquiries made to the Icelandic Poison Center from 1997-2000 and formal reports submitted to the Icelandic Medicines Control Agency and the Surgeon General were examined. RESULTS: Of the 410 physicians that responded, 134 had become aware of adverse effects and 25 had become aware of herbal/drug interactions. Details on 253 adverse effects and 13 interactions were presented. Hospitalization was estimated to have been the consequence of 38 cases, 14 of which had been considered life-threatening. Of those who responded, 17% reported asking their patients always/frequently if they used herbal medicines or dietary supplements, whilst 62% reported asking occasionally/ seldom and 19% never asking. Approximately 55% of the respondents regard it as being very important/important that patients consult a physician before using herbal products or dietary supplements. CONCLUSIONS: Adverse effects and interactions between herbal medicines/dietary supplements and prescribed drugs appear to be under-reported in Iceland. It is important to increase awareness and education in this field amongst physicians and other health-care professionals in Iceland.