Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 43 year old woman presented with chronic eosinophilic pneumonia characterised by a high alveolar eosinophilic count, which allowed biochemical study of these cells. Alveolar eosinophils spontaneously produced high amounts of oxygen free radicals and exhibited an increased level of cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) activity compared to blood eosinophils from control or allergic subjects. This activity was preferentially located in the plasma membrane, whilst the PDE activity of blood eosinophils from asthmatics or controls predominated in the cytosol. Because of the potential role of phosphodiesterase during eosinophil activation and recruitment, phosphodiesterase inhibitors may be useful in the treatment of eosinophilic pneumonia.
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PMID:Increased respiratory burst and phosphodiesterase activity in alveolar eosinophils in chronic eosinophilic pneumonia. 877 80

Prostaglandin E(2) is a potent lipid mediator of inflammation that effects changes in cell functions through ligation of four distinct G protein-coupled receptors (E-prostanoid (EP)1, EP2, EP3, and EP4). During pneumonia, PGE(2) production is enhanced. In the present study, we sought to assess the effect of endogenously produced and exogenously added PGE(2) on FcRgamma-mediated phagocytosis of bacterial pathogens by alveolar macrophages (AMs), which are critical participants in lung innate immunity. We also sought to characterize the EP receptor signaling pathways responsible for these effects. PGE(2) (1-1000 nM) dose-dependently suppressed the phagocytosis by rat AMs of IgG-opsonized erythrocytes, immune serum-opsonized Klebsiella pneumoniae, and IgG-opsonized Escherichia coli. Conversely, phagocytosis was stimulated by pretreatment with the cyclooxygenase inhibitor indomethacin. PGE(2) suppression of phagocytosis was associated with enhanced intracellular cAMP production. Experiments using both forskolin (adenylate cyclase activator) and rolipram (phosphodiesterase IV inhibitor) confirmed the inhibitory effect of cAMP stimulation. Immunoblot analysis of rat AMs identified expression of only EP2 and EP3 receptors. The selective EP2 agonist butaprost, but neither the EP1/EP3 agonist sulprostone nor the EP4-selective agonist ONO-AE1-329, mimicked the effects of PGE(2) on phagocytosis and cAMP stimulation. Additionally, the EP2 antagonist AH-6809 abrogated the inhibitory effects of both PGE(2) and butaprost. We confirmed the specificity of our results by showing that AMs from EP2-deficient mice were resistant to the inhibitory effects of PGE(2). Our data support a negative regulatory role for PGE(2) on the antimicrobial activity of AMs, which has important implications for future efforts to prevent and treat bacterial pneumonia.
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PMID:Prostaglandin E2 inhibits alveolar macrophage phagocytosis through an E-prostanoid 2 receptor-mediated increase in intracellular cyclic AMP. 1521 Aug 17

Pulmonary hypertension is a severe life-limitating disease often affecting younger patients. The connection between HIV infection and the development of pulmonary hypertension is well documented. The underlying pathobiology still remains unclear. Given that the prognosis of HIV infection has been improved by highly active antiretroviral therapy (HAART), severe pulmonary hypertension is becoming a life-limiting factor.HIV patients suffering from exercise-induced dyspnea should be tested for pulmonary hypertension, if other pulmonary or cardiac disorders (e. g., restrictive or obstructive ventilation disorders, pneumonia, coronary heart disease) can be excluded. The incidence of pulmonary hypertension is 1,000 times higher in HIV patients as compared to the general population. Estimated numbers of unreported cases are not included.A suspected diagnosis of pulmonary hypertension can be substantiated by noninvasive diagnostic methods (e. g., echocardiography), however, right heart catheterization remains the diagnostic gold standard. As new therapeutic options with prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors are now available, early and accurate diagnosis is essential.
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PMID:[HIV-associated pulmonary hypertension ]. 1617 Jun 78

We have previously reported that the phosphodiesterase inhibitor cilostazol, an antiplatelet agent, is effective and safe for secondary prevention of recurrent cerebral infarction (Cilostazol Stroke Prevention Study; CSPS). We now report the efficacy of this drug in the prevention of pneumonia in the chronic stage of cerebral infarction as a part of our CSPS subgroup analysis. The analysis was conducted in 1,049 subjects; 524 in the cilostazol group and 525 in the placebo group. The incidences of pneumonia during the 3.3-year follow-up were 2.86% (15 in 525 patients) in the placebo group and 0.57% (3 in 524 patients) in the cilostazol group, with a significant reduction in the cilostazol group. The rates of complications and pneumonia risk factors showed no difference between the two groups. We conclude that the administration of cilostazol to patients with cerebral infarction in the chronic stage does not only reduce the recurrence of infarction but also the incidence of pneumonia at least in Japanese patients.
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PMID:Antiplatelet cilostazol is effective in the prevention of pneumonia in ischemic stroke patients in the chronic stage. 1664 67

Type IV pili (Tfp) are polar surface structures of Pseudomonas aeruginosa required for twitching motility, biofilm formation and adherence. One protein required for the assembly of tfp is FimX, which possesses both GGDEF and EAL domains characteristic of diguanylate cyclases and phosphodiesterases respectively. In this work we demonstrate that FimX has phosphodiesterase activity towards bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), but does not show diguanylate cyclase activity. Instead, the imperfect GGDEF domain of FimX likely serves to activate phosphodiesterase activity when bound to GTP, as has recently been described for the Caulobacter crescentus composite GGDEF-EAL protein, CC3396. Bacteria expressing FimX in which either the GGDEF or EAL domain is deleted or mutated have phenotypes indistinguishable from a DeltafimX strain, demonstrating the importance of both domains to function. Previous work has shown that FimX localizes to the bacterial pole. In this work we show that restriction of FimX to a single pole requires intact GGDEF and EAL domains. Deletion of the amino-terminal REC domain of FimX, which contains a putative polar localization signal, results in a protein that still supports intermediate levels of pilus assembly and function. RFP-FimXDeltaREC, unlike RFP-FimX, is no longer localized to the bacterial pole, while transmission electron microscopy shows that surface pili can originate from non-polar sites in this mutant. Although DeltafimX mutants show limited in vitro cytotoxicity, they are as virulent as the wild-type strain in a murine model of acute pneumonia.
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PMID:Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa. 1667 12

Pneumonia is a common complication with the highest attributable proportion of deaths in patients with stroke. Cilostazol is a potent type III phosphodiesterase inhibitor, approved as an anti-platelet aggregation agent. The present study was designed to determine the protective mechanism of cilostazol against post-stroke pneumonia using a rat chronic cerebral hypoperfusion model. Rats were subjected to bilateral common carotid artery ligation (LBCCA) and divided randomly into the vehicle group (n=72) and cilostazol group (n=72). Rats of each group were sacrificed at baseline and at days 14, 28 and 42 after LBCCA. Cilostazol significantly improved the swallowing reflex by shortening the latency to elicited swallowing and increasing the numbers of swallows (P<0.05) at 14 days of hypoperfusion. It also decreased the numbers of bacterial colonies grown in cultures from homogenized lungs. Cilostazol markedly upregulated cyclic AMP responsive element binding protein (CREB) phosphorylation, increased tyrosine hydroxylase (TH) expression in the substantial nigra, and maintained dopamine (84.7+/-2.3 vs. 79.2+/-4.1% control; P=0.0512) and substance P levels (86.6+/-7.9 vs. 73.9+/-6.5% control; P<0.05) in the striatum, compared with the vehicle group. Our results indicate that cilostazol improves the swallowing reflex by enhancing the expression of TH through the CREB phosphorylation signaling pathway, and suggest that cilostazol could be useful in preventing pneumonia in the chronic stage of stroke.
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PMID:Activation of tyrosine hydroxylase prevents pneumonia in a rat chronic cerebral hypoperfusion model. 1903 75

Nearly two thirds of patients with cancer will undergo radiation therapy as part of their treatment plan. Given the increased use of radiation therapy and the growing number of cancer survivors, family physicians will increasingly care for patients experiencing adverse effects of radiation. Selective serotonin reuptake inhibitors have been shown to significantly improve symptoms of depression in patients undergoing chemotherapy, although they have little effect on cancer-related fatigue. Radiation dermatitis is treated with topical steroids and emollient creams. Skin washing with a mild, unscented soap is acceptable. Cardiovascular disease is a well-established adverse effect in patients receiving radiation therapy, although there are no consensus recommendations for cardiovascular screening in this population. Radiation pneumonitis is treated with oral prednisone and pentoxifylline. Radiation esophagitis is treated with dietary modification, proton pump inhibitors, promotility agents, and viscous lidocaine. Radiation-induced emesis is ameliorated with 5-hydroxytryptamine3 receptor antagonists and steroids. Symptomatic treatments for chronic radiation cystitis include anticholinergic agents and phenazopyridine. Sexual dysfunction from radiation therapy includes erectile dysfunction and vaginal stenosis, which are treated with phosphodiesterase type 5 inhibitors and vaginal dilators, respectively.
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PMID:Managing the adverse effects of radiation therapy. 2070 69

Surgical excellence in pulmonary thromboendarterectomy (PTE) for chronic thromboembolic pulmonary hypertension (CTEPH) has begun to spread around the world. The perioperative mortality for this procedure is typically under 10%. The maximal benefit from PTE is derived in those patients who have a high proximal clot burden that is surgically accessible, as outlined by the Jamieson classification. Residual pulmonary hypertension after successful PTE is common and increasingly is managed with maintenance oral pulmonary vasodilator therapy such as endothelin antagonists, phosphodiesterase inhibitors, and/or prostaglandins. The role of pulmonary vasodilator therapy in CTEPH before PTE is limited and should not delay definitive surgical therapy. Although plain deep hypothermic circulatory arrest (DHCA) is the classic technique for CTEPH, alternatives such as DHCA with antegrade cerebral perfusion are feasible as well. Prolonged mechanical ventilation after PTE remains common in part because of reperfusion pulmonary edema. Careful perioperative management can reduce the incidence of this syndrome. Because ventilator-associated pneumonia is also a common complication after PTE, it represents a major opportunity for outcome improvement, particularly because there are multiple modalities for its prevention and prompt diagnosis.
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PMID:Recent advances in chronic thromboembolic pulmonary hypertension. 2162 Jul 30

The significance of acute exacerbations in chronic obstructive pulmonary disease (AECOPDs) is increasingly appreciated. AECOPDs result in significant morbidity and mortality and are a significant driver of health care costs. Frequent AECOPDs are associated with poor quality of life and more rapid decline in lung function. As such, reducing their frequency or severity is a key paradigm of COPD therapy. Bronchodilators alone and in combination with inhaled corticosteroids are the current standards of care and decrease AECOPDs. Prevention of infection with chronic macrolide antibiotics or pulsed quinolones has demonstrated some promise. Vaccination against Streptococcus pneumonia and influenza is likely beneficial. Therapeutics with antiinflammatory properties, including phosphodiesterase enzyme 4 inhibitors and HMG-CoA reductase inhibitors, may reduce AECOPD frequency. Inhibiting the formation of reactive oxidant species has also been studied, with varying results. Antioxidants, including N-acetylcysteine and S-carbomethylcysteine, may reduce exacerbation frequency, but further investigation is needed. As new therapies are developed, it will be helpful to know in which patient phenotypes they are most effective and how they compare in efficacy and side-effect profiles with inhaled coricosteroids, bronchodilators, or their combination.
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PMID:Pharmacotherapeutic approaches to preventing acute exacerbations of chronic obstructive pulmonary disease. 2181 92

Cyclic di-AMP (c-di-AMP) and cyclic di-GMP (c-di-GMP) are signaling molecules that play important roles in bacterial biology and pathogenesis. However, these nucleotides have not been explored in Streptococcus pneumoniae, an important bacterial pathogen. In this study, we characterized the c-di-AMP-associated genes of S. pneumoniae. The results showed that SPD_1392 (DacA) is a diadenylate cyclase that converts ATP to c-di-AMP. Both SPD_2032 (Pde1) and SPD_1153 (Pde2), which belong to the DHH subfamily 1 proteins, displayed c-di-AMP phosphodiesterase activity. Pde1 cleaved c-di-AMP into phosphoadenylyl adenosine (pApA), whereas Pde2 directly hydrolyzed c-di-AMP into AMP. Additionally, Pde2, but not Pde1, degraded pApA into AMP. Our results also demonstrated that both Pde1 and Pde2 played roles in bacterial growth, resistance to UV treatment, and virulence in a mouse pneumonia model. These results indicate that c-di-AMP homeostasis is essential for pneumococcal biology and disease.
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PMID:Two DHH subfamily 1 proteins in Streptococcus pneumoniae possess cyclic di-AMP phosphodiesterase activity and affect bacterial growth and virulence. 2401 31


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