Modifications of the chemical structure of terpenes in antiplasmodial and antifungal drug research.

Pure natural monoterpenes were evaluated in vitro for their antiplasmodial activities against Plasmodium falciparum. Chemically modified terpenes were also tested to see whether the introduction of an alkyne, a cyclopropane, a diene, or a cyclopentenone moiety had an influence on the biological activity. The IC(50) obtained on a chloroquine-resistant strain of Plasmodium (FcM29-Cameroon) showed moderate activity, but with the alkyne and the cyclopentenone derivatives showing a promising enhancement of activity compared with the parent molecules. On the contrary, no antifungal activity was found in vitro using Candida albicans. Given the observed antiplasmodial activity of some of these modified monoterpenes, new monoterpene derivatives could be the basis for new antimalarial drugs to be researched.

Acute severe mitral regurgitation during first attacks of rheumatic fever: clinical spectrum, mechanisms and prognostic factors.

BACKGROUND AND AIM OF THE STUDY: The study aim was to describe the clinical spectrum and mechanism of acute severe mitral regurgitation (MR) observed during first episodes of rheumatic fever (RF), and to identify prognostic factors related to the short-term outcome. METHODS: Since 1990, 44 patients (mean age 9.2 +/- 0.1 years; range: 4-17 years) have been admitted to the authors' institution with severe MR related to a first episode of RF, fulfilling revised Jones' criteria. Twenty-three patients admitted between 1995 and 2002 were included prospectively, and 21 admitted before 1994 were studied retrospectively. RESULTS: Left ventricular end-diastolic and end-systolic dimensions were 51 +/- 2 mm (46 +/- 3 mm/m2 BSA) and 32 +/- 2 mm (28 +/- 2 mm/m2 BSA), respectively; mean fractional shortening of the left ventricle was 39.0 +/- 1.0% (range: 31-52%); Doppler-derived pulmonary arterial systolic pressure (PAPS) was 51 +/- 6 mm (range: 27-90 mm). The mitral valve annulus was enlarged in all patients (mean diameter 31 +/- 2 mm; 27 +/- 4 mm/m2 BSA). MR resulted from prolapse of the anterior mitral valve leaflet (P of AMVL) in 16 patients (36%), and from prolapse of the posterior mitral valve leaflet (P of PMVL) in nine (20%); the other 19 patients (43%) had restrictive motion of the PMVL, with normal motion of the AMVL, resulting in a 'false prolapse' of the AMVL (FP of AMVL). During the six-month interval following the RF episode, mitral valve surgery was required in 11 patients (25%); three patients (7%) died from cardiogenic shock before they could undergo surgery, while the other 30 patients were stabilized under medical treatment. Using univariate analysis, death or mitral valve surgery was associated with PAPS > 50 mm (OR = 1.7, p = 0.04), male gender (OR = 1.88, p = 0.008), clinical signs of congestive heart failure at admission (OR = 2.7, p < 10(-4)), and prolapse of the PMVL (OR = 5.2, p = 0.01). Death occurred, or mitral valve surgery was necessary, in eight patients with P of PMVL (89%), in four with P of AMVL (25%), and in two with FP of AMVL (11%) (p < 0.001). Despite limitations due to co-linearities and small sample size, multivariate analysis identified P of PMVL as the most potent predictor of adverse outcome. The long-term follow up (mean 6.3 years) of patients without P of PMVL, alive and not operated on during the first six-month interval after an RF episode, demonstrated a sharp decrease in the mean severity of MR (from grade 4 to 1.7; range: 1-3). CONCLUSION: In contrast to previous reports of chronic rheumatic MR, acute severe MR due to RF is more frequently related to P of AMVL or P of PMVL, than to FP of AMVL. Patients with P of AMVL or FP of AMVL tend to improve with medical treatment; however, those with P of PMVL carry a poor medical prognosis, and most often require early mitral valve surgery.

Does rheumatic myocarditis really exists? Systematic study with echocardiography and cardiac troponin I blood levels.

AIMS: Revised guidelines for diagnosis of rheumatic fever indicate that rheumatic myocarditis may 'contribute' to the genesis of congestive heart failure. Our objective was to assess non-invasively the presence of non-clinical markers of myocardial involvement in acute rheumatic fever. METHODS: Echocardiography and assessment of cardiac troponin I (cTnI) blood levels were systematically performed in 95 consecutive patients with acute rheumatic fever, who were divided into three groups. Group 1: patients without carditis (n=22); group 2: patients with carditis and without congestive heart failure (n=59); group 3: patients with carditis and congestive heart failure (n=14). RESULTS: Left ventricular ejection fraction was normal in all patients and did not differ between groups (group 1: 0.72+/-0.08, group 2: 0.69+/-0.06, and group 3: 0.66+/-0.07, p=0.09). Left ventricular diameters tend to be larger in group 3, but all patients had severe mitral and/or aortic regurgitation. Mean cTnI was 0.077+/-0.017 ng/ml (normal <0.1 ng/ml), did not differ between groups (p=0.45), and only 13 patients (seven with pericardial effusion) had detectable levels (0.2-0.4 ng/ml). CONCLUSIONS: Our study neither detected cTnI elevations nor echocardiographic abnormalities suggesting significant myocardial involvement during rheumatic fever. Congestive heart failure was always associated to severe valve regurgitation.