Antimicrosporidial Activities of Fumagillin, TNP-470, Ovalicin, and Ovalicin Derivatives In Vitro and In Vivo

Didier, Peter J.; Phillips, Jennifer N; Kuebler, Dorothy; Nasr, Mohamed; Brindley, Paul J.; Stovall, Mary E.; Bowers, Lisa C.; Didier, Elizabeth S.

doi:10.1128/aac.00020-06

Cited by 65 publications

(34 citation statements)

References 54 publications

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“…Albendazole has demonstrated good antimicrosporidial activity against Encephalitozoon spp., particularly E. hellem (69,71) (in vivo and in vitro), though it is only partially active against E. bieneusi (57,73,85,105,157,162,193). The drug nitazoxanide has demonstrated activity against E. bieneusi, with the symptoms of one patient receiving nitazoxanide therapy resolving in the absence of antiretroviral therapy (22).…”

Section: Microsporidiamentioning

confidence: 99%

Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

et al. 2009

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SUMMARY Globally, the number of immunosuppressed people increases each year, with the human immunodeficiency virus (HIV) pandemic continuing to spread unabated in many parts of the world. Immunosuppression may also occur in malnourished persons, patients undergoing chemotherapy for malignancy, and those receiving immunosuppressive therapy. Components of the immune system can be functionally or genetically abnormal as a result of acquired (e.g., caused by HIV infection, lymphoma, or high-dose steroids or other immunosuppressive medications) or congenital illnesses, with more than 120 congenital immunodeficiencies described to date that either affect humoral immunity or compromise T-cell function. All individuals affected by immunosuppression are at risk of infection by opportunistic parasites (such as the microsporidia) as well as those more commonly associated with gastrointestinal disease (such as Giardia). The outcome of infection by enteric protozoan parasites is dependent on absolute CD4+ cell counts, with lower counts being associated with more severe disease, more atypical disease, and a greater risk of disseminated disease. This review summarizes our current state of knowledge on the significance of enteric parasitic protozoa as a cause of disease in immunosuppressed persons and also provides guidance on recent advances in diagnosis and therapy for the control of these important parasites.

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Section: Microsporidiamentioning

confidence: 99%

Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

et al. 2009

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“…The two most common drugs currently used to treat microsporidiosis in animals and humans are albendazole and fumagillin (10,11,12). However, most drug treatments do not fully eradicate the parasites, and preventive measures should be implemented, including the use of physical or chemical methods to destroy or inactivate infective spores present in the environment (10).…”

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confidence: 99%

Effect of Three Drugs against Encephalitozoon cuniculi Infection in Immunosuppressed Mice

Lallo

Costa

Castro³

2013

Antimicrob Agents Chemother

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bMicrosporidia comprise a large group of obligate intracellular parasites. The microsporidian Encephalitozoon cuniculi causes disseminated infection in immunosuppressed patients with HIV, cancer, or transplants and in the elderly. In vivo and in vitro studies on the effectiveness of drugs are controversial. Currently, there is no effective treatment. We tested albendazole, albendazole sulfoxide, metronidazole, and cyclosporine in mice immunosuppressed with cyclophosphamide and inoculated by the intraperitoneal route with 10 7 E. cuniculi spores. One week after experimental inoculation, the mice were treated with albendazole, albendazole sulfoxide, metronidazole, and cyclosporine. Histological and morphometric analyses were performed to compare the treated groups. The state of immunosuppression was evaluated by phenotyping CD4؉ and CD8 ؉ T cells by flow cytometry. Nontreated mice showed acute disseminated and fatal encephalitozoonosis. The treatment with benzimidazoles significantly reduced infection until 30 days posttreatment (p.t.), but at 60 days p.t., the infection had recurred. Metronidazole decreased infection by a short time, and cyclosporine was not effective. All animals were immunosuppressed by all the experiments, as demonstrated by the low number of CD4 ؉ and CD8 ؉ T cells. We conclude that no drug was effective against E. cuniculi, but the benzimidazoles controlled the infection transiently.

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“…anisopliae. [17][18][19][20] The compound consisted of C 16 H 24 O 5 with a molecular weight of 296.359, and showed anti-cancer, antifungal, anti-microsporidal, and anti-trypanosomal activities, [21][22][23] indicating that it has great potential for pharmaceutical application to various clinical fields. In initial purpose, we screened the isolate for an anti-inflammatory agent and purified it to identify the active compound as ovalicin.…”

Section: Resultsmentioning

confidence: 99%

Ovalicin Ameliorates Compound 48/80-Induced Atopic Dermatitis-Related Symptoms

Yoon¹,

Nam

Jeon³

et al. 2011

Biological & Pharmaceutical Bulletin

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It is of great concern that recent allergic diseases-including atopic dermatitis, allergic rhinitis, asthma, allergic conjunctivitis, contact dermatitis, occupational allergies, and drug allergy have become prevalent over the last few decades, especially in infants and young children in developing countries.1) These kinds of allergic symptoms may result from increasing industrial pollutants and environmental risk factors like antigens, endocrine disruptors, artificial foodstuffs, etc. Over the last several decades, the incidence of allergic diseases-especially atopic dermatitis-in developed countries has been constantly increasing 3-5 times; however, the treatment for such allergic diseases and their frequently-recurring symptoms are limited. 2)On the other hand, inflammation-related diseases-such as atopic dermatitis, allergic rhinitis and asthma-are considered chronic diseases caused by severe immune imbalances between Th1 and Th2 cell subsets.3) It has now been revealed that some of all cytokines 10,13,25, 31, 32, 33) and chemokine receptors are associated with the balance of these two subsets of T cell lineage in atopic dermatitis.4) The activation of mast cells during immune stimulation requires several kinds of events, most of which happen successively in mast cells: 1) Fc receptor-mediated triggering, 2) an increase in intracellular calcium concentration and decreased levels of cAMP signaling via a process of degranulation of mast cells, and 3) histamine or mediator release.5) A variety of signs and symptoms-vascular permeability, edema, itching, allergies, bronchial smooth muscle contraction-caused by the mediators released from mast cells then appear.6,7) If we can estimate the expression profiles between the cells, this will result in a preventive remedy against atopic dermatitis that will be especially rewarding because at present there are few potent natural agents or other non-steroidal drugs.The underlying mechanism for atopic dermatitis is still not clearly known. Temporary treatment with steroids and antihistamines relieves the symptoms, but the possibility of side effects still remains with these kinds of drugs. 8) Nevertheless, there are under researching on clinical efficacy test of chemicals or natural products. This research is guided by the activation of mast cells on atopic dermatitis-induced mast cells using a compound 48/80-induced mouse model in order to verify whether ovalicin has potential in ameliorating atopic dermatitis symptoms.In the course of screening anti-allergic agents, we found that a culture broth from Metarhizium anisopliae var. anisopliae has potential activity against atopic dermatitis-related symptoms when we used a compound 48/80-induced animal model. We isolated and purified the active constituent and finally identified the compound as ovalicin. In this report, we investigate whether ovalicin ameliorates atopic dermatitis symptoms in vivo. To further confirm the decrease of atopic dermatitis symptoms, we isolated the mast cells from mice, and examined whether the gr...

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Antimicrosporidial Activities of Fumagillin, TNP-470, Ovalicin, and Ovalicin Derivatives In Vitro and In Vivo

Cited by 65 publications

References 54 publications

Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

Effect of Three Drugs against Encephalitozoon cuniculi Infection in Immunosuppressed Mice

Ovalicin Ameliorates Compound 48/80-Induced Atopic Dermatitis-Related Symptoms

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