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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 36-year-old woman who developed extreme erythrocytosis following partial correction of severe bilateral hydronephrosis by bilateral ureterolithotomy is presented. Hydronephrosis appears to stimulate renal synthesis and release of erythropoietin. The mechanism could involve increase in medullary hypoxia by increased pressure of the renal pelvis on the medullary vasculature. This might be especially marked when the renal blood supply is compromised by concomitant atherosclerosis, as in this case.
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PMID:[Bilateral hydronephrosis and erythrocytosis]. 262 Aug 75

The aging kidney suffers reduction both in mass and in glomerular filtration rate. These changes may be totally or partially due to atherosclerosis and hypertension, which reduce renal blood flow. Superimposed on these processes, and perhaps responsible for primary loss of renal mass irrespective of renal vascular disease, is glomerular damage and involution that is a consequence of adaptive increases in glomerular perfusion pressure that occurs as the number of nephrons decline with age. The data available at this time do not allow us to distinguish between these two potential mechanisms of renal senescence. The decline in GFR is in turn responsible for reduced renal acidification and the reduced renal clearance of drugs that are normally removed by the kidney. Certain renal functions, however, are depressed to a greater extent than is GFR. Both the ability to maximally dilute the urine and to maximally concentrate it are controlled by serum ADH concentrations and by the action of that hormone on the collecting duct. Aged rats do not maximally secrete ADH under conditions of dehydration and the effect of ADH on the kidney is also attenuated. Elderly humans also cannot maximally suppress ADH secretion when serum osmolality is reduced. Likewise, the renin-angiotensin-aldosterone axis is poorly responsive to volume depletion in aging subjects. As a result, elderly individuals cannot maximally retain sodium under conditions of plasma volume contraction out of proportion to reduction in GFR. The kidney is the site of vitamin D1 hydroxylation. Hydroxylation of vitamin D is reduced out of proportion to any reduction in GFR in the rat. There are no data as yet available on the effect of aging and the production of erythropoietin, a principal regulator of red blood cell mass. Neither are there data available on changes that might occur with advancing age in the ability of the aging kidney to metabolize various hormones, such as parathyroid hormone, glucagon, and insulin. The mechanisms and the full biochemical and physiologic consequences of renal senescence remain to be fully elucidated.
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PMID:The aging kidney. 391

There is a need to change the policy of unselective iron supplementation during periods of life with physiologically increased cell proliferation. Levels of iron stores to be regarded as adequate during infancy and pregnancy are still not well established. Recent data support the view that it is not justified to interfere with physiological adaptations developed through millions of years by sophisticated and precisely coordinated regulation of iron absorption, utilization and storage. Recent data suggest that the chelatable intracellular iron pool regulates the expression of proteins with central importance in cellular iron metabolism (TfR, ferritin, and erythroid 5-aminolevulinic synthetase) in a coordinately controlled way through an iron dependent cytosolic mRNA binding protein, the iron regulating factor (IRF). This factor is simultaneously a sensor and a regulator of iron levels. The reduction of ferritin levels during highly increased cell proliferation is a mirror of the increased density of TfRs. An abundance of data support the vigorous competition for growth-essential iron between microbial pathogens and their vertebrate hosts. The highly coordinated regulation of iron metabolism is probably crucial in achieving a balance between the blockade of readily accessible iron to invading organisms and yet providing sufficient iron for the immune system of the host. The most evident adverse clinical effects of excess iron have been observed in immunodeficient patients in tropical countries and in AIDS patients. Excess iron also increases the risk of initiation and promotion of malignant processes by iron binding to DNA and by the iron-catalysed release of free radicals. Oxygen radicals were shown to damage critical biomolecules leading, apart from cancer, to a variety of human disease states, including inflammation and atherosclerosis. They are also involved in processes of aging and thrombosis. Recent clinical trials have suggested that the use of iron-chelators, natural and synthetic antioxidants, and anti-TfR monoclonal antibodies can contribute in retarding malignant cell proliferation. Hypoferraemia during pregnancy is--like haemodilution--an adaptation to the risks involved in the natural hypercoagulable state of pregnancy. It may also serve to prevent the risk of infections and mutagenicity in the highly proliferating tissues of the foetus. Blunted erythropoiesis has been revealed during the first 30 weeks of pregnancy by the use of the newly developed method of determining the soluble serum transferrin receptor. The lack of increase in erythropoietin levels proves that there is no hypoxia. Decreases in Hb and iron levels are parts of a physiological adaptation. As a consequence they should neither be treated nor prevented. It is stressed that whenever a widespread and ingrained routine medical intervention has to be changed it is essential to first monitor the potential health effects of the recommended change in a national policy.
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PMID:Adequate iron stores and the 'Nil nocere' principle. 824 2

In this study, we examined the modulation of hemopoietic factor production by human umbilical vein endothelial cells in relation to aging and the cell cycle under conditions of interleukin-1 (IL-1) induction and noninduction. Under conditions of IL-1 noninduction, messenger RNA expression levels of macrophage colony-stimulating factor (M-CSF) were three times higher in non-S-phase cells of young cultures than those in S-phase cells. Expression levels decreased in non-S-phase cells of old culture and approached levels similar to that of S-phase cells. The expression of neither E-selectin nor erythropoietin (Epo) was detected in cells from the noninduced state. The expression of granulocyte colony-stimulating factor (G-CSF) was not affected by either cellular aging or the cell cycle; however, the amount of product secreted increased significantly in old cells, suggesting that G-CSF production is under posttranscriptional regulation. Under conditions of IL-1 induction G-CSF and M-CSF expression levels were enhanced in both young and old cells. Expression of Epo was not detected whereas E-selectin was induced. Significant M-CSF product was detected in young cells but not in old cells, whereas G-CSF product increased dramatically in both types of cells. The modulation of these factors is discussed in relation to the maintenance of neutrophil concentration, differentiation, and maturation of leukocytes and their possible effect on atherosclerosis.
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PMID:Modulation of hemopoietic factor production in relation to endothelial cell aging by interleukin-1 induction. 880 39

Most women on dialysis are amenorrheic and do not ovulate, but little information about menstrual patterns in women on dialysis exists, especially since the introduction and use of recombinant human erythropoietin, a therapy that may improve sexual interest and function. In this study, women who were < or = 55 years of age at the start of dialysis (n = 76) completed questionnaires and form the study group. Women older than 55 years at the start of dialysis did not complete the entire questionnaire (n = 115), but their medication records were reviewed for estrogen replacement therapy. The questionnaire asked about pregnancies, menstrual periods (regularity, frequency, duration, character of flow, menopause), and menopause before beginning dialysis and currently. Women also responded to questions about sexual activity, use of birth control, contraception counseling by physicians, yearly Papanicolaou smears, and mammograms. Demographic data (age, race, age at the time dialysis started, mode of dialysis, use of recombinant human erythropoietin, and history of renal transplant) were also obtained through the questionnaires. Fifty-nine percent of the 76 women who completed the study were white and had been on dialysis a median of 3 years (range, 0.1 to 18 years). The median age was 43 years, 68% were on hemodialysis, 90% were receiving recombinant human erythropoietin, and 70% had been pregnant (a total of 179 pregnancies; four pregnancies in four women occurred after the start of dialysis). Significantly more women were menstruating before dialysis started than currently (63% v 42%; P < 0.025), but the difference could be explained by patient age: currently menstruating women were younger (37 +/- 9 v 46 +/- 11 years; P = 0.0002). More women reported menstrual regularity before beginning dialysis (75% v 42% currently; P < 0.005), but there were no differences in number of days between or number of days of menstruation before beginning dialysis and currently. Menstrual flow was reported as heavier currently by more women (64% heavy flow with clots v 38% before dialysis started; P < 0.05). The median age at menopause was 47 years; 28% of the women were postmenopausal. Fifty percent of the women were sexually active, but only 36% used birth control. Discussions between the women and their nephrologist about possible pregnancy and contraception were reported by only 13% of women. Sixty-three percent of the women reported having yearly Papanicolaou smears and 73% had had a mammogram. Only 5% of the 113 women who were older than 55 years when they began dialysis were receiving estrogen replacement therapy. Amenorrhea was reported in this study by a smaller proportion of women than in studies conducted before the introduction of recombinant human erythropoietin. The possibility that erythropoietin may restore normal hormonal cyclic function in women with end-stage renal disease requires further study. Nephrologists as well as primary care physicians and gynecologists need to focus more on the gynecologic concerns of women on dialysis, including the potential for pregnancy. The effects of estrogen replacement on atherosclerosis and osteoporosis, and consideration of such therapy in women on dialysis warrants attention.
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PMID:Gynecologic and reproductive issues in women on dialysis. 915 1

The biological effects of reactive oxygen species and other radicals controlled by antioxidant mechanisms are modified by various enzymes and other substrates. Antioxidant substrates are divided into those with lipophilic and hydrophilic groups. Retinol and tocopherol are the main representations of lipophilic antioxidants. The aim of the present study was to describe the changes of retinol and alpha-tocopherol which occurred in hemodialysis (HD) patients in respect to the influence of antioxidant systems. The experimental group consisted of 14 patients on regular HD treatment. The control group consisted of 14 healthy blood donors. HPLC was used to measure retinol and alpha-tocopherol in serum. We found that the retinol concentration was significantly higher in HD patients compared to controls (2.35 +/- 0.95 versus 0.90 +/- 0.23 mg/L, p < 0.0001). The concentration of alpha-tocopherol in serum was not different in both study groups (7.32 +/- 3.01 versus. 8.94 +/- 3.57 mg/L). A review of the MEDLINE database since 1985 found a few references concerning these important antioxidant vitamins in HD patients and these contained contrasting results. It has been suggested that some of the complications related to HD including cardiovascular complications, anemia and atherosclerosis may be due to ineffective antioxidant systems and/or to increased free oxygen radical production. The question about supplementation of antioxidants in HD patients is open although there are some positive data regarding the use of moderate and safe selenium supplementation in HD patients. HD patients treated by erythropoietin had increased plasma concentration of retinol and normal level of alpha-tocopherol compared to healthy group. However, this positive finding did not affect lipid peroxidation, which is increased in HD patients and leads to some complications during HD treatment.
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PMID:Retinol and alpha-tocopherol in hemodialysis patients. 960 38

Clinical effects of recombinant human erythropoietin (rHuEPO) such as thrombosis, convulsions, hyperviscosity, hypertension, and angiogenic effect in culture cells have been described. We studied the rHuEPO effect on endothelial damage markers and endothelial function markers: tissue-type plasminogen activator (t-PA), nitrate (NO3), thrombomodulin (TM), and von Willebrand factor (vWF). Twenty-six peritoneal dialysis patients treated with rHuEPO and 19 controls were included. The study design for rHuEPO patients consisted of four periods: long-term treatment (rHuEPO-1); 2 months of withdrawal (rHuEPO-2); and 4 months on 5000 IU/week rHuEPO subcutaneously, with markers being measured after 2 months (rHuEPO-3) and after 4 months (rHuEPO-4). After 2 months of rHuEPO withdrawal, a decrease in hemoglobin level appeared (11+/-1.8 g/dL to 9.2+/-1.5 g/dL, p < 0.01). After rHuEPO reintroduction, this value reached 10.6+/-1.5 g/dL at two months, and 11.1+/-1.4 g/dL at four months. A significant increase in t-PA ratio was observed from two months without rHuEPO to two months on rHuEPO, returning to previous values after four months. Similarly, TM increased for patients with creatinine clearances (CrC) < 5 mL/min. No changes in the higher-than-normal plasma vWF levels were found during the various periods. A statistically significant lower value was found in controls compared with rHuEPO-4 patients. A statistically significant increase in NO3 levels was observed in the pre-venous occlusion (VO) test immediately after the re-introduction of rHuEPO. This increment returned to prior values four months after rHuEPO was reintroduced. Our results show that rHuEPO treatment causes an increase in some endothelial damage markers (TM, t-PA) and modifies endothelial function markers (t-PA ratio, NO3). These changes might favor thrombosis and atherosclerosis.
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PMID:Effects of recombinant human erythropoietin on functional and injury endothelial markers in peritoneal dialysis patients. 1040 11

So far it is not clear how erythropoietin affects the anticoagulant properties of vascular endothelium in uremia. Since serotonin is also thought to play a role in the pathogenesis of thrombosis, the aim of the study was to evaluate major components of extrinsic coagulation pathway, markers of endothelial cell injury, lipoprotein (a) and peripheral serotonergic mechanisms during rHuEPO therapy in hemodialyzed patients. The study was performed on chronically hemodialyzed patients divided into two groups: with rHuEPO treatment and without rHuEPO therapy in relation to the control group. In uremic patients, thrombomodulin and von Willebrand factor, activity of factor VII, tissue factor pathway inhibitor (TFPI) activity, TFPI and tissue factor (TF) concentrations, lipoprotein (a) level were significantly higher when compared to healthy volunteers. Treatment with rHuEPO resulted in a further significant rise in markers of endothelial cell injury: thrombomodulin and von Willebrand factor and TFPI concentration. Extrinsic coagulation factors: activities of factor VII and X, TFPI activity and TF activity and concentration, lipoprotein (a) and vitronectin remained unchanged during rHuEPO therapy. Platelet serotonin content and whole blood serotonin were significantly lower in uremic patients relative to healthy volunteers and during rHuEPO treatment they increased significantly. Whole blood serotonin reached normal values. Plasma serotonin, significantly elevated in uremia, did not change during rHuEPO therapy. Serotonin uptake by uremic platelets was significantly impaired and remained unaltered during rHuEPO administration. Serotonin release by uremic platelets was also significantly depressed but a significant improvement was observed in rHuEPO-treated patients. Our data suggest that endothelial injury, TF pathway components and peripheral serotonergic system disturbances may predispose to thromboembolic complications and play a role in the pathogenesis of atherosclerosis in uremic patients, particularly treated with rHuEPO. Increase in TFPI may compensate the increase in TF in these patients.
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PMID:Importance of serotonergic mechanisms in the thrombotic complications in hemodialyzed patients treated with erythropoietin. 1075 6

Patients undergoing hemodialysis are at risk for atherosclerosis and its complications. The aim of this study was to examine the effect of erythropoietin therapy and hemodialysis duration on some of the atherosclerotis risk factors. The patients were divided into four groups: I: patients undergoing hemodialysis for less than 10 years (n=22); II: patients undergoing hemodialysis for more than 10 years (n=17); III: patients on no erythropoietin (n=21); IV: patients on erythropoeitin therapy (n=18). A control group of 20 subjects was also examined. Triglycerides, total cholesterol, low-density lipoprotein and high-density lipoprotein, lipoprotein(a), apolipoprotein-A1, apolipoprotein-B and lipid peroxidation were examined. There was a significant increase in triglycerides, to 2.59+/-1.2 mmol/l (p<0.001) and in lipid peroxidation in hemodialysis patients, to 5.02+/-0.9 micromol/l vs. controls (p<0.001). Significantly elevated triglycerides and lipid peroxidation levels were found in the patients with longer hemodialysis duration. Triglycerides were elevated in group II vs. group I, to 2.90+/-1.0 mmol/l. (p<0.05). Lipid peroxidation in group II, 5.40+/-1.0 micromol/l, showed significant difference compared to group I (p<0.05). Erythropoietin treatment did not affect any of the examined parameters. These results indicate increased risk for atherosclerosis related to hemodialysis duration. Besides the renal disease itself, hemodialysis may also be one of the risk factors for atherosclerosis.
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PMID:Atherosclerosis risk factors related to hemodialysis duration and erythropoietin therapy. 1150 57

Anaemia is a frequent complication of many diseases but the mechanisms that link reduced blood oxygen content to the long-term consequences of anaemia are incompletely understood. The maintenance of oxygen supply to the tissues during anaemia involves complex cardiovascular adaptations, including an increase in cardiac output, reduced peripheral resistance and increased oxygen extraction from haemoglobin (Hb). In addition, hypoxia-inducible factors are associated with the transcriptional activation of genes involved in adaptive mechanisms that increase oxygen delivery and provide alternative metabolic pathways. The complex pathophysiology of chronic kidney disease alters the adaptations to anaemia in uraemic patients. The increased cardiac output induced by anaemia is associated with left ventricular hypertrophy and cardiac disease in renal patients. Alterations in endothelial cell function, common in renal disease, may diminish endothelium-induced vasodilatation, increase the risk of atherosclerosis and impair angiogenesis. Many potential reasons for erythropoietin-induced hypertension in uraemic patients have been postulated, including increased blood viscosity as haematocrit rises, a reversal of hypoxic vasodilatation, increased blood volume that is not compensated by haemodialysis, ultrafiltration and impaired nitric oxide synthesis, preventing vascular relaxation in response to increased blood viscosity. In view of this impaired vascular reactivity, rapid increases in haematocrit should be avoided during epoetin treatment. As the interaction between anaemia and uraemia is very complex, it is not possible to derive the optimal Hb concentration for individual patients by using simple physiological or pathophysiological models and there is a need for good randomized controlled clinical trials to address this issue.
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PMID:Anaemia in end-stage renal disease: pathophysiological considerations. 1159 Feb 49


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