A case of ulcerative colitis combined with esophageal ulcer

Sato, Noriyosi; Kurakata, Hidenori; Hirano, Naoki; Sakai, Kaname; Watanabe, T.; Sato, Shinji; Gomi, Shina; Takahashi, K.; Hara, Hiroshi; Hachiya, Akihiko; Igarashi, Yoshinori; Sumino, Yasukiyo; Hamatani, Shigeharu

doi:10.11641/pde.65.2_90

Cited by 3 publications

(3 citation statements)

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“…Until very recently, the parasite has been effectively treated with chloroquine, but resistance to this drug has now been reported in several areas (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Affordable alternative treatments for vivax malaria are urgently needed.…”

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confidence: 99%

Pyrimethamine and WR99210 exert opposing selection on dihydrofolate reductase from Plasmodium vivax

Hastings

Sibley

2002

Proc. Natl. Acad. Sci. U.S.A.

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Plasmodium vivax is a major public health problem in Asia and South and Central America where it is most prevalent. Until very recently, the parasite has been effectively treated with chloroquine, but resistance to this drug has now been reported in several areas. Affordable alternative treatments for vivax malaria are urgently needed. Pyrimethamine-sulfadoxine is an inhibitor of dihydrofolate reductase (DHFR) that has been widely used to treat chloroquine-resistant Plasmodium falciparum malaria. DHFR inhibitors have not been considered for treatment of vivax malaria, because initial trials showed poor efficacy against P. vivax. P. vivax cannot be grown in culture; the reason for its resistance to DHFR inhibitors is unknown. We show that, like P. falciparum, point mutations in the dhfr gene can cause resistance to pyrimethamine in P. vivax. WR99210 is a novel inhibitor of DHFR, effective even against the most pyrimethamine-resistant P. falciparum strains. We have found that it is also an extremely effective inhibitor of the P. vivax DHFR, and mutations that confer high-level resistance to pyrimethamine render the P. vivax enzyme exquisitely sensitive to WR99210. These data suggest that pyrimethamine and WR99210 would exert opposing selective forces on the P. vivax population. If used in combination, these two drugs could greatly slow the selection of parasites resistant to both drugs. If that is the case, this novel class of DHFR inhibitors could provide effective and affordable treatment for chloroquine-and pyrimethamine-resistant vivax and falciparum malaria for many years to come. T he parasite Plasmodium vivax is a major public health problem in Asia and South and Central America where it is most prevalent (1). Until very recently, the parasite has been effectively treated with chloroquine, but resistance to this drug has now been reported in several areas (1-13). Affordable alternative treatments for vivax malaria are urgently needed. Pyrimethamine-sulfadoxine is an inhibitor of dihydrofolate reductase (DHFR) that has been widely used to treat chloroquineresistant Plasmodium falciparum malaria (14). DHFR inhibitors have not been considered for treatment of vivax malaria, because initial trials showed poor efficacy against P. vivax (15, 16). P. vivax cannot be grown in culture; the reason for its resistance to DHFR inhibitors is unknown.DHFR (E.C. 1.5.1.3) is a key enzyme in the metabolism of all cells. Inhibition of DHFR activity depletes the cellular pool of tetrahydrofolate, a cofactor that is essential for both DNA and protein synthesis, and specific inhibitors have been designed for both prokaryotic and eukaryotic pathogens (17). Pyrimethamine is a specific competitive inhibitor of DHFR from P. falciparum, (18) and with sulfadoxine, is one component of the antimalaria drug, Fansidar. In P. falciparum, extensive field and laboratory studies have shown that resistance to pyrimethamine is caused by point mutations in the dhfr gene (reviewed in refs. 15 and 19-21). However, in contrast to P. falciparum, P. ...

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confidence: 99%

Pyrimethamine and WR99210 exert opposing selection on dihydrofolate reductase from Plasmodium vivax

Hastings

Sibley

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…We reviewed these 20 cases and summarized their findings in Table 1 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). The average age of the patients was 28.2 years (range 14-53), and the ratio of men to women was 14:6.…”

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confidence: 99%

Esophageal Ulcers Associated with Ulcerative Colitis: A Case Series and Literature Review

et al. 2020

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Ulcerative colitis, a chronic and recurrent inflammatory disease, is localized to the colonic mucosa but can affect other organs and lead to various complications. Gastroduodenitis associated with ulcerative colitis has been reported. However, little is known about esophageal ulcers. We herein report two rare cases of esophageal ulcers associated with ulcerative colitis. Furthermore, the clinical and histological characteristics of 18 previously reported cases are summarized. This case series and literature review will encourage the accurate diagnosis and treatment of esophageal ulcers associated with ulcerative colitis.

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“…There are relatively few reports of esophageal ulcers associated with UC. Until now, there have been only 20 cases of esophageal ulcers (including ours) accompanied by UC[ 23 , 24 , 35 - 45 ]. The clinical characteristics of these patients are listed in Table 2 .…”

Section: Esophageal Mucosal Lesionsmentioning

confidence: 99%

Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: A review

Sun¹,

Zhang²,

Cheng³

et al. 2021

WJG

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Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. The colorectum is considered the chief target organ of UC, whereas upper gastrointestinal (UGI) tract manifestations are infrequent. Recently, emerging evidence has suggested that UC presents complications in esophageal, stomachic, and duodenal mucosal injuries. However, UC-related UGI tract manifestations are varied and frequently silenced or concealed. Moreover, the endoscopic and microscopic characteristics of UGI tract complicated with UC are nonspecific. Therefore, UGI involvement may be ignored by many clinicians. In addition, no standard criteria have been established for patients with UC who should undergo fibrogastroduodenoscopy. Furthermore, specific treatment recommendations may be needed for patients with UC-associated UGI lesions. Herein, we review the esophageal, gastric, and duodenal mucosal lesions of the UC-associated UGI tract, as well as the potential pathogenesis and therapy.

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A case of ulcerative colitis combined with esophageal ulcer

Cited by 3 publications

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Pyrimethamine and WR99210 exert opposing selection on dihydrofolate reductase from Plasmodium vivax

Pyrimethamine and WR99210 exert opposing selection on dihydrofolate reductase from Plasmodium vivax

Esophageal Ulcers Associated with Ulcerative Colitis: A Case Series and Literature Review

Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: A review

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