Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pentoxifylline (PTX), a phosphodiesterase inhibitor, is known to downregulate tumor necrosis factor-alpha (TNF-alpha) secretion induced by lipopolysacchride (LPS) and gamma interferon (IFN-gamma). We have had limited success in treating leprosy reactions, including erythema nodosum leprosum (ENL), in which TNF-alpha has been identified as a major proinflammatory cytokine. PTX inhibited production of NO (IC50 approximately equal to 1.0 mg/ml) and TNF-alpha (IC50 approximately equal to 0.05 mg/ml) in a dose-dependent fashion. As little as 0.5 mg/ml of PTX decreased NO production and 0.01 mg/ml of PTX inhibited TNF-alpha production. Western blot analyses demonstrated that iNOS was suppressed by PTX. Northern blot analyses showed significant reduction of TNF-alpha mRNA. We conclude that PTX is an effective inhibitor of lipoarabinomannan (LAM)-induced TNF-alpha production at both the product and transcriptional levels in our macrophage cell line. PTX also showed moderate inhibition of NO at the product level as well as translation of iNOS.
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PMID:Pentoxifylline downregulates nitric oxide and tumor necrosis factor-alpha induced by mycobacterial lipoarabinomannan in a macrophage cell line. 1187 67

Thalidomide has recently shown considerable promise in the treatment of a number of conditions, such as leprosy and cancer. Its effectiveness in the clinic has been ascribed to wide-ranging properties, including anti-TNF-alpha, T-cell costimulatory and antiangiogenic activity. Novel compounds with improved immunomodulatory activity and side effect profiles are also being evaluated. These include selective cytokine inhibitory drugs (SelCIDs), with greatly improved TNF-alpha inhibitory activity, and immunomodulatory drugs (IMiDs) that are structural analogs of thalidomide, with improved properties. A third group recently identified within the SelCID group, with phosphodiesterase type 4-independent activity, is in the process of being characterized in laboratory studies. This review describes the emerging immunological properties of thalidomide, from a historical context to present-day clinical applications, most notably in multiple myeloma but also in other cancers, inflammatory disease, and HIV. We also describe the laboratory studies that have led to the characterization and development of SelCIDs and IMiDs into potentially clinically relevant drugs. Early trial data suggest that these novel immunomodulatory compounds may supercede thalidomide to become established therapies, particularly in certain cancers. Further evidence is required, however, to correlate the clinical efficacy of these compounds with their known immunomodulatory, antiangiogenic, and antitumor properties.
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PMID:Immunological effects of thalidomide and its chemical and functional analogs. 1280 19

The genus Symplocos has been reviewed for its chemical constituents and biological activities including traditional importance of some common species. The plants of this genus contain terpenoids, flavonoids, lignans, phenols, steroids, alkaloids, and iridoids. Terpenoids are the major constituents within the genus Symplocos and most of them exhibit antiproliferative effects. Some phenolic glycoside derivatives showed inhibitory activity against snake-venom phosphodiesterase I and human nucleotide pyrophosphatase phosphodiesterase I. The members of genus Symplocos are well known for their traditional uses in the treatment of various diseases like leprosy, gynecological disorders, ulcers, leucorrhea, menorrhagia, malaria, and tumefaction. The aim of the present paper is to review the comprehensive knowledge of the plants of this genus including the traditional uses, chemistry, and pharmacology.
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PMID:Chemical constituents and biological applications of the genus Symplocos. 2112 48

Erythema nodosum leprosum (ENL) is a severe immune reaction commonly encountered as a complication in patients with multibacillary leprosy. Management of chronic ENL in leprosy is challenging and necessitates the use of systemic immunosuppressants, including corticosteroids and thalidomide. No single drug is universally effective and most current therapeutic agents carry a significant risk of systemic toxicity. Apremilast is an orally effective phosphodiesterase-4 inhibitor with a potent immunomodulatory action and is clinically effective in inflammatory conditions like chronic plaque psoriasis. We report two patients with poorly controlled chronic ENL, despite the use of multiple therapeutic agents. Both patients demonstrated significant clinical improvement with apremilast, without any adverse effects, thereby suggesting its potential as a novel therapeutic option in chronic ENL. What's already known about this topic? Erythema nodosum leprosum (ENL) is an immune-mediated reaction in patients with multibacillary leprosy, with chronicity and recurrences frequently reported. Management of chronic ENL requires systemic immunosuppressants like corticosteroids, which may not be universally effective and carry a risk of serious toxicity. Apremilast is an oral immunomodulator with good efficacy in inflammatory conditions like chronic plaque psoriasis. What does this study? Apremilast may be an effective therapeutic agent in patients with chronic ENL.
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PMID:Apremilast in chronic recalcitrant erythema nodosum leprosum: a report of two cases. 3162 Oct 65