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Biomedical subjects

A Theron

Publications and source records attributed to A Theron.

At least 19 recordsLinked to original sources

Schistosoma: cross-reactivity and antigenic community among different species.

It is not unusual to find common molecules among different species of the genus Schistosoma. When those molecules are antigenic, they may be used in immunodiagnosis and vaccines, but they could also be applied to taxonomic and evolutionary studies. To study cross-reactivity and antigenic community among different species of schistosomes, plasmas from laboratory animals infected with Schistosoma bovis, S. guineensis, S. rodhaini, S. haematobium, and four strains of S. mansoni were evaluated with a crude extract of adult worms of S. mansoni by Western blot. Using the multiple antigen blot assay, plasmas from these infected animals were exposed to a selected group of synthetic peptides from Sm28GST, Sm28TPI, Sm elastase, Sm97, Sm32, Sm31, and Sm Cathepsin L. The results presented herein demonstrate differential cross-reactivity and antigenic community among the Mansoni and Haematobium groups of schistosomes, which is of relevance as an additional new tool for phylogenetic studies of schistosomes as well as for diagnosis and vaccine purposes.

Animals↗

Molecular ecology of Schistosoma mansoni transmission inferred from the genetic composition of larval and adult infrapopulations within intermediate and definitive hosts.

We investigated the genotypic composition of the digenetic parasite Schistosoma mansoni for its adult stages within the definitive host (the wild rat, Rattus rattus) and for the larval stages within the intermediate host (the snail, Biomphalaria glabrata) both collected at the same transmission site. Our analyses are based upon the recognition and distribution of 200 different multilocus genotypes generated by RAPD markers. While intramolluscan larval infrapopulations are characterized by a low infection rate (0.6 % on average) and low intra-host genetic diversity (1.1 genotype on average per infected snail), adult infrapopulations within rats showed a high infection rate (94%) and a substantial intra-host genetic diversity (34 genotypes on average) linked to high intensities (160 worms per host on average). A single definitive host bearing 105 different genotypes harboured 52 % of the total genetic diversity detected within the whole parasite population. Analysis of the genetic data allowed the identification of various ecological, behavioural and immunological factors which are likely to enhance transmission of multiple parasite genotypes towards the vertebrate hosts. From the distribution of repeated identical multilocus genotypes within the parasite population and among the hosts, we have inferred different parameters of the cercarial transmission efficiency as well as patterns and processes by which vertebrate hosts acquire infection in the field.

Animals↗

The effects of ketolides on bioactive phospholipid-induced injury to human respiratory epithelium in vitro.

The potential of the novel ketolide antimicrobial agents, HMR 3004 and HMR 3647, to antagonize the injurious effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the ciliary beat frequency and structural integrity of human ciliated respiratory epithelium in vitro was investigated, in the presence or absence of polymorphonuclear leukocytes (PMNL). The ciliary beat frequency of human nasal respiratory epithelium, obtained by nasal brushing of healthy volunteers, was measured using a photo-transistor technique, while superoxide generation by activated human PMNL and membrane-stabilizing activity were measured by lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively. All three PL, at concentrations of 2.5 microg x mL(-1), caused significant (p<0.005) ciliary slowing and epithelial damage, while treatment of the epithelial strips with the ketolides, in particular HMR 3004, caused dose-related attenuation of these direct adverse effects of the PL on ciliated epithelium, apparently by a membrane-stabilizing mechanism. When epithelial strips were exposed to the combination of PMNL (1 x 10(6) cells x mL(-1)) and PAF (1 microg x mL(-1)), significant ciliary dysfunction and epithelial damage were also observed, which were mediated predominantly by neutrophil-derived oxidants. These injurious effects of PAF were antagonized by preincubation of the epithelial strips or the PMNL with HMR 3004 (10 microg x mL(-1)). The ketolide antimicrobial agents, in particular HMR 3004, antagonize the direct and polymorphonuclear leukocyte-mediated injurious effects of phospholipids on human ciliated epithelium and may have beneficial effects in inflammatory disorders of the airways, such as asthma, chronic bronchitis, diffuse panbronchiolitis and bronchiectasis.

Anti-Bacterial Agents↗

Exposure of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-activated human neutrophils to the Pseudomonas aeruginosa-derived pigment 1-hydroxyphenazine is associated with impaired calcium efflux and potentiation of primary granule enzyme release.

The effects of pathologically relevant concentrations (0.38 to 12.5 microM) of the proinflammatory, Pseudomonas aeruginosa-derived pigment 1-hydroxyphenazine (1-hp) on Ca2+ metabolism and intracellular cyclic AMP (cAMP) in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 1 microM)-activated human neutrophils, as well as on the release of myeloperoxidase (MPO) and elastase from these cells, have been investigated in vitro. Ca2+ fluxes were measured by the combination of a fura-2/AM-based spectrofluorimetric method and radiometric procedures, which together enable distinction between net efflux and influx of the cation, while radioimmunoassay and colorimetric methods were used to measure cAMP and granule enzymes, respectively. Coincubation of neutrophils with 1-hp did not affect intracellular cAMP levels or the FMLP-activated release of Ca2+ from intracellular stores but did retard the subsequent decline in the chemoattractant-induced increase in the concentration of cytosolic free Ca2+. These effects of 1-hp on the clearance of Ca2+ from the cytosol of activated neutrophils were associated with decreased efflux of the cation from the cells and increased release of MPO and elastase, while the delayed store-operated influx of the cation into the cells was unaffected by the pigment. The plasma membrane Ca2+-ATPase rather than a Na+-Ca2+ exchanger appeared to be the primary target of 1-hp. These observations suggest that the proinflammatory interactions of 1-hp with activated human neutrophils are a consequence of interference with the efflux of cytosolic Ca2+ from these cells.

Adenosine Triphosphate↗

Failure of Schistosoma mansoni to reinfect Biomphalaria glabrata snails: acquired humoral resistance or intra-specific larval antagonism?

Failure of snail reinfection by Schistosoma mansoni has been demonstrated in susceptible Biomphalaria glabrata infected with 1 miracidium and subsequently re-exposed to 1 or 5 homologous parasite larvae. The acquisition of 'resistance' to secondary parasite infection was time dependent since complete inhibition was observed at 2 weeks and longer following monomiracidial exposure. This phenomenon was still observed in snails challenged 8 weeks after primary infection. Histological observations revealed that sporocysts from the challenge infection were free of encapsulation, their development was stopped and they degenerated slowly in the absence of haemocytic reaction of the host. Under the hypothesis of an acquired homologous resistance mechanism, this strongly suggests that 1 or several unidentified humoral factors are responsible for the non-development of the sporocysts from the challenge infection. However, considering the time-dependent nature of the phenomenon, an intraspecific larval antagonism process between sporocysts resulting from the primary infection and those from the challenge infection may be involved.

Animals↗

Investigation of the relationships between plasma levels of ascorbate, vitamin E and beta-carotene and the frequency of sister-chromatid exchanges and release of reactive oxidants by blood leucocytes from cigarette smokers.

In this study the frequencies of sister-chromatid exchanges (SCEs) were correlated with measurements of the release of reactive oxidants by phagocytes, as determined by luminol-enhanced chemiluminescence (LECL), and levels of the anti-oxidants ascorbate, beta-carotene and vitamin E in blood specimens taken from 65 young asymptomatic cigarette smokers. Increased SCE frequencies correlated with LECL responses (p less than 0.0075) of activated blood phagocytes. Anti-oxidant levels did not correlate with either LECL or SCEs. These findings indicate that increased generation of reactive oxidants by circulating phagocytes from cigarette smokers are associated with cytogenetic changes.

Adult↗

[Factors responsible for preventing the carrying out of the Schistosoma mansoni cycle in the waters of Grande Terre of Guadeloupe (French Antilles)].

Different surveys which have been conducted in ponds and pools in the Grande Terre of Guadalupe, have demonstrated the absence of Schistosoma mansoni transmission in spite of apparent favourable ecological conditions. Four hypothesises can explain this absence of transmission: 1 - the presence of Biomphalaria glabrata populations non-susceptible to the infestation by S. mansoni. 2 - Ecological conditions unfavourable to the survival of parasitized snails. 3 - Ecological conditions unfavourable to the production, survival and infectivity of the S. mansoni cercariae. 4 - Factors causing the non-contamination of the snails. The results show that the transmission of schistosomiasis mansoni is possible in the ponds and pools of Grande Terre. Only human behaviour is responsible for the absence of actual transmission in the waterbodies of this area. Man breaks the life-cycle of the parasite by avoiding all fecal pollution and therefore all snail contamination.

Animals↗

Investigation of the protective effects of the antioxidants ascorbate, cysteine, and dapsone on the phagocyte-mediated oxidative inactivation of human alpha-1-protease inhibitor in vitro.

Oxidants derived from the atmosphere or from activated pulmonary phagocytes mediate functional inactivation of alpha-1-protease inhibitor (alpha-1-PI). Chronic exposure to these oxidants may cause emphysema. In this study we have investigated the effects of the antioxidants ascorbate, cysteine (10(-4) M to 10(-1) M), and dapsone (10(-6) M to 10(-3) M) on the oxidative inactivation of human alpha-1-PI by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. During exposure of alpha-1-PI to stimulated PMNL in the presence of ascorbate and cysteine at concentrations of greater than 10(-4) M and dapsone at greater than 10(-6) M, the elastase inhibitory activity of alpha-1-PI was preserved. However, exposure of the alpha-1-PI to the antioxidants subsequent to PMNL-mediated oxidative inactivation was not associated with reactivation of elastase inhibitory capacity. Ascorbate, cysteine, and dapsone at concentrations that caused 50% protection of alpha-1-PI did not affect degranulation or the binding of radiolabeled leukoattractant to PMNL. It is suggested that the protective effects of the antioxidants are related to their ability to scavenge superoxide and oxidants generated by the PMNL-myeloperoxidase/H2O2/halide system. Because the effects of ascorbate and especially those of dapsone were observed at concentrations of these agents that are attainable in vivo, our results may have clinical significance.

Antioxidants↗

[Physiological dangers of the use of Cannabis sativa].

The increasing use of Cannabis sativa (dagga) raises the question whether it could cause physical harm to the user. The earlier belief that cannabis could be used effectively in the treatment of various illnesses contributes to the tendency of cannabis users to reject the possibility that it may be harmful to their health. Scientific research, however, indicates that cannabis has no medicinal value. On the contrary, it may cause serious physical damage.

Animals↗

[Activities of a Schistosoma mansoni focus of transmission in Martinique (French Antilles)].

A focus of intestinal schistosomiasis was discovered in november 1981 in Martinique in the Saint-Pierre area. An analysis of its structure and of the mecanisms of the transmission of the parasite was carried out between 1981 and 1983. This focus presents the following particularities: a transmission site very small constituted by water cress beds; a small human population infected with a prevalence of 13% (positive stools) to 41,3% (positive serologies); a weak fecal contamination of the water; a non functioning sewage stabilization tank is responsible for this contamination; a rich population of the snail host Biomphalaria glabrata (40,5 to 256,3 Bg/m2) with a low prevalence of infestation (0,13 to 0,59%); low cercarial densities in the water cress bed waters; a very low contamination of the Roxelane river water in to which the water from the water cress beds flows. The epidemiological importance of this contamination has proved very low but not altogether absent. This focus appears as a particular case in Martinique because all the surveys which have been conducted in the island to date has not uncovered a similar example.

Animals↗

The effects of benoxaprofen on mononuclear and polymorphonuclear leucocyte motility. An in vitro and in vivo study.

Benoxaprofen at concentrations well within the normal therapeutic range was found to cause significant inhibition of both mononuclear leucocyte (MNL) and polymorphonuclear leucocyte (PMNL) motility in vitro. The ingestion of benoxaprofen 600 mg also resulted in a significant reduction of MNL migration, while co-incubation of control PMNLs with 25% heat-inactivated serum from healthy subjects resulted in a very significant inhibition of PMNL motility. Serum IgG levels also dropped significantly after benoxaprofen ingestion. These results show that human PMNL and MNL migration is significantly suppressed by benoxaprofen both in vitro and in vivo and that the anti-inflammatory activity of the drug is mediated at least partly by inhibition of the migration of both the cell types and suppression of immunoglobulin production, possibly by induction of suppressor MNL activity.

Adult↗

Ascorbic acid in bronchial asthma.

Sixteen White children with bronchial asthma were divided into two groups; one received standard anti-asthma chemoprophylaxis (SAC) and the other SAC supplemented with 1 g ascorbic acid (Redoxon) given as a single daily dose for a 6-month period. In 10 patients the effects of ascorbic acid on exercise-induced bronchoconstriction (EIB) were assessed by comparing the pre-ascorbic acid results with those obtained 2 1/2 hours after the intravenous injection of 1 g ascorbic acid. Immunological investigations performed on the two groups were assessment of polymorphonuclear leucocyte (PMNL) motility, phagocytosis and nitroblue tetrazolium reduction and measurement of secretory IgA, serum immunoglobulin and total haemolytic complement levels and levels of the components C3 and C4, alpha 1-antitrypsin, antistreptolysin O (ASO), C-reactive protein and antibodies to certain respiratory viruses. These investigations were performed before and 1, 3 and 6 months after the commencement of therapy. Radio-allergosorbent testing for sensitivity to four common allergens was carried out at the outset and after 6 months of therapy. Injection of ascorbic acid had no detectable effects on the degree of EIB. Slight but not significant immunological changes were observed in the SAC group over the 6-month study period. However, in the SAC plus ascorbic acid group significantly improved PMNL motility and decreased ASO levels and reduced (although not to a significant extent) IgE levels and titres of antibodies to the respiratory viruses were observed.

Adolescent↗

Immunological assessment of patients with rheumatoid arthritis--evaluation of the effects of propranolol.

Some humoral and cellular immune functions were evaluated in a group of 10 patients with rheumatoid arthritis before and after 3 months of treatment with the beta-blocking agent propranolol. Humoral parameters measured were serum immunoglobulins including IgE, auto-antibodies, C-reactive protein, total haemolytic complement activity and the complement components C3 and C4. Cellular functions assessed were polymorphonuclear leucocyte chemotaxis, phagocytosis and postphagocytic nitroblue tetrazolium reduction, hexose monophosphate shunt activity and myeloperoxidase-mediated iodination of ingested protein; lymphocyte transformation to the mitogens phytohaemagglutinin and concanavalin A was also investigated. No alteration of humoral factors and neutrophil functions was observed following propranolol administration (40 mg 3 times a day), but lymphocyte transformation was significantly increased. Improved lymphocyte function did not correlate with clinical improvement.

Adult↗