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

Although there have been extensive studies of serum lipid levels in psoriasis, the data are conflicting. In the present study, 38 male psoriatic patients and 40 age-matched male control subjects were studied. In addition, a 75 g oral glucose tolerance test (OGTT) was performed in 28 patients and 28 age-matched control subjects, in order to exclude subjects with abnormal OGTT values from the study. Twenty-two patients and 26 control subjects had normal OGTT values. There was a tendency for psoriatic patients with normal glucose tolerance to have increased triglyceride levels, but this was not statistically significant. Total cholesterol and high-density lipoprotein-cholesterol levels in patients were normal. However, serum apo B (P < 0.005), C-II (P < 0.005) and C-III (P < 0.005) levels in patients were significantly elevated compared with control subjects. When control subjects and patients with abnormal OGTT values were also included, a significant increase in triglyceride and apo E levels, and a significant decrease in the apo A-I level were observed in psoriatic patients. These findings suggest that psoriasis per se is associated with increases in apo B, C-II and C-III levels, but that this does not profoundly affect lipid levels. The abnormal lipoprotein metabolism may be related to the high incidence of atherosclerosis in psoriasis.
 ...
PMID:Serum lipid and apolipoprotein levels in patients with psoriasis. 801 99

Psoriasis, a chronic inflammatory skin disease characterized by an aberration of lipid metabolism, has been associated with an increased risk for atherosclerosis. Since oxidatively modified lipoproteins are involved in the pathogenesis of atherosclerosis, we investigated the lipid composition and in vitro induced peroxidation of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) from psoriatic patients. 11 male adult psoriatics and 16 male age-matched healthy subjects were studied. Lipid peroxidation of VLDL and LDL was performed by incubation with CuSO4 for 24 h at 37 degrees C. The compositional analysis showed a significant increase in triglycerides and phospholipids, both in VLDL (p < 0.05) and in LDL (p < 0.001) from psoriatic patients, compared with controls. Moreover a significant increase in total cholesterol (TC) (p < 0.01) and apoprotein (P) (p < 0.05) was found in LDL from psoriatics. The levels of thiobarbituric acid reactive substances (TBARS), as a measurement of lipid peroxidation, were significantly higher in Ox-VLDL and in Ox-LDL from psoriatics (p < 0.01) than the corresponding values in controls. Moreover, basal values of TBARS were significantly higher in VLDL and LDL from psoriatic patients than those from controls. In conclusion, the lipoprotein compositional changes associated with the modifications of TBARS before and after Cu2+ treatment of lipoproteins may suggest an increased risk for atherosclerosis in adult psoriatic patients.
 ...
PMID:Lipoprotein peroxidation in adult psoriatic patients. 807 34

In diseases leading to massive acute cell damage, e.g., myocardial infarction or spontaneous inflammation, increased amounts of hydroperoxides of unsaturated fatty acids (LOOH) are found. An even higher production of LOOH is observed in homogenized tissue. If cells are injured, dormant lipoxygenases (LOX) are inevitably activated. They oxidize unsaturated membrane fatty acids to LOOH. This process involves not only arachidonic acid - as tacitly assumed up to now - but also linoleic acid. LOOH are decomposed to chemically highly reactive species, some of which were previously unknown (e.g, alpha-hydroxyaldehydes). LOO. radicals can also transform any molecule with a double bond to an epoxide. Therefore, epoxides are found in injured tissue. The same degradation products of hydroperoxides have been observed in elevated amounts in acute cell injury and in chronic diseases, e.g., atherosclerosis, psoriasis, and rheumatoid diseases. Therefore, we conclude that in these cases too, increased generation of hydroperoxides is caused by gradual cell injury liberating lipoxygenases.
 ...
PMID:[Cell damage as reason for the formation of unsaturated fatty acid hydroperoxides]. 852 16

Hydroperoxides of unsaturated fatty acids (LOOHs) are generated by homogenisation of liver tissue, but not if the liver is boiled before homogenisation. This observation indicates that the LOOHs are produced in an enzymatic reaction. This assumption is corroborated by an analysis of the reduction products of LOOHs by gas chromatography/mass spectrometry (GC/MS). A main part of LOOHs is derived from linoleic acid and not from arachidonic acid. Massive cell damage occurs by myocardial infarction or other severe injuries; these events were found to be connected with generation of LOOHs. We suspect--considering the above outlined experiment--that the LOOH production is also mainly caused in these cases by activation of enzymes and not--as postulated--by an autocatalytic process. Increased amounts of LOOHs are found in many chronic diseases, e.g. in rheuma, atherosclerosis or psoriasis, obviously caused by a gradual damage of cells. Thus, the common root of an increased LOOH level might be cell injury.
 ...
PMID:Enzymatic production of hydroperoxides of unsaturated fatty acids by injury of mammalian cells. 864 Aug 99

Leukocyte recruitment from the circulation into inflammatory tissues requires a series of soluble and cell-bound signals between the responding leukocyte and vascular endothelial barrier. Chemotactic factors are believed to be responsible for this selective adhesion and transmigration. A superfamily of small, soluble, structurally-related molecules called 'chemokines' have been identified and shown to selectively promote the rapid adhesion and chemotaxis of a variety of leukocyte subtypes both in vivo and in vitro. Chemokines are produced by almost every cell type in the body in response to a number of inflammatory signals, in particular those which activate leukocyte-endothelial cell interactions. These molecules also appear to play important roles in hematopoesis, cellular activation, and leukocyte effector functions. In addition, chemokines have been found in the tissues of a variety of disease states characterized by distinct leukocytic infiltrates, including rheumatoid arthritis, sepsis, atherosclerosis, asthma, psoriasis, ischemia/reperfusion injury, HIV replication, and a variety of pulmonary disease states. This review will primarily focus on the role of chemokines in cell adhesion and trafficking as well as their role as effector molecules.
 ...
PMID:Chemokine-leukocyte interactions. The voodoo that they do so well. 902 58

MCAF (MCP-1) a member of the chemokine-beta-family known to be chemotactic for monocytes is believed to play a significant role in several inflammatory processes, both immuno-pathological disorders, such as atherosclerosis, psoriasis, chronic inflammatory diseases of the liver and lungs, and during the normal immune response against microorganisms. This chemokine is produced spontaneously by monocytes, and in the present article we also demonstrate that MCAF induces its own production in monocytes. The methods used are two dimensional SDS-PAGE gel electrophoresis. Western-blotting and ELISA quantification of supernatant from monocyte cultures stimulated with MCAF (1, 10, 100 ng ml). Also, we found that this process is regulated by IL-10 (100 ng ml). Our results suggest that monocytes migrating to a site of inflammation due to the local production of the chemokine MCAF/MCP-1 further enhance the focal accumulation of monocytes by producing and releasing bioactive MCAF MCP-1.
 ...
PMID:Monocyte chemotactic and activating factor (MCAF/MCP-1) has an autoinductive effect in monocytes, a process regulated by IL-10. 918 8

Receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor (PDGFR), are critically involved in the transduction of mitogenic signals across the plasma membrane and therefore in the regulation of cell growth and proliferation. Enhanced RTK activity is associated with proliferative diseases such as cancer, psoriasis and atherosclerosis, while decreased function may be associated for instance with diabetes. EGFR and PDGFR are selectively inhibited by analogues of the marine natural product aeroplysinin. The synthetic inhibitors display IC50 values in the low micromolar range and in contrast to the natural product show pronounced inhibitory activity in cultured cells in vivo. The mechanism of inhibition is likely based on a covalent modification of the target enzymes by reaction of epoxy ketone 8 with various nucleophiles.
 ...
PMID:Synthesis and biological evaluation of aeroplysinin analogues: a new class of receptor tyrosine kinase inhibitors. 978 57

Psoriasis is associated with changes in plasma lipid and lipoproteins, which may play a role in the development of occlusive vascular disease. The oxidation of low-density lipoprotein (LDL) is considered a key event in the development and progression of atherosclerosis. Autoantibodies against oxidized LDL (auAb-oxLDL) may contribute to understanding the relationship between oxidative processes and development of atherosclerosis. Thirty-three patients with psoriasis and 30 matched control subjects were investigated. LDL oxidation was evaluated as the presence of autoantibodies against LDL oxidatively modified with Cu++, by an ELISA system in the patients and control sera. AuAb-ox LDL levels of the patients were found to be significantly increased compared with a control group. 42% of the patients and 3.3% of the control subjects had higher auAb-ox LDL levels than the cut-off point (352 mU/ml). The levels of auAb-ox LDL were found to be correlated with PASI score (r = 0.67, p < 0.01). Also, The antibody level was found to be correlated with polymorphonuclear elastase and alpha-1 antitrypsin levels (r = 0.58, p < 0.05; r = 0.51, p < 0.05, respectively). It was concluded that increased levels of auAb-oxLDL in the psoriatic patients may be a consequence of the interaction between imbalance of oxidant-antioxidant system and lipoproteins, and the measurement of auAb-oxLDL in the patients may mirror in vivo occurrence of oxidative processes.
 ...
PMID:The significance of autoantibodies against oxidatively modified low-density lipoprotein (LDL) in patients with psoriasis. 1043 45

Cyclin-dependent kinases (CDKs) trigger and co-ordinate the cell division cycle phases. They also play a role in neuronal cells and in the control of transcription. Intensive screening has led in the past few years to the identification of a series of chemical inhibitors of CDKs. Some of these compounds display remarkable selectivity and efficiency (IC50 <25 nM). Many have been co-crystallised with CDK2, and their atomic interactions with the kinase have been analysed in detail: all are located in the ATP-binding pocket of the enzyme. These inhibitors are antimitotic, they arrest cells in G1 and, at higher doses, in G2/M. Furthermore, they facilitate or even trigger apoptosis in proliferating cells. In contrast, they protect neuronal cells from apoptosis. The potential use of these inhibitors is being extensively evaluated in cancer chemotherapy (clinical trials, Phase I and II). Possible clinical applications are being investigated in other fields: cardiovascular (restenosis, tumoural angiogenesis, atherosclerosis), nephrology (glomerulonephritis), dermatology (psoriasis), parasitology (unicellular parasites such as Plasmodium, Trypanosoma, Toxoplasma, etc.), neurology (Alzheimer's disease), viral infections (cytomegalovirus, human immunodeficiency virus, herpes). We anticipate the discovery of novel selective and powerful inhibitors in the near future, and hope for their efficient applications in various human diseases.
 ...
PMID:Properties and potential-applications of chemical inhibitors of cyclin-dependent kinases. 1045 5

Essential fatty acids (EFAs) form an important component of cell membranes, are eicosanoid precursors and are therefore required for both the structure and function of every cell in the body. EFAs can modulate the activity of protein kinase C, T and B cell response, free radical generation and lipid peroxidation, lymphokine secretion and cell proliferation. EFAs also have anti-mutagenic, anti-bacterial, anti-fungal and anti-viral properties. EFAs and their metabolites lower serum cholesterol, triglycerides and blood pressure. EFAs appear to be of benefit in atopic eczema, premenstrual syndrome, psoriasis, auto-immune disorders especially rheumatoid arthritis and systemic lupus erythematosus, prevention of target organ damage in diabetes mellitus, peptic ulcer disease, ulcerative colitis, coronary heart disease and atherosclerosis. EFAs and their metabolites can selectively kill tumor cells both in vitro and in vivo without harming normal cells. In addition, EFAs seem to play a fundamental role in inflammation and immune response. In view of their actions and relative safety, it is anticipated that EFAs may be useful in the management of several diseases.
 ...
PMID:Essential fatty acids in health and disease. 1077 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>