Therapeutic Approaches for Aids-Related Toxoplasmosis

Behbahani, Roya; Moshfeghi, Mersedeh; Baxter, John D.

doi:10.1177/106002809502907-819

Cited by 18 publications

(6 citation statements)

References 43 publications

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“…Atovaquone has been used alone with success as well (230). Patients infected with HIV and who show signs of previous infection as demonstrated by serologic testing and show evidence of CD4 depletion (CD4 count of Ͻ100 cells/mm 3 ) should receive primary prophylaxis with trimethoprim-sulfamethoxazole (27). In patients with AIDS who have demonstrated toxoplasmic chorioretinitis, chronic suppressive therapy with sulfadiazine, pyrimethamine, and folinic acid should continue indefinitely following initial therapy.…”

Section: Ocular Disease Caused By Protozoansmentioning

confidence: 99%

Fungal and Parasitic Infections of the Eye

et al. 2000

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SUMMARY The unique structure of the human eye as well as exposure of the eye directly to the environment renders it vulnerable to a number of uncommon infectious diseases caused by fungi and parasites. Host defenses directed against these microorganisms, once anatomical barriers are breached, are often insufficient to prevent loss of vision. Therefore, the timely identification and treatment of the involved microorganisms are paramount. The anatomy of the eye and its surrounding structures is presented with an emphasis upon the association of the anatomy with specific infection of fungi and parasites. For example, filamentous fungal infections of the eye are usually due to penetrating trauma by objects contaminated by vegetable matter of the cornea or globe or, by extension, of infection from adjacent paranasal sinuses. Fungal endophthalmitis and chorioretinitis, on the other hand, are usually the result of antecedent fungemia seeding the ocular tissue. Candida spp. are the most common cause of endogenous endophthalmitis, although initial infection with the dimorphic fungi may lead to infection and scarring of the chorioretina. Contact lens wear is associated with keratitis caused by yeasts, filamentous fungi, and Acanthamoebae spp. Most parasitic infections of the eye, however, arise following bloodborne carriage of the microorganism to the eye or adjacent structures.

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Section: Ocular Disease Caused By Protozoansmentioning

confidence: 99%

Fungal and Parasitic Infections of the Eye

et al. 2000

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Section: Ocular Disease Caused By Protozoansmentioning

confidence: 99%

Fungal and Parasitic Infections of the Eye

Klotz

Penn

Negvesky

et al. 2000

Clinical Microbiology Reviews

181

145

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“…29,30 Two of the most prevalent opportunistic infections which are the major cause of mortality in patients with AIDS are caused by Pneumocystis carinii (pc) 31 and Toxoplasma gondii (tg). 32 Several nonclassical 2,4-diaminopyrido[2,3-d]pyrimidines, 33 quinazolines, 34 pyrrolo[2,3-d]pyrimidines, 5,8,[33][34][35] and furo[2,3-d]pyrimidines 36 have been evaluated as inhibitors of P. carinii and T. gondii DHFR. Some of these have been found to be selective for DHFR from these pathogens.…”

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confidence: 99%

Synthesis, Antifolate, and Antitumor Activities of Classical and Nonclassical 2-Amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines

et al. 2001

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Classical and nonclassical isosteric C8-N9 bridged analogues of the multitargeted antifolate LY231514 were synthesized as inhibitors of thymidylate synthase (TS), dihydrofolate reductase (DHFR), and as antitumor and antiopportunistic infection agents. The syntheses of the analogues were accomplished by reductive amination of the appropriate anilines with 2-amino-4-oxo-5-cyanopyrrolo[2,3-d]pyrimidine (28) followed by saponification of the ethyl esters, for the classical analogue 6. The N9-methyl analogues were obtained from the N9-H precursors by reductive methylation. In general, the nonclassical compounds 7-17 were similar in potency to TMP against Toxoplasma gondii DHFR, with selectivity ratios greater than 38 and 21 for 11 and 16, respectively. These compounds were poor inhibitors of Pneumocystis carinii DHFR and rat liver DHFR. The nonclassical analogues were also inactive against TS. The classical analogue 6 was a marginal inhibitor of isolated human TS (IC50 = 46 microM) and of human DHFR (IC50 = 10 microM), however, it was a potent inhibitor of the growth of two human head and neck squamous cell carcinoma cell lines and of CCRF-CEM human lymphoblastic leukemia cells in culture and was similar to LY231514 against ZR-75-1 human breast carcinoma cell line. Evaluation of 6 against MTX-resistant sublines indicated that DHFR is not the major target of 6. Metabolite protection studies of the growth inhibitory activity of 6 suggest that TS is a major target of this drug and that polyglutamyl forms of 6 may serve as the intracellular TS inhibitors. These studies also suggest that 6 has a site of action in addition to sites in the folate pathway.

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Therapeutic Approaches for Aids-Related Toxoplasmosis

Abstract: TMP/SMX remains a useful agent in prophylaxis against toxoplasmosis. Pyrimethamine/sulfadiazine is the most effective combination in the treatment of acute toxoplasmosis.

Cited by 18 publications

References 43 publications

Fungal and Parasitic Infections of the Eye

Fungal and Parasitic Infections of the Eye

Fungal and Parasitic Infections of the Eye

Synthesis, Antifolate, and Antitumor Activities of Classical and Nonclassical 2-Amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines

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