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At least 127 records · Page 7Linked to original sources

Babesia bovis: common protein fractions recognized by oligoclonal B. bovis-specific CD4+ T cell lines from genetically diverse cattle.

CD4+ helper T cells are believed to be important for inducing protective immunity against Babesia bovis through the production of cytokines, including IFN-gamma, that will provide help to B lymphocytes for IgG production and activate macrophages to become parasiticidal. To provide maximum protection in an outbred population, an effective vaccine against B. bovis should contain antigens that would elicit an IFN-gamma response and would be recognized by cattle with diverse genetic backgrounds. To identify potentially protective "universal" T helper (Th) cell antigens, fractions of homogenized B. bovis merozoites were tested for the ability to stimulate proliferation of oligoclonal CD4+, IFN-gamma-producing T cell lines derived from four immune animals previously shown to differ in major histocompatibility complex class II expression. Homogenized B. bovis merozoites were separated by denaturing continuous flow electrophoresis (CFE) on 15, 10, and 7.5% polyacrylamide gels into fractions containing proteins ranging from <14.5 to approximately 95 kDa. Eighteen of 280 CFE fractions elicited anamnestic proliferative responses in all T cell lines tested. Nine of these cross-stimulatory fractions contained proteins of <14.5 to 24.5 kDa, and the remaining ones contained proteins with estimated molecular weights of 30, 31.5, 44.5, 49, 49.5, 54, 62, 72, and 82 kDa. Immunoblot analysis showed that four cross-stimulatory fractions contained a predicted known B. bovis antigen of similar molecular size. Previous studies had demonstrated that fractionated merozoite proteins stimulatory for CD4+ Th cell clones had apparent molecular weights similar to those present in 7 of the 18 stimulatory fractions. In the present study, two Th cell clones responded to cross-stimulatory CFE fractions, underscoring the potential to use both oligoclonal and monoclonal Th cell lines to identify commonly recognized polypeptides as potential vaccine antigens.

Animals↗

Flow cytometric analysis of Eimeria tenella sporozoite populations exposed to salinomycin sodium in vitro: a comparative study using light and electron microscopy and an in vitro sporozoite invasion-inhibition test.

Eimeria tenella sporozoites exposed to 100, 70, 60 and 50 micrograms salinomycin sodium (SAL)/ml medium 199 at 41 degrees C and then stained with propidium iodide/fluorescein diacetate were analysed by means of flow cytometry (FCM). After 20 min exposure, they showed dose-dependent alterations in their size and shape, i.e. ballooning of most cells, and enhanced intracellular esterase activity as compared with untreated controls. After longer exposure periods (40 and 70 min), inflated cells gradually changed into shrivelled or crumpled, nonviable ones, thereby showing a gradual decrease in esterase activity and a gradual loss of membrane integrity (RFA+). As compared with untreated controls, sporozoites treated with 10 micrograms SAL/ml showed negligible RFA+ values (0.4%-2%), whereas those exposed to 1 and 0.1 microgram SAL ml and to the solvent dimethylsulfoxide (DMSO, 1%) did not, even after 70 min exposure. Slight to severe structural changes manifesting as an extremely wavy surface (1 microgram SAL/ml), vacuolization of the cytoplasm, distension or destruction of the mitochondrion and rupture of cell membranes (10 micrograms SAL/ml) were seen not only at higher SAL concentrations but also (rarely) at lower ones. The ability of sporozoites to invade primary chick-kidney cells was significantly inhibited by 70, 60 and 50 micrograms SAL/ml. In general, there were close relationships between findings obtained using FCM, electron microscopy and an invasion-inhibition test. The results indicate that FCM is a reliable and sensitive technique for characterizing the parasiticidal effects on and the possible mode of action of drugs in free coccidian sporozoites.

Animals↗

Results of surgical treatment of hepatic hydatidosis: current therapeutic modifications.

Hepatic hydatidosis is an endemic disease that affects vast segments of the populations of various countries in the Mediterranean region, South America, the Pacific, and temperate zone nations that possess large numbers of sheep. Four hundred and ten patients bearing 561 hydatid cysts were treated at 2 major hospitals in Madrid, Spain in the period 1974-1989. In order to establish the modifications in diagnostic and therapeutic management introduced as a result of modernization of our clinical facilities and improved technological standards, they were divided into 2 groups: group A corresponded to the period 1974-1984, and group B, corresponded to the period 1985-1989. Since no effective parasiticide agent is available, hepatic hydatidosis must be treated surgically. Today's better knowledge and advancements in liver surgery have made it possible to extirpate the cyst completely with little risk and improved results; hepatic resection should only be considered in exceptional cases; aspiration, drainage procedures, or partial resections of the cyst yield inferior results. We have had no relapse of the hydatid disease in the liver or in any other abdominal site.

Echinococcosis, Hepatic↗

Eosinophils: a review.

The eosinophil was discovered by Jones in 1846 (Dessein and David, 1982) but its proclivity to stain with aniline dyes was first described by Paul Ehrlich in 1879 (Hirsch and Hirsch, 1980). Recognized and named for this quality, eosinophils possess an abundance of highly basic proteins within their granules which confer their affinity for acidic dyes (Gleich and Loegering, 1984). Eosinophils are traditionally viewed as killer-effector cells in parasitic infestations and as modulators of Type I hypersensitivity reactions (Butterworth and David, 1981; Kay, 1985). The eosinophils' reserve of cationic proteins and enzymes which imparts their profound parasiticidal effects (Butterworth and David, 1981) contrasts with this leukocyte's purported regulatory function in inflammation (Kay, 1985; Fechter et al., 1986). The opposing functions possessed by this leukocyte exemplify the enigma of the eosinophil. Recent evidence suggests that although the eosinophil does posses some regulatory capabilities, its presence is, in fact, a harbinger of tissue destruction (Gleich and Adolphoson, 1986, Wardlaw and Kay, 1987; Spry, 1988). Nor does the presence of the eosinophil automatically infer IgE mediated hypersensitivity, as evidenced by studies examining the interaction of the eosinophil with the cellular arm of the immune system (Basten and Beeson, 1970; Ruscetti et al., 1976; Beeson and Bass, 1977; Raghavachar et al., 1987; Ohnishi et al., 1988). The purpose of this review is to provide a brief overview of the structure and biology of the mammalian eosinophil and to emphasize the fact that eosinophils fulfil a paradoxical role as effectors of tissue damage and as benign modulators of inflammation.

Animals↗

In vitro assessment of anti-Leishmania immunity of man acquired with a vaccine.

Monocytes, obtained from a human volunteer immunized with a Leishmania infantum-derived vaccine, when cultured in vitro displayed a strong parasiticidal activity against L. major promastigotes. In addition, immune serum conferred leishmanicidal activities to monocytes of normal, unexposed donors, and to murine macrophages.

Animals↗

Control of cattle mange in southern Africa using ivermectin.

Seven trials including 768 cattle were conducted in South Africa and Namibia to evaluate the efficacy of the systemic parasiticide ivermectin when administered subcutaneously at a dose rate of 200 micrograms/kg against sarcoptic (Sarcoptes scabiei var. bovis), chorioptic (Chorioptes bovis) and psoroptic (Psoroptes ovis var. bovis) mange mites. The efficacy of a single treatment against Psoroptes and Sarcoptes was greater than against Chorioptes. There was marked clinical cure in all treated cases with loss of crusts and hair regrowth. The number of cases of psoroptic mange in two large herds, of which 42.4% of 724 animals were clinically affected prior to mass treatment, was reduced by 99.3% following a single subcutaneous treatment with ivermectin; a single animal from which mites were recovered may not have been treated. The apparent prevalence and prospects for control and eradication of cattle mange in South Africa and Namibia are discussed.

Administration, Oral↗

Differential cytotoxic effects of Annona squamosa seed extracts on human tumour cell lines: role of reactive oxygen species and glutathione.

Annonaceous acetogenins are a new class of compounds that have been reported to have potent pesticidal, parasiticidal, anti-microbial, cell growth inhibitory activities. In this study, organic and aqueous extracts from the defatted seeds of Annona squamosa (custard apple) were tested on different human tumour cell lines for antitumoural activity. While organic and aqueous extracts induced apoptosis in MCF-7 and K-562 cells, they failed to do so in COLO-205 cells. Treatment of MCF-7 and K-562 cells with organic and aqueous extracts resulted in nuclear condensation, DNA fragmentation, induction of reactive oxygen species (ROS) generation and reduced intracellular glutathione levels. In addition downregulation of Bcl-2 and PS externalization by Annexin-V staining suggested induction of apoptosis in MCF-7 and K-562 cells by both the extracts through oxidative stress. On the contrary, COLO-205 cells showed only PS externalization but no change in ROS and glutathione levels. These observations suggest that the induction of apoptosis by A. squamosa extracts can be selective for certain types of cancerous cells.

Acetogenins↗

[Effect of pasta ulmi on malaria parasites].

The extract of Pasta ulmi was examined in vivo and in vitro for antimalaria effect. During animal experiments lipophil extract appeared to have a stronger effect than whole extract, whereas the water diluted extract had no therapeutic effect. In the cell culture the isolated fraction of lipophil extract C1, C2 and C4 showed no inhibitory effect on P. falciparum, but the fraction C0 and C3 with a concentration of 10 micrograms/ml medium demonstrated a totally parasiticidal effect on parasites on the 5th day of culture.

Animals↗

Assessment of a liposomal formulation of ivermectin in rabbit after a single subcutaneous administration.

Ivermectin is a member of the macrocyclic lactone family widely used in livestock, pets, and humans as a potent parasiticide. Slight differences in formulation may change the plasma kinetics and efficacy of these compounds. The aim of the study is to evaluate the ability of a liposomal formulation of ivermectin to generate an efficient exposure of the animal to the drug. Ten rabbits were subcutaneously administered with 0.3 mg kg(-1) of ivermectin using Ivomec (n=5) or a liposomal formulation (n=5). The areas under serum concentration-time curve were similar after both treatments, indicating the same bioavailability for the two formulations. However, the liposomal formulation gave a higher C(max) value (33.33 ng ml(-1)) compared with Ivomec (20.82 ng ml(-1)) and a significantly faster absorption as indicated by the T(max) of 0.23 days compared with 1.13 days for the Ivomec formulation. The use of liposomal formulation shows promise as this system improves the efficacy of ivermectin and related drugs.

Animals↗

Flavin analogs with antimalarial activity as glutathione reductase inhibitors.

10-(4'-Chlorophenyl)-3-methylflavin has antimalarial activity in vitro and in vivo (Cowden et al., J Med Chem 31: 799, 1988). This flavin analog and two of its derivatives were found to inhibit the antioxidant flavoenzyme glutathione reductase from human erythrocytes in its isolated form as well as in hemolysates. The mixed-type inhibition was completely reversible, the Ki-values being of the order of 1 microM. Surprisingly, the drugs were not competitive with FAD, but with GSSG, one of the enzyme's substrates. Malaria parasite glutathione reductase, extracted from Plasmodium falciparum, could also be inhibited by the compounds. Studies on the effects of the substances on P. falciparum in vitro, which were demonstrated morphologically and by growth inhibition, confirmed previous observations with 10-(4'-chlorophenyl)-3-methylflavin and showed similar parasiticidal characteristics for the two new derivatives. The activities of five other erythrocytic enzymes tested were not impaired by the drugs, nor was the nucleotide metabolism of erythrocytes and/or parasites significantly changed. Permeation into red blood cells was demonstrated for one compound by 19F-NMR-spectroscopy. Inhibition of glutathione reductase might contribute to, or account for, the antimalarial activity of this group of flavin analogs.

Animals↗

Experience with doxorubicin-bound polyisohexylcyanoacrylate nanoparticles on murine alveolar echinococcosis of the liver.

The parasiticidal properties of doxorubicin against the metacestode of Echinococcus multilocularis were investigated after binding of that drug to polyisohexylcyanoacrylate nanoparticles, a colloidal biodegradable drug carrier. A reduction of the hepatic parasite development and a reduced viability of the metacestode were observed in mice injected with 5 mg kg-1 body weight-1, but 7.5 mg kg-1 body weight-1 did not appear more efficient. Free doxorubicin or unbound nanoparticles had no antiparasitic activity.

Animals↗

A fast and objective assay for cell mediated intra- and extracellular killing of Leishmania promastigotes.

An in vitro radiometric assay is described for the detection of cytolytic activity against the obligate intracellular parasite Leishmania enriettii. The assay system can be equally well applied to non-cellular (humoral), cellular non-phagocytic, and cellular phagocytic effector situations. Leishmania promastigote organisms are DNA-labeled with [methyl-3H]thymidine [( 3H]dThd) with high efficiency. Spontaneous label release remains very low even in non-ideal culture conditions. We have modeled a leishmanicidal situation by co-cultivating L. enriettii with starch-elicited murine peritoneal macrophages for different time periods. At an effector-to-target ratio of 1:6 a highly significant [3H]dThd release can be observed after 4 h of co-cultivation, reaching 60% after 18 h. The principle advantages of this assay system are speed, high sensitivity and objectivity. This makes it suitable for mass screening of, e.g., immunomodulatory or parasiticidal agents and equally useful in both phagocytic and non-phagocytic situations.

Animals↗

A flow cytometric method for assessing viability of intraerythrocytic hemoparasites.

We have developed a rapid, reliable method of evaluating growth and viability of intraerythrocytic protozoan hemoparasites. The assay involves the selective uptake and metabolic conversion of hydroethidine to ethidium by live parasites present in intact erythrocytes. The red fluorescence imparted by ethidium intercalated into the DNA of the parasite permits the use of flow cytometry to distinguish infected erythrocytes with viable parasites from uninfected erythrocytes and erythrocytes containing dead parasites. Comparison of the fluorochromasia technique of enumerating the number and viability of hemoparasites in cultured erythrocytes with enumeration in Giemsa-stained films and uptake of [3H]hypoxanthine demonstrated the fluorochromasia technique yields comparable results. Studies with the hemoparasite, Babesia bovis, have shown the fluorochromasia technique can also be used to monitor the effect of parasiticidal drugs on parasites in vitro. The cumulative studies with the fluorochromasia assay suggest the assay will also prove useful in investigations focused on analysis of the immune response to hemoparasites and growth in vitro.

Animals↗

Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid during treatment of Trypanosoma gambiense infection in Côte d'Ivoire.

Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid (CSF) were determined in 11 patients with Trypanosoma gambiense infection without involvement of the central nervous system in Côte d'Ivoire. Blood samples were drawn during a 48 h period after the first and last dose of pentamidine dimesylate given as 10 intramuscular injections on alternate days. Maximum plasma concentrations were generally attained within one hour after injection but varied extensively (420-13420 nmol/litre). The median plasma concentration 48 h after the last dose was approximately 5 times higher than that after the first dose. The ratio between whole blood and plasma concentration was approximately 2. Small amounts of the drug were found in the CSF after the last dose. The findings showed inter-individual differences in the pharmacokinetics of pentamidine. The currently recommended daily dose regimen could be questioned, as drug accumulation was pronounced. All patients were cured and the concentrations attained should be considered as parasiticidal. Further studies on the kinetics and distribution after single and multiple doses of pentamidine as well as studies on the possible relationship between adverse effects and plasma concentrations are, however, needed.

Adolescent↗

Long-term exposure of Trypanosoma brucei gambiense to pentamidine in vitro.

In order to study the sensitivity in vitro of Trypanosoma brucei gambiense to pentamidine, 5 x 10(4) parasites were exposed to 0, 0.1, 1.0, 2.0, 10, 100, 1000 and 10,000 micrograms/L of pentamidine isethionate for up to 10 d. The viability of parasites was determined each day by microscopy. Multiplication was retarded during continuous exposure to 2 micrograms/L. After 4 d no further multiplication took place, although the trypanosomes remained alive for another 3 d. The parasiticidal effect was more pronounced when higher concentrations were used; when exposed to 10 and 100 micrograms/L, all parasites were dead after 4 and 3 d, respectively. Despite exposure to 1000 micrograms/L, 74% of the parasites were still alive the next day. 10,000 micrograms/L killed all parasites within 24 h of exposure. Our results show that the time period of exposure to pentamidine plays a major role in determining the sensitivity in vitro of T. b. gambiense, and we suggest that prolonged exposure in vivo may be more important than attaining high but brief peak concentrations.

Animals↗

Molecular vaccines against animal parasites.

Vaccines against parasites have been significantly more difficult to develop than vaccines for other infectious agents. However much has been published within the very recent past which indicates that it is not only possible to induce protective immune responses to a broad range of parasites of veterinary importance with subunit materials but it appears that cross-isolate and cross-species immunogens may be obtainable. Advances in molecular immunology now provide technical approaches to vaccine design which directly address the question of improving the immunogenicity of parasite vaccines and the very wide potential range of prospective live vectors for recombinant vaccine antigens help to ensure the availability of practical commercial vaccine vectors for the future. From the technical-scientific aspect therefore the feasibility for developing molecular parasite vaccines for animal health is sound. On the commercial side, the need to keep discovering novel and effective parasiticidal drugs because of resistance development presents a major financial and research burden. Growing concerns on drug residues and environmental issues mitigates in favour of controlling parasitic diseases by biological methods among which vaccines would appear to be pre-eminently suitable. It is conceivable that we are now coming to the end of the era in which animal parasites are controlled very well by prophylactic chemotherapy and slowly moving into an era where vaccination will prevail. The deployment of molecular parasite vaccines in animal health can be envisaged within five years.

Animals↗

Elimination of the gametocytes of Theileria annulata of cattle by primaquin phosphate.

Calves were experimentally infected with Theileria annulata and five drugs were administered in an attempt to exterminate the gametocytes of the parasite. The results of the experiment proved that primaquin phosphate is an effective parasiticide. The gametocytes from 30 calves treated with primaquin phosphate were exterminated completely. A further eight calves were treated with sulfamethoxypyrazine, trimethoprim, naganin and acaprin, but these drugs were not found to be effective in eliminating the gametocytes. The phase, size and colour of the gametocytes in these calves were the same as those of the four untreated control calves.

Animals↗

A review of regional and temporal use of avermectins in cattle and horses worldwide.

Ivermectin and abamectin are two members of the group of parasiticides known as the avermectins; ivermectin was first registered as an injectable treatment for cattle in 1981. Since then, abamectin has been registered for cattle and ivermectin for horses. The relative popularity of the avermectins amongst farmers and veterinarians can be attributed to their spectrum of activity, convenience, wide margin of safety and the improved health and performance of stock following their use. Patterns of use in grazing animals apply equally to the avermectins as to other antiparasitics, particularly anthelmintics; these are based on a knowledge of epidemiology integrated with practical management considerations. For cattle, programs are commonly aimed at control of abomasal nematodes of the genera Ostertagia and Haemonchus. Use of avermectins is largely strategic in cattle, treatments being favored at the end of the period of transmission of these parasites; this frequently coincides with housing, entry into a feedlot or movement to another pasture. Simultaneous control of important ectoparasites at this time is an added benefit. Prophylactic use of avermectins at pasture is primarily targeted at the young first season grazing animal. In horses, a bimonthly treatment schedule during the period of risk has proved effective in helping prevent adverse effects of the main target parasites, including large and small strongyles and stomach bots. These patterns of use can be applied to the evaluation of the potential for avermectin residues in feces to have impact on pasture ecology. The evidence presented suggests that any effects are temporally and spatially limited. After more than a decade of practical use, there is no indication that avermectins have had a significant impact on pasture ecology and the environment.

Animals↗