Resíduos madeireiros do alburno de pau-rainha (Brosimum rubescens): investigação de metabólitos secundários e alguns aspectos tecnológicos

Estudos fitoquímicos prévios com resíduos do cerne de pau-rainha (Brosimum rubescens), identificaram um alto teor de xantiletina, uma cumarina com potencial biológico. Dando prosseguimento aos estudos com serragens desta espécie, este estudo relata a densidade básica bem como o isolamento e identificação do triterpeno 3β-acetoxi-olean-12-eno-28-al e do β- sitosterol nos extratos hexânico e metanólico do alburno da planta. A estrutura do triterpeno foi determinada com base nos espectros de RMN em 1D (¹H e 13C) e 2D (HSQC e HMBC) além de comparação com dados da literatura. A densidade básica encontrada para o alburno foi de 0,58 g cm-3 que, embora seja inferior a do cerne, poderá ser utilizada na confecção de vários produtos, inclusive em técnicas de marchetaria.

Correlação e concordância entre medidas ecocardiográficas obtidas durante o exame no ecocardiógrafo com medidas de imagens digitalizadas: estudo transversal

OBJETIVO: Avaliar a correlação e concordância entre medidas ecocardiográficas das dimensões cardíacas, obtidas através do aplicativo Echo off-line (programa para obtenção de medidas de imagens digitalizadas em estação de trabalho dedicada), com as realizadas convencionalmente. MÉTODOS: Estudo transversal, contemporâneo, sendo randomizados 56 pacientes. Através do programa Echo off-line foram mensuradas as medidas ao modo M e 2D ao nível dos ventrículos, do átrio esquerdo e da aorta. Estas medidas foram comparadas às realizadas por outro profissional, através do teste de correlação de Pearson (r), com alfa crítico de 0,05 e pela análise de concordância (Bland e Altman). RESULTADOS: As mensurações realizadas no sistema Echo off-line demonstraram r de 0,85 a 0,98. A análise de concordância mostrou que, para a maioria das medidas, a diferença média entre os métodos foi aproximadamente zero. A variação de valores absolutos não apresentou, em média, significância clínica. O aplicativo Echo off-line permite uma redução de, aproximadamente, 30% no tempo para realização das medidas. CONCLUSÃO: Este trabalho demonstrou a acurácia do programa Echo off-line para mensurar as dimensões cardíacas em estação de trabalho dedicada, podendo ser utilizado rotineiramente nos laboratórios de ecocardiografia.

Índice de dissincronia ventricular: comparação com a fração de ejeção bidimensional e tridimensional

FUNDAMENTO: O acoplamento eletromecânico (sincronia) do ventrículo esquerdo (VE) tem importância na análise da performance sistólica, especialmente para a indicação da terapia de ressincronização cardíaca em pacientes com ICC avançada. OBJETIVO: Comparar a sincronia do VE analisada com ecocardiograma (eco) tridimensional (3D) em tempo real com medidas de FEVE obtidas com ECO 2D e 3D. MÉTODOS: Estudo prospectivo de 92 indivíduos (56 homens, 47±10 anos), 60 com anatomia cardíaca (eco) e ECG normais (Grupo N), 32 com cardiomiopatia dilatada (Grupo CMD). Com o emprego do ECO 3D foram aferidos FEVE, volumes e índice de dissincronia (ID)% para 16 segmentos do VE; com o ECO 2D foram medidos FEVE (método de Simpson) e volumes sistólico e diastólico do VE. Análise estatística: coeficiente de correlação (Pearson), 95% IC, teste de regressão linear, teste de Bland & Altman, p<0,05. RESULTADOS: O ID% variou de 0,2900 a 28,1000 (5,2014±6,3281), a FEVE 3D variou de 0,17 a 0,81 (0,52±0,17); a FEVE 2D variou de 0,3 a 0,69 (0,49±0,11). A correlação entre ID e FEVE 3D foi (r): -0,7432, p<0,0001, IC: -0,8227 a -0,6350, a relação linear entre ID (x) e FEVE 3D (y) foi y = 19,8124 + (-27,9578) x , p<0,0001. A correlação entre ID e FEVE 2D foi (r): -0,7012, p<0,0001, IC: -0,7923 a -0,5797. CONCLUSÃO: Nesta casuística foi observada boa correlação negativa entre o acoplamento sistólico tridimensional eletromecânico do VE e a FEVE medida ao ecocardiograma (3D e 2D).

Parâmetros ecocardiográficos de deposição de gordura epicárdica e sua relação com doença arterial coronariana

FUNDAMENTO: Gordura epicárdica tem sido associada com a presença de doença arterial coronariana (DAC) significante. Entretanto, a associação entre infiltração lipomatosa do septo atrial e a infiltração de gordura do ventrículo direito (VD) permanece incerta. Nenhum desses parâmetros foi totalmente estudado em pacientes hispânicos. OBJETIVO: Determinar a associação entre a gordura epicárdica, infiltração lipomatosa do septo atrial e a infiltração de gordura do VD na presença de DAC. MÉTODOS: Duzentos e cinquenta pacientes hispânicos (86 mulheres e 164 homens, média da idade 61,5 ± 8 vs 62 ± 10 respectivamente), submetidos à sua primeira angiografia coronariana invasiva (ACI) foram estudados. No dia seguinte ao ACI, parâmetros de deposição de gordura epicárdica foram avaliados através de ecocardiografia modo 2D. Variáveis clínicas (idade, sexo, antecedentes pessoais do hábito de fumar, hipertensão e diabete melito, bem como a apresentação clínica da DAC) e antropométricas (circunferência da cintura e índice de massa corporal [IMC]) também foram coletadas. RESULTADOS: A gordura epicárdica (OR 1,27 p = 0,009), bem como a infiltração de gordura no VD (OR 2,94 p = 0,027), apresentaram uma associação significante e independente com a presença, mas não com a extensão (p = 0,516) e apresentação clínica (p = 0,153) da DAC. A extensão da deposição da gordura epicárdica mostrou uma associação proporcional e significante (p = 0,001) com a presença de DAC. CONCLUSÃO: A Gordura epicárdica e a infiltração de gordura do VD foram fatores significantes e independentes associados com a presença de DAC, a qual estava proporcionalmente aumentada de acordo com a extensão da deposição de gordura epicárdica.

Estudo da Mecânica Cardíaca pelo Speckle Tracking

Speckles, ou marcadores naturais do miocárdio, originam se da interferência construtiva e destrutiva do feixe de ultrassom que incide sobre os tecidos, podem fornecer um diagnóstico precoce das alterações miocárdicas e atuar na predição de certos eventos cardíacos. Devido à sua relativa estabilidade temporal, os speckles podem ser rastreados durante o ciclo cardíaco por software dedicados, promovendo a análise da função sistólica e diastólica. São identificados tanto pela escala de cinza da ecocardiografia 2D convencional quanto pela ecocardiografia 3D, sendo independentes do ângulo de incidência do ultrassom, permitindo assim a avaliação da mecânica cardíaca nos três planos espaciais: longitudinal, circunferencial e radial. O objetivo do presente artigo é discutir o papel e o significado da deformação cardíaca obtida por meio do speckle tracking durante a avaliação da fisiologia cardíaca, e discutir as aplicações clínicas desta tecnologia ecocardiográfica inovadora.

A Comparison of Radiation Dose Between Standard and 3D Angiography in Congenital Heart Disease

Background: The use of three-dimensional rotational angiography (3D-RA) to assess patients with congenital heart diseases appears to be a promising technique despite the scarce literature available. Objectives: The objective of this study was to describe our initial experience with 3D-RA and to compare its radiation dose to that of standard two-dimensional angiography (2D-SA). Methods: Between September 2011 and April 2012, 18 patients underwent simultaneous 3D-RA and 2D-SA during diagnostic cardiac catheterization. Radiation dose was assessed using the dose-area-product (DAP). Results: The median patient age and weight were 12.5 years and 47.5 Kg, respectively. The median DAP of each 3D-RA acquisition was 1093µGy.m2 and 190µGy.m2 for each 2D-SA acquisition (p<0.01). In patients weighing more than 45Kg (n=7), this difference was attenuated but still significant (1525 µGy.m2 vs.413µGy.m2, p=0.01). No difference was found between one 3D-RA and three 2D-SA (1525µGy.m2 vs.1238 µGy.m2, p = 0.575) in this population. This difference was significantly higher in patients weighing less than 45Kg (n=9) (713µGy.m2 vs.81µGy.m2, P = 0.008), even when comparing one 3D-RA with three 2D-SA (242µGy.m2, respectively, p<0.008). 3D-RA was extremely useful for the assessment of conduits of univentricular hearts, tortuous branches of the pulmonary artery, and aorta relative to 2D-SA acquisitions. Conclusions: The radiation dose of 3D-RA used in our institution was higher than those previously reported in the literature and this difference was more evident in children. This type of assessment is of paramount importance when starting to perform 3D-RA.

Right Ventricular Doppler Echocardiographic Study of Indeterminate Form of Chagas Disease

Background: Patients with indeterminate form of Chagas disease/cardiac normality (ICD/CN) exhibited normal electrocardiograms and chest X-rays; however, more sophisticated tests detected some degree of morphological and functional changes in the heart. Objective: To assess the prevalence of systolic and diastolic dysfunction of the right ventricle (RV) in patients with ICD/CN. Methods: This was a case–control and prevalence study. Using Doppler two-dimensional echocardiography (2D), 92 patients were assessed and divided into two groups: group I (normal, n = 31) and group II (ICD/CN, n = 61). Results: The prevalence of RV systolic dysfunction in patients in groups I and II was as follows: fractional area change (0.0% versus 0.6%), mobility of the tricuspid annulus (0.0% versus 0.0%), and S-wave tissue Doppler (6.4% versus 26.0%, p = 0.016). The prevalence of global disorders such as the right myocardial performance index using tissue Doppler (16.1% versus 27.8%, p = 0.099) and pulsed Doppler (61.3% versus 68%, p = 0.141) and diastolic disorders such as abnormal relaxation (0.0% versus 6.0%), pseudonormal pattern (0.0% versus 0.0%), and restrictive pattern (0.0% versus 0.0%) was not statistically different between groups. Conclusion: The prevalence of RV systolic dysfunction was estimated to be 26% (S wave velocity compared with other variables), suggesting incipient changes in RV systolic function in the ICD/CN group.

Subclinical Ventricular Dysfunction Detected by Speckle Tracking Two Years after Use of Anthracycline

Background: Heart failure is a severe complication associated with doxorubicin (DOX) use. Strain, assessed by two-dimensional speckle tracking (2D-STE), has been shown to be useful in identifying subclinical ventricular dysfunction. Objectives: a) To investigate the role of strain in the identification of subclinical ventricular dysfunction in patients who used DOX; b) to investigate determinants of strain response in these patients. Methods: Cross-sectional study with 81 participants: 40 patients who used DOX ±2 years before the study and 41 controls. All participants had left ventricular ejection fraction (LVEF) ≥55%. Total dose of DOX was 396mg (242mg/ms2). The systolic function of the LV was evaluated by LVEF (Simpson), as well as by longitudinal (εLL), circumferential (εCC), and radial (εRR) strains. Multivariate linear regression (MLR) analysis was performed using εLL (model 1) and εCC (model 2) as dependent variables. Results: Systolic and diastolic blood pressure values were higher in the control group (p < 0.05). εLL was lower in the DOX group (-12.4 ±2.6%) versus controls (-13.4 ± 1.7%; p = 0.044). The same occurred with εCC: -12.1 ± 2.7% (DOX) versus -16.7 ± 3.6% (controls; p < 0.001). The S’ wave was shorter in the DOX group (p = 0.035). On MLR, DOX was an independent predictor of reduced εCC (B = -4.429, p < 0.001). DOX (B = -1.289, p = 0.012) and age (B = -0.057, p = 0.029) were independent markers of reduced εLL. Conclusion: a) εLL, εCC and the S’ wave are reduced in patients who used DOX ±2 years prior to the study despite normal LVEF, suggesting the presence of subclinical ventricular dysfunction; b) DOX was an independent predictor of reduced εCC; c) prior use of DOX and age were independent markers of reduced εLL.

Biologia da Arsenura xanthopus (Walker, 1855) ( Lepidoptera - Adelocephalidae ), praga do «Açoita-Cavalo» (Luehea spp.) e notas sôbre seus inimigos naturais

Biology of Arsenura xanthopus (Walker, 1855) (Lep., Adelocephalidae), a pest of Luehea spp. (Tiliaceae), and notes on its natural enemies. In the beginning of 1950, one of the Authors made some observations about the biology of Arsenura xanthopus (Walker), in Piracicaba, State of S. Paulo, Brazil. From 1951 to 1953, both Authors continued the observations on such an important Adelocephalidae, the caterpillars of which represent a serious pest of Luehea spp. leaves. Actually, in some occasions, the caterpillars can destroy completely the leaves of the trees. The species is efficientely controlled by two natural enemies: an egg parasite (Tetrastichus sp., Hym., Eulophidae) and a fly attacking the last instar caterpillar (Winthemia tricolor (van der Wulp), Dip., Tachinidae). Tetrastichus sp. can destroy 100% of the eggs and the fly, 70 to 100% of the caterpillars. Indeed, facts as such are very interesting because we rarely know of a case of so complete a control of a pest by an insect. A. xanthopus had not yet been mentioned in our literature. Actually neither the systematic bibliography nor the economic one has treated of this species. However, a few other species of Arsenura are already known as living on Luehea spp. According to the Authors' observations, W. tricolor was also unknown by the Brazilian entomological literature. Arsenura xanthopus (Walker, 1855) After giving the sinonimy and a few historical data concerning the species, and its geographical distribution, the Authors discuss its placing in the genus Arsenura Duncan or Rhescyntis Huebner, finishing by considering Arsenura xanthopus as a valid name. The Authors put the species in the family Adelocephalidae, as it has been made by several entomologists. The host plant The species of Tiliaceae plants belonging to the genus Luehea are called "açoita-cavalo" and are well known for the usefulness of their largely utilized wood. The genus comprises exclusively American plants, including about 25 species distributed throughout the Latin America. Luehea divaricata Mart, is the best known species and the most commonly cultivated. Biology of Arsenura xanthopus Our observations show that the species passes by 6 larval stages. Eggs and egg-postures, all the 6 instars of the caterpillars as well as the chrysalid are described. The pupal period is the longest of the cycle, taking from 146 to 256 days. Data on the eclosion and habits of the caterpillars are also presented. A redescription of the adult is also given. Our specimens agreed with BOUVIER's description, except in the dimension between the extremities of the extended wings, which is a little shorter (107 mm according to BOUVlErVs paper against from 80 to 100mm in our individuals). Winthemia tricolor (van der Wulp, 1890) Historical data, geographical distribution and host are first related. W. tricolor had as yet a single known host-; Ar^-senura armida (Cramer). This chapter also contains some observations on the biolcn gy of the fly and on its behaviour when trying to lay eggs on the caterpillars' skin. The female of W. tricolor lays from 1 to 33 eggs on the skin of the last instar caterpillar. The mam region of the body where the eggs are laid are the membranous legs. Eggs are also very numerous oh the ventral surface of the thorax and abdomen. The. preference for such regions is easily cleared up considering the position assumed by the caterpillar when fixed motionless in a branch. In such an occasion, the fly approaches, the victim, puts the ovipositor out and lays the eggs on different parts of the body, mainly on the mentioned regions, which are much more easily reached. The eggs of the fly are firmly attached to the host's skin, being almost impossible to detach them, without having them broken. The minute larvae of the fly enter the body of, the host when it transforms into chrysalid. Chrysalids recentely formed and collected in nature f requentely show a few small larvae walking on its skin and looking for an adequate place to get into the body. A few larvae die by remaining in the skin of the caterpillar which is pushed away to some distance by the active movements of the chrysalid recentely formed. From 1 to 10 larvae completely grown may emerge from the attacked chrysalid about 8 days after their penetrating into the caterpillars' body and soon begin to look for an adequate substratum where they can transform themselves into pupae. In natural conditions, the metamorphosis occurs in the soil. The flies appear within 15 days. Tetrastichus sp. This microhymenoptera is economically the most interesting parasite, being commonly able to destroy the whole pos^ ture of the moth. Indeed, some days after the beginning of the infestation of the trees, it is almost impossible to obtain postures completely free of parasites. The active wasp introduces the ovipositor into the egg of the moth, laying its egg inside, from 80 to 120 seconds after having introduced it. A single adult wasp emerges from each egg. Sarcophaga lambens Wiedemann, 1830 During the observations carried out, the Authors obtained 10 flies from a chysalid that were recognized as belonging to the species above. S. lambens is a widely distributed Sarcophagidae, having a long list of hosts. It is commonly obtained from weak or died invertebrates, having no importance as one of their natural enemies. Sinonimy, list of hosts and distribution are presented in this paper. Control of Arsenura xanthopus A test has been carefully made in the laboratory just to find out the best insecticide for controlling A. xanthopus caterpillars. Four different products were experimented (DDT, Pa-rathion, BHC and Fenatox), the best results having been obtained with DDT at 0,25%. However, the Authors believe in spite of the initial damages of the trees, that the application of an insecticide may be harmful by destroying the natural agents of control. A biological desiquilibrium may in this way take place. The introduction of the parasites studied (Tetrastichus sp. and Winthemia tricolor) seems to be the most desirable measure to fight A. xanthopus.

Análise citológica e cariométrica da ação da colchina sôbre a espermatogênese dos hemípteros

The action of colchicine upon the spermatogenesis of Triatoma infestans, (Hemipt. Heteroptera), has been studied and the different categories of giant spermatids that appear during the treatment have been compared with the nuclear volumes of the whole series of normal spermatogenetic stages. The following facts have been ascertained: 1) 4 hours after the treatment the gonial mitotic metaphases, and the 1st. and 2nd. metaphases of meiosis are stopped. The prophasic stages of meiosis and diakynesis appear to be normal. After 9 days of treatment, all the tetrads are broken in the meiotic metaphases and the cells appear with 44 and 22 chromosomes respectively, scattered in the cytoplasm. 2) At 9 days, practically all spermatogenetic stages have disappeared except for a few cysts of spermatogonia, and practically the whole testicle is full of cysts of spermatozoa and spermatid, with some large zones of necrosis with pycnotic nuclei. The spermatids appear to be of different sizes and the statistical analysis of the nuclear volumes gives a polymodal hystogram with 4 modes, whose volumes are in the ratio of 1:2:4:8. Ripe spermatozoa seem to have a certain volume variability, that has not been possible to analyse quantitatively. All these facts confirm what DOOLEY found in the colchicinized Orthoptera testicle. 3) The caryometric analysis conducted statistically on the normal stages of the spermatogenesis (resting spermatogonia, gonial prophases, leptotene, "confused stage", diakynesis, and spermatid) revealed the following facts: a) Considering the volume of the resting, spermatogonia as 1, their mitotic prophases have a volume of 2. Some rare prophases appear to have a volume of 4 and probably belong to tetraployd spermatogonia normally present in the testicle of Hemiptera. b) The first spermatocyte at the beginning of the auxocitary growth (leptotene) has a volume of 2, which is equal to that of them gonial prophase. It grows further during the "confused stage" and reduplicates, reaching thus the volume of 4. Diakynesis has a rather variable nuclear volume and it is higher than volume 4. This is probably of physico-chemical nature and not a growth increase. c) The spermatid at the beginning of the spermiogenetic process has a volume of 1 which is very constant and homogeneous. 4) These results can be summarized concluding that the meiotic process begins from a spermatogonium at the end of his mitotic interphasic growth (vol. 2) and instead of entering into the mitotic prophase transforms itself into the leptotene spermatocyte. During the diplotene ("confused stage") the volume of the nucleus doubles once more and reaches volume 4. In consequence of the two successive meiotic divisions the spermatid, although having an haploid number of chromosomes, has a nuclear volume of 1, just like the diploid spermatogonium. The interpretation of this strange result probably comes from the existence of the "tertiary split" in the chromosomes of the haploid set, that has been illustrated in the Hemiptera by HUGUES SCHRADER and in Orthoptera by MICKEY and co-workers. The tertiary split indicates that the chromosomes of the haploid set are constituted from almost two chromonemata, and this double constitution corresponds to the double cycle of reduplication that takes place during the spermatogenesis starting from the resting gonia. In Triatoma infestans the tertiary split appears in the chromosomes in the 1st. and 2nd. metaphases and in the diakynesis. In the blocked metaphases at the 9th. day of colchicinization some of the 44 elements scattered in the cytoplasm, show, when properly oriented, the split very clearly. Some new and strange facts revealed by SCHRADER and LEUCHTEMBERGER in Arvelius suggest the possibility of other interpretations of the rhythmic growth in special cases. There appears the necessity of more knowledge about the multiple or simple constitution of the chromosomes in somatic and spermatogonial mitosis.

Studies on bioactive components from Chinese medicinal plants

Several novel bioactive components isolated from Chinese medicinal plants will be presented. These include novel maytansinoid tumor, inhibitors, some new ent-kaurane and rosane diterpenoids from Mallotus anomalus Meer et Chun (Euphorbiaceae), as well asnovel insecticide, stemona alkaloids from Stemona parviflora C. H. Wright (Stemonaceae). Both are native plants of Hainan island, Chine. 2D NMR techniques such as mono and hetero-COSY, NOESY, COLOC as well as H-NMR line broadening effect were utilized for structure elucidation. The separation techniques, struture elucidations and bioassay results will be reported.

Separation and Mapping of Chromosomes of Parasitic Protozoa

Many protozoan parasites represent an important group of human pathogens. Pulsed Field Gradient Gel Electrophoresis (PFGE) analysis has been an important tool for fundamental genetic studies of parasites like Trypanosoma, Leishmania, Giardia or the human malaria parasite Plasmodium falciparum. We present PFGE conditions allowing a high resolution separation of chromosomes ranging from 500 to 4000 kb within a two day electrophoresis run. In addition, we present conditions for separating large chromosomes (2000-6000 kb) within 36 hr. We demontrate that the application of two dimentional PFGE (2D-PFGE) technique to parasite karyotypes is a very useful method for the analysis of dispersed gene families and comparative studies of the intrachomosomal genome organization

Trypanosoma cruzi: Maintenance in Culture Modify Gene and Antigenic Expression of Metacyclic Trypomastigotes

In this study we examined whether the maintenance of Trypanosoma cruzi by long-time in axenic culture produces changes in gene expression and antigenic profiles. The studies were made with a Dm30L-clone from a low-virulent strain and a non-cloned virulent EP-strain of T. cruzi. Both parasites were maintained, for at least seven years, by successive alternate passage triatomine/mouse (triatomine condition), or by serial passage in axenic medium (culture condition). The comparison of the [35S]methionine metabolic labeling products of virulent and non-virulent parasites by 2D-SDS-PAGE, clearly indicates that the expression of metacyclic trypomastigotes (but not of epimastigotes) proteins have been altered by laboratory maintenance conditions. Western blot analysis of EP and Dm30L-epimastigotes using a serum anti-epimastigotes revealed that although most of antigens are conserved, four antigens are characteristics of triatomine condition parasites and three other are characteristics of culture condition parasites. Anti-metacyclics serum revealed significative differences in EP- and Dm30L-metacyclic trypomastigotes from triatomine condition. However, avirulent metacyclic forms were antigenically very similar. These results suggest that besides a possible selection of avirulent subpopulation from T. cruzi strains genetically heterogeneous when maintained by long time in axenic culture, changes in virulence might be due to post-translational modifications of the antigens induced by the absence of the natural alternability (vertebrate-invertebrate) in the life-cycle of T. cruzi

In Vitro and in Vivo Assays of 3,5-Disubstituted-Tetrahydro-2H-1,3,5-Thiadiazin-2-Thione Derivatives against Trypanosoma cruzi

Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives were performed. The 17 compounds with higher anti-epimastigote activity and lower cytotoxicity were, thereafter, screened against amastigote of Trypanosoma cruzi. Out of these 17 derivatives S-2d was selected to be assayed in vivo, because of its remarkable trypanocidal properties. To determine toxicity against J774 macrophages, a method based on quantification of cell damage, after 24 h, was used. Cell respiration, an indicator of cell viability, was assessed by the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to formazan. Anti-amastigote activity was estimated after 48 h by microscopic counts of May Grünwald-Giemsa-stained monolayers. Nifurtimox and benznidazole were used as reference drugs. For the in vivo experiences, mice were infected with 10(4) blood trypomastigotes and then treated during 15 days with S-2d or nifurtimox by oral route. All of the compounds were highly toxic at 100 µg/ml for macrophages and a few of them maintained this cytotoxicity even at 10 µg/ml. Of the derivatives assayed against amastigotes 3k and S-2d showed an interesting activity, that was held even at 1µg/ml. It is demonstrated that the high anti-epimastigote activity previously reported is mainly due to the non-specific toxicity of these compounds. In vivo assays assessed a reduction of parasitemia after administration of S-2d to infected mice.

From genomes to vaccines via the proteome

An effective vaccine against schistosomiasis mansoni would be a valuable control tool and the high levels of protection elicited in rodents and primates by radiation-attenuated cercariae provide proof of principle. A major obstacle to vaccine development is the difficulty of identifying the antigens that mediate protection, not least because of the size of the genome at 280Mb DNA encoding 14,000 to 20,000 genes. The technologies collectively called proteomics, including 2D electrophoresis, liquid chromatography and mass spectrometry, now permit any protein to be identified provided there is extensive DNA data, and preferably a genome sequence. Applied to soluble (cytosolic) proteins from schistosomes, proteomics reveals the great similarity in composition between life cycle stages, with several WHO vaccine candidates amongst the most abundant constituents. The proteomic approach has been successfully applied to identify the secretions used by cercaria to penetrate host skin, the gut secretions of adult worms and the proteins exposed on the tegument surface. Soluble proteins can also be separated by 2D electrophoresis before western blotting to identify the full range of antigenic targets present in a parasite preparation. The next step is to discover which target proteins represent the weak points in the worm's defences.