Abstract:
:Clinical experience has indicated that the effects of RU 486 can be divided into dose-dependent and dose-independent effects. Examples of the dose-dependent effects include the antiglucocorticoid effects of RU 486, whereas pregnancy termination or dilatation of the cervix can be considered dose-independent with the various regimens tested so far. Following oral intake in man, the serum levels of RU 486 are in the micromolar range, and the half-life is approximately 30 hours. The concentrations of RU 486 in myometrial tissue are approximately one-third of those measured in serum. However, due to saturation of alpha 1-acid glycoprotein (AAG), the serum binding protein for RU 486, the serum levels remain similar within the dose range of 100-800 mg of RU 486. The unbound RU 486 is metabolized by two-step demethylation or by hydroxylation. The demethylated and hydroxylated metabolites of RU 486 retain considerable affinities of 9-21% towards the human progesterone receptor, and 45-61% towards the human glucocorticoid receptor (RU 486 = 100%), suggesting a biological role for the metabolites. Rat serum lacks a specific binding protein for RU 486. Even though the levels of RU 486 in rat adipose tissue are 40 times as high as those seen in serum, the concentrations of RU 486 in rat brain are only 28% of the serum levels. This indicates that diffusion of RU 486 into the central nervous system is restricted by the blood-brain barrier. Hence, the dose-dependency of certain centrally mediated effects of RU 486 might be explained by the limited diffusion of RU 486 into hypothalamic/hypophyseal sites, which seem to be reached only after ingestion of high doses of RU 486. However, the peripheral effects of RU 486, such as termination of pregnancy, are mediated via steroid receptors in target tissues. This suggests that similar biological effects can be attained at considerably lower doses than the ones currently in use. :RU-486 has both dose-dependent effects and dose-independent effects. Acute treatment of single doses of at least 400 mg RU-486 increase secretion of adrenocorticotropic hormone. 50-100 mg RU-486 activate the hypothalamo-pituitary-adrenal (HPA) axis. Pregnancy termination and dilatation of the cervix are dose-independent effects. Oral ingestion in humans results in RU-486 serum concentrations in the micromolar range with a half-life of about 30 hours. RU-486 levels in myometrial tissue are about 33% lower than those in the serum. 2-step demethylation or hydroxylation metabolizes unbound R-486. The resulting RU-486 metabolites are able to bond strongly to the human progesterone receptor and to the human glucocorticoid receptor (9-21% and 45-61%, respectively, vs. 100% for RU-486), indicating that the metabolites have a biological role. Research in rats suggests that the blood-brain barrier prevents the diffusion of RU-486 into the central nervous system. Limited diffusion of RU-486 into hypothalamic/hypophyseal sites may account for the dose-dependency of certain centrally mediated effects of RU-486. Oral intake of high doses of RU-486 appears to be the only route to hypothalamic/hypophyseal sites. Steroid receptors in target tissues, e.g., endometrium, mediate RU-486's indirect effects, e.g., pregnancy termination, indicating much lower doses of RU-486 than are now being used can have the same effects.
journal_name
Ann Medjournal_title
Annals of medicineauthors
Heikinheimo O,Kekkonen Rdoi
10.3109/07853899309147861subject
Has Abstractpub_date
1993-02-01 00:00:00pages
71-6issue
1eissn
0785-3890issn
1365-2060journal_volume
25pub_type
杂志文章abstract::INTRODUCTION. Premature ovarian failure (POF) can occur naturally at an early age or be due to iatrogenic agents. Indeed, ovaries are very sensitive to cytotoxic treatment, especially to radiation and alkylating agents. METHODS. Several options are currently available to preserve fertility in cancer patients and allow...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853890.2010.546807
更新日期:2011-01-01 00:00:00
abstract::Autoantibodies directed to intracellular antigens can be detected in many systemic rheumatic diseases. In this review, we discuss the clinical significance of antinuclear antibodies (ANA) associated with systemic lupus erythematosus (SLE), Slögren's syndrome, scleroderma and polymyositis/dermatomyositis, the immunogen...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899608999081
更新日期:1996-08-01 00:00:00
abstract::The metabolic syndrome, which is very common in the general population, is defined by the clustering of several classic cardiovascular risk factors, such as type 2 diabetes, hypertension, high triglycerides and low high-density lipoprotein cholesterol (HDL). Central obesity and insulin resistance, which are the two un...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890500401234
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Finnish type of hereditary gelsolin amyloidosis (FGA) is one of the most common diseases of Finnish disease heritage. Existing FGA knowledge is based only on smaller patient series, so our aim was to elucidate the natural course of the disease in a comprehensive sample of patients and to build up a national ...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853890.2015.1075063
更新日期:2015-01-01 00:00:00
abstract::Pulmonary arterial hypertension is a rapidly progressing disease characterized by an over- expression of endothelin. In addition to its potent pulmonary vasoconstrictor effects, endothelin has been shown to produce many of the aberrant changes, such as hypertrophy, fibrosis, inflammation, and neurohormonal activation ...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890310017477
更新日期:2003-01-01 00:00:00
abstract::The mucosal surfaces are the first portals of entry for most infectious agents, among which respiratory and intestinal viruses are of greatest epidemiological importance. To combat these infections, the immune system uses unspecific and specific mechanisms. Unspecific responses include the production of virus-induced ...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853890109002074
更新日期:2001-04-01 00:00:00
abstract::Diabetes in childhood and adolescence is a difficult, lifelong, evolving disorder. Insulin treatment is essential for the establishment and maintenance of optimal metabolic control but it is only part of a comprehensive child-focused management strategy which must be initiated at the time of diagnosis. Attention must ...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899708999372
更新日期:1997-10-01 00:00:00
abstract::Depression, among other mood disorders, represents one of the most common health problems worldwide, with steadily increasing incidence and major socio-economic consequences. However, since the knowledge about the underlying pathophysiological principles is still very scanty, depression and other mood disorders are cu...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853891003769957
更新日期:2010-05-06 00:00:00
abstract::Low back pain as a research topic has been treated in this symposium, as in other contexts, as though it were an illness. It is, however, a complaint - and as such, even, potentially not a genuine one. Appreciation of the true character of back pain is essential for the proper orientation and setting of priorities for...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853898909149228
更新日期:1989-10-01 00:00:00
abstract::Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting w...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853890.2016.1168936
更新日期:2016-01-01 00:00:00
abstract::BACKGROUND. Non-steroidal anti-inflammatory drugs are associated with poor upper gastrointestinal (UGI) tolerability and increased ulcer risk, but patient adherence to gastroprotective co-therapy is frequently inadequate. A fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole mag...
journal_title:Annals of medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.3109/07853890.2011.625971
更新日期:2011-12-01 00:00:00
abstract::The associations between candidate gene polymorphisms and coronary heart disease (CHD) are complex as a consequence of pleiotropy, variation with age, selection due to the high lethality of the disease, and interactions with other genes and with environmental factors. Identification of the gene variants that contribut...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899608999109
更新日期:1996-10-01 00:00:00
abstract::Among the approximately 7,000 cytogenetically abnormal childhood and adult B- and T-lineage acute lymphoblastic leukemias (ALL) published to date, numerous recurring chromosomal aberrations and abnormality patterns have been identified, and it has been clearly shown that the cytogenetic features often correlate closel...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890410018808
更新日期:2004-01-01 00:00:00
abstract::Congruence of evidence from all medical research methodologies has established the major causal influences in cardiovascular disease. Causation thus established, epidemiological observations are the best available evidence on which to base estimates of the potential of preventive strategies. From population comparison...
journal_title:Annals of medicine
pub_type: 临床试验,杂志文章,评审
doi:10.3109/07853898909149926
更新日期:1989-06-01 00:00:00
abstract::The circadian rhythms of night shift workers do not usually adjust to their unusual work and sleep schedules, reducing their quality of life and producing potentially dangerous health and safety problems. This paper reviews field studies of simulated night work in which shifted light-dark cycles were constructed with ...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899908998783
更新日期:1999-04-01 00:00:00
abstract:INTRODUCTION:The objective of the present study was to examine the association between low-grade albuminuria and hearing impairment in the non-diabetic population. MATERIALS AND METHODS:Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853890.2015.1093163
更新日期:2015-01-01 00:00:00
abstract::Epstein-Barr virus (EBV) expresses genes that stimulate cells to divide in culture. This property, coupled with the close association of the virus with numerous malignancies, has prompted its designation as a human DNA tumour virus. Before human herpesvirus 8 (HHV-8, alternatively KS virus) was discovered, EBV was uni...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899809005852
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:There is an unmet need for a straightforward and cost-effective assessment of multiple lipoprotein risk factors for vascular diseases. AIMS:1) To study the relation of various lipoprotein lipid and apolipoprotein (apo) measures on the Friedewald inputs, i.e. plasma triglycerides (TG), cholesterol (TC), and ...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.1080/07853890902893392
更新日期:2009-01-01 00:00:00
abstract::Twenty-three randomly selected plasma samples from apparently healthy, middle aged men were analysed for coenzyme Q10 (CoQ10), alpha-tocopherol (AT) and free cholesterol (FC) in: 1) whole plasma, 2) the HDL lipoprotein fraction after LDL precipitation (VLDL + LDL). CoQ10, AT and FC in plasma averaged 0.69 +/- .11, 6.7...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853899109148098
更新日期:1991-12-01 00:00:00
abstract::Adding to the difficulty of interpreting the human genome sequence and annotating protein sequence databases is the observation that a single protein can 'moonlight' or perform multiple, apparently unrelated, functions. This review summarizes examples of moonlighting proteins in cellular activities and biochemical pat...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890310004101
更新日期:2003-01-01 00:00:00
abstract::A comprehensive study of coronary heart disease (CHD) risk factors and their determinants in children and adolescents in Finland was initiated in the late 1970's. The main cross-sectional study was undertaken in 1980, with 3596 subjects aged from 3 to 18 years participating. The first follow-up study was carried out i...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853898909149938
更新日期:1989-06-01 00:00:00
abstract::During recent decades an increasing number of case reports have pointed at a relation between atrophic gastritis type A and gastric carcinoid. This relation has now been quantitatively documented in endoscopic screening studies. Among patients with pernicious anaemia the prevalence of gastric carcinoid was 2-9%. Many ...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853898909149210
更新日期:1989-08-01 00:00:00
abstract::The effect of different clinical conditions on urinary dolichols was studied in 219 hospital patients and in 24 pregnant women. Significantly increased urinary dolichol levels were found in patients with severe bacterial infections (mean +/- SEM, 37.5 +/- 8.0 micrograms/mmol creatinine, P less than 0.001), in patients...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853898909149176
更新日期:1989-02-01 00:00:00
abstract::In Europe around 1970 there were only a few small and often poorly known epidemiological studies on risk factors and the incidence of coronary heart disease. In order to enhance the utilization of the information contained in them, the Medical Clinic in Heidelberg offered uniform data analysis to qualifying contributi...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853898909149931
更新日期:1989-06-01 00:00:00
abstract::The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over ...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899309147317
更新日期:1993-10-01 00:00:00
abstract::Obesity in males is accompanied by a significant decrease in testosterone levels. This decrease is essentially a consequence of the decrease of the sex hormone binding hormone (SHBG) binding capacity, itself probably the consequence of the increased insulin levels. In moderate obesity, free testosterone levels are nor...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899608999068
更新日期:1996-02-01 00:00:00
abstract::Mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) are autoimmune diseases with a genetic background, and it is reasonable to suggest that aberrations in T cell receptor (TCR) genes could contribute to these diseases, as they play an important role in immune regulation. We studied TCR beta-c...
journal_title:Annals of medicine
pub_type: 杂志文章
doi:10.3109/07853899409147342
更新日期:1994-04-01 00:00:00
abstract:INTRODUCTION:Ambient air pollution is associated with adverse cardiovascular events. This meta-analysis aimed to investigate the short-term association between air pollution and cardiovascular effects on healthy volunteers. METHODS:We searched databases to identify randomized trials with controlled human exposures to ...
journal_title:Annals of medicine
pub_type: 杂志文章,meta分析
doi:10.1080/07853890.2016.1252054
更新日期:2017-03-01 00:00:00
abstract::Despite striking extensions of lifespan, leading causes of death in most countries now constitute chronic, degenerative diseases which outpace the capacity of health systems. Cardiovascular disease is the most common cause of death in both developed and undeveloped countries. In America, nearly half of the adult popul...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.1080/07853890.2016.1271957
更新日期:2017-05-01 00:00:00
abstract::Steroids diffuse through polysiloxone at a constant rate, and steroids placed in the vagina rapidly pass through the vaginal epithelium into the circulation. Combining these principles led to the development of contraceptive vaginal rings (CVR) consisting of various progestins, with and without oestrogen, placed in fl...
journal_title:Annals of medicine
pub_type: 杂志文章,评审
doi:10.3109/07853899309164167
更新日期:1993-04-01 00:00:00