Pneumocystis Carinii Pneumonia

Ivady, G; L, Páldy; Koltay, M; Toth, Gellert; Kovács, Zsolt

doi:10.1016/s0140-6736(67)90464-3

Cited by 69 publications

(11 citation statements)

References 8 publications

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“…Both pneumocystis infection and auto-immune processes have to be con-sidered in this role because each was present in several children listed in Table II. However, pneumocystis infection has been described in many persistently hypo-y-globulinaemic cases; and the neonatal form of this infection, with an even more intense pulmonary plasmacytosis than that in our patient, occurs without an immunoglobulin response, or one limited to IgM (Ivady et al, 1967). Coombs positivity was demonstrated in 3 patients in Table II, including the only child with hyper-y-globulinaemia comparable to that in our patient, and a similar association between auto-immunity and hyper-yglobulinaemia has been described in the experimentally thymectomized animal (Sutherland et al, 1965).…”

Section: Sibs Of 7 Children With Immunoglobulins Listed Incontrasting

confidence: 47%

Thymic alymphoplasia, monoclonal gammopathy, and Pneumocystis carinii pneumonia in an infant.

Becroft¹,

Douglas²

1968

Archives of Disease in Childhood

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Section: Sibs Of 7 Children With Immunoglobulins Listed Incontrasting

confidence: 47%

Thymic alymphoplasia, monoclonal gammopathy, and Pneumocystis carinii pneumonia in an infant.

Becroft¹,

Douglas²

1968

Archives of Disease in Childhood

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“…In the syntheses of this series of compounds, the pentamidine structure (Fig. 1A) was modified by inserting a 1,4-piperazinediyl linker between the two benzamidine groups (R ϭ amidine, compound 19). The N-substituted derivatives were obtained by a Pinner reaction performed with 4,4Ј-(1,4-piperazinediyl)bisbenzonitrile 29 and the appropriate amine.…”

Section: Resultsmentioning

confidence: 99%

“…The effective use of pentamidine isethionate for the treatment of human Pneumocystis pneumonia was first reported in 1958 (18), and the early experience with the drug was summarized in 1967 (19). Trimethoprim-sulfamethoxazole (TMP-SMZ) later became the therapy of choice for this pneumonia due to increased efficacy and reduced toxicity (16).…”

mentioning

confidence: 99%

Highly Active Anti- Pneumocystis carinii Compounds in a Library of Novel Piperazine-Linked Bisbenzamidines and Related Compounds

Cushion

Walzer

Collins

et al. 2004

Antimicrob Agents Chemother

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Trimethoprim-sulfamethoxazole and pentamidine isethionate have been used extensively for the prophylaxis and therapy of pneumonia caused by Pneumocystis jirovecii. Problems associated with toxicity and potential emerging resistance for both therapies necessitate the development of safe and effective analogs or new treatment strategies. In the present study, a library of 36 compounds was synthesized by using the pentamidine molecule as the parent compound modified by a 1,4-piperazinediyl moiety as the central linker to restrict conformation flexibility. The compounds were evaluated for anti-Pneumocystis carinii activity in a bioluminescent ATP-driven assay. Four of the compounds were highly active, with 50% inhibitory concentration (IC 50 ) values of <0.01 g/ml; four had very marked activity (IC 50 < 0.10 g/ml); ten had marked activity (IC 50 < 1.0 g/ml); nine had moderate activity (IC 50 < 10 g/ml); one had slight activity (IC 50 ‫؍‬ 34.1 g/ml); and the remaining eight did not demonstrate activity in this assay system. The high level of activity was specifically associated with an alkyl chain length of five to six carbons attached to one of the nitrogens of the bisamidinium groups. None of the highly active compounds and only one of the very marked compounds exhibited any toxicity when evaluated in three mammalian cell lines. The strategy of substitution of 1,4-piperazine-linked bisbenzamidines produced compounds with the highest level of activity observed in the ATP assay and holds great promise for the development of efficacious anti-P. carinii therapy.Despite advances in the treatment of human immunodeficiency virus infection, Pneumocystis jirovecii pneumonia remains a leading cause of opportunistic infection and mortality in human immunodeficiency virus-infected patients. Currently available anti-Pneumocystis drugs are limited by significant problems of efficacy, toxicity, and emerging resistance (14,21,37,38). No member of the genus Pneumocystis can be maintained continuously outside the mammalian lung. Thus, drug development, as well as other aspects of investigation of this organism family, has been hindered.The effective use of pentamidine isethionate for the treatment of human Pneumocystis pneumonia was first reported in 1958 (18), and the early experience with the drug was summarized in 1967 (19). Trimethoprim-sulfamethoxazole (TMP-SMZ) later became the therapy of choice for this pneumonia due to increased efficacy and reduced toxicity (16). Despite concerted efforts focusing on modifications of the dihydrofolate reductase and dihydropteroate inhibitor portions of TMP-SMZ and the diamidine structure of pentamidine, no compound with increased anti-Pneumocystis carinii properties without toxicity has emerged as a clinical drug (11). With the potential problem of emerging resistance to the sulfa component of TMP-SMZ (1, 21, 26), the significant failure rate of prophylactic pentamidine, and its limited spectrum (17) and associated toxicity (2), it is necessary to identify new therapies or modifications of ...

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“…This organism, first described by Chagas in 1909, and named by Delanoe and Delanoe in 1912, was first reported t o produce pneumonia in 1942 (van der Meer and Brug, 1942). Since t h a t time the disease has been reported with increasing frequency in patients with impaired host resistance (Vogel et al, 1968), and until the introduction of the antiprotozoan agent, pentamidine isethionate (Ivady et al, 1963), treatment of the infection had been uniformly unsuccessful (Gajdusek, 1957).…”

Section: Introductionmentioning

confidence: 99%

An evaluation of the mechanism of action of pentamidine isethionate

Bornstein

Yarbro

1970

Journal of Surgical Oncology

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The effect of pentamidine on DNA, RNA, phospholipid, and protein synthesis was evaluated in 6C3HED ascites tumor of C3H mice by incorporation in vitro of 3H-thymidine, 3H-uridine, 3H-algal protein hydrolysate, and 32P-orthophosphate. Inhibition of all parameters measured was observed, suggesting that pentamidine does not, as has been suggested, selectively inhibit DNA synthesis or act as an antifol. A reduced incorporation of 32P into charcoal adsorbable acid soluble phosphate was observed, suggesting that pentamidine may impair nucleotide formation.

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Pneumocystis Carinii Pneumonia

Cited by 69 publications

References 8 publications

Thymic alymphoplasia, monoclonal gammopathy, and Pneumocystis carinii pneumonia in an infant.

Thymic alymphoplasia, monoclonal gammopathy, and Pneumocystis carinii pneumonia in an infant.

Highly Active Anti- Pneumocystis carinii Compounds in a Library of Novel Piperazine-Linked Bisbenzamidines and Related Compounds

An evaluation of the mechanism of action of pentamidine isethionate

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