In vivo and in vitro antimalarial activity of 4-nerolidylcatechol

4‐Nerolidylcatechol (4‐NC) isolated from Piper peltatum L. (Piperaceae) was evaluated for in vitro antiplasmodial activity against Plasmodium falciparum (cultures of both standard CQR (K1) and CQS (3D7) strains and two Amazonian field isolates) and for in vivo antimalarial activity using the Plasmodium berghei‐murine model. 4‐NC exhibits significant in vitro and moderate in vivo antiplasmodial activity. 4‐NC administered orally and subcutaneously at doses of 200, 400 and 600 mg/kg/day suppressed the growth of P. berghei by up to 63% after four daily treatments (days 1–4). Also, 4‐NC exhibited important in vitro antiplasmodial activity against both standard and field P. falciparum strains in which 50% inhibition of parasite growth (IC₅₀) was produced at concentrations of 0.05–2.11 μg/mL and depended upon the parasite strain. Interestingly, healthy (non‐infected) mice that received 4‐NC orally presented (denatured) blood plasma which exhibited significant in vitro activity against P. falciparum. This is evidence that mouse metabolism allows 4‐NC or active metabolites to enter the blood. Further chemical and pharmacological studies are necessary to confirm the potential of 4‐NC as a new antimalarial prototype. Copyright © 2011 John Wiley & Sons, Ltd.     

Determination of left ventricular volume by cardiac angio-scintigraphy at equilibrium. Comparison with a radiologic method

Cardiac angioscintigraphy at equilibrium was performed after in vitro red cell labelling in the left anterior oblique and anterior views. A syringe of 10 ml labelled blood was placed on the patient's chest over the left ventricle and in contact with the camera's collimator in the LAO incidence. This syringe plays a dual part: as a direct reference for left ventricular radio-activity and as a marker for measuring the distance between the centre of gravity of the LV and the collimator by Links' method. The correction factor for absorption varies with each individual. An algorithm integrating this data automatically calculates the EDV in millilitres (ml) and the end diastolic and systolic volumes from the ejection fraction (EF) determined by an independent method. The study group was 100 patients (91 men, 9 women; 81 coronary, 11 valvular heart and 8 other diseases) with radiological EDV ranging from 107 to 1 283 ml and radiological EF ranging from 14 to 75 p. 100. A very significant correlation was observed between the radiological and scintigraphic EDV with a regression line close to that of identity: EDVs = 1.05 . EDVR-5 ml (or -3 ml/m2); SD = 48 ml; r = 0.953; p less than or equal to 0.001. The mean deviation between the methods was 35.7 ml (median 24 ml) or 13.7 p. 100 (median 9.4 p. 100) of EDVR. A large discrepancy (over 90 ml or 30 p. 100) was observed in only 7 patients, 4 of whom had severe mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)     

16S rRNA gene sequences from bacteria associated with adult Anopheles darlingi (Diptera: Culicidae) mosquitoes

The microbial flora associated with Anopheles darlingi Root (Diptera: Culicidae), a major Neotropical malaria vector, was investigated for the development of a paratransgenesis-based approach to control malaria transmission in Brazil. Female mosquitoes were collected using human land catches and captured insects provided a bloodmeal. The controlled blood feeding resulted in increased detection of mosquito bacterial population because it was possible to retrieve bacterial DNA from all blood-fed mosquitoes. The 16S sequences of bacteria recovered, include some closely related to those found in other vector mosquitoes, including Aeromonas, Pantoea and Pseudomonas species.     

In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives

4-Nerolidylcatechol (1) is an abundant antiplasmodial metabolite that is isolated from Piper peltatum roots. O-Acylation or O-alkylation of compound 1 provides derivatives exhibiting improved stability and significant in vitro antiplasmodial activity. The aim of this work was to study the in vitro inhibition of hemozoin formation, inhibition of isoprenoid biosynthesis in Plasmodium falciparum cultures, and in vivo antimalarial activity of several 4-nerolidylcatechol derivatives. 1,2-O,O-Diacetyl-4-nerolidylcatechol (2) inhibited in vitro hemozoin formation by up to 50%. In metabolic labeling studies using [1-(n)-³H]geranylgeranyl pyrophosphate, diester 2 significantly inhibited the biosynthesis of isoprenoid metabolites ubiquinone 8, menaquinone 4, and dolichol 12 in cultures of P. falciparum 3D7. Similarly, 2-O-benzyl-4-nerolidylcatechol (3) significantly inhibited the biosynthesis of dolichol 12. P. falciparum in vitro protein synthesis was not affected by compounds 2 or 3. At oral doses of 50 mg per kg of body weight per day, compound 2 suppressed Plasmodium berghei NK65 in infected BALB/c mice by 44%. This in vivo result for derivative 2 represents marked improvement over that obtained previously for natural product 1. Compound 2 was not detected in mouse blood 1 h after oral ingestion or in mixtures with mouse blood/blood plasma in vitro. However, it was detected after in vitro contact with human blood or blood plasma. Derivatives of 4-nerolidylcatechol exhibit parasite-specific modes of action, such as inhibition of isoprenoid biosynthesis and inhibition of hemozoin formation, and they therefore merit further investigation for their antimalarial potential.     

Role of egg buster in hatching of Aedes aegypti: scanning electron microscopy study

Egg hatching has been studied in Aedes aegypti (L.) through scanning electron microscopy. The first sign of egg hatching is a small protrusion on the eggshell in the anterior pole. The larval movement provokes a crack in the eggshell with the egg buster located in the dorsal head. The egg buster provokes a small transverse fissure in the eggshell that gradually increases in the chorion. Then, the rupture is completed around the eggshell. The separation of the anterior pole occurs, showing the dorsal region of the larva head with the egg buster and the cap. After sequential movements, the larva looses the cap. Finally, the first instar is ready to be free showing details of its body with the egg buster over its head. This structure is a cuticular formation, similar to a cone structure that ends in a very fine tip and emerges from a pear-like depression with high rounded borders. Our results describe the anatomy of the egg hatching process in Ae. aegypti, showing details of the participation of the egg buster.     

Reciprocal changes in the ST segment in acute inferior myocardial infarction. Value of delay in appearance

The significance of a "reciprocal" ST depression (ST(-)) in the acute phase of myocardial infarction remains controverted. This may be due to ST(-) not having the same determinants when studied at an early stage (less than 6 hours) or later (greater than 6 hours). The purpose of this study was to find out whether "reciprocal" ST(-) correlates with the same parameters when measured on very early ECG's (before 6 hours) or at a distance from the onset of infarction. The parameters concerned are coronary lesions, extent of the infarction and left ventricular function. ECG was performed in 46 patients with inferior infarct aged from 26 to 70 years (mean 50.8 +/- 9.2 years) between 2-6 h, 6-12 h, 12-24 h and 24-48 h from the beginning of pain. The sum of ST(-) on V1V2V2V4 (V1-4), D1aV1V1 to V6 and L1aV1V5V6, and the sum of ST elevation on L2L3aVf were measured at each period of time. The extent of global and anterior territory hypokinesia, the ejection fraction and the left coronary impairment were evaluated between the 2nd and 4th weeks. At 2-6 hours (a) the sum of ST(-) was greater (though not significantly), and the sum of ST elevation on L2L3aVf was significantly greater (p less than 0.001) when the left anterior descending artery (LAD) was not involved than when it was involved; (b) there was no difference between patients with and without ST depression (on all lead groups) in the degree of left ventricular hypokinesia and ejection fraction value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the residual effect of temephos on Aedes aegypti (Diptera,Culicidae) larvae in artificial containers in Manaus,Amazonas State,Brazil

Trial tests and container observations were conducted in households to verify the residual effect of temephos in Manaus, Amazonas State, Brazil. Three plastic buckets, three tin cans, and three tires filled with water from an artesian well and larvicide were used in the experiment, with twenty-five third-instar larvae, which remained exposed for 24h, followed by mortality readings. The same types of containers were selected from common households. Collection and counts followed by chemical treatment were carried out on the larvae that were found. Follow-up was performed weekly to verify recolonization by Aedes aegypti.The experiment showed 100% mortality in the plastic buckets until day 90, and 80% in the tin cans until day 30, decreasing from day 45 onwards. Mortality in the tires decreased to 35% in the first month. Household results showed 100% mortality for all containers after 24h and differentiated values in the subsequent readings. Larvae were observed on day 35 in a tin can and on day 21 in a gallon can. There was a large diversity of results in the tires, with recolonization observed from day 7 onwards.     

Natural history of syncope of undetermined origin with inconclusive electrophysiologic examination]

Between 1985 and 1986, 109 consecutive patients with unexplained syncope after clinical and standard electrocardiographic examination underwent electrophysiological investigation. In 61 cases (56%), 35 men and 26 women (mean age 69 +/- 13 years) no firm diagnosis could be made. These patients were the study group. Underlying cardiac disease was present in 23%, coronary artery disease in 10% of cases. In 33 cases, the basal ECG was normal (54%). Sixty patients (one lost to follow-up) were studied over an average of 38 +/- 12 months. Global mortality and recurrence rate were 13 and 18% respectively. There were no sudden deaths in the 8 fatalities. The mechanism of the 17 recurrent syncopes was cardiac in 5 cases, vasovagal in 1 case, uncertain in 11 cases. Of the 5 cardiac syncopes, 3 were related to 3rd degree atrioventricular block occurring 7 to 49 months after the initial electrophysiological investigation. No predictive criteria of recurrence could be identified. Empiric treatment proposed to 28% of patients did not prevent recurrent syncope and did not improve global survival. Inconclusive electrophysiological investigation of patients with unexplained syncope defines a population with a low risk of sudden death. Recurrent syncope is common. The recurrence of symptoms is an indication to repeat the aetiological investigations which should include a tilt-test ot another electrophysiological investigation. Empiric treatment has not been shown to be effective.     

Relation between serum levels and inotropic effect of digoxin in advanced cardiac failure during long-term treatment

The aim of this study was to determine the relationship of digoxin serum levels to their inotropic effects in advanced cardiac failure during long-term therapy with different dosages. The study was based on the analysis of left ventricular systolic time intervals (STI) measured at 97 follow-up appointments of 20 patients in advanced, stable cardiac failure over an average period of 37 days. The dosage of digoxin was varied at successive consultations so that the serum digoxin levels reached 0.50 ng/ml on at least one occasion. The serum digoxin levels (SD) varied between 0 and 4 ng/ml. Four levels of SD were individualised: A) "control" SD less than 0.25 ng/ml (22 consultations); B) SD: 0.25 to 1 ng/ml (n = 25); C) SD: 1.0 to 2.0 ng/ml (n = 29); D) SD greater than 2 ng/ml (n = 21) including 6 cases with clinical and/or ECG signs of digoxin toxicity. A progressive significant shortening of the electromechanical systolic index (Q-S2 I) was observed up to levels of 2 ng/ml (B and C, -18 ms and -28 ms respectively). The same phenomenon was observed with the ejection time index (ETi) and pre-ejection time index (PETi) (-7 ms and -14 ms; -11 ms and -15 ms respectively) compared to the basal values. At SD greater than 2 ng/ml the reduction remained stable and then started to decrease (positive difference between C and D). These changes were observed in the absence of significant variations of the heart rate. There was a significant linear relationship between the variations of the STI and SD in 15 out of 18 patients (in whom the regression could be calculated, these patients having attended at least 3 appointments). These linear relationships were observed for the Q-S2 i (11-18), the ETi (9-18) and/or PETi (10-18). An unexpected increase in the pre-ejection period was observed in 2 patients. In conclusion, a linear relationship has been shown between SD and inotropic effect which is particularly noticeable at SD levels less than 2 ng/ml. When SD is greater than 2 ng/ml, further increases in SD are associated with smaller variations of the STI. On the other hand, a significant inotropic effect is observed with small doses and SD levels less than 1 ng/ml. This inotropic effect persists unchanged at long-term.