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)

Many recent advances in fertility control have involved progestin-only contraception. The progestin-only oral contraceptive, which has a failure rate of 1-2.5%, is especially suited to women who are breastfeeding or cannot tolerate estrogen. The levonorgestrel implant, Norplant, is effective for 5 years and has a 1.5% failure rate. Currently under development is Norplant-2--a system that requires 2 rather than 6 capsules, lasts for 3 years, and is as effective as Norplant-1. Also under development is a biodegradable progestin-only implant. However, there are many side effects associated with these methods. Irregular bleeding occurs in 60-70% of Norplant acceptors and leads 12-20% of these women to discontinue implant use. Headaches and acne occur in 5-20% of users of levonorgestrel methods. More significant are concerns that progestin tends to increase low density lipoprotein levels. Although initial human trials have indicated a drop of 5-15% in both these levels, studies in macaque monkeys have found that progestin-only contraception is more likely to cause atherosclerosis than an estrogen-progestin formulation.
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PMID:Progestin-only contraception. 202 98

Twenty men with nodulocystic acne were treated with oral isotretinoin (13-cis-retinoic acid) for four months. Plasma lipids and lipoprotein determinations were obtained before and during treatment to quantitate the effects of oral isotretinoin on lipid metabolism. Maximum isotretinoin-induced elevations in plasma triglyceride and cholesterol levels were 67% and 16%, respectively. Additional maximal changes included very-low-density lipoprotein cholesterol increases of 56%, low-density lipoprotein cholesterol increases of 22%, and high-density lipoprotein decreases of 10% from pretreatment values. Chronic increases in plasma cholesterol levels, increases in low-density lipoprotein cholesterol levels, and decreases in high-density lipoprotein cholesterol levels may predispose subjects to premature atherosclerosis. Because of the potential for unmasking an occult lipid or lipoprotein disorder, the plasma lipid and lipoprotein profiles of subjects receiving isotretinoin should be carefully monitored.
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PMID:Changes in plasma cholesterol and triglyceride levels after treatment with oral isotretinoin. A prospective study. 622 96

The combination hormonal contraceptive has been effectively used since 1956. Current developments in hormonal contraception involve efforts to make the pill safer by reducing both estrogen and progestogen content. Publications of a few years ago pointed out that the pill was hazardous to health (hypertension) and could cause life-threatening complications in the form of thromboembolic accidents (ischemic heart disease and stroke). This risk increased with cigarette smoking. Lowering of the estrogen content (less than 50 mcg) lessened the risk of thromboembolism and lowering of the progestogen component (150 mcg levonorgestrel) led to the conclusion that further modification of the pill's composition was no longer necessary. The 1981 follow-up study by the Royal College of General Practitioners reversed some of the earlier conclusions about the risks of hormonal contraceptives. New research on the effects of steroids on lipid metabolism found that estrogen increased and progestogen decreased the serum HDL-cholesterol level; the latter has a beneficial effect in preventing atherosclerosis. The androgen effect of the progestogen component is thought to lie in its capacity to bind to sex hormone-binding globulin and steroid receptors. New research and publicity are based on the fact that desogestrel (3-ketodesogestrel) has no androgenic side effects, hence is used as the progestogen in the combination pill. Side effects of pill use can be classified as follows: 1) effects occurring within weeks to months: cardiovascular disorders, acne, weight increase; lowering of estrogen dosage in pill will decrease risk; 2) effects occurring within months to years: IHD and CVA; lowering progestogen dosage and stop smoking cigarettes will reduce risk; and 3) effects occurring from years to decades: possible carcinogenic effect; lowering of estrogen and progestogen dosage is recommended plus careful individual prescription.
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PMID:[Current developments in hormonal contraception]. 717 11

The development of a new generation of progestins deemed less androgenic than their earlier counterparts has led to a number of misconceptions regarding their possible benefits in combination oral contraceptives. All combination oral contraceptives are beneficial for treating such androgenic conditions as acne and hirsutism. The only expressed androgenic effect of some first- and second-generation combined oral contraceptives are changes in plasma lipid and lipoprotein levels. However, the overall effect of today's low-dose oral contraceptives is largely lipid neutral, and human and monkey studies have shown that oral contraceptive use is associated with reduced, not increased, atherosclerosis rates. Myocardial infarction rates are not increased among oral contraceptive users, except among those who are heavy smokers.
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PMID:Update on androgenicity. 998 32

The general benefits of the use of methods of contraception are the documented decrease of maternal and fetal mortality and morbidity, the diminution of the rate of prematurity and low birth weight, the decrease in induced abortion and sexually transmitted diseases (STDs) and certain gynecological cancer types. Natural methods of contraception pose the benefit of lacking effects on the organs and not introducing any external factors into the body. Barrier methods provide protection against STDs (a 50% reduction) and against cervical cancer (human papilloma virus), especially for adolescents and those with multiple sex partners. The chemical methods provide local antiseptic and antibiotic action that can be beneficial for vaginal and cervical infections. Hormonal methods, namely the oral contraceptive (OC) pill, also possess noncontraceptive benefits: regulation of the menstrual cycle, including diminution of dysmenorrhea, menstrual pain, menstrual flow, and anemia; reduced risk of pelvic inflammatory disease, endometrial and ovarian cancer, benign breast pathology, acne, and hirsutism; in addition to the therapy of polycystic ovarian syndrome, hypothalamic amenorrhea, and dysfunctional hemorrhage. Further benefits include the decrease of the risk of osteoporosis, rheumatoid arthritis by 60% in families at risk, ectopic pregnancy, atherosclerosis, uterine myomas by up to 31%, and ovarian cysts. Contraceptives that contain progestational hormones (oral, injectable, implant, or IUD forms) are also beneficial for endometrial hyperplasia and uterine polyps. IUDs (except for progestational IUDs) have local effect without the potential side effects of hormones. Terminal methods of contraception (tubal ligation and ligation of the vas deferens) are reliable without causing alterations in the physiology of the organs.
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PMID:[Non-contraceptive benefits of contraception]. 1217 57

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

Many studies show that low-dose OCs have little adverse effect on carbohydrate metabolism and are safe for healthy women, women with a history of gestational diabetes, and women with insulin-dependent diabetes to use. In fact, large epidemiologic studies indicate that OCs, even the high-dose OCs (=or 50 mcg) for long periods, do not increase the risk of diabetes. There is some evidence indicating that OC use does not heighten the progression of diabetic retinopathy, nephropathy, or cardiovascular complications among women with insulin-dependent diabetes. There is no significant difference in carbohydrate metabolism among the different OC formulations. One must carefully consider the risk:benefit ratio of OC use in diabetic women since pregnancy has serious consequences for both mother and fetus. Cardiovascular complications in OC users do not originate from atherogenesis. The androgenic properties of the progestin in low-dose OCs and their effect on lipids are inconsequential for later development of coronary atherogenesis. The estrogen in OCs may protect against atherosclerosis, particularly among women at high risk of atherosclerosis. Former OC users are not at an increased risk of coronary heart disease, stroke, or other heart disease. Lipid changes in OC users tend to remain within the normal range and return to pretreatment values during the pill-free week. All OCs suppress gonadotropins and subsequent ovarian androgen production. They partially suppress androgen production by the adrenals as well. This suppression from two fronts outweighs any androgenic action of the progestin alone. Further, androgenic action probably cannot overpower the estrogen effect. The dose of levonorgestrel used in OCs is too low to express androgenic effects. Since OCs suppress androgen production, all OCs tend to improve acne. OCs reduce free testosterone and increase sex hormone binding globulin levels.
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PMID:Metabolic effects of oral contraceptives: fact vs. fiction. 1232 11

Hydrophobic attractive force is the major force in maintaining the stability of biomembranes, yielding coordinated functionality to the embedded proteins that they contain. This force between the composite linear hydrocarbons of the biomembranes is a function of their length and their mutual parallel distance from each other, and is extremely sensitive to this distance. Extracellular, natural linear hydrocarbons of certain length and shape can intercalate into lipid matrix of the biomembranes, reducing their innate hydrophobic net strength in a concentration-dependent manner, making them loose, leaky, and thus gaining the credence of stimulus-generating agents. In physiological circulatory concentration, these molecules may have a role for the maintenance of cellular homeostasis. However, in stagnating physiological excess, these same agents can become acutely or chronically stimulating and, therefore, disease-precipitating. Such situations do exist in the clinical disorders of acne, atherosclerosis, acute pancreatitis, diabetes, diabetic retinopathy, homocysteinemea, and stress. A systematic approach, beginning with surface film studies with the suspect linear hydrocarbons, can be followed up with in vitro and in vivo studies. This should substantiate or negate the view presented here. Isolated information, along these lines, already exist in literature. The example of acne is a suitable starting point to elaborate this view, for sebaceous gland of the human pilosebaceous unit (PSU) contains all the exemplary, stimulus-inducing linear hydrocarbons to generate surface-reaction on the pilosebaceous ductal surface.
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PMID:Disruption of hydrophobic stability of biomembranes is the earliest event in several clinical disorders. 1528 77

Isotretinoin treatment alters the plasma lipid levels but the mechanisms and the effects on the metabolism of triglyceride-rich lipoproteins such as chylomicrons and very-low-density lipoproteins remain unclear. We investigated the effect of isotretinoin on the plasma kinetics of emulsion models of triglyceride-rich lipoproteins and the lipid profile. Ten patients with acne were treated with 0.8 mg/kg of isotretinoin over 4 weeks for comparison with non-treated acne patients. In both groups the plasma kinetic study of a triglyceride-rich emulsion double-labeled with 14C-cholesterol oleate and 3H-triolein was performed after intravenous injection of the emulsion and radioactive counting in plasma samples collected over 60 min. Patients using isotretinoin showed decreased removal from the plasma of the 3H-triglyceride (median 0.019 min-1 TG) compared with controls (median 0.044 min-1, P=0.007), and the removal of the emulsion 14C-cholesterol oleate also tended to be decreased (treatment: 0.011 min-1; controls: 0.024 min-1, P=0.06). The values of total and LDL cholesterol and triglycerides were increased post-treatment (P<0.03). In conclusion, while increasing the fasting plasma concentration of VLDL and LDL, which are traditional risk factors for atherosclerosis, isotretinoin treatment also slows down the metabolism of triglyceride-rich lipoproteins such as chylomicrons, as tested by the emulsion model, an effect that is also increasingly recognized as atherogenic.
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PMID:Effects of isotretinoin on the metabolism of triglyceride-rich lipoproteins and on the lipid profile in patients with acne. 1642 99

Activators of metabolic PPAR receptors are used in diabetology and lipidology. Many substance influancing PPAR (beta/delta) are in research. These substances will be perhaps used in obesitology and in atherosclerosis treatment. Much quicker is approaching the use in dermatology. The effect of receptor stimulation will be used in wound healing and in the treatment of allergic and proliferative diseases. Some realeted substancies influencing heterodimers with RXR or RAR receptors are used in the treatment of acne and skin lymfomas. Dermatology will be after internal medicine the second field where influencing of PPAR receptors will be very important.
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PMID:[Metabolic PPAR nuclear receptors and skin]. 1677 Oct 88


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