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At least 217 records · Page 12Linked to original sources

Induction of antigen-specific human cytotoxic T cells by Toxoplasma gondii.

To further the understanding of the role of T cells in immunity to the parasite Toxoplasma gondii, antigen-specific T cell clones were generated using peripheral blood mononuclear cells from seropositive individuals. Whole parasites were used to stimulate a proliferative expansion of antigen-reactive cells, followed by limiting dilution cloning in the presence of irradiated, autologous PBMC and rIL-2. Three parasite antigen-specific T cell clones expressing the CD3+ phenotype were selected for further characterization. Phenotypic analysis with monoclonal antibodies revealed two clones reactive with CD8 (RTg1 and RTg3) while the other (RTg2) phenotyped as CD4+, CD8-. When tested in a proliferation assay using a panel of different T. gondii proteins, clone RTg1 reacted with a single large protein (Mr greater than 180,000) as well as smaller components (less than 12,000), clone RTg2 reacted with a protein of Mr = 28,000 and clone RTg3 reacted with a protein of 116,000 plus smaller components (less than 12,000). Only the 28,000 = Mr antigen recognized by RTg2 was reactive on Western blot with autologous donor antisera. All three clones produced IFN-gamma and IL-2 in varying amounts upon antigenic stimulation in the presence of irradiated APC. Moreover, one clone RTg1, exhibited direct parasite cytotoxicity, inhibiting extracellular T. gondii by greater than 70% when incubated at an effector/target ratio of 40:1. This clone was alpha, beta TCR heterodimer positive and exerted its cytotoxic parasiticidal activity in the apparent absence of MHC restriction. The results provide evidence for the existence of circulating antigen-specific cytotoxic T cells in normal humans who are toxoplasma antibody seropositive.

Animals↗

Topical treatment of tungiasis: a randomized, controlled trial.

Tungiasis is caused by the penetration of the female sand flea Tunga penetrans into the epidermis of its host. Human infestation with this ectoparasite is hyper-endemic in many resource-poor communities in sub-Saharan Africa, the Caribbean and South America and is associated with considerable morbidity. Currently, there is no effective drug available to treat tungiasis (or at least none for which a parasiticidal effect has been clearly demonstrated). In an attempt to fill this gap, the effects of treatment with topical ivermectin (lotion), thiabendazole (ointment and lotion), metrifonate (lotion) or placebo lotion were compared in a randomized trial. A total of 108 subjects with 169 tungiasis-infested feet participated in the study. The results show that topical ivermectin, metrifonate or thiabendazole can each significantly reduce the number of lesions caused by embedded sand fleas. Further studies are needed to optimise the doses and administration of these compounds.

Administration, Topical↗

The types and timing of the degenerative changes seen in the cysts during and after benzimidazole treatment of cystic echinococcosis.

In a large-scale Bulgarian study, 122 patients with abdominal and/or lung echinococcosis were randomly selected for treatment with albendazole or mebendazole. The main aims were to evaluate the effect of each drug on the hydatid cysts, to follow the changes in cyst morphology during and after treatment, and to determine how quickly each drug produced the first, detectable, degenerative changes in the cysts. Follow-up was based on periodic ultrasonography, chest radiography and computed tomography. The abdominal cysts were categorised as small (<5 cm in diameter) or large. As albendazole treatment had effects that were almost identical to those of mebendazole treatment, the results for the two drugs were combined. In the lungs and, particularly, in the abdomen, the size of the cysts being treated influenced the character and timing of the degenerative changes seen in them. The initial change seen in each abdominal cyst was detachment of the endocyst, which occurred 1-3 months (small cysts) or 2-5 months (large cysts) after the initiation of treatment (P<0.05). The abdominal cysts then developed a hyper-echoic/hyper-dense appearance, became smaller, and finally disappeared 3.3-9.3 months (small cysts) or 5.6-13.9 months (large cysts) after treatment began (P<0.05). The first degenerative change noted in the lung cysts was cyst rupture, which occurred as early as day 10 of therapy but was generally observed 1 or 2 months after treatment began. After their complete evacuation, the ruptured lung cysts shrank and became deformed, some disappearing within 5-9 months of the initiation of treatment. The degenerative changes recorded, which began significantly earlier in the lung cysts than in abdominal cysts, indicate serious damage to the cysts and the parasiticidal, curative effect of each of the two benzimidazoles employed.

Adolescent↗

Head lice: changing the expensive chemotherapy culture.

The revulsion prompted by the discovery of head lice on a child's head, and the money spent by the NHS each year on supplying licensed medicines for head lice, is disproportionate to the medical impact that lice have on their hosts. This article discusses the evidence available on the effectiveness of the commonest parasiticidal preparations, and argues the case for a more rational, simpler and cost-effective response to this common problem.

Community Health Nursing↗

A rapid, reliable method of evaluating growth and viability of intraerythrocytic protozoan hemoparasites using fluorescence flow cytometry.

Fluorescence flow cytometry was employed to assess the potential of a vital dye, hydroethidine, for use in the detection and monitoring of the viability of hemoparasites in infected erythrocytes, using Babesia bovis as a model parasite. The studies demonstrated that hydroethidine is taken up by B. bovis and metabolically converted to the DNA binding fluorochrome, ethidium. Following uptake of the dye, erythrocytes containing viable parasites were readily distinguished and quantitated. Timed studies with the parasiticidal drug, Ganaseg, showed that it is possible to use the fluorochrome assay to monitor the effects of the drug on the rate of replication and viability of B. bovis in culture. The assay provides a rapid method for evaluation of the in vitro effect of drugs on hemoparasites and for analysis of the effect of various components of the immune response, such as lymphokines, monocyte products, antibodies, and effector cells (T, NK, LAK, ADCC) on the growth and viability of intraerythrocytic parasites.

Animals↗

Superoxide: a two-edged sword.

Superoxide (O2-) is the compound obtained when oxygen is reduced by one electron. For a molecule with an unpaired electron, O2- is surprisingly inert, its chief reaction being a dismutation in which it reacts with itself to form H2O2 and oxygen. The involvement of O2- in biological systems was first revealed by the discovery in 1969 of superoxide dismutase, an enzyme that catalyzes the dismutation of O2-. Since then it has been found that biological systems produce a bewildering variety of reactive oxidants, all but a few arising ultimately from O2-. These oxidants include O2- itself, H2O2 and alkyl peroxides, hydroxyl radical and other reactive oxidizing radicals, oxidized halogens and halamines, singlet oxygen, and peroxynitrite. These various oxidants are able to damage molecules in their environment, and are therefore very dangerous. They are thought to participate in the pathogenesis of a number of common diseases, including among others malignancy, by their ability to mutate the genome, and atherosclerosis, by their capacity for oxidizing lipoproteins. Their properties are put to good use, however, in host defense, where they serve as microbicidal and parasiticidal agents, and in biological signalling, where their liberation in small quantities results in redox-mediated changes in the functions of enzymes and other proteins.

Animals↗

Plasma evaluation for ivermectin in llamas (Lama glama) after standard subcutaneous dosing.

Plasma levels of the parasiticide ivermectin were studied by high-performance liquid chromatography in five llamas (Lama glama) after single 200 microg/kg s.c. injections. Ivermectin levels were undetectable in plasma samples drawn up to 4 wk after injection, suggesting that the dosage used was insufficient to reach therapeutic concentrations in this species.

Animals↗

Ivermectin toxicosis in a chameleon (Chamaeleo senegalensis) infected with Foleyella furcata.

Both male and female Foleyella furcata were found in the subcutaneous tissue and abdominal cavity of an adult male wild-caught Senegalese chameleon (Chamaeleo senegalensis). This nematode species is endemic to Madagascar but has never been recorded from the continent of Africa. Prior to the chameleon's death, a migrating worm was seen under the skin in the abdominal and thoracic region. Huge numbers of small, sheathed microfilariae were detected in the blood smears. The chameleon was treated with a single dose (0.2 mg/kg s.c.) of ivermectin. Serious adverse reactions (complete inertia) developed within 24 hr after injection and lasted for 7 days, indicating either ivermectin toxicity or a systemic reaction involving the release of endotoxins from the microfilariae dying in the bloodstream as a result of parasiticide therapy. Therefore, ivermectin treatment of chameleons infected with Foleyella should be avoided.

Animals↗

Gastrointestinal helminths of ponies in Louisiana: a comparison of species currently prevalent with those present 20 years ago.

A survey in Louisiana of gastrointestinal helminths recovered at necropsy from 117 ponies with minimal exposure to anthelmintics between 1989 and 2000 is compared with a survey conducted 20 yr earlier in the same region. An objective of this study was to determine whether species diversity has been affected by the advent and use of the macrocyclic lactone (ML) parasiticides and by the increased anthelmintic pressure on the helminth species infecting the general equine population. Twenty-six cyathostome species and 8 strongyle species were recovered. Two cyathostome species that were not found before, Cylicostephanus asymetricus and C. bidentatus, and 1 species of large strongyle, Oesophagodontus robustus, were added to the list of species found in Louisiana. All cyathostome and large strongyle species found previously were still present. But prevalences and intensities were significantly reduced for almost all large and small strongyle species. Prevalences and intensities of Oxyuris equi adults and larvae were reduced, whereas the prevalence of Parascaris equorum remained constant. The tapeworm Paranoplocephala mamillana was added to the list of parasite species found in Louisiana. Anoplocephala perfoliata remained the most common cestode. This species was found at the same level of intensity but increased slightly in prevalence. Anoplocephala magna was found less frequently than previously. The overall diversity of species remained reatively unchanged. The reasons for the differences in intensity and prevalence of strongyles between these 2 periods are unknown but might be related to the development and use of the broad-spectrum ML anthelmintics in the intervening period, a difference in the population of equids surveyed, different techniques used to identify the parasites, or differences in numbers of parasites identified (or to all).

Animals↗

Problems associated with drug residues in beef from feeds and therapy.

Drug residues in beef have been reported internationally. These include antimicrobials, anti-inflammatories, growth promotants, parasiticides and insecticides. The main factors associated with residues are animal age and use, and failure to observe withdrawal time for regular or extra-label use. Public health concerns include toxic and anaphylactic reactions, and development of drug-resistant strains of bacteria. The maximum residue level (MRL) is the current standard for residues in food adopted by the Codex Committees of the Food and Agriculture Organisation and World Health Organisation, but is not universally accepted or standardised. Detection of residues at slaughter is a critical point in residue control. Several live animal tests are available, but these vary in reliability and usage. After slaughter, tissues sampled and tests used are more uniform. To prevent international trade barriers associated with drug residues in beef, the following conditions should be implemented: standardisation of testing methods used to detect drug residues; standardisation of methods for determining MRLs; establishment of active surveillance programmes to monitor residues.

Age Factors↗

Accumulation, distribution, and toxicity of copper in sediments of catfish ponds receiving periodic copper sulfate applications.

Copper sulfate (CuSO4) is applied periodically to commercial channel catfish (Ictalurus panctatus) ponds as an algicide or parasiticide. Current understanding of the chemistry of copper in soil-water systems suggests that copper may accumulate in pond sediments, although the forms and potential bioavailability of copper in catfish pond sediments are not known. This study investigated the accumulation and distribution of copper in the sediment of catfish ponds receiving periodic additions of CuSO4.5H2O. All ponds were constructed in Sharkey (very-fine, smectitic, thermic Chromic Epiaquert) soil. Nine 0.40-ha ponds received 59 applications of 2.27 kg CuSO4.5H2O per application per pond over 3 yr; no CuSO4.5H2O applications were made to nine additional ponds. Total Cu concentration in the sediments of CuSO4.5H2O-amended catfish ponds (172.5 mg kg(-1)) was four to five times higher than that in the sediments of nonamended ponds (36.1 mg kg(-1)). Copper accumulated in catfish pond sediments at a rate of 41 microg kg(-1) dry sediment for each 1 kg ha(-1) of CuSO4. 5H2O applied to ponds. Copper in the sediments of amended ponds was mainly in the organic matter-bound (30.7%), carbonate-bound (31.8%), and amorphous iron oxide-bound (22.1%) fractions with a considerable fraction (3.4%; 3 to 8 mg kg(-1)) in soluble and exchangeable fractions. This indicates that Cu accumulates differentially in various fractions, with proportionally greater initial accumulation in potentially bioavailable forms. However, toxicity bioassays with amphipods (Hyallela azteca) and common cattail (Typha latifolia L.) indicated that the effect of exposure to amended or nonamended pond sediments was not different.

Animals↗

Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action.

The discovery that the sesquiterpene peroxide yingzhaosu A (13) and 1,2,4-trioxane artemisinin (14) are active against chloroquine-resistant strains of Plasmodium falciparum, has opened a new era in the chemotherapy of malaria. In vitro and in vivo tests with synthetic structurally simpler trioxanes clearly demonstrate that much of the skeleton of 14 is redundant and that chirality is not required for activity. In addition, structure-activity relations and the search for the pharmacophore reveal that high antimalarial activity can be displayed by molecules which do not resemble the geometry of 13 and 14 at all. The possible mode of action of 13, 14, and synthetic peroxides is examined. They are believed to kill intraerythrocytic Plasmodium by interacting with the heme discarded by proteolysis of ingested hemoglobin. Complexation of heme with the peroxide bond followed by electron transfer generates an oxy radical that evolves to the ultimate parasiticidal agent. Experiments with ferrous reagents indicate that active peroxides including 14 and its congeners kill the parasite by alkylation with a sterically non-encumbered C-centered radical. However, another possibility is the involvement of a Fe(IV)=O species as the toxic agent. The review covers our own and other contributions to this timely topic and evaluates the different mechanisms proposed for the mode of action of peroxidic antimalarials.

Animals↗

Underlying medical conditions in cats with presumptive psychogenic alopecia.

OBJECTIVE: To identify underlying medical conditions in cats with a presumptive diagnosis of psychogenic alopecia. DESIGN: Case series. ANIMALS: 21 adult cats referred with a presumptive diagnosis of psychogenic alopecia. PROCEDURES: A detailed behavior and dermatologic questionnaire was completed by the primary caregiver, and complete behavioral and dermatologic examinations were performed. A standard diagnostic testing protocol that included cytologic examination of skin scrapings, fungal culture of hairs, evaluation of responses to parasiticides and an exclusion diet, assessment for atopy and endocrinopathies, and histologic examination of skin biopsy specimens was used to establish a definitive diagnosis in all cats. Cats that did not respond to an elimination diet were treated with methylprednisolone acetate to determine whether pruritus was a factor. RESULTS: Medical causes of pruritus were identified in 16 (76%) cats. Only 2 (10%) cats were found to have only psychogenic alopecia, and an additional 3 (14%) cats had a combination of psychogenic alopecia and a medical cause of pruritus. An adverse food reaction was diagnosed in 12 (57%) cats and was suspected in an additional 2. All cats with histologic evidence of inflammation in skin biopsy specimens were determined to have a medical condition, but of 6 cats without histologic abnormalities, 4 had an adverse food reaction, atopy, or a combination of the 2, and only 2 had psychogenic alopecia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that psychogenic alopecia is overdiagnosed in cats. Thorough diagnostic testing should be done before ascribing a behavioral cause to hair loss in cats.

Alopecia↗

The significance of autoimmunity in the pathogenesis of Chagas heart disease.

Chagas heart disease develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Among the many possible mechanisms responsible for this illness, an autoimmune mechanism has received much experimental support during the past several decades. Initial observations of the absence or near absence of parasites from the inflamed tissues suggested the autoimmunity hypothesis, and the finding of measurable autoimmune responses in humans and experimental animals has bolstered this idea. The rigorous testing of the hypothesis has been difficult, primarily because other mechanisms are likely to play a role during active infection, particularly immunity to parasite antigens that may persist in the infected animal. While the role autoimmunity plays in disease pathogenesis is not known, it is clear that autoimmune responses are induced during infection of some humans and animals. A number of mechanisms may explain the induction of autoimmunity during T. cruzi infection, including parasite-induced polyclonal lymphocyte activation, molecular mimicry, bystander activation, and presentation of cryptic self epitopes. The genetic makeup of both the parasite and host are also critical to the outcome of infection. The autoimmune hypothesis deserves further exploration, while public health interventions should focus on control of the insects that transmit the parasite, development of parasiticidal drugs and vaccines, and testing of blood products, which have become an important threat of new infections.

Animals↗

Antimalarial activity of the ethanol/alcohol oxidase system in vitro.

Among other macrophage secretory products, H2O2 plays an important role in the host's defense against malaria (Wozencraft et al., Infect. Immun., 43, 664, (1984]. In our in vitro studies on the human malaria parasite Plasmodium falciparum, hydrogen peroxide was produced by the alcohol oxidase-catalyzed reaction ethanol + O2----acetaldehyde + H2O2 (EC 1.1.3.13). At concentrations of 8.7 mM (= 0.5%) ethanol and 0.1 U alcohol oxidase per ml culture, more than 95% of the parasites were irreversibly damaged. Acetaldehyde was found to be parasiticidal per se--probably by releasing immature forms of P. falciparum from erythrocytes--but CH3CHO concentrations as high as 90 mM were required for complete elimination of the parasites. Ethanol (less than 20 mM) or alcohol oxidase alone had no significant effect on parasite viability. As discussed, the ethanol/alcohol oxidase system might be of interest as a potential chemotherapeutic principle, especially since metabolism and pharmacology of the substrates and products are well understood.

Acetaldehyde↗

Effect of Australian tea tree oil on Gyrodactylus spp. infection of the three-spined stickleback Gasterosteus aculeatus.

Gyrodactylus spp. infections of commercially farmed fishes are responsible for significant economic losses. Existing treatments have proved uneconomic, stressful to the fishes, and ecologically damaging. Essential oils are naturally occurring compounds that exhibit a wide range of anti-microbial and anti-fungal activities. This study explored the possibility of using Australian tea tree (Melaleuca alternifolia) oil (TTO) to treat Gyrodactylus spp. infection on the three-spined stickleback Gasterosteus aculeatus. In the presence of 0.01 % Tween 80 as an emulsifier, TTO treatments at concentrations between 3 and 30 ppmv (parts per million by volume) lowered the prevalence and significantly reduced the parasite burden of sticklebacks naturally infected with Gyrodactylus spp. In addition, Tween 80 alone exhibited parasiticidal activity against Gyrodactylus spp. These findings show the potential of TTO in combination with Tween 80 as an effective treatment of Gyrodactylus spp. infection of fishes.

Animals↗

Heat shock protein 70 is a potential virulence factor in murine toxoplasma infection via immunomodulation of host NF-kappa B and nitric oxide.

We propose that the 70-kDa heat shock protein (HSP70) protects virulent Toxoplasma gondii from the effects of the host by immunomodulation. This hypothesis was tested using quercetin and antisense oligonucleotides targeting the start codon of the virulent T. gondii HSP70 gene. Oligonucleotides were transiently transfected into two virulent (RH, ENT) and two avirulent (ME49, C) strains of T. gondii, significantly reducing HSP70 expression in treated parasites. Virulent parasites with reduced HSP70 expression displayed reduced proliferation in vivo, as measured by the number of tachyzoites present in spleens of infected mice. They also exhibited an enhanced rate of conversion from tachyzoites to bradyzoites in vitro. Our results implicate HSP70 as a means by which virulent strains of T. gondii evade host proinflammatory responses: when RAW 264.7 cells were exposed to parasites with reduced HSP70 expression, differential expression of inducible NO synthase (iNOS) and cell NO production were observed between infections with normal and HSP70-deficient T. gondii. iNOS message levels were significantly increased when host cells were infected with HSP70 reduced virulent tachyzoites and HSP70-related inhibition of iNOS transcription resulted in altered host NO production by virulent T. gondii infection. Virulent parasites expressing reduced levels of HSP70 initiated significantly more NF-kappa B activation in host splenocytes than infections with untreated parasites. Neither proliferative ability nor conversion from tachyzoites to bradyzoites was affected by lack of HSP70 in avirulent strains of T. gondii. Furthermore, avirulent T. gondii strains induced high levels of host iNOS expression and NO production, regardless of HSP70 expression in these parasites, and inhibition of HSP70 had no significant effects on translocation of NF-kappa B to the nucleus. Therefore, the 70-kDa parasite stress protein may be part of an important survival strategy by which virulent strains down-regulate host parasiticidal mechanisms.

Active Transport, Cell Nucleus↗