Analysis of additivity and synergism in the anti-plasmodial effect of purified compounds from plant extracts

In the search for antimalarials from ethnobotanical origin, plant extracts are chemically fractionated and biological tests guide the isolation of pure active compounds. To establish the responsibility of isolated active compound(s) to the whole antiplasmodial activity of a crude extract, the literature in this field was scanned and results were analysed quantitatively to find the contribution of the pure compound to the activity of the whole extract. It was found that, generally, the activity of isolated molecules could not account on their own for the activity of the crude extract. It is suggested that future research should take into account the “drugs beside the drug”, looking for those products (otherwise discarded along the fractionation process) able to boost the activity of isolated active compounds

Treating leishmaniasis in Amazonia : a review of ethnomedicinal concepts and pharmaco-chemical analysis of traditional treatments to inspire modern phytotherapies

Ethnopharmacological relevance: Cutaneous and mucocutaneous leishmaniasis are neglected tropical diseases that occur in all intertropical regions of the world. Amazonian populations have developed an abundant knowledge of the disease and its remedies. Therefore, we undertook to review traditional antileishmanial plants in Amazonia and have developed new tools to analyze this somewhat dispersed information. Material and methods: A literature review of traditional remedies for cutaneous/mucocutaneous leishmaniasis in the Amazon was conducted and the data obtained was used to calculate distribution indexes designed to highlight the most relevant uses in Amazonia. The cultural distribution index represents the distribution rate of a given taxon among different cultural groups and was calculated as the ratio of the number of groups using the taxon to the total number of groups cited. The geographical distribution index allowed us to quantify spatial distribution of a taxon's uses in Amazonia and was calculated geometrically by measuring the average distance between the points where uses have been reported and the barycenter of those points. The general distribution index was defined as an arithmetic combination of the previous two and provides information on both cultural and spatial criteria. Results: 475 use reports, concerning 291 botanical species belonging to 83 families have been gathered depicted from 29 sources. Uses concern 34 cultural groups. While the use of some taxa appears to be Pan Amazonian, some others are clearly restricted to small geographical regions. Particular attention has been paid to the recipes and beliefs surrounding treatments. Topical application of the remedies dominated the other means of administration and this deserves particular attention as the main treatments against Neotropical leishmaniasis are painful systemic injections. The data set was analyzed using the previously defined distribution indexes and the most relevant taxa were further discussed from a phytochemical and pharmacological point of view. Conclusions: The Amazonian biodiversity and cultural heritage host a fantastic amount of data whose systematic investigation should allow a better large-scale understanding of the dynamics of traditional therapies and the consequent discovery of therapeutic solutions for neglected diseases. Distribution indices are indeed powerful tools for emphasizing the most relevant treatments against a given disease and should be very useful in the meta-analysis of other regional pharmacopeia. This focus on renowned remedies that have not yet benefitted from extended laboratory studies, could stimulate future research on new treatments of natural origin for leishmaniasis

Quassinoids: Anticancer and Antimalarial Activities

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L'assistance circulatoire en attente de transplantation. Sélection des patients et choix du système d'assistance [Circulatory assistance while waiting for heart transplantation. Patient selection and choice of the assist system]

TWO CLINICAL SITUATIONS: Mechanical circulatory assistance can be indicated in two clinical situations: i) patients on the waiting list for heart transplantation who have chronic heart failure unresponsive to drug therapy and whose clinical status worsens; ii) patients with acute heart failure. The exact indications for mechanical circulatory assistance are difficult to establish. Hemodynamic criteria are no longer sufficient. Circulatory assistance may be proposed for chronic heart failure patients with a high risk of death or in a situation of acute deterioration. Among these patients, several risk factors can be used to establish scores that have a better predictive value than risk factors taken alone. Two predictive models have been recently established. The first one takes into account 7 independent variables: etiology, heart rate at rest, left ventricle ejection fraction, mean blood pressure, intraventricular rhythm disorder, VO2max and serum sodium). In addition to these variables, the second model also includes pulmonary wedge pressure. In selected patients with acute heart failure, circulatory assistance is needed as early as possible to avoid irreversible multiple organ failure. The crucial problem is rapid assessment of the feasibility of heart transplantation. Several variables can be used to predict survival in candidates for mechanical circulatory assistance on the heart transplantation waiting list. They include hemodynamic criteria, renal function, liver function, preoperative infection and the emergency nature of the need for circulatory assistance. The choice depends both on the patient (surface area is important) and the underlying disease

L'assistance circulatoire en attente de transplantation. Résultats de la transplantation cardiaque après assistance mécanique de la circulation [Circulatory assistance while waiting for heart transplantation. Outcome of heart transplantation after mechanical circulatory assistance]

In most of the published (uncontrolled) studies, survival after transplantation is similar for patients who required mechanical circulatory assistance and those who did not. Two controlled studies have reported a better survival rate in patients who had preoperative circulatory assistance. Infections are more frequent in transplanted patients who had a period of circulatory assistance preoperatively than in those who were transplanted after medical treatment. The effect of circulatory assistance on heart graft rejection is debated. The same is true for coronary grafts

Platelet activation and aggregation profile in prolonged external ventricular support.

Platelet function plays a major role in the understanding of thromboembolic events in prolonged mechanical support. We studied the platelet activation, platelet aggregation profile, and efficacy of aspirin in patients in whom an external ventricular assist device had been implanted. Fifteen patients were studied prospectively up to 6 weeks after implantation of the same type of ventricular assist device. Platelet function was studied weekly before daily aspirin administration. Aspirin efficacy was tested ex vivo by measuring platelet aggregation triggered by arachidonic acid. Flow cytometry was used to quantify the spontaneous and induced (adenosine diphosphate stimulation) expression of glycoproteins alphaIIbbeta3, Ibalpha, and CD62P on platelet membranes. The plasma levels of von Willebrand factor (von Willebrand factor activity and von Willebrand factor antigen) and fibrinogen were also determined. Six of the 15 patients (26%) maintained an arachidonic acid-induced platelet aggregation despite daily aspirin treatment (250 mg). CD62P values remained increased during a 5-week postoperative period. Spontaneous levels of glycoproteins alphaIIbbeta3 and Ibalpha on platelet membranes remained within a normal range with a preserved reactivity. The plasma levels of fibrinogen and von Willebrand factor remained increased during the entire study period. In patients with an implanted external ventricular assist device, the platelet activation profile displays a persistent activation with a preserved reactivity associated with a persistent high inflammatory state and endothelial activation

From Tonic-cups to Bitter-cups: Kwasi bita beker from Suriname. Determination, past and present use of an ancient galenic artefact.

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In vitro antifungal activity of Otacanthus azureus (Linden) Ronse essential oil alone and in combination with azoles

International audienceWe determined the chemical composition and investigated the antifungal activity of Otacanthus azureus (Linden) Ronse essential oil alone or combined with azoles antifungals against a range of human yeasts and dermatophytes. The oil was shown to be composed in majority of sesquiterpenes. Using broth microdilution techniques, it was found to exert interesting in vitro antifungal activities, more particularly against human dermatophytes, with minimum inhibitory concentrations as low as 4µg/ml against a clinical isolate of Trichophyton rubrum. The analysis of the combined effect of this oil with azoles highlighted a pronounced synergism between the oil and ketoconazole or itraconazole, against Candida albicans, C. parapsilosis and Trichophyton mentagrophytes, with fractional inhibitory concentration indices in the 0.1–0.5 range. Interestingly, the oil showed no cytotoxicity on VERO cells (ED50>100µg/ml). According to these results, O. azureus essential oil may be considered a promising natural product in the treatment of human mycoses, more particularly those originating from dermatophytic fungi. Also, it is likely to reduce the minimum effective dose of ketoconazole and itraconazole against Candida species, thus minimizing the side effects of these drugs, and the risk to develop resistances

Therapeutic switching : from antidermatophytic essential oils to new leishmanicidal products

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydro-distilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50 : 4.7 mu g/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis

Picrasin K, a new quassinoid from Quassia amara L. (Simaroubaceae)

A new quassinoid Picrasin K 1 was isolated from a decoction made of Quassia amara leaves, traditionally used in French Guiana to treat malaria. The structure and relative stereochemistry of 1 was determined through extensive NMR analysis. Picrasin K showed a low activity against Plasmodium falciparum in vitro (IC50 = 8 mu M), and a similar low activity on human cancerous cells line (IC50 = 7 mu M on MCF-7 cells line)