Schistosoma mansoni Adult Worm Protective and Diagnostic Proteins in n-Butanol Extracts Revealed by Proteomic Analysis.

The S. mansoni adult worm n-butanol extract (Sm-AWBE) has been previously shown to contain specific S. mansoni antigens that have been used for immunodiagnosis of schistosomiasis in solid phase alkaline phosphatase immunoassay (APIA) and western blot (WB) analyses. Sm-AWBE was also used in immunoprotection studies against a fatal live-cercariae challenge in experimental mouse vaccination (~43% protection). The Sm-AWBE fraction was prepared by mixing adult worm membranous suspensions with aqueous-saturated n-butanol, centrifuging and recovering n-butanol-resistant proteins in the aqueous phase. Here we report a preliminary identification of Sm-AWBE protein components as revealed from a qualitative proteomic study after processing Sm-AWBE by 1D-gel electrophoresis, in-gel and in-solution tryptic digestions, and mass spectrometry analyses. We identified 33 proteins in Sm-AWBE, all previously known S. mansoni proteins and antigens; among them, immunomodulatory proteins and proteins mostly involved in host-parasite interactions. About 81.8% of the identified Sm-AWBE proteins are antigenic. STRING analysis showed a set of Sm-AWBE proteins configuring a small network of interactive proteins and a group of proteins without interactions. Functional groups of proteins included muscle contraction, antioxidant, GPI-anchored phosphoesterases, regulatory 14-3-3, various enzymes and stress proteins. The results widen the possibilities to design novel antigen combinations for better diagnostic and immunoprotective strategies for schistosomiasis control.

Angiogenesis and evading immune destruction are the main related transcriptomic characteristics to the invasive process of oral tongue cancer.

Metastasis of head and neck tumors is responsible for a high mortality rate. Understanding its biochemistry may allow insights into tumorigenesis. To that end we carried out RNA-Seq analyses of 5 SCC9 derived oral cancer cell lines displaying increased invasive potential. Differentially expressed genes (DEGs) were annotated based on p-values and false discovery rate (q-values). All 292 KEGG pathways related to the human genome were compared in order to pinpoint the absolute and relative contributions to the invasive process considering the 8 hallmarks of cancer plus 2 new defined categories, as well as we made with our transcriptomic data. In terms of absolute contribution, the highest correlations were associated to the categories of evading immune destruction and energy metabolism and for relative contributions, angiogenesis and evading immune destruction. DEGs were distributed into each one of all possible modes of regulation, regarding up, down and continuum expression, along the 3 stages of metastatic progression. For p-values twenty-six genes were consistently present along the tumoral progression and 4 for q-values. Among the DEGs, we found 2 novel potentially informative metastatic markers: PIGG and SLC8B1. Furthermore, interactome analysis showed that MYH14, ANGPTL4, PPARD and ENPP1 are amenable to pharmacological interventions.

Differential distribution and biochemical characteristics of hydrolases among developmental stages of Schistosoma mansoni may offer new anti-parasite targets.

Schistosoma mansoni enzymes play important roles in host-parasite interactions and are potential targets for immunological and/or pharmacological attack. The aim of this study was to comparatively assess the presence of hydrolytic activities (phosphatases, glycosidases, aminopeptidases) in soluble (SF) and membrane (MF) fractions from different S. mansoni developmental stages (schistosomula 0 and 3h, juveniles, and adult worms of 28 and 45days-old, respectively), by using simple enzyme-substrate microassays. Our results show and confirm the prominent presence of alkaline phosphatase (AlP) activity in the MF of all the above parasite stages, highlighting also the relevant presence of MF-associated α-mannosidase (α-MAN) activity in juveniles. A soluble AlP activity, together with ß-N-D-acetylglucosaminidase (ß-NAG), and α-MAN activities, was detected in SF of schistosomulum 0h. Soluble ß-NAG, α-MAN, acid phosphatase (AcP), leucin (LAP) and alanine (AAP) aminopeptidase activities were also seen in the SF of the other different developmental stages. This work shows different soluble and membrane-associated hydrolytic capacities in each S. mansoni developmental stage from schistosomula to adults that might be exploitable as potential new targets for immune and/or chemoprophylactic strategies.

Immunocapture of circulating Schistosoma mansoni cathepsin B antigen (Sm31) by anti-Sm31 polyclonal antibodies.

Adult Schistosoma mansoni parasites have the capacity to degrade ingested host hemoglobin and other host plasma proteins by using a series of gut proteolytic enzymes, including cathepsin B; this enzyme is released to the host intravascular environment during regurgitations of adult worms. Cathepsin B becomes thus a circulating parasite component that has been shown to be specifically recognized as the Sm31 antigen by antibodies present in most S. mansoni infected patients. Taking advantage of this immunological property, we attempted here to immunocapture Sm31 from sera of infected patients using specific polyclonal rabbit antibodies raised against a highly enriched preparation of Sm31 and detect its intrinsic proteolytic activity using a previously described solid-phase procedure called Cysteine Protease Immuno Assay (CPIA). To produce highly specific anti-Sm31/cathepsin B antibodies, cathepsin B (Sm31 or SmCB) was enriched more than 3000-folds from an adult worm preparation using a series of conventional biochemical steps including ion exchange and affinity chromatography. Anti-cathepsin B antibodies were generated by immunizing rabbits with the enriched cathepsin B fraction; these antibodies recognized a band of Mr.~31 kDa in Western-blot (WB) analysis of this fraction and were able to capture, in a modified CPIA procedure, Sm31/SmCB present in sera from infected Venezuelan patients living in low endemic areas for schistosomiasis. CPIA showed 100% sensitivity and 100% specificity; representing a new diagnostic tool to detect circulating Sm31 antigen in actual infections.

nzimas y glicoproteínas presentes en extractos de vermes adultos de Fasciola hepatica / Enzymes and glycoproteins present in extracts of adult Fasciola hepatica worms

Fasciola hepatica es un trematodo que causa lesiones en el hígado y vías biliares afectando a herbívoros y al hombre, constituyendo un problema de salud pública en zonas agrícolas a nivel mundial. El parásito posee glicoproteínas y enzimas que facilitan su penetración y migración en los tejidos hospederos. El objetivo fue evaluar estos componentes en extractos [fracción soluble (FS) y fracción particulada (FP)] de vermes adultos de F. hepatica. Las fracciones fueron analizadas para proteínas, carbohidratos, actividades enzimáticas, y por electroforesis (SDS-PAGE-15%) en condiciones no reductoras (NR) y reductoras (R). En FS, la concentración de carbohidratos fue 5,63 μmol/mL; se detectó la presencia de fosfohidrolasas, glicosidasas y peptidasas, sobresaliendo la actividad Fosfatasa Acida (1,19 μmol/h/mg, pH 5,0). En FP, la concentración de carbohidratos fue más elevada (7,89 μmol/mL); se observaron valores elevados de Fosfatasa Alcalina (5,79 μmol/h/mg), Fosfatasa Acida (1,67 μmol/h/mg) y moderados de Fosfodiesterasa (0,280 μmol/h/mg pH 9,6). Se detectó actividad Acetilcolinesterasa mayor en FS que en FP (3,95 A/h vs. 1,68 A/h). En SDS-PAGE ambos extractos mostraron polipéptidos de ~80 a 10-kDa; el pre-tratamiento de las muestras con sodio-metaperiodato redujo el número de bandas en cada extracto, sugiriendo la presencia de glicocomponentes. En conclusión, se hallaron enzimas y glicocomponentes en los extractos de F. hepatica estudiados, lo cual constituye un aporte en la búsqueda de posibles blancos inmunológicos y farmacológicos para el control de esta parasitosis.

Fasciola hepatica is a trematode that causes damage to the liver and biliary tract in both herbivores and man, and is thus an important public health concern in agricultural areas worldwide. This parasite contains glycoproteins and enzymes that facilitate its penetration of, and migration through, host tissues. The aim of this study was to evaluate the relative proportions of these components in the soluble fraction (SF) and n-butanol-solubilized extracts of the particulate fraction (PF) of whole homogenates of adult F. hepatica worms. Extracts were analyzed for protein and carbohydrate content, and hydrolytic activity. In addition, 15% SDS-PAGE electrophoresis was performed under non-reducing (NR) and reducing (R) conditions to identify other components. The SF contained 5.63 μmol carbohydrate/mL, as well as phosphohydrolases, glycosidases and peptidases, with a high acid phosphatase activity (1.19 μmol/h/mg, pH 5.0) that seemed to be characteristic of this fraction. The PF contained 7.89 μmol carbohydrate/mL, with high alkaline phosphatase (5.79 μmol/h/mg) and acid phosphatase (1.67 μmol/h/mg), and moderate phosphodiesterase (0.280 μmol/h/mg pH 9.6) values. Acetylcholinesterase activity was higher in the SF than the PF (3.95 A/h vs. 1.68 A/h). SDS-PAGE analysis showed the presence of polypeptides in both the SF and the PF of ~80 to 10-kDa . Pretreatment with sodium-metaperiodate reduced the number of bands in each extract suggesting the presence of glycocomponents. The notable presence of enzymes and glycocomponents in the SF and PF extracts of adult F. hepatica worms is a first step towards the eventual identification of new immunological and pharmacological targets for the control of this disease.

Methyl jasmonate: putative mechanisms of action on cancer cells cycle, metabolism, and apoptosis.

Methyl jasmonate (MJ), an oxylipid that induces defense-related mechanisms in plants, has been shown to be active against cancer cells both in vitro and in vivo, without affecting normal cells. Here we review most of the described MJ activities in an attempt to get an integrated view and better understanding of its multifaceted modes of action. MJ (1) arrests cell cycle, inhibiting cell growth and proliferation, (2) causes cell death through the intrinsic/extrinsic proapoptotic, p53-independent apoptotic, and nonapoptotic (necrosis) pathways, (3) detaches hexokinase from the voltage-dependent anion channel, dissociating glycolytic and mitochondrial functions, decreasing the mitochondrial membrane potential, favoring cytochrome c release and ATP depletion, activating pro-apoptotic, and inactivating antiapoptotic proteins, (4) induces reactive oxygen species mediated responses, (5) stimulates MAPK-stress signaling and redifferentiation in leukemia cells, (6) inhibits overexpressed proinflammatory enzymes in cancer cells such as aldo-keto reductase 1 and 5-lipoxygenase, and (7) inhibits cell migration and shows antiangiogenic and antimetastatic activities. Finally, MJ may act as a chemosensitizer to some chemotherapics helping to overcome drug resistant. The complete lack of toxicity to normal cells and the rapidity by which MJ causes damage to cancer cells turn MJ into a promising anticancer agent that can be used alone or in combination with other agents.

Immunoprotection of mice against Schistosomiasis mansoni using solubilized membrane antigens.

BACKGROUND: Schistosomiasis continues to be one of the most prevalent parasitic diseases in the world. Despite the existence of a highly effective antischistosome drug, the disease is spreading into new areas, and national control programs do not arrive to complete their tasks particularly in low endemic areas. The availability of a vaccine could represent an additional component to chemotherapy. Experimental vaccination studies are however necessary to identify parasite molecules that would serve as vaccine candidates. In the present work, C57BL/6 female mice were subcutaneously immunized with an n-butanol extract of the adult worm particulate membranous fraction (AWBE) and its protective effect against a S. mansoni challenge infection was evaluated. METHODOLOGY AND FINDINGS: Water-saturated n-butanol release into the aqueous phase a set of membrane-associated (glyco)proteins that are variably recognized by antibodies in schistosome-infected patients; among the previously identified AWBE antigens there is Alkaline Phosphatase (SmAP) which has been associated with resistance to the infection in mice. As compared to control, a significantly lower number of perfuse parasites was obtained in the immunized/challenged mouse group (P<0.05, t test); and consequently, a lower number of eggs and granulomas (with reduced sizes), overall decreasing pathology. Immunized mice produced high levels of sera anti-AWBE IgG recognizing antigens of ∼190-, 130-, 98-, 47-, 28-23, 14-, and 9-kDa. The ∼130-kDa band (the AP dimer) exhibited in situ SmAP activity after addition of AP substrate and the activity was not apparently inhibited by host antibodies. A preliminary proteomic analysis of the 25-, 27-, and 28-kDa bands in the immunodominant 28-23 kDa region suggested that they are composed of actin. CONCLUSIONS: Immunization with AWBE induced the production of specific antibodies to various adult worm membrane molecules (including AP) and a partial (43%) protection against a challenging S. mansoni infection by mechanism(s) that still has to be elucidated.

Insights into blood feeding by schistosomes from a proteomic analysis of worm vomitus.

Whilst the schistosome tegument has been intensively studied there is little information about processes in the gut, the other major interface with the bloodstream, apart from the well characterised cascade of proteases involved in haemoglobin digestion. To gain insights into gut function we undertook a proteomic analysis of worm vomitus and performed in vitro erythrocyte feeding experiments. Additional to known gut constituents we identified two proline carboxypeptidases as well as enzymes capable of hydrolysing carbohydrate and ester linkages. Schistosome serpin and a2 macroglobulin protease inhibitors were also present. A series of "carrier proteins", principally lipid-binding saposins and cholesterol-binding NPC-2 were also detected, together with ferritins and calumenin that bind ferric iron and calcium, respectively. The presence of these lysosomal proteins and other lysosomal markers in the vomitus, plus observations on the cytology of the gut epithelium suggest that lysosomes directly secrete their contents into the gut lumen to digest incoming plasma constituents as well as haemoglobin. It is also likely that the carrier proteins function to sequester essential organic and inorganic nutrients for uptake into the epithelium. The feeding experiments indicate that erythrocytes are uncoated as they pass through the oesophagus, intersecting with its secretions, whilst the endocytosis of space-filling dextran into the gut epithelium provides a potential mechanism for carrier uptake by macropinocytosis.

Diversidad enzimática de la fracción soluble de un aislado venezolano de adultos Paragonimus sp / Enzymatic diversity of enzymes in the soluble fraction of adult worms from a Venezuelan isolate of Paragonimus sp

Paragonimus sp. es un trematodo que causa inflamación crónica del pulmón en mamíferos carnívoros y en el hombre, constituyendo un problema de salud pública en países asiáticos y latinoamericanos. Los trematodos poseen enzimas que facilitan la penetración y migración en diferentes hospederos a fin de garantizar su ciclo evolutivo. Con el objetivo de evaluar la diversidad enzimática de la fracción soluble (FSPA, 100.000 g) de un aislado venezolano de adultos de Paragonimus sp. se realizaron determinaciones enzimáticas a diferentes pH, usando curvas de calibración (A 405 nm vs. nmol) para interpolar la absorbancia de grupos p-nitrofenol o p-nitroanilina liberados por la hidrólisis de sustratos sintéticos; se utilizaron también sustratos 2-naftilamídicos y 2-naftólicos para determinar esterasas, peptidasas, fosfomonoesterasas y glicosidasas. Se demostró que fosfohidrolasas, glicosidasas y peptidasas están presentes en la FSPA, destacándose la β-NAG (0,55 μmol/h/mg, pH 5,5) y la cistein proteasa (0,4 μmol/h/mg, pH 5,5) como las actividades más elevadas, señalando la importancia funcional de la actividad glicosídica y peptídica en este parásito, las cuales están probablemente relacionadas con su hábitat y su necesidad de degradación de secreciones pulmonares. Estos resultados representan los primeros estudios enzimáticos registrados en vermes adultos de un aislado venezolano de Paragonimus sp. obtenidos del reservorio Didelphis marsupialis

Paragonimus sp. is a trematode that causes chronic inflammation of the lung in carnivorous mammals and humans, which constitute a public health problem in Asian and Latin American countries. Trematodes have enzymes that facilitate their penetration and migration through different host organs to ensure their life cycle. To evaluate the enzymatic diversity of the soluble fraction (FSPA, 100,000 g) of a Venezuelan isolate of Paragonimus sp. adult worms, several enzyme determinations were conducted at different pH. The activities of enzymes releasing p-nitrophenol or p-nitroanilina from the corresponding dye-related synthetic peptides were assessed by interpolating absorbance (A 405 nm) values in the corresponding calibration curve (A 405 nm vs. nmol); on the other hand, absorbances82 Bol. Mal. Salud Amb.Diversidad enzimatica de Paragonimus sp. en Venezuelaof 2-naphtylamine and 2-naphtols released from another series of synthetic substrates were read at different wavelengths between 450 nm and 620 nm to assess for the activity of the corresponding hydrolases. Phosphohydrolase, glycosidase and peptidase activities were detected in FSPA, β-N-acetyl-β-D-glucosaminidase (0.55 μmol/h/mg, pH 5.5) and cystein protease (0.4 μmol/h/mg, pH 5.5) being higher than all the other detected activities. These activities are probably related to the adult worm habitat and its need for glycan and peptide degradation of lung secretions. These results represent the first enzymatic study done with a Venezuelan isolate of adult Paragonimus sp. worms collected from the common reservoir Didelphis marsupialis

Immunoblot analysis of membrane antigens of Schistosoma mansoni, Schistosoma intercalatum, and Schistosoma haematobium against Schistosoma-infected patient sera.

Antigens present in aqueous n-butanolic extracts (BE) of Schistosoma mansoni (Venezuelan JL strain), Schistosoma intercalatum (Cameroon EDEA strain), and Schistosoma haematobium (Yemen strain) adult worm membranes were compared in immunoblot against sera of patients infected with S. mansoni, S. intercalatum, S. haematobium, Schistosoma japonicum, or Schistosoma mekongi looking for similarities (common antigens) and differences (species-specific antigens). About 17 S. mansoni BE polypeptides (M (r) approximately 8 to >80 kDa) were commonly recognized by S. mansoni-infected patient sera from Venezuela, Senegal, and Ethiopia. S. intercalatum-, S. haematobium-, or S. japonicum-infected sera were almost unreactive with S. mansoni BE. Nonetheless, S. mekongi-infected sera weakly cross-reacted with a approximately 10-15-kDa subset of S. mansoni BE. About 72.7% of S. intercalatum-infected patient sera reacted with a approximately 19-21-kDa complex in S. intercalatum BE and cross-reacted with a similar complex in S. haematobium BE. Conversely, all S. haematobium-infected patient sera reacted with a approximately 19-21-kDa complex in S. haematobium BE and cross-reacted with the approximately 19-21-kDa complex in S. intercalatum BE; S. mansoni- and S. japonicum-infected patient sera did not react with S. intercalatum or S. haematobium BE. Results showed the presence of a common membrane antigen between African schistosome species and species-specific antigens in S. mansoni BE that could be useful to discriminate between species and/or to detect Schistosoma infections.

Controlled chaos of polymorphic mucins in a metazoan parasite (Schistosoma mansoni) interacting with its invertebrate host (Biomphalaria glabrata).

Invertebrates were long thought to possess only a simple, effective and hence non-adaptive defence system against microbial and parasitic attacks. However, recent studies have shown that invertebrate immunity also relies on immune receptors that diversify (e.g. in echinoderms, insects and mollusks (Biomphalaria glabrata)). Apparently, individual or population-based polymorphism-generating mechanisms exists that permit the survival of invertebrate species exposed to parasites. Consequently, the generally accepted arms race hypothesis predicts that molecular diversity and polymorphism also exist in parasites of invertebrates. We investigated the diversity and polymorphism of parasite molecules (Schistosoma mansoni Polymorphic Mucins, SmPoMucs) that are key factors for the compatibility of schistosomes interacting with their host, the mollusc Biomphalaria glabrata. We have elucidated the complex cascade of mechanisms acting both at the genomic level and during expression that confer polymorphism to SmPoMuc. We show that SmPoMuc is coded by a multi-gene family whose members frequently recombine. We show that these genes are transcribed in an individual-specific manner, and that for each gene, multiple splice variants exist. Finally, we reveal the impact of this polymorphism on the SmPoMuc glycosylation status. Our data support the view that S. mansoni has evolved a complex hierarchical system that efficiently generates a high degree of polymorphism-a "controlled chaos"-based on a relatively low number of genes. This contrasts with protozoan parasites that generate antigenic variation from large sets of genes such as Trypanosoma cruzi, Trypanosoma brucei and Plasmodium falciparum. Our data support the view that the interaction between parasites and their invertebrate hosts are far more complex than previously thought. While most studies in this matter have focused on invertebrate host diversification, we clearly show that diversifying mechanisms also exist on the parasite side of the interaction. Our findings shed new light on how and why invertebrate immunity develops.

Preliminary characterization of an adult worm "vomit" preparation of Schistosoma mansoni and its potential use as antigen for diagnosis.

Schistosoma mansoni is a parasitic trematode of the portal-mesenteric veins with a closed-end intestine. Adult worms regurgitate their intestinal content after digestion, together with constituents of the lining gut. Some of these molecules circulate in the blood and are antigenic. We obtain a "vomit" preparation and preliminary evaluate its biochemical composition and antigenic capacity. The "vomit" preparation was obtained after changes in temperature and solutions of incubation of adult worms between 4 and 37 degrees C. Supernatant was assayed for protein, carbohydrate concentration and enzymatic activities associated to the intestine and to the worm tegument. The antigenicity of the product was evaluated using Western blot (WB) analysis against sera of experimentally infected mice, before and after drug cure, sera from people infected with S. mansoni and from individuals infected with other parasitoses. More carbohydrate than protein was detected in the preparations. Cysteine proteinase (CP), N-acetyl-beta-D: -glucosaminidase and alkaline phosphatase activities were detected. The latter enzyme activity is a marker of the tegument, suggesting that in spite of careful conditions used to avoid the presence of tegumental material, manipulation of the worms always resulted in the release of tegumental molecules. Cationic exchange chromatography was useful to separate various components of this "vomit" preparation, particularly enzymes responsible for CP activity. Two highly immunogenic and specific duplets were observed in the WB analysis, 31/32- and 38/40-kDa components, the former probably referring to the intestinal CPs Sm31/Sm32. None of the two duplets disappeared after successful chemotherapy during the time of evaluation in mice or humans.

Origin and diversification of the human parasite Schistosoma mansoni.

Schistosoma mansoni is the most widespread of the human-infecting schistosomes, present in 54 countries, predominantly in Africa, but also in Madagascar, the Arabian Peninsula, and the Neotropics. Adult-stage parasites that infect humans are also occasionally recovered from baboons, rodents, and other mammals. Larval stages of the parasite are dependent upon certain species of freshwater snails in the genus Biomphalaria, which largely determine the parasite's geographical range. How S. mansoni genetic diversity is distributed geographically and among isolates using different hosts has never been examined with DNA sequence data. Here we describe the global phylogeography of S. mansoni using more than 2500 bp of mitochondrial DNA (mtDNA) from 143 parasites collected in 53 geographically widespread localities. Considerable within-species mtDNA diversity was found, with 85 unique haplotypes grouping into five distinct lineages. Geographical separation, and not host use, appears to be the most important factor in the diversification of the parasite. East African specimens showed a remarkable amount of variation, comprising three clades and basal members of a fourth, strongly suggesting an East African origin for the parasite 0.30-0.43 million years ago, a time frame that follows the arrival of its snail host. Less but still substantial variation was found in the rest of Africa. A recent colonization of the New World is supported by finding only seven closely related New World haplotypes which have West African affinities. All Brazilian isolates have nearly identical mtDNA haplotypes, suggesting a founder effect from the establishment and spread of the parasite in this large country.

Detection of Schistosoma mansoni membrane antigens by immunoblot analysis of sera of patients from low-transmission areas.

Schistosoma mansoni surface membrane components play a relevant role in the host-parasite interaction, and some are released in vivo as circulating antigens. n-Butanol extraction favors the release of membrane antigens like alkaline phosphatase, which has been shown to be specifically recognized by antibodies from S. mansoni-infected humans and animals. In the present study, components in the n-butanol extract (BE) of the adult S. mansoni worm membrane fraction were separated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE [15%]) and further analyzed by immunoblotting (immunoglobulin G) using defined sera. S. mansoni-infected patient sera, but not sera of uninfected patients or sera obtained from patients infected with other parasite species, specifically and variably recognized up to 20 polypeptides in the molecular mass range of approximately 8 to >80 kDa. There were some differences in the number, intensity, and frequency of recognition of the BE antigens among sera from Venezuelan sites of endemicity with a different status of schistosomiasis transmission. Antigens in the 28- to 24-kDa molecular mass range appeared as immunodominants and were recognized by S. mansoni-positive sera from all the sites, with recognition frequencies varying between 57.5 and 97.5%. Immunoblotting with BE membrane antigens resulted in a highly sensitive (98.1%), specific (96.1.0%), and confirmatory test for the immunodiagnosis of schistosomiasis in low-transmission areas.

Quimioterapia de la esquistosomiasis: antiguos y nuevos fármacos / Chemotherapy of the schistosomiasis; antiques and new medicine

La quimioterapia es utilizada actualmente como la principal estrategia de control de la esquistosomiasis. Antimoniales, tioxantonas, derivados imidazólicos, organofosforados, nitrotiazoles y ditioltionas fueron utilizados por años contra esta parasitosis. La mayoría de esta drogas fueron abandonadas por problemas de toxicidad, efectos neurosíquicos e inmunosupresores, entre otros. En la actualidad, el tratamiento se realiza con praziquantel (PZQ), una pirazinoisoquinolina de amplio espectro , eficaz y capaz de reducir la morbilidad, aunque no de prevenir la reinfección. Por otra parte, las drogas anti-maláricas artemisinina y sus derivados, poseen propiedades anti-esquistosoma con buen perfil de seguridad. El artemeter actúa contra los esquistosómulos y es complementario al PZQ, que actúa sobre los vermes adultos. En la presente revisión, se evalúa la quimioterapia anti-bilharziana y se discuten los mecanismos de acción de las diferentes drogas, incluyendo nuevos posibles blancos de intervención farmacológicas, con el propósito de estimular el desarrollo de alternativas quimioterapéuticas

Immunological similarity between Schistosoma and bovine cathepsin D.

IgG antibodies from sera of rabbits immunized with a mixture of three synthetic peptides of highly conserved surface-exposed sequences between Schistosoma japonicum and S. mansoni cathepsin D, and a rabbit anti-bovine cathepsin D serum strongly recognized a 45 kDa molecule on immunoblots of adult S. mansoni worm saline extracts (AWSE). This recognition was abolished by immunoadsorption with two of the three selected peptides. The anti-peptide antibodies fixed onto Protein A-Sepharose specifically immunoprecipitated a S. mansoni AWSE component that was able to degrade bovine hemoglobin at pH 3.8. This reaction was inhibited by 7 microM pepstatin A, a classical aspartyl protease inhibitor, suggesting that the parasite cathepsin D was immunoprecipitated. The anti-peptide antibodies also recognized on a dot-blot assay a purified, commercially obtained bovine cathepsin D preparation but not the purified human counterpart. On the other hand, the anti-bovine cathepsin D serum recognized the two above-mentioned schistosome peptides. In addition, S. mansoni-infected patient sera recognized on immunoblots the bovine but not the human cathepsin D. These results, together with a comparative analysis of the selected peptide sequence regions between the schistosome and the two mammal enzymes, allowed us to pinpoint to one amino acid the cross-reactivity between parasite and bovine cathepsin D and the lack of it with human cathepsin D. This difference might be of relevance for immunodiagnosis.

Prevalencia de las parasitosis intestinales y esquistosomosis en comunidades de área centro norte de Venezuela / Prevalence of the intestinal parasite and schistosomiasis in communinities of the center-north area of Venezuela

Con el fin de evaluar las prevalencias de parásitos intestinales y los casos de esquistosomosis, se estudiaron seis comunidades ertenecientes a tres Estados, Aragua, Carabobo y Vargas, del centronorte de Venezuela. Se evaluaron 1603 personas por varios exámenes coprológicos para el diagnóstico de helmintos y protozoarios y 2175 personas para descartar esquistosomosis, en 1532 de los cuales se practicaron exámenes coprológicos y serológicos simultáneamente. Los helmmintos más frecuentes en las comunidades estudiadas fueron: Trichuris trichiura (29,63 por ciento) y Ascaris lumbricoides (12,91 por ciento). Entre los protosuarios destacaron, Entamoeba coli (12,41 por ciento), Blastocystis hominis (12,10 por ciento), Endolimax nana (9,85) y Giardia duodenalis (9,35 por ciento). Se diagnosticaron 251 casos de esquistosomosis, resultando una prevalencia de 11,5 por ciento. El rango de eliminación de huevos de Schistosoma mansoni fue de 24 a 1928 huevos/gramo de heces, siendo el 71 por ciento de las personas con leve intensidad de infección. En dos localidades del Estado Carabobo, Belén y Barrio José Leonardo Chirinos, se encontraron casos con eliminación de huevos en las heces en personas menores de 30 años. Los estudios de prevalencias de parasitosis intestinales y los trabajos de campo basados en coprología y serología para esquistosomosis, deben ser la base del Programa de Control para la vigilancia epidemiológica de estas entidades

Overview of some biomedical research projects in tropical medicine conducted at the Institute Venezolano de Investigaciones Cientificas

The Instituto Venezolano de Investigaciones Cientificas (IVIC) is a government-funded multidisciplinary academic institution dedicated to research, development and technology in many areas of knowledge. Biomedical projects and publications comprise about 40 percent of the total at IVIC. In this article, we present an overview of some selected research and development projects conducted at IVIC which we believe contain new and important aspects related to malaria, ancylostomiasis, dengue fever, leishmaniasis and tuberculosis. Other projects considered of interest in the general area of tropical medicine are briefly described. This article was prepared as a small contribution to honor and commemorate the centenary of the Instituto Oswaldo Cruz

Overview of some biomedical research projects in tropical medicine conducted at the Instituto Venezolano de Investigaciones Cientificas

The Instituto Venezolano de Investigaciones Cientificas (IVIC) is a government-funded multidisciplinary academic institution dedicated to research, development and technology in many areas of knowledge. Biomedical projects and publications comprise about 40 percent of the total at IVIC. An overview of some selected research and development projects conducted at IVIC related to malaria, ancylostomiasis, dengue fever, leismaniasis and tuberculosis are presented.(AU)