Marine organisms: an alternative source of potentially valuable natural products

This paper recalls the outcoming of marine natural products research and reviews a selection of marirne bioactive metabolites in current use together with promising trends in marine pharmacology.

Trypanosoma cruzi: effect of phenothiazines on the parasite and its interaction with host cells

Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and,to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxity between anti-trypanossomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypothesis for the mechanism of action of phenothiazines are discussed.

A new host of Trypanosoma cruzi from Jujuy, Argentina: octodontomys gliroides (Gervais & D'Orbigny, 1844) (Rodentia, Octodontidae)

To identify wild hosts of Trypanosoma cruzi, surveys were conducted in the subandean valleys of Jujuy Province, Argentina, between June 1986 and March 1987. Seventy two mammals from 13 different species were examined by xenodiagnosis. Fifty two of them were mostly roedents trapped at the localities of Maimará, León and Tilcara, and the remainder had been kept in captivity at the Estación Biológica Experimental, in Jujuy. Trypanosoma cruzi infection was detected only in 2 Octodontomys gliroides (2 pos./8 exam. 25%) from all 72 examined mammals. Isolates were called Octodontomys Argentina 1 and 2 (OA1 and OA2). Both infected animals were caught at the archaelogical ruin of Pucará, at Tilcara. Repeated searches for triatomines in the ruin itself and in neighbour houses rendered negative results. Groups of mice inoculated with either OA1 or OA2 isolates became infected between 7 (OA1) to 12 days (OA2) postinoculation PI. Parasitemia peaks were observed between day 12th - 14th PI. Scarce amastigote nests were found in myocardium and skeletal muscle. Mortality was observed only for mice inoculated with OA1. Isoenzyme patterns of OA1 and OA2 were identical to one found in dogs and slightly different from that of human parasites in Argentina. Bones from Octodontomys sp., were recently found in a cave, dated 10200-8600 BC, in Pumamarca, near Tilcara, Jujuy. There are evidences that O. gliroides cohabited with man in ancient times and was associated to the domestic cycle of T. cruzi transmission, playing a role like that of domestic cavies. in Bolivia.

Pterigodermatites (Paucipectines) spinicaudatis n.sp. (Nematoda: Rictularidae) from Dromiciops australis (Marsupialia: Microbiotheriidae) in Bariloche, Rio Negro, Argentina, biogeographical distribution and host-parasite relationships

Pterigodermatites (P.) spinicaudatis sp.n. from Dromiciops australis is proposed and described. The simple morphology of the ovijector and the presence of a well developed spine between the two cuticular projections at the caudal extremity of the female distinguish the studied nematode from the remainder species of the genus parasitizing South American Edentata, marsupials and cricetid rodents. The distribution area of the hosts of the different species of P. (P.) are given. The studied genus does not parasitize any Australian marsupials. It was found in the endemic South American Microbiotheriidae. This fact suggests from a parasitological point of view that D. australis is not related to the Australian marsupials but to the South American ones.

Nomimoscolex touzeti n. sp. (Cestoda), a parasite of ceratophrys cornuta (L.): first record of a monticellidae in an amphibian host

Nomimoscolex touzeti n. sp. is described from one Ceratophrys cornuta (L.) caught in Amazonian Ecuador. Its taxonomic relationships to the others species are discussed. This new species is characterized by a cortical position of vitellaria; by the presence in the uteroduct of conglomerates of 20-40 eggs; by a weak ovary width/proglottis width ratio; by ventral excretory canals anastomosed; by a powerful vaginal sphincter and by a long cirrus. N. touzeti is the first record of Monticellidae in an amphibian host.

New host records and localities of some Monogenea from brazilian marine fishes with scanning electron microscopy of Bicotylophora trachinoti (Mac Callum, 1921)

Bicotylophora trachinoti (Mac Callum, 1921) from Trachinotus carolinus L.; Pseudanthocotyloides heterocotyle (Van Beneden, 1871) from Cetengraulis edentulus (Cuvier), and Decapterus punctatus (Cuvier), new host records; Pseudomazocraes selene Hargis, 1957 from Selene vomer (L.) and Caranx latus Agassiz, new host record, are reported for the first time in Brazil from the coast of Rio de Janeiro State. The marine fishes Diplectrum sp. and Pomatomus saltatrix (L.) are respectively new host records for Pseudotagia cupida (Hargis, 1956) and Macrovalvitrema sinaloense Caballero & Bravo Hollis, 1955. Measurements, original figures and photos in scanning electron microscopy of B. trachinoti are presented. The egg with filaments is reffered for the first time in the genus Pseudanthocotyloides.

On Thelazia anolabiata (Molin, 1860) Railliet & Henry, 1910 (Nematoda, Thelazioidea): a new host record and systematic considerations

Thelazia anolabiata (Molin, 1860) Raillet & Henry, 1910, parasite of eyes of birds, is reported in s new host, Ortalis canicolis pantanalensis Cher & Reich from Salobra, Mato Grosso do Sul State; T. digitata Travassos, 1918 and T. lutzi Travassos, 1918 are considered its synonyms.

Mechanisms of protective immunity against asexual blood stages of Plasmodium falciparum in the experimental host Saimiri

In the Saimiri monkey, an experimental host for human malaria, acquired protection against Plasmodium falciparum blood stages depends on the IgG antibody populations developed. In vivo protective anti-falciparum activity of IgG antibodies is correlated with the in vivo opsonizing activity promoting phagocytosis of parasited red bloood cells. In contrast, non protective antibodies inhibit this mechanism by competing at the target level. A similar phenomenon can be and human infection. Anti-cytoadherent and anti-rosette antibodies developed by Saimiri and humans prevent the development of physiopathological events like cerebral malaria which can also occur in this experimental host. Furthermore, transfer to protective human anti-falciparum IgG antibodies into infected Saimiri monkeys exerts an anti parasite activity as efficient as that observed when it is transfered into acute falciparum malaria patients, making the Saimiri an even more attractive host. Studies on the role of immunocompetent cells in the protective immune reponse are still in their infancy, however the existance of a restricted polymorphism of MHC II class molecules in the Saimiri confers additional theoretical and practical importance to this model.

Influence of the host related factors in the development of the hepatosplenic form of schistosomiasis mansoni

The frequency of hepatosplenomegaly in endemic areas is not proportional to the fecal ova count. This may be explained by epidemiological genetic. The occurrence of two or more cases of schistosomal hepatosplenomegaly in nuclear family is much higher than expected. The concentration is higher among siblings than it is among mothers and children of further and children. It is not significant between father and mother. If the mother, instead of the father has hepatosplenic schistosomiasis the relative risk for the child to acquire hepatosplenomegaly is at least five times (the maternal affect). The inbreeding is highler in the hepatosplenic than in the hepatointestinal patients. In some areas in Brazil the hepatosplenic form of the schistosomiasis mansoni occurs with much higher frequency in whites than in blacks. After treatment, reversion of hepatosplenic schistosomiasis occurs more frequently in non-whithers. It seems that the resistance of blacks to the hepatosplenic form of schistosomiasis may be related to the glyoxalase system , perhaps associated to another genetic marker. The hepatosplenic schistosomiasis is less frequent in longilineal individuals. In some areas the hepatosplenic form of schistosomiasis is more frequent in A blood group of ABO sistem. The family heredograms do not suggest a single mendelian inheritance, but probably a multifactorial and possibility poligenic one.

Alternative approaches in schistosomiasis control

Measures for for the control of schistosomiasis were implemented in Egypt begining 1922. This shows that developing endemic countries are facing this problem for near 70 years. However, results in the control of this infection have not been satisfactorily obtained in spite of the technologies and strategies recently developed. The idea that the social and economic components are relevant in the control of schistosomiasis is not new although its extension and profundity have not usually been well understood. More recently; most of the workers have recognized that the distribution of the prevalence rates of schistosomiasis should not be neglected in the control of the infection. At present field work projects on the control of schistosomiasis are being developed in rural areas of two Brazilian states (Espirito Santo and Pernanbuco). The adopted strategy aims to interfere in the complex relationships between amn and his bio-social-cultural environment, without forgeting tha the unequal distribution of the space is a consequence of the political and economic organization of the Society.

Coevolution of hosts and microorganisms: an analysis of the involvment of cytokines in host-parasite interactions

Parasites may employ particular strategies of eluding an immune response by taking advantage of those mechanisms that normally guarantee immunological self-tolerance. Much in the way as it occurs during the establishment of self-tolerance, live pathogens may induce clonal deletion, functional inactivation(anergy) and immunosupression. At this latter level, it appears that certain pathogens produce immunosupresive cytokine-like mediators or provoke like host the secrete cytokines that will compromise the anti-parasite immune response. It appears that immune responses that preferentially involve T helper l cells (secretors of interleukin-2-and interferon-y) tend to be protective, whereas T helper 2 cells (secretors of IL-4, IL5, IL-6, and IL-10), a population that antagonizes T helper cells, mediate disease susceptibility and are immunopathological reactions. Cytokines produced by T helper 2 cells mediate many symptoms of infection, including eosinophilia, mastocytosis, hyperimmunoglobulinemia, and elevated IgE levels. Administration of IL-2 and IFN-y has beneficial effects in many infections mediated by viruses, bacteria, and protozoa. The use of live vaccinia virus might be an avenue for the treatment of or vaccination against infection. We have found that a vaccinia virus expressing the gene for human IL-2, though attenuated, precipitates autoimmune disease in immunodeficient athymic mice. Thus, although T helper l cytokines may have desired immunostimulatory properties, they also may lead to unwarranted autoaggressive responses.

Host tissue destruction by Entamoeba histolytica: molecules mediating adhesion, cytolysis, and proteolysis

Entamoeba histolytica, the protozoan parasite causing human amoebisis, has recently been found to comprise two genetically distinct forms, potentially pathogenic and constitutively nonpathogenic ones. Host tissue destruction by pathogenic forms is belived to result from cell functions mediaed by a lectin-type adherence receptor, a pore-forming peptide involved in host cell lysis, and abundant expression of cysteine proteinase(s). Isolation and molecular cloning of these amoeba products have provided the tools for structural analyses and manipulations of cell functions including comparisons between pathogenic and nonpathogenic forms.

Human B19 parvovirus infetion: an example of multiple pathogenic effects determined by differences in host susceptibility

B19 infection offers some general lessons about human viruses and their possible effects on the human host, as follows: (1) Ubiquitous apparently benign viruses may have severe effects on a compromissed host. The virus may be invariable but the host can have diverse susceptibilities. (2) B19 and some other human viruses (through for none is the evidence so clear as for B19) have narrowly targetted effects. The host cell of B19 is a specialised progenitor of mature red cells: impairment of the function of this cell by B19 may cause profound anaemia. (3) The 'normal'host response to B19 may also cause disease, though this is slef limiting. (4) The effects of malfunction of the virus'target cell are exacerbated when the immune response is impaired by congenital or acquired immunodeficiency, immunosupressive therapy or, in the case of the fetus, developmental immaturity that allows the virus to persist.

Improved enzyme-linked immunoadsorbent assay (ELISA) for the study of Trypanosoma cruzi-host cell interaction in vitro

We herein present an improved assay for detecting the presence of Trypanosoma cruzi in infected cultures. Using chagasic human sera (CHS), we were able to detect T. cruzi infection in primary cultures of both peritoneal macrophages and heart muscle cells (MHC). To avoid elevated background levels - hitherto observed in all experiments especially in those using HMC - CHS were preincubated with uninfected cells in monolayers or suspensions prior to being used for detection of T. cruzi in infected monolayers. Preincubation with cell suspensions gave better results than with monolayers, reducing background by up to three times and increasing sensitivity by to twenty times. In addition, the continous fibroplastic cell line L929 was shown to be suitable for preadsorption of CHS. These results indicate that the high background levels observed in previous reports may be due to the presence of human autoantibodies that recognize surface and/or extracellular matrix components in cell monolayers. We therefore propose a modified procedure that increases the performance of the ELISA method, making it an useful tool even in cultures that would otherwise be expected to present low levels of infection or high levels of background

Sialoglycoconjugates in Trypanosoma cruzi-host cell interaction: possible biological model - a review

A number of glycoconjugates, including glycolipids and glycoproteins, participate in the process of host-cell invasion by Trypanosoma cruzi and one of the most important carbohydrates involved on this interaction is sialic acid. It is known that parasite trans-sialidase participates with sialic acid in a coordinated fashion in the initial stages of invasion. Given the importance of these sialogycoconjugates, this review sets out various possible biological models for the interaction between the parasite and mammalian cells that possess a sialylated receptor/ligand system.