Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

Bonnevie, O; Svendsen, Lars Bo; Holst-Christensen, J; Johansen, Torben; Söltoft, J.; Christiansen, P. M.

doi:10.1136/gut.20.7.624

Cited by 16 publications

(4 citation statements)

References 15 publications

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“…(35); oral medication of ulcer patients with pepstatin A at 700 mg/day for 6 weeks did not cause any side effects (36). It was not the purpose of this preliminary study to determine accurately a decrease of released virus particles or the activity of the RT, because these parameters do not necessarily reflect viral infectivity.…”

Section: Discussionmentioning

confidence: 96%

Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A.

Seelmeier

Schmidt²,

Türk³

et al. 1988

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

301

149

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The protease encoded by the human immunodeficiency virus (H1V) processes the viral gag and gag-pol protein precursor by posttranslational cleavage. In this study we have demonstrated by site-specific mutagenesis (Asp -* Thr) and by pepstatin A inhibition that the recombinant HIV protease is an aspartic-type protease. Furthermore, incubation of HIV-infected H9 cells with pepstatin A inhibited part of the intracellular processing of the HIV gag protein yet had no apparent toxicity on HIV-infected cells during 48 hr of incubation.

show abstract

Section: Discussionmentioning

confidence: 96%

Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A.

Seelmeier

Schmidt²,

Türk³

et al. 1988

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

301

149

View full text Add to dashboard Cite

show abstract

“…Drugs with antipepsin activity have been used in several clinical studies in patients with peptic ulcer but were found not to be effective. Examples are amylopectin sulphate [ 70 – 72 ] and pepstatin [ 73 ].…”

Section: Medical Therapymentioning

confidence: 99%

Reflux Revisited: Advancing the Role of Pepsin

Bardhan

Strugala

Dettmar

2012

International Journal of Otolaryngology

133

129

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Gastroesophageal reflux disease is mediated principally by acid. Today, we recognise reflux reaches beyond the esophagus, where pepsin, not acid, causes damage. Extraesophageal reflux occurs both as liquid and probably aerosol, the latter with a further reach. Pepsin is stable up to pH 7 and regains activity after reacidification. The enzyme adheres to laryngeal cells, depletes its defences, and causes further damage internally after its endocytosis. Extraesophageal reflux can today be detected by recognising pharyngeal acidification using a miniaturised pH probe and by the identification of pepsin in saliva and in exhaled breath condensate by a rapid, sensitive, and specific immunoassay. Proton pump inhibitors do not help the majority with extraesophageal reflux but specifically formulated alginates, which sieve pepsin, give benefit. These new insights may lead to the development of novel drugs that dramatically reduce pepsinogen secretion, block the effects of adherent pepsin, and give corresponding clinical benefit. “For now we see through a glass, darkly.” —First epistle, Chapter 13, Corinthians

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“…New therapies to reduce apoptotic cell death during AKI are already under study (caspase inhibitors 37 , p53 inhibitors 38 and PARP inhibitors 39 ). Pepstatin A have been safely used in clinical trials for duodenal ulcer 40 41 however, it presents problems such as poor solubility and low bioavailability. New drugs against CtsD can be developed 42 , allowing more effective and better targeting of CtsD.…”

Section: Discussionmentioning

confidence: 99%

Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury

Cocchiaro

Fox

Tregidgo

et al. 2016

Sci Rep

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Acute kidney injury (AKI) is an abrupt reduction in kidney function caused by different pathological processes. It is associated with a significant morbidity and mortality in the acute phase and an increased risk of developing End Stage Renal Disease. Despite the progress in the management of the disease, mortality rates in the last five decades remain unchanged at around 50%. Therefore there is an urgent need to find new therapeutic strategies to treat AKI. Lysosomal proteases, particularly Cathepsin D (CtsD), play multiple roles in apoptosis however, their role in AKI is still unknown. Here we describe a novel role for CtsD in AKI. CtsD expression was upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion (IRI) induced AKI. CtsD inhibition using Pepstatin A led to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or IRI induced AKI. Pepstatin A treatment slowed interstitial fibrosis progression following IRI induced AKI. Renal transplant biopsies with acute tubular necrosis demonstrated high levels of CtsD in damaged tubular cells. These results support a role for CtsD in apoptosis during AKI opening new avenues for the treatment of AKI by targeting lysosomal proteases.

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Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

Cited by 16 publications

References 15 publications

Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A.

Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A.

Reflux Revisited: Advancing the Role of Pepsin

Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury

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