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)

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
 ...
PMID:[Interferon-alpha, beta, gamma]. 799 28

The tea plant Camellia sinesis is cultivated in >30 countries. Epidemiologic observations and laboratory studies have indicated that polyphenolic compounds present in tea may reduce the risk of a variety of illnesses, including cancer and coronary heart disease. Most studies involved green tea, however; only a few evaluated black tea. Results from studies in rats, mice, and hamsters showed that tea consumption protects against lung, forestomach, esophagus, duodenum, pancreas, liver, breast, colon, and skin cancers induced by chemical carcinogens. Other studies showed the preventive effect of green tea consumption against atherosclerosis and coronary heart disease, high blood cholesterol concentrations, and high blood pressure. Because the epidemiologic studies and research findings in laboratory animals have shown the chemopreventive potential of tea polyphenols in cancer, the usefulness of tea polyphenols for humans should be evaluated in clinical trials. One such phase 1 clinical trial is currently under way at the MD Anderson Cancer Center in collaboration with Memorial Sloan-Kettering Cancer Center. This study will examine the safety and possible efficacy of consuming the equivalent of > or =10 cups (> or =2.4 L) of green tea per day. The usefulness of tea polyphenols may be extended by combining them with other consumer products such as food items and vitamin supplements. This "designer-item" approach may be useful for human populations, but it requires further study.
 ...
PMID:Tea polyphenols: prevention of cancer and optimizing health. 1083 21

Obesity is related to cardiovascular disease (CVD) morbidity and mortality, however, the mechanisms for the development of obesity-induced CVD risk remain unclear. Hyperinsulinemia and insulin resistance are considered key components in the metabolic cardiovascular syndrome and as independent risk factors for CVD. Plasma leptin and tumor necrosis factor-alpha (TNF-alpha), two adipocyte products, are also proposed to be associated with the development of CVD risk. The purpose of this study is to evaluate the association of plasma leptin, soluble TNF receptors (sTNF-R), and insulin levels as possible mediators of the effect of obesity on atherogenic and thrombogenic CVD risk factors among men. From the Health Professionals Follow-up Study (HPFS), we selected 268 men, aged 47--83 years, who were free of CVD, diabetes, and cancer (except non-melanoma skin cancer), and who had provided a fasting blood sample in 1994. We measured plasma insulin and leptin levels by radioimmunoassay and sTNF-R levels by ELISA. Men in the highest quintile of body mass index (BMI, mean=30.5 kg/m(2)) were less physically active and had a more adverse cardiovascular lipid and homeostatic profile, as indicated by levels of insulin, triglyceride (TG), tissue plasminogen activator (t-PA) antigen levels, and apolipoprotein A1 (Apo-A1). In a multivariate regression model controlling for age, smoking, alcohol intake, physical activity and diet, BMI was inversely associated with HDL-cholesterol (HDL-C) and Apo-A1 and positively associated with TG, Apo-B and t-PA antigen levels. The associations between BMI and these CVD risk factors were only slightly changed after adjusting for leptin and/or sTNF-R; but were substantially attenuated after controlling for insulin levels. These data suggest that the association between obesity and biological predictors of CVD may be mediated through changes in plasma insulin, rather than leptin or sTNF-R levels. However, plasma leptin may still play a role in CVD through independent effects on lipid metabolism.
Atherosclerosis 2001 Aug
PMID:Plasma insulin, leptin, and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular disease risk factors among men. 1147 52

The arsenic-related peripheral vascular disease found to be endemic along the southwestern coast of Taiwan is reviewed. In the early 20th century a strange disease involving the lower extremities characterized by typical clinical symptoms and signs of progressive arterial occlusion was reported in a confined area located along the southwestern coast of Taiwan. The disease was locally called "blackfoot disease" because of its gangrenous appearance involving the feet of the patients. The prevalence of this disease ranged from 6.51 to 18.85 per 1,000 population in different villages. Epidemiologic studies revealed that blackfoot disease was associated with the consumption of artesian well water containing high levels of arsenic. High co-occurrence of blackfoot disease and arsenic-related skin lesions such as hyperpigmentation, hyperkeratosis, and skin cancer was also observed. Recent studies also confirmed the association of preclinical peripheral vascular disease with arsenic exposure in a dose-response pattern. Subclinical arterial insufficiency and defects in cutaneous microcirculation can also be demonstrated in seemingly normal subjects living in the endemic villages. The incidence of clinical manifestation of blackfoot disease decreased dramatically after the implementation of tap water in these villages over the past 2-3 decades. The atherogenicity of arsenic could be associated with its effects on hypercoagulability, endothelial injury, smooth muscle cell proliferation, somatic mutation, oxidative stress, and apoptosis. However, its interaction with some trace elements and its association with hypertension and diabetes mellitus could also explain part of its higher risk of developing atherosclerosis.
 ...
PMID:An overview on peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan. 1236 59

Many normal biological processes, such as reproduction, fetal development and wound healing, are critically dependent on controlled degradation of extracellular matrix (ECM) macromolecules. However, excessive degradation of matrix components occurs in pathologic tissue destruction, e.g. in atherosclerosis, rheumatoid arthritis, and cancer. Matrix metalloproteinases (MMPs) are degradative enzymes that play an important role in all aspects of tumor progression by enhancing tumor-induced angiogenesis and destroying local tissue architecture and basement membranes to allow tumor invasion and metastasis. Efficient breakdown of the ECM surrounding invasive cancer islands involves interplay between tumor cells, stromal cells, and inflammatory cells, all of which express a distinct set of MMPs. Besides the classical role of MMPs in degradation of ECM, MMPs may also indirectly influence the tumor microenvironment through the release of growth factors, cryptic sites or angiogenic factors, or through the generation of matrix fragments that inhibit tumor cell proliferation, migration and angiogenesis. This makes the contribution of MMPs to tumorigenesis much more complex than initially thought. Currently, a number of clinical studies have focused on testing MMP inhibitors as potential antineoplastic agents. In this review we discuss the present role of MMPs in the development and progression of cancer, focusing on non-melanoma skin cancers basal (BCC) and squamous (SCC) cell carcinoma, and the possible influence of MMPs in their differences.
 ...
PMID:Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer. 1270 39

Previous studies of leptin with cardiovascular disease (CVD) risk factors have been limited by clinical samples or lack of representation of the general population. This cross-sectional study, designed to examine whether leptin or insulin may mediate the endogenous relation of obesity with metabolic, inflammatory, and thrombogenic cardiovascular risk factors, included 522 men and 514 women aged >or=40 years who completed a physical examination during the third National Health and Nutrition Examination Survey. Participants were free of existing CVD, cancer (except non-melanoma skin cancer), diabetes, or respiratory disease. In multivariable analyses adjusted for race/ethnicity and lifestyle factors, waist circumference (WC) was positively associated with blood pressure, triglyceride, LDL cholesterol, total cholesterol:HDL ratio, apolipoprotein B, C-reactive protein (CRP), and fibrinogen concentrations, and negatively associated with HDL cholesterol and apolipoprotein A1 levels. The associations of WC with the metabolic CVD risk factors were largely attenuated after adjustment for insulin levels, while the associations of WC with the inflammatory and thrombogenic factors (CRP and fibrinogen, respectively) were largely explained by adjustment for leptin concentrations. However, leptin levels were not independently associated with CRP and fibrinogen in men and CRP in women when adjusted for WC. Positive associations of leptin and insulin with fibrinogen in women, independent of WC, were noted. These results suggest that insulin may be an important mediator of the association of obesity with metabolic but not inflammatory or thrombogenic CVD risk factors, while leptin does not appear to influence cardiovascular risk through a shared association with these risk factors. However, we cannot rule out the possibility that leptin and insulin influence cardiovascular risk in women through independent effects on fibrinogen concentrations.
Atherosclerosis 2008 Sep
PMID:The relation of leptin and insulin with obesity-related cardiovascular risk factors in US adults. 1816 70

Tissue damage caused by oxidative stress has been implicated in aging, carcinogenesis, atherosclerosis and neurodegeneration. In xeroderma pigmentosum (XP) and Cockayne syndrome (CS), oxidative stress is associated with promoted occurrence of skin cancers and progressive neurodegeneration, because decreased DNA repair and persistent DNA damage can result in augmented oxidative nucleotide damage. Oxidative nucleotide damage has been investigated mainly in isolated human skin and blood cells or their cell lines, in which CS cells may be more sensitive to oxidative DNA lesions than XP cells. However, cells from patients with XP group A (XPA) show defective repair of 8, 5'-(S)-cyclo-2'-deoxyadenosine, a free radical-induced endogenous DNA lesion and antioxidant system seems to be disturbed variously in cells from XP patients. We have neuropathologically investigated the involvement of oxidative stress in the brains of XPA and CS autopsy cases and clarified the enhanced lipid peroxidation and protein glycation in the pallidal and cerebellar degeneration. Also, oxidative nucleotide damage with reduced expression of superoxide dismutases has been identified in the basal ganglia lesions, lending further weight involvement of oxidative stress in neurodegeneration in XPA patients. Additionally, we are developing ELISA analysis of oxidative stress markers in the urine and cerebrospinal fluid from XP patients, which will aid with further data on oxidative stress in pathogenesis of XP.
 ...
PMID:Roles of oxidative stress in xeroderma pigmentosum. 1918 Nov 17

A French maritime pine bark extract, Flavangenol, is widely used as a nutritional supplement for protection against atherosclerosis, hypertension, diabetes, etc. Chronic exposure to solar UV radiation damages skin, increasing cutaneous thickness, wrinkling and pigmentation, as well as reducing elasticity, and causes skin cancer. The aim of this study was to examine the effects of flavangenol on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in melanin-possessing hairless mice. The oral administration of flavangenol (60, 200 or 600 mg kg(-1), twice daily) significantly inhibited increases in skin thickness, and the formation of wrinkles and melanin granules, as well as increases in the diameter and length of skin blood vessels. Furthermore, it prevented increases in numbers of apoptotic, Ki-67-positive and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells, and the expression of skin vascular endothelial growth factor (VEGF) induced by chronic UVB irradiation. The effect on these biomarkers was associated with a reduction in the incidence of tumors in mice. The antiphotoaging and anticarcinogenetic activities of flavangenol may be due to inhibition of the expression of Ki-67, 8-OHdG and VEGF through a scavenging effect on reactive oxygen species.
 ...
PMID:French maritime pine bark (Pinus maritima Lam.) extract (Flavangenol) prevents chronic UVB radiation-induced skin damage and carcinogenesis in melanin-possessing hairless mice. 2049 64

Human health in the past and presently is influenced by the amounts and proportion of chemical elements to which humans have been exposed. Arsenic, as a therapeutic agent was known to ancient Greeks and Romans. Ehrlick introduced organic arsenicals as anti linetic agents but with advent of penicillin these have nearly become obsolete. Once considered toxic, harmful to humans, arsenic is now considered an essential ultra trace element at least in animals. Now the impact of arsenic on health is more from industrial and environmental than medicinal exposure. This article reviews human exposure to arsenic in non occupational population, mostly through drinking water which is a worldwide problem, more so in south East Asia. Sources of arsenic, normal and abnormal levels in blood and tissues levels, old and new methods of estimation of arsenic, mechanism of action of arsenic in experimental animal is briefly reviewed. Old described clinical manifestation of arsenic in humans is briefly reviewed and newly described clinical manifestations in human with special emphasis on atherosclerosis, liver and diabetes are discussed. Proposed biological mechanisms in experimental animals included up regulation of inflammatory signals like cytokines and TNF-alpha, oxidative stress, hypomethylation, decreased DNA repair and apoptosis, cell proliferation, angiogenesis, activation of several enzymes like methyl transferase which converts inorganic arsenic to MMA and DMA, and GSH in in-vivo and in-vitro in experimental rat liver slices. Experimentally NAC (N-Acetyl Cysteine) treatment attenuates oxidative stress in atherosclerosis apoptosis and liver injury. GSH probably plays an important role in deactivation of the intermediate products of arsenic metabolism and prevents peroxidation of membrane lipids. Chronic human exposure has been linked to several systems in the human body: dermal (exfoliative dermatitis, keratosis, vitiligo, skin cancer), peripheral neuropathy, encephalopathy, bronchitis, pulmonary fibrosis, hepatosplenomegaly resembling NCPF, portal hypertension, peripheral vascular disease and BFD, arteriosclerosis and cancers of lung, urinary bladder, other internal organs and diabetes. Experimental and epidemiological evidence support diabetes effect of high level arsenic exposure. Low and moderate exposure to arsenic in drinking water is widely prevalent and may play a role in diabetes prevalence and needs to be studied further. Role of arsenic in Indian arteriosclerosis, diabetes and liver diseases, (cirrhosis, NCPF), need to be studied further. Study of mechanisms and enzymes mentioned need to be studied in humans exposed to arsenic and other xenobiotics. Measuring arsenic exposure, metabolic and biologic effects by newly described and simpler urine proteomics may accelerate our understanding of arsenic on health consequences.
 ...
PMID:Arsenicosis: review of recent advances. 2175 19

It is on the tip of everyone's tongue in the transplant community that recent improvements in short-term survival of solid organ allografts have not translated into the expected increase in long-term survival. Besides chronic immune-mediated damage to the transplanted organ, the poor long-term survival of allografts has been attributed to the nephrotoxic effects of the calcineurin inhibitors. Moreover, the immunosuppressive burden and metabolic side effects of the current anti-rejection drugs are clearly related to increased rates of malignancies, infections and accelerated atherosclerosis, all of which make up for the premature death of a considerable proportion of transplant recipients with a functioning allograft. Therefore, attempts have been made over the last decade to either reduce or withdraw both steroids and calcineurin inhibitors from maintenance regimens. Furthermore, there is an ongoing intensive search for new less toxic and more specific drugs which would ideally selectively impair the alloimmune response while preserving the immune system's capacity to fight infection and malignancy (i.e. induce tolerance). Moreover, new concepts have emerged to individualize a patient's immunosuppressive therapy based on an improved pretransplant risk assessment. With the causes of chronic allograft damage being increasingly well defined, better and more personalized long-term follow-up strategies are being developed to ultimately prevent late allograft loss. These aspects will be reviewed here with a focus on kidney transplantation and the possible impact of these new approaches on the incidence of skin cancer.
 ...
PMID:Future trends in organ transplant recipients--important issues for dermatologists. 2237 21


1 2 Next >>