Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is widely used in Japan for improving prognosis and relieving symptoms in patients suffering from ischemic stroke or bronchial asthma. These clinical applications are based on the properties of ibudilast that inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory activity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks. Ibudilast was also reported to significantly attenuate inflammatory cell infiltration in the lumbar spinal cord in an animal model of encephalomyelitis. Future investigations should include effects of ibudilast on inflammatory reactions between endothelium and blood cells, which may initiate the development of atherosclerosis.
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PMID:Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall. 1160 39

The chemokines participate in an exceptional range of physiological and pathological processes, including the control of lymphocyte trafficking, tumor growth, wound healing, allograft rejection, regulation of T-cell differentiation, asthma, infection with HIV and atherosclerosis. This vast array of activities is triggered by the interaction of nearly 50 different chemokines with a relatively modest number of 20 G-protein-coupled receptors. The asymmetry between the number of receptors and ligands suggests an underlying, shared control mechanism activated at a very early stage of the response. One of the first events triggered by the binding of chemokines is the homo- and hetero-dimerization of their receptors; here, we outline these events and their consequences in chemokine signaling.
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PMID:Chemokine receptor dimerization: two are better than one. 1169 22

Clinical studies have suggested a causal or contributory role of Chlamydia pneumoniae infection in asthma and atherosclerosis. The activation of synthetic functions of smooth muscle cells (SMC) including the production of cytokines and growth factors plays a major role in the formation of fibrous atherosclerotic plaques as well as in structural remodelling of the airway wall in chronic asthma. In this study we demonstrated that C. pneumoniae induced the production of low levels of interferon (IFN)-beta in bronchial and vascular SMC when infected cells were treated with tumour necrosis factor-alpha (TNF-alpha). IFN-beta production was analysed by reverse transcription-PCR and enzyme-linked immunosorbent assay. The upregulation of IFN-beta was paralleled by an increase in mRNA levels of interferon regulatory factor-1 and interferon-stimulated gene factor 3gamma, two transcription factors activating the expression of the IFN-beta gene. In addition, C. pneumoniae infection enhanced the mRNA level of indoleamine 2,3-dioxygenase, an IFN-inducible factor mediating the restriction of intracellular chlamydial growth, in TNF-alpha-stimulated SMC. C. pneumoniae-induced IFN-beta production by SMC may modulate inflammation and tissue remodelling during respiratory and vascular infection.
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PMID:Interferon-beta induction by Chlamydia pneumoniae in human smooth muscle cells. 1175 Feb 16

Persistent infections with Chlamydia pneumoniae have been implicated in the development of chronic diseases, such as atherosclerosis and asthma. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratory C. pneumoniae infections, little is known about the dose and duration of therapy needed to treat a putative chronic C. pneumoniae infection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability of C. pneumoniae and cytokine production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminate C. pneumoniae in continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1beta, IL-4, IL-10, tumor necrosis factor alpha, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronic C. pneumoniae infection.
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PMID:Effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on Chlamydia pneumoniae in a continuous-infection Model. 1179 50

Chlamydia pneumoniae is the most commonly occurring intracellular bacterial pathogen. It is frequently involved in respiratory tract infections and to a lesser degree in extrapulmonary diseases. According to seroepidemiologic surveys, C. pneumoniae infection seems to be both endemic and epidemic. Such studies indicate that C. pneumoniae infection is widespread, with frequent reinfection during a lifetime. In Western countries the highest rate of new infections occurs between the ages of 5 and 15. The antibody prevalence worldwide is higher in adult males than in females. Currently available data suggest that C. pneumoniae is primarily transmitted from human to human without any animal reservoir. Transmission seems to be inefficient, although household outbreaks with high transmission rates are reported. Most reports rank C. pneumoniae among the three most common etiologic agents of community-acquired pneumonia, with an incidence ranging from 6% to 25%, and generally presenting a mild and, in some cases, self-limiting clinical course. Recent reports also indicate a possible role for C. pneumoniae in severe forms of community-acquired pneumonia and in respiratory infections in immunocompromised patients. C. pneumoniae infection has also been implicated in the pathogenesis of asthma in both adults and children. The hypothesis that C. pneumoniae infection could lead to asthma is based on clinical studies and on the evidence of specific IgE production, direct epithelial damage, induction of T-cell immunopathologic diseases, and vascular smooth cell infection. Chronic C. pneumoniae infection seems to be common in patients with chronic bronchitis whether exacerbated or not, and is characterized by a strong humoral immune response to this intracellular microorganism, which is present in the majority of patients with severe chronic bronchitis. More than 60% of subjects with chronic bronchitis have specific C. pneumoniae antibody titers, and the microorganism may be identified by culture or PCR in almost 40% of these patients. This pathogen has also been recently associated with atherosclerosis and coronary heart disease (CHD). Seroepidemiological evidence indicates that the majority of patients with CHD present an anti-C. pneumoniae antibody pattern consistent with chronic infection. Furthermore, C. pneumoniae has been detected in atherosclerotic coronary plaques by several methods, including immunocytochemistry, transmission electron microscopy and molecular biology techniques. Recently, we detected C. pneumoniae DNA in a high percentage (51%) of aortic aneurysm plaques. Moreover, our serologic data support the hypothesis that a chronic C. pneumoniae antibody pattern may be a possible risk marker for atherosclerosis. Recently, C. pneumoniae has been isolated by culture from the coronary artery of a patient with coronary atherosclerosis, providing direct evidence of the presence of viable organisms in atheromatous lesions. Moreover, we recently demonstrated an association between C. pneumoniae reinfection and acute myocardial infarction.
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PMID:Epidemiology of Chlamydia pneumoniae. 1186 64

Oxidative stress which results from an imbalance between oxidant production and antioxidant defense mechanisms can promote modifications of lipids, proteins and nucleic acids. This review focuses on the different pathways leading to Reactive Oxygen Species (ROS) production in particular on NADPH oxidase activation. This enzyme is localized in numerous cells including phagocytes and vascular cells and composed of membrane and cytosolic sub-units. The activation of the NADPH oxidase is largely involved in inflammation associated diseases such as asthma, Systemic Inflammatory Response Syndrome and aging associated diseases such as atherosclerosis and neurodeneratives diseases. The modulation of NADPH oxidase could be a way to limit or prevent the development of these diseases.
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PMID:[Oxygen and the superoxide anion. Modulation of NADPH oxidase?]. 1193 57

Atherosclerosis in childhood has a slowly progressive course and its clinical features usually become prominent in middle ages. Hypercholesterolemia is one of the major risk factors for the development of atherosclerosis. A clear correlation exists between hypercholesterolemia in childhood and atherosclerotic lesions extending into adulthood.In this study, we evaluated the effect of slow release theophylline (SRT) treatment on plasma lipid profile and assessed the risk for atherosclerotic coronary heart disease in children with bronchial asthma. Group 1 consisted of 15 children with a mean age of 10.8 3.19 years who received SRT for bronchial asthma for a mean period of 9.13 2.17 months. Group 2 was composed of 15 children with a mean age of 11.40 3.78 years and followed up for bronchial asthma, who received no SRT treatment. Group 3 comprised 15 children with a mean age of 9.00 3.76 years and no history of asthma or wheezing. In all patients lipid profiles were assessed by measuring levels of plasma triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) apolipoprotein A (Apo-A) and apolipoprotein B (Apo-B). In group 1, the mean total cholesterol level was 175.53 24.36 mg/dl, LDL-C level was 91.00 24.07 mg/dl and Apo-B level was 87.27 12.74 mg/dl after SRT treatment. In group 1, group 2 (control group with asthma) and group 3 (the non-asthmatic control group), the mean plasma lipid level after SRT treatment was significantly higher than that before SRT treatment. In conclusion, long-term SRT treatment in children with bronchial asthma may alter lipid profile and may increase the risk for developing atherosclerotic coronary heart disease.
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PMID:Lipoprotein profile in long term theophylline administration in children with asthma. 1195 39

Persistent infection with Chlamydia pneumoniae (Chlamydophila pneumoniae) has been implicated in the development of atherosclerosis, asthma and other chronic diseases. However, data on treatment of C. pneumoniae infections are limited. Microbiological failure of antimicrobial therapy has been described, even after prolonged courses of treatment with azithromycin, doxycycline and erythromycin. Gemifloxacin is an enhanced-affinity fluoroquinolone with excellent activity against most common respiratory pathogens, including C. pneumoniae. The effect of prolonged treatment with gemifloxacin, compared with azithromycin, on viability of C. pneumoniae was investigated in a continuous infection model. Gemifloxacin at final con-centrations of 0.25 and 2.5 mg/L reduced the viability of C. pneumoniae by 5 log(10), which was similar to the effect of azithromycin. However, both antimicrobials failed to completely eliminate C. pneumoniae from continuously infected cells, even after 30 days of treatment. Both antibiotics decreased levels of interleukin-6 and interleukin-8 in this model, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms.
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PMID:Effect of gemifloxacin on viability of Chlamydia pneumoniae (Chlamydophila pneumoniae) in an in vitro continuous infection model. 1200 69

Lipoxygenase (LO) is a biological target for many diseases such as asthma, atherosclerosis, and cancer. Our labs have synthesized and investigated nordihydroguaiaretic acid (NDGA) derivatives and have established that the reductive inhibition of soybean and 15-human LO can be affected by the strength of the electron-withdrawing substituents on the phenyl rings of NDGA. In addition, we have determined that hydrophobic NDGA derivatives activate 15-HLO, suggesting a hydrophobic allosteric site.
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PMID:Structure-activity relationship studies of nordihydroguaiaretic acid inhibitors toward soybean, 12-human, and 15-human lipoxygenase. 1203 75

Nuclear factor kappa B (NF-kappaB) is a family of inducible transcription factors found virtually ubiquitously in all cells. Since its discovery by Sen and Baltimore in 1986, much has been discovered about its mechanisms of activation, its target genes, and its function in a variety of human diseases including those related to inflammation, asthma, atherosclerosis, AIDS, septic shock, arthritis, and cancer. Due to its role in a wide variety of diseases, NF-kappaB has become one of the major targets for drug development. Here, we review our current knowledge of NF-kappaB, the possible mechanisms of its activation, its potential role in cancer, and various strategies being employed to target the NF-kappaB signaling pathway for cancer drug development.
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PMID:Nuclear transcription factor-kappaB as a target for cancer drug development. 1204 Apr 37


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