Late Clinical Outcomes of the Fontan Operation in Patients with Tricuspid Atresia

OBJECTIVE: Evaluation of the long-term clinical results of the Fontan operation in patients with tricuspid atresia. METHODS: A retrospective analysis was made at the Instituto de Cardiologia do Rio Grande do Sul (Institute of Cardiology of Rio Grande do Sul), from August 1980 through January 2000, of 25 patients with a long-term follow-up, out of a series of 36 patients who underwent the Fontan operation or one of its variants due to tricuspid atresia. Their mean age at surgery was 5.4±3.1 years, and their mean weight was 15.8±6.1 kg, the majority of them (63.9%) being males. Four patients underwent the classical Fontan operation, 12 the Kreutzer variant, 6 the Björk variant, 9 total cavopulmonary shunt with a fenestrated tube, and 5 total cavopulmonary shunt with a nonfenestrated tube. RESULTS: The patients were followed-up on an outpatient basis, with a mean long-term survival time of 5.5±4.2 years (50 days to 17.8 years) and a late mortality rate of 8%. Arterial saturation increased from 77.2±18.8% in the preoperative period to 91±6.7% upon the last outpatient visit (p>0.05). At the final check, most (67%) patients were asymptomatic and 87% could tolerate exercise. Ten (40%) patients experienced some kind of complication during the long-term follow-up, such as cardiac arrhythmia, cyanosis, protein-losing enteropathy, neurological events, right heart failure, intolerance to exercise and reoperation. CONCLUSION: The results indicate that, once the immediate postoperative period is over, during which the adaptations to the new circulatory physiology occur, the evolution of patients with tricuspid atresia who underwent the Fontan operation is satisfactory, in spite of a low, yet significant, morbidity.

Stratification of the Risk of Sudden Death in Nonischemic Heart Failure

Despite significant therapeutic advancements, heart failure remains a highly prevalent clinical condition associated with significant morbidity and mortality. In 30%-40% patients, the etiology of heart failure is nonischemic. The implantable cardioverter-defibrillator (ICD) is capable of preventing sudden death and decreasing total mortality in patients with nonischemic heart failure. However, a significant number of patients receiving ICD do not receive any kind of therapy during follow-up. Moreover, considering the situation in Brazil and several other countries, ICD cannot be implanted in all patients with nonischemic heart failure. Therefore, there is an urgent need to identify patients at an increased risk of sudden death because these would benefit more than patients at a lower risk, despite the presence of heart failure in both risk groups. In this study, the authors review the primary available methods for the stratification of the risk of sudden death in patients with nonischemic heart failure.

Hereditariedade da homeose

A preliminary account on the normal development of the imaginai discs in holometabolic Insects is made to serve as an introduction to the study of the hereditary homoeosis. Several facts and experimental data furnished specially by the students of Drosophila are brought here in searching for a more adequate explanation of this highly interesting phenomenon. The results obtained from the investigations of different homoeotic mutants are analysed in order to test Goldschmidt's theory of homoeosis. Critical examination of the basis on which this theory was elaborated are equally made. As a result from an extensive theoretical consideration of the matter and a long discussion of the most recent papers on this subject the present writer concludes that the Goldschmidt explanation of the homoeotic phenomena based on the action of diffusing substances produced by the genes, the "evocators", and on the alteration of the normal speed of maturation of the imaginai discs equally due to the activity of the genes, could not be proved and therefore should be abandoned. In the same situation is any other explanation like that of Waddington or Villee considered as fundamentally identical to that of Goldschmidt. In order to clear the problem of homoeosis in terms which seem to put the phenomenon in complete agreement with the known facts the present writer elaborated a theory first published a few years ago (1941) based entirely on the assumption that the imaginai discs are specifically determined by some kind of substances, probably of chemical nature, contained in the cytoplam of the cells entering in the consti- tution of each individual disc. These substances already present in the blastem of the egg in which they are distributed in a definite order, pass to different cells at the time the blastem is transformed into blastoderm. These substances according to their organogenic potentiality may be called antenal-substance, legsubstance, wing-substance, eye-substance, etc. The hipoderm of the embryo resulting from the multiplication of the blastoderm cells would be constituted by a series of cellular areas differing from each other in their particular organoformative capacity. Thus the hypoderm giving rise to the imaginai discs, it follows that each disc must have the same organogenic power of the hypodermal area it came from. Therefore the discs i*re determinated since their origin by substances enclosed in the cytoplasm of their cells and consequently can no longer alter their potentiality. When an antennal disc develops into a leg one can conclude that this disc in spite of its position in the body of the larva is not, properly speaking, an antennal disc but a true leg disc whose cells instead of having in their cytoplasm the antennal substance derived from the egg blastem have in its place the leg-substance. Now, if a disc produces a tarsus or an antenna or even a compound appendage partly tarsus-like, partly antenna-like, it follows tha,t both tarsal and antennal substances are present in it. The ultimate aspect of the compound structure depends upon the reaction of each kind of substance to the different causes influencing development. For instance, temperature may orient the direction of development either lowards arista or tarsus, stimulating, or opposing to the one or the other of these substances. Confering to the genes the faculty of altering the constitution of the substances containing in the cytoplasm forming the egg blastem or causing transposition of these substances from one area to another or promoting the substitution of a given substance by a different one, the hereditary homoeocis may be easily explained. However, in the opinion of the present writer cytoplasm takes the initiative in all developmental process, provoking the chromosomes to react specifically and proportionally. Accordingly, the mutations causing homoeotic phenomena may arise independently at different rime in the cytoplasm and in the chromosomes. To the part taken by the chromosomes in the manifestation of the homoeotic characters is due the mendalian ratio observed in homoeotic X normal crosses. Expression, in itself, is mainly due to the proportion of the different substances in the cells of the affected discs. Homoeotic phenomena not presenting mendelian ratio may appear as consequence of cytoplasmic mutation not accompanied by chromosomal mutation. The great variability in the morphology of the homoeotic characteres, some individual being changed towards an extreme expression of the mutant phenotype while others in spite of their homozigous constitution cannot be distinguished from the normal ones, strongly supports the interpretation based on the relative proportion of the determining substances in the discs. To the same interpretation point also asymetry and other particularities observed in the exteriorization of the phenomenon. In conformity with this new conception homoeosis should not prove homology of Insect appendages (Villee 1942) since a more replacement of substances may cause legs to develop in substitution of the wings, as it was already observed (requiring confirmation in the opinion of Bateson 1894, p. 184) and no one would conclude for the homology of these organs in the usual meaning of the term.

Soldadura por uma das extremidades de dois cromossômios homólogos do tityus

In this paper the author describes a very interesting case of union of two homologous chromosomes of the scorpion Tityus bahiensis just by the opposite extremities. The two normal pairs of chromosomes behave as ordinarily, the members of each pair showing at times a slight disturbance in their regular parallelism. The complex chromosome, on the contrary, behaves itself as if it were devoid of kinetochores, that is, it does not orient like normal chromosomes nor reveal any kind of active movement. The fusion of the chromosomes has resulted from terminal breakage at the opposite ends, the correspondig fragments having been found unpaired in a cell in which two pairs of chromosomes were present. Consequently, the compound chromosome, like the normal ones, is provided with a kinetochore at each one of the free ends. Being thus a centric chromosome its behavior, or more exactly, its kinetic inactivity may be compared with that of the monovalents found elsewhere in meioses. It is due o the failure of a partner. The fusion of two homologous chromosomes has transformed them into a new chromosomal unit in whose corresponding parts the ability of pairing was entirely abolished. This result is in full contradiction with the theory of a point-to point attraction between homologous chromosomes attributed to particular power of the genes, since, if genes really exist, being placed in their original loci, they would promote the union side by side of the members of the compound chromosome. If an attraction loci-to-loci should prevail the compound chromosome would be bent as in Fig. 8, C or form a ring similar to the loops observed in the inverted segment of sailvary chromosomes of Drosophila, as represented in the Fig. 8, D and this, in accordance with the order of the loci resulting from an union of corresponding or opposite ends of the fused chromosomes, as indicated in the Fig, 8 A and B. The evidence in hand points to a fusion by non homologous extremities. The expected rings, however, have never been found in metaphase plates. From this fact the author concludes that there is no point-to-point attraction between chromosomes, a conclusion in full agreement with the behavior of Hemipteran chromosomes which, in spite of geing composed of two equivalent halves do not bend in order to adjust the corresponding loci. (Cf. the papers on Hemiptera published by the author in this volume).

Tracer studies in the coffee plant (Coffea arabica L.)

Due to the great importance of coffee to the Brazilian economy, a good deal of the work carried out in the "Laboratório de Isótopos", E. E. A. "Luiz de Queiroz", Piracicaba, S. Paulo, Brazil, was dedicated to the study of some problems involving that plant. The first one was designed to verify a few aspects of the control of zinc deficiency which is common in many types of soils in Brazil. An experiment conducted in nutrient solution showed that the leaf absorption of the radiozinc was eight times as high as the root uptake; the lower surface of the leaves is particularly suited for this kind of absorption. Among the heavy metal micronutrients, only iron did not affect the absorption of the radiozinc; manganese, copper, and molybdenum brought about a decrease of fifty per cent in total uptake. In another pot experiment in which two soils typical of the coffee growing regions were used, namely, a sandy soil called "arenito de Bauru" and a heavy one, "terra roxa", only O.l and 0.2 per cent of the activity supplied to the roots was recovered", respectively. This indicates that under field conditions the farmer should not attempt to correct zinc deficiency by applying zinc salts to the soil: leaf sprays should be used wherever necessary. In order to find out the most suitable way to supply phosphatic fertilizers to the coffee plant, under normal farm conditions, an experiment with tagged superphosphate was carried out with the following methods of distribution of this material: (1) topdressed in a circular area around the trees; (2) placed in the bottom of a 15 cm deep furrow made around the plant; (3) placed in a semicircular furrow, as in the previous treatment; (4) sprayed directly to the leaves. It was verified that in the first case, circa 10 per cent of the phosphorus in the leaves came from the superphosphate; for the other treatments, the results ware, respectively: 2.4, 1.7, and 38.0 per cent. It is interesting to mention that the first and the last methods of distribution were those less used by the farmers; now they are being introduced in many coffee plantations. In a previous trial it was demonstrated that urea sprays were an adequate way to correct nitrogen deficiency under field conditions. An experiment was then set up in which urea-C14 was used to study the metabolism of this fertilizer in coffee leaves. In was verified that in a 9 hours period circa 95 per cent of the urea supplied to the leaves had been absorbed. The distribution of the nitrogen of the urea was followed by standard chemical procedures. On the other hand the fate of the carbonic moiety was studied with the aid of the radiochromatographic technique. Thus, the incorporation of C14 in aminoacids, sugars and organic acids was ascertained. Data obtained in this work gave a definite support to the idea that in coffee leaves, as in a few other higher plants, a mechanism similar to the urea cycle of animals does exist.

Contribuição para. o conhecimento da "saúva de vidro" Atta laevigata Fred. Smith, 1858

In 1961, field investigations on "saúva de vidro" (parasol ant, Atta laevigata (Fred. Smith, 1858) were carried out at Piracicaba and other regions of the State of São Paulo (Brazil). This species was found to be a serious pest of cultivated plants, specially Eucalyptus and cotton. The ant makes its colony in any kind of soil, but it prefers to live in the poor ones.

Geographic distribution and morphological variation in Mimon bennettii (Chiroptera, Phyllostomidae)

We studied discrete and quantitative data from 88 specimens of the subgenus Mimon previously identified as Mimon bennettii (Gray, 1838) and M. cozumelae Goldman, 1914 from diverse parts of their range. Our data indicate that specimens of Mimon bennetii in Brazil presented geographic variation in morphometrical characters and mosaic variation in qualitative traits. Specimens from the Cerrado biome collected in Brazilian states like Piaui, Tocantins, and Goiás have longer forearms than those distributed in the Atlantic and Amazon forested domains. Based on morphometrics, as showed by t-tests, specimens of M. bennettii from the Brazilian Cerrado resemble phenetically more with M. cozumelae than the M. bennettii from Atlantic Forest. Characters presently used to diagnosis M. cozumelae also were also recorded to M. bennettii in diverse parts of Brazil, making that validity of M. cozumelae questionable based on this kind of traits. This research also updated the geographic distribution to the M. bennettii in Brazil.

New records, distribution and status of six seabird species in Brazil

Distribution records of poorly-known species are currently the most explored theme in the Brazilian seabird literature. If properly evaluated, this kind of information can improve our knowledge on distribution, migration and status of occurrence of these species. In this note we present new records for six species of poorly-known seabirds in the Brazilian coast, reviewing distribution records and defining their status of occurrence in the country. We consider Chionis albus (Gmelin, 1789) a pseudo-vagrant in Brazil and define its status as a scarce seasonal visitor from southern South America. We present the first records of Leucophaeus atricilla (Linnaeus, 1758) for Trindade Island, and of Leucophaeus pipixcan (Wagler, 1831) for the state of Rio Grande do Sul, and determined that the former is a vagrant in eastern Brazil and the latter a vagrant across the country. Anous stolidus (Linnaeus, 1758) is a vagrant in southernmost Brazil. We were unable to determine if records of Chlidonias niger (Linnaeus, 1758) for Brazil and southern South America refer to vagrancy or pseudo-vagrancy. Additionally, we verified the occurrence of breeding individuals of Anous minutus Boie, 1844 on Martin Vaz Island and confirmed that there is no evidence of breeding on neighboring Trindade Island.

Review of the breeding status of birds in Rio Grande do Sul, Brazil

Information on the breeding biology of birds is essential for improving avian life-history theory and implementing sound management and conservation actions for these organisms. Comprehensive reviews of this kind of information are lacking for most Neotropical regions, including Rio Grande do Sul, the southernmost Brazilian state. Aiming to update the knowledge on the reproductive status of birds in Rio Grande do Sul, we reviewed breeding records of all potential breeding species recorded in the state using a set of predefined, restrictive criteria for accepting breeding evidences as effective. Data satisfying our criteria were available for 165 species in the literature. We also collected novel breeding information obtained in the state for an additional 126 species, including observations for several species whose reproductive biology is poorly known. Among these are birds previously unknown to breed in Brazil. This new data and the critical review of the previous information resulted in a total of 291 species for which breeding evidences are accepted as effective. This corresponds to 54.7% of the 532 species considered either confirmed or potential breeders in the state. In addition to providing information on nesting dates, clutch size, nest architecture and breeding behavior of south Brazilian birds, our review serves as a benchmark for the adequate assessment of avian breeding records elsewhere. We hope to stimulate observers to rigorously document breeding events, especially for taxa for which basic information is lacking.

Influence of seasonal changes in daily activity and annual life cycle of Geotrigona mombuca (Hymenoptera, Apidae) in a Cerrado habitat, São Paulo, Brazil

The foraging activity of Geotrigona mombuca Smith, 1863 was studied under natural conditions aiming to verify the influence of seasonal changes on daily flight activity and annual cycle of the colony. Daily flight activity was monitored for a year based on the observation and counting of foragers leaving and entering the hive, as well as the kind of material transported and meteorological factors such as day time, temperature and relative humidity. The influence of seasonal changes was evidenced by alterations on daily rhythm of flight activity and by differences on transportation of food resources, building material and garbage. These data indicate that forager behavior is related to daily microclimate conditions and it is synchronized with the requirements of colony annual cycle, which determines an intense pollen collection in the summer. Thus, the recomposition of the intranidal population in spring and summer can be ensured, which is characterized both for a higher intensity of flight activity and increase in garbage and resin transport, as well as the swarming process in the spring. In this way, an action targeting the preservation or management of the species in a natural environment should consider that survival and reproduction of the colony depends greatly on the amount of available pollen in late winter.

Atividades da estação biológica de Perús

The author who was appointed entomologist of the Biological Station in Perus, São Paulo, describes in this paper, the kind of work he has been doing there. He begins with a description of the organization of the Station and of the routine work as it was daily carried on there, by himself and his staff, during nearly 6 months. During the day as well as during the night, captures of jungle were made in the forest and the same was done by night, in the Station House chiefly when the athmosphere was damp, just before, during, or after a rain. There was also an intensive search for foci of mosquitoes' larves in the bromelias, in holes, in trees and in the soil. The larves found in these breeding places were brought to a larvarium established in the forest in a place close to the station where they were bred in holes of bambus which were very suitable for them. During daytime, only new hatched mosquitoes have been captured, but during the night it has been possible to catch, inside the Station house, many female mosquitoes, with developped eggs, so confirming Aragão's opinion, that mosquitoes biting during the day are always, newly hatched ones. Some species of Sabetini were captured only inside the Biological Station House, during the night. The habits of the following species were subjected to more accurate investigations. Aedes scapularis, Aedes leucocelaenus, Lutzia braziliae, Culex (Carolia) iridescens, Orthopodomyia albicosta, Goeldia palidiventer, Joblotia compressum, Wyeomyia longirostris, Sabetoides intermedius, Limatus durhami. The conditions of the temperature of the Station, did not permit the authour to obtain breedings of Aedes aegypti in the larvarium of the Station, even during he summer months. A great diminuitions of species of the jungle mosquitoes was observed, from January till June, that is, when temperature gets lower and lower. The author has made the interesting observation that some species of mosquitoes (Joblotia and Limatus), must take a meal of flowers or bee honey before they suck blood. A list of the mosquitoes captured during the months of February to June, in the Station is given.

O virus do mixoma no coelho do mato (Sylvilagus minenses), sua transmissão pelos Aedes scapularis e aegypti

The brazilian wild rabbit (Sylvilagus minensis) is sensible to the virus of the mixomatosis but the desease takes on it a mild character, lasts for long time and generally do not kill the animal. The tumors are generally smaller and less numerous than those of the domestic rabbit, but sometimes there were noted large and flat lesions (fig. 3). The natural infection of the wild rabbit may be quite common not only because many rabbits caught in the country were found to be immune as also because it was found among the animals caught in the country near Rio, one that was infected with mixomatosis. The experimental infection of the Sylvilagus may be easily obtained by cutan, subcutan or conjuntival way and also when a health wild rabbit is placed in the same cage with a sick domestic animal. It is also possible to obtain the infection of the wild and domestic rabbits by the bite of infected blood sucking insects as fleas and mosquitoes. The infected mosquito can transmit the disease 2 or 3 times til 17 days after an infective meal on a sick rabbit. The transmission is a mecanical one and only the proboscis of the insect contains the virus as it was shown by the inoculation of emulsions of the proboscis, thorax and abdomen of the mosquito. Though mecanical this kind of transmission acts as an important epidemiological mean of dissemination of the deseasse and splains the suddendly outbreaks of mixomatosis in rabbits breedings where no new rabbits were introduced since very long time. The transmition of mixomatosis by fleas (Slenopsylla) was at first demonstrated by us, then S. Torres pointed out the capacity of Culex fatigans to transmit the desease and now we have proved that Aedes scapularis and Aedes aegypti were also able to transmit it (Foto 1 and 2). The virus of the mixomatosis (Chlamidozoon mixoma) is seen on the smeavs of the tumors of the wild reabbit with the same morphology, as in the material of the domestic animal.

A vegetação no município de Ilhéus Estado da Bahia: IV - Caracaterísticas analíticas e periodicidade sociológica

It is well-known that diverse groups of vegetation with an analogous but not identical floristic composition show an ecological similarity which leads to a determined type of vegetation. Starting from this fact it becomes evident that the scope of phytosociological work is the establishing of the significance of the species within the association and the discovery of the rules which govern associations. The floristic surveys made in the field have to be analysed statistically so as to obtain satisfactory results. The usefulness of this method depends largely on the possibilities of comparing the results with previous studies of the same kind, in the same country, or elsewhere. The method used in this paper is that of measuring circumferences and counting individuals in the different associations studied because it permits the presentation of the results in tables which show the phytosociological complexity of the Brazilian rain-forests. The classical method of characteristics is valuable because the more evolved an association is the less sociable are the species it contains, so that such groups do not show clear differences between species but rather between sinusia or strata of individuals. Five tables are presented in which several of the qualitative and quantitative characteristics are studied with a view to discussing their value in relation to groups and species. They are: I - Abundance (number of individuals). II - Density (distance in meters between the individuals belonging to each stratum). III - Basal coverture (circles measured in square meters of the mean projection of the individuals on the surface). IV - Basal area (mean circle in square meters occupied by individuals on the surface). V - Frequency, abundance and sociability in relation to occurrence. TABLE I. This table indicates first the number of individuals in relation to the sinusia studied: next, the sum total of the individuals belanging to the strata are given for each association, thus providing the numeric value of the sinusia: finally, the relation between the total number of individuals in the association and the total for the sinusium thus fursnishing the abundance per sinusium, in the classic sence, that is the percentage, or rather the relative number, of the elements which compose the group. CONCLUSIONS. The general character of abundance of the regional vegetation of Ilheos may be summed up in the following way: as an association evolves towards permanent equilibirum the number of individuals the inferior strata diminishes in relation to those of the superior strata which increase. For the shrub sinusium, two important facts were observed: a) in a given association the number of elements of the inferior strata diminishes as the diameter of the individuals increases; b) the percentage of individuals belonging to the shrub sinusium in the sere diminishes as the association evolve. In the subarboreal sinusium it is seen that: in the sere the number of subarboreal individuals does not vary much; whereas in the climax or the prisere there is a fall owing to the equilibrum of the biologic forms. In the arboreal sinusium the following conclusion can be deduced from analogous facts: the number of individuals of the lower strata diminishes as circumference increases. Also, in the sere there is a progressive sequence for the individuals belonging to the superior strata. TABLE II. The relation between the mean distances of individuals belonging to the same stratum and the area of an association is equal to the density. The table shows that the mean density of the association and the distance between the individuals belonging to the strata of the same sinusium in relation to the total number of individuals belonging to the association. CONCLUSIONS. As rule, the density of individuals in the associations studied follows a very general character or at least a regional one: the distance between the individuals in the diverse strata varies according to their abundance and sociability. Two other facts of some sociological importance are: a) in identical strata of the same sere the density of individuals oscillates in an analogous manner in teh subclimaces and varies in the stages which have reached equilibrium. b) the density of individuals varias in accordance with the sinusium and the distances between individuals of the same sinusium varg in accordance with the strata. TABLE III. This table presents the mean basal individual coverture, that is the mean projection of the frond of the various individuals belonging to the same stratum. The means were obtained by measurement in the field, of 100 individuals belonging to each stratum and their projection on the surface. In the latoratory these measurements were converted into mean circles (in square meters) and the result was multiplied by the individuals belonging to the strata corresponding to the sinusium of each association. The result obtained is named basal coverture. CONCLUSIONS. As a rule, the basal coverture of the vegetation of the county of Ilhéus indicates that: in the evolution of the vegetation the basal coverture of the arbustive sinusium diminishes progressively whereas that of the arboreal one increases. The special norms obtained are: 1) in the shrub sinusium the basal coverture seems to follow a uniform norm, that is, in stages of evolution of the subclimax the basal coverture oscillates with a certain uniformity. 2) in the subarboreal sinusium this fact is related to the vitality and age of the species, as in the subclimax the number of young trees is large and the vitality of the species very variable. This permits the conclusion that: in the sere the basal coverture increases with the evolution of the vegetation and diminishes when an equilibrium is reached. 3) in the tree sinusium the climax association of the prisere and subsere seem to obey a binomial rule, as the coverture (density-abundance) increases until a determined stratum is reached and...

Health education for children in the control of Schistosomasis

Health education for children is an important measure in the control of schistosomiasis especially considering the characteristics of the disease during childhood, such as high prevalence, high percent of treatment resistance, high rates of egg elimination and high level of reinfection, as reported in studies conducted in endemic areas. All of these facts indicate that children play a role in the maintenance and transmission of schistosomiasis. Historically in Brazil, Health Education concerning the major Brazilian endemies consists of a kind of vertical, interventionist and temporary action. An alternative would be to create a permanent health education process by assigning health education teachers to elementary schools. This would require expansion and improvement of teacher training and the development of programs taking into account: 1) the cognitive aspects of the child, the child's perception of reality and of the health/illness process; 2) the adaptation of instruction means and materials to the age group; 3) a "pedagogy of liberation" approach emphasizing the possibility of transforming life conditions since schistosomiasis is related to the lack of public services such as basic sanitation and clean domestic water supply.

Present development concerning antimalarial activity of phospholipid metabolism inhibitors with special reference to in vivo activity

The systematic screening of more than 250 molecules against Plasmodium falciparum in vitro has previously shown that interfering with phospholipid metabolism is lethal to the malaria parasite. These compounds act by impairing choline transport in infected erythrocytes, resulting in phosphatidylcholine de novo biosynthesis inhibition. A thorough study was carried out with the leader compound G25, whose in vitro IC50 is 0.6 nM. It was very specific to mature parasites (trophozoïtes) as determined in vitro with P. falciparum and in vivo with P. chabaudi -infected mice. This specificity corresponds to the most intense phase of phospholipid biosynthesis activity during the parasite cycle, thus corroborating the mechanism of action. The in vivo antimalarial activity (ED50) against P. chabaudi was 0.03 mg/kg, and a similar sensitivity was obtained with P. vinckei petteri, when the drug was intraperitoneally administered in a 4 day suppressive test. In contrast, P. berghei was revealed as less sensitive (3- to 20-fold, depending on the P. berghei-strain). This difference in activity could result either from the degree of synchronism of every strain, their invasion preference for mature or immature red blood cells or from an intrinsically lower sensitivity of the P. berghei strain to G25. Irrespective of the mode of administration, G25 had the same therapeutic index (lethal dose 50 (LD50)/ED50) but the dose to obtain antimalarial activity after oral treatment was 100-fold higher than after intraperitoneal (or subcutaneous) administration. This must be related to the low intestinal absorption of these kind of compounds. G25 succeeded to completely inhibiting parasitemia as high as 11.2% without any decrease in its therapeutic index when administered subcutaneously twice a day for at least 8 consecutive days to P. chabaudi -infected-rodent model. Transition to human preclinical investigations now requires a synthesis of molecules which would permit oral absorption.