The role of thymic accessory cells in cytokine production and in the intra-thymic T cell differentiation pathway

Intrathymic T lymphocyte differentiation proceeds from complex interactions between prothymocytes of bone marrow origin and cells of the thymic stroma, epithelial cells and "acessory" cells (macrophages and/or interdigitating cells). The present paper describes the role of the accessoty cell compartment in this intrathymic process. Acessory cells produce factors which are involved in thymocyte proliferation (interleukin 1, prostaglandins, deoxynucleosides). Cell-cell interaction between "accessory" cells and thymocytes is required for the regulation of interleukin production. Prothymocytes, the precursors of all thymocyte subsets, need the accessory cell compartment for their IL2 dependent proliferation and their differentiation. Accessory cells of the thymic stroma may be involved in the intrathymic selection process at the prothymocyte level.

Chemical transformations of neolignans

Neolignans, generated by oxydative dimerization of propenylphenol and/or allylphenol, undergo further modifying steps. These biosynthetic reactions, confirmed in vitro, include Cope, retro-Claisen and Claisen rearrangements. Additionally acid catalysis effects convertions of bicyclo [3.2.1] octanoid neolignans into hydrobenzofuranoid neolignans, or inversely of hydrobenzofuranoid neolignans into bicyclo [3.2.1] octanoid neolignans, of hydrobenzofuranoid neolignans into futoenone type neolignans, of tetrahydrofuran neolignans into aryltetralin neolignans, as well as modifications by Friedel - Crafts reactions and the transformation of aryltetralin neolignans into arylindanones by pinacoline - pinacolone type rearrangement.

Medium-term protocols for in vivo evaluation of chemical modifiers of carcinogenesis

Cancer development is a long-term multistep process which allows interventional measure before the clincial disease emerges. the detection of natural substances which can block the process of carcinogenesis is a important as the identification of anti-tumoral drugs since they might be used in chemoprevention of cancer in high-risk groups. In vivo rodent models of chemical caecinogenesis have been used to study plant-derived inhibitors of carcinofenesis such as indols, coumarins, isothiocyanates, flavones, phenols and allyl-sulfides. Since the standard in vivo rodent bioassay is prolonged and expensive, shorter reliable protocols are needed. Two in vivo medium-term protocols for evaluation of modifiers of carcinogenesis are presented, one related to liver and the other to bladder cancer. Both protocols use rats, last 8 and 36 weeks and are based on the two-step concept of carcinogenesis: initiation and promotion. The protocols use respectively the development of altered foci of hepatocytes expressing immunochistochemically the placental form of gluthation S-transferase and the appearence of pre-neoplastic urothelium and papillomas as the "end-points". the use of these protocols for detection of plantpderived inhibitors of carcinogenesis appear warranted.

Antitumor activity of chemical modified natural compounds

Search of new activity substances starting from chemotherapeutic agents, continously appears in international literature. Perhaps this search has been done more frequently in the field of anti-tumor chemotherapy on account of the unsuccess in saving advanced stage patients. The new point in this matter during the last decade was computer aid in planning more rational drugs. In near future "the accessibility of supercomputers and emergence of computer net systems, willopen new avenues to rational drug design" (Portoghese, P. S. J. Med. Chem. 1989, 32, 1). Unknown pharmacological active compounds synthetized by plants can be found even without this eletronic devices, as tradicional medicine has pointed out in many contries, and give rise to a new drug. These compounds used as found in nature or after chemical modifications have produced successful experimental medicaments as FAA, "flavone acetic acid" with good results as inibitors of slow growing animal tumors currently in preclinical evaluation for human treatment. In this lecture some international contributions in the field of chemical modified compounds as antineoplasic drugs will be examined, particularly those done by Brazilian researches.

Chemical and pharmacological investigation of Solanum species of Brazil: a search for solasodine and other potentially useful therapeutic agents

A systematic search for solasodine, an important staring material for the partial synthesis of steroidal hormones as well as other potentially bioactive constituents of various Solanum species of Brazil has been undertaken. Thus, the fruits of S. paludosum, S. asperum, S. sessiliforum and Solanum sp. were found to contain significant amounts of solasodine. The root bark of S. paludosum which showe durare like activity yelded tomatidenol and another yet unidentified alkaloid responsible for the biological activity. The fruits of S. asperum yelded a new spirosolane alkaloid, solaparnaine. The stem bark of S. pseudo-quina showed convulsive and exitatory activity from which (25S)-isosolafloridine was identified as the active principle. In addition, the latter alkaloid was also found to show antimicrobial activity.

Plant lectins, chemical and biological aspects

Lectins, carbohydrate-binding proteins of non-immune origin, that agglutinate cells or precipitate polysaccharides and glycoconjugates, are well distributed in nature, mainly in the Plant Kingdom. The great majority of the plante lectins are present in seed cotyledons where they are found in the cytoplasm or int he protein bodies, although they have also been found in roots, stems and leaves. Due to their peculiar properties, the lectins are used as a tool both for analytical and preparative purposes in biochemistry, cellular biology, immunology and related areas. In agriculture and medicine the use of lectins greatly improved in the last few years. The lextins, with few exceptions, are glycoproteins, need divalent cations to display full activity and are, in general, oligomers with variable molecular weight. Although the studies on lectins have completed a century, their role in nature is yet ynknown . Several hypotheses on their physiological functions have been suggested. Thus, lectins could play important roles in defense against pathogens, plant-microorganism symbiosis, cell organization, embryo morphogenesis, phagocytosis, cell wall elongation, pollen recognition and as reserve proteins. A brief review on the general properties and roles of the lectins is given.

Intratypic differentiation of polioviruses isolated from suspected cases of poliomyelitis in Brazil during the period of 1990 to 1993

This study analyzed 3129 fecal samples derived from 1626 patients with sudden onset acute flaccid paralysis clinically compatible with poliomyelitis. The samples were collected in the period ranging from January 1990 to September 1993 in all regions of Brazil. Among the 1626 cases studied, 196 had isolation of poliovirus. Nevertheless, it was observed that some factors influenced the isolation rate and the intratypic characterization of these polioviruses. No cases of acute flaccid paralysis has been found to be etiologically related with wild polioviruses.

In vivo differentiation of Trypanosoma cruzi - 1. Experimental evidence of the influence of vector species on metacyclogenesis

Vector species has not hitherto been studied as influencing metacyclogenesis of Trypanosoma cruzi, while the role of the parasite strain has been frequently stressed as of dominant importance in this process. In order to fill this gap in our knowledge, metacyclogenesis was monitored in nine triatomine species. The first part of this paper presents photographs of the main and intermediate parasite stages in each vector species studied. In the second part of the study the proportional distribution of all these forms, as seen in Giemsa stained smears is summarized, thus providing an opportunity to analyze both: the length of time between the ingestion of the blood trypomastigotes and the appearance of metacyclic forms and the rates of developmental stages leading to these latter. The most remarkable observation was that metacyclogenesis rates in vivo appear to be vector dependent, reaching 50 in Rhodnius neglectus, 37 in its congener R. prolixus and being dramatically lower in the majority of Triatoma species (5 in T. sordida, 3 in T. brasiliensis and 0 in T. pseudomaculata) at the 120th day of infection. These observations suggest that through screening of different vector species it is possible to find some that are capable of minimizing or maximizing metacyclic production.

Genetic variability and differentiation between populations of Rhodnius prolixus and R. pallescens, vectors of Chagas' Disease in Colombia

Enzyme polymorphism in Rhodnius prolixus and R. pallescens (Hemiptera, Reduviidae), principal vectors of Chagas' disease in Colombia, was analyzed using starch gel electrophoresis. Three geographic locations were sampled in order to determine gene flow between populations and to characterize intra- and interspecific differences. Of 25 enzymes assayed 10 were successfully resolved and then used to score the genetic variation. The enzymes PEPD, GPI, PGM and ICD were useful to differentiate these species and PGD, PGM and MDH distinguished between sylvatic and domiciliary populations of R. prolixus. Both polymorphism and heterozygosity indicated greater genetic variability in sylvatic habitats (H = 0.021) compared to domiciliary habitats (H = 0.006) in both species. Gene flow between sylvatic and domiciliary populations in R. prolixus was found to be minimal. This fact and the genetic distance between them suggest a process of genetic isolation in the domiciliary population.

The serological differentiation of acute and chronic schistosomiasis japonica using IgA antibody to egg antigen

Two groups of Schistosoma japonicum infected patients (acute and chronic ) and non-infected individuals were studied using IgA antibody to egg antigen (SEA) and IgG and IgM antibodies to keyhole limpet haemocyanin (KLH). The means and standard deviation of the optical density in ELISA of acute, chronic and negative groups for IgA anti-SEA were 583±124.7, 98.2±78.8 and 82.2±39. 3, respectively. There was a statistically significance between acute patients and chronic patients (P<0.01). The means and standard deviation of IgG and IgM antibodies to KLH were 501.5±150.6, 113.0±79.1, 28.8±56.3 and 413.6±148.5, 70.2±14.8, 65.3±45.3, respectively. The detection results of IgA to SEA compared with the IgG and IgM to KLH did not demonstrate a significant difference (P>0.01). The sensitivities of IgA to SEA and IgG and IgM antibodies to KLH for the detection of acute infection were 95.24%, 90.48% and 85.71%, respectively. Therefore, this study showed that the detection of IgA to SEA is also a useful new method for the serological differentiation of acute and chronic schistosomiasis japonica in humans.

Evaluation of Chemical and Physical-morphological Factors as Potential Determinants of Biomphalaria pfeifferi (Krauss, 1848) Distribution

This study was carried out in five sites along a small perennial river system in south-central Tanzania, which had been identified as the focus for transmission of intestinal schistosomiasis in the area. Malacological surveys preceding the study showed a focal distribution of Biomphalaria pfeifferi, intermediate host snail of Schistosoma mansoni, the snails being present in three sites but absent from the other two sites. The objective of this study was to evaluate to what extent chemical and/or physical-morphological factors determine the distribution of B. pfeifferi between these five sites. It was found that none of the chemical constituents in the waters examined were outside the tolerance range of B. pfeifferi snails. Moreover, the composition of water from B. pfeifferi-free sites was not different from that in those sites where snails occurred. Furthermore, none of the physical-morphological constituents seemed likely to be a determinant for the absence of B. pfeifferi. In view of these findings, and those of previous studies, it is concluded that the focal distribution of B. pfeifferi cannot be associated with a single environmental factor and is rather the result of more complex interactions of habitat factors

A Preliminary Investigation on the Chemical Composition of the Cell Surface of Five Enteropathogenic Escherichia coli Serotypes

The cell surfaces of five enteropathogenic Escherichia coli serotypes (O111:H2; O111:H12; O125:H9; O119:H6; O26:H11) were assayed by chemical methods, lectin agglutination tests and spectroscopy associated to transmission electron microscopy. Results of lectin agglutination assays showed that all strains reacted with mannosebinding lectins. Strains belonging to serotype O125:H9 also agglutinated with lectins which recognize galactose and Nacetylgalactosamine residues. The bacterial cells were treated with 0.01M phosphate buffered saline (pH 7.0) at 100oC for 2 hr and the extracts were submitted to precipitation and fractionated by Cetavlon. Phosphate, total sugar and protein contents were determined. Gas liquid chomatography-mass spectrometry analysis of alditol acetates showed the presence of galactose, mannose, fucose, glucose and traces of ribose. Spectroscopic analysis of intact cells showed the presence of a capsule-like structure which was not totally preserved after extraction. Some cells were still surrounded by an amorphous capsular-like material after polysaccharide extraction.