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

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