Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of synthetic progestogens are currently available which differ greatly among themselves in various ways. The common property of all progestogens is that they transform a proliferative endometrium into a secretory or luteal endometrium by fixing the progestogen or 1 of its metabolites to the progesterone receptor. Most progestogens also have a greater or lesser affinity for other hormonal receptors, and some cause modifications in metabolism, especially of lipids and glucose. Synthetic progestogens can be classified according to their chemical formulas, biologic properties, and efficiency in relation to hormone receptors, but none of the current classification systems is a satisfactory guide to use. It is not yet definitively known whether pro-hormones, which must be transformed into norethindrone in vivo before taking effect, are advantageous or disadvantageous for therapeutic use. Synthetic progestogens have been found to have varying metabolic effects according to their content and dosage; hepatic function, lipid metabolism, glucose metabolism, coagulation factors, and the renin-angiotensin-aldosterone system are among the functions affected. The metabolic effects of synthetic progestogens are the principal criteria of choice. High dose 19 norsteroids are recommended only for cancer treatment, 19 nor-pregnane derivatives and progesterone isomers appear suitable for treatment of conditions such as endometriosis, premenopausal menstrual irregularities, and menstrual irregularity resulting from luteal insufficiency in younger women. Low-dose 19 norsteroids remain the best choice for contraception. Levonorgestrel has been preferred over norethindrone for some time because it is effective at a dose of .150 mcg compared to 1 mg for norethindrone, but some recent research suggests that even at a much smaller dose, levonorgestrel may cause more metabolic modifications than norethindrone. The pro-hormones ethynodial diacetate and lynestrel have additional metabolic effects whose consequences are as yet unknown. Preparations containing levonorgestrel should be preferred until the expected appearance on the market of triphasic preparations containing norethindrone and desogestrel, which permit excellent cycle control. Among progestogen-only contraceptives, 10 mg/daily of lynestrenol is associated with high rate of side effects. Microdose synthetic progestogen preparations are sometimes useful but offer imperfect efficacy, poor cycle control, higher risk of extrauterine pregnancy and ovarian cysts, and creation of iatrogenic luteal insufficiency.
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PMID:[Choosing the right synthetic progestogen]. 1231 5

Although the dehydration-rehydration problem in end-of-life care is one of the most important issues, clinical indications of hydration therapy have not been clarified because the pathophysiology is poorly understood. To explore the physiological changes of fluid status in terminally ill cancer patients, a prospective observational study was performed. We obtained 9 pairs of blood samplings from hospice inpatients with irreversible bowel obstruction who underwent two or more laboratory examinations during the admission periods. The plasma renin activity (PRA) and brain natriuretic peptide (BNP) were measured, in addition to basic laboratory tests performed as clinically required. A chart review evaluated the degree of fluid retention symptoms. In 7 patients receiving intravenous rehydration of 700-2200 ml/day, the mean PRA level significantly increased from 3.5+/-2.5 ng ml(-1) h(-1) to 11+/-8.2 ng ml(-1) x h(-1) ( P=0.047), and the mean BNP level significantly decreased from 52+/-34 pg/ml to 22+/-14 pg/ml ( P=0.047). Edema, ascites, and pleural effusion/pulmonary edema deteriorated in 5, 3, and 5 patients, respectively. In 2 patients without rehydration therapy, peripheral edema deteriorated with increased PRA levels (0.5 to 20 ng ml(-1) x h(-1), 0.4 to 8.7 ng ml(-1) x h(-1), respectively). In conclusion, intravenous volume depletion with fluid retention symptoms was observed in terminally ill cancer patients with intestinal obstruction both receiving and not receiving intravenous hydration. The pathological mechanism hypothesized is the fluid shift from the intravascular compartment to the interstitial spaces.
Support Care Cancer 2002 Sep
PMID:Fluid status of terminally ill cancer patients with intestinal obstruction: an exploratory observational study. 1235 26

The incidental finding of an unsuspected adrenal mass ranges from 0.5% to 5% in abdominal CT series. The optimal diagnostic approach to such masses is to diagnose malignant or secretory tumors requiring excision and to otherwise avoid unnecessary surgery. Physical examination generally contributes little. A standard biochemical evaluation should include the measurement of 24 hour urinary catecholamines and metanephrine, urinary free cortisol and plasma cortisol levels at 8 a.m. and 8 p.m. combined with an overnight low-dose dexamethasone suppression test, serum potassium assay, and determination of upright plasma aldosterone to plasma renin activity. These tests will serve to screen for pheochromocytoma, subclinical Cushing's syndrome, and primary hyperaldosteronism respectively. Imaging characteristics suggestive of malignancy include: size greater than 4 cm., heterogeneous lesion and/or density greater than 20 Hounsfield Units on CT scan, slow enhancement with delayed washout after intravenous contrast injection on CT scan, and slightly decreased signal intensity in out of phase (fat suppressed) MR acquisition. Fine-needle aspiration biopsy should be performed only if metastatic disease is suspected. Adrenal scintigraphy with iodocholesterol may be useful where adenoma with subclinical Cushing's syndrome or solid tumor is suspected. In summary, the following strategy is recommended for the management of adrenal incidentalomas : mass lesions larger than 4 cm. and hormone-secreting tumors should be removed. All non-secreting adrenal incidentalomas smaller than 4 cm. in diameter should be followed by serial imaging at regular intervals (6, 12, and 36 months) and by endocrine reevaluation at one year.
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PMID:[Diagnostic and therapeutic strategy for an incidental finding of an adrenal mass]. 1241 Jan 36

This minireview is an update of a 1997 review on erythropoietin (EPO) in this journal. EPO is a 30,400-dalton glycoprotein that regulates red cell production. In the human, EPO is produced by peritubular cells in the kidneys of the adult and in hepatocytes in the fetus. Small amounts of extra-renal EPO are produced by the liver in adult human subjects. EPO binds to an erythroid progenitor cell surface receptor that includes a p66 chain, and, when activated, the p66 protein becomes dimerized. EPO receptor activation induces a JAK2 tyrosine kinase, which leads to tyrosine phosphorylation of the EPO receptor and several proteins. EPO receptor binding leads to intracellular activation of the Ras/mitogen-activated kinase pathway, which is involved with cell proliferation, phosphatidylinositol 3-kinase, and STATS 1, 3, 5A, and 5B transcriptional factors. EPO acts primarily to rescue erythroid cells from apoptosis (programmed cell death) to increase their survival. EPO acts synergistically with several growth factors (SCF, GM-CSF, 1L-3, and IGF-1) to cause maturation and proliferation of erythroid progenitor cells (primarily colony-forming unit-E). Oxygen-dependent regulation of EPO gene expression is postulated to be controlled by a hypoxia-inducible transcription factor (HIF-1alpha). Hypoxia-inducible EPO production is controlled by a 50-bp hypoxia-inducible enhancer that is approximately 120 bp 3' to the polyadenylation site. Hypoxia signal transduction pathways involve kinases A and C, phospholipase A(2), and transcription factors ATF-1 and CREB-1. A model has been proposed for adenosine activation of EPO production that involves protein kinases A and C and the phospholipase A(2) pathway. Other effects of EPO include a hematocrit-independent, vasoconstriction-dependent hypertension, increased endothelin production, upregulation of tissue renin, change in vascular tissue prostaglandins production, stimulation of angiogenesis, and stimulation of endothelial and vascular smooth muscle cell proliferation. Recombinant human EPO (rHuEPO) is currently being used to treat patients with anemias associated with chronic renal failure, AIDS patients with anemia due to treatment with zidovudine, nonmyeloid malignancies in patients treated with chemotherapeutic agents, perioperative surgical patients, and autologous blood donation. A novel erythropoiesis-stimulating factor (NESP, darbepoetin) has been synthesized and when compared with rHuEPO, NESP has a higher carbohydrate content (52% vs 40%), a longer plasma half-life, the amino acid sequence differs from that of native human EPO at five positions, and has been reported to maintain hemoglobin levels just as effectively in patients with chronic renal failure as rHuEPO at less frequent dosing. The use of rHuEPO and darbepoetin to enhance athletic performance is officially banned by most sports-governing bodies because the excessive erythrocytosis can lead to increased thrombogenicity and can cause deep vein, coronary, and cerebral thromboses.
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PMID:Erythropoietin: physiology and pharmacology update. 1252 67

Angiotensin II has been shown to have possible mitogenic and angiogenic effects in human cell lines and animal models of breast cancer. It is converted from its precursor to its active form by the angiotensin I-converting enzyme (ACE). A recent epidemiological study observed lower breast cancer incidence in female users of ACE inhibitors relative to nonusers with comparable cardiovascular conditions. To study the hypothesis that reduced ACE activity is associated with reduced risk of breast cancer, we conducted a nested case-control study within the Singapore Chinese Health Study Cohort to investigate the associations between the ACE A-240T and I/D gene polymorphisms, and breast cancer risk. For this analysis, 189 incident breast cancer cases and 671 female cohort control subjects were compared. The low-activity A and I alleles were the putative "low-risk" alleles. The I/D and A-240T genotypes exhibited significant linkage disequilibrium among Singapore Chinese (contingency coefficient = 0.74; P < 0.001). With adjustment for breast cancer risk factors, women with one or two copies of the low activity A allele showed a statistically significant reduction in risk compared with those with the TT genotype [odds ratio (OR), 0.55; 95% confidence interval (CI), 0.34-0.90]. The risk reduction was enhanced after excluding subjects with medical conditions for which ACE inhibitors are commonly prescribed (OR, 0.49; 95% CI, 0.27-0.89). Comparable results were obtained with respect to the I/D genotype and risk of breast cancer. When the I/D and A-240T genotypes were considered simultaneously, compared with women with the high-activity genotypes (either TT or DD or both), those with the low-activity genotypes (presence of both A and I alleles) exhibited lower breast cancer risk (OR, 0.46; 95% CI, 0.27-0.81). Our findings support experimental data implicating ACE and angiotensin II in breast cancer, and suggest that the renin-angiotensin system may serve as a therapeutic target for breast cancer treatment and prevention.
Cancer Res 2003 Feb 01
PMID:Angiotensin I-converting enzyme (ACE) gene polymorphism and breast cancer risk among Chinese women in Singapore. 1256 98

It has been demonstrated that some myeloid blasts express renin, but normal bone marrow (BM) does not display this expression. The aim of the present work was to analyze the renin expression in different hematological malignancies and different myeloid cell lines. We investigated the expression of renin by RT-PCR in BM from patients with hematological malignancies (106 patients), in nine normal BM from healthy donors and in leukemic cell lines (K562, KU812, MEG-01, U-937 and HL60), as well in K562 cell line subjected to differentiation treatments. We have observed renin expression in cells from acute myeloid leukemia (AML), chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cases. The highest frequency was observed in AML-non acute promyelocytic leukemia(APL) cases (47.2% of the cases). The disappearance of this expression was associated with the status of complete remission of AML. Renin is expressed in some myeloid human leukemia cell lines such as K562, KU812 and MEG-01. However, when K562 cells were treated with inducers of growth inhibition and/or differentiation, the expression did not disappear, indicating that renin expression is associated with a blastic phenotype rather than with cell proliferation. The obtained findings suggest that the renin expression could have a role on the disease development and could be used as an aberrant marker of leukemia.
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PMID:Renin expression in hematological malignancies and its role in the regulation of hematopoiesis. 1261 27

Malignant ascites occurs in association with a variety of neoplasms. It is a frequent cause of morbidity and presents significant problems for which there are no clear management guidelines. In this article we discuss various modalities which are available including diuretic therapy, paracentesis, peritoneovenous shunts and intraperitoneal chemotherapy. There are no randomized trials of diuretic drugs to assess their efficacy in malignant ascites. Phase II data suggest that they are effective in approximately one-third of patients with malignancy, and their efficacy may be determined by plasma renin/aldosterone concentrations. Paracentesis provides relief in up to 90% of patients; because of varying reports of hypovolaemia, some advocate simultaneous intravenous fluid infusion. Permanent percutaneous drains may prevent the need for repeated paracentesis, although there is potential for infection. A peritoneovenous shunt also prevents the need for repeated paracenteses, whilst maintaining normal serum albumin concentrations. Blockage occurs in 25% of shunts, which are contraindicated in the presence of heavily bloodstained ascites because of the risk of occlusion. The preclinical and clinical experience with anti-angiogenic agents such as the matrix metalloproteinase inhibitors and the VEGF antagonists suggests that these agents may have a role in the treatment of malignant ascites.
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PMID:The current and future management of malignant ascites. 1270 13

It is remarkable that phytoplankton and zooplankton have been producing vitamin D for more than 500 million years. The role of vitamin D in lower non-vertebrate life forms is not well understood. However, it is critically important that most vertebrates obtain an adequate source of vitamin D, either from exposure to sunlight or from their diet, in order to develop and maintain a healthy mineralized skeleton. Vitamin D deficiency is an unrecognized epidemic in most adults who are not exposed to adequate sunlight. This can precipitate and exacerbate osteoporosis and cause the painful bone disease osteomalacia. Once vitamin D is absorbed from the diet or made in the skin by the action of sunlight, it is metabolized in the liver to 25-hydroxyvitamin D [25(OH)D] and then in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)2D]. 1,25(OH)2D interacts with its nuclear receptor (VDR) in the intestine and bone in order to maintain calcium homeostasis. The VDR is also present in a wide variety of other tissues. 1,25(OH)2D interacts with these receptors to have a multitude of important physiological effects. In addition, it is now recognized that many tissues, including colon, breast and prostate, have the enzymatic machinery to produce 1,25(OH)2D. The insights into the new biological functions of 1,25(OH)2D in regulating cell growth, modulating the immune system and modulating the renin-angiotensin system provides an explanation for why diminished sun exposure at higher latitudes is associated with increased risk of dying of many common cancers, developing type 1 diabetes and multiple sclerosis, and having a higher incidence of hypertension. Another calciotropic hormone that is also produced in the skin, parathyroid hormone-related peptide, is also a potent inhibitor of squamous cell proliferation. The use of agonists and antagonists for PTHrP has important clinical applications for the prevention and treatment of skin diseases and disorders of hair growth.
Recent Results Cancer Res 2003
PMID:Evolution and function of vitamin D. 1289 11

The expression and function in growth and apoptosis of the renin-angiotensin system (RAS) was evaluated in human glioblastoma. Renin and angiotensinogen (AGT) mRNAs and proteins were found by in situ hybridisation and immunohistochemistry in glioblastoma cells. Angiotensinogen was present in glioblastoma cystic fluids. Thus, human glioblastoma cells produce renin and AGT and secrete AGT. Human glioblastoma and glioblastoma cells expressed renin, AGT, renin receptor, AT(2) and/or AT(1) mRNAs and proteins determined by RT-PCR and/or Western blotting, respectively. The function of the RAS in glioblastoma was studied using human glioblastoma cells in culture. Angiotensinogen, des(Ang I)AGT, tetradecapaptide renin substrate (AGT1-14), Ang I, Ang II or Ang III, added to glioblastoma cells in culture, did not modulate their proliferation, survival or death. Angiotensin-converting enzyme inhibitors did not diminish glioblastoma cell proliferation. However, the addition of selective synthetic renin inhibitors to glioblastoma cells decreased DNA synthesis and viable tumour cell number, and induced apoptosis. This effect was not counterbalanced by concomitant addition of Ang II. In conclusion, the complete RAS is expressed by human glioblastomas and glioblastoma cells in culture. Inhibition of renin in glioblastoma cells may be a potential approach to control glioblastoma cell proliferation and survival, and glioblastoma progression in combination therapy.
Br J Cancer 2004 Mar 08
PMID:Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma. 1499 8

Drospirenone (DRSP) is a novel progestogen derived from 170alpha-spirolactone. Its pharmacodynamic profile is closer to progesterone than any other currently available progestogen. DRSP has progestational, antialdosterone and antiandrogenic properties, but is devoid of any estrogenic, androgenic, glucocorticoid, antiglucocorticoid or mineralocorticoid activities. The affinity of DRSP for the mineralocorticoid receptor makes it an antagonist of aldosterone, which is not only important in the renin-angiotensin-aldosterone system (RAAS), but also acts directly on the cardiovascular system. DRSP (1, 2 or 3 mg) in combination with 1 mg 17beta-estradiol (E2) is being developed by Schering AG as a continuous combined product for hormone replacement therapy (HRT). Phase II/III trials of E2/DRSP combinations have demonstrated clinical efficacy for the treatment of hot flushes, as well as improvement of bone density in the hip. Within 1 year of treatment with E2/DRSP, more than 80% of recipients regained amenorrhea. E2/DRSP at all three doses of DRSP is associated with a highly favorable safety profile, with excellent endometrial protection after 1 and 2 years (no cases of hyperplasia or cancer), favorable lipid profiles, with no evidence of attenuation of the beneficial effects on lipids of E2, probably due to DRSP's lack of androgenicity. Recipients of E2/DRSP combinations showed a small decrease in body weight, probably due to DRSP's antialdosterone properties. Adverse events with E2/DRSP did not differ significantly from those observed with standard HRT preparations. Phase III studies with E2/DRSP show that DRSP does not antagonize the well-documented reductions of blood pressure associated with E2; rather, small DRSP dose-related reductions in systolic and diastolic blood pressures were observed, which should be beneficial for recipients, especially those who are mildly hypertensive. These effects on blood pressure are probably due to DRSP displaying aldosterone receptor antagonism, a property which, in other settings, has been shown to convey benefits in terms of cardiovascular disease. Further studies of the cardiovascular effects of E2/DRSP combinations are anticipated.
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PMID:Drospirenone: a new cardiovascular-active progestin with antialdosterone and antiandrogenic properties. 1501 48


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