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)

The combined progestogen/estrogen oral contraceptive is the most common form of contraception in the US. They contain 1 of 5 synthetic progestogens (derived from 19-nortestosterone) and 1 of 2 estrogens. 3 new progestin compounds are in use in Europe and Asia. They are norgestimate, desogestrel, and gestodene. Estrogen seems to cause vascular complications. Progestin may cause atherosclerosis. Desogestrel and gestodene were studied for 6 months. They have little effect on glucose and lipid metabolism. Triphasal ethinyl estradiol/levonorgestrel and ethinyl estradiol/norethindrone (Ortho Novum 7/7/7) were compared in a 12-month prospective clinical trial. There seems to be no consensus of a pattern of increased breast cancer associated with oral contraceptive use. The UK National Case Control Study Group analyzed women younger than 36 years at the time breast cancer was diagnosed. 91% of their cohort had used pills. A significant trend was found when risk was analyzed with duration of taking pills. Women who had taken the pill for 4 years had no increased risk of breast cancer. However, there was an increased relative risk of 1.7 (P0.001) for women who took pills for more than 8 years. Among women using the pill for 8 years, the relative risk was 2.6 (p0.0001). AMong women using pills with 50 ug. of estrogen, the trend to increased risk was (P0.10). The 1988 National Survey of adolescent males showed that 60% of men never married were active sexually. Among 17- to 19-year-old-men who live in metropolitan areas, condom use has more than doubled, compared with 1979. In 1988, a "new" copper-containing IUD was approved for use in the US by the Food and Drug Administration, the Copper T 380 A. Pregnancy rates are less with this than with older devices. IUDs may cause pelvic inflammatory disease with resulting tubal infertility. However, the risk was overstated earlier. Women who have only 1 sexual partner in their lifetime had no significant risk of tubal infertility. "lost" IUDs continue to be a problem.
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PMID:Contraception. 210 26

Benzo(a)pyrene (BaP), a major environmental pollutant and component of cigarette smoke, is both carcinogenic and atherogenic in experimental models. We investigated the effect of long-term administration of BaP on atherogenesis in both atherosclerosis-susceptible White Carneau (WC) and atherosclerosis-resistant Show Racer (SR) pigeons. The number and size of arterial lesions in the brachiocephalic arteries in WC and SR females but not males were significantly enhanced after long-term dosing with BaP. Metabolic activation appears to be required for BaP atherogenicity, since benzo(e)pyrene (BeP), a noncarcinogenic analogue of BaP, did not enhance lesion development. Studies with 3H-BaP revealed no significant differences between male and female or between WC and SR pigeons in the arterial distribution of BaP and/or its metabolites. There were no consistent differences in blood pressure or plasma cholesterol levels between breeds or sexes. However, chronic administration of BaP did result in complete infertility in female birds, concomitant with grossly visible changes in ovarian appearance. These results clearly show that long-term dosing with BaP alters ovarian structure and function in treated birds, at the same time aggravating the development of arterial lesions. Thus, BaP-induced atherogenicity in female pigeons may be a consequence of an alteration in estrogen production or of antiestrogenic properties of BaP at the level of the arterial wall and may serve as a highly useful animal model to examine the well-known rapid development of atherosclerosis in postmenopausal women.
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PMID:Benzo(a)pyrene enhances atherosclerosis in White Carneau and Show Racer pigeons. 824 Oct 91

It is now known that human exposure to certain chemicals e.g. benzene, halocarbons, ketones, nitrosamines, etc. can result in adverse health effects that are often not easily recognised as manifestations of chemical toxicity. These are inflammatory states, such as hepatitis, nephritis, scleroderma, and lupus, due to production of reactive oxygen species (ROS) through activation of cytochrome P4502E1 by the chemical, or by metabolism of the chemical to reactive intermediates and neoantigens which initiate immunotoxic effects. Intracellular glutathione (GSH), vitamins C, E and A protect against this ROS toxicity and inflammation; fasting and consumption of alcohol exacerbate it. Chronic inflammatory states may subsequently develop, including rheumatoid disease, atherosclerosis, diabetes, infertility and birth defects, multiple system organ failure (MSOF), Alzheimer's disease, and cancer.
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PMID:Chemical-induced inflammation and inflammatory diseases. 897 63

Reactive oxygen species (ROS) are cytotoxic, causing inflammatory disease, including tissue necrosis, organ failure, atherosclerosis, infertility, birth defects, premature aging, mutations and malignancy. ROS are produced in the metabolism of drugs and industrial chemicals by (i) one-electron peroxidase oxidations to form cation radicals, (ii) cytochrome P450 metabolism to free radical products, (iii) stabilisation of the ROS-generator, CYP2E1, and (iv) futile cycling of other cytochromes P450. ROS production initiates inflammation which unless quenched may result in chronic inflammatory disease states, e.g. hepatitis, nephritis, myositis, scleroderma, lupus erythematosus, multiple system organ failure. Quenching of ROS is affected by the redox buffer, glutathione (GSH), and the antioxidants, ascorbic acid, tocopherols, retinoids, in conjunction with the redox enzymes, GSH reductase, GSH peroxidase, catalase and superoxide dismutase. Many industrial workers with symptoms of systemic inflammation, resulting from exposure to toxic chemicals, are diagnosed as having rheumatoid arthritis, virus infections, or other microbial lesions, largely because many physicians are unaware that exposure to certain chemicals can initiate inflammatory disease states.
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PMID:Chemical toxicity and reactive oxygen species. 911 92

Macrophage colony-stimulating factor (M-CSF) is critically involved in the survival, proliferation, and differentiation of cells of the mononuclear phagocyte system. These cells acquire specialized functions depending on the tissue in which they reside, suggesting that the development of mature phenotypes is determined by the cooperative effect of other growth factors, and also by the various biologically active isoforms of M-CSF which are differentially regulated. Alteration of M-CSF expression is associated with many pathologic processes, implying that the cells of the mononuclear phagocyte system are critical in maintaining the balance between health and disease in conditions such as infertility, osteopetrosis, osteoporosis, atherosclerosis, uremia, and Alzheimer's disease
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PMID:Update on the biologic effects of macrophage colony-stimulating factor. 966 57

Programmed cell death is an evolutionarily conserved cell death process that plays a major role during normal development and homeostasis. In many cases, the ordered execution of this internal death programme leads to typical morphological and biochemical changes that have been termed apoptosis. The crucial role of this mode of cell death in the pathogenesis of diverse human diseases including cancer, acquired immunodeficiency syndrome, neurodegeneratives disorders, atherosclerosis and cardiomyopathy is now supported by a wealth of data. In adult mammals, including humans, germ cell death is conspicuous during normal spermatogenesis and plays a pivotal role in sperm output. Withdrawal of gonadotrophins and testosterone further enhances the degeneration of germ cells in the testis. The availability of a quantitative method for analysing the testicular DNA fragmentation and in situ methods to localize specific germ cells undergoing apoptosis, either spontaneously or in response to a variety of death triggering signals, opens new avenues in the understanding of the significance of germ cell apoptosis during normal and abnormal states of spermatogenesis. A growing body of evidence demonstrates that both spontaneous (during normal spermatogenesis) and accelerated germ cell death triggered by deprivation of the gonadotrophic support or moderately increased scrotal temperature in adult rats occur almost exclusively via apoptosis. Although there has been spectacular progress in the understanding of the molecular mechanisms of apoptosis in various systems other than spermatogenesis, elucidation of the biochemical and molecular mechanisms by which germ cell apoptosis is regulated has only just begun. It is likely that germ cell apoptosis is controlled in a cell-type specific fashion, but the basic elements of the death machinery may be universal. In addition, there is increasing evidence that homozygous disruption of a number of genes in mice results in infertility through accelerated germ cell apoptosis. Manipulation of spermatogenesis by survival factor(s) deprivation or increases in extrinsic death signals in loss-of-function or gain-of-function mouse models provides a basis for further attempts to define the intrinsic regulation of various death-related genes by external death signals. Such information is crucial for effective management of male factor infertility as well as more targeted approaches to male contraception.
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PMID:Hormonal and genetic control of germ cell apoptosis in the testis. 1005 Nov 1

The mucosal pathogen Chlamydia trachomatis affects hundreds of millions of people worldwide and is a significant cause of sexually transmitted disease. Although most acute infections can be easily managed, complications often occur that can be especially severe in women. It has been proposed that increased exposure to conserved chlamydial antigens, such as through reinfection or persistent infection, results in chronic inflammation and tissue scarring and contributes to the pathogenesis of endometrial and fallopian tube damage. This immunopathologic damage is believed to be a principal cause of ectopic pregnancy and tubal factor infertility. The chlamydial heat shock protein Hsp60, a homolog of Escherichia coli GroEL, has been identified as one protein capable of eliciting intense mononuclear inflammation. Furthermore, several studies have revealed a correlation between Hsp60 responses and the immunopathologic manifestations of human chlamydial disease. The role of additional antigens in the immunopathologic response to chlamydiae is currently undefined. A prime candidate, however, is the chlamydial GroES homolog Hsp10, which is genetically and physiologically linked to Hsp60. Recent studies provide data to suggest that immune reactivity to Hsp10 is significantly associated with tubal infertility in a chlamydiae-exposed population. Chlamydia pneumoniae is a more recently defined chlamydial species that has been implicated in a variety of ways with chronic disease processes, such as adult onset asthma and atherosclerosis. Evidence indicates that Hsp60 is present in human atheroma and may play a role in lesion development by direct activation of macrophages. Hsp60 causes the elaboration of inflammatory cytokines, the induction of metalloproteinase, and the oxidation of low density lipoprotein. Each of these events is directly associated with the progress of atherosclerosis. Thus, chlamydial heat shock proteins may function in at least two ways to promote chronic disease: first by direct antigenic stimulation and second as signal transducers that result in macrophage activation. These concepts in disease pathology are discussed in the context of chlamydial infections.
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PMID:Chlamydial heat shock proteins and disease pathology: new paradigms for old problems? 1023 Oct 12

Several decades after the discovery of selenium as an essential trace element in vertebrates approximately 20 eukaryotic and more than 15 prokaryotic selenoproteins containing the 21st proteinogenic amino acid, selenocysteine, have been identified, partially characterized or cloned from several species. Many of these proteins are involved in redox reactions with selenocysteine acting as an essential component of the catalytic cycle. Enzyme activities have been assigned to the glutathione peroxidase family, to the thioredoxin reductases, which were recently identified as selenoproteins, to the iodothyronine deiodinases, which metabolize thyroid hormones, and to the selenophosphate synthetase 2, which is involved in selenoprotein biosynthesis. Prokaryotic selenoproteins catalyze redox reactions and formation of selenoethers in (stress-induced) metabolism and energy production of E. coli, of the clostridial cluster XI and of other prokaryotes. Apart from the specific and complex biosynthesis of selenocysteine, selenium also reversibly binds to proteins, is incorporated into selenomethionine in bacteria, yeast and higher plants, or posttranslationally modifies a catalytically essential cysteine residue of CO dehydrogenase. Expression of individual eukaryotic selenoproteins exhibits high tissue specificity, depends on selenium availability, in some cases is regulated by hormones, and if impaired contributes to several pathological conditions. Disturbance of selenoprotein expression or function is associated with deficiency syndromes (Keshan and Kashin-Beck disease), might contribute to tumorigenesis and atherosclerosis, is altered in several bacterial and viral infections, and leads to infertility in male rodents.
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PMID:Selenium in biology: facts and medical perspectives. 1107 17

The peroxisome proliferator-activated receptors (PPARs) are a group of three nuclear receptor isoforms, PPAR gamma, PPAR alpha, and PPAR delta, encoded by different genes. PPARs are ligand-regulated transcription factors that control gene expression by binding to specific response elements (PPREs) within promoters. PPARs bind as heterodimers with a retinoid X receptor and, upon binding agonist, interact with cofactors such that the rate of transcription initiation is increased. The PPARs play a critical physiological role as lipid sensors and regulators of lipid metabolism. Fatty acids and eicosanoids have been identified as natural ligands for the PPARs. More potent synthetic PPAR ligands, including the fibrates and thiazolidinediones, have proven effective in the treatment of dyslipidemia and diabetes. Use of such ligands has allowed researchers to unveil many potential roles for the PPARs in pathological states including atherosclerosis, inflammation, cancer, infertility, and demyelination. Here, we present the current state of knowledge regarding the molecular mechanisms of PPAR action and the involvement of the PPARs in the etiology and treatment of several chronic diseases.
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PMID:The mechanisms of action of PPARs. 1181 83

This work describes oral contraceptives (OCs) in current use and examines their risks. OC pills are composed of synthetic estrogens, usually either ethinyl estradiol or mestranol, and progestins. Either estrogens or progestins can be used alone, but combinations permit smaller doses to be used. Combined pills are available in monophasic, biphasic, or triphasic formulations. Different modalities of administration are also available for progestin-only pills. The "morning after" pill containing high doses of steroids to be taken within 72 hours of unprotected intercourse can contain either estrogen or progestin alone or combined. The mechanisms of action of OCs vary according to the type of pill. Classic combined OCs inhibit ovulation, render the cervical mucus inhospitable to sperm, and cause endometrial atrophy which hinders nidation. Low-dose pills have various effects but in general depend on changes in the cervical mucus for their contraceptive effect. Pregnancy may result from forgetting pills or using them incorrectly, or in the case of low-dose pills may occur even if they are used correctly. Some drugs can lower the concentrations of the OC hormones at the level of the receptors by hindering their intestinal absorption or by increasing the metabolic power of the liver. Considerable individual variability limits the incidence of pill failure due to drug interactions, but OC use should be avoided if rifampicine or certain other drugs are used. Among undesirable effects of OCs on endocrine glands and reproductive function are the adaptation syndrome characterized by symptoms similar to those of early pregnancy and reversible in most but not all women; galactorrhea resulting from diminished levels of "prolactin inhibiting factor"; and virilizing effects such as alopecia, hirsutism, and acne usually occurring during use of high-dose formulations. Pills should be carefully adapted to the hormonal profile of the user to avoid these side effects. OCs very rarely entail longterm infertility. OCs in current use do not appear to be teratogenic but it is advisable to wait 2 months after termination of use before becoming pregnant. Lactation is a contraindication to OC use. Combined OCs frequently cause problems in glucose tolerance of variable significance. Low-dose progestins do not seem to affect lipid metabolism, but low and normal dose combined pills may provoke increases in the levels of cholesterol and triglycerides. OCs are implicated in vascular accidents of various kinds, but low-dose pills are better tolerated. Cardiovascular risks are increased by age, smoking, use of alcohol, and excess fat in the diet. Hepatobiliary complications may occur during pill use. The carcinogenic role of OCx remains controversial, although growth of preexisting breast cancers is accelerated with pill use. The multifactorial etiologies of cardiovascular ailments, atherosclerosis, and cancerous tumors make the role of OCs difficult to assess. OCs can interact with various drugs, heightening the undesirable effects of each. Research on hormonal methods of contraception is currently directed toward achieving a better tolerance and administration of both male and female methods.
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PMID:[Oral contraception: failures and risks]. 1228 May 90


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