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)

The inflammatory nature of multiple sclerosis (MS) implicates the participation of cytokines as immune response mediators. Targeting the cytokine balance by downregulating proinflammatory cytokines and/or upregulating immunosuppressive cytokines could benefit patients with MS. This article reports on the in vitro effects of the phosphodiesterase i.v. inhibitor Rolipram on the production of pro- and anti-inflammatory cytokines in MS and, for reference, in myasthenia gravis (MG). Blood mononuclear cells (MNC) were cultured in the presence of the organ-specific autoantigens myelin basic protein (MBP) or acetylcholine receptor (AChR), and in the absence of antigens, with and without Rolipram. In situ hybridization with synthetic oligonucleotide probes was used to detect and enumerate blood MNC expressing IFN-gamma, TNF-alpha, LT, TGF-beta, IL-4, and IL-10 mRNA. Numbers of MNC-secreting IFN-gamma and IL-4 in blood blood were examined by ELISPOT assays. Rolipram reduced the numbers of MBP-reactive IFN-gamma- and TNF-alpha mRNA-expressing blood MNC in MS, and numbers of AChR-reactive IFN-gamma-, TNF-alpha-, and LT mRNA-positive cells in MG. In contrast, expression of the Th2 cell related IL-4 and the anti-inflammatory IL-10, and TGF-beta was not affected. These data support a role for Rolipram in the treatment of diseases such as MS.
 ...
PMID:The phosphodiesterase i.v. inhibitor rolipram in vitro reduces the numbers of MBP-reactive IFN-gamma and TNF-alpha mRNA expressing blood mononuclear cells in patients with multiple sclerosis. 970 65

Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are T cell-dependent antibody-mediated autoimmune disorders, in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. DNA microarray analysis revealed increased levels of several phosphodiesterase (PDE) subtypes in lymph node cells (LNC) and muscles of EAMG rats compared with healthy controls. Quantitative real-time PCR analysis indicated that EAMG is characterized by an increase of PDE subtypes 1, 3, 4, and 7 in LNC and of PDE subtypes 2, 3, 4, and 7 in muscles. Pentoxifylline (PTX), a general PDE inhibitor, inhibited the progression of EAMG when treatment started at either the acute or chronic stages of disease. This suppression was associated with down-regulation of humoral and cellular AChR-specific responses, as well as down-regulation of PDE4, TNF-alpha, IL-18, IL-12, and IL-10 in LNC and of PDEs 1, 4, 7, and TNF-alpha in muscles. The expression of Foxp3, a transcription factor essential for CD4+CD25+ regulatory T cell function, was increased in splenocytes although the number of these cells remained unchanged. PTX also reduced the expression of the endopeptidase cathepsin-l, a marker of muscle damage, in EAMG muscles. This study demonstrates the involvement of PDE regulation in EAMG pathogenesis and suggests that PDE inhibitors may be considered for immunotherapy of MG.
 ...
PMID:Overexpression of phosphodiesterases in experimental autoimmune myasthenia gravis: suppression of disease by a phosphodiesterase inhibitor. 1636 86

Myasthenia gravis (MG) is frequently treated by corticosteroids such as methylprednisolone. However, continuous treatment with steroids often results in adverse effects. In the present study we evaluated the therapeutic potential of a combination of suboptimal doses of methylprednisolone (Solumedrol) and Pentoxifylline (PTX), a general phosphodiesterase (PDE) inhibitor, in rat experimental autoimmune MG (EAMG). This combined treatment resulted in a pronounced suppressive effect on EAMG and was by far more effective than each of the drugs administered separately at these low doses. The suppressive effect on EAMG was accompanied by decreased humoral and cellular responses to AChR as well as down-regulated mRNA expression levels of Th1 cytokines and IL-10 in lymph node cells and of PDE-4 and cathepsin-l in the muscle. This study demonstrates the potential of PTX as a steroid-sparing agent in the management of myasthenia gravis.
 ...
PMID:Suppression of experimental autoimmune myasthenia gravis by combination therapy: pentoxifylline as a steroid-sparing agent. 1863 63

We have previously shown that several phosphodiesterase (PDE) subtypes are up-regulated in muscles and lymph node cells (LNC) of rats with experimental autoimmune myasthenia gravis (EAMG). In the present study we investigated PDE expression during the course of EAMG and experimental allergic encephalomyelitis (EAE) and found that the up-regulated expression of selected PDE subtypes in both experimental models is correlated with disease severity. In EAMG, PDE expression is correlated also with muscle damage. A similar up-regulation of PDE was also observed in the respective human diseases, MG and multiple sclerosis (MS). Our findings suggest that change in PDE expression levels is a general phenomenon in autoimmune diseases and may also be used as a marker for disease severity.
 ...
PMID:Involvement of phosphodiesterases in autoimmune diseases. 2010 Jun 27

Neuro-ophthalmology focuses on the diagnosis and treatment of visual disorders related to the neurological system rather than the globe itself. Being a subspecialty of both neurology and ophthalmology, it requires specialized training and expertise in diseases of the eye, brain, nerves and muscles. Commonly encountered pathologies in neuro-ophthalmology include: optic neuropathies (such as optic neuritis and ischemic optic neuropathy), visual field loss (transient, constant, unexplained), transient visual loss, unspecified visual disturbances, diplopia, abnormal eye movements, thyroid eye disease, myasthenia gravis, anisocoria, and eyelid abnormalities. The current issue of "Harefuah" is dedicated to contemporary knowledge in neuro-opthalmology, and spans from studies of neuromyelitis optica (NMO), ischemic optic neuropathies, and optic neuropathies induced by phosphodiesterase inhibitors, to the management of sight-threatening carotid-cavernous fistulas, and more. These studies emphasize the importance of an interdisciplinary treatment team consisting of a neuro-ophthalmologist, a neuro-radiologist, and sometimes, even a neuro-surgeon. Such an approach may prove to be beneficial to the patient, by optimizing follow-up and treatment decisions. This issue emphasizes how a correct and timely diagnosis is of paramount significance in patients with neuro-ophthalmological disorders.
 ...
PMID:[Neuro-ophthalmology: the eye as a window to the brain]. 2351 93